Early viral kinetics and treatment outcome in combination of high‐dose interferon induction vs. pegylated interferon plus ribavirin for naïve patients infected with hepatitis C virus of genotype 1b and high viral load

Abstract

An investigation was carried out to determine whether early viral monitoring could predict efficiently the virological response to combination therapy of two different regimens in treatment-naive chronic hepatitis C patients infected with genotype 1b with high baseline viral load. Patients were randomly assigned to receive interferon (IFN) alpha-2b induction (6 MU daily for 2 weeks) followed by 6 MU thrice weekly for 46 weeks (IFN/R group; n = 20), or pegylated IFN alpha-2b (1.5 microg/kg) weekly for 48 weeks (PEG/R group; n = 28), in combination with ribavirin (600-1,000 mg daily). Serum HCV RNA was quantitated at 0, 6, 12, 24, and 48 hr post-dose, weekly during the first 4 weeks, and thereafter viral kinetics were assessed every 4 weeks. The sustained virological response rates in the IFN/R and PEG/R groups were 40% (8/20) and 43% (12/28), respectively. The non-virological response rates were 40% (8/20) and 39% (11/28), respectively. The cumulative virological response rates were similar in both groups. Multivariate analyses identified no independent baseline variables linked to sustained virological or non-virological response. Early log viral load changes from baseline in both groups were significantly greater at all time-points after 24 hr in virological response patients than in non-virological response patients (P < 0.001 for all). On the receiver operating characteristics curves for prediction of non-virological response, the area under the curves (0.951-1.000), sensitivity (90%-100%), and negative predictive value (96%- 100%) were similar at any time-points after 24 hr. For prediction of sustained virological response, sensitivity of 80% with 86% negative predictive value was observed for negative HCV RNA at week 12, with the highest area under the curves value of 0.919. The results suggest that early monitoring of viral kinetics is a useful measure to predict virological response, and might facilitate development of rational and effective therapeutic strategies.

Prediction of Response to Pegylated Interferon and Ribavirin in Hepatitis C by Polymorphisms in the Viral Core Protein and Very Early Dynamics of Viremia

“…Early HCV dynamics may differ between patients receiving Peg-IFN and standard IFN [28] , because it takes 3 days before the maximum serum level is reached with Peg-IFN. In our previous study [29] , however, decreases in HCV RNA levels were significantly greater in patients with than without SVR from 24 h to 12 weeks after the start of combined Peg-IFN and ribavirin; they all were infected with HCV-1b in high loads. We have reported that polymorphisms of aa 70 and/or aa 91 in the core protein are associated with SVR in patients infected with HCV-1b in high loads ( 6 100 KIU/ ml) and useful in predicting response to Peg-IFN and ribavirin prior to the institution of therapy [13,14] .…”

Amino Acid Substitution in HCV Core Region and Genetic Variation near the <b><i>IL28B</i></b> Gene Affect Viral Dynamics during Telaprevir, Peginterferon and Ribavirin Treatment

“…At present, treatments based on interferon (IFN), in combination with ribavirin, are mainstay for combating HCV infection. In Japan, HCV genotype 1b (HCV-1b) in high viral loads (>100 kIU/ml) accounts for more than 70% of HCV infections, making it difficult to treat patients with chronic hepatitis C [3]. Such a background calls for efficient treatments of Japanese patients with chronic HCV infection.…”

Amino Acid Substitutions in the Hepatitis C Virus Core Region and Lipid Metabolism Are Associated with Hepatocarcinogenesis in Nonresponders to Interferon plus Ribavirin Combination Therapy

“…Previous studies on Japanese patients infected with HCV-1b reported that IFN+RIB therapy increases the proportion of patients who achieve SVR [3,28] and that the incidence of HCC among patients who achieve SVR is lower than that among patients who do not [7]. In the present study, we examined the incidence and risk factors of HCC in HCV-1b patients who did not achieve SVR after IFN+RIB therapy.…”

“…At present, interferon (IFN), in combination with ribavirin (RIB), is the mainstay for treatment of HCV infection. In Japan, more than 70% of HCV infections are caused by HCV genotype 1b (HCV-1b) and are associated with a high viral load, making their treatment difficult [3]. …”