Abstract
BackgroundInsulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients. The aim of this study was to assess the effect of insulin resistance on the development of HCC by non-cirrhotic chronic hepatitis C patients treated with pegylated interferon alpha-2b (PEG-IFNα2b) and ribavirin.MethodsThis retrospective study consisted of 474 Japanese non-cirrhotic patients with chronic hepatitis C. The cumulative incidence of HCC was estimated using the Kaplan-Meier method, according to insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) and treatment outcome.ResultsThe overall sustained virological response (SVR) rate was 45.1 % (214/474, genotype 1: 35.4 % [129/364] and genotype 2: 77.3 % [85/110]). Twenty-one (4.4 %) patients developed HCC during the follow-up period. The 5-year cumulative incidence of HCC of the SVR group (2.6 %) was significantly lower than that of the non-SVR group (9.7 %) (log-rank test: P = 0.025). In multivariable logistic regression analysis, HOMA-IR (≥2.5) (hazard ratio [HR] 12.8, P = 0.0006), fibrosis status (F3) (HR 8.85, P < 0.0001), and post-treatment alanine aminotransferase (ALT) level (≥40 U/L) (HR 4.33, P = 0.036) were independently correlated to the development of HCC. Receiver operating characteristic analysis to determine the optimal threshold value of HOMA-IR for predicting the development of HCC in the non-SVR group showed that the areas under the curve was high (0.80, cutoff value: 3.0). Only three patients (1.4 %) who achieved SVR developed HCC. Two of them had severe insulin resistance and did not show improvement in HOMA-IR after achieving SVR.ConclusionsInsulin resistance has a strong impact on the development of HCC by non-cirrhotic patients who have PEG-IFNα2b and ribavirin treatment failure.
Highlights
Insulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients
We recently reported that insulin resistance undermined the efficacy of Hepatitis C virus (HCV) clearance in PEG-IFNα2b and ribavirin treatment [18], no reports of the possible association of insulin resistance with the development of HCC after antiviral treatment for non-sustained virological response (SVR) patients have been provided
The development of HCC was associated with older age (≥60 years) (P = 0.0085), higher pre-treatment Alanine aminotransferase (ALT) level (≥40 U/L) (P = 0.042), higher post-treatment ALT level (≥40 U/L) (P < 0.0001), higher AFP level (≥10.0 ng/mL) (P = 0.0030), higher fasting serum insulin level (≥15.0 μU/mL) (P = 0.0033), higher homeostasis model assessment of insulin resistance (HOMA-IR) (≥2.5) (P < 0.0001), advanced fibrosis (METAVIR F3), and non-SVR (P < 0.0001)
Summary
Insulin resistance is considered to be an important factor in the progression of fibrosis and the enhancement of the risk of hepatocellular carcinoma (HCC) for chronic hepatitis C patients. The aim of this study was to assess the effect of insulin resistance on the development of HCC by non-cirrhotic chronic hepatitis C patients treated with pegylated interferon alpha-2b (PEG-IFNα2b) and ribavirin. HCV-infected patients who obtain a sustained virological response (SVR) by IFN monotherapy or pegylatedIFN-alpha (PEG-IFNα) and ribavirin demonstrate significant improvement in liver fibrosis [11, 12] and Hayashi et al Infectious Agents and Cancer (2016) 11:9 a decrease in the occurrence of decompensated liver disease and HCC [4,5,6,7,8,9] compared with untreated or non-SVR patients. Male, older age, cirrhosis, non-SVR, and alpha-fetoprotein (AFP) level were reported to be associated with the development of HCC [6, 7]
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