title: Risk of end-stage liver disease, hepatocellular carcinoma, and liver-related death by fibrosis stage in the hepatitis C Alaska Cohort.
abstract: Long-term prospective studies of the outcomes associated with hepatitis C virus (HCV) infection are rare and critical for assessing the potential impact of HCV treatment. Using liver biopsy as a starting point, we analyzed the development of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), and liver-related death (LRD) according to fibrosis stage among a cohort of American Indian/Alaska Native persons in Alaska. Persons were classified as having no/mild (Ishak = 0,1), moderate (Ishak = 2), or severe (Ishak = 3,4) fibrosis or cirrhosis (Ishak = 5,6). We examined time until development of ESLD, HCC, and LRD and report survival probabilities at 3, 5, 7, and 10 years. Of 407 persons, 39% (n = 150) had no/mild fibrosis, 32% (n = 131) had moderate fibrosis, 22% (n = 88) had severe fibrosis, and 9% (n = 38) had cirrhosis. The average time of follow-up was 7.3 years. Within 5 years of biopsy, 1.7% (95% confidence interval [CI]: 0.4-6.8) of persons with no/mild fibrosis developed ESLD compared with 7.9% (95% CI, 4.0-15.2), 16.4% (95% CI, 9.6-27.2), and 49.0% (95% CI, 33.0-67.7) with moderate, severe fibrosis, and cirrhosis, respectively (P < 0.01). The 5-year outcome of HCC was 1.0% (95% CI, 0.1-7.0), 1.0% (95% CI, 0.1-6.6), 1.1% (95% CI, 0.2-7.7), and 13.4% (95% CI, 4.4-36.7) among persons with no/mild fibrosis, moderate fibrosis, severe fibrosis, and cirrhosis, respectively (P < 0.01). Five years after biopsy, 0.0% (95% CI, 0.0-14.8) of persons with no/mild fibrosis had suffered an LRD compared with 1.0% (95% CI, 0.2-7.5) of persons with moderate fibrosis, 4.7% (95% CI, 1.5-14.1) with severe fibrosis, and 16.3% (95% CI, 7.0-35.1) with cirrhosis (P < 0.01).
  
  
  
  For prevention of HCC, LRD, and ESLD in the short term, HCV therapy should target individuals who have more than mild fibrosis. (Hepatology 2017;66:37-45).
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Anchorage, Alaska.
authors.forename: Dana J T
authors.initials: DJT
authors.lastname: Bruden
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Anchorage, Alaska.|Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McMahon
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Lisa
authors.initials: L
authors.lastname: Townshend-Bulson
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Anchorage, Alaska.
authors.forename: Prabhu
authors.initials: P
authors.lastname: Gounder
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Jim
authors.initials: J
authors.lastname: Gove
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Julia
authors.initials: J
authors.lastname: Plotnik
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Chriss
authors.initials: C
authors.lastname: Homan
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Annette
authors.initials: A
authors.lastname: Hewitt
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Barbour
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Spradling
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Brenna C
authors.initials: BC
authors.lastname: Simons
authors.affiliation: University of Washington, Department of Virology, School of Medicine, Seattle, Washington.
authors.forename: Susan
authors.initials: S
authors.lastname: McArdle
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Anchorage, Alaska.
authors.forename: Michael
authors.initials: M
authors.lastname: Bruce
mesh_terms: D000328:Adult; D000368:Aged; D000413:Alaska / Q000453:epidemiology; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000503:physiopathology / Q000628:therapy; D002423:Cause of Death; D015331:Cohort Studies; D015897:Comorbidity; D016001:Confidence Intervals; D016208:Databases, Factual; D018450:Disease Progression; D058625:End Stage Liver Disease / Q000453:epidemiology* / Q000503:physiopathology / Q000628:therapy; D005260:Female; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult