Dendritic cells in chronic viral hepatitis B and C: victims or guardian angels?

Hepatitis viruses, of which the common types are A, B and C, are hepatotropic and primarily infect hepatocytes. Both hepatitis B virus (HBV) and hepatitis C virus (HCV) can cause chronic liver disease and may elicit progressive liver injury leading to increased risk of developing liver cirrhosis, liver failure and liver cancer.1 2 The outcome of infection, and the development of liver disease are determined by viral and host factors (fig 1). Figure 1 Hepatitis B virus (HBV) and hepatitis C virus (HCV) disease pathogenesis. (A) Following infection with HBV, there will be an initial acute hepatitis that could be symptomatic (nausea and icterus). Successful clearance and resolution of HBV infection (10–90%) depends on the route of infection, age and immune status of the individual, with most infections of immunocompetent adults being self-limiting. Most cases of chronic HBV infection are caused by vertical transmission from mother to neonate. If the infection is not controlled, continuing liver inflammation, tissue injury and aberrant repair result in chronic hepatitis, liver fibrosis and cirrhosis. Pro-oncogenic features of HBV itself in combination with ongoing inflammation and tissue injury result in an increased risk for the development of hepatocellular carcinoma (HCC). Persistent immune control over the HBV can be achieved in up to 20–30% of the patients after treatment with pegylated interferon α (PEG-IFNα), which has several side effects. Sustained response rates after nucleos(t)ide analogue treatment, which directly interferes with viral replication and probably has to be given life long, are even lower due to higher off-treatment relapses. In addition, breakthrough of resistant HBV variants limits long-term use. (B) Acute HCV infection is asymptomatic in most cases. HCV readily establishes chronic infection in otherwise immunocompetent adults (70–90% of HCV-infected individuals). If the infection is not controlled, continuing liver inflammation, tissue injury and aberrant repair result in …