Patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis are at the highest risk for progressing to end-stage liver disease. We constructed and validated a scoring system consisting of routinely measured and readily available clinical and laboratory data to separate NAFLD patients with and without advanced fibrosis. A total of 733 patients with NAFLD confirmed by liver biopsy were divided into 2 groups to construct (n ‫؍‬ 480) and validate (n ‫؍‬ 253) a scoring system. Routine demographic, clinical, and laboratory variables were analyzed by multivariate modeling to predict presence or absence of advanced fibrosis. Age, hyperglycemia, body mass index, platelet count, albumin, and AST/ALT ratio were independent indicators of advanced liver fibrosis. A scoring system with these 6 variables had an area under the receiver operating characteristic curve of 0.88 and 0.82 in the estimation and validation groups, respectively. By applying the low cutoff score (؊1.455), advanced fibrosis could be excluded with high accuracy (negative predictive value of 93% and 88% in the estimation and validation groups, respectively). By applying the high cutoff score (0.676), the presence of advanced fibrosis could be diagnosed with high accuracy (positive predictive value of 90% and 82% in the estimation and validation groups, respectively). By applying this model, a liver biopsy would have been avoided in 549 (75%) of the 733 patients, with correct prediction in 496 (90%). Conclusion: a simple scoring system accurately separates patients with NAFLD with and without advanced fibrosis, rendering liver biopsy for identification of advanced fibrosis unnecessary in a substantial proportion of patients. (HEPATOLOGY 2007;45:846-854.)

No abstract

No abstract

Drug-induced autoimmune hepatitis (DIAIH) has been reported to be caused by several drugs. There is a lack of data comparing these patients with other patients with autoimmune hepatitis (AIH). A search was performed using the Mayo Clinic diagnostic medical index for AIH patients and DIAIH patients identified over 10 years. Individuals with overlap syndromes and decompensated liver disease were excluded. Overall, 261 patients (204 females, median age 52) were identified, and 24 (9.2%) were DIAIH cases with a median age of 53 (interquartile range, 24-61). Two drugs, nitrofurantoin (n 5 11) and minocycline (n 5 11), were the main causes. A similar proportion of DIAIH patients had positive antinuclear antibodies (83% versus 70%) and smooth muscle antibodies (50% versus 45%) as compared with AIH patients. Histological grade and stage were similar in patients with DIAIH versus AIH; however, none of the DIAIH patients had cirrhosis at baseline; this was present in 20% of matched AIH cases. Liver imaging was normal in all minocycline cases. Eight of 11 (73%) nitrofurantoin patients had abnormalities on hepatic imaging (mainly liver atrophy), a finding seen in only 8 of 33 (24%) of a random sample of the rest of the AIH group (P 5 0.0089). Corticosteroid responsiveness was similar in DIAIH and the AIH patients. Discontinuation of immunosuppression was tried and successful in 14 DIAIH cases, with no relapses (0%), whereas 65% of the AIH patients had a relapse after discontinuation of immunosuppression (P < 0.0001). Conclusion: A significant proportion of patients with AIH have drug-induced AIH, mainly because of nitrofurantoin and minocycline. These two groups have similar clinical and histological patterns. However, DIAIH patients do not seem to require long-term immunosuppressive therapy.

Although there are small animal platforms that recapitulate some of the histological features of nonalcoholic fatty liver disease, there are no small animal models of nonalcoholic steatohepatitis (NASH) with consistent hepatocellular ballooning and progressive fibrosis that also exhibit fidelity to the human condition physiologically. We examined the metabolic and histological effects of a diet on the basis of the composition of “fast food” (high saturated fats, cholesterol, and fructose). Mice ( n = 8 in each group) were assigned to diets as follows: 1) standard chow (SC), i.e., 13% energy as fat [1% saturated fatty acids (SFA)], 2) high fat (HF), i.e., 60% energy as fat (1% SFA), and 3) fast food (FF), i.e., 40% energy as fat (12% SFA, 2% cholesterol). All three diets were supplemented with high fructose. All diets produced obesity. The HF and FF diets produced insulin resistance. Liver histology was normal in animals fed the SC diet. Steatohepatitis with pronounced ballooning and progressive fibrosis (stage 2) was observed in mice fed the FF diet. Although the HF diet produced obesity, insulin resistance, and some steatosis; inflammation was minimal, and there was no increase in fibrosis. The FF diet produced a gene expression signature of increased fibrosis, inflammation, and endoplasmic reticulum stress and lipoapoptosis. A diet based on high cholesterol, high saturated fat, and high fructose recapitulates features of the metabolic syndrome and NASH with progressive fibrosis. This represents a novel small animal model of fibrosing NASH with high fidelity to the human condition. These results highlight the contribution of dietary composition to the development of nonalcoholic fatty liver disease and NASH.