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

<i>Amanita phalloides</i> 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 <i>Amanita</i> 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（Amanita phalloides）中毒可引发严重肝损伤，甚至存在致命风险。目前临床已有多种治疗方案，但尚未对其疗效开展系统性评估。本研究通过系统综述，探究了乙酰半胱氨酸（N-acetylcysteine, NAC）、苄青霉素（benzylpenicillin, PEN）及水飞蓟宾（silibinin, SIL）这三种最常用治疗手段对患者预后的影响，并明确了其他影响患者预后的相关因素。我们检索了MEDLINE与Embase数据库，筛选收录了描述含鹅膏毒肽的鹅膏属（Amanita）蘑菇中毒后患者预后的病例系列与病例报告。研究提取了患者的临床特征、治疗细节及转归结局，并采用中毒严重程度评分（Poisoning Severity Score, PSS）中的肝脏相关条目对中毒严重程度进行分级。本研究共纳入131篇文献，涉及877例独立病例。所有患者的总体生存率为84%；仅接受支持治疗的患者生存率为59%。单独使用水飞蓟宾或苄青霉素治疗的患者生存率分别为90%（比值比OR=6.40，95%置信区间3.14~13.04）与89%（OR=5.24，95%置信区间2.87~9.56）；乙酰半胱氨酸联合水飞蓟宾治疗组的生存率为85%（OR=3.85，95%置信区间2.04~7.25）；乙酰半胱氨酸、苄青霉素联合水飞蓟宾治疗组的生存率为76%（OR=2.11，95%置信区间1.25~3.57）。由于病例数量有限，无法评估单独使用乙酰半胱氨酸的治疗效果。对“确诊病例（检出鹅膏毒肽）”“疑似病例（经真菌学家鉴定蘑菇种类）”及“可能病例（既未检出鹅膏毒肽也未鉴定蘑菇种类）”的亚组分析结果相似，但未达到统计学显著性。与接受肝移植的幸存者及死亡患者相比，未接受肝移植的幸存者的天冬氨酸氨基转移酶（aspartate aminotransferase, AST）、丙氨酸氨基转移酶（alanine aminotransferase, ALT）、血清总胆红素（total serum bilirubin, TSB）及国际标准化比值（international normalized ratio, INR）峰值水平显著更低。较高的中毒严重程度评分峰值与死亡率升高显著相关。基于现有数据，在确诊含鹅膏毒肽蘑菇中毒的患者中，未观察到乙酰半胱氨酸、苄青霉素或水飞蓟宾单药治疗的疗效存在统计学差异。但相较于单纯支持治疗，单独使用水飞蓟宾或苄青霉素，以及乙酰半胱氨酸联合水飞蓟宾治疗似乎与更高的生存率相关。AST、ALT、TSB及INR峰值水平可作为潜在致命结局的预测指标。