Regression of liver cirrhosis: Orthodoxy or paradigm shift?

Liver fibrosis is a wound-healing process that happens in almost patients with ongoing chronic liver injury. For instance, patients surviving acute liver failure do not undergo scar change despite a plenty of fibrogenic stimuli, unless chronic liver injury follows. Moreover, even liver fibrosis related to certain kind of sustained liver injury is often reversible. The reason for fibrosis reversibility in chronic liver disease is not fully understood, but may be associated with the balance of matrix-degrading enzymes and their inhibitors, in addition to the relative range of collagen cross-linking. Complications of end stage liver disease are related to the underlying fibrotic response. Therefore, fibrosis is harmful both by its indirect mechanical role to increased portal resistance and by its direct damages on cellular function. Ultimately, liver fibrosis leads to the end stage of liver fibrosis, cirrhosis, characterized by architectural distortion, abnormal hepatocyte regeneration, nodular change, vascular alterations and organ contraction. Cirrhosis significantly increases the risk of cirrhotic complications, hepatocellular carcinoma, and death. Therefore it is important to exactly predict the rate of liver fibrosis progression in patients with chronic viral hepatitis, which has important clinical impact in terms of prognostic and treatment implications. The exact moment when liver fibrosis becomes irreversible is still not known, in terms of either a histological marker or a specific change in the matrix content or composition. Dense cirrhosis, with regenerating nodule formation and portal hypertension, is usually considered irreversible, but several studies have demonstrated that prolonged antiviral therapy improves liver histology and even reverses cirrhosis in patients with chronic hepatitis B (CHB). However, the evidences existing so far is based on limited number of patients, especially in case of advanced liver fibrosis or cirrhosis. Moreover, there is a possibility of bias due to selection of patients undergoing repeat biopsy and the important concern of the right staining for elastic fibers in liver biopsies. Indeed, mostly in existence of high grade of necroinflammation, there is a parenchymal collapse mimicking septa, and in these cases collagen stains including Sirius Red and Masson’s Trichrome could lead to a misdiagnosis of liver cirrhosis which disappeared in the successive liver biopsies. Since the amount of liver fibrosis could be decreased by a switching off of necroinflammation, liver stiffness which is mainly associated with fibrosis is also affected by alanine aminotransferase (ALT) level. In this issue, Yo et al reported the factors associated with longitudinal change of liver stiffness in patients with CHB. In this See Article on Page 32 Regression of liver cirrhosis: Orthodoxy or paradigm shift?