Subjects with bland steatosis without severe fibrosis or cirrhosis at the time of

biopsy exhibited no increased risk of death. When patients with cirrhosis or severe fibrosis are excluded from the group with bland steatosis, deaths attributable to either cirrhosis or liver cancer are much less common. Both for subjects with fatty liver and for the whole study population, we found that persistently elevated serum levels of liver enzymes were associated with an increased risk of death during the study period. As a group, subjects with NAFLD demonstrated a significantly increased risk of death, but this risk was not as high as for patients with chronic viral hepatitis or alcoholic liver disease (Fig. 2C). In our population, those with NAFLD exhibited poorer Selleck NVP-LDE225 survival than those with autoimmune hepatitis, hemochromatosis, or alpha-1-antitrypsin

deficiency taken combined. It is currently unknown why certain patients diagnosed by biopsy as suffering from NAFLD and elevated serum levels of liver enzymes develop inflammation and fibrosis (NASH). One of the main findings presented here is that survival among these subjects is lower than among the matched reference population. Recently, Adams and co-workers9, 11, 19 also reported that survival among NAFLD subjects is lower than expected in comparison with the general population. In most cases, their diagnosis of NAFLD was based on imaging

rather than histological examination. MCE公司 Moreover, in a 14-year follow-up, Ekstedt et al.11 demonstrated that survival of patients with NASH was BKM120 lower than expected in comparison with the general population. In the current 28-year follow-up, we have confirmed these findings. The main causes of death among our subjects with NASH were cardiovascular disease, followed by extrahepatic cancers and next hepatic diseases. As expected, cardiovascular diseases were found to be the major cause of death in the current investigation. Recent epidemiological studies indicate an increased incidence of major cardiovascular events in subjects with NAFLD, independent of traditional risk factors and aspects of the metabolic syndrome.19–21 A higher risk for cardiovascular mortality compared with the reference population has been shown in subjects shown to have NAFLD though biopsy11 as well as in a population-based cohort study.22 Liver diseases, including hepatocellular carcinoma (HCC), were found to be the third largest cause of death among subjects with NAFLD. HCC is a major health problem worldwide, with more than 500,000 cases diagnosed annually.23 Whereas the incidence of HCC has been increasing during the last 5 to 8 years, the survival of those affected has not changed significantly during the past two decades.