Amanitin intoxication: effects of therapies on clinical outcomes – a review of 40 years of reported cases

Amanita phalloides poisoning causes severe liver damage which may be potentially fatal. Several treatments are available, but their effectiveness has not been systematically evaluated. We performed a systematic review to investigate the effect of the most commonly used therapies: N-acetylcysteine (NAC), benzylpenicillin (PEN), and silibinin (SIL) on patient outcomes. In addition, other factors contributing to patient outcomes are identified. We searched MEDLINE and Embase for case series and case reports that described patient outcomes after poisoning with amanitin-containing Amanita mushrooms. We extracted clinical characteristics, treatment details, and outcomes. We used the liver item from the Poisoning Severity Score (PSS) to categorize intoxication severity. We included 131 publications describing a total of 877 unique cases. The overall survival rate of all patients was 84%. Patients receiving only supportive care had a survival rate of 59%. The use of SIL or PEN was associated with a 90% (OR 6.40 [3.14–13.04]) and 89% (OR 5.24 [2.87–9.56]) survival rate, respectively. NAC/SIL combination therapy was associated with 85% survival rate (OR 3.85 [2.04, 7.25]). NAC/PEN/SIL treatment group had a survival rate of 76% (OR 2.11 [1.25, 3.57]). Due to the limited number of cases, the use of NAC alone could not be evaluated. Additional analyses in ‘proven cases’ (amanitin detected), ‘probable cases’ (mushroom identified by mycologist), and ‘possible cases’ (neither amanitin detected nor mushroom identified) showed comparable results, but the results did not reach statistical significance. Transplantation-free survivors had significantly lower peak values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total serum bilirubin (TSB), and international normalized ratio (INR) compared to liver transplantation survivors and patients with fatal outcomes. Higher peak PSS was associated with increased mortality. Based on data available, no statistical differences could be observed for the effects of NAC, PEN or SIL in proven poisonings with amanitin-containing mushrooms. However, monotherapy with SIL or PEN and combination therapy with NAC/SIL appear to be associated with higher survival rates compared to supportive care alone. AST, ALT, TSB, and INR values are possible predictors of potentially fatal outcomes.

毒鹅膏中毒可导致严重的肝脏损伤，其潜在致命性不容忽视。目前有多种治疗方法可供选择，但其疗效尚未得到系统性的评估。本研究对最常使用的治疗方案进行了系统综述，包括N-乙酰半胱氨酸（NAC）、苄青霉素（PEN）和硅酸素（SIL）对患者预后的影响。此外，我们还确定了影响患者预后的其他因素。通过检索MEDLINE和Embase数据库，我们找到了描述毒鹅膏中毒患者预后的病例系列和病例报告。我们提取了临床特征、治疗细节和预后结果。利用中毒严重度评分（PSS）中的肝脏项目对中毒程度进行分类。共纳入了描述877例独特病例的131篇出版物。所有患者的总体生存率为84%。仅接受支持性治疗的患者生存率为59%。使用SIL或PEN的患者生存率分别达到90%（OR 6.40 [3.14–13.04]）和89%（OR 5.24 [2.87–9.56]）。NAC/SIL联合治疗组的生存率为85%（OR 3.85 [2.04, 7.25]）。NAC/PEN/SIL治疗组的生存率为76%（OR 2.11 [1.25, 3.57]）。由于病例数量有限，NAC单药使用的效果无法评估。在‘证实病例’（鹅膏毒碱检测阳性）、‘疑似病例’（蘑菇经真菌学家鉴定）和‘可能病例’（未检测到鹅膏毒碱也未鉴定到蘑菇）的额外分析中，结果显示相似，但未达到统计学意义。未接受移植的存活者与接受肝脏移植的存活者及死亡病例相比，天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、总血清胆红素（TSB）和国际标准化比率（INR）的峰值显著降低。较高的PSS峰值与死亡率增加相关。根据现有数据，NAC、PEN或SIL在证实鹅膏毒碱中毒中的效果无统计学差异。然而，SIL或PEN的单药治疗和NAC/SIL的联合治疗似乎与支持性治疗相比，与更高的生存率相关。AST、ALT、TSB和INR值可能是预测潜在致命结果的可能指标。