Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes.

UNLABELLED: It is uncertain whether patients with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) have a milder disease and should undergo liver biopsy. We reviewed the histological data of 458 Italian patients with NAFLD in whom liver biopsy was indicated by altered liver enzymes (395 cases, 86%), or persistently elevated ferritin or long-lasting severe steatosis (63 cases). Factors associated with nonalcoholic steatohepatitis (NASH) and fibrosis >/= 2 were identified by multivariate analysis. Patients with normal ALT were significantly older, had lower body mass index, fasting triglycerides, insulin resistance according to homeostasis model assessment (HOMA-IR), ALT, and gamma-glutamyltransferase, but a higher prevalence of hypertension. NASH was diagnosed in 59% and 74% of the patients with normal and increased ALT, respectively (P = 0.01). In the overall series of patients, NASH was independently predicted by ALT (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04-1.19 per 10-IU/mL increase) and diabetes (OR, 1.5; 95% CI, 1.1-2.0). The same variables were selected in patients with increased ALT, whereas in those with normal ALT, HOMA-IR and ALT were independent predictors. Severe fibrosis was independently predicted by serum ferritin (OR, 1.04; 95% CI, 1.001-1.08 per 50-ng/mL increase), ALT (OR, 1.07; 95% CI, 1.02-1.14), and diabetes (OR, 1.8; 95% CI, 1.4-2.3) in the overall series, serum ferritin and diabetes in those with increased ALT, and only HOMA-IR (OR, 1.97; 95% CI, 1.2-3.7) in patients with normal ALT. CONCLUSION: Normal ALT is not a valuable criterion to exclude patients from liver biopsy. Alterations in glucose metabolism and insulin resistance in subjects with normal ALT should also be considered in the selection of NAFLD cases for histological assessment of disease severity and progression.

Accuracy of a predictive model for severe hepatic fibrosis or cirrhosis in chronic hepatitis C.

AIM: To assess the accuracy of a model in diagnosing severe fibrosis/cirrhosis in chronic hepatitis C virus (HCV) infection. METHODS: The model, based on the sequential combination of the Bonacini score (BS: ALT/AST ratio, platelet count and INR) and ultrasonography liver surface characteristics, was applied to 176 patients with chronic HCV infection. Assuming a pre-test probability of 35%, the model defined four levels of post-test probability of severe fibrosis/cirrhosis: <10% (low), 10-74% (not diagnostic), 75-90% (high) and >90% (almost absolute). The predicted probabilities were compared with the observed patientso distribution according to the histology (METAVIR). RESULTS: Severe fibrosis/cirrhosis was found in 67 patients (38%). The model discriminated patients in three comparable groups: 34% with a very high (>90%) or low (<10%) probability of severe fibrosis, 33% with a probability ranging from 75% to 90%, and 33% with an uncertain diagnosis (i.e., a probability ranging from 10% to 74%). The observed frequency of severe fibrosis/cirrhosis was within the predefined ranges. CONCLUSION: The model can correctly identify 67% of patients with a high (>75%) or low (<10%) probability of cirrhosis, leaving only 33% of the patients still requiring liver biopsy.

Severe liver fibrosis or cirrhosis: accuracy of US for detection--analysis of 300 cases.

PURPOSE: To determine the accuracy of various ultrasonographic (US) signs for assessment of the degree of liver fibrosis, with histologic results as reference standard. MATERIALS AND METHODS: Three hundred consecutive asymptomatic patients with at least 6 months of increased levels of aspartate aminotransferase and/or alanine aminotransferase underwent liver US and biopsy. The estimated pretest probability of severe fibrosis or cirrhosis was 35%. Three US parameters were investigated: liver surface nodularity, caudate lobe hypertrophy, and pattern of hepatic venous blood flow. US results were compared with histologic results obtained after liver biopsy, which constituted the reference standard for diagnosis of severe fibrosis or cirrhosis. The degree of fibrosis was graded according to METAVIR criteria, with stages 3 and 4 considered together. Data were analyzed with kappa and chi2 statistics. Sensitivity, specificity, positive and negative likelihood ratios, and posttest probability were calculated for each US sign. RESULTS: In 107 (36%) patients with severe fibrosis (n = 34) or cirrhosis (n = 73), liver surface nodularity had the highest diagnostic accuracy, with specificity of 95% and positive and negative likelihood ratios 11.6 and 0.51, respectively. When liver surface nodularity was considered alone, posttest probability of severe fibrosis or cirrhosis increased from 35% to 86%. When caudate lobe hypertrophy and hepatic venous blood flow were also taken into account, posttest probability increased by only 2% (ie, to 88%). CONCLUSION: US determination of liver surface nodularity is an accurate method for identifying the subset of asymptomatic patients with severe liver fibrosis or cirrhosis, which indicates a worse prognosis.