A prognostic model for development of significant liver fibrosis in HIV-hepatitis C co-infection

• Published in: PloS one 2017-05, Vol.12 (5), p.e0176282
• Main Authors: Moqueet, Nasheed, Kanagaratham, Cynthia, Gill, M John, Hull, Mark, Walmsley, Sharon, Radzioch, Danuta, Saeed, Sahar, Platt, Robert W, Klein, Marina B
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Alcoholic beverages; Bioindicators; Biology and life sciences; Canada; Care and treatment; Cohort Studies; Cost benefit analysis; Epidemiology; Ethics; Female; Fibrosis; Genotypes; Hazards; Health care networks; Health sciences; Hepatitis; Hepatitis B; Hepatitis C; Hepatitis C - complications; Hepatitis C virus; Hepatology; HIV; HIV Infections - complications; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Inflammation; Interferon; Interleukin 8; Internal medicine; Liver; Liver Cirrhosis - complications; Liver Cirrhosis - pathology; Liver diseases; Male; Markers; Mathematical models; Medical prognosis; Medical research; Medicine; Medicine and Health Sciences; Middle Aged; Models, Biological; Occupational health; Population; Predictions; Prognosis; Prospective Studies; RANTES; Reclassification; Ribonucleic acid; Risk; Risk factors; RNA; Sexually transmitted diseases; Single nucleotide polymorphisms; STD; Survival analysis; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0176282

Liver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV) co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis. A case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119). HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679) were eligible. A random subcohort (n = 236) was selected from those eligible. Pro-fibrogenic markers and Interferon Lambda (IFNL) rs8099917 genotype were measured from first available sample in all fibrosis cases (APRI ≥ 1.5 during follow-up) and the subcohort. We used Cox proportional hazards and compared Model 1 (selected clinical predictors only) to Model 2 (Model 1 plus selected markers) for predicting 3-year risk of liver fibrosis using weighted Harrell's C and Net Reclassification Improvement indices. 113 individuals developed significant liver fibrosis over 1300 person-years (8.63 per 100 person-years 95% CI: 7.08, 10.60). Model 1 (age, sex, current alcohol use, HIV RNA, baseline APRI, HCV genotype) was nested in model 2, which also included IFNL genotype and IL-8, sICAM-1, RANTES, hsCRP, and sCD14. The C indexes (95% CI) for model 1 vs. model 2 were 0.720 (0.649, 0.791) and 0.756 (0.688, 0.825), respectively. Model 2 classified risk more appropriately (overall net reclassification improvement, p