Progression of biopsy-measured liver fibrosis in untreated patients with hepatitis C infection: non-Markov multistate model analysis

• Published in: PloS one Vol. 6; no. 5; p. e20104
• Main Authors: Bacchetti, Peter, Boylan, Ross, Astemborski, Jacquie, Shen, Hui, Mehta, Shruti H, Thomas, David L, Terrault, Norah A, Monto, Alexander
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.05.2011; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adolescent; Adult; African Americans; Age; Aging - pathology; AIDS; Alcohol use; Antiretroviral agents; Biopsy; Confidence intervals; Disease Progression; Fibrosis; Geriatrics; Health risks; Hepatitis; Hepatitis C; Hepatitis C - complications; Highly active antiretroviral therapy; HIV; HIV infections; Human immunodeficiency virus; Humans; Infection; Infections; Interferon; Liver; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - pathology; Liver transplants; Markov Chains; Mathematics; Measurement; Medicine; Middle Aged; Models, Biological; Race; Risk analysis; Risk Factors; Risk reduction; Sensitivity and Specificity; Time Factors; Viruses; Young Adult; San Francisco California; California; United States > US; Maryland; Baltimore Maryland
• DOI: 10.1371/journal.pone.0020104
• ISSN: 1932-6203

Fibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times. We used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR) quantified the estimated effects of covariates on progression risk at any given time. Models estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018), and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002). When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80). There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059). Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection. The analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating active disease and high risk, while longer time already spent in a stage indicates quiescent disease and low risk.