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Hepatitis B: Liver fibrosis and hepatocellular carcinomaHépatite B : fibrose hépatique et carcinome hépatocellulaire

https://doi.org/10.1016/j.gcb.2009.06.001Get rights and content

Summary

Chronic hepatitis B virus (HBV) infection is estimated to be the cause of 55–60% of hepatocellular carcinoma (HCC) in the world. It has been estimated that up to 40% of HBV-related HCC occur in persons who do not have cirrhosis while almost all cases of hepatitis C virus (HCV)-related HCC occur in the setting of cirrhosis. Data on the performance of non-invasive tests for liver fibrosis in patients with hepatitis B are limited. FibroTest may be superior to the Forns index, APRI, Goteborg University Cirrhosis Index (GUCI) and Hui model in detecting significant fibrosis (Metavir > F2) or cirrhosis (Metavir F4) but an algorithm that uses APRI for screening, FibroTest for confirmation, and biopsy for indeterminate cases has the greatest accuracy. Liver stiffness correlates with fibrosis stages but may be influenced by necroinflammatory activity with falsely high values in patients with alanine aminotransferase (ALT) flares and falsely low values in patients with viral suppression and ALT normalization during antiviral therapy. Therefore, additional studies are needed to determine the clinical settings in which liver stiffness measurement can accurately predict liver fibrosis and to establish cutoff values for differentiating different stages of fibrosis or cirrhosis. These studies should also compare the performance of liver stiffness measurement with serum markers of fibrosis in patients with varying degrees of necroinflammation and in untreated patients as well as patients receiving antiviral therapy. Until recently, older age, male gender and cirrhosis were the major risk factors associated with HCC development. Recent studies showed that HBV replication status, HBV genotype and mutations in the basal core promoter region play an important role in HCC development. These data indicate that algorithms incorporating demographics, viral factors, degree of necroinflammation and extent of fibrosis may be more accurate in predicting the risk of HBV-related HCC than fibrosis staging alone.

Résumé

Dans le monde, l’infection chronique par le virus de l’hépatite B (VHB) serait la cause de 55 à 60 % des cas de carcinome hépatocellulaire (CHC). Près de 40 % des CHC liés à une infection par le VHB surviennent chez des malades sans cirrhose tandis que la majorité des CHC compliquant les infections par le virus de l’hépatite C surviennent chez des patients cirrhotiques. Au cours de l’hépatite B, les performances des tests non-invasifs de diagnostic de la fibrose ont été peu évaluées. Le FibroTest serait plus performant que le score de Forns, le score APRI, l’index de cirrhose de l’université de Goteborg (GUCI), et le modèle de Hui pour diagnostiquer la fibrose significative (Metavir > F2) ou la cirrhose (Metavir F4), mais un algorithme utilisant l’APRI en première intention, le FibroTest en confirmation et la ponction-biopsie hépatique pour les cas indéterminés aurait la meilleure performance. L’élasticité hépatique est corrélée aux différents stades de fibrose mais pourrait être influencée par l’activité nécrotico-inflammatoire avec des valeurs plus élevées au cours des réactivations virales et des valeurs plus basses chez les patients avec virosuppression et normalisation du taux des transaminases au cours du traitement. De ce fait, d’autres études sont nécessaires pour définir les situations cliniques au cours desquelles la mesure de l’élasticité hépatique peut diagnostiquer la fibrose hépatique et pour établir les valeurs seuils permettant de différencier les différents stades de fibrose et la cirrhose. Ces études devraient aussi comparer la performance de la mesure de l’élasticité hépatique avec les marqueurs sériques de fibrose chez les patients avec différents degrés d’inflammation et chez les malades traités et non traités. Jusqu’à récemment, un âge élevé, le sexe masculin et la présence d’une cirrhose étaient les facteurs de risque les plus importants de CHC. Les études récentes ont montré que la réplication virale, le génotype du VHB, et les mutations de la région précore étaient importantes dans le développement d’une CHC. Des algorithmes intégrant des données démographiques, des facteurs viraux, le degré d’inflammation et la sévérité de la fibrose pourraient être plus performants pour prédire le risque de CHC au cours de l’hépatite B que l’évaluation seule de la fibrose.

Introduction

Chronic hepatitis B virus (HBV) infection is estimated to be the cause of 55–60% of hepatocellular carcinoma (HCC) in the world. The annual incidence of HCC has been estimated to be less than 1% for non-cirrhotic carriers and 2%–3% for patients with cirrhosis [1]. Several lines of evidence indicate that the incidence of HCC is higher among Asians than Caucasians. This difference may be partly related to a longer duration of infection among Asians (perinatal vs. adult acquired infection) but several studies suggest that other factors such as HBV genotype and exposure to aflatoxin may contribute to this difference. This article will review:

  • the frequency in which HBV-related HCC is found in the absence of cirrhosis;

  • the utility of non-invasive tests for assessment of hepatic fibrosis or cirrhosis;

  • the risk factors for HCC in persons with chronic HBV infection.

Section snippets

HBV-related HCC in patients without significant fibrosis or cirrhosis

Cirrhosis, regardless of etiology, is considered to be the most important risk factor for HCC. It has been estimated that up to 40% of HBV-related HCC occur in persons who do not have cirrhosis while almost all cases of hepatitis C virus (HCV)-related HCC occur in the setting of cirrhosis. The explanation for the more frequent occurrence of HBV-related HCC in the absence of cirrhosis has been attributed to the direct oncogenic effects of HBV. It should be emphasized that the proportion of HCC

Non-invasive tests for hepatic fibrosis or cirrhosis

Liver biopsy is the gold standard for assessment of hepatic fibrosis or cirrhosis but it is an invasive procedure with a risk of significant bleeding of one in 2500 to one in 10,000 and a risk of death of less than or equal to one in 10,000 and is subject to sampling error [8]. During the last 15 years, there has been extensive research into non-invasive tests for hepatic fibrosis or cirrhosis. These tests include indices or algorithms based on routine laboratory tests, panels of serum fibrosis

Risk factors for HBV-related HCC

Until recently, older age, male gender and cirrhosis were the major risk factors associated with HCC development. Recent studies showed that HBV replication status, HBV genotype and mutations in the basal core promoter region play an important role in HCC development. These data indicate that algorithms incorporating demographics, viral factors, degree of necroinflammation and extent of fibrosis may be more accurate in predicting the risk of HBV-related HCC than fibrosis staging alone [22].

Conclusion

Most cases of HBV-related HCC occur in the setting of cirrhosis but HBV-related HCC can occur in non-cirrhotic livers. Besides cirrhosis, host and viral factors contribute to the risk of HCC. Data on non-invasive assessment of liver fibrosis in persons with chronic HBV infection are limited. Available data suggest that biomarkers and serum panels of routine laboratory tests / fibrosis makers have similar accuracies in predicting advanced fibrosis or cirrhosis in persons with HBV infection as

Conflicts of interest

None.

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