Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance.
OBJECTIVE
Both spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groupsMethods: A total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis.


RESULTS
Nineteen (2.2%) of the 877 patients developed HCC during 6,963 person-years of follow-up. Fourteen (2.5%) SVR patients and 5 (1.6%) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27-26.88), diabetes (HR/CI:3.41/1.21-9.58), and age (HR/CI: 1.07/1.01-1.14). Of the 564 SVR patients, eleven (5.9%) of the 187 patients with fibrosis stage 2-4 (F2-4) and 2 (0.9%) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2-4 (P<0.001) but not F0-1(P=0.60) had a higher risk of HCC development. Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2-4 (versus SC: HR/CI: 10.06/2.20-45.98), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15).


CONCLUSIONS
Compared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision-making regarding the prioritization of current direct antiviral agents in resource-limited countries.
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chung-Feng
CF
Huang
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ming-Lun
ML
Yeh
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ching-I
CI
Huang
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Yu-Ju
YJ
Lin
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Pei-Chien
PC
Tsai
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Zu-Yau
ZY
Lin
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Soa-Yu
SY
Chan
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shinn-Cherng
SC
Chen
The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Hwai-I
HI
Yang
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jee-Fu
JF
Huang
The Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.|Chang Gung University School of Medicine, Kaohsiung, Taiwan.
Sheng-Nan
SN
Lu
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chia-Yen
CY
Dai
The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Chin-Lan
CL
Jen
The Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, United States of America.
Yong
Y
Yuan
The Yale University School of Medicine, New Haven, CT, United States of America.
Gilbert
G
L'Italien
MacKay Medical College, Taipei, Taiwan.
Li-Yu
LY
Wang
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Mei-Hsuan
MH
Lee
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.|Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
Ming-Lung
ML
Yu
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wan-Long
WL
Chuang
Academia Sinica, Taipei, Taiwan.
Chien-Jen
CJ
Chen
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology*; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications / Q000209:etiology; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000072230:Sustained Virologic Response
D000998:Antiviral Agents; D015415:Biomarkers
HCC; HCV; spontaneous clearance; treatment