title: The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study.
abstract: Information on the long-term prognosis of nonalcoholic fatty liver disease (NAFLD) is limited. We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis by prospectively studying 247 such patients from four international centers (in Australia, USA, UK and Italy). Their natural history was then compared with 264 patients with HCV infection who were either naïve or non-responders to treatment. Both cohorts were Child-Pugh class A and had advanced fibrosis (stage 3) or cirrhosis (stage 4) confirmed by liver biopsy at enrollment. In the NAFLD cohort, followed up for a mean of 85.6 months (range, 6-297), there were 48 (19.4%) liver-related complications and 33 (13.4%) deaths or liver transplants. In the HCV cohort, followed up for 74.9 months (mean; range, 6-238), there were 47 (16.7%) liver-related complications and 25 (9.4%) deaths or liver transplants. When adjusting for baseline differences in age and gender, the cumulative incidence of liver-related complications was lower in the NAFLD than the HCV cohort (P = 0.03), including incident hepatocellular cancer (6 versus 18; P = 0.03), but that of cardiovascular events (P = 0.17) and overall mortality (P = 0.6) were similar in both groups. In the NAFLD cohort, platelet count, stage 4 fibrosis, lowered platelet count, and lowered serum cholesterol and alanine aminotransferase (ALT) levels were associated with liver-related complications; an aspartate aminotransferase/ALT ratio >1 and older age were associated with overall mortality, and higher serum bilirubin levels and stage 4 fibrosis were associated with liver-related mortality.
  
  
  CONCLUSIONS
  Patients with NAFLD with advanced fibrosis or cirrhosis have lower rates of liver-related complications and hepatocellular cancer than corresponding patients with HCV infection, but similar overall mortality. Some clinical and laboratory features predict liver-related complications and other outcomes in patients with NAFLD.
authors.affiliation: Clinical Trial Service Unit & Epidemiological Studies Unit, Richard Doll Building, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. neeraj.bhala@ctsu.ox.ac.uk
authors.forename: Neeraj
authors.initials: N
authors.lastname: Bhala
authors.forename: Paul
authors.initials: P
authors.lastname: Angulo
authors.forename: David
authors.initials: D
authors.lastname: van der Poorten
authors.forename: Eric
authors.initials: E
authors.lastname: Lee
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hui
authors.forename: Giorgio
authors.initials: G
authors.lastname: Saracco
authors.forename: Leon A
authors.initials: LA
authors.lastname: Adams
authors.forename: Phunchai
authors.initials: P
authors.lastname: Charatcharoenwitthaya
authors.forename: Joanne H
authors.initials: JH
authors.lastname: Topping
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000328:Adult; D001315:Australia; D001707:Biopsy, Needle; D002423:Cause of Death; D015331:Cohort Studies; D016001:Confidence Intervals; D018450:Disease Progression; D005234:Fatty Liver / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D005260:Female; D019698:Hepatitis C, Chronic / Q000401:mortality* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007391:International Cooperation; D007558:Italy; D008103:Liver Cirrhosis / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D014481:United States