Management of Chronic Hepatitis B: Evidence Report / Technology Assessment Number 174

Publisher Marketing: Hepatitis B is a highly prevalent disease with 350 million chronic cases worldwide and more than 4,000 incident cases in the U. S. in 2006. An estimated 2,000 to 4,000 deaths per year are related to Chronic Hepatitis B (CHB) liver diseases. The natural history of CHB is variable but generally indolent for many years to decades. Only 5% of acutely infected immunocompetent adults develop CHB. Demographic, clinical, and hepatitis B disease factors are believed associated with the development of CHB and poorer prognosis among those who develop CHB. Treatment goals include prevention of cirrhosis, hepatocellular cancer, and liver failure. Suppressing replication of hepatitis B virus (HBV) is believed a key process to achieving this goal. Hepatitis B treatments include nucleos(t)ide analogues that suppress viral replication and interferons, naturally occurring cytokines with antiviral and immunomodulatory properties. Six agents used as monotherapy or in combination have been approved, as of June 2008, for use in the U. S. A seventh, tenovir, was approved in August 2008. Two basic therapeutic approaches exist. A defined self-limited course (e.g., 4-12 months) followed by monitoring off treatment is generally used with interferon-based therapy. Long-term continuous suppressive therapy is used for other direct antiviral agents. Researchers have proposed clinical outcomes and biochemical, virologic, and histologic measures to determine an individual's risk for disease progression, identify candidates for treatment, and assess treatment effectiveness and harms. The Minnesota Evidence-based Practice Center (EPC) conducted a review to address the following questions for a National Institutes of Health (NIH) Consensus Conference related to Management of Chronic Hepatitis B in Adults. Consensus conference question 1. What is the natural history of Hepatitis B? EPC question 1. What is the evidence that the following population characteristics or clinical features associated with hepatitis B are predictive of hepatocellular carcinoma, liver failure, cirrhosis, liver-related death, and all-cause mortality? Consensus conference question 2. What are the benefits and risks of the current therapeutic options for hepatitis B with defined or continuous courses of treatment? EPC question 2a. What is the efficacy (or effectiveness) of interferon therapy, oral therapy, and various combinations in treating hepatitis B with defined or continuous courses of treatment? EPC question 2b. What are the known harms of interferon therapy, oral therapy, and various combinations in treating hepatitis B with defined or continuous courses of treatment? Surrogate outcomes of interest. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels, HBV viral load, change in Hepatitis B e antigen (HBeAg) status, hepatitis B surface antigen (HBsAg) conversion, liver biopsy findings (necroinflammatory activity or stage of fibrosis), and drug resistance. Clinical outcomes of interest include hepatocellular carcinoma, liver failure, cirrhosis, liver related death, all-cause mortality. Consensus conference question 3. Which persons with hepatitis B should be treated? EPC question 3a. Are there differences in efficacy/effectiveness of treatments for treatment naive versus drug-resistant patients, chronic HBeAg-positive versus HBeAg-negative patients, or for other subpopulations? EPC question 3b. Is there evidence that specific subpopulations do not require treatment for hepatitis B? Consensus conference question 4. What measures are appropriate to monitor therapy and assess outcomes? EPC question 4. What is the evidence that changes in surrogate endpoints in response to treatment are reliable predictors of long-term resolution or slowed progression of disease? Patient Population: Adults (18 years of age or older), including elderly and members of racial/ethnic minority populations.