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

Background/Aims According 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. Methods The 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. Results A 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. Conclusion These 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.背景/目的 根据临床诊疗指南，若需为重度酒精性脂肪性肝炎（alcoholic steatohepatitis, ASH）患者制定特异性治疗方案，通常需通过肝活检完成组织学诊断。血液检测试剂AshTest（BioPredictive，法国巴黎）最初是在大规模重度饮酒者人群中针对ASH的无创诊断完成验证的。本研究旨在针对疑似重度ASH患者的特定临床场景，验证AshTest的诊断准确性，以期在制定治疗决策前减少经颈静脉肝活检的实施需求。 方法 本研究的金标准为经颈静脉途径获取的肝活检标本，依据组织学严重程度分为无病变、轻度、中度或重度。所有活检标本均由同一位经验丰富的病理学家在对同步AshTest检测结果设盲的情况下进行阅片评估。 结果 本研究共纳入123例符合重度临床ASH诊断标准的患者（近期出现黄疸，且Maddrey评分≥32），所有患者均合并肝硬化，其中80%符合欧洲肝病学会（EASL）定义的ASH组织学特征。95%的患者接受了泼尼松龙治疗，患者2年死亡率达63%。AshTest的优异检测性能得到验证：针对二分类结局的受试者工作特征曲线下面积（AUROC）为0.803（95%CI 0.684~0.881），显著高于AST/ALT比值的AUROC值0.603（0.462~0.714；P<0.001）；采用Obuchowski指标评估的ASH严重程度评分系统中，AshTest的均值（标准误）为0.902（0.017），亦显著高于AST/ALT比值的0.833（0.023；P=0.01）。此外，AshTest在气球样变、中性粒细胞浸润（PMN）及马洛里小体的诊断与严重程度评估中同样表现优异。根据不一致结果的归因分析，AshTest出现2个等级错分的风险为2%~7%。 结论 本研究结果证实，在需接受糖皮质激素治疗的重度临床ASH肝硬化患者场景中，AshTest具备可靠的诊断性能，可作为经颈静脉肝活检的合适无创替代方案。