Data on the long-term outcome of nonalcoholic steatohepatitis (NASH)-associated cirrhosis are few, and most reports describe cases of cryptogenic cirrhosis associated with risk factors for NASH but without histologic definition. In this prospective cohort study, we describe the longterm morbidity and mortality of 23 patients with NASH-associated cirrhosis defined by strict clinicopathologic criteria. Outcomes were compared with 46 age-and gender-matched patients with cirrhosis from chronic hepatitis C virus (HCV) infection: 23 untreated and 23 nonresponders to antiviral therapy. During follow-up (mean, 84 months; median, 60 months; range, 5-177 months), 9 of the 23 NASH-associated cirrhosis cases developed liver-related morbidity (8 ascites and/or encephalopathy, 1 variceal bleeding). The probability of complication-free survival was 83%, 77%, and 48% at 1, 3, and 10 years, respectively, and the cumulative probability of overall survival was 95%, 90%, and 84% at 1, 3, and 10 years, respectively. Five deaths were from liver failure, 1 from a non-liver-related cause. By multivariate analysis, bilirubin (P ‫؍‬ .02) and platelet (P ‫؍‬ .04) were independent predictors of complication-free survival; bilirubin (P ‫؍‬ .05) was the only predictor for overall survival. After controlling for these factors, there was no difference in complication-free or overall survival between the NASH-cirrhosis cohort and either group of HCV-cirrhosis. However, 8 cases of liver cancer occurred in the HCV-cirrhosis groups compared with none among NASH cases. In conclusion, liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis, except that HCC appears less common. (HEPATOLOGY 2003;38:420-427.) L iver-related morbidity and mortality in nonalcoholic steatohepatitis (NASH) occurs principally among those with cirrhosis, a finding similar to the natural history of hepatitis C. There is, however, a paucity of data on the natural history of cirrhosis attributable solely to host metabolic factors (NASH). In large part, this relates to the lack of accepted histologic and clinical criteria for the diagnosis of "NASH-associated cirrhosis" as opposed to "cryptogenic cirrhosis" occurring in people with risk factors for NASH. These definitional problems are compounded by reports that the features of steatohepatitis on liver biopsy may disappear with fibrotic progression. 1 Although disease progression in NASH is slow, 1 it is unclear whether clinical progression and liver complications are inevitable or whether the rate of progression is faster or slower than that in other liver diseases, such as hepatitis C. Prospective outcome studies of NASH are difficult to perform because of the need for extended follow-up, the possibility of death from other causes (especially cardiovascular disease and cancer), 2 and the reluctance to undertake serial liver biopsy because of the perceived benign natural history and lack of specific therapies.In chronic hepatit...

To identify variables that are independent predictors of adverse outcomes in chronic hepatitis C, we analyzed a cohort of 455 patients followed for a median of 4.7 years. Associations were sought between demographic and behavioral factors, hepatitis C virus (HCV) genotype, liver histology and liver tests at entry, and development of liver complications, hepatocellular carcinoma (HCC), hepatic transplantation and liver-related death. Independent predictors were identified by multivariate analysis. The following were associated with a significantly higher rate of liver complications: age; birth in Asia, Europe, Mediterranean region, or Egypt; transmission by blood transfusion or sporadic cases; HCV genotypes 1b and 4 (compared with 1/1a); fibrosis stage 3 or 4 (cirrhosis); serum albumin; bilirubin; prothrombin time; and ␣-fetoprotein. However, the only independent predictors of liver-related complications were sporadic transmission (P F .001), advanced fibrosis (P ‫؍‬ .004), and low albumin (P F .001). The corresponding independent risk factors for HCC were male gender (P ‫؍‬ .07), sporadic transmission (P F .001), and albumin (P F .001); bilirubin (P ‫؍‬ .02) was an additional predictor of transplantation or liver-related death. It is concluded that only patients with advanced hepatic fibrosis or cirrhosis, are at risk of developing hepatic complications of chronic hepatitis C during 5-year follow-up. Among such patients, abnormalities in serum albumin, bilirubin, or prothrombin time indicate a high probability of complications. The rate of fibrotic progression in chronic hepatitis C is highly variable, 1 and the natural history of the disease usually extends over several decades. In some patients, it may culminate in the life-threatening liver complications of portal hypertension, hepatocellular carcinoma (HCC), and liver failure requiring hepatic transplantation or leading to liverrelated death. Such complications are rarely noted in the absence of cirrhosis. The factors that influence the rate of fibrotic progression in hepatitis C virus (HCV) include age at the time of HCV infection and at initial evaluation, male sex, HCV genotype, and alcohol consumption. [1][2][3][4][5][6][7][8] It is less clear as to whether any of these factors influence the onset of liver-related complications other than by their effects on the rate of fibrotic progression.The proportion of all patients with hepatitis C who develop life-threatening complications is also unclear. Many studies are confined to either the first 20 years of HCV infection when complications appear to be unusual, [8][9][10][11][12][13][14][15] or to the late stage of the disease when cirrhosis is present. [13][14][15][16] Thus some cohort studies have found low mortality rates at 17 to 20 years, particularly among younger individuals and among those who have a risk factor other than blood transfusion. 8,9,11,12,17 Others have indicated that approximately 18% of patients develop liver-related complications or HCC or succumb to liver-related death within 18 year...