Elsevier

Journal of Hepatology

Volume 38, Issue 3, March 2003, Pages 257-265
Journal of Hepatology

A comparison of fibrosis progression in chronic liver diseases

https://doi.org/10.1016/S0168-8278(02)00413-0Get rights and content

Abstract

Background/Aims: No study has compared the liver fibrosis progression rates among chronic liver diseases and the risk factors in order to better organize screening strategies.

Methods: A total of 4852 patients were retrospectively studied (chronic hepatitis C (HCV) [n=2313], human immunodeficiency virus (HIV)–HCV co-infection (HIV–HCV [n=180]), hepatitis B (HBV [n=777]), alcoholic liver disease (ALD [n=701]), primary biliary cirrhosis (PBC [n=406]), genetic hemochromatosis (GH [n=383]) auto-immune hepatitis (AIH [n=57]) and delta hepatitis (n=35). The fibrosis progression rates were estimated from birth and from the date of exposure, when known, to the first biopsy.

Results: There were highly significant differences in the rates of fibrosis progression, the most rapid being HIV–HCV co-infection (50% cirrhosis percentile at 52 years of age) and the slowest being PBC (50% cirrhosis percentile at 81 years). There was an acceleration of fibrosis progression with aging. Fibrosis progression was slower in females compared with males for HCV, HBV, GH, and PBC. In contrast, in ALD, the fibrosis progression was more rapid in females.

Conclusions: Rates of fibrosis progression differ markedly between the predominant causes of chronic liver disease, and according to age and gender. Patients with HIV–HCV co-infection are at particularly high risk of fibrosis progression.

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.

Section snippets

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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