A comparison of fibrosis progression in chronic liver diseases
Introduction
Fibrosis is deleterious but is the variable consequence of chronic liver disease [1]. Mortality associated with chronic liver diseases is almost always due to the development of cirrhosis, the final stage of fibrosis progression, and its complications [2], [3], [4], [5], [6], [7], [8].
Determining optimal screening strategies for fibrosis is important since there are currently available treatments which reduce fibrosis progression: pegylated-interferon and ribavirin for chronic hepatitis C [9], lamivudine and for hepatitis B [10], reduction of alcohol consumption for alcoholic liver disease (ALD) [5], [6], venesection for genetic hemochromatosis (GH) [7], and ursodesoxycholic acid for primary biliary cirrhosis (PBC) [11]. There are also better non-invasive markers of liver fibrosis that may prove useful for screening at-risk patients [12], [13], [14].
Therefore, an estimate of fibrosis progression represents an important surrogate endpoint that may facilitate treatment decisions by clarifying the vulnerability of an individual patient to progression. The concept of fibrosis progression estimation was first developed and applied to patients with chronic hepatitis C virus (HCV) infection [3]. In these patients, this concept has permitted us to explain discordances observed in the literature regarding the natural history of hepatitis C and to reconstruct the epidemic [3], [14], [15], [16], [17], [18], [19]. Among the other main chronic liver diseases, no study has assessed rates of fibrosis progression using this concept.
The aim of this study was to assess the rates of fibrosis progression in the other most frequent chronic liver diseases: hepatitis C with HIV co-infection, hepatitis B, delta hepatitis, ALD, GH, PBC and auto-immune hepatitis (AIH) and to identify the risk factors for progression.
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Patients and methods
Databases of patients with chronic liver diseases were studied. The inclusion criteria were an interpretable liver biopsy prior to any specific treatment for the underlying disorder. Patients with more than one cause of liver disease (with the exception of significant alcohol consumption) were excluded. A total of 4852 patients were included (Table 1).
For chronic hepatitis C, the databases have been previously described [3], [16]. The first database included 2313 patients [20], [21] and a
Comparison between diseases
The probability of fibrosis progression to cirrhosis and to septal fibrosis and the corresponding cumulative percentage of patients beyond these stages are shown in Fig. 1. The common features among the diseases were the late occurrence of cirrhosis beyond 40 years of age and a roughly linear progression of fibrosis by decades. Almost all of the comparisons between the diseases were highly significant (P<0.001). The ages at which the probability for cirrhosis was 50% were 52 years for HCV–HIV
Discussion
The major finding of this study is the variability of fibrosis progression according to the aetiology of liver disease, age and gender. These results have important implications for the implementation of screening strategies for fibrosis. The modelling methodology allowed us to assess the cumulative prevalence of fibrosis progression according to age and to the duration of exposure.
It is difficult to use cross-sectional, observational data to estimate longitudinal parameters. The main
Acknowledgements
This study was supported by grants from Association pour la Recherche sur le Cancer, Assistance Publique des Hôpitaux de Paris and Association pour la Recherche sur les Maladies Hépatiques Virales. The ‘Observatoire de l'Hépatite C’ is supported by DRC-EMUL-GERMED, Schering Plough, Roche, GlaxoWellcome and Chiron companies and monitored by Quanta Medical.
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