Natural History of Non-Alcoholic Fatty Liver Disease: A Study With Paired Liver Biopsies

Background: Although there is unequivocal evidence for progression of nonalcoholic steatohepatitis (NASH) to cirrhosis, there is uncertainty with regard to the progression to nonalcoholic fatty liver (NAFL) and NASH. Aims: We investigated the rate of progression to NASH and advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and assessed the factors associated with such progression. Methods: Histological assessment was performed in 36 patients with NAFLD with paired liver biopsies (≥1 year apart; median, 3.8 years; range, 1–10.33 years). NASH Clinical Research Network (NASH CRN) criteria were used to assess NAFLD Activity Score (NAS). Results: At baseline, 26 (72%) patients had NAFL and 10 (28%) patients had NASH. At follow-up, 27% NAFL progressed to NASH (NAS score ≥5), and 50% of patients with NASH no longer met the criteria of NASH. Fibrosis progressed in 15 (42%), regressed in 9 (25%), and remained stable in 12 (33%) patients overall. Thirty-five percent of patients with NAFL had fibrosis progression. The incidence of type 2 diabetes mellitus (T2DM) was higher in patients with NASH versus NAFL (40% vs. 27%). Both at the time of baseline and follow-up, liver biopsies, composite models of noninvasive scores such as Fibrosis-4 (FIB-4) score and NAFLD fibrosis score, and ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) were all significantly higher in progressors than in nonprogressors. Conclusions: NAFLD is a dynamic liver disease with varying degrees of progression and regression. T2DM was strongly associated with fibrosis progression. Noninvasive fibrosis scores such as AST/ALT ratio, FIB-4 score, and NAFLD fibrosis score can identify those at risk of fibrosis progression

Accuracy of noninvasive fibrosis scoring systems in african american and white patients with nonalcoholic fatty liver disease

OBJECTIVES: Nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4) score, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) score, and AST-alanine aminotransferase (ALT) ratio are noninvasive fibrosis scoring systems for the staging of liver fibrosis in patients with chronic liver disease. METHODS: In a large cohort of patients with nonalcoholic fatty liver disease, we compared AST-ALT ratio, NFS, FIB-4 score, and APRI score in predicting advanced fibrosis (defined as fibrosis stage ‡ 3) in histologically confirmed African American (AA) and white patients. We identified 907 patients: 677 (74.6%) white and 230 (25.3%) AA patients with nonalcoholic fatty liver disease. RESULTS: Of the 907 patients, 115 (12.8%) patients had advanced fibrosis (stages 3 and 4) in the total cohort: 6 (2.6%) AAs, and 109 (16.2%) whites. In AAs, the area under the receiver operating characteristic (area under the curve) for predicting advanced fibrosis was 0.58 by NFS, 0.86 by APRI score, 0.77 by FIB-4 score, and 0.65 by AST-ALT ratio. In whites, the area under the receiver operating characteristic for predicting advanced fibrosis was 0.82 by NFS, 0.82 by APRI score, 0.88 by FIB-4 score, and 0.76 by AST-ALT ratio. In the AA population, NFS \u3e 0.675, FIB-4 score \u3e 2.67, and APRI score \u3e 1.5 each has a negative predictive value of 98%, whereas the negative predictive values in whites are 91%, 88%, and 85%, respectively. DISCUSSION: Noninvasive fibrosis scoring systems can reliably exclude advanced fibrosis in both AAs and whites and have acceptable discriminatory ability to predict advanced fibrosis in whites. The utility of noninvasive fibrosis scoring systems in predicting advanced fibrosis in AAs needs further validation in a larger multicenter cohort