Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Hepatology, Amrita Institute of Medical Sciences and Research, Faridabad, Haryana, India.
Hepatol Commun. 2024 Mar 18;8(4). doi: 10.1097/HC9.0000000000000404. eCollection 2024 Apr 1.
The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We systematically reviewed the literature to answer these questions.
Four databases were searched for studies describing the precision of clinical criteria (National Institute on Alcohol Abuse and Alcoholism, European Association for Study of Liver, or classical) and the role of histology in AH. The precision(positive predictive value) of criteria was pooled through random-effects meta-analysis, and its variation was investigated through subgroups and meta-regression of study-level factors with their percent contribution to variation (R2). The risk of bias among studies was evaluated through the QUADAS2 tool (PROSPERO-ID-CRD4203457250).
Of 4320 studies, 18 in the systematic review and 15 (10/5: low/high risk of bias, N=1639) were included in the meta-analysis. The pooled precision of clinical criteria was 80.2% (95% CI: 69.7-89.7, I2:93%, p < 0.01), higher in studies with severe AH (mean-Model for End-Stage Liver Disease > 20) versus moderate AH (mean-Model for End-Stage Liver Disease < 20): 92% versus 67.1%, p < 0.01, and in studies with serum bilirubin cutoff 5 versus 3 mg/dL (88.5% vs.78.8%, p = 0.01). The factors contributing to variation in precision were Model for End-Stage Liver Disease (R2:72.7%), upper gastrointestinal bleed (R2:56.3%), aspartate aminotransferase:aspartate aminotransferase ratio (R2:100%), clinical criteria (R2:40.9%), bilirubin (R2:22.5%), and Mallory body on histology (R2:19.1%).The net inter-pathologist agreement for histologic findings of AH was variable (0.33-0.97), best among 2 studies describing AH through simple and uniform criteria, including steatosis, ballooning, and neutrophilic inflammation. Few studies reported the utility of histology in estimating steroid responsiveness (N = 1) and patient prognosis (N = 4); however, very broad septa, pericellular fibrosis, and cholestasis were associated with mortality. Bilirubinostasis was associated with infection in 1 study.
Clinical criteria are reasonably precise for diagnosing severe AH, while there is an unmet need for better criteria for diagnosing moderate AH. Histologic diagnosis of AH should be simple and uniform.
酒精性肝炎（AH）患者的临床标准的准确性和肝活检在诊断或预后方面的作用仍不清楚。我们系统地回顾了文献，以回答这些问题。
我们在四个数据库中搜索了描述临床标准（美国国立酒精滥用和酒精中毒研究所、欧洲肝脏研究协会或经典标准）和 AH 中组织学作用的研究。通过随机效应荟萃分析汇总了标准的准确性（阳性预测值），并通过亚组和研究水平因素的荟萃回归及其对变异的百分比贡献（R2）来研究其变异。通过 QUADAS2 工具（PROSPERO-ID-CRD4203457250）评估研究中的偏倚风险。
在 4320 项研究中，有 18 项在系统评价中，15 项（10/5：低/高偏倚风险，N=1639）被纳入荟萃分析。临床标准的汇总准确性为 80.2%（95%CI：69.7-89.7，I2：93%，p<0.01），在严重 AH（平均终末期肝病模型>20）与中度 AH（平均终末期肝病模型<20）中更高：92%与 67.1%，p<0.01，在血清胆红素截断值为 5 与 3 mg/dL 的研究中更高：88.5%与 78.8%，p=0.01。导致精度变异的因素包括终末期肝病模型（R2：72.7%）、上消化道出血（R2：56.3%）、天冬氨酸氨基转移酶：天冬氨酸氨基转移酶比值（R2：100%）、临床标准（R2：40.9%）、胆红素（R2：22.5%）和组织学上的 Mallory 体（R2：19.1%）。AH 组织学表现的病理间一致性差异较大（0.33-0.97），在 2 项通过简单统一标准描述 AH 的研究中最佳，包括脂肪变性、气球样变和中性粒细胞炎症。很少有研究报告了组织学在估计类固醇反应性（N=1）和患者预后（N=4）方面的作用；然而，广泛的间隔、细胞周纤维化和胆汁淤积与死亡率相关。在 1 项研究中，胆红素淤积与感染有关。
临床标准对于诊断严重 AH 具有相当的准确性，而对于诊断中度 AH 则存在未满足的需求。AH 的组织学诊断应简单而统一。
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