title: Infection With Hepatitis C Virus Genotype 3 Is an Independent Risk Factor for End-Stage Liver Disease, Hepatocellular Carcinoma, and Liver-Related Death.
abstract: Few studies have examined factors associated with disease progression in hepatitis C virus (HCV) infection. We examined the association of 11 risk factors with adverse outcomes in a population-based prospective cohort observational study of Alaska Native/American Indian persons with chronic HCV infection.
  
  
  
  We collected data from a population-based cohort study of liver-related adverse outcomes of infection in American Indian/Alaska Native persons with chronic HCV living in Alaska, recruited from 1995 through 2012. We calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for end-stage liver disease (ESLD; presence of ascites, esophageal varices, hepatic encephalopathy, or coagulopathy), hepatocellular carcinoma (HCC), and liver-related death using a Cox proportional hazards model.
  
  
  
  We enrolled 1080 participants followed up for 11,171 person-years (mean, 10.3 person-years); 66%, 19%, and 14% were infected with HCV genotypes 1, 2, and 3, respectively. On multivariate analysis, persons infected with HCV genotype 3 had a significantly increased risk of developing all 3 adverse outcomes. Their aHR for ESLD was 2.1 (95% CI, 1.5-3.0), their aHR for HCC was 3.1 (95% CI, 1.4-6.6), and their aHR for liver-related death was 2.4 (95% CI, 1.5-4.0) compared with genotype 1. Heavy alcohol use was an age-adjusted risk factor for ESLD (aHR, 2.2; 95% CI, 1.6-3.2), and liver-related death (aHR, 2.9; 95% CI, 1.8-4.6). Obesity was a risk factor for ESLD (aHR, 1.4; 95% CI, 1.0-1.9), and diabetes was a risk factor for ESLD (aHR, 1.5; 95% CI, 1.1-2.2). Male sex was a risk factor for HCC (aHR, 3.6; 95% CI, 1.6-8.2).
  
  
  
  In a population-based cohort study of American Indian/Alaska Native persons with chronic HCV infection, we found those infected with HCV genotype 3 to be at high risk for ESLD, HCC, and liver-related death.
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska; Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control, Anchorage, Alaska. Electronic address: bdm9@cdc.gov.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McMahon
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control, Anchorage, Alaska.
authors.forename: Dana
authors.initials: D
authors.lastname: Bruden
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: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Brenna
authors.initials: B
authors.lastname: Simons
authors.affiliation: Division of Viral Hepatitis, Centers for Human Immunodeficiency Virus, Tuberculosis Prevention, Sexually Transmitted Diseases, and Viral Hepatitis, Centers for Disease Control, Atlanta, Georgia.
authors.forename: Phillip
authors.initials: P
authors.lastname: Spradling
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Stephen
authors.initials: S
authors.lastname: Livingston
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: James
authors.initials: J
authors.lastname: Gove
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: 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: Hannah
authors.initials: H
authors.lastname: Espera
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Susan
authors.initials: S
authors.lastname: Negus
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Mary
authors.initials: M
authors.lastname: Snowball
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: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control, Anchorage, Alaska.
authors.forename: Michael
authors.initials: M
authors.lastname: Bruce
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control, Anchorage, Alaska.
authors.forename: Prabhu
authors.initials: P
authors.lastname: Gounder
mesh_terms: D000328:Adult; D000413:Alaska / Q000453:epidemiology; D000072957:Alaska Natives; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000401:mortality; D018450:Disease Progression; D058625:End Stage Liver Disease / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology*; D006801:Humans; D007198:Indians, North American; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis
keywords: AK-HEPC; American Indian/Alaska Native; Hepatitis C Outcome; Liver Cancer Risk