HBRN: Hepatitis B Research Network Adult Cohort Study

Sponsor

University of Pittsburgh (Other)

Overall Status

Completed

CT.gov ID

NCT01263587

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), National Center for Research Resources (NCRR) (NIH)

2,051

Enrollment

Locations

126.3

Duration (Months)

97.7

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B

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

Secondary Aims:
To describe clinical, virological, and immunological characteristics of participants with HBV in the US and Canada
To evaluate changes in HBV infection status and quantitative hepatitis B surface antigen (HBsAg) levels and factors associated with those changes
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
To develop a bank of biospecimens (e.g., serum, plasma, DNA, lymphocytes, liver tissue) obtained from participants with HBV infection
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)
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

Actual Enrollment :

2051 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Observational Study of Persons With Hepatitis B Virus Infection in North America (Cohort Study)

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Jun 9, 2021

Actual Study Completion Date :

Jun 9, 2021

Outcome Measures

Primary Outcome Measures

Hepatitis Exacerbation marked by alanine aminotransferase (ALT) Flare [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 [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.
Cirrhosis [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.
Hepatic decompensation [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.
Hepatocellular carcinoma (HCC) [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 [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

The study population will be recruited from multi-site clinical centers in the United States and Canada including primary care hospitals and community centers.

Inclusion criteria

Written informed consent
At least 18 years of age
Hepatitis B surface antigen (HBsAg) positive and either:
Pregnant
Anti-Hepatitis D positive
Diagnosed with acute Hepatitis B infection or experiencing a hepatitis flare
Immune tolerant or immune active phenotype
Potentially eligible for the Immune Regulation and Costimulation in Natural History of Chronic Hepatitis B ancillary study (NCT01298037).

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
2	University of California Los Angeles	Los Angeles	California	United States	90095
3	California Pacific Medical Center	San Francisco	California	United States	94115
4	University of California San Francisco	San Francisco	California	United States	94143
5	The Queen's Medial Center	Honolulu	Hawaii	United States	96813
6	NIH Clinical Center	Bethesda	Maryland	United States	20892
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
8	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
9	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
10	University of Minnesota	Minneapolis	Minnesota	United States	55455
11	Mayo Clinic	Rochester	Minnesota	United States	55905
12	Saint Louis University	Saint Louis	Missouri	United States	63104
13	Washington University	Saint Louis	Missouri	United States	63108
14	University of North Carolina	Chapel Hill	North Carolina	United States	27599
15	Duke University Medical Center	Durham	North Carolina	United States	27710
16	Baylor University Medical Center	Dallas	Texas	United States	75246
17	University of Texas Southwestern	Dallas	Texas	United States	75390
18	Virginia Commonwealth University Medical Center	Richmond	Virginia	United States	23298
19	Virginia Mason Medical Center	Seattle	Washington	United States	98101
20	Harborview Medical Center	Seattle	Washington	United States	98104
21	Toronto Western Hospital Liver Centre	Toronto	Ontario	Canada