Hepatic steatosis in chronic hepatitis C: Baseline host and viral characteristics and influence on response to therapy with peginterferon α-2a plus ribavirin

GI Division, University of Pennsylvania, Philadelphia, PA 19104, USA.
Journal of Viral Hepatitis (Impact Factor: 3.91). 02/2008; 15(2):129-36. DOI: 10.1111/j.1365-2893.2007.00901.x
Source: PubMed


Hepatic steatosis is common in hepatitis C virus (HCV)-infected patients and may be associated with the metabolic syndrome. We studied steatosis in patients treated with peginterferonalpha-2a plus ribavirin. Forty-five of 207 patients (22%) had >5% hepatic steatosis at baseline. Significantly more patients with steatosis than without were HCV genotype 3 (51%vs 14%; P < 0.0001) had higher HCV-RNA (P = 0.0045), body weight (P = 0.0176), body mass index (BMI, P = 0.0352) and serum triglycerides (TG) (P = 0.0364), hypertriglyceridaemia (P = 0.0009), elevated blood pressure/history of hypertension (P = 0.0229) and lower cholesterol (P = 0.0009). Significant steatosis predictors were genotype 3 (OR 9.04, 95% CI 3.85-21.21, P < 0.0001), HCV-RNA (OR 2.96, 1.49-5.88, P = 0.0019) and triglycerides (OR 1.06, 1.02-1.11, P = 0.0071). In genotype 3 patients, HCV-RNA was the only significant predictor (OR 11.15, 2.60-47.81, P = 0.0012). In non-genotype 3 patients, hypertriglyceridaemia was the only significant predictor (OR 1.07, 1.02-1.12, P = 0.0041). 134 of 207 patients (65%) achieved an sustained virological response (SVR) with peginterferon alpha-2a plus ribavirin, similar to the overall response rate. In genotype 3 patients with an SVR, steatosis decreased from 48% to 13% (baseline to end-point). No change was seen in the steatosis rate in non-genotype 3 patients with an SVR. This large and comprehensive analysis of a large data base from a multinational trial further adds to the observations that chronic HCV is associated with hepatic steatosis in approximately a fifth of patients. Further, features of the metabolic syndrome are associated with hepatic steatosis in most of these patients. Steatosis is significantly more common in genotype 3 compared with other genotypes, and in these patients, an SVR is associated with steatosis clearance.

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    • "For this reason, these results need to be confirmed in a larger data-set of patients. Second, several published studies analyzed genetic[12] [13] [14] [15], metabolic[19] [20] [21] [22] [23] and viral factors[27] [28] which are possibly associated with sustained virological response, but, to our knowledge, there are not studies that analyzed all together the factors assessed in our research so far. "
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    ABSTRACT: We assessed, in real-life practice, viral, demographic, genetic and metabolic factors influencing the sustained virologic response (SVR), with a gender-oriented analysis, in patients with chronic hepatitis C virus (HCV) treated with pegylated interferon and ribavirin. Six hundred and seventy naïve patients were treated with dual therapy and evaluated by gender and HCV genotype. Associations between baseline variables and SVR were assessed by multivariate logistic regression analysis. Among 362 genotype 1 patients, SVR was achieved in 158 patients (44%), and SVR was independently associated with age less than 50 years (OR 2.12; CI 95% 1.09-4.30; p=0.039) and C/C genotype rs12979860 SNP (OR 2.83; 1.19-6.74; p=0.002) in 163 females, while absence of visceral obesity (OR 2.491; 1.131-5.487; p=0.023), HCV-RNA lower than 400,000 IU/mL (OR2.66; 1.273-5.558; p=0.009) and C/C genotype rs12979860 SNP (OR 4.969; 2.401-10.283; p<0.001) were independently associated with SVR in 199 males. Combining favorable baseline variables, the probability of obtaining SVR ranged from 27.6% to 84.2% in females, and from 14.3% to 85.7% in males. The rate of SVR was 81.1% in 175 genotype 2 patients, and 69% in 100 genotype 3 patients. Rapid virologic response was the only valid predictor of SVR regardless of other features. In conclusions, in the setting of HCV genotype 1 chronic hepatitis, combining rapid virologic response and predictive factors, which are different for females and males, allows clinicians tosingle out a group of patients whose likelihood of SVR exceeds 80%. For these patients, triple therapy with first-generation protease inhibitors may be unwarranted.
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    ABSTRACT: Steatosis is a common histologic feature in chronic hepatitis C virus (HCV) infection. Viral steatosis, seen in genotype 3a, is strongly related to viral replication; metabolic steatosis, reported in genotype 1, has been associated with obesity, type 2 diabetes, and metabolic syndrome. HCV promotes lipid accumulation in hepatocytes, increasing free fatty acid synthesis and decreasing lipid oxidation and secretion. Several amino acid changes in core protein have been strongly related to steatosis development; for example, the Y164F change has been related to greater cumulative lipid droplets. Steatosis-induced HCV seems to act as an organelle supporting stable viral replication. HCV proteins promote insulin receptor substrate-1 (IRS-1) degradation by several mechanisms, including oxidative stress, peroxisome proliferator-activated receptor (PPAR) downregulation, and enhancement of tumor necrosis factor production in a genotype-dependent manner. In genotype 1, IRS-1 degradation was induced by mammalian target of rapamycin and in genotype 3, by suppressor of cytokine signaling-7 and PPAR. Steatosis and insulin resistance have been associated with fibrosis progression.
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