hepatitis a case study ppt

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Patient Case Presentation

Our patient, Mr. Smith, is a 43 year old caucasian male who came in today with complaints of fatigue, anorexia, malaise, nausea, vomiting, abdominal pain, and low grade fever for the past month, and recently has been alarmed by the discoloration of his skin and sclera turning yellow. He states that his urine has become dark and stool has become clay colored.

Past Medical History:  Blood transfusion in 1992 due to major blood loss in a motor vehicle accident, arthralgia, peripheral neuropathy, hospitalization due to drug overdose in 2010. Patient states that he is fully up to date on vaccination.

Social History : Patient is an injectable drug user for the past 12 years and is currently sexually active with multiple male partners and states he uses protection “sometimes”. His current occupation is a car mechanic.

Family History: Mother: history of hyperlipidemia and diabetes father died of myocardial infarction, no other siblings or family history available .

pictured: jaundice on an individual’s eye; “Jaundice.” Assignment Point , 5 Oct. 2017, www.assignmentpoint.com/science/medical/jaundice.html.

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Hepatitis A: A Case Report Example of a Growing Epidemiological Threat

Affiliation.

• 1 McLaren Macomb.
• PMID: 33655155
• PMCID: PMC7746049
• DOI: 10.51894/001c.7436

Hepatitis A is a common worldwide cause of acute hepatitis. It has been classically associated with epidemics and is increasingly prevalent in the developing world. Generally, the illness is self-limited and only requires supportive management, reassurance, and proper hygiene instructions. This case involves a male in his early 30s who presented non-emergently with jaundice and a weeklong history of fatigue, nausea, and flu-like symptoms. The patient underwent laboratory and radiological evaluation. Test results revealed a significant transaminitis, hyperbilirubinemia, and suggestion of cholecystitis. Further testing did reveal hepatitis A infection. This case illustrates the importance of clinicians having a high clinical suspicion for the disease based on individual risk factors as this disease can have a profound epidemiological impact in terms of local outbreaks and public health expenses.

Keywords: epidemiology; hepatitis a; jaundice; public health.

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Conflict of interest statement

The authors declare no conflict of interest.

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Viral Hepatitis Clinical Presentation

• Author: Naga Swetha Samji, MD; Chief Editor: BS Anand, MD  more...
• Sections Viral Hepatitis
• Pathophysiology
• Epidemiology
• Patient Education
• Physical Examination
• Approach Considerations
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Hepatitis D and E
• Histologic Findings
• Acute Hepatitis A
• Acute Hepatitis B
• Chronic Hepatitis B
• Acute Hepatitis C
• Chronic Hepatitis C
• Treatment of Hepatitis D and E
• Medication Summary
• Interferons
• Corticosteroids
• Vaccines, Viral, Prevention
• Immune Globulins
• Questions & Answers
• Media Gallery

The clinical presentation of infectious hepatitis varies with the individual, as well as with the specific causative virus. Some patients may be entirely asymptomatic or only mildly symptomatic at presentation. Others may present with rapid onset of fulminant hepatic failure (FHF). The classic presentation of infectious hepatitis involves four phases, as follows:

Phase 1 (viral replication phase): Patients are asymptomatic; laboratory studies demonstrate serologic and enzyme markers of hepatitis

Phase 2 (prodromal phase): Patients experience anorexia, nausea, vomiting, alterations in taste, arthralgias, malaise, fatigue, urticaria, and pruritus, and some develop an aversion to cigarette smoke; when seen by a healthcare provider during this phase, patients are often diagnosed as having gastroenteritis or a viral syndrome

Phase 3 (icteric phase): Patients may note dark urine, followed by pale-colored stools; in addition to the predominant gastrointestinal (GI) symptoms and malaise, patients become icteric and may develop right upper quadrant pain with hepatomegaly

Phase 4 (convalescent phase): Symptoms and icterus resolve, liver enzymes return to normal

The incubation period of hepatitis A virus (HAV) is 2-7 weeks (average, 28 days). Clinical symptoms then develop, often with a presentation similar to that of gastroenteritis or a viral respiratory infection. The most common signs and symptoms include fatigue, nausea, vomiting, fever, hepatomegaly, jaundice, dark urine, anorexia, and rash.

HAV infection usually occurs as a mild self-limited disease and confers lifelong immunity to the virus. Chronic HAV infection does not occur. [ 9 ]

The incubation period for hepatitis B virus (HBV) is 30-180 days (average, approximately 75 days). Patients then enter the prodromal or preicteric phase, characterized by the gradual onset of anorexia, malaise, and fatigue. During this phase, as the liver becomes inflamed, the liver enzymes start to elevate, and the patient may experience right upper quadrant pain. About 15% of patients develop an illness resembling serum sickness. These patients may experience fever, arthritis, arthralgias, or an urticarial rash.

As the disease progresses to the icteric phase, the liver becomes tender, and jaundice develops. Patients may note that their urine darkens and their stools lighten in color. Other symptoms in this stage include nausea, vomiting, and pruritus.

From this point on, the clinical course may be highly variable. Whereas some patients experience fairly rapid improvements in their symptoms, others go on to experience prolonged disease with slow resolution. Still others may have symptoms that periodically improve, only to worsen later (relapsing hepatitis). Finally, there is an unfortunate subset of patients in whom the disease rapidly progresses to FHF; this may occur over days to weeks.

The incubation period for hepatitis C virus (HCV) is 15-150 days, with symptoms developing anywhere from 5-12 weeks after exposure. During acute HCV infection, symptoms may appear similar to those of HBV infection. In up to 80% of cases, however, the patients are asymptomatic and do not develop icterus. [ 1 , 18 ]

Hepatitis D

The incubation period of hepatitis D virus (HDV) is approximately 35 days. Patients simultaneously infected with HBV and HDV often have an acute, self-limited infection. [ 48 , 55 ] Fewer than 5% of these patients develop chronic HDV infection.

Chronic HBV carriers who become superinfected with HDV tend to have a more severe acute hepatitis; 80% of these patients go on to develop chronic HDV infection. Chronic infection with HBV and HDV may lead to fulminant acute hepatitis and severe chronic active hepatitis with progression to cirrhosis. [ 48 , 55 ] Over the long term, as many as 70-80% of these patients have evidence of chronic liver disease with cirrhosis, compared with only 15-30% of patients with chronic HBV alone.

Hepatitis E

The incubation period of hepatitis E virus (HEV) is 2-9 weeks (average, 45 days). HEV usually causes an acute self-limited disease similar to HAV infection. Fulminant disease does occur in about 10% of cases. In women who are pregnant, HEV infection has a case-fatality rate of 15-20%. [ 34 ] No reports exist of chronic infection with HEV. [ 34 ]

Physical findings in patients with hepatitis vary with the type of hepatitis and the time of presentation.

Patients often present with low-grade fever. Those experiencing significant vomiting and anorexia may show signs of dehydration, such as tachycardia, dry mucous membranes, loss of skin turgor, and delayed capillary refill.

Patients in the icteric phase may have icterus of the sclerae or mucous membranes, or discoloration of the tympanic membranes. The skin may be jaundiced and may reveal macular, papular, or urticarial rashes.

In viral hepatitis, the liver may be tender and diffusely enlarged with a firm, sharp, smooth edge. If the patient has a nodular liver or a mass is palpated, clinicians should suspect an abscess or tumor.

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Xu HQ, Wang CG, Xiao P, Gao YH. Efficacy and safety of glecaprevir/pibrentasvir for chronic hepatitis C patients: a systematic review and meta-analysis. J Clin Transl Hepatol . 2020 Sep 28. 8(3):267-76. [QxMD MEDLINE Link] . [Full Text] .

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Nishiguchi S, Kuroki T, Nakatani S, et al. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet . 1995 Oct 21. 346 (8982):1051-5. [QxMD MEDLINE Link] .

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Yurdaydin C, Bozkaya H, Onder FO, et al. Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon. J Viral Hepat . 2008 Apr. 15 (4):314-21. [QxMD MEDLINE Link] .

Fiore AE, Wasley A, Bell BP, for the Advisory Committee on Immunization Practices (ACIP). Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep . 2006 May 19. 55(RR-7):1-23. [QxMD MEDLINE Link] . [Full Text] .

Vento S, Garofano T, Renzini C, et al. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med . 1998 Jan 29. 338(5):286-90. [QxMD MEDLINE Link] . [Full Text] .

Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2009*. Ann Intern Med . 2009 Jan 6. 150 (1):40-4. [QxMD MEDLINE Link] .

Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC). Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep . 2007 Oct 19. 56 (41):1080-4. [QxMD MEDLINE Link] .

Centers for Disease Control and Prevention. Hepatitis B FAQs for health professionals. Available at https://www.cdc.gov/hepatitis/HBV/HBVfaq.htm#recctbl . Updated: August 4, 2016; Accessed: June 13, 2017.

Halperin SA, Ward B, Cooper C, et al. Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age. Vaccine . 2012 Mar 28. 30(15):2556-63. [QxMD MEDLINE Link] .

Chang MH, Chen TH, Hsu HM, et al, for the Taiwan Childhood HCC Study Group. Prevention of hepatocellular carcinoma by universal vaccination against hepatitis B virus: the effect and problems. Clin Cancer Res . 2005 Nov 1. 11 (21):7953-7. [QxMD MEDLINE Link] .

Moorman AC, de Perio MA, Goldschmidt R, et al. Testing and clinical management of health care personnel potentially exposed to hepatitis C virus - CDC guidance, United States, 2020. MMWR Recomm Rep . 2020 Jul 24. 69(6):1-8. [QxMD MEDLINE Link] . [Full Text] .

McHutchison JG, Dusheiko G, Shiffman ML, et al, for the TPL102357 Study Group. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med . 2007 Nov 29. 357 (22):2227-36. [QxMD MEDLINE Link] .

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Brown RS Jr, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology . 2016 Jan. 63 (1):319-33. [QxMD MEDLINE Link] .

• Viral Hepatitis. Hepatitis A virus as viewed through electron microscopy.
• Viral Hepatitis. Liver biopsy specimen showing ground-glass appearance of hepatocytes in a patient with hepatitis B.
• Viral Hepatitis. Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in a patient with hepatitis B.
• Viral Hepatitis. Liver biopsy with trichrome stain showing stage 3 fibrosis in a patient with hepatitis B.
• Viral Hepatitis. Hepatic carcinoma, primary. Large multifocal hepatocellular carcinoma in an 80-year-old man without cirrhosis.
• Viral Hepatitis. Triple-phase computed tomography scan depicting liver cancer, revealing classic findings of enhancement during the arterial phase and delayed hypointensity during the portal venous phase.
• Table 1. Diagnostic Tests for Hepatitis B
• Table 2. Histologic Grading for Hepatitis C–Induced Liver Disease

Contributor Information and Disclosures

Naga Swetha Samji, MD Physician, Bellin Clinic, Bellin Health Systems Naga Swetha Samji, MD is a member of the following medical societies: American College of Gastroenterology , American College of Physicians , Wisconsin Medical Society Disclosure: Nothing to disclose.

Adrienne M Buggs, MD, FACEP, FAAEM Medical Policy Advisor, Office of Merchant Mariner Credentialing, United States Coast Guard Adrienne M Buggs, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine , American College of Emergency Physicians , American College of Occupational and Environmental Medicine Disclosure: Nothing to disclose.

Praveen K Roy, MD, MSc Clinical Assistant Professor of Medicine, University of New Mexico School of Medicine Praveen K Roy, MD, MSc is a member of the following medical societies: Alaska State Medical Association , American Gastroenterological Association Disclosure: Nothing to disclose.

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases , American College of Gastroenterology , American Gastroenterological Association , American Society for Gastrointestinal Endoscopy Disclosure: Nothing to disclose.

Eugene Hardin, FAAEM, FACEP Former Chair and Associate Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science; Former Chair, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases , American College of Physicians , and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology , American College of Physicians , American Gastroenterological Association , American Geriatrics Society , American Medical Association , American Society for Gastrointestinal Endoscopy , American Society of Law, Medicine & Ethics , American Trauma Society , Association of American Medical Colleges , and Physicians for Social Responsibility

Joseph K Lim, MD Associate Professor of Medicine, Director, Yale Viral Hepatitis Program, Section of Digestive Diseases, Yale University School of Medicine

Joseph K Lim, MD is a member of the following medical societies: American Association for the Study of Liver Diseases , American College of Gastroenterology , American College of Physicians , American Gastroenterological Association , and American Society for Gastrointestinal Endoscopy

Robert M McNamara, MD, FAAEM Chair and Professor, Department of Emergency Medicine, Temple University School of Medicine

Robert M McNamara, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine , American Medical Association , Pennsylvania Medical Society , and Society for Academic Emergency Medicine

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rajeev Vasudeva, MD, FACG Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Rajeev Vasudeva, MD, FACG is a member of the following medical societies: American College of Gastroenterology , American Gastroenterological Association , American Society for Gastrointestinal Endoscopy , Columbia Medical Society, South Carolina Gastroenterology Association, and South Carolina Medical Association

Disclosure: Pricara Honoraria Speaking and teaching; UCB Consulting fee Consulting

David C Wolf, MD, FACP, FACG, AGAF Medical Director of Liver Transplantation, Westchester Medical Center; Professor of Clinical Medicine, Division of Gastroenterology and Hepatobiliary Diseases, Department of Medicine, New York Medical College

David C Wolf, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases , American College of Gastroenterology , American College of Physicians , and American Gastroenterological Association

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Hepatitis A Surveillance Guidance

Uses of surveillance data, cases and clusters of potential public health importance, interpretation of laboratory test results, recommended reportable laboratory markers, surveillance case definition, case ascertainment, case investigation, case reporting and national notification.

Hepatitis A is typically a self-limited disease caused by hepatitis A virus (HAV), primarily transmitted fecal-orally after close contact with an infected person or consumption of contaminated food or water ( 31 ). Clinical symptoms are indistinguishable from acute hepatitis B and hepatitis C. Hepatitis A is an acute illness and does not result in chronic disease. The United States is considered a low endemicity country with most infections occurring among adults reporting risk behaviors or exposures such as SUD, homelessness, sexual practices resulting in fecal-oral contact, and international travel to hepatitis A-endemic countries ( 3 , 32 ).

A safe and effective hepatitis A vaccine was licensed in 1995 ( 33 ). Prior to vaccine licensure and use, the number of reported hepatitis A cases was around 21,000 annually, and infections were common among children ( 34 , 35 ). With the widespread adoption of the universal childhood vaccination recommendations in 2006, the overall incidence rate of hepatitis A decreased by 95% across all age groups from 1995 through 2014 ( 3 , 33 ). However, the incidence rate of hepatitis A increased during 2016–2019 due to widespread person-to-person outbreaks, primarily among PWUD and people experiencing homelessness ( 3 ). Increases in hepatitis A have also been reported among MSM ( 36 ). A study published in 2020 showed that approximately three-fourths of US-born adults ≥20 years of age were susceptible to hepatitis A during 2007–2016 ( 37 ). During 2016–2018, approximately 15,000 hepatitis A cases were reported to CDC, representing a 294% increase compared with 2013–2015 ( 38 ). In 2019, the number of hepatitis A cases reported to CDC peaked at 18,846 cases, corresponding to 37,700 estimated infections after adjusting for case under-ascertainment and underreporting ( 3 ). The annual number of hepatitis A cases reported to CDC has since declined as more states declared an end to their outbreaks. Disruptions to health care access and health department surveillance capacity during the COVID-19 pandemic may have affected the ability to detect and report all hepatitis A cases.

The purpose of this section is to provide jurisdictional guidance to implement and improve hepatitis A surveillance. Information about reporting requirements, collection of relevant laboratory data, and case investigation is provided. Given that current systems for surveillance differ by jurisdiction, the standards outlined in this document are designed to provide models for best practices based on jurisdictional resources, recognizing that not every jurisdiction is able to meet those standards with available resources.

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Hepatitis A surveillance data can be used to inform and improve public health interventions in the following ways:

• Monitoring trends in disease incidence and determining risk behaviors or exposures . Hepatitis A surveillance data should be analyzed at a minimum of weekly by person, place, and time to monitor disease incidence. The proportion of cases reporting specific risk behaviors or exposures should be determined to monitor disease transmission patterns.
• Identifying outbreaks. The identification of a hepatitis A geotemporal cluster or increase in incidence can be an early signal of an outbreak and should prompt further investigation. This investigation should include collection of additional information, including risk behaviors or exposures for person-to-person transmission (e.g., non-injection and injection drug use, homelessness, and sexual and other practices leading to fecal-oral contact) or potential exposures to a common-source (e.g., suspected foods and infected food handler). Surveillance data should be analyzed to determine affected areas (e.g., rates by local jurisdiction or zip code) and groups (e.g., age-specific incidence rates and frequencies of reported risk behaviors or exposures). Prospective surveillance should be conducted to identify additional outbreak cases, identify candidates for post-exposure prophylaxis (if indicated), enhance vaccination efforts for populations at risk, and inform communication and infection control measures. If an outbreak is identified, DVH staff are available to provide consultation.
• Identifying cases among people who might expose others. The identification of a hepatitis A case in someone in a certain occupation (e.g., food handler) or congregate living situations is important because of the potential to expose additional people. This information can facilitate prompt contact tracing and coordination of postexposure prophylaxis.
• Molecular sequencing of viral isolates might help guide response measures. When investigating a possible outbreak, in some instances, collecting sera from patients for diagnosis and molecular characterization (genome sequencing and genotype identification) might provide additional information to guide control efforts and identify outbreaks within outbreaks (e.g., foodborne-related cases during person-to-person outbreak). Public health professionals who need guidance regarding use of nucleic acid testing (NAT) for the investigation of hepatitis A outbreaks should contact CDC’s DVH at [email protected] .
• Assessing missed opportunities for prevention. Patients whose infection source was reported as a household or sexual contact with suspected or confirmed hepatitis A should be investigated to determine if the patient received post-exposure prophylaxis when the source case was identified. In addition, surveillance data can be used to provide information about people at high risk for infection to provide education and awareness about the importance of vaccinating populations as recommended by the Advisory Committee on Immunization Practices (ACIP).
• Assessing the impact of vaccination programs. Age-specific incidence rates for the priority groups and the community as a whole can be compared to historical rates for the same age groups to assess the impact of routine vaccination programs.

Jurisdictions should review and analyze hepatitis A data regularly to identify cases and clusters of hepatitis A that merit further investigation. Ideally, all cases of reported hepatitis A should be investigated. In jurisdictions with limited resources, cases and clusters should be prioritized for investigation in accordance with the degree of public health importance. The following are examples of cases that are high priority for further follow-up:

• Cases in people who are in higher risk groups (e.g., PWUD, people experiencing homelessness) or who live in congregate settings (e.g., shelters, correctional facilities) to assure that interventions to prevent further spread are implemented in a timely fashion
• Cases who were previously vaccinated to characterize possible vaccine failures (see Section 1.10 ).
• Cases of hepatitis A in people born after 2005 to distinguish between failure of vaccine and failure to vaccinate
• Cases without common risk behaviors or exposures
• Two or more cases among patrons at the same store or food service establishment

Immunoglobulin M antibody to hepatitis A virus (anti-HAV IgM) and viremia identified by HAV NAT using polymerase chain reaction (PCR) can detect recent or current acute infection with HAV. A description of hepatitis A laboratory markers can be found in Appendix B . Figure 2-1 illustrates the typical serologic course of HAV infection and recovery.

Figure 2-1. Typical serologic course of hepatitis A virus infection and recovery

Figure obtained from https://www.cdc.gov/mmwr/pdf/rr/rr5304.pdf . Downloads of this figure: PDF | PPT

Caution should be exercised when interpreting a positive anti-HAV IgM laboratory result, as positive tests can occur in people >1 year after infection and false-positive tests can also occur in those without clinical or epidemiologic evidence of recent infection ( 39 ). A person with a positive anti-HAV IgM result may also be positive for anti-HAV IgG and total anti-HAV. Because of the risk of misinterpreting positive results, anti-HAV IgM testing should be limited to people with clinical presentation of hepatitis who are suspected of having hepatitis A. Anti-HAV IgM testing should not be used as a screening tool or as part of testing panels in the workup of abnormal liver function tests. Some conditions might cause cross-reactivity with anti-HAV IgM tests, including infection with the Epstein-Barr virus ( 40 ) and hepatitis C virus ( 41 ). Furthermore, some infected people might initially test negative for anti-HAV IgM during the first few days of symptoms ( 42 ). If there is high clinical suspicion of hepatitis A in a person who has a negative test for anti-HAV IgM early in their clinical course, repeat testing may be indicated ( 42 ). One study found that the optimal time for repeat testing is at least 2 days after ALT levels have peaked ( 42 ).

Table 2-1 interprets the combinations of total anti-HAV and anti-HAV IgM laboratory results frequently available in viral hepatitis test panels, following the biomarker changes over the course of infection as shown in Figure 2-1 . If HAV RNA testing is performed, a detectable HAV RNA level indicates the presence of infection.

Table 2-1. Interpretation of hepatitis A laboratory results

*Ingestion of high levels of biotin can significantly interfere with certain commonly used biotinylated immunoassays, such as those used to detect anti-HAV, and cause false-positive or false-negative laboratory test results. Currently, the US Food and Drug Administration (FDA) is investigating thresholds associated with false-positive and false-negative tests. This section will be updated as more information becomes available. Reference: https://www.fda.gov/medical-devices/safety-communications/update-fda-warns-biotin-may-interfere-lab-tests-fda-safety-communication . Downloads of this table: PDF | PPT

To aid in hepatitis A surveillance, the following laboratory markers should be reported to public health agencies:

• Positive anti-HAV IgM;
• Positive/detectable HAV RNA (including qualitative, quantitative, or genotype testing); and
• All concurrent ALT and total bilirubin results reported with positive hepatitis A laboratory results, which can also be helpful in classifying hepatitis A cases that do not have an HAV RNA laboratory result.

Table 2-2 specifies the surveillance case definition for hepatitis A, adopted by CSTE and CDC in 2019. This definition should be used for hepatitis A case classification and national notification ( 12 , 43 ). See Appendix C  for classification scenarios of cases of hepatitis A.

Table 2-2. US Centers for Disease Control and Prevention (CDC) and Council of State and Territorial Epidemiologists (CSTE) case definition for hepatitis A, 2019

Up to 10% of people with hepatitis A might experience a relapse of symptoms during the 6 months after acute illness. Cases of relapsing hepatitis A should not be enumerated as new cases. In addition, a case should not be counted as a hepatitis A case if there is an alternate, more likely diagnosis.

The primary method of ascertaining cases is by reviewing reports from clinical laboratories, health care facilities, and health care providers. All states should have rules or regulations requiring that these facilities report evidence of hepatitis A to public health agencies. See Section 1.6. and Section 2.5.  for information on the recommended reporting requirements for hepatitis A.

Laboratory Reporting

All states require clinical laboratories to report hepatitis A laboratory markers, such as positive anti-HAV IgM and positive HAV RNA results.

Health Care Facility and Provider Reporting

All states require health care facilities and providers to report hepatitis A diagnoses.

Additional sources that will facilitate case ascertainment and case characterization include medical records, hospital discharge databases, and death certificates. Section 5.4  describes the usefulness of select data sources in supplementing case ascertainment.

Figure 2-2 illustrates one approach for hepatitis A case ascertainment and classification. Specific procedures might vary by jurisdiction, but should generally follow the scheme outlined in Figure 2-2 , in accordance with the CDC/CSTE Position Statement for the 2019 hepatitis A case definition  ( 12 , 43 ). See Appendix C  for case classification scenarios for hepatitis A.

Figure 2-2. Process for hepatitis A case ascertainment and classification

Reports from laboratories, health care providers, and other data sources indicative of hepatitis A should be submitted to HDs (as specified by local regulations) and investigated as soon as possible to ensure adequate time to implement preventive measures (e.g., vaccination of contacts). Suspected cases of hepatitis A should be reported with appropriate laboratory results and clinical information ( Table 2-2 ). For general information on conducting viral hepatitis case investigations, see Section 1.10.  The following is a description of the follow-up activities that should be conducted for reported hepatitis A cases:

Information from the Laboratory

Positive anti-HAV IgM and positive/detectable HAV RNA laboratory results should be reported to the HD and investigated immediately. Other laboratory information that can assist with case classification includes ALT and total bilirubin levels.

Information from the Provider or Medical Records

The following information might be available from medical records to confirm the diagnosis, inform case classification, and determine public health priority.

• Diagnostic test results. Hepatitis A laboratory markers (e.g., positive anti-HAV IgM and positive/detectable HAV RNA) should be reportable to the HD. If additional laboratory testing (e.g., for ALT and total bilirubin levels) is needed to classify the case, HD staff will work with the provider to obtain these test results.
• Clinical features. Includes reason for testing, illness onset date, clinical signs and symptoms (including the presence of jaundice), coinfections, hospitalization status and date of death, and whether hepatitis A or an alternate diagnosis is suspected.
• Demographic information. Includes name, date of birth, sex at birth, current gender, race, ethnicity, and residential address (including zip code).
• Patients who deny known risk behaviors or exposures for infection can be interviewed with a supplemental food history questionnaire.
• At the earliest possible point, information regarding whether the patient is in a sensitive occupation (e.g., food handler) or an attendee or resident of a congregate setting should be obtained.
• Occupation. While no documented evidence indicates that food handlers or health care workers are at higher risk for infection than people in other occupations, jurisdictions routinely obtain this information to inform contact tracing. Special attention should be given to the job duties of people in sensitive occupations, including whether the patient was symptomatic while at work, which symptoms (if any) were experienced while at work, and the patient’s work schedule during their infectious period. Food handlers should be restricted from working in a food handling capacity while infectious, and patrons from food service establishments or health care providers should be notified as appropriate ( 44 ).
• Vaccination information . Hepatitis A vaccination has been recommended for infants since 2006 in all US states. Depending on age of the HAV-infected person, some cases of hepatitis A should have been vaccinated in childhood, whereas others should have been vaccinated as adults because they met specific risk criteria. Though rare, recent vaccination might result in transient anti-HAV IgM positivity. Obtaining vaccination history can be done via the patient’s provider or state immunization registries and is useful in identifying vaccine failure or transient anti-HAV IgM positivity.

Information from the Patient

Resources permitting, all patients with hepatitis A should be contacted for an interview using the jurisdiction-specific case investigation form. At a minimum, all patients who are classified as “confirmed” per the CDC/CSTE case definition should be interviewed. The patient interview should ideally include the following components:

• Epidemiologic link. For all laboratory-confirmed cases of hepatitis A, obtain information on contacts where exposure occurred 15–50 days prior to the onset of symptoms and investigate whether contacts met the clinical criteria.
• Risk behaviors or exposures. To determine the most likely mode of transmission, ask patients about behaviors and exposures during the 15–50 days prior to illness onset. Patients who deny other risks for infection should be interviewed with a supplemental food history questionnaire.
• Education and referral for follow-up. Assess whether the patient requires education or other medical follow-up services, including hepatitis B vaccination, as appropriate. People with hepatitis A should be counseled on how to prevent transmission to others.
• Identification of contacts requiring post-exposure prophylaxis. If resources allow, identify contacts and coordinate referral for post-exposure prophylaxis if contact occurred within 14 days. Information regarding hepatitis A vaccination and post-exposure prophylaxis can be found on the Hepatitis A ACIP Vaccine Recommendations website .

Special Considerations when Investigating Certain Populations or Settings at Risk for Rapid Disease Transmission

Certain populations and settings are associated with increased risk for rapid transmission of hepatitis A. Considerations when investigating hepatitis A cases among people experiencing homelessness, PWUD, people engaging in high-risk sexual practices, and people in correctional facilities are provided in Section 1.10.

Outbreak Reporting and Notification

All hepatitis A outbreaks should be reported to the appropriate local authorities for further investigation within the timeframe each jurisdiction has specified. The reporting timeframe to local authorities varies by jurisdiction. Notification to CDC is done through NNDSS and by contacting [email protected] , as indicated in CDC-RFA-PS21-2103. See Section 5.3  for guidance on reporting outbreak source to NNDSS.

Cases of hepatitis A should be reported to HDs as specified by state, territorial, and local regulations. Hepatitis A is a nationally notifiable condition ( 9 ). Hepatitis A cases are identified using an event code ( Table 1-2 ).  Data are sent weekly or more frequently, depending on the infrastructure of the jurisdiction sending the data. Cases might be re-classified or removed as needed after the initial transmission to CDC, if the changes occur before surveillance data are finalized each year.

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Hepatitis A and B Case Study

Jon and Laura Green are siblings sharing similar symptoms. Both have a yellow tinge to their skin and the whites of their eyes. Both have flu-like symptoms. Jon, however, has been living in Brazil while Laura has been in San Francisco. Is this a weird sibling connection? Find out what’s causing their unusual symptoms in Case #5.

Mudule 10: Hepatitis

This case is actually two separate cases that address viral hepatitis. This format was selected...

Hepatitis - Page 1

When Jon arrived home, Jon and Laura’s father arranged for both of his children to see Dr. Lyon...

Hepatitis - Page 2

Dr. Lyon ordered the following laboratory tests on both Jon and Laura Green...

Hepatitis - Page 3

Since Jon's diagnosis was confirmed by his immune response to the presence of the virus, the physicians agreed...

Hepatitis - Page 4

Case Summary

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Acute Hepatitis in a 44-Year-Old Woman

Miles Medrano, MD; Richard W. Goodgame, MD

January 03, 2002

Case Presentation

The patient was a previously healthy 44-year-old Mexican American woman whose chief complaint was jaundice and right upper quadrant pain.

For about 1 year, she had the sensation of dry mouth; there were no oral lesions or dysphagia. She had no dry eyes or other features of the complete sicca syndrome. Six weeks prior to admission, she sought advice from an herbalist and was given several herbal medications including desiccated liver, "Texas elixir," peppermint leaf, and nopal. These medications worsened her oral symptoms, and she stopped taking them after a few days. Over the next few weeks, she developed fatigue and a poor appetite. The following week she developed jaundice, right upper quadrant abdominal pain, dark urine, and clay-colored stool. At this point in time, the patient saw a physician and was told that she had hepatitis. She was given esomeprazole, promethazine, clotrimazole, and rofecoxib.

Her past medical history was positive for 2 cesarean sections and an elective surgical abortion (performed 4 months previously). She had no history of arthritis, pleurisy, thyroid disease, diabetes, diarrhea, or Raynaud's syndrome. She has had no blood transfusions, no alcohol or tobacco use, no substance abuse, no travel in the last 10 years, and no relevant family history of serious disease.

Physical examination showed a mildly obese, deeply jaundiced woman in mild distress due to fatigue and right upper quadrant discomfort. There was a hint of palmar erythema (Figure 1) and a single cutaneous vascular lesion on her anterior chest (Figure 2). There was no clubbing, edema, or enlarged parotid glands. The liver was felt 3 cm below the right costal margin in the mid-clavicular line; it was smooth, soft, and mildly tender. The spleen was not palpable.

Laboratory investigations disclosed the following values:

Hemoglobin: 12.6 g/dL

White blood cell count: 6200/mm 3

Platelets: 170,000/mm 3

Creatinine: 0.8 mg/dL

Prothrombin time: 18.2 sec

Partial thromboplastin time 52.7 sec

Total bilirubin: 24.7 mg/dL

Direct bilirubin: 13.7 mg/dL

Total protein 7.9 g/dL

Albumin: 2.5 g/dL

Alkaline phosphatase: 128 U/L

Aspartate aminotransferase (AST): 3017 U/L

Alanine aminotransferase: 2262 U/L

The patient had an ultrasound examination of the liver (Figures 3, 4) which showed hepatomegaly but no mass lesions, gallstones, or dilated bile ducts. Doppler sonography showed normal portal and hepatic venous flow (not shown).

What is the differential diagnosis of this patient's liver disease, based on medical history, results of physical examination, and liver chemistries?

This patient presented with an acute hepatitis: jaundice, right upper quadrant pain, fatigue, and markedly elevated aminotransferases. The ultrasound excluded obstruction, mass lesions, and infiltrative diseases (although these were not suspected given the high aminotransferase levels and mildly increased alkaline phosphatase).Viral hepatitis, which includes hepatitis A, B, C, and coinfection or superinfection with D, were possibilities in this patient. However, she had few risk factors. Drug- or toxin-induced hepatitis was also a consideration. The patient had taken several herbal medications, which could have played a contributory role. Additionally, many medications can have hepatotoxic effects. Several of the more commonly noted reactions occur with isoniazid, sodium valproate, phenytoin, antibiotics, statins, nonsteroidal anti-inflammatory drugs, and the -azole antifungals. Acetaminophen causes a dose-dependent direct toxic effect on the liver and could give this clinical picture with acute ingestion of greater than 12 g (or less, if alcohol is also ingested). Other agents that have toxic effects on the liver include carbon tetrachloride, trichloroethylene, and mushroom poisons. [ 1 ] Additional considerations include veno-occlusive disease, severe acute hepatic congestion, and acute ischemic injury. However, history, physical examination, and ultrasound ruled out these diagnoses.The final important cause of acute hepatitis is acute autoimmune hepatitis. This patient had no history of autoimmune diseases, but the possibility of the sicca syndrome prompted close questioning for any suggestion of collagen vascular and rheumatologic disorders. The globulin fraction of the serum proteins was very high: 5.4 gm/dL. Although this finding can be seen in a variety of acute and chronic liver diseases, it is part of the diagnostic criteria for autoimmune hepatitis.

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If the cutaneous vascular lesion and palmar erythema are from chronic liver disease, how does this affect your differential diagnosis?

Causes of chronic hepatitis were also considered in the differential diagnosis of this patient. Chronic viral and autoimmune hepatitis can have acute exacerbation and present as an acute hepatitis. These diseases and some of the hereditary causes of chronic liver disease such as Wilson's disease, hereditary hemochromatosis, and alpha-1-antitrypsin deficiency may be more susceptible to acute hepatic injury from drugs or toxins. The very high aminotransferases made alcoholic liver disease unlikely. Primary biliary cirrhosis and primary sclerosing cholangitis do not present as an acute severe hepatitis, and in the chronic phase have very high alkaline phosphatase.

What blood tests should be obtained to arrive at a diagnosis?

Important laboratory studies for liver diseases or other autoimmune disorders included in the differential diagnosis are as follows: serologic testing for hepatitis A, B, and C; testing for autoantibodies and IgG concentrations for autoimmune hepatitis; iron studies; serum ceruloplasmin; alpha-1-antitrypsin level; and serum thyroid-stimulating hormone (TSH).

© 2001 Medscape

Cite this: Richard W Goodgame. Acute Hepatitis in a 44-Year-Old Woman -  Medscape  - Oct 15, 2001.

Authors and Disclosures

Dr. Medrano is a GI Fellow in the Department of Gastroenterology, Baylor College of Medicine, Houston, Texas.

Goodgame R, Medrano M. Acute Hepatitis in a 44-Year-Old Woman. MedGenMed 3(4), 2001 [formerly published in Medscape Gastroenterology eJournal 3(5), 2001]. Available at: https://www.medscape.com/viewarticle/412587

Richard W Goodgame, MD

Professor of Medicine, Baylor College of Medicine, Houston, Texas; Chief of Endoscopy, Ben Taub General Hospital, Houston, Texas

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Hepatitis A: A Case Report Example of a Growing Epidemiological Threat

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Hepatitis A is a common worldwide cause of acute hepatitis. It has been classically associated with epidemics and is increasingly prevalent in the developing world. Generally, the illness is self-limited and only requires supportive management, reassurance, and proper hygiene instructions. This case involves a male in his early 30s who presented non-emergently with jaundice and a weeklong history of fatigue, nausea, and flu-like symptoms. The patient underwent laboratory and radiological evaluation. Test results revealed a significant transaminitis, hyperbilirubinemia, and suggestion of cholecystitis. Further testing did reveal hepatitis A infection. This case illustrates the importance of clinicians having a high clinical suspicion for the disease based on individual risk factors as this disease can have a profound epidemiological impact in terms of local outbreaks and public health expenses.

INTRODUCTION

Hepatitis is a generic term that refers to some manner of liver inflammation. The most common causes leading to such a diagnosis include viral infections and chronic alcohol abuse. 1 Other causes can include bacterial, fungal, parasitic, immunologic, and toxic exposures. Hepatitis A Virus (HAV) is a virus that is spread almost exclusively through the fecal-oral route, although there does exist a very rare ability for blood transmission. 1 HAV is an acute illness and there is no associated chronic carrier state (i.e., asymptomatic person capable of transmitting) such as seen with Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). Typically, cases occur in association with epidemics, as opposed to sporadic cases, with the most common risk factor for transmission being travel outside of the US. 1

The incubation period for HAV ranges from 14 to 45 days, with a relatively short duration of viremia (i.e., detectable virus in the blood) and maximum infectivity to others that is most prominent before symptom onset. 1 Differentiation of the cause of hepatitis generally requires a broad laboratory evaluation and thorough history and physical exam.

Although HAV is rarely diagnosed initially in the Emergency Department (ED) due to serology testing times, 1 a high clinical suspicion for the disease can lead to timely intervention including contact precautions and prevention of complications. Primary and secondary prophylaxis is available, however vaccination is not mandatory as the disease is rarely fatal, has no chronic carrier state, and has an overall low incidence in the United States. 2

Case Report

A Caucasian male in his early 30s presented to the ED with the chief complaint of yellowing of his skin and typically white sclera of his eyes. This was preceded by five days of progressive fatigue and flu-like symptoms. He also admitted to having produced several tan-colored bowel movements, dark urine, subjective fevers, and nausea. He denied any abdominal pain, vomiting, diarrhea, hematuria, or rashes. He also denied having completed any recent travel, insect or chemical exposures, or any known sick contacts.

He did not recall any peculiar food exposures during the prior week. He denied ever having experienced symptoms like this in the past but did admit to current HIV prophylaxis medication for the reason of “being smart.” He did admit to previous intravenous drug use with last administration three years prior. He had a history of mild well-controlled asthma and denied any previous surgeries.

The patient’s immediate vitals revealed hemodynamic stability with heart rate of 106, respiratory rate of 18, temperature of 97.6 degrees axillary, blood pressure of 140/86, and oxygen saturation of 100% on room air. His physical exam revealed a well-nourished, diffusely jaundiced male in no acute distress. The patient was alert and oriented and answering all questions appropriately, albeit with short answers.

Further examination revealed prominent bilateral yellow discoloration of the eyes (i.e., scleral icterus) and abdominal examination demonstrated a mildly distended abdomen with mild tenderness in the right upper quadrant. There were no other indications of peritonitis and the remainder of the physical examination was within normal limits. The patient was provided with intravenous (IV) fluids and a broad laboratory evaluation and computerized axial tomography (CT) of the abdomen and pelvis with IV contrast was obtained.

CT of the abdomen and pelvis was interpreted as gall bladder contraction with wall edema and mucosal hyper-enhancement. (Figure 1) No gallstones were identified and the liver, common bile duct and pancreas were all within normal limits. Laboratory evaluation was obtained to evaluate for the degree of liver impairment and was pertinent for thrombocytopenia (88,000), hyperglycemia (451 mg/dL), hyperbilirubinemia (9.2 mg/dL), transaminitis (2238 U/L and 3806 U/L), and elevated PT-INR (i.e., prothrombin time-international normalized ratio) of 15.9 sec/1.54. (Table 1). These laboratory abnormalities suggested possible new-onset Diabetes Mellitus as well as significant liver dysfunction.

Given the radiological findings and suspicion for obstructive jaundice with possible gall bladder infection (i.e., cholecystitis), the authors discussed the case with general surgery. Orders for a magnetic resonance cholangiopancreatography (MRCP) and a viral hepatitis panel were placed for suspected concomitant acute hepatitis. The patient was initiated on IV antibiotics for suspected cholecystitis.

The case was then discussed with the Gastroenterology (GI) service who had also recommended a MRCP, avoidance of hepatotoxic medications (e.g., acetaminophen and ciprofloxacin) and hepatitis panel. The patient was subsequently admitted to the hospital in hemodynamically stable status with MRCP and hepatitis panel pending. Gastrointestinal (GI), general surgery and endocrinology for suspected new-onset Diabetes Mellitus were consulted on the case.

During the patient’s two-day hospital course, he underwent a MRCP which showed no gallstones (i.e., cholelithiasis), intra or extra-hepatic biliary dilatation, choledocholithiasis, or pancreatic ductal dilatation. The patient’s newly diagnosed Diabetes Mellitus (Hemoglobin A1c of 9.2) was managed by Endocrinology. A hepatitis panel indicated no evidence of HBV or HCV reactivity but was reactive for anti-HAV immunoglobulin (IgM), suggesting acute HAV.

The patient was again evaluated by the same consulting services with further recommendations of no surgical intervention being required and trending of the hepatic function panel. On the patient’s hospital Day 2, his repeat hepatic function lab panel revealed improvement in the patient’s liver enzymes and function as well as his PT-INR. The patient was subsequently discharged after receiving medical clearance from the consultants with strict clinic-based follow-up. This entailed appropriate counseling with regards to risk factor modification as well as ensuring resolution of jaundice and viral shedding.

Patients affected by HAV can have a highly variable clinical presentation ranging from asymptomatic to fulminant (i.e., a severe sudden onset) liver failure. 1 A significant number of those patients affected are actually asymptomatic, but malaise, fever, and anorexia are the most common presenting symptoms if they occur. 1 These vague symptoms are generally followed by nausea, vomiting, diarrhea, abdominal discomfort, and the eventual development of jaundice. 3 Fulminant HAV, on the other hand, is exceedingly rare occurring in only 1-2% of cases. 4 This is characterized by hepatic failure and progressive encephalopathy (i.e., brain pathology) over a period of days. 4

Patients may also present with rare and specific symptoms as in this case including pale (i.e., acholic) stools and dark urine, both of which are indicative of a conjugated hyperbilirubinemia. This suggests an inability of the liver to expel bilirubin from the bile ducts, either from intrinsic hepatocyte dysfunction or an external obstruction or both. This is compared to an unconjugated hyperbilirubinemia that would typically suggest an abundance of bilirubin being produced for a myriad of reasons. 3 Physical examination findings typically include scleral and/or cutaneous icterus, abdominal tenderness and palpable hepatomegaly. 3 Aside from fever, other vital sign abnormalities may be present, especially with concomitant vomiting, such as orthostatic hypotension and tachycardia.

When managing a patient presenting with jaundice and suspicion for hepatitis, it is especially important to gather a thorough history from the patient and their recent contacts if possible. This history should include any known sick contacts, travel history, illicit drug use, animal exposures, family history, or similar occurrences in the past. Any of these risk categories should lead clinicians to suspect some form of hepatitis as a cause of the patients’ presenting symptoms.

Clinicians being aware of current local epidemiological trends can also be of diagnostic benefit. As of the time of this writing, there had been a dramatic rise in the number of reported cases of acute HAV in Southeastern Michigan. The Michigan Department of Health and Human Services had reported that as of 3/21/18 (beginning 8/1/16) there have been 789 reported cases of HAV related to the outbreak. 5 This condition contributed to 635 hospitalizations (80.5%) and 25 deaths (3.2%).

Of note, Macomb County has the highest number of reported cases at 212 cases which is more than the city of Detroit (i.e, 166 cases). 5 The outbreak is believed to be linked to county-wide opioid and heroin use patterns as over half of the reported cases has some connection with this factor. As in this case, our patient admitted to a history of IV drug use and as was later determined during his hospitalization he also admitted to engaging in other high-risk behaviors including sex with other men. 6

The economic impact of HAV outbreaks has been reviewed both globally as well as on a national level. One 2003 study in particular looked at a Spokane, Washington outbreak and estimated each case of HAV cost $2,683. 7 Most of the expenditures were associated with hospital admissions and lost productivity in the community was also a major indirect factor. The expense of these endemics when compared to vaccination programs and other preventative public health initiatives continues to be an area of epidemiological interest. 8

A HAV diagnosis is typically not made in the ED but suspected cases can be managed expectantly (i.e., monitored closely before treatment) while definitive studies are pending. The differential diagnosis includes bacterial, viral, fungal, parasitic, and alcoholic hepatitis. 1 Also included are causes of extra-hepatic obstruction such as cholelithiasis, cholecystitis, choledocholithiasis, and malignancy of the biliary and pancreatic tissue. 1 Diagnostic imaging is usually indicated in the form of a right upper quadrant ultrasound and possible CT of the abdomen and pelvis. 3

More advanced imaging may be indicated in the form of a MRCP to further distinguish biliary pathology and possibly intervene on a cause of obstruction. The most critical laboratory studies to obtain include a hepatic function panel to assess degree of liver enzyme elevation (transaminitis), hyperbilirubinemia, and PT-INR which serves as the most accurate representation of hepatic impairment. 4 Definitive studies for acute HAV (as well as HBV and HCV) can be obtained through a viral hepatitis panel. Acute HAV is indicated by positive Anti-HAV IgM whereas IgG indicates past exposure (when not co-existing with IgM). 9

Management of acute HAV includes IV fluids and electrolyte correction, anti-emetics, and avoidance of hepatotoxic medications (e.g., acetaminophen and ciprofloxacin) and alcohol intake. 1 Antiviral and antibiotic medications are not indicated in uncomplicated acute HAV. 1 Hospitalization is generally reserved for those with intractable vomiting, severe electrolyte or fluid imbalance, altered mental status, a PT-INR greater than 1.5, or any other evidence of fulminant disease. 1 Otherwise stable individuals can be safely discharged with a presumptive diagnosis and strict clinic-based gastroenterology follow-up. Patients should be instructed on strict hand hygiene and those working in the food industry should delay return to work until their jaundice has resolved. 6

According to the latest federal Centers for Disease Control (CDC) guidelines, unvaccinated persons who have been exposed recently to HAV should be administered one dose of the single-antigen HAV vaccine or immune globulin (IG) as soon as possible and within two weeks after exposure. 9 IG is preferred for those less than 12 months old and greater than 40 years old, immunocompromised persons with chronic liver disease, and those who are allergic to the vaccine. 9

As for primary prophylaxis, the CDC and the Advisory Committee on Immunization Practices (ACIP) recommends that all children at one year of age, those at increased risk for infection or complications from HAV, and any person wishing to obtain immunity should receive the vaccination. 6 The HAV vaccine has been available since 1995 and has resulted in a 95% decline in the incidence of disease. 6 Despite the apparent success of the vaccine, mandatory administration is not the norm owing largely to the fact that the disease is rarely fatal, has no chronic carrier state, and has an overall low incidence in the United States. 2

CONCLUSIONS

In this paper, the authors reported on the presentation of a patient with an acute HAV infection. A presumptive diagnosis of hepatitis was made in the ED based on the patient’s historical risk factors with symptomatology, coupled with supporting laboratory findings. The case was complicated by the findings on imaging suggestive of acute cholecystitis. Appropriate lab value serologies were obtained and supportive care was provided which resulted in a short hospital admission with gradual improvement in symptoms and liver function. This case illustrates the importance of clinicians observing a broader differential diagnosis as well as having an understanding of the illness course and possible complications. This case report example further stresses the significance of clinicians considering local epidemiological trends and how this may aid in diagnosis and appropriate management thereafter.

Conflict of Interest

The authors declare no conflict of interest.

The authors report no external funding source for this study.

Submitted : September 15, 2018 EDT

Accepted : December 15, 2018 EDT

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Hepatitis A

WHO position paper on Hepatitis A vaccines

WHO position paper on hepatitis A vaccines – October 2022

This version updates and replaces the previous vaccine position paper published in June 2012.

Additional materials

Related pages, who hepatitis a vaccine global market study, february 2023 who hepatitis a vaccine global market study, february 2023.

Vaccines and immunization

Water, sanitation and hygiene (WASH)

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• Published: 11 August 2024

The spatial-temporal distribution of hepatitis B virus infection in China,2006–2018

• Liping Jiao 1 ,
• Tuo Shen 1 ,
• Yingzi Han 1 ,
• Wen Liu 2 ,
• Wei Liu 1 ,
• Lin Dang 1 ,
• Mingmin Wei 1 ,
• Yunyun Yang 1 ,
• Jingjing Guo 1 ,
• Meirong Miao 1 &
• Xiangming Xu 1  

BMC Infectious Diseases volume  24 , Article number:  811 ( 2024 ) Cite this article

219 Accesses

Metrics details

Hepatitis B is a liver disease caused by Hepatitis B virus (HBV) infection and is highly prevalent in China. To better understand the epidemiological characteristics of hepatitis B in China and develop effective disease control strategies, we employed temporal and spatial statistical methods.

We obtained HBV incidence data from the Public Health Science Data Center of the Chinese Center for Disease Control and Prevention for the years 2006 to 2018. Using Geographic Information System (GIS) and SaTScan scanning technology, we conducted spatial autocorrelation analysis and spatiotemporal scan analysis to create a map and visualize the distribution of hepatitis B incidence.

While hepatitis B incidence rebounded in 2011 and 2017, the overall incidence in China decreased.In the trend analysis by item, the incidence varies from high to low. The global spatial autocorrelation analysis revealed a clustered distribution, and the Moran index analysis of spatial autocorrelation within local regions identified five provinces as H-H clusters (hot spots), while one province was an L-L cluster (cold spot). Spatial scan analysis identified 11 significant spatial clusters.

Conclusions

We found significant clustering in the spatial distribution of hepatitis B incidence and positive spatial correlation of hepatitis B incidence in China. We also identified high-risk times and regional clusters of hepatitis B incidence.

Peer Review reports

Hepatitis B virus (HBV) infection is a major global public health challenge due to its high prevalence worldwide. HBV causes liver disease which can lead to serious complications such as fulminant hepatitis, cirrhosis, liver failure, hepatocellular carcinoma, and even death [ 1 ]. The virus can replicate indefinitely and infect liver cells, posing a significant risk to human health [ 2 , 3 ]. Clinical manifestations of the disease include weakness, anorexia, nausea, abdominal distension, and pain in the liver area. Chronic liver disease, spider nodes, laminitis, splenomegaly, and abnormal or persistent liver function can also accompany severe disease, which can be classified as mild, moderate, or severe depending on the clinical presentation.

HBV spreads through contact with blood and bodily fluids, and it is highly infectious, with the ability to survive for more than seven days in a stable external environment [ 4 ]. Chronic hepatitis B affects an estimated one in 12 people and the virus infects approximately 257 million people worldwide, with about 800,000 deaths annually due to cirrhosis and hepatocellular carcinoma [ 5 ]. HBV carriers are more likely to develop hepatocellular carcinoma (HCC) and end-stage liver disease, while patients with chronic hepatitis B (CHB) are more likely to develop cirrhosis and HCC, leading to approximately one million deaths each year [ 6 , 7 ]. In 2016, the World Health Organization (WHO) set a goal to eliminate hepatitis B as a public health threat by 2030, aiming to reduce new cases of chronic infection by 95% and mortality by 65% [ 8 ].

Hepatitis B is the third communicable disease among cancers in China [ 9 ], with over 93 million people carrying the virus, of whom approximately 20 million have chronic hepatitis B [ 10 ]. HBV infection is responsible for 56% of hepatocellular carcinoma (HCC) [ 11 ], which is the major histologic type of primary liver cancer. More than half of the world’s HCC incident and mortality occur in China [ 12 ], with an estimated annual number of cases and deaths from liver cancer for men and women being 360,000 and 350,000, respectively [ 13 ]. The Sustainable Development Goals (SDGs) prioritize combating hepatitis, waterborne diseases, and other infectious diseases, which are significant impediments to achieving the SDGs [ 14 ].

Serologic surveys conducted in 1979 and 1992 revealed that HBV was extremely common in China, with a hepatitis B surface antigen (HBsAg) prevalence of 10% [ 15 ]. The second national cross-sectional seroepidemiological hepatitis survey in China, conducted in 1992, revealed that the prevalence of hepatitis B surface antigen in people aged 1–59 years was 9.75%, indicating a large prevalence area for hepatitis B. According to the findings of this survey, an estimated 120 million Chinese people have HBsAg, 20 million have chronic viral hepatitis B, and nearly 300,000 die each year from HBV chronic infection [ 16 ].

Disease spread can vary significantly depending on time and location [ 17 ], making spatial and temporal distribution an important factor to consider when planning disease control measures for severe infectious disease outbreaks [ 18 ]. Epidemiological studies have shown that spatio-temporal analysis is critical for identifying trends in disease spread and determining the geographical distribution of infectious diseases [ 19 ]. To this end, researchers have utilized geographic information systems (GIS) to examine the spatio-temporal distribution of various infectious diseases, including H7N9 [ 18 ], cutaneous leishmaniasis [ 20 ], hepatitis B [ 21 ], and hepatitis C [ 22 , 23 ].

This study utilised the spatial autocorrelation, spatial clustering, and spatiotemporal scanning functionalities of Geographic Information Systems (GIS) to gain a new perspective on the geographical distribution and temporal changes of hepatitis B in China. The spatio-temporal distribution of different types of hepatitis (A, B, C, E) in various regions of China has been examined in prior studies [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. For instance, significant characteristics of spatio-temporal distribution in hepatitis incidence have been unveiled through the application of descriptive epidemiology, spatial autocorrelation analysis, and spatio-temporal scan statistics [ 24 , 26 , 28 ]. The INLA method was utilized to incorporate spatio-temporal models and reveal noteworthy features of spatio-temporal distribution in hepatitis B within Xinjiang [ 27 ]. Spatio-temporal epidemiological methods were employed to identify clustering patterns and dynamic changes in HCV genotype distribution in Shanghai. This indicates that the composition of different transmission routes for HCV infection is constantly evolving [ 23 , 29 ]. Furthermore, a study investigated the spatio-temporal changes and spatial drivers influencing hepatitis-related mortality across 183 countries [ 25 ].

However, prior to this research, no systematic and comprehensive GIS study had been conducted to assess the incidence rate of hepatitis B in China. Therefore, our study fills this research gap by offering a new viewpoint for gaining deeper insights into the spatiotemporal distribution of hepatitis B in China.

This research collected data on the incidence rate of hepatitis B in China from 2006 to 2018. GIS technology was used for spatial autocorrelation analysis and spatio-temporal scanning analysis to examine the spatiotemporal distribution characteristics of hepatitis B across different provinces in China. Spatial autocorrelation analysis was used to identify hotspot areas for hepatitis B, while spatiotemporal scanning analysis revealed transmission trends and patterns at various times and locations. This research contributes to a deeper understanding of the geographical epidemiological characteristics of hepatitis B and provides a scientific foundation for developing targeted prevention and control strategies.

Materials and methods

Data collection of hepatitis b.

Data Collection for Hepatitis B: We collected data on hepatitis B infectious diseases from the Public Health Science Data Center [ 30 ], which is published by the Chinese Center for Disease Control and Prevention’s Information System, for the period from 2006 to 2018. This database has been collecting hepatitis B data from all 31 provinces (excluding Hong Kong, Macau, and Taiwan) since 2005. The data includes case numbers, deaths, incidence, and mortality. All cases of hepatitis B infectious diseases were identified using the diagnostic criteria and management principles for notifiable infectious diseases of the National Health Commission of the People’s Republic of China. We obtained the provincial population data from the China Statistical Yearbook of the China National Bureau of Statistics for the same period. To calculate the incidence of hepatitis B, we used the number of hepatitis B cases and the total population in each province as the numerator and denominator, respectively. We created a comprehensive spatial analysis database by linking and matching the hepatitis B incidence data with the national vector map (1:1,000,000) using the serial number in the attribute database.

Trend analysis of different project segments

We divided the analysis points into five categories: the number of provinces with incidence rates greater than 100/100,000 per year, the season, the age group, the geographical area, and the dynamics of hepatitis B case development, which we used to show the trend of hepatitis B changes from 2006 to 2018. We counted and plotted the incidence rate of hepatitis B for each year, as well as the number of provinces with incidence rates greater than 100/100,000 in the current year, to observe the trend over time. We used seasonal analysis to statistically analyze the hepatitis B incidence by dividing it into four seasons (spring, summer, autumn, and winter). We divided the population into four groups for age group analysis, based on the WHO age classification criteria: adolescents (0–19), youth (19–45), middle-aged (46–59), and the elderly (60+), and investigated the incidence of hepatitis B in each group. Geographic regional analysis was carried out by dividing China into seven regions: North China, South China, Central China, East China, Northwest China, Southwest China, and Northeast China, and analyzing the change in the hepatitis B incidence rate in each. We examined the dynamics of hepatitis B case development from 2006 to 2018 based on absolute growth, development rate, and growth rate. Finally, we subdivided each group into corresponding components for synthetic statistical analysis using Excel to observe overall incidence trends and dynamics from 2006 to 2018 [ 31 , 32 , 33 , 34 , 35 , 36 ].(Annual Absolute increment = Current period incidence cases — Previous period incidence cases; Cumulative absolute increment = Current period incidence cases — Base period incidence cases; Fixed-base development Speed = Current period incidence cases ÷ Base period incidence cases × 100%; Link-Relative development Speed = Current period incidence cases ÷ Base period incidence cases× 100%; Fixed-period increase Velocity = Fixed-base development Speed — 1; Link-Relative increase Velocity = Link-Relative development Speed — 1).

Spatial autocorrelation analysis

We calculated the annual incidence of hepatitis B in China from 2006 to 2018 using spatial autocorrelation analysis and geographic information system localization. To create a spatial weight matrix, we used the spatial conceptualization approach based on inverse distance, which takes into account the geographically adjacent relationships between China’s province administrative regions. We employed ArcGIS 10.2 software to determine both the global and local Moran’s I indices based on the specified weight matrix [ 37 ]. The global Moran’s I assesses the overall spatial autocorrelation and spatial distribution of the research objects, while the local Moran’s I describes the spatial autocorrelation and clustering areas in local areas. The global Moran’s I shows the overall level of clustering and the distribution of hepatitis B, while the local Moran’s I specifies the specific clustering regions and categories of hepatitis B, as well as the hotspot analysis of hepatitis B [ 38 ]. Moran’s I statistic is a commonly used spatial autocorrelation statistic, with values ranging from − 1 to 1. A value of I > 0 indicates positive correlation, and the higher the value, the stronger the correlation of the spatial distribution, that is, the more evident the phenomenon of spatial clustering. A value of I < 0 indicates negative correlation, and the lower the value, the weaker the correlation. When I tends to 0, this means that the spatial distribution exhibits a random distribution [ 39 ].

Spatial clustering analysis

Moran’s I is typically assessed using the Z-score test statistics, where differences with P  < 0.05 are considered statistically significant. Local Moran’s I avoids the drawback of global spatial autocorrelation by analyzing the spatial autocorrelation of some of the features within a local area. We classified the local Moran’s I clustering results into four categories: high-high, high-low, low-high, and low-low clustering. High-high clustering (HH) indicates that the high-incidence area is surrounded by other high-incidence areas and is a hotspot; high-low clustering (HL) indicates that the high-incidence area is surrounded by low-incidence areas; low-high clustering (LH) indicates that the low-incidence area is surrounded by high-incidence areas; and low-low clustering (LL) indicates that the low-incidence area is surrounded by other low-incidence areas. We identified spatial clusters of hepatitis B by detecting where high-prevalence areas bordered other high-prevalence areas (H-H) and where high-prevalence areas bordered low-prevalence areas (H-L).

This paper investigates the incidence of hepatitis B from 2006 to 2018 and analyzes the time trend of this infectious disease. Kulldorff spatial scanning statistical analysis software SaTScan 9.6 was used to perform clustering analysis [ 40 , 41 ]. SaTScan calculates circular windows of varying sizes and locations to identify high-risk and low-risk areas for hepatitis B clusters in China. We analyze the log-likelihood ratio (LLR) of the inner and outer spatial unit attributes of different window regions and use Poisson distribution for statistical analysis. We then arrange the LLR values of scanned circular windows by size, with larger values indicating statistically significant differences, which suggests the regions contained in this window can identify the most important hepatitis B clusters. The method of arranging LLR values in order of size can identify different levels of clusters, ranging from important to unimportant, which are classified as first, second, third, and so on. In this paper, we use the Monte Carlo method for log-likelihood ratio testing, with 999 tests, a 1-year temporal clustering interval, and a significance level of 0.05. We set the maximum spatial cluster size for the high-risk population in this study at 50% [ 42 ].

We also use ArcGIS 10.2 software to visualize the spatial distribution of hepatitis B incidence in provincial areas of China from 2008 to 2018. We classify similar incidence rates and use the natural segmentation method in ArcMap to divide the hepatitis B incidence in each province in ArcGIS 10.2 software. We mark the incidence rate using the method of grade division, with a dark color system indicating a high incidence rate and a light color system indicating a low incidence rate.

The distribution and temporal trends of HBV cases

Between 2006 and 2018, there was a gradual decrease in the reported annual incidence of hepatitis B in China. The number of provinces with incidence rates greater than 100/100,000 decreased from 13 in 2006 to a minimum of 7 between 2014 and 2016. There was a peak in the number of cases in 2009 and a trough in 2015.Although the incidence of hepatitis B rebounded in 2011 and 2017, the overall trend was downward.(Fig.  1 B). The cumulative analysis of the number of hepatitis B cases nationwide found that, Guangdong Province had the highest number of reported hepatitis B cases (1,748,392 people), followed by Henan Province (1,459,351 people), Hubei Province (858,795 people), Hebei Province (725,426 people), and Sichuan Province (695,962 people) (Fig.  1 A). In 2006, there were 1,109,130 reported cases of hepatitis B in China, and in 2018, there were 999,985 reported cases, indicating a 10.91% decrease in the number of cases over a 13-year period. The average incidence rate was 73.07 cases per 100,000 population (Table  1 ). The overall development of reported cases of hepatitis B followed a downward trend, with the average rate of development was 99.14% and the average growth rate of -0.86% between 2006 and 2018. Although the growth rate fluctuated between years, ranging from − 11.42 to 6.33%, it remained generally downward.

From 2006 to 2018, spring was the season with the highest incidence of hepatitis B, except in 2006(Fig.  2 A1). Except for 2006, summer is the second highest incidence of hepatitis B(Fig.  2 A3).The lowest incidence occurred in the fall or winter, with the lowest incidence in the fall of 2015 at 5.28/100,000 (Fig.  2 A4). The lowest incidence of hepatitis B in winter is 5.70/100,000 in 2015(Fig.  2 A5).The highest incidence in the spring was in 2008 at 8.13/100,000 (Fig.  2 A2). The youth group had the highest incidence rate before 2011, while the midlife group had the highest incidence rate after 2011(Fig.  2 B1). In 2018, the teenager group had the lowest incidence rate at 4.47/100,000 (Fig.  2 B2), and the group of youth had the highest incidence rate in 2007 at 127.36/100,000 (Fig.  2 B3). There was an overall increasing trend in the number of incidences in the midlife and senium groups, with the lowest incidence in these two groups at 2015, with 74.67/100,000 in the midlife group (Fig.  2 B4) and 45.11/100,000 in the senium group (Fig.  2 B5).Before 2013, Northwest China had the highest prevalence while South China had the highest prevalence after 2013 (Fig.  2 C1). The regions with the lowest prevalence were East and Southwest China before 2012 and Northeast China after 2013 (Fig.  2 C1). The highest incidence rate of 212.02/100,000 occurred in Northwest China in 2009, and the lowest rate of 33.11/100,000 people occurred in the Northeast in 2016 (Fig.  2 C1).Overall, the incidence of hepatitis B in North China (Fig.  2 C2), Central China (Fig.  2 C4), Southwest China (Fig.  2 C6),Northwest China (Fig.  2 C7), and Northeast China (Fig.  2 C8)showed an overall decreasing trend during 2006–2018, however, South China (Fig.  2 C5) and East China (Fig.  2 C3)showed an overall increasing trend.

Based on the results of the global spatial autocorrelation analysis, the incidence of hepatitis B decreased from 84.824/100,000 in 2006 to 71.988/100,000 in 2018. Although the hepatitis B.

Number of reported cases of hepatitis B by province, 2006–2018

Number of provinces with more than 100/100,000 hepatitis B prevalence and hepatitis B incidence rates per 100,000 habitants reported in China during 2006–2018 period. The plotted points correspond to incidence rates and the lines consist in short term trends

Analysis of the incidence of hepatitis B by season from 2006 to 2018

Analysis of the incidence of hepatitis B by age group from 2006 to 2018

Analysis of the incidence of hepatitis B by geographic region from 2006 to 2018

incidence rate increased between 2011 and 2017, the overall incidence rate decreased. The Moran index ranged from 0.180 to 0.349 for the mean incidence of hepatitis B. This result showed that it was statistically significant in all years except for 2011 when P  > 0.05, indicating a significant spatial correlation of hepatitis B cases. (Table  2 )

The local spatial autocorrelation analysis revealed that the distribution of hepatitis B incidence in the study area exhibited a clear clustering phenomenon, indicating that it was not random. Figure  3 illustrates the incidence of hepatitis B in different provinces from 2006 to 2018, divided into six tiers based on the severity of the incidence. Different colors indicate varying degrees of incidence, with darker colors indicating higher incidence. For example, the highest hepatitis B incidence rate was 267.44/100,000 in 2007, and the grade range was divided into six tiers from 0.01 to 267.44, namely 0.01–42.75, 42.75–59.48, 59.48–82.46, 82.46–126.9, 126.90-177.96, and 177.96-267.44. During the 13-year period from 2006 to 2018, Qinghai, Xinjiang, Gansu, Guangdong, Fujian, and Shanxi had the highest incidence rates, while Jiangsu, Beijing, Tianjin, Shanghai, and Tibet had the lowest incidence rates (Fig.  3 ).

Figure  4 depicts the spatial clustering map of hepatitis B. The Moran index was used to examine spatial autocorrelation within local regions. Between 2006 and 2018, five H-H clustering areas (hot spots) were identified, namely Xinjiang, Qinghai, Gansu, Ningxia, and Guangdong, but no hot spot clustering area was identified in 2014. Jiangsu is the L-L clustering area (cold spot) that was discovered in 2006, 2011, 2012, and 2014. Tibet was identified as an L-H cluster area for seven consecutive years from 2006 to 2012.

Spatio-temporal scan analysis

Distribution of annual hepatitis B incidence rates in different provinces in China from 2006 to 2018

Annual spatial clustering map for hepatitis B from 2006 to 2018

We employed spatio-temporal scanning analysis to investigate the likelihood of clusters, which were identified based on LLR values. The clusters were divided into the most probable cluster, sub-clusters 1 to 6, and cluster time. Between 2006 and 2018, the spatio-temporal scanning method detected 11 significant spatial clusters, including two most likely spatial clusters and eight sub-clusters. The results showed that Xinjiang and Henan were the most probable clusters with a time span of 2006–2011 and an RR value of 2.31 ( p  < 0.001). Gansu was the center of Sub-cluster 1, with a time span of 2006–2011 and an RR value of 2.97 ( p  < 0.001). Sub-cluster 2 was centered in Hubei and covered five provinces: Hubei, Shandong, Hunan, Fujian, and Guangdong. It had a time span of 2006–2011 and an RR value of 1.32 ( p  < 0.001). Sub-cluster 3 was centered in Shanxi, with a time span of 2010–2015 and an RR value of 1.68 ( p  < 0.001). Sub-cluster 4 was centered in Inner Mongolia, with a time span of 2006–2011 and an RR value of 1.61 ( p  < 0.001). Finally, Sub-cluster 5 was centered in Shaanxi, with a time span of 2006–2009 and had an RR value of 1.07 ( p  < 0.001) (Table  3 ; Fig.  5 ).

After conducting a spatial and temporal scan analysis of 31 provinces and autonomous regions in China, it was found that the most likely clusters in 2006–2011 were centered in Xinjiang and Henan provinces. Specifically, the most likely clusters were centered in Xinjiang 6 times with a cluster center at 23.73’N, 120.96’E and a cluster radius of 398.15 km. Within this range, the average annual incidence rate was 172.58/100,000. The most likely clusters in 2012 and 2017–2018 included eight provinces: Hunan, Hubei, Anhui, Fujian, Henan, Guangdong, Shandong, and Xinjiang. The most likely cluster was centered in Hunan three times with a cluster center located at 23.34’N, 113.36’E, and a cluster radius of 775.30 km. The average annual incidence within this range was 103.87/100,000. The most likely clusters from 2013 to 2016 were found in Guangdong and Hubei. The most likely cluster was centered in Guangdong four times with a cluster center at 19.18’N, 109.74’E and a cluster radius of 524.47 km. Within this range, the average annual incidence was 124.37/100,000. Typically, there are 8 to 12 clusters per year, with 1 to 8 provinces per cluster ( Fig.  6 A).The analysis classified Xinjiang, Gansu, and Qinghai as hotspot areas, areas with high disease incidence, while Jiangsu was classified as a coldspot area, an area with low disease incidence. The results of the local hotspot analysis revealed a total of four cold hotspot areas for the local autocorrelation of hepatitis B incidence nationwide (Fig.  6 B).

Temporal and spatial epidemiological analysis has grown in importance over the years with the advancement of spatial statistics. However, few studies have conducted spatio-temporal analysis of hepatitis B samples. This study employs analytical techniques, such as ArcGIS visual analysis and SatScan scanning statistics, to analyze the spatio-temporal epidemiology of hepatitis B incidence in 31 Chinese provinces from 2006 to 2018. The hepatitis B spatio-temporal analysis provides an understanding of the epidemiological characteristics of the distribution of hepatitis B infectious diseases in China, as well as a scientific basis and reference for effective hepatitis B prevention and treatment policies, as well as more in-depth research and analysis.

The study found that China is transitioning from being highly endemic to moderately endemic for hepatitis B. While the country’s reported cases of hepatitis B are generally decreasing, there is an increasing trend of incidence in some provinces, possibly due to increased access to diagnosis and medical care, as well as improved ability to detect viral hepatitis. These factors could be potential determinants of the temporary trend of HBV infection.

Annual satscan cluster analysis of hepatitis B from 2006 to 2018

Hepatitis B cold hotspot analysis between 2006 and 2018

Hepatitis B spatiotemporal clustering analysis between 2006 and 2018

In recent years, the Chinese government has implemented several measures to improve hepatitis B prevention and control. On the one hand, the risk of hepatitis B virus transmission through blood has been effectively reduced through improved regulation of blood-using institutions and blood collection processes, as well as increased supervision. On the other hand, the hepatitis B vaccination program has been widely implemented in China for the past 30 years, preventing many people from becoming infected with HBV [ 43 ].

The incidence of hepatitis B shows a clear seasonal pattern, with the highest incidence in spring (6.92/100,000) and the lowest in autumn and winter (6.22/100,000). This is consistent with Zhang’s study [ 44 ]. Changes in extrinsic and intrinsic factors that come with the changing of seasons, such as stressful low temperatures and energy metabolism changes in winter, may suppress the immune system during the winter [ 45 , 46 , 47 , 48 , 49 ], leading to increased HBV replication. We suggest that the increase in HBV replication in winter may activate the immune system in some patients, which, coupled with the gradually increasing temperature and other factors in spring, results in the reactivation of chronic HBV infection, leading to chronic hepatitis B flares in the spring.

Before 2011, the majority of hepatitis B cases in China occurred in young people aged 20–45, but after 2011, the majority of cases were in the middle-aged population aged 46–59. This is due in part to a lack of public awareness of hepatitis B, a lack of health awareness among community hepatitis B-positive patients, and a lack of awareness of hepatitis B prevention among medical professionals [ 50 ]. However, the incidence of hepatitis B in the youth group has decreased since China’s hepatitis B vaccine immunization strategy, which includes neonatal hepatitis B vaccination [ 51 ], a combined immunization strategy of mother-infant interruption [ 52 ], and the policy of “catch-up vaccination” for children under 15 years of age [ 53 ]. These measures have had significant prevention and control effects, as previous studies have shown [ 54 , 55 ]. Due to increased vaccination rates, the incidence of hepatitis B in young people has gradually decreased. Prior to the implementation of the EPI, the highest incidence was in the youth group, which later changed to the peak middle-aged group several years later.

From 2006 to 2018, Guangdong Province, Henan Province, and Hubei Province had the highest number of reported hepatitis B cases. Meanwhile, Qinghai Province, Xinjiang Uygur Autonomous Region, and Gansu Province were identified as the top three provinces with the highest incidence rates. Although the number of hepatitis B cases in Guangdong Province was ten times higher than in Qinghai Province, the incidence rate in Qinghai Province was 1.75 times higher than in Guangdong Province. Hepatitis B was primarily found in northwest China before 2013, but after that, the incidence rate of hepatitis B in southern China increased annually, as also reported by Song [ 56 ]. Regional factors, such as geographical conditions, slow economic development, a lack of medical resources, and low public awareness of infectious diseases, are primarily responsible for the higher prevalence of hepatitis B in northwest China compared to the eastern region. China has better medical resources and health investment power in the eastern region than in the central and western regions, such as in the number of medical and health institutions, the number of health personnel, the number of beds in health institutions, equipment, health funding, etc [ 57 ].

The spatial distribution of hepatitis B was not random, with positive correlation and strong spatial aggregation in specific regions. Moran’S I values were all greater than 0 that indicated a significant spatial autocorrelation. The H-H clustering areas were primarily concentrated in five provinces, namely Xinjiang, Qinghai, Gansu, Ningxia, and Guangdong. This suggests that hepatitis B prevention and control measures should be strengthened in these areas. Jiangsu had the highest concentration of L-L clustering areas. According to the results of the local hot spot analysis, Xinjiang, Gansu, and Qinghai were classified as positive hot spots, while Jiangsu was identified as a cold spot region. The economic development, medical resources, customs and habits, and public awareness level were considered to be the primary reasons behind the variation in the incidence rates of hepatitis B in different regions. Since 2013, the hotspot of hepatitis B clusters shifted from northwest to south China, indicating a gradual decrease in hepatitis B incidence in the former region due to national policies. However, the recent increase in incidence in southern China can be attributed to the reduction in misreporting and underreporting of hepatitis B cases, low awareness rate of hepatitis B vaccination, and repeated reporting of infectious disease cards [ 58 ].

While spatial autocorrelation analysis can detect the presence of local aggregation around a region, spatio-temporal scan analysis is necessary to determine the size and extent of the aggregation [ 59 ]. The analysis of the spatial and temporal distribution of hepatitis B incidence revealed that before 2011, the provinces with high incidence were mainly concentrated in Xinjiang and Henan, particularly in Xinjiang, while after 2011, the provinces with high incidence were concentrated in Hunan, Guangdong, and Hubei, followed by Anhui, Fujian, Henan, Guangdong, Shandong, and Xinjiang. This suggests that the incidence of hepatitis B has gradually shifted from western regions to southern China. Over the years, Guangdong and Henan have had the highest number of hepatitis B cases in the country. The risk of clustering has remained high in the Xinjiang, Qinghai, and Henan regions, which may be associated with the persistence of high-risk factors in these regions. Hepatitis B prevalence in these areas is influenced by several factors, including poor living conditions, slow economic development, limited medical resources, and people’s lifestyle habits. The increased incidence of hepatitis B in the south is due to increased mobility resulting from economic development and a lower rate of infectious disease underreporting. Consequently, the government should develop corresponding measures based on the current situation and actively intervene in areas prone to hepatitis B outbreaks to control hepatitis B cases promptly through early detection, early diagnosis, and early treatment.

For this research, all data on hepatitis B since the direct reporting of infectious diseases network in 2006 were collected. Firstly, the trend analysis of five aspects, such as the number of provinces with an annual incidence over 100/100,000, season, age group, geographical area, and the development dynamics of hepatitis B cases, was conducted. Secondly, spatial autocorrelation analysis was used to identify disease spatial aggregation at the survey area scale. Thirdly, local autocorrelation analysis and spatial clustering analysis were used to identify clustering hotspots and positive and negative “hotspot” areas. Finally, the time and extent of aggregation were ascertained using spatial and temporal scan analysis. Combining the above four methods and using a combined spatio-temporal approach, taking into account both the temporal dimension and the spatial-geographic dimension, coinciding with the infectious characteristics of the disease, and gradually deepening the analysis, the study results were made more systematic and complete. The spatio-temporal distribution characteristics and some triggering causes of hepatitis B cases nationwide from 2006 to 2018 were discovered, which are of great importance.

Although spatio-temporal scanning is a valuable tool for analyzing disease distribution and identifying high-risk areas [ 60 ], there are some limitations to our research. Ecological studies are subject to ecological bias [ 61 ], which is an inherent limitation. It is important to note that the data we used can only be used to investigate the spatial and temporal distribution of hepatitis B incidence at the provincial level, but not at the prefecture-level city or local town or district and county levels. Due to the large and imprecise study area, differences in the intensity and quality of hepatitis B disease reporting exist among provinces ( municipalities directly under the Central Government and autonomous regions), as well as regional differences between provinces. Moreover, this research did not assess the potential environmental risk factors and demographic characteristics associated with the different spatial and temporal distributions of hepatitis B. Therefore, further research is necessary to identify geographic factors and develop targeted regional control measures. Follow-up studies at the county and township levels are necessary to develop different models for different regions, which can investigate the underlying causes of spatial autocorrelation and hepatitis B aggregation. This will provide a more comprehensive and targeted framework for developing hepatitis B prevention and control strategies in each province (municipality directly under the Central Government and autonomous region).

Our combined temporal and spatial analysis-revealed significant clustering of hepatitis B incidence across China. The global Moran’s I index confirmed a positive spatial correlation, with high-incidence areas adjacent to other high-incidence areas and low-incidence areas adjacent to other low-incidence areas.The highest incidence rates were observed in Qinghai and Xinjiang, with increasing rates in Guangdong and Fujian over time. Northwest China showed the highest incidence rates, possibly due to local lifestyle and habits, economic development, medical conditions, and personal perceptions.To prevent and control the spread of infectious diseases like hepatitis B, it is critical for the government to closely monitor and implement effective interventions, including timely vaccination and locally appropriate preventive measures.

Data availability

The datas that support the findings of this study are available from the Public Health Science Data Center Database (China CDC), but restrictions apply to the availability of these datas, which were not publicly available. Requests for access to these datas should be sent to the Public Health Science Data Center Database(China CDC). All data generated or analysed during this study are included in this published article and its supplementary information files.

Abbreviations

• Geographic information system

Hepatitis B Virus

Hepatocellular carcinoma

Chronic hepatitis B

World Health Organization

Sustainable Development Goals

Hepatitis B surface antigen

Expanded Program on Immunization

Human Immunodeficiency Virus

Preventing mother-to-child transmission

I Global Moran’s I coefficient

Relative risk

Log likelihood ratio

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Acknowledgements

The authors would like to thank the Chinese Center for Disease Control and Prevention for sharing the valuable data.

The study was funded by the Central public health-related project subsidy funds-Major public health projects: (grant number 2100409). The funder had no role in the study design, data collection and analysis, interpretation of data, and writing the manuscript.

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Liping Jiao, Tuo Shen, Yingzi Han, Wei Liu, Lin Dang, Mingmin Wei, Yunyun Yang, Jingjing Guo, Meirong Miao & Xiangming Xu

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LP J drafted and revised the manuscript, and analyzed the data. LP J, TS designed and implemented the research, and reviewed the manuscript. YZ H, WL1 and WL2 revised the manuscript.LD, MM W, YY Y, JJ G collected and managed the data.MM M, XM X provided the analytical tools for the study. All authors read and approved the final manuscript.

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The study was approved by the Ethical Committee of Weinan Center for Disease Prevention and Control.Because this study constituted public health surveillance rather than research in human beings, and was a retrospective analysis with no ethical issues.Therefore, our study was exempt from ethical review by the Ethics Committee of Weinan Center for Disease Control and Prevention. The datas provided did not have any individual patient details, so the requirement for informed consent was waived by the Ethical Committee of Weinan Center for Disease Prevention and Control.All methods were carried out in accordance with relevant guidelines and regulations.The original datas uesd in this study were obtained from “Public Health Science Data Center Database” with the approval by Public Health Science Data Center of China CDC.

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Jiao, L., Shen, T., Han, Y. et al. The spatial-temporal distribution of hepatitis B virus infection in China,2006–2018. BMC Infect Dis 24 , 811 (2024). https://doi.org/10.1186/s12879-024-09716-z

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The Great Mimicker Gets Caught: A Rare Case of Syphilis in the Gastrointestinal Tract

Carlos cantu lopez.

1 Internal Medicine, Saint Michael's Medical Center, Newark, USA

Sarahi Herrera-Gonzalez

2 Gastroenterology and Hepatology, Saint Michael's Medical Center, Newark, USA

Dema Shamoon

Theodore jr dacosta, yatinder bains.

Syphilis is a sexually transmitted disease that impacts multiple organ systems and can mimic various diseases and is an extremely rare cause of proctitis in men who have sex with men and transgender females. We present a case of a 49-year-old transgender female with a medical history significant for diabetes mellitus and hyperlipidemia who presented to the emergency department with dull abdominal pain in the left upper and lower quadrants for two days. She had non-bloody, nonbilious emesis, 10-pound weight loss over 1 month, and constipation for 2 weeks. Laboratory results showed a cholestatic pattern. Computed tomography of the abdomen showed rectal wall thickening, multiple enlarged perirectal adenopathy, and mild inflammatory infiltration around the rectum suggesting superimposed proctitis. On colonoscopy, a possible rectal mass or severe proctitis with near complete obstruction was seen with initial pathology concerning for lymphoma or a rare type of colitis. The patient was empirically started on ceftriaxone and doxycycline leading to improvement in inflammation. Special stains requested were positive for Treponema pallidum confirming the diagnosis of syphilitic proctitis and highly suggestive syphilitic hepatitis. Few cases of syphilitic proctitis imitating rectal malignancy and syphilitic hepatitis have been reported. Syphilis requires exclusion as well as confirmation of spirochetes for high-risk populations with special staining. It is important to diagnose syphilis in special populations that are at high risk of contraction.

Introduction

Syphilis is a sexually transmitted disease (STD) that presents in a vast number of organ systems. It has been called the “great mimicker,” as it may resemble many other pathologies, therefore, it is important to have a high degree of suspicion in patients with high-risk sexual practices.

Syphilitic proctitis represents only 1% of sexually transmitted proctitis in men who have sex with men (MSM) and transgender females [ 1 ] while syphilitic hepatitis has a described incidence of 0.25% to 38% [ 2 ]. This is a rare case of syphilis presenting in the gastrointestinal tract (GIT) with simultaneous hepatitis and biopsy-proven proctitis, representing the first case reported in the literature since 2011 [ 3 ].

This article was previously presented as a meeting abstract at the 2022 American College of Gastroenterology Annual Scientific Meeting and Postgraduate Course on October 23, 2022.

Case presentation

A 49-year-old transgender female, with a medical history significant for diabetes mellitus and hyperlipidemia, presented to the emergency department, complaining of dull abdominal pain located in the left upper and lower quadrants for two days and associated with multiple episodes of non-bloody, non-bilious emesis. On review of systems, she had unintentional 10-pound weight loss in the last months and a two-week history of constipation with mucous and small-volume bowel movements. She denied fever, dysuria, and rectal bleeding. Laboratory results were significant for a sodium level of 129 (136-145 mmol/L), aspartate aminotransferase (AST) of 397 (10-36 U/L), alanine aminotransferase (ALT) of 224 (6-46 U/L), alkaline phosphatase (ALP) of 889 (33-130 U/L), and total bilirubin of 7.3 (0.2-1.2 mg/dL). Cell counts were all unremarkable. Subsequent testing showed carbohydrate antigen 19-9 of 125.2 (0.0-34 U/mL) and a carcinoembryonic antigen 3.0 (0.0-3.0 ng/mL (Table ​ (Table1 1 ).

Computed tomography (CT) of the abdomen and pelvis with IV contrast showed hepatic steatosis with the normal caliber of the biliary system, focal moderate wall thickening of the rectum with multiple enlarged perirectal adenopathy concerning for a rectal mass, as well as mild inflammatory infiltration around the rectum suggesting superimposed proctitis (Figure ​ (Figure1 1 ).

Images showing hepatic steatosis with a normal caliber of the biliary system (arrowhead), focal moderate wall thickening of the rectum (arrows), and multiple enlarged perirectal adenopathy (A. Axial; B. Coronal; C. Sagittal)

Our differential diagnoses consisted of infectious proctitis, viral hepatitis, primary biliary cholangitis (PBC), ulcerative colitis with primary sclerosing cholangitis, and, of course, rectal malignancy with metastatic liver disease.

A colonoscopy was performed the following day, which revealed a possible rectal mass versus severe proctitis with erythema and inflammation with near complete obstruction which was unable to be traversed (Figure ​ (Figure2 2 ).

Images of initial colonoscopy showing severe inflammation, erythema, and thickened rectal folds with near luminal obstruction prior to the initiation of syphilis treatment (blacked out identifying patient information in the left upper corner of images).

Initial pathology demonstrated a possible lymphoma versus a very rare type of colitis (Figure ​ (Figure3 3 ).

Pathology image of colonic mucosa with marked expansion of the lamina propria by mixed neutrophilic and lymphoplasmacytic infiltrate (arrows), suggestive of lymphoma or a very rare form of colitis

Immunohistochemistry would later rule out lymphoma. Magnetic resonance cholangiopancreatography (MRCP) was unremarkable. Anti-smooth muscle antibody (ASMA), anti-nuclear antibody (ANA), immunoglobulin G (IgG), and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were negative while anti-mitochondrial antibody (AMA) was equivocal at 23.7 (negative <20 Units, equivocal 20.1-24.9 and positive > 24.9) (Table ​ (Table1). 1 ). The viral hepatitis panel showed immunity to Hepatitis A and B, and negative Hepatitis C. Human immunodeficiency virus (HIV) was also negative. The patient was empirically started on ceftriaxone and doxycycline while waiting for an infectious proctitis workup for syphilis, chlamydia, and gonorrhea.

A second colonoscopy was performed four days later, and although still present, a significant decrease in overall inflammation was noted. Colonoscopy was otherwise grossly unremarkable proximal to the rectum. Chlamydia and gonorrhea tests were both negative, while rapid plasma reagin (RPR) was weakly positive at 1:4 titer. A fluorescent treponemal antibody-absorption test was sent for confirmation and was positive. One month prior to the presentation, all labs including RPR were negative. Special stains were requested and resulted in positive for Treponema pallidum (Figure ​ (Figure4) and 4 ) and negative for human Herpesvirus-8 (HH8), confirming the diagnosis of syphilitic proctitis and highly suggestive syphilitic hepatitis. Prior to discharge, transaminases and bilirubin were significantly decreased. She received a one-month course of doxycycline with a resolution of symptoms.

Syphilis is the cause of sexually transmitted proctitis in only 1% of MSM and transgender females [ 1 ]. Diagnosis requires a high index of suspicion in populations who engage in high-risk sexual behaviors. Given that spirochetes are not seen on pathology specimens with routine hematoxylin and eosin stains, special staining for spirochetes must be explicitly requested of the pathologist [ 4 ].

Syphilitic proctitis may mimic rectal tumors on imaging and endoscopy, as well as clinical presentation such as in our patient. Bronson et al. (2021) described a case of rectal syphilis presenting with a palpable mass and imaging studies showing rectal wall thickening and enlarged pelvic lymph nodes [ 5 ]. Initial pathology was suggestive of lymphoma but was subsequently ruled out by immunohistochemistry. Finally, the diagnosis of syphilitic proctitis was made by positive spirochetes staining [ 5 ]. A few other cases of syphilitic proctitis imitating rectal malignancy have been reported [ 6 , 7 ]. Treatment is with benzathine penicillin G, and doxycycline or tetracycline for patients with penicillin allergy [ 8 ].

Syphilitic hepatitis is also very rare, with priorly reported incidence ranging between 0.25% and 38% [ 2 ]. It presents mostly with elevation of liver function tests (LFTs) in a cholestatic pattern. Presents by causing intrahepatic cholestasis with normal biliary tract anatomy on imaging. Tissue diagnosis is not generally required and may be done by a combination of abnormal LFTs, serological evidence of syphilis, exclusion of other causes of liver disease, and normalization of LFTs after treatment (all four criteria required) [ 9 ]. When histopathologic samples are obtained, commonly seen findings include hepatic granulomas and biliary ductal inflammatory infiltration [ 10 ].

A case of syphilis hepatitis mimicking PBC was described by Kern et al. In their case, a positive AMA was seen, which also turned negative after treatment for syphilis [ 11 ]. While our patient had an equivocal result, this was likely elevated due to syphilis involvement of the liver.

Conclusions

Syphilis is an uncommon yet potentially severe cause of pathology in the GIT. It most frequently presents impersonating serious causes of pathology. It is imperative to perform careful evaluation and proper history-taking in high-risk populations, with particular attention to sexual history. Like in our patient’s case, recognizing that multiple organ systems may be simultaneously involved may facilitate the prompt diagnosis and management of this great mimicker.

The authors have declared that no competing interests exist.

Author Contributions

Concept and design:   Sarahi Herrera-Gonzalez, Dema Shamoon, Theodore Jr Dacosta, Yatinder Bains, Carlos Cantu Lopez

Acquisition, analysis, or interpretation of data:   Sarahi Herrera-Gonzalez, Dema Shamoon, Theodore Jr Dacosta, Yatinder Bains, Carlos Cantu Lopez

Drafting of the manuscript:   Sarahi Herrera-Gonzalez, Dema Shamoon, Theodore Jr Dacosta, Yatinder Bains, Carlos Cantu Lopez

Critical review of the manuscript for important intellectual content:   Sarahi Herrera-Gonzalez, Dema Shamoon, Theodore Jr Dacosta, Yatinder Bains, Carlos Cantu Lopez

Supervision:   Theodore Jr Dacosta, Yatinder Bains

Human Ethics

Consent was obtained or waived by all participants in this study