Clinical-liver, pancreas, and biliary tractThe impact of competing risks on the observed rate of chronic hepatitis C progression
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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The Placebo Response in Randomized Trials in Nonalcoholic Steatohepatitis Simply Explained
2022, Clinical Gastroenterology and HepatologyCitation Excerpt :The net fibrosis progression rate described accounts all possible changes. Fibrosis progression in liver diseases has been modeled using a gamma distribution, where the majority of persons have little progression over time, whereas an important minority show more rapid progression.11 A sequence of distributions were applied to the baseline sampling variability estimates with escalating mean rates of net fibrosis progression to identify what rate of progression produced simulated outcomes in keeping with the reported trials.
Fibrosis progression in interferon treatment-naive Chinese plasma donors with chronic hepatitis C for 20 years: A cohort study
2014, International Journal of Infectious DiseasesCitation Excerpt :Another aim of our study was to explore the possible factors associated with the presence of moderate to severe fibrosis (F ≥2). Currently, several well-accepted factors are reported to be associated with the development of fibrosis in CHC, including age at onset of infection23 and sex.24 For a similar infection period in the present study, the age at biopsy should have a similar meaning as the age at onset of infection.
Patient-important benefits of clearing the hepatitis C virus through treatment: A simulation model
2014, Journal of HepatologyCitation Excerpt :However, results will rest on certain assumptions. In particular, as per hitherto HCV models [22,24,25,27], and as is consistent with observational data [56], the HIT-model assumes a linear course of fibrosis progression over the lifetime of the patient. There is uncertainty in this assumption.
Epidemiological assessment of liver disease in northeastern Brazil by means of a standardized liver biopsy protocol
2011, Annals of HepatologyCitation Excerpt :In addition, the liver of older patients is more susceptible to lesions and less capable of regeneration.3 In an attempt to annul the effect of other possible confounding variables, a study was conducted in 2004 using a complex simulation model.22 The results of this study corroborated with previous data, confirming that the rate of progression to advanced stages of fibrosis was faster, both, in patients over fifty years of age, the longer time of infection and in male gender.
Aging of Hepatitis C Virus (HCV)-Infected Persons in the United States: A Multiple Cohort Model of HCV Prevalence and Disease Progression
2010, GastroenterologyCitation Excerpt :Taken together, our findings suggest that the CH-C that we have become familiar with during the last 30 years is much different than the hepatitis C we will come to know during the next decade or 2. Although we purposefully chose conservative estimates of disease progression and complications, it is still possible that we and others might have overestimated the number of cases that will progress to liver failure from CH-C due to the influence of competing risks.11,12,20,57 Indeed, when we increased the background (nonhepatic) mortality by just 50%, there was a striking reduction in the number of cases of cirrhosis, liver failure, and cancer.
The Changing Epidemiology and Natural History of Hepatitis C Virus Infection
2006, Clinics in Liver DiseaseCitation Excerpt :Thus, fibrosis progression is unlikely to be linear, and some models suggest that the risk of fibrosis progression increases with age [103]. However, the effect of age on risk of progression may be overestimated by a failure to account for competing risks related to deaths from natural causes [104]. Male gender is consistently associated with higher risk of fibrosis progression (∼ 2.5-fold) [101] and higher rates of cirrhosis and HCC than seen in females.