Insulin resistance predicts response to peginterferon-alpha/ribavirin combination therapy in chronic hepatitis C patients☆
Introduction
Hepatitis C virus (HCV) has hepatotropic and lymphotropic characteristics leading to a wide spectrum of extrahepatic manifestations [1], [2]. The association between a higher prevalence of type 2 diabetes mellitus (DM), with multifactorial pathogenetic mechanisms, and HCV infection has been reported [3], [4], [5], [6], [7]. In development of glucose abnormalities, insulin resistance (IR) and alteration of β-cell function have an important role. IR, caused by many metabolic factors, is also a common feature of disturbed carbohydrate metabolism in liver disease with or without cirrhosis, and precedes the development of type 2 DM [8], [9]. The associations between IR and the clinical features of chronic hepatitis C (CHC) have been observed. Hui et al. [10] reported that HCV may induce IR irrespective of the severity of liver disease and IR may be associated with severe hepatic fibrosis and contribute to fibrotic progression in chronic HCV infection, as shown in other studies [10], [11], [12].
Combination therapy with peginterferon-alpha (PEG-IFN)/ribavirin has been recommended as standard therapy for patients with HCV infection with favorable efficacy [13], [14]. Several clinical predictors of the sustained virologic response (SVR) to combination therapy have been elucidated, such as the viral factors (e.g. viral genotype 2 or 3, lower pretreatment viral load) and host factors (younger age, high body mass index, non-African–American or Asian races and host immune responses etc.) [13], [14], [15], [16], [17], [18]. The Bureau of National Health Insurance in Taiwan has been reimbursing HCV treatment using a 24-week combination therapy for all CHC patients. The high SVR rates of combination therapy have been observed in either genotype 2/3-(up to 95.0%) or genotype 1b-infected patients (up to 73.5%) in Taiwan [19], [20], [21]. Whether insulin sensitivity plays a role in the response to combination therapy in Taiwanese CHC patients deserves further investigation.
Since IR has been demonstrated to be associated with treatment responses to combination therapy among Caucasian CHC patients [22], [23], the present study aimed to elucidate the impacts of IR on the efficacy of combination therapy with (PEG-IFN)/ribavirin in Taiwanese (Asian) patients without known type 2 DM history. With stratification of patients according to the major predictors for responses, the predictive role of IR and β-cell function assessed before combination therapy were evaluated.
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Patients and study design
The present study was an open-label study in which 330 consecutive Taiwanese patients who had CHC and required therapy in the Kaohsiung Medical University Hospital were enrolled. All patients were included if they were positive for HCV antibodies and serum HCV RNA. They received combination therapy with at least >80% of total (PEG-IFN) and total ribavirin doses and for at least 80% of the total duration of 24 weeks of therapy (80/80/80 adherence). An overnight (12-h) fasting blood sample was
Results
The baseline characteristics of the 330 patients are shown in Table 1. Of 330 patients with combination therapy, 258 [78.2%, 95% confidence interval (CI): 73.8–82.7%] patients achieved SVR. Comparison of factors between patients with SVR and NR is shown in Table 2. Patients with SVR had significantly lower frequency of genotype 1b infection, a lower pretreatment HCV RNA level, and a lower fibrosis score than those who were nonresponders (37.4% vs. 73.6%, 5.20 ± 1.06 vs. 5.31 ± 0.98 log IU/mL and
Discussion
In the present study, we enrolled the largest number of cases Taiwanese (Asian) CHC patients, to our knowledge, and provided evidence that the baseline HOMA-IR had impact on the response to combination therapy with (PEG-IFN)/ribavirin. The association between higher HOMA-IR and poor response was observed and we particularly elucidated firstly the association among a specific group of “difficult-to-treat” patients who had genotype 1b infection and high pretreatment HCV RNA levels.
Glucose
Acknowledgement
The authors thank the Taiwan Liver Research Foundation for secretarial and serum processing help. The foundation did not influence how the study was conducted or the way the manuscript was approved.
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The authors who have taken part in the research of this paper declared that they do not have a relationship with the manufacturers of the drugs involved either in the past or present and they did not receive funding from the manufacturers to carry out their research.
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These authors contributed equally to this work.