High tumor necrosis factor-α/interleukin-10 ratio is associated with hepatocellular carcinoma in patients with chronic hepatitis C.

Hepatitis C virus (HCV) is the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC) worldwide. The risk for the development of HCC increases with the severity of liver inflammation and fibrosis. The hepatic inflammation caused by HCV involves host regulatory immune response, which is mediated by cytokines with anti-viral role upon the interaction of viral polypeptides with innate and adaptive immunity. Two cytokines; tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) play key roles in the regulation of cellular immune response in HCV infection. The aim of the present study was to determine the levels of IL-10 and TNF-α, as well as the ratio of TNF-α and IL-10 serum levels in patients with HCV and HCC caused by HCV (HCC-HCV). The study included 173 patients with chronic HCV. TNF-α and IL-10 serum levels were measured by ELISA (R&D Systems, Inc.). In the present study, 54 patients presented liver mild fibrosis, 68 had severe fibrosis and 51 patients had HCC. After adjustment in the multivariate regression analysis, the following variables remained significantly associated with HCC-HCV occurrence: diabetes (p=0.012 OR 10.44 CI 1.66-65.60), IL-10 lower levels (p<0.0001 OR 0.83 CI 0.78-0.89) and TNF-α higher levels (p<0.0001 OR 1.19 CI 1.11-1.28). Individuals with HCC presented higher TNF-α/IL-10 ratio than those with fibrosis grade F4, F3 or F0+F1+F2 (p=0.0003, p<0.0001, p<0.0001, respectively). Patients with HCC were associated to higher index TNF-α/IL-10 ratio, suggesting that the unbalanced production of these cytokines may represent progression to the liver disease severity in HCV infected patients.

MTP -493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients.

The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.

MTP -493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients

The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson’s disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8 percent of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3 percent of the patients with fibrosis grade 1+2 (OR = 1.8; 95 percentCI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95 percentCI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.