Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis.

Dominique Thabut,Mona Munteanu,Sarah Mouri,Yen Ngo,Marika Rudler,Thierry Poynard,Frederic Charlotte,Pascal Lebray,Vlad Ratziu,Philippe Cluzel

doi:10.1371/journal.pone.0134302

Abstract

Background/AimsAccording to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment.MethodsThe reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results.ResultsA total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462–0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2–7% risk of 2 grades misclassification.ConclusionThese results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy.

Highlights

In patients with suspected alcoholic liver disease, recent guidelines recognized that the precise indications of liver biopsy are not well established in routine practice due to significant morbidity/mortality related to liver biopsy
The high AshTest performance was confirmed both for the binary outcome [area under the ROC curves (AUROC) = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462– 0.714); P
SM, FC, PC, PL, VR, and DT: These authors have no possible conflict of interest to disclose. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment

Summary

Introduction

In patients with suspected alcoholic liver disease, recent guidelines recognized that the precise indications of liver biopsy are not well established in routine practice due to significant morbidity/mortality related to liver biopsy. There is a consensus that transjugular liver biopsy "should be considered" for the diagnosis of severe alcoholic steatohepatitis (ASH) that is amenable to specific therapy such as corticosteroids, both in the EASL and AASLD guidelines,[1,2] These guidelines have recommended studies validating diagnostic algorithms including liver biopsy and non-invasive tests.[1,2]. In 2006 we published the first accuracy validation study of a non-invasive biomarker called AshTest (BioPredictive, Paris, France).[3] Two hundred and twenty-five heavy-drinker patients were included: 70 in the training group, 155 in the validation groups, and 299 controls. The AshTest area under the ROC curves (AUROC) for histologically moderate to severe ASH was 0.90 in the training group, and 0.88 to 0.89 in the validation groups.

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Results

Conclusion