Effects of Fatty Liver and Related Factors on HCV Therapy
Effects of Fatty Liver and Related Factors on HCV Therapy
Objective: Hepatic steatosis is a histological feature in patients with chronic hepatitis C (CHC) and adversely affects the virologic response rates to anti-hepatitis C virus (HCV) therapy. The aim of this study is to investigate whether the fatty liver and related factors have impact on the efficacy in CHC treated with peginterferon and ribavirin, and the associations between HCV genotyping and fatty liver.
Methods: Ninety-eight patients received subcutaneously 180 µg peginterferon α-2a once a week plus ribavirin. HCV genotypes and the levels of plasma insulin of patients were measured. Fatty liver was detected by B ultrasound. The body mass index (BMI), waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated.
Results: Among 98 CHC patients, 38 (38.8%) were infected with genotype 1; 44 (44.9%) with genotype 2; 13 (13.3%) with genotype 3; 3 (3.0%) with indeterminate genotype. The prevalence of fatty liver was 10.5%, 11.4%, 38.5% in patients infected with HCV genotype 1, 2, 3, respectively, which suggested that the distribution of fatty liver in different HCV genotypes was imbalanced (χ = 6.758, P = 0.034). In univariate analysis, the efficacy of combination therapy was significantly associated with BMI (P = 0.011), WHR (P = 0.024), the levels of plasma insulin (P = 0.001), genotype (P = 0.036), presence of fatty liver (P = 0.028), treatment dosage and duration (P = 0.012) and HOMA-IR (P = 0.002). With binary logistic regression analysis, the plasma insulin levels and HOMA-IR showed independent predictors to the efficacy of antiviral therapy.
Conclusion: The prevalence of fatty liver in HCV genotype 3 was markedly higher than that of other genotypes. The BMI, WHR, the levels of plasma insulin, genotype, presence of fatty liver, treatment dosage and duration and HOMA-IR were associated with the sustained virologic response. The level of plasma insulin and HOMA-IR were independent factors for predicting effect of antiviral therapy.
Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease affecting approximately 130 million individuals worldwide, with 20% of these patients potentially progressing to cirrhosis. Currently standard treatment includes a combination of pegylated interferon a and ribavirin with a sustained viral eradication rate of 55%.
Hepatic steatosis is a histological feature in patients with chronic hepatitis C (CHC) and present in about 50% of the subjects with HCV. In HCV, both viral and host factors (conditions associated with the metabolic syndrome: obesity, high body mass index (BMI), high waist-to-hip ratio (WHR)) contribute to development of hepatic steasosis. It has been suggested that genotype 3 is especially associated with steatosis. HCV genotype 3 core protein could inhibit very low-density lipoprotein (VLDL) liver secretion and induce liver steatosis.
Both fatty liver and obesity are associated with the metabolic syndrome, which is characterized by insulin resistance (IR) and hyperinsulinemia. It is now universally accepted that IR and subsequent hyperinsulinemia are key factors that lead to hepatic steatosis, steatohepatitis and cirrhosis. The oxidative stress associated with IR syndrome can cause the production of reactive-oxygen species and peroxidation of membrane lipids producing toxic by-products, which lead to hepatic fibrosis. Hepatic steatosis in Taiwanese patients with CHC was associated with features of the metabolic syndrome. IR and hyperinsulinemia often accompanied with CHC superimposed fatty liver. Steatosis and IR may be important cofactors in accelerating fibrosis in CHC. Hepatic steatosis also adversely affects the virologic response rates to anti-HCV therapy. Fatty liver and obesity are risk factors for failure of interferon (IFN) therapy in subjects with HCV. IR and hyperinsulinemia may block the IFN-mediated inhibition of HCV replication by interacting with the IFN-inducible protein kinase (PKR) and IFN regulatory factor, preventing its activation by IFN.
We hypothesized that the low response rates to antiviral therapy in CHC patients with fatty liver may be associated with IR. Ninety-eight Chinese CHC patients were selected to receive peginterferon α-2a combination with ribavirin. We studied the effect of fatty liver and related factors on antiviral combination treatment in patients with CHC.
Abstract and Introduction
Abstract
Objective: Hepatic steatosis is a histological feature in patients with chronic hepatitis C (CHC) and adversely affects the virologic response rates to anti-hepatitis C virus (HCV) therapy. The aim of this study is to investigate whether the fatty liver and related factors have impact on the efficacy in CHC treated with peginterferon and ribavirin, and the associations between HCV genotyping and fatty liver.
Methods: Ninety-eight patients received subcutaneously 180 µg peginterferon α-2a once a week plus ribavirin. HCV genotypes and the levels of plasma insulin of patients were measured. Fatty liver was detected by B ultrasound. The body mass index (BMI), waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated.
Results: Among 98 CHC patients, 38 (38.8%) were infected with genotype 1; 44 (44.9%) with genotype 2; 13 (13.3%) with genotype 3; 3 (3.0%) with indeterminate genotype. The prevalence of fatty liver was 10.5%, 11.4%, 38.5% in patients infected with HCV genotype 1, 2, 3, respectively, which suggested that the distribution of fatty liver in different HCV genotypes was imbalanced (χ = 6.758, P = 0.034). In univariate analysis, the efficacy of combination therapy was significantly associated with BMI (P = 0.011), WHR (P = 0.024), the levels of plasma insulin (P = 0.001), genotype (P = 0.036), presence of fatty liver (P = 0.028), treatment dosage and duration (P = 0.012) and HOMA-IR (P = 0.002). With binary logistic regression analysis, the plasma insulin levels and HOMA-IR showed independent predictors to the efficacy of antiviral therapy.
Conclusion: The prevalence of fatty liver in HCV genotype 3 was markedly higher than that of other genotypes. The BMI, WHR, the levels of plasma insulin, genotype, presence of fatty liver, treatment dosage and duration and HOMA-IR were associated with the sustained virologic response. The level of plasma insulin and HOMA-IR were independent factors for predicting effect of antiviral therapy.
Introduction
Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease affecting approximately 130 million individuals worldwide, with 20% of these patients potentially progressing to cirrhosis. Currently standard treatment includes a combination of pegylated interferon a and ribavirin with a sustained viral eradication rate of 55%.
Hepatic steatosis is a histological feature in patients with chronic hepatitis C (CHC) and present in about 50% of the subjects with HCV. In HCV, both viral and host factors (conditions associated with the metabolic syndrome: obesity, high body mass index (BMI), high waist-to-hip ratio (WHR)) contribute to development of hepatic steasosis. It has been suggested that genotype 3 is especially associated with steatosis. HCV genotype 3 core protein could inhibit very low-density lipoprotein (VLDL) liver secretion and induce liver steatosis.
Both fatty liver and obesity are associated with the metabolic syndrome, which is characterized by insulin resistance (IR) and hyperinsulinemia. It is now universally accepted that IR and subsequent hyperinsulinemia are key factors that lead to hepatic steatosis, steatohepatitis and cirrhosis. The oxidative stress associated with IR syndrome can cause the production of reactive-oxygen species and peroxidation of membrane lipids producing toxic by-products, which lead to hepatic fibrosis. Hepatic steatosis in Taiwanese patients with CHC was associated with features of the metabolic syndrome. IR and hyperinsulinemia often accompanied with CHC superimposed fatty liver. Steatosis and IR may be important cofactors in accelerating fibrosis in CHC. Hepatic steatosis also adversely affects the virologic response rates to anti-HCV therapy. Fatty liver and obesity are risk factors for failure of interferon (IFN) therapy in subjects with HCV. IR and hyperinsulinemia may block the IFN-mediated inhibition of HCV replication by interacting with the IFN-inducible protein kinase (PKR) and IFN regulatory factor, preventing its activation by IFN.
We hypothesized that the low response rates to antiviral therapy in CHC patients with fatty liver may be associated with IR. Ninety-eight Chinese CHC patients were selected to receive peginterferon α-2a combination with ribavirin. We studied the effect of fatty liver and related factors on antiviral combination treatment in patients with CHC.