Serum GGT Predicts Virological Response to Pegylated-Interferon and Ribavirin Therapy in Patients with Chronic Hepatitis C

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Purpose: Currently, the ability of clinicians to predict response to pegylated-interferon and ribavirin therapy in chronic hepatitis C (CHC) is based on measurements of viral load, early virological response (EVR) and rapid virological response (RVR). However, a recent study of non-responding patients suggests that serum GGT may also predict response in patients treated with pegylated-interferon and ribavirin. The aim of our study was to assess the association of baseline GGT level and sustained virological response (SVR) in treatment-naïve patients with CHC. Methods: We conducted a retrospective chart review that included all patients with CHC who were treated with pegylated-interferon and ribavirin from 2004 to 2006. Patients were excluded if they were not naive to interferon-based therapy, were non-compliant, or lost to follow-up. Demographic data, including age, gender, body weight, comorbidities, baseline HCV RNA levels, and baseline ALT, AST, GGT, and platelet level were obtained. SVR was confirmed by an undetectable HCV RNA at week 24 of treatment. Univariate and multivariate regression analyses were performed to assess the association of the baseline enzyme levels with treatment response. Results: Eighty-three patients were included in the study, mean age 47.2 ± 9.4 years old, 57 (59%) were female. There were 38 pts (45.8%) with genotype 1 infection and 36 pts (43.4%) with genotype 2 or 3 infection. The mean baseline HCV RNA level was 5.5 ± 0.8 log IU/mL. The mean baseline ALT, AST, and GGT levels were 84.01 ± 50.1 IU/dL, 61.79 ± 40.62 IU/dL, and 92.57 ± 166.49 IU/dL respectively. Thirty-eight pts achieved SVR (45.8%). In multivariate analysis, age (odds ratio [OR] 0.94; 95% CI 0.89–0.98; P= 0.01) and elevated baseline GGT levels (>1× ULN, 55 IU/dL) were negatively associated with SVR (OR 0.12; 95% CI 0.04–0.20; P < 0.001), while gender, baseline ALT/AST levels, and baseline HCV RNA levels did not show significant association with SVR. In subgroup analysis, the negative association of elevated GGT and SVR was only observed in patients with genotype 1 infection (OR 0.07; 95% CI 0.01–0.50; P= 0.008), but not with genotype 2 or 3 infection. Conclusion: In our study, age and elevated baseline GGT levels (>1× ULN) are negatively associated with SVR in treatment-naïve patients with CHC. Normal baseline GGT levels, in adjunct to RVR and EVR, may be used to predict treatment response in pts with CHC genotype 1 infection. Further study is needed to explain the underlying pathophysiology and confirm these findings.