Immune responses and immunopathology in acute and chronic viral hepatitis
Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that is determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not. HBV is effectively controlled in adults, although it persists for a lifetime after neonatal infection. In this article, we reviewed the similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections, which may explain the distinct course and outcome of each hepatitis virus infection.
Several human viruses display hepatotropism; that is, they preferentially infect hepatocytes and cause liver inflammation, known as viral hepatitis. Most cases of viral hepatitis worldwide are caused by hepatitis A virus (HAV), hepatitis B virus (HBV) or hepatitis C virus (HCV). HCV infection often progresses to chronic persistent infection. Acute HBV infection spontaneously resolves in more than 90% of infected adults, although HBV can sometimes result in chronic persistent infection, particularly when neonates are infected by vertical transmission. As a result, approximately 170 million and 350 million people worldwide are chronically infected with HCV and HBV, respectively, and infected individuals are at risk of liver cirrhosis and hepatocellular carcinoma. However, HAV infection is effectively controlled by the host and does not progress to chronic infection.
HAV, HBV and HCV differ in terms of their virological characteristics, and HAV, HBV and HCV infections follow typical courses and outcomes depending on the infecting virus. The distinctive courses and outcomes of each hepatitis virus infection are determined by both the virological characteristics and the immune responses elicited by each hepatitis virus. Therefore, this review discusses and compares innate and adaptive immune responses to HAV, HBV and HCV. Furthermore, the mechanisms of immune-mediated liver injury are described, because comparison of the similarities and differences in immune responses elicited by HAV, HBV and HCV will help us to understand the mechanisms of virus persistence. In particular, understanding the immune responses in acute HAV infection may aid the development of a prophylactic HCV vaccine, and understanding immune dysfunction in chronic HBV and HCV infections will facilitate the development of novel HBV therapeutics.
Nature Reviews Immunology 2016, 16:509-523