title: Reduction of chronic hepatitis B-related hepatocellular carcinoma with anti-viral therapy, including low risk patients.
abstract: Anti-viral therapy in chronic hepatitis B (CHB) is associated with a reduced risk of hepatocellular carcinoma (HCC) primary described in patients with cirrhosis.
  
  
  
  To examine the effects of treatment on HCC incidence in CHB with and without cirrhosis, after adjustment for background risks.
  
  
  
  A total of 2255 CHB patients from a US cohort (973 received anti-viral therapy) and 3653 patients from the community-based Taiwanese REVEAL-HBV study, none of whom received treatment. We used Cox proportional hazard models to calculate the risk of developing HCC after adjustment with the previously validated REACH-B risk score.
  
  
  
  We found 273 incident cases of HCC. After adjustment, therapy lowered the risk of HCC development in the US treated cohort when compared to the US untreated cohort (HR 0.31; 95% CI: 0.15-0.66; P = 0.002). HCC risk reduction was also confirmed when compared to the REVEAL cohort (HR 0.22; 95% CI: 0.12-0.40; P < 0.001). Each REACH-B point was associated with a 53% increased risk of HCC (HR 1.53; 95% CI 1.46-1.59; P < 0.001). We found a significant statistical reduction in HCC incidence with therapy regardless of gender, age, cirrhosis status, HBeAg serology, alanine aminotransferase level, REACH-B score or treatment medication. Therapy was beneficial to those with mildly- to moderately elevated HBV DNA levels (>2000 IU/mL) and of even greater benefit to those with levels >200 000 IU/mL.
  
  
  
  After adjustment for background risk, anti-viral therapy was associated with a significant reduction in HCC incidence in both community and real-life clinical cohorts, including in those patients previously thought to be at low risk.
authors.affiliation: Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan. hiyang@gate.sinica.edu.tw.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. hiyang@gate.sinica.edu.tw.
authors.forename: H-I
authors.initials: HI
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.|Department of Medicine, University of California San Diego, San Diego, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Nguyen
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hoang
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Vu
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Le
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.|Pacific Health Foundation, San Jose, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Chaung
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.|Pacific Health Foundation, San Jose, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: San Jose Gastroenterology, San Jose, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Trinh
authors.affiliation: Mountain View Division, Palo Alto Medical Foundation, Mountain View, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Chinese Hospital, San Francisco, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Stanford Cancer Institute, Stanford School of Medicine, Palo Alto, CA, USA.|Health Research and Policy Department, Stanford School of Medicine, Standford, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hsing
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: C-J
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA. mindiehn@stanford.edu.
authors.forename: M H
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens