Histological characteristics in patients admitted to the hospital with alcoholic hepatitis complicated by acute-on-chronic liver failure

Alcoholic hepatitis (AH) is a frequent precipitating event for the development of acute-on-chronic liver failure (ACLF), a syndrome characterised by organ failures due to immune dysfunction. The histological features of this complication are not well characterized. We investigated whether ACLF has specific histological characteristics. Prospective cohort study in consecutive adult patients admitted between 03-2008 and 04-2021 to a tertiary referral centre with suspected AH. Diagnosis of AH was based on clinical presentation and confirmed by transjugular liver biopsy. All biopsies were assessed by a dedicated liver pathologist, blinded for clinical data and outcome. Diagnosis of ACLF was based on EASL-CLIF criteria. Histological and clinical characteristics of patients with and without ACLF at baseline were compared. 184 patients with biopsy-proven AH were enrolled. Median time from hospital admission to transjugular biopsy was 4.5 days (IQR 2-8). At baseline, ACLF was present in 73 patients (39.7%). Out of the 110 patients without ACLF at baseline, 30 (27.3%) developed ACLF within 28 days (median 7.5 days (IQR 2-20)). At baseline, ductular bilirubinostasis (DB) was the only histological feature significantly more frequently present in patients with ACLF compared to patients without ACLF (50.7% vs. 30.6%, <i>p</i> = 0.003). No clear association between histological features and the development of ACLF later on could be demonstrated. In this well-defined cohort of patients with biopsy-proven AH, DB was associated with the presence of ACLF. This finding fits with the pathophysiology of this syndrome, which is characterized by systemic inflammation and an increased risk of infections.

酒精性肝炎（Alcoholic hepatitis, AH）是慢加急性肝衰竭（acute-on-chronic liver failure, ACLF）的常见诱因，而ACLF是一种以免疫功能异常导致器官衰竭为特征的综合征。目前该并发症的组织学特征尚未得到充分阐明。本研究旨在探讨ACLF是否存在特异性组织学特征。本研究为一项前瞻性队列研究，纳入2008年3月至2021年4月期间于某三级转诊中心就诊的疑似AH成年连续患者。AH的诊断基于临床表现，并经经颈静脉肝活检（transjugular liver biopsy）证实。所有活检标本均由专职肝脏病理学家评估，病理学家对患者的临床数据及转归设盲。ACLF的诊断依据欧洲肝病学会慢加急性肝衰竭研究小组（EASL-CLIF）标准。研究比较了基线时合并与未合并ACLF患者的组织学及临床特征。本研究共纳入184例经活检证实的AH患者。从入院至经颈静脉肝活检的中位时间为4.5天（四分位间距（interquartile range, IQR）：2~8天）。基线时，73例患者（39.7%）合并ACLF。在基线时未合并ACLF的110例患者中，30例（27.3%）在28天内进展为ACLF，中位进展时间为7.5天（IQR：2~20天）。基线时，胆管内胆色素淤积（ductular bilirubinostasis, DB）是唯一在ACLF患者中发生率显著更高的组织学特征（50.7% vs. 30.6%，*P*=0.003）。未观察到组织学特征与后续ACLF发生之间存在明确关联。在本定义明确的经活检证实AH患者队列中，胆管内胆色素淤积与ACLF的存在显著相关。这一发现与该综合征的病理生理学特征相符，后者以全身炎症反应及感染风险升高为核心表现。