hepatic fibrosis

Hepatic fibrosis is a wound-healing response to chronic hepatic injury from causes such as chronic viral hepatitis (HBV, HCV), alcoholic liver disease, nonalcoholic fatty liver disease/NASH, autoimmune hepatitis, and biliary obstruction (e.g., primary biliary cholangitis, primary sclerosing cholangitis). The central pathophysiologic event is activation of quiescent, vitamin A-storing hepatic stellate cells (located in the space of Disse) into proliferative, contractile, fibrogenic myofibroblasts. This activation is driven by cytokines and growth factors released from injured hepatocytes, activated Kupffer cells, and infiltrating inflammatory cells—most notably TGF-β1, PDGF, and reactive oxygen species. Activated stellate cells produce excess type I and III collagen, along with other ECM components, which accumulate in the space of Disse, converting it from a low-resistance sinusoidal space to a high-resistance capillarized structure. This leads to loss of hepatocyte microvilli, sinusoidal endothelial fenestrae, and impaired hepatocyte-blood exchange, contributing to portal hypertension. Fibrosis is initially reversible in early stages if the underlying cause is removed, but progressive fibrosis leads to cirrhosis—characterized by bridging fibrous septa connecting portal tracts and central veins, and regenerative nodules, resulting in irreversible architectural distortion. Clinically, fibrosis stage is assessed via liver biopsy (METAVIR or Ishak scoring) or noninvasively via elastography (FibroScan) or serum biomarkers (e.g., FIB-4 index, APRI score). Cirrhosis complications include portal hypertension (varices, ascites, splenomegaly), hepatic encephalopathy, coagulopathy, and increased risk of hepatocellular carcinoma. Antifibrotic therapies are an active area of research, but the mainstay of management remains treating the underlying etiology (e.g., antivirals for HBV/HCV, alcohol cessation, weight loss for NAFLD) to halt or reverse fibrosis progression.