Host Factors (Fibrosis and Overweight, etc) in HCV Non Responders

Some studies reveal that high BMI is a negative predictor of nonresponse to HCV therapy. Bressler et al. analyzed 174 patients with HCV having normal BMI (<25 kg/m2) in 70 (40.2%), overweight according to BMI (25-30 kg/ m2) in 69 (39.7%), and obese according to BMI (>30 kg/m2) in 35 (20.1%)(8). Several other factors included into the analysis and showed that obese patients had an odds ratio of 0.23 compared with normal and overweight patients. They concluded that a BMI greater than 30 kg/ m2, independent of genotype and cirrhosis is a negative predictor of response to hepatitis C treatment. Although the grade of steatosis was statistically greater in the obese group compared with the overweight and normal patients, steatosis grade of 1 or more was not a statistically significant predictor of response in that study. Some other studies reveal that the presence of co-existent nonalcoholic fatty liver disease has been associated with more rapid fibrosis progression and a higher prevalence of cirrhosis in patients with chronic HCV (9,10). Recent data report low response rates to the therapy in HCV patients with steatosis (11,12) and diabetes (13). Hypercholesterolemia, insulin resistance, and other metabolic factors may affect the response rates (14,15). It is recommended that HCV nonresponders lose weight, exercise regularly, and improve the control of their diabetes mellitus and hyperlipidemia if possible.

Cirrhotics have poor response to HCV therapy: In the study of Bressler et al. cirrhotic patients had an odds ratio of 0.15 compared with noncirrhotic patients (8). In patients with cirrhosis, analysis of individual patient data of six controlled trials revealed that the ribavirin/ interferon combination achieved a sustained virologic response in 20% versus 5% by interferon alone (p=0.01) (16). The combination of pegylated interferon 1.5μg per kg and ribavirin in patients with compensated cirrhosis maintained a 55% sustained response rate (24 out of 44) (17). Pegylated interferon combined with standard dose ribavirin seemed to be more effective (52%) than that with pegylated interferon/low ribavirin (38%) (18). Adverse events were seen more; dose reductions for intolerance were required in 78% and 57%, and treatment was terminated early in 23% and 27% of patients.

Female gender is associated with 10 times less rapid progression to cirrhosis than male whatever the age (19). It is suggested that estrogen modulates fibrogenesis and modify the expression of transforming growth factor and other soluble mediators. Combining extreme favorable population (women, ≤40 years, no of portal fibrosis, genotype 2,3, viral load ≤3.5×106 copies/ml) may yield a response rate of 79% (from a combination therapy of interferon and ribavirin for 48 weeks; on the other hand, only 9% of extreme unfavorable population (men, >40 years, septal fibrosis or more, genotype 1, 4, 5, 6, viral load >3.5×106 copies/ml) respond (20).