Observational Study of Persons With Hepatitis B Virus Infection in North America (Cohort Study)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Pittsburgh
- Enrollment
- 2,051
- Locations
- 21
- Primary Endpoint
- Hepatitis Exacerbation marked by alanine aminotransferase (ALT) Flare
Study Overview
Brief Summary
The primary purpose of this study is to describe participants with hepatitis B virus (HBV) infection and identify factors that may cause the disease to activate or worsen.
Detailed Description
Aims
- Primary Aim:
o To describe participants with hepatitis B virus (HBV) infection in a prospective cohort in the United States (US) and Canada and identify predictors of disease activation and progression
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Secondary Aims:
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To describe clinical, virological, and immunological characteristics of participants with HBV in the US and Canada
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To evaluate changes in HBV infection status and quantitative hepatitis B surface antigen (HBsAg) levels and factors associated with those changes
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To verify whether a baseline HBsAg below 1,000 IU/mL and HBV DNA below 1,000 IU/mL is an accurate predictor of people who are, or who will become, inactive carriers, defined as people who are HBsAg positive, hepatitis B "e" antigen (HBeAg) negative, have normal Alanine transaminase (ALT) and HBV DNA under 1,000 IU/mL on at least two occasions over a period of at least 6 months
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To develop a bank of biospecimens (e.g., serum, plasma, DNA, lymphocytes, liver tissue) obtained from participants with HBV infection
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To identify participants with HBV infection who are potential candidates in one of the treatment studies to be conducted by the Hepatitis B Research Network (HBRN)
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To describe the natural history of hepatitis B infection in pregnancy including the frequency of, and clinical and virological characteristics associated with, hepatic flares during pregnancy and post-partum.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Hepatic decompensation
- •Hepatocellular carcinoma (HCC)
- •Liver transplantation
- •Current hepatitis B antiviral treatment (except pregnant women and patients who are anti-HDV positive)
- •Known Human immunodeficiency virus (HIV) co-infection (patients with Hepatitis D (HDV) or Hepatitis C (HCV) co-infection are not excluded).
- •Medical or social condition which in the opinion of the investigator will interfere with or prevent follow-up per protocol
- •Unable or unwilling to return for follow-up visits
Outcomes
Primary Outcomes
Hepatitis Exacerbation marked by alanine aminotransferase (ALT) Flare
Time Frame: up to 288 weeks
A flare is defined as serum ALT greater than or equal to 10 times the upper limit of normal which corresponds to 300 IU/L in males or 200 IU/L in females. This definition will also be applied to hepatitis B surface antigen (HBsAg) positive pregnant women whose ALT levels increase during pregnancy or postpartum. Once a flare is detected, participants will be followed more closely until its resolution.
Antigen loss: e and s
Time Frame: up to 288 weeks
Loss of these viral markers may be associated with appearance of corresponding antibodies in serum (anti-HBe or anti-HBs). HBsAg loss appears to represent a "cure" of HBV infection and is associated with reduction, but not necessarily elimination, of the risk of future complications, such as Hepatocellular carcinoma (HCC) which may occur, particularly in those who lose HBsAg at an older age (after 50 years) or after the development of cirrhosis. When HBeAg or HBsAg loss occurs, participants will be followed more closely initially and then return to the regular follow-up schedule.
Hepatic decompensation
Time Frame: up to 288 weeks
Development of hepatic decompensation will be defined by any of the following events: * Ascites or hepatic hydrothorax * Variceal or portal hypertensive bleeding * Hepatic encephalopathy * Child-Turcotte-Pugh (CTP) score of 7 or above It is anticipated that there will be a small number of participants who will develop hepatic decompensation during follow-up.
Cirrhosis
Time Frame: up to 288 weeks
Once cirrhosis is diagnosed, follow-up will include hepatocellular carcinoma (HCC) surveillance. HCC surveillance will also be performed in non-cirrhotic participants who meet American Association for the Study of Liver Disease guidelines criteria.
Hepatocellular carcinoma (HCC)
Time Frame: up to 288 weeks
Hepatocellular carcinoma (HCC) may be detected by routine surveillance or may become clinically apparent. The diagnosis of HCC will be made using the American Association for the Study of Liver Disease criteria.
Death
Time Frame: up to 288 weeks
Death may occur related to liver disease (typically hepatic decompensation or Hepatocellular carcinoma) or may occur unrelated to hepatitis B or liver disease. Date and cause of death will be recorded.
Liver transplantation
Time Frame: up to 288 weeks
Liver transplantation will be recorded upon notification. Date of transplantation, indication for transplantation, and occurrence of incidental Hepatocellular carcinoma (HCC) will be recorded. Follow-up ends with liver transplantation.
Secondary Outcomes
No secondary outcomes reported
Investigators
Anna Lok
Study Chair
University of Michigan