Hammd Mohamed, Elghezewi Abdelwahap, Abdulhadi Ahmed, Alabid Abdelwahhab, Alabid Abdulfatah, Badi Yasra, Kamal Ibrahem, Hesham Gamal Mohamed, Mohamed Fisal Khalid, Mujtaba Mohamed, Sherif Ahmed, Frandah Wesam
Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA.
Internal Medicine, Faculty of Medicine, Tripoli University, Tripoli, LBY.
Cureus. 2024 Jan 31;16(1):e53341. doi: 10.7759/cureus.53341. eCollection 2024 Jan.
There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine the most effective possible treatment among the single treatment options or the combined treatment options for decreasing the morbidity and mortality of HE. We evaluated the outcomes by various parameters such as the quality of life, reduction in ammonia, all causes of mortality, adverse events, reversal of minimal HE, and development of overt HE. We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023 for studies that assess various treatment options for HE. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The Cochrane Tool was used to assess the randomized controlled trials' quality (RCT), while the NIH tool was used to assess the quality of the included cohort studies. Utilizing the R software, the network meta-analysis was conducted. In addition to a significant variation in cases of (Lactulose and Rifaximin) compared with Rifaximin (RR= 0.39, 95% CI [0.17; 0.89]), the results demonstrated a significantly lower incidence of overt HE in (Lactulose and Rifaximin) compared with placebo (RR=0.19, 95% CI [0.09; 0.40]). Most arms demonstrated a statistically significant reduction in the incidence of overt HE compared to albumin and placebo. The results also demonstrated a significant reduction in ammonia between L-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07]). This network meta-analysis has significant data for managing subclinical HE in people without a history of overt HE. Our analysis showed that (Lactulose and Rifaximin), followed by (Rifaximin and L-carnitine), followed by (Lactulose and Rifaximin with zinc) were the best combinations regarding overt HE. LOLA reduced ammonia best, followed by Nitazoxanide and finally Lactulose. (Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly.
目前尚无关于降低肝性脑病（HE）或相关死亡率的最有效药物的指南。本研究的目的是确定在单一治疗方案或联合治疗方案中，最有可能有效降低HE发病率和死亡率的治疗方法。我们通过各种参数评估结果，如生活质量、氨水平降低情况、全因死亡率、不良事件、轻微型HE的逆转以及显性HE的发生情况。我们系统检索了截至2023年1月19日的PubMed、Cochrane、Web of Science和Scopus数据库，以查找评估HE各种治疗方案的研究。从符合条件的研究中提取数据，并使用基于网络的MetaInsight工具将其汇总为频率学派网络Meta分析中的标准化均值差（SMD）及其95%置信区间（CI）。使用Cochrane工具评估随机对照试验（RCT）的质量，而使用NIH工具评估纳入队列研究的质量。利用R软件进行网络Meta分析。结果显示，与利福昔明相比，（乳果糖和利福昔明）组的病例有显著差异（RR = 0.39，95% CI [0.17; 0.89]），与安慰剂相比，（乳果糖和利福昔明）组显性HE的发生率显著更低（RR = 0.19，95% CI [0.09; 0.40]）。与白蛋白和安慰剂相比，大多数治疗组显性HE的发生率在统计学上有显著降低。结果还显示，L-鸟氨酸-L-天冬氨酸（LOLA）与益生菌之间氨水平有显著降低（MD = -19.17，95% CI [-38.01; -0.32]），与安慰剂相比，LOLA的发生率也有显著差异（MD = -22.62，95% CI [-39.16; -6.07]）。该网络Meta分析为管理无显性HE病史患者的亚临床HE提供了重要数据。我们的分析表明，就显性HE而言，（乳果糖和利福昔明）、其次是（利福昔明和L-肉碱）、然后是（含锌的乳果糖和利福昔明）是最佳组合。LOLA降低氨的效果最佳，其次是硝唑尼特，最后是乳果糖。（乳果糖和硝唑尼特）的不良反应最少，其次是（利福昔明和L-肉碱），然后是益生菌。然而，所有死亡率结果和生活质量变化均未得出有用的结果。必须开展如RCT等未来研究以直接比较我们的治疗方法。
