Pegylated Interferon Alfa in HBeAg-positive Chronic Hepatitis B

Word-wide, infection with the hepatitis B virus (HBV) is a major health problem. Over 2 billion people have been exposed to HBV, and approximately 400 million are chronic carriers of the virus. Chronic hepatitis B (CHB) infection may lead in term to liver cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC), and is responsible for an estimated 1 million deaths annually. The efficacy of the established treatment for CHB is limited.Treatment with conventional interferon (IFN) is only effective in 20-35%. Lamivudine needs to be given long-term to maintain response and leads to emergence of viral resistant strains. Several studies have investigated different treatment options such as peginterferon, adefovir and entecavir.The first randomized controlled trial in HBeAg-positive CHB with peginterferon - which had proven to be more effective than conventional IFN in chronic hepatitis C patients demonstrated that a 52-week course of peginterferon alfa-2b leads to HBeAg seroconversion in 36%, ALT normalization in 35% and HBV DNA < 2.0 x 105 copies/mL in 32% of patients at the end of post treatment follow-up.The addition of lamivudine did not enhance response rates compared to peginterferon alfa-2b alone.The use of conventional IFN is not suited for all patients due to the significant side effects and early treatment discontinuation that may occur.Although the safety profile of peginterferon has been studied in chronic hepatitis C, the side effects of peginterferon in CHB patients have not previously been investigated. We assessed the safety of peginterferon treatment in 266 HBeAg-positive patients who received peginterferon alfa-2b alone or in combination with lamivudine (chapter 2). The most common side effects were similar to those reported for conventional IFN. Flu-like symptoms, headache, fatigue, myalgia, local reaction at the injection, abdominal discomfort and psychiatric symptoms were most frequently reported, but in general subsided during the course of therapy. Hematologic abnormalities (leucopenia, neutropenia and thrombocytopenia) were frequent but did not lead to serious infections or bleeding complications. Neutropenia was the major cause for dose reductions of peginterferon, whereas psychiatric symptoms (depression, psychosis) were the most important reasons for early treatment discontinuation. Pre-existing cirrhosis at baseline was an important risk factor for thrombocytopenia and (minor) bleeding complications

Close monitoring of hepatitis B surface antigen levels helps classify flares during peginterferon therapy and predicts treatment response

Background. Alanine aminotransferase (ALT) flares occur frequently during peginterferon (PEG-IFN) therapy. We related occurrence of flares to presence of precore (PC) and/or basal core promoter (BCP) mutants and studied kinetics of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels during flares.Methods. Fifty of 214 (23%) patients treated with PEG-IFN ± lamivudine for 52 weeks experienced flares. Flares were host-induced (ALT elevation followed by HBV DNA decline, n = 19), virus-induced (HBV DNA increase with subsequent ALT elevation, n = 17) or indeterminate (n = 14

Sustained HBeAg and HBsAg loss after longterm follow-up of HBeAg positive patients treated with peginterferon alpha-2B

58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases -- NOV 02-06, 2007 -- Boston, MAWOS: 000249910401228Amer Assoc Study Liver Di

Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b

Background & Aims: The aim of this study was to evaluate the long-term sustainability of response in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with pegylated interferon (PEG-IFN) alpha-2b alone or in combination with lamivudine. Methods: All 266 patients enrolled in the HBV99-01 study were offered participation in a long-term follow-up (LTFU) study. Patients were treated with PEG-IFN alpha-2b (100 mu g/wk) alone or in combination with lamivudine (100 mg/day) for 52 weeks. Initial response was defined as HBeAg negativity at 26 weeks posttreatment. For the LTFU study, patients had one additional visit after the initial study (mean interval, 3.0 +/- 0.8 years). Results: of 266 patients enrolled in the initial study, 72 (65%) participated in the LTFU study. At LTFU, HBeAg and hepatitis B surface antigen (HBsAg) negativity were observed in 37% and 11% of 172 patients, respectively. Sixty-four patients were classified as initial responders and 108 as nonresponders. Among the initial responders, sustained HBeAg negativity and HBsAg loss were observed in 81% and 30%, respectively. Significantly higher rates of HBeAg negativity were observed in genotype A-infected initial responders compared with those with genotype non-A (96% vs 76%; P = .06) as well as HBsAg loss (58% vs 11%; P <.001). Conclusions: HBeAg loss after treatment with PEG-IFN alpha-2b alone or in combination with lanlivudine is sustained in the majority of patients and is associated with a high likelihood of HBsAg loss, particularly in genotype A-infected patients. Therefore, PEG-IFN alpha-2b remains an important treatment option in this era of nucleos(t)ide analogue therapy