HCV Genotype 6 Increased the Risk for Hepatocellular... : Official journal of the American College of Gastroenterology | ACG (original) (raw)

ORIGINAL CONTRIBUTIONS: LIVER

HCV Genotype 6 Increased the Risk for Hepatocellular Carcinoma Among Asian Patients With Liver Cirrhosis

Lee, Mei-Hsuan PhD1,8; Hsiao, Tiffany I MS2,3,8; Subramaniam, Shreenidhi R4; Le, An K BA2; Vu, Vinh D BA2; Trinh, Huy N MD5; Zhang, Jian DNP6; Jin, Mingjuan MD, PhD7; Wong, Vincent Wai-Sun MD4; Wong, Grace Lai-Hung MD4; Nguyen, Mindie H MD, MAS2

1Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA

3School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

4Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China

5San Jose Gastroenterology, San Jose, Califonia, USA

6Chinese Hospital, San Francisco, Califonia, USA

7Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, Hangzhou, China

Correspondence: Grace K.-H. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, Califonia 94304, USA. E-mail: [email protected]

Correspondence: Grace K.-H. Wong, MD, Institute of Digestive Disease, The Chinese University of Hong Kong, 9/F, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong, China. E-mail: [email protected]

8These authors contributed equally to this work

Received 14 November 2016; accepted 14 March 2017

Guarantor of the article: Dr Mindie H. Nguyen, MD, MAS.

Specific author contributions: Study concept and design: Mindie H. Nguyen, Grace Lai-Hung Wong; acquisition of data: Tiffany I. Hsiao, Shreenidhi R. Subramaniam, An K. Le, Vinh D. Vu, Huy N. Trinh, Jian Zhang, Grace Lai-Hung Wong, Mindie H. Nguyen; analysis and interpretation of data and drafting of the manuscript: Mei-Hsuan Lee, Tiffany I. Hsiao, Mindie H. Nguyen; data interpretation and critical review of the manuscript: Shreenidhi R. Subramaniam, An K. Le, Vinh D. Vu, Huy N. Trinh, Jian Zhang, Mingjuan Jin, Vincent Wai-Sun Wong, Grace Lai-Hung Wong; study supervision: Mindie H. Nguyen.

Financial support: None.

Potential competing interests: Mindie H. Nguyen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Mindie H. Nguyen has received research support from Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals and has served as advisory board member or consultant with honoraria for Janssen Pharmaceuticals, Gilead Sciences, Intercept Pharmaceuticals, Alynam Pharmaceuticals, Roche Laboratories, and Dynavax Laboratories. Grace Lai-Hung Wong serves as an advisory board member for Gilead Sciences, and Otsuka, and has received lecture fees from Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Furui, Gilead and Otsuka. Vincent Wai-Sun Wong serves as advisory board member for AbbVie, Gilead Sciences, Otsuka, and Roche, and has received lecture fees from Echosens, Gilead Sciences, Merck; and also was a consultant for Merck, NovoMedica. Mei-Hsuan Lee serves as anadvisory board member for Gilead Sciences, has received lecture fees from Gilead Sciences, Abbvie, and Bristol-Myers Squibb, and hasreceived funding from the Ministry of Science and Technology (MOST 104-2628-B-010-001-MY3 and MOST 105-2628-B-010-003-MY4), Taipei, Taiwan. The remaining authors declare no conflict of interest.

Abstract

Objectives:

Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes.

Methods:

This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes. The incidence of HCC per 1,000 person-years of various HCV genotypes was estimated by dividing the new HCC cases to the person-years of follow-up. The adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox's proportional hazards models.

Results:

After 4072 person-years of follow-up, there were 96 newly-developed HCC cases, confirming an incidence of 23.6 per 1000 person-years. By stratifying cirrhosis at study entry, the cumulative risk of HCC among HCV genotype 6 vs. non-6 was 2.9 vs. 2.2% for those without cirrhosis ( P =0.45) and 76.2% (95% CI: 55.6–96.8%) vs. 36.2% (95% CI: 28.7–39.1%) for those with cirrhosis ( P <0.05), respectively. Among patients with cirrhosis, HCV genotype 6 was significantly associated with HCC compared to patients with non-6 genotypes, with the adjusted HR=2.12 (1.33–3.39), P <0.05. In a model treating patients with genotypes other than 1 or 6 as the reference, the adjusted HR for HCC for HCV genotypes 1 and 6 were 1.13 (0.56–2.27) and 2.34 (1.12–4.86), respectively.

Conclusions:

Among patients with cirrhosis, those with HCV genotype 6 infection should be given high priority for antiviral therapy to decrease HCC risk and for vigilant adherence to HCC surveillance.