LAUSR

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). Conclusion: 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).