title: Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B.
abstract: OBJECTIVE
  Concurrent fatty liver in hepatitis B virus (HBV)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem because of the non-alcoholic fatty liver disease pandemic. The risk of HBV-related hepatocellular carcinoma (HCC) development was increased by concomitant obesity and diabetes. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically proven fatty liver in HBV hepatocarcinogenesis.
  
  
  METHODS
  We conducted a retrospective cohort study on a liver biopsy cohort of HBV-infected patients without significant alcohol intake to evaluate the prevalence of concurrent histologically proven fatty liver and its association with subsequent HCC development. We also examined nine polymorphisms on six non-alcoholic fatty liver disease-related candidate genes (ADIPOQ, APOC3, GCKR, LEPR, PNPLA3, and PPARG).
  
  
  RESULTS
  Among 270 HBV-infected patients, concurrent fatty liver was found in 107 patients (39.6%) and was associated with metabolic risks, cirrhosis (P = 0.016) and PNPLA3 rs738409 CG/GG genotype (P = 0.002). At a median follow-up of 79.9 months, 11 patients (4.1%) developed HCC, and nine of them had concurrent fatty liver. By multivariable Cox analysis, concurrent fatty liver (HR 7.27, 95% confidence interval: 1.52-34.76; P = 0.013), age, cirrhosis, and APOC3 rs2854116 TC/CC genotype (HR 3.93, 95% confidence interval: 1.30-11.84; P = 0.013) were independent factors predicting HCC development.
  
  
  CONCLUSIONS
  Concurrent fatty liver is common in HBV-infected patients and an independent risk factor potentiating HBV-associated HCC development by 7.3-fold. The risk of HBV-related HCC is increased by APOC3 gene polymorphism, and further characterization is required by its role.
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Science, Sir Y. K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Anthony W H
authors.identifier: http://orcid.org/0000-0002-1771-163X
authors.initials: AW
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.|Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Grace L H
authors.initials: GL
authors.lastname: Wong
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.|Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Hoi-Yun
authors.initials: HY
authors.lastname: Chan
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Science, Sir Y. K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Joanna H M
authors.initials: JH
authors.lastname: Tong
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Science, Sir Y. K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Yau-Hei
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Paul C L
authors.initials: PC
authors.lastname: Choi
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.|Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Henry L Y
authors.initials: HL
authors.lastname: Chan
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.|Li Ka Shing Institute of Health Science, Sir Y. K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong.|Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: To
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.|Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Vincent W S
authors.initials: VW
authors.lastname: Wong
mesh_terms: D000328:Adult; D001056:Apolipoproteins C / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000150:complications; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D009765:Obesity / Q000150:complications; D011110:Polymorphism, Genetic; D015995:Prevalence; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors
chemical_list: D001056:Apolipoproteins C
keywords: APOC3; PNPLA3; liver biopsy; steatosis