Natural course and effects of treatment in chronic hepatitis B : Cohort study in non-Asian women in Amsterdam

Abstract

From its discovery in 1965 up to now, hepatitis B (HBV) has had a major impact worldwide. Globally, it is estimated that 240 million people are chronically infected with HBV and annually almost 800.000 people die due to complications of HBV-related liver disease. HBV causes an inflammation of the liver with liver damage and loss of hepatocytes which is replaced by fibrotic tissue. Persisting inflammation leads to hepatic fibrosis and ultimately liver cirrhosis. Also, chronic HBV patients are at risk of developing hepatocellular carcinoma (HCC). These conditions negatively influence the prognosis of chronic HBV patients. Liver inflammation is an asymptomatic process and the formation of liver fibrosis and cirrhosis in chronic HBV patients can take several decades. Due to the liver complications of HBV, it is important that patients who are at risk of developing liver cirrhosis and HCC are early identified. In Asian chronic HBV patients, viral load (the amount of hepatitis B virus per millilitre of blood) at a random moment in time has been predictive for the development of liver cirrhosis and HCC. However, it is not known whether the hepatitis B viral load in non-Asian chronic HBV patients also is predictive for liver cirrhosis development. The natural course of HBV differs in Asian patients compared to non-Asian patients in several aspects, such as the route of transmission, the genotypic distribution of HBV and prevalence of HBe seroconversion. This thesis outlines the natural course of chronic hepatitis B in non-Asian patients in Amsterdam. The study population consisted of a cohort of treatment-naïve, multi-ethnic chronic HBV positive women in Amsterdam, who participated in a vaccination program between 1990 and 2004 and of whom serum samples were stored at the Public Health Service Amsterdam. The main topic of this thesis concerned whether the association between HBV viral load and liver cirrhosis, which was found in Asian HBV patients, could also be found in non-Asian chronic HBV patients. The aim of this thesis was (1) to study the predictive value of HBV viral parameters and fibrosis-related serological tests to identify patients with liver cirrhosis; (2) to identify serological determinants related to HBsAg loss and (3) focus on immunological effects and renal complications of antiviral therapy in chronic HBV patients.