Metabolic Factors That Predict Rapid Virologic Response to Peginterferon/Ribavirin in HCV Patients
Tarek Hassanein, MD, FACP, FACG, AGAF
Posting Date: November 05, 2009
Professor of Medicine
Department of Medicine
University of California , San Diego
San Diego , California
Director, Clinical Trials Center
Southern California Liver & GI Centers
Coronado , California
Hepatitis C virus (HCV) negativity at Week 4, defined as rapid virologic response (RVR), has been accepted as the best predictor of sustained virologic response (SVR) among HCV-infected individuals receiving antiviral therapy (Capsule Summary). Viral factors that predict RVR include HCV RNA, genotype, and quasispecies. In addition, retrospective studies have shown that the response to therapy can be affected by certain host factors, such as age, platelet count, body mass index (BMI), levels of low density lipoprotein (LDL) and total cholesterol, insulin resistance, hepatic steatosis, and the presence of metabolic syndrome.[2-4]
The aim of the study conducted by Angelico and colleagues was to investigate the metabolic factors predictive of RVR in a prospective fashion among patients with chronic HCV infection who were treated with peginterferon and weight-based ribavirin for the standard duration based on HCV genotype (ie, 24 weeks for genotype 2/3 infection, 48 weeks for genotype 1 infection) (Capsule Summary). The study population consisted of 65 Italian patients with chronic hepatitis C who were consecutively recruited from 2 university hospitals. Patients using medications that affect lipoprotein metabolism (eg, statins) were specifically excluded from the study.
Overall, 57% of patients were infected with genotype 1 HCV, and 43% were infected with genotype 2/3 HCV. At baseline, 30.8% of patients were classified as overweight, 21.5% were obese, 20.0% had type 2 diabetes mellitus, and 24.6% had metabolic syndrome.
As expected, significantly more patients infected with genotype 2/3 vs genotype 1 HCV attained RVR (60.7% vs 27.0%, respectively; P < .01). However, among patients who attained RVR, the SVR rates were comparable between patients infected with genotype 2/3 and genotype HCV 1 (80.0% and 77.8%, respectively). A comparison of patients who achieved RVR vs those who did not revealed that patients with RVR had significantly higher total cholesterol (190.9 vs 163.3 mg/dL, respectively; P = .003) and LDL cholesterol (126.7 vs 96.7 mg/dL, respectively; P = .005) at baseline. Bivariate analyses showed that RVR correlated positively with low baseline serum insulin, HOMA-IR, BMI, and the number of risk factors for metabolic syndrome. Rapid virologic response correlated with high plasma total cholesterol. Using multiple logistic regression models controlling for patient sex, metabolic syndrome, HCV RNA, and alanine aminotransferase at baseline, several independent predictors of RVR were identified, including young age (younger than 50 years), non–genotype 1 infection, high total cholesterol (≥ 165 mg/dL), and low serum 8-iso-prostaglandin F2α (< 50 pmol/mL).
Whereas the relationship between baseline lipid profile and virologic response to therapy has primarily been reported in the literature in retrospective studies, this prospective study showed that high levels of total cholesterol at baseline significantly increased the probability of RVR. The relationship between HCV viral clearance and serum lipids during therapy is still obscure. However, there are well-documented observations in the literature attesting to such an interaction:
The study investigators used 8-iso-prostaglandin F2α as a marker of lipid peroxidation, free radical generation, and oxidative stress. The data revealed that a higher baseline level of this marker was an independent predictor of failure to achieve RVR. Moreover, patients who achieved RVR demonstrated a much greater decline in serum 8-iso-prostaglandin F2α within the first 4 weeks of therapy than patients who failed to achieve RVR, although the difference was not statistically significant. Other studies have also shown that when HCV is cleared by therapy, lipid peroxidation as detected by 8-iso-prostaglandin F2α dramatically decreases.
In summary, the study by Angelico and colleagues confirms previous observations indicating that RVR is the best predictor of SVR and that independent predictors of RVR include young age and non–genotype 1 infection. The study also sheds light on the potential significance of baseline lipid profile as a predictor of RVR and, therefore, suggests that clinicians should emphasize more strongly healthy cholesterol levels in these patients. These findings require more comprehensive testing to clarify the interaction between HCV and serum lipids. However, if confirmed, they may provide in the future yet another marker for gauging the potential efficacy of HCV treatment and may further guide individualized treatment initiation.
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