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Comparative Efficacy of Treatment Options for Minimal Hepatic Encephalopathy: A Systematic Review & Network Meta-analysis

Radha K Dhiman, Kiran K Thumburu, Nipun Verma, Madhu Chopra, Sahaj Rathi, Usha Dutta, Ashwani K Singal, Sunil Taneja, Ajay Duseja, Meenu Singh
Clinical Gastroenterology and Hepatology 2019 August 30

BACKGROUND & AIMS: To synthesize evidence for most effective treatment for minimal hepatic encephalopathy (HE).

METHODS: A systematic search of the PubMed, EMBASE, OvidSP and CENTRAL databases for randomized-controlled-trials evaluating treatments for minimal HE in cirrhotics was conducted from their inception to 26th July2018. Primary outcomes were reversal of minimal HE and prevention of overt HE. Meta-analysis (MA) followed by network meta-analysis (NMA) and surface under cumulated ranking (SUCRA) was conducted to pool the direct and indirect estimates and rank the different treatments. Quality appraisal was done using GRADE.

RESULTS: Twenty-five trials (1563 participants) were inlcuded in MA and NMA. Rifaximin [OR:7.53; 95%predictive interval(PrI): 4.45-12.73, SUCRA:89.2%; moderate quality], lactulose [OR:5.39; 95% PrI:3.60-8.07, SUCRA:67.2%; moderate quality], probiotics+lactulose [OR:4.66; 95% PrI:1.90-11.39, SUCRA:52.4%; low quality], L-ornithine L-aspartate [OR:4.45; 95% PrI:2.67-7.42, SUCRA:47.2%; moderate quality] and probiotics [OR: 3.89; 95% PrI: 2.52-6.02, SUCRA:34.1%; low quality] were effective in reversing minimal HE as compared with placebo/no-treatment. L-Ornithie L-Aspartate [OR:0.19; 95% PrI:0.04-0.91, SUCRA:75.1%; moderate quality], lactulose [OR:0.22; 95% PrI:0.09-0.52, SUCRA73.9%; moderate quality] and probiotics [OR: 0.27; 95% PrI:0.11-0.62, SUCRA:59.6%; low quality] were effective in preventing episodes of overt HE, as compared with placebo/no-treatment. On comparative analysis, no superiority was identified between agents, except rifaximin over probiotics (very low quality) for reversal of minimal HE.

CONCLUSIONS: Rifaximin and lactulose were most effective for reversal of minimal HE. L-Ornithine L-Aspartate and lactulose were most effective in prevention of overt HE. Lactulose was the only agent effective in reversing minimal HE, preventing overt HE, reducing ammonia and improving quality of life; but with tolerable adverse effects. (PROSPERO-ID:107003).


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