title: Development of hepatocellular carcinoma in chronic hepatitis B patients with advanced fibrosis is independent of viral genotype.
abstract: Hepatitis B is leading cause of liver related morbidity in Asia with predominant genotypes B and C in East-Asia. Data on Serum, intrahepatic viral-markers, and long-term follow-up of prevalent genotypes (GT) B and C in patients with biopsy proven advanced fibrosis are sparse. To compare serum, intrahepatic viral-markers and development of hepatocellular carcinoma (HCC) in GT-B and C in patients with advanced fibrosis (Ishak ≥ 4). Sixty-three treatment-naïve patients identified with advanced fibrosis on liver-biopsy performed between 1998 and 2000 at Singapore General Hospital. FFPE tissue was available for 59 patients and serum for 42 patients. HBV-DNA was quantified in serum and liver while qHBsAg quantified in serum. Patients were followed-up till December 2015. The median age was 47 ± 16 years, with 77.7% males. About 19 were GT-B, 43 patients were GT-C, and 1 had both GT-B and C. Mean follow-up was 13.5 years. The median serum HBV-DNA was 6.25 ± 2.17 and 6.58 ± 1.85 log IU/ml, serum HBsAg was 3.29 ± 0.80 and 3.45 ± 1.85 log IU/ml, and intrahepatic HBV-DNA was 0.52 ± 3.73 copies/cell and 0.4 ± 1.37 copies/cell in the GT-B and C, respectively (P > 0.1 in all). Complete cirrhosis (Ishak-6) was present in 47.6%, Ishak-5 fibrosis in 33.3%, and Ishak-4 fibrosis in 19% at recruitment. On follow-up HCC developed in 8/43 in GT-C and in 3/19 GT-B (P = 0.86). Advanced age and cirrhosis were significant factors for development of HCC. No difference in serum HBV-DNA, qHBsAg or intrahepatic HBV-DNA was seen in the two genotypes. HCC development seen over long-term follow-up was independent of genotypes in patients with advanced fibrosis. J. Med. Virol. 89:845-848, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Cancer Research Centre of Lyon, INSERM U1052, CNRS 5286, Lyon, France.|Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Cancer Research Centre of Lyon, INSERM U1052, CNRS 5286, Lyon, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Testoni
authors.affiliation: Cancer Research Centre of Lyon, INSERM U1052, CNRS 5286, Lyon, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Fresquet
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Tony Kiat Hon
authors.initials: TK
authors.lastname: Lim
authors.affiliation: Division of Medicine, Singapore General Hospital, Singapore, Singapore.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Cancer Research Centre of Lyon, INSERM U1052, CNRS 5286, Lyon, France.
authors.forename: Hui Hui
authors.initials: HH
authors.lastname: Tan
authors.affiliation: Cancer Research Centre of Lyon, INSERM U1052, CNRS 5286, Lyon, France.
authors.forename: Wan Cheng
authors.initials: WC
authors.lastname: Chow
authors.affiliation: Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
mesh_terms: D000328:Adult; D000368:Aged; D001208:Asia; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: advanced fibrosis; hepatitis B genotypes; hepatocellular carcinoma