Immune Responses of Chronic HCV Infection

Abstract The hepatitis B virus (HBV) is one of the smallest enveloped double-stranded DNA viruses, belonging to the family of hepadnaviridae. HBV replicates via an RNA intermediate and causes both acute and chronic hepatitis. The Australia antigen, now known as the hepatitis B surface antigen (HBsAg) – which is the hallmark of a chronic hepatitis B (CHB) infection – was discovered by Dr. Baruch Samuel Blumberg, for which he received the Nobel prize in Medicine in 1976. Approximately 2 billion people worldwide have been in contact with HBV. Of these, circa 240 – 400 million people are chronically infected. The prevalence of CHB infection is high (> 8%) in resource poor countries, such as in East Asia, sub-Saharan Africa, and in the Amazon, and intermediate (2 – 7%) in the Mediterranean basin, Eastern Europe and Russia. The prevalence in Western countries is low (less than 2%). HBV can survive outside the body for at least 7 days. During this period, it may still cause an acute or chronic infection to people who are not protected by vaccination. HBV is transmitted by percutaneous and mucous membrane exposure to infected body fluids such as serum, saliva and semen. The major route of transmission is thought to be vertical, especially in high-endemic areas. Also horizontal infections occur during early childhood. Among adults, high-risk sexual behavior is the most important risk factor for HBV infection. HBV is predominantly found in the liver as it has a strong preference for infecting hepatocytes. It is thought that HBV is not directly cytopathic, while the proteins produced by the virus and the viral mini-chromosome – also known as covalently closed circular DNA (cccDNA) – may have carcinogenic effects. Moreover, the host immune response directed at infected hepatocytes leads to inflammation of the liver, which results in liver damage, fibrosis, and the development of liver cirrhosis, decompensation and hepatocellular carcinoma (HCC). Overall, 30% of cirrhosis and 53% of all HCC is attributable to CHB infection. Worldwide, approximately 780.000 patients die each year due to an HBV infection: 650.000 due to the sequelae of CHB (cirrhosis, HCC) and another 130.000 from acute HBV