Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR).We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n ‫؍‬ 143) or NAFLD (n ‫؍‬ 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild <30%, or moderate-severe >30%. Thirty nondiabetic, nonobese blood donors served as controls. RBP4 levels were measured by a human competitive enzyme-linked immunosorbent assay kit (AdipoGen). Mean values of RBP4 were similar in NAFLD and CHC (35.3 ؎ 9.3 g/L versus 36.8 ؎ 17.6; P ‫؍‬ 0.47, respectively), and both were significantly higher than in controls (28.9 ؎ 12.1; P ‫؍‬ 0.02 and P ‫؍‬ 0.01, respectively). RBP4 was higher in CHC patients with steatosis than in NAFLD (42.1 ؎ 19.7 versus 35.2 ؎ 9.3; P ‫؍‬ 0.04). By linear regression, RBP4 was independently linked to steatosis only (P ‫؍‬ 0.008) in CHC, and to elevated body mass index (P ‫؍‬ 0.01) and low grading (P ‫؍‬ 0.04) in NAFLD. By linear regression, steatosis was independently linked to homeostasis model assessment score (P ‫؍‬ 0.03) and high RBP4 (P ‫؍‬ 0.003) in CHC. By logistic regression, RBP4 was the only variable independently associated with moderate-severe steatosis in CHC (odds ratio, 1.045; 95% confidence interval, 1.020 to 1.070; P ‫؍‬ 0.0004), whereas waist circumference was associated with moderate-severe steatosis in NAFLD (odds ratio, 1.095; 95% confidence interval, 1.007 to 1.192; P ‫؍‬ 0.03). Conclusion: In nondiabetic, nonobese patients with genotype 1 CHC, serum RBP4 levels might be the expression of a virus-linked pathway to steatosis, largely unrelated to IR. (HEPATOLOGY 2008;48:28-37.)

The prevalence of CD in patients with chronically abnormal liver tests of unexplained etiology is 4%, with no relation with the degree of liver steatosis. Screening should be done by testing for IgA and IgG antibodies and then evaluating by endoscopy and biopsy only patients positive for both.

Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis virus C-RNA negative) the liver iron concentration (median 2.4 mg/gr dry liver weight) was closely related to serum ferritin levels (R = 0.58; p<0.0001). Male gender (OR 4.12) and serum hepatitis virus C-RNA positivity (OR 11.04) were independent risk factors for advanced liver fibrosis. The majority of hepatitis virus C-RNA negative patients with low iron load did not develop liver fibrosis, while hepatitis virus C-RNA positive patients infected with genotype 1 or 4 and iron overload more frequently developed advanced fibrosis. Hepatitis virus C infection is the main risk factor for liver fibrosis in transfusion-dependent thalassemics. Adequate chelation therapy usually prevents the development of liver fibrosis in thalassemics free of hepatitis virus C-infection and reduces the risk of developing severe fibrosis in thalassemics with chronic hepatitis C.

AIM:To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS:One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only.RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and g-glutamyltransferase were independent predictors of steatosis. Ferritin levels were significantly related to low platelet count, steatosis and hepatitis C virus infection. CONCLUSION:In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.

Immunostaining for IgM and IgG plasma cells on liver tissue can be a valuable parameter for better diagnosis of autoimmune liver disease and also for variant or mixed syndromes.