GASTROENTEROLOGY 1997;113:1660 – 1667 Long-term Follow-up of Patients With Chronic Hepatitis B Treated With Interferon Alfa DARYL T. – Y. LAU,* JAMES EVERHART, ‡ DAVID E. KLEINER, § YOON PARK, x JOHN VERGALLA,* PETER SCHMID, Ø and JAY H. HOOFNAGLE* ,‡ *Liver Diseases Section, Digestive Diseases Branch, ‡ Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, § Laboratory of Pathology, National Cancer Institute, and x Clinical Center, National Institutes of Health, Bethesda, Maryland; and Ø National Genetics Institute, Los Angeles, California Background & Aims: Therapy with interferon alfa (IFN- or death. Small follow-up studies 10,11 have reported that a) leads to remission of disease in one third of patients remissions in chronic hepatitis B induced by IFN-a are with chronic hepatitis B. The aim of this study was to of long duration, but the survival of treated patients has better define the long-term prognosis of this outcome. not been well defined. A recent study reported that the Methods: One hundred three patients with chronic hep- frequency of death, liver transplantation, and severe com- atitis B who underwent IFN-a therapy in three clinical plications due to cirrhosis was significantly lower among trials between 1984 and 1991 were followed up for patients who responded to IFN-a treatment than those serological status, biochemical evidence of liver dis- who did not. 12 ease, and liver complications or mortality through The aim of the current study was to further evaluate 1994. Results: Among 103 patients, 31 (30%) re- the long-term survival and clinical outcome of a cohort sponded to therapy with loss of hepatitis B e antigen of patients with chronic hepatitis B who were treated and viral DNA from serum. Responders were more likely with IFN-a. than nonresponders to be women, black, and to have more severe liver disease including cirrhosis (P õ Materials and Methods 0.05). Up to 11 years (mean, 6.2 years) after therapy, a higher percentage of responders than nonresponders Patients were still negative for hepatitis B e antigen (94% vs. A total of 103 patients with chronic hepatitis B re- 40%; P õ 0.001) and hepatitis B surface antigen (71% ceived IFN-a-2b (Intron A; Schering Corp., Kenilworth, NJ) vs 8.3%; P õ 0.001). Overall, the rate of liver-related in three clinical research protocols conducted at the National complications and death did not differ by IFN-a re- Institutes of Health between 1984 and 1991. 3,7 All patients sponse, but with adjustment for cirrhosis, nonrespond- had chronic hepatitis B with elevations of serum aspartate ers had higher rates of liver-related complications and aminotransferase (AST) and/or alanine aminotransferase (ALT) mortality (hazard ratio, 13.7; 95% confidence interval, levels for 6 months or more and hepatitis B surface antigen 3.0 – 63.5). Conclusions: The response to IFN-a ther- (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA in apy in chronic hepatitis B is usually a sustained im- serum before therapy. Pretreatment liver biopsies were per- provement in disease markers and, when cirrhosis is formed, and all patients had histological evidence of chronic considered, patient outcome. hepatitis B. Patients with decompensated liver disease, with other major illnesses, with other known causes of liver disease, or with serological evidence of hepatitis delta virus (HDV) C coinfection were excluded. Tests for antibody to human immu- hronic infection with hepatitis B virus (HBV) affects Ç5% of the world’s population and at least 1 mil- nodeficiency virus (HIV) became available during the course lion Americans. 1 Hepatitis B is an important cause of of these studies, and patients with antibody to HIV were not chronic hepatitis and cirrhosis and perhaps the major excluded until 1988. cause of hepatocellular carcinoma worldwide. There are The initial study was conducted between 1984 and 1986 no completely satisfactory therapies for hepatitis B. Most in 45 patients who were randomly assigned to receive either extensively evaluated has been interferon alfa (IFN-a), IFN-a in doses of 5 MU daily for 16 weeks (total dose, 560 which has been reported to induce remissions of disease MU; n Å 16) or in doses of 10 MU every other day for 16 in 25%–40% of patients. 2–9 The duration of follow-up Abbreviations used in this paper: bDNA, branched DNA; HIV, human in most studies of IFN-a therapy has been 1–2 years, immunodeficiency virus; IFN-a, interferon alfa; PCR, polymerase which is too short to predict the ultimate prognosis of chain reaction. these patients regarding the development of cirrhosis,  1997 by the American Gastroenterological Association 0016-5085/97/$3.00 decompensated liver disease, hepatocellular carcinoma, / 5E22$$0040 10-07-97 23:35:45 gasa WBS-Gastro