Fibrosis Progression in African Americans and Caucasian Americans With Chronic Hepatitis C

Abstract

Background & Aims Prior studies suggest the rate of liver fibrosis progression is slower in African-Americans (AA) than Caucasian-Americans (CA) with chronic hepatitis C virus (HCV) infection. Methods Using a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use. Results The distribution of Ishak fibrosis stages were 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%) and 5/6 (6.3%), and was similar in AA and CA (p= 0.22). After adjusting for biopsy adequacy, AA had a 10% lower rate of fibrosis progression than did CA, but the difference was not statistically significant (hazard ratio = 0.90, 95% confidence intervals = 0.72, 1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4 and 5/6 were 59.3%, 28.8% and 4.7%. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort, and 74 and 83 years for CA and AA, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score. Conclusions The rates of fibrosis progression were slow and did not appear to differ substantially between AA and CA.

Non-Markov Multistate Modeling Using Time-Varying Covariates, with Application to Progression of Liver Fibrosis due to Hepatitis C Following Liver Transplant

“…Although some studies have analyzed "fibrosis units per year" by assuming numeric equivalence of the differences between all consecutive stages and a constant rate of progression within each patient (Poynard, Bedossa and Opolon, 1997), a multistate model would likely be more realistic and useful. Standard multistate Markov models, such as implemented in the msm() function available in the R statistical package (cran.us.r-project.org/src/contrib/Descriptions/msm.html), have been used for HCV progression modeling (Deuffic-Burban, Poynard and Valleron, 2002;Terrault et al, 2008), but the Markov assumption-that prior history has no effect on disease progression-is questionable.…”

Applying a system approach to forecast the total hepatitis C virus‐infected population size: model validation using US data

“…Considerable work has been undertaken to forecast the epidemiology of hepatitis C and numerous authors have developed Markov models to estimate the disease burden (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, these models have limitations resulting from the assumption that the studied cohorts remain homogeneous and traverse through different states at a fixed rate over time when, in reality, populations are very heterogeneous (17).…”

Effective use of FibroTest to generate decision trees in hepatitis C

“…However, age has consistently been reported as an important risk factor for fibrosis progression in chronic viral hepatitis, either at the onset of the disease or during its evolution. The changes with age tend mostly to be subtle and are consistent with a disease of long duration associated with the progression of nor mal aging [20][21][22][23] . How and why variants arise probably relates to changes in extracellular matrix [24,25] , liver regeneration [26] and repair mechanisms [27] .…”