title: Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication.
abstract: OBJECTIVE
  Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR.
  
  
  METHODS
  A total of 642 patients with an SVR after peginterferon/ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6-133 months).
  
  
  RESULTS
  Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI 2.32-10.71, p<0.001), followed by age (HR 1.06, 95% CI 1.02-1.11, p=0.005) and γGT levels (HR 1.008, 95% CI 1.004-1.013, p<0.001). The incidence of HCC did not differ between patients with high and low baseline γGT levels among patients with cirrhosis (p=0.53), but the incidence of HCC was significantly higher in non-cirrhotic patients with high γGT levels compared with those with low γGT levels (p=0.001). Cox regression analysis revealed that the strongest factors associated with HCC development in non-cirrhotic sustained responders were baseline γGT levels (HR 6.44, 95% CI 2.20-18.89, p=0.001) and age (HR 3.68, 95% CI 1.33-10.17, p=0.012). The incidence of HCC was not different between older non-cirrhotic patients with high γGT levels and cirrhotic patients (p=0.34).
  
  
  CONCLUSIONS
  HCC remains a threat in non-cirrhotic patients with an SVR. Serum γGT levels helped to identify potential patients at high risk.
authors.affiliation: Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Hsieh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Yang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsieh
authors.affiliation: Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jeng-Fu
authors.initials: JF
authors.lastname: Yang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Liang-Yen
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address: fish6069@gmail.com.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: fish6069@gmail.com.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D012254:Ribavirin; D005723:gamma-Glutamyltransferase
keywords: HCC; HCV; SVR; Treatment; γGT