Pegylated Interferon Alfa in HBeAg-positive Chronic Hepatitis B
Gepegyleerde Interferon Alfa in HBeAg-positieve Chronische 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.