Mechanisms of Hepatocellular Injury in Hepatitis A

• Main Authors: Minghang Wang, Zongdi Feng
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Viruses
• Subjects: hepatitis A virus; liver injury; bystander T cell activation; MAVS signaling; TIM-1 polymorphism; IL-18BP deficiency
• Online Access: https://www.mdpi.com/1999-4915/13/5/861

Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8⁺ T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.