Figure 3. The natural course of acute and chronic liver disease.

Chronic liver disease includes various heterogeneous disease conditions depending on etiology and time. Chronic exposures to different insults lead to various kinds of chronic hepatitis. If causal factors are not corrected and continue the harmful effects on the liver, hepatic inflammation progresses to hepatic fibrosis and further cirrhosis. In this stage, cirrhosis often accompanies portal hypertension, which is a main pathophysiologic cause of cirrhosis-related death and complications such as variceal hemorrhage and ascites formation. Hepatocellular carcinoma can develop at any stage of chronic liver disease even though advanced cirrhosis is the most risky stage. Ischemic-reperfusion injury after major liver surgery or transplantation can progress to sudden acute hepatic liver failure and death. The roles of NO derived from eNOS or iNOS vary, depending on disease etiologies and conditions. In general, NO produced by eNOS can be protective, but iNOS-derived NO or its derivatives such as peroxynitrite have been shown to promote inflammation.