Gastroenterology

Gastroenterology

Volume 127, Issue 3, September 2004, Pages 749-755
Gastroenterology

Clinical-liver, pancreas, and biliary tract
The impact of competing risks on the observed rate of chronic hepatitis C progression

https://doi.org/10.1053/j.gastro.2004.06.052Get rights and content

Background & aims In previous studies about the natural history of chronic hepatitis C (CHC), age at the time of infection correlated with the rate at which hepatic fibrosis progresses. The presence of a competing risk, namely higher mortality from natural causes, may contribute to this observation. A simulation experiment was conducted to measure the magnitude of the effect of competing risks on the observed rate of fibrosis progression of CHC. Methods A computer-based probabilistic model was created in which fibrosis of CHC progressed from stage 0 to 4 (cirrhosis) in 20-year-old and 50-year-old male and female cohorts. The rate of fibrosis progression was randomly assigned to each simulated individual from a distribution common to all age- and sex-specific cohorts. The cohorts also experienced mortality from natural causes according to the 2000 census data. Results The observed median time to reach cirrhosis for the 50-year-old cohorts was 20.4 ± 0.2 years compared with 29.7 ± 0.2 for the 20-year-old cohorts (P < 0.01). The median time to reach cirrhosis in men was 24.2 ± 0.6 years compared with 25.9 ± 0.6 in women (P = 0.01). Overall, the observed rate of progression was slowest among young women. Similarly, accelerating mortality from natural causes, simulating the impact of comorbid conditions that shorten survival, reduced the observed time to reach cirrhosis. Conclusions Even if the underlying rate of fibrosis progression in CHC was held constant, the time to reach cirrhosis will be observed to be substantially shorter in subjects with a higher competing mortality.

Section snippets

Study design

The goal of this experiment was to measure the impact of competing risks on the observed rate of fibrosis progression while the underlying biologic rate of progression was held constant. Thus, we constructed a probabilistic model in which the progression of fibrosis in patients with chronic hepatitis C was simulated. At the beginning of the simulation (time 0), chronic hepatitis C was first established in cohorts of individuals. Four age- and sex-specific cohorts, consisting of 20-year-old men

Results

Figure 2 shows representative cumulative incidence curves in 4 simulated age- and sex-specific cohorts. The lower curve in each panel represents the cumulative proportion of cohort members that reached F4 before they died. The upper curves represent the cumulative proportion of cohort members who have reached either end point (F4 or death). Because the underlying biologic rate of fibrosis progression was held to be identical in all of the cohorts, the differences in median time to either end

Discussion

In this simulation experiment, the observed rate of disease progression was faster in older individuals than younger counterparts when an identical underlying biologic rate was used for both age groups. These are clear examples that show that naive observational data, without completely taking into account competing risks, introduce unexpected artifacts in estimating the natural history of disease progression. Competing risk analyses have been used in cancer and transplantation literature to

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