A. Maraschi

Carotid Artery Intima-media Thickness in Nonalcoholic Fatty Liver Disease

PURPOSE To evaluate, in patients with nonalcoholic fatty liver disease with no or mild alterations of liver function tests, carotid artery intima-media thickness and the presence of plaques and to define determinants of vascular damage. METHODS A paired-sample case-control study: 125 patients with nonalcoholic fatty liver disease and 250 controls, without a prior diagnosis of diabetes, hypertension, and cardiovascular disease, matched for sex, age, and body mass index. B-mode ultrasound was used for evaluation of carotid intima-media thickness and presence of small plaques. RESULTS A significant difference in mean values of intima-media thickness (0.89+/-0.26 and 0.64+/-0.14 mm, P = .0001) and prevalence of plaques (26 [21%] and 15 [6%], P < .001) was observed in nonalcoholic fatty liver disease patients and controls. Variables significantly associated with intima-media thickness higher than 0.64 mm (median value in controls), in both patients and controls were: age (P = .0001), systolic blood pressure (P = .004), total and low-density lipoprotein cholesterol (P < or = .02 and P = .01, respectively), fasting glucose (P = .0001), and cardiovascular risk (P = .0001) and, only in controls, metabolic syndrome (P = .0001), HOMA-insulin resistance (P = .01), and body mass index (P = .0003). At multivariate logistic regression performed in the overall series of subjects, independent risk predictors of intima-media thickness higher than 0.64 mm were presence of steatosis (odds ratio [OR] = 6.9), age (OR 6.0), and systolic blood pressure (OR 2.3). CONCLUSION Patients with nonalcoholic fatty liver disease, even with no or mild alterations of liver tests, should be considered at high risk for cardiovascular complications.

Hemochromatosis in Italy in the last 30 years: Role of genetic and acquired factors

The clinical presentation of hereditary hemochromatosis has changed markedly in recent years. The aim of this study was to analyze a large series of consecutive Italian patients with hemochromatosis diagnosed between 1976 and 2007 to determine whether the genetic background and the presence of acquired risk factors influenced the severity of iron overload and the natural history of the disease. A cohort of 452 Italian patients with iron overload—338 HFE‐related (C282Y homozygotes or compound C82Y/H63D heterozygotes) and 114 non–HFE‐related—were followed prospectively for a median of 112 months. Alcohol intake, smoking habits, and iron removed to depletion were similar in patients with and without HFE‐related iron overload. Hepatitis B virus (4% and 9%; P = 0.04) and hepatitis C virus (6% and 19%; P = 0.002) infections were more frequent in patients with non–HFE‐related iron overload. Seventy‐three percent of patients with HFE and 61% of patients with non–HFE‐related disease had no acquired risk factor. Cirrhosis was significantly more frequent in non‐HFE patients independent of the presence of acquired risk factors (P = 0.02). Sex, alcohol intake, prevalence of smoking, hepatitis C virus infection, glucose, lipids, iron‐related parameters, and prevalence of C282Y/H63D differed significantly over the years. At enrollment, cirrhosis was present in 145 cases and was significantly more frequent in the first decade (80%, 47%, and 13%; P = 0.001). Survival did not differ across the decades in cirrhotic patients; hepatocellular carcinoma occurred similarly in HFE and non‐HFE patients. Conclusion: Patients with HFE and non–HFE‐related iron overload have comparable iron overload and similar clinical history. Patients who were diagnosed during the last 10 years and were not identified as cirrhotic at enrollment have less severe disease and lower prevalence of acquired risk factors, independent of genetic background. (HEPATOLOGY 2010;51:501–510.)

Sustained response to combination therapy in patients with chronic hepatitis C who failed to respond to interferon

BACKGROUND/AIMS The best treatment for chronic hepatitis C patients who do not respond to interferon is still unknown. Reported rates of response to treatment vary as the result of heterogeneous definitions of non-responders and small study size. METHODS One hundred nineteen hepatitis C virus (HCV) RNA-positive non-responders to high-dose interferon monotherapy received alpha-interferon, 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 48 weeks (Group A, n=74) or alpha-interferon, 5 MU daily for 4 weeks, followed by 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 44 weeks (Group B, n=45) according to the Institution where they were followed. Persistently normal alanine aminotransferase and negative HCV RNA up to 72 weeks from treatment onset defined a sustained response. RESULTS Eighteen patients discontinued treatment (13 developed anemia, two mucositis, one granulocytopenia; two were dropouts), none for serious adverse events. There were 24 (20%) sustained responders, with similar final response rates in Groups A and B. Sustained response was more frequent in patients aged </=40 years (36% vs. 13%; P=0.006) and in those with non-1 genotype (44% vs. 14%; P=0.002). Among genotype 1 patients, the younger ones showed higher response rates (32% vs. 7%; P=0.005). Compared with patients harboring non-1 genotypes, the odds ratio of being a non-responder was 1.68 (confidence interval (CI): 0.53-5.37; P=0.381) in younger genotype 1 patients and 9.53 (CI: 2.84-32; P<0.001) in older genotype 1 patients. CONCLUSIONS Chronic hepatitis C patients who are non-responders to interferon monotherapy and infected by non-1 genotypes should undergo re-treatment with combination therapy. Treatment should be extended to younger genotype 1 patients who are more susceptible to liver disease worsening because of longer life expectancy and have a higher probability of being long lasting responders than their older counterparts.