Cirrhosis of the liver: new concepts

Cirrhosis is a histologic term that requires liver biopsy for definitive diagnosis. Although we may usefully classify cirrhosis by cause, such as alcoholic cirrhosis, the morphologic diagnosis is confined to only a few descriptive terms. Cirrhosis is the end result of hepatocellular necrosis that initiates the inflammatory process. Hepatocellular necrosis induced by the hepatoviruses is caused by the host response to the parasitized cells rather than by the viruses themselves. Inflammatory cells, apparently by diverse mechanisms that include the immune system, stimulate the deposition of collagen around hepatocytes and in sinusoidal membranes, causing profound alteration in hepatocyte function and hepatic blood flow. Fully developed cirrhosis cannot be reversed with therapy presently available. Efforts to change morbidity and mortality of this common disease include preventive measures, attempts to manipulate the immune response, efforts to influence the biologic process of fibrosis, and, finally, attempts to induce resorption of established collagen. No acceptable therapy to prevent cirrhosis currently exists, but there is reason to believe that one can and will be developed in the future, probably through the discovery of better methods of eliminating the persistent infection by hepatoviruses. The most encouraging results to date come from experiments using prednisone followed by interferon, and from very preliminary results with methotrexate in specific circumstances. In the meantime, the clinician will continue to support the existing physiology, minimize and treat the complications, and offer support to the patient and family.