Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients.</p> <p>Methods</p> <p>Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples.</p> <p>Results</p> <p>HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001).</p> <p>Conclusions</p> <p>IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.</p

Association of <i>VDR</i> ApaI and TaqI Gene Polymorphisms with the Risk of Scleroderma and Behçet’s Disease

<p>Vitamin D deficiency and vitamin D receptor (<i>VDR</i>) gene polymorphisms have been reported in autoimmune diseases. However, their role in Behçet’s disease (BD) and scleroderma remains inconclusive. Our aim was to evaluate vitamin D receptor (ApaI, TaqI) gene polymorphisms in relation to Behçet’s disease and scleroderma in Egyptians. The study was conducted on 54 patients with BD, 30 scleroderma patients, and 60 healthy control subjects. <i>VDR</i> (ApaI, TaqI) gene polymorphisms were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. The “a” allele of ApaI (A/a) polymorphism was significantly associated with increased BD risk (OR = 2.09, 95% CI = 1.18–3.71, <i>p</i> = 0.011), while the TaqI “tt” genotype was significantly lower in BD patients as compared to control subjects (OR = 0.35, 95% CI = 0.13–0.9, <i>p</i> = 0.026). Carriage of “aT” <i>VDR</i> haplotype was significantly associated with higher BD risk (OR = 2.28, 95% = 1.14–4.56, <i>p</i> = 0.022). In conclusion, our findings suggest that <i>VDR</i> gene polymorphisms have a significant association with BD in Egyptian patients.</p