title: Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy.
abstract: Although diabetes mellitus (DM) is known to increase the risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the impact of dynamic glucose status on HCC occurrence in chronic hepatitis C (CHC) patients receiving antiviral therapy is unclear. In total, 1112 biopsy-proven patients treated with peginterferon/ribavirin were enrolled in this study. Both pretreatment and post-treatment glucose status, including 75 g oral glucose tolerance test (OGTT), were measured to evaluate the association between glucose status and the development of HCC. Of the 1112 patients evaluated, 93 (8.4%) developed HCC >5183.8 person-years of follow-up (annual incidence rate: 1.79%). DM only influenced the risk of developing CC in patients with mild liver disease (F0-2) and a sustained virological response (SVR) but not in other patient subpopulations. Cox-regression analysis demonstrated that the strongest factor associated with HCC in patients with mild liver disease and SVR was the presence of DM (hazard ratio [HR]/95 % confidence intervals [CI]: 3.79/1.420-10.136, P = 0.008), followed by age (HR/CI: 1.06/1.001-1.117, P = 0.046) and platelet count (HR/CI: 0.989/0.979-1.000, P = 0.05). The percentages of SVR patients with F0-2 with normoglycemia, pre-DM, sub-DM (pre-sDM), and DM before treatment were 45.3% (n = 267), 29.9% (n = 176), 15.6% (n = 92), and 9.2% (n = 54), respectively. The percentages of HCC in patients with normoglycemia, pre-sDM, and DM were 1.1%, 3.7%, and 11.1%, respectively (trend P < 0.001). Sixteen of the 19 (84.2 %) HCC patients possessed glucose abnormality (including 6 patients with DM and 10 patients with pre-sDM) before antiviral therapy. Compared to patients with normoglycemia, the incidence of HCC increased gradually from pre-sDM (HR: 3.6, P = 0.05) to DM (HR: 11.6, P = 0.001) (adjusted trend P = 0.004). We concluded that DM is a critical determinant for the development of HCC in SVR patients with mild liver disease. Pre-sDM status carried an additional risk for HCC, and these patients should also be carefully monitored for HCC after viral eradication.
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan Institute of Biomedical Sciences, National Sun Yat-Sen University.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.forename: Cing-Yi
authors.initials: CY
authors.lastname: Huang
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Ko
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology; D048909:Diabetes Complications / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D000998:Antiviral Agents; D001786:Blood Glucose