Hepatitis due to non-hepatotropic viruses is an important often under recognized cause of liver disease. Failure to diagnose or delayed diagnosis results in poor outcome. Majority of the non-hepatotropic viruses that cause hepatitis are Dengue viral hepatitis (DENV) and viruses in the herpesviridae family such as Herpes Simplex virus (HSV), Epstein Barr virus (EBV), Cytomegalovirus (CMV) and Herpes Zoster virus (HZV). Others include adenovirus associated hepatitis, and COVID-19 virus. Although it occurs more commonly in immunosuppressed individuals, immunocompetent individuals are not exempt from the conditions, although the disease is milder in them.
The spectrum of liver disease can vary from asymptomatic liver biochemistry abnormalities to severe acute hepatitis sometimes leading to acute liver failure that can result in death or the need for liver transplantation, particularly for HSV and DENV-induced hepatitis. While mild abnormalities in liver biochemistry is common as a part of systemic infection in the aforementioned viruses, subtle clues that aid diagnosis in severe disease particularly mimicking acute liver injury/failure from HSV and DENV include the presence or ongoing history of fever with marked rise in aminotransferases with minimal or no rise in bilirubin and mild coagulopathy. Timely diagnosis is the key to provide appropriate treatment such as acyclovir for herpes simplex virus or ganciclovir for cytomegalovirus hepatitis and supportive care in others.
The pathogenesis of liver injury could be secondary to a bystander effect on the liver from the systemic immune reaction to a robust extrahepatic antiviral response or to a direct hepatocyte cytopathic effect as demonstrated by immunohistochemistry to specific viral antigen. This review will focus on the current knowledge on hepatitis caused by DENV, HSV, EBV, CMV, VZV, COVID-19 and indeterminate hepatitis in children.