The Outcomes of Glucose Abnormalities in Pre-diabetic Chronic Hepatitis C Patients Receiving Peginterferon Plus Ribavirin Therapy

Jee-Fu Huang; Ming-Lung Yu; Chung-Feng Huang; Suh-Hang Hank Juo; Chia-Yen Dai; Ming-Yen Hsieh; Nei-Jen Hou; Ming-Lun Yeh; Meng-Hsuan Hsieh; Jeng-Fu Yang; Zu-Yau Lin; Shinn-Chern Chen; Shyi-Jang Shin; Wan-Long Chuang


Liver International. 2012;32(6):962-969. 

In This Article

Abstract and Introduction


Background/Aims Pre-diabetes is a risk factor for type 2 diabetes mellitus (DM) development. This study aimed to elucidate the impact of treatment response on sequential changes in glucose abnormalities in pre-diabetic chronic hepatitis C (CHC) patients.
Methods Chronic Hepatitis C patients with a baseline haemoglobin A1C (A1C) range 5.7–6.4% who achieved 80/80/80 adherence were prospectively recruited. All patients received current peginterferon-based recommendations. The primary outcome measurement was their A1C level at the end of follow-up (EOF). The interaction between variants of the IL28B gene and outcomes of glucose metabolism was also measured.
Results A total of 181 consecutive CHC patients were enrolled. The mean A1C at EOF was 5.82 ± 0.41%, which was significantly lower than the baseline level (5.93 ± 0.21%, P < 0.001). At EOF, 63 (34.8%) patients became normoglycaemic, whereas 10 (5.5%) patients developed DM. The sustained virological response (SVR) rates of 63 normoglycaemics, 108 pre-diabetics and 10 diabetic patients at the EOF were 92.1%, 84.3% and 50% respectively (normoglycaemics vs. diabetics P = 0.003; pre-diabetics vs. diabetics P = 0.02). Achievement of an SVR was the only predictive factor associated with normoglycaemia development at EOF by multivariate logistic regression analysis (Odds ratio = 2.6, P = 0.04). The prevalence of the interleukin 28B rs8099917 TT variant in patients who developed DM (70.0%) at EOF tended to be lower than that in patients with pre-diabetics (87.0%) or normoglycaemics (92.1%).
Conclusion Successful eradication of HCV improves glucose abnormalities in pre-diabetic CHC patients.


Hepatitis C virus (HCV) infection is the major cause of cirrhosis and hepatocellular carcinoma worldwide.[1,2] There is robust experimental and clinical data showing the prominent association between chronic HCV (CHC) and type 2 diabetes mellitus (DM).[3–7] For those without known DM, there was a 3.5-folds increase in the prevalence of glucose abnormalities in CHC patients in comparison with that in controls.[8] In addition to its various extrahepatic manifestations [9-12], HCV infection is currently considered to be a diabetogenic factor.

Diabetes Mellitus, a common endocrine disorder develops in a stepwise fashion manifesting from normoglycaemia, pre-diabetes, subclinical DM, to clinical DM.[13,14] Recently, serum haemoglobin (A1C) level has been adapted as a simple tool for the identification of persons with glucose abnormalities. Pre-diabetes, defined as A1C between 5.7% and 6.4%, carries a relatively high risk for future development of DM and even dyslipidemia and cardiovascular disease.[15] However, little information has been obtained in this special group of CHC patients in terms of treatment efficacy, treatment outcomes, sequential change of insulin resistance (IR) and the interaction with genomic profiles.

Pegylated interferon (PegIFN)-α plus ribavirin (RBV) combination therapy has become the mainstream for the treatment of CHC.[16,17] Previous studies have demonstrated that IR, the main drive of glucose abnormalities, is a predictor of sustained virological response (SVR) to antiviral therapy.[18] Meanwhile, clearance of HCV improved IR and β-cell function, and may ameliorate inflammation.[19,20] However, IFN can exacerbate an existing autoimmune tendency, which may subsequently precipitate immune-mediated abnormalities de novo, thus leading to emergence of IR and subsequent DM.[21–24] Therefore, the outcomes of pre-diabetic CHC patients after receiving PegIFN/RBV therapy remain to be determined.

Recently, studies based on genome-wide associated studies (GWAS) have showed that single nucleotide polymorphisms (SNPs) at and/or near the interleukin 28B (IL28B) gene, which encodes interferon-λ, play a critical role in the treatment efficacy of HCV infection.[25–29] Therefore, the interplay between IL28B genetic variants and IR and its related outcomes after antiviral therapy in CHC patients deserves to be elucidated.

This study aimed to elucidate the treatment outcome with respect to glucose abnormalities in pre-diabetic CHC patients receiving PegIFN/RBV combination therapy. The associated factors, including host factor of interleukin 28B-related genomic data, leading the treatment outcome were also analysed.


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