Hepatitis

Hepatitis is liver inflammation caused by various factors, with hepatotropic viruses A through E being leading infectious causes. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most prevalent. Non-infectious causes include alcohol and drugs. Each virus has distinct transmission routes and disease progression patterns.

HBV binds to the NTCP receptor on hepatocytes and enters via receptor-mediated endocytosis. The viral nucleocapsid is released into the cytoplasm and transported to the nucleus. There, relaxed circular DNA converts to covalently closed circular DNA, serving as a template for transcription. Viral proteins and RNA are synthesized in the cytoplasm, assembled, and released through the endoplasmic reticulum and Golgi apparatus.

Hepatitis A virus transmits via the fecal-oral route through contaminated food or water, entering through the oropharynx or intestinal epithelium. Hepatitis B virus transmits through blood, sexual contact, or perinatally. HAV causes self-limiting disease, while HBV can establish chronic infection due to persistent covalently closed circular DNA in hepatocytes.

Hepatitis A is self-limiting because the immune response, particularly CD8+ T cells and natural killer cells, effectively clears the virus. Hepatitis B establishes chronic infection because covalently closed circular DNA persists in hepatocyte nuclei, evading complete immune clearance. This persistence allows continuous viral replication and can lead to severe inflammation, fibrosis, and cirrhosis.

Hepatitis C virus evades immunity through high genetic variability, allowing it to escape immune recognition. HCV binds to multiple receptors including CD81 and claudin-1 to enter hepatocytes. Replication occurs entirely in the cytoplasm, where viral RNA is translated into a polyprotein later cleaved into structural and nonstructural proteins, contributing to chronic infection in over half of infected individuals.

When HBV infects hepatocytes, T cells recognize infected cells and attack them, triggering an immune response. This cellular immune response causes liver inflammation as infected hepatocytes are destroyed. If the virus is not cleared, chronic infection develops, leading to persistent inflammation, progressive fibrosis, and potentially cirrhosis of the liver.

Hepatitis A requires only supportive care since it is self-limiting and resolves without intervention. Chronic hepatitis B and C infections require antiviral therapies to suppress viral replication and prevent complications such as cirrhosis and hepatocellular carcinoma. These antivirals target different stages of viral replication to reduce disease progression and are similar to approaches used for viral meningitis management in controlling viral spread.