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 longlasting 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. (HEPATOLOGY 2008;48:792-798.)

SummaryBeta-thalassaemia isa congenital haemolytic anaemia characterized by partial (intermedia, TI) or complete (major, TM) deficiency in the production of β-globin chains.The primary aim of this study was to determine the prevalence of thromboembolic events in patients with β-thalassaemia.To achieve this,a multiple-choice questionnaire was sent to 56 tertiary referral centres in eight countries (Lebanon, Italy, Israel, Greece, Egypt, Jordan, Saudi Arabia and Iran), requesting specific information on patients who had experienced a thromboembolic event.The study demonstrated that thromboembolic events occurred ina clinically relevant proportion (1.65%) of 8,860 thalassaemia patients (TI – 24.7% or TM – 75.3%) from the Mediterranean and Iran. Thromboembolism occurred 4.38 times more frequently in TI thanTM (p<0.001), with more venous events occurring inTI and more arterial events occurring in TM.Thrombosis in thalassaemia was also more common in females, splenectomized patients and those with profound anaemia (haemoglobin <9 g/dl). Due to the increased risk of thromboembolic events, the rationale for splenectomy should perhaps be re-assessed and the role of transfusion therapy for the prophylaxis of thrombosis, among other complications, be evaluated prospectively.

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Venous thromboembolic events, such as pulmonary embolism, deep venous thrombosis, and portal vein thrombosis, have been observed in adult thalassemia patients, mainly in β‐thalassemia intermedia. The clinical findings are consistent with the observation of several alterations that indicate a state of activation of the hemostatic mechanisms in thalassemias. These alterations have usually been related to high platelet counts due to splenectomy and/or liver dysfunction. In a retrospective study of a large cohort of adults with thalassemia, we found a larger prevalence of venous thromboembolic events in transfusion‐independent patients with thalassemia intermedia (29%) than in regularly transfused patients with thalassemia major (2%); moreover, the higher prevalence occurred particularly in splenectomized thalassemia intermedia patients. More recently, a multicenter study involving 56 tertiary referral centers in 7 countries was planned to assess the magnitude of thrombotic risk in thalassemia patients. The total number of patients who had thrombotic events was 146 (1.65%) out of 8860, with a prevalence of 0.9% in thalassemia major and 4% in thalassemia intermedia. The highest prevalence was confirmed in splenectomized patients. The observation that thrombotic events are more frequent in β‐thalassemia patients who are not receiving regular transfusions (thalassemia intermedia or thalassemia major patients in less developed countries with limited transfusion resources) or in thalassemic patients who have undergone splenectomy strongly supports the procoagulant activity of circulating damaged red blood cells.