Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

BACKGROUND: Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied. AIMS: To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies. METHODS: In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status RESULTS: Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P < 0.001). Advanced fibrosis was present with even minimal haemosiderosis, independently of ferritin values or HCV history. CONCLUSIONS: These data suggest that in the late stages of liver disease in BTM patients, iron overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history.

Thrombotic risk factors and liver histologic lesions in non-alcoholic fatty liver disease.

BACKGROUND/AIMS: The pathogenetic mechanisms of development of non-alcoholic steatohepatitis (NASH) and fibrosis are not clear, although thrombosis of small intrahepatic veins has been suggested to trigger liver tissue remodelling and thrombotic risk factors have been associated with more advanced fibrosis in chronic viral hepatitis (CVH). We evaluated the prevalence of thrombotic risk factors (RFs) in non-alcoholic fatty liver disease (NAFLD) and their possible association with fatty liver or NASH. METHODS: We included 60 patients with histologically documented NAFLD and a historical cohort of 90 patients with chronic hepatitis B (n=39) or C (n=51). Thrombophilic factors were evaluated on the day of the liver biopsy. RESULTS: One or more thrombotic RFs were detected in 37% of NAFLD patients, and >or= 2 RFs were detected in 12% of NAFLD patients, being less frequently present than in CVH patients (37% and 68%, respectively; P

Hepatic steatosis in genotype 4 chronic hepatitis C is mainly because of metabolic factors.

BACKGROUND/AIM: Hepatic steatosis is considered to be mostly associated with viral factors in genotype 3 and metabolic factors in genotype 1 chronic hepatitis C, while there are rather few data for genotype 4. We determined the parameters associated with steatosis in 350 chronic hepatitis C patients, focusing on genotype 4. METHODS: Histological lesions were evaluated according to Ishak's classification and steatosis was semiquantitatively graded. Several patient characteristics on the biopsy day were also evaluated. RESULTS: Steatosis was present in 73% of patients without significant differences among genotypes. Moderate/severe steatosis was more frequent in genotype 3 than 4 (44% vs 26%, P= 0.025) and similar between genotype 4 and 1 patients. Moderate/severe steatosis was associated with body mass index (BMI) in genotype 4 (P= 0.023) and gamma-glutamyl-transpeptidase in genotype 3 patients (P= 0.044). In 150 nondiabetic patients with BMI < or =25 kg/m(2), moderate/severe steatosis was present in 15, 40, and 11% of genotype 1, 3, and 4 patients, respectively, (P= 0.005) and was independently associated only with genotype 3. In multivariate analysis, steatosis grade or moderate/severe steatosis was independently associated with higher BMI, genotype 3, and lower cholesterol. CONCLUSIONS: Moderate or severe steatosis is significantly less frequent in genotype 4 than 3 chronic hepatitis C patients and similar between genotype 4 and 1. In nondiabetic, nonoverweight patients, moderate or severe steatosis is present in only 10-15% of genotype 4 or 1 compared with 40% of genotype 3 patients. Thus, hepatic steatosis in genotype 4 is mostly associated with metabolic factors, similar to those in genotype 1.

Aspartate aminotransferase to platelet ratio index for fibrosis evaluation in chronic viral hepatitis.

OBJECTIVE: We assessed the value of the recently developed aspartate aminotransferase to platelet ratio index (APRI) for predicting significant fibrosis or cirrhosis in patients with chronic hepatitis C or HBeAg-negative chronic hepatitis B. METHODS: In total, 489 patients (chronic hepatitis C, 284 patients; HBeAg-negative chronic hepatitis B, 205 patients) were included. APRI values of 0.50 or less and greater than 1.50 were evaluated for predicting significant fibrosis, and APRI values of 1.00 or less and greater than 2.00 for predicting cirrhosis. Liver biopsies were evaluated according to the Ishak's classification. Fibrosis was considered to be significant in cases with scores 3-6, and cirrhosis to be present in cases with fibrosis scores of 5 and 6. RESULTS: Significant fibrosis was observed in 56/148 (38%) patients with APRI< or = 0.50, 130/227 (57%) patients with 0.501.50 (P<10). Cirrhosis was observed in 47/311 (15%) patients with APRI< or = 1.00, 29/93 (31%) patients with 1.002.00 (P<10). The areas under receiver-operating characteristic curves were 0.65 and 0.70 for prediction of significant fibrosis or cirrhosis, respectively. The combination of APRI< or = 0.50 and APRI>1.50 classified correctly 36% of patients with or without significant fibrosis, while the combination of APRI< or = 1.00 and APRI>2.00 classified correctly 62% of patients with or without cirrhosis. There was no significant difference in the predictive values of APRI between patients with chronic hepatitis C and chronic hepatitis B. CONCLUSIONS: APRI is significantly associated with the extent of fibrosis, but it does not classify correctly 40-65% of patients with chronic hepatitis C or HBeAg-negative chronic hepatitis B, and thus it cannot replace liver biopsy.