Lee William M, Barnard Carson, Rule Jody A, Orandi Babak J, James Laura P, Stravitz R Todd, Durkalski Valerie, Fontana Robert J
Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA.
Departments of Surgery and Medicine, New York University, New York, New York, USA.
Am J Gastroenterol. 2025 Mar 1;120(3):584-592. doi: 10.14309/ajg.0000000000002941. Epub 2024 Jul 12.
Acute viral hepatitis (AVH) comprises 11% of acute liver failure (ALF) in North America while acetaminophen (APAP) toxicity represents 46%. The use of APAP to treat prodromal hepatitis symptoms is common. It is unknown if concurrent APAP use impacts liver injury in AVH-induced ALF.
In this prospective, multicenter cohort study, 356 patients meeting criteria for AVH including hepatitis A, B, Epstein-Barr virus, and herpes simplex virus, all leading to ALF (hepatic encephalopathy after acute illness, international normalized ratio ≥1.5), or acute liver injury (acute liver injury, international normalized ratio >2.0, no hepatic encephalopathy) were reviewed for evidence of APAP use: APAP ingestion history or measurement of serum APAP level or APAP-CYS adducts, a specific biomarker released into blood with APAP injury. Patients were grouped by APAP exposure level, from high (measurable APAP levels or toxic APAP-CYS), medium (therapeutic APAP-CYS), low (history of APAP ingestion only and/or barely detectable APAP-CYS), or no exposure recorded.
Two hundred five of 356 patients (57.5%) with AVH-ALF had evidence of APAP use: 87 out of 356 (24%) demonstrated high or medium exposures. The aminotransferase and bilirubin levels of high/medium group resembled a mixed APAP-viral injury. Mortality was the highest (51.6%, 21.4%, 28.8%, and 30.5%), and transplant-free survival was the lowest (22.6%, 44.6%, 41.5%, and 40.4%) in the high exposure group compared with medium, low, and no exposure groups. However, the specific comparisons of mortality and transplant-free survival between the high exposure and no exposure groups were not statistically different even after adjusting for baseline patient characteristics differences.
APAP use in AVH-ALF is common and may negatively impact outcomes compared with little or no APAP exposure. Prospective studies of the safest and effective dose of APAP to use in patients with AVH are needed.
在北美，急性病毒性肝炎（AVH）占急性肝衰竭（ALF）的11%，而对乙酰氨基酚（APAP）中毒占46%。使用APAP治疗前驱性肝炎症状很常见。目前尚不清楚同时使用APAP是否会影响AVH所致ALF的肝损伤。
在这项前瞻性多中心队列研究中，对356例符合AVH标准的患者进行了回顾，这些患者包括甲型、乙型肝炎病毒、EB病毒和单纯疱疹病毒感染，均导致ALF（急性发病后出现肝性脑病，国际标准化比值≥1.5）或急性肝损伤（急性肝损伤，国际标准化比值>2.0，无肝性脑病），以寻找使用APAP的证据：APAP摄入史或血清APAP水平或APAP - CYS加合物的检测，APAP - CYS加合物是一种在APAP损伤时释放到血液中的特定生物标志物。患者按APAP暴露水平分组，分为高暴露组（可检测到APAP水平或毒性APAP - CYS）、中暴露组（治疗性APAP - CYS）、低暴露组（仅有APAP摄入史和/或APAP - CYS几乎检测不到）或未记录到暴露组。
356例AVH - ALF患者中有205例（57.5%）有使用APAP的证据：356例中有87例（24%）显示高暴露或中暴露。高/中暴露组的转氨酶和胆红素水平类似于APAP与病毒混合损伤。与中暴露组、低暴露组和未暴露组相比，高暴露组的死亡率最高（分别为51.6%、21.4%、28.8%和30.5%），无移植生存率最低（分别为22.6%、44.6%、41.5%和40.4%）。然而，即使在调整了基线患者特征差异后，高暴露组和未暴露组之间的死亡率和无移植生存率的具体比较也没有统计学差异。
在AVH - ALF中使用APAP很常见，与很少或不使用APAP相比，可能对预后产生负面影响。需要对AVH患者使用APAP的最安全有效剂量进行前瞻性研究。
