The treatment of hepatic encephalopathy.
ABSTRACT Current recommendations for the treatment of hepatic encephalopathy are based, to a large extent, on open or uncontrolled trials, undertaken in very small numbers of patients. In consequence, there is ongoing discussion as to whether the classical approach to the treatment of this condition, which aims at reducing ammonia production and absorption using either non-absorbable disaccharides and/or antibiotics, should be revisited, modified or even abandoned. Pros and cons of present therapeutic strategies and possible future developments were discussed at the fourth International Hannover Conference on Hepatic Encephalopathy held in Dresden in June 2006. The content of this discussion is summarized.
- Hepatology 03/2013; · 12.00 Impact Factor
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ABSTRACT: Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use. We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, n= 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n=140). In the all-rifaximin population, median exposure was 427.0 days (range, 2-1427 days), with 510.5 person-y of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure, (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72). Long-term treatment (≥24 months) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920.Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2013; · 5.64 Impact Factor
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ABSTRACT: BACKGROUND AND AIM: Several randomized, controlled trials that evaluated the effectiveness of L-ornithine-L-aspartate (LOLA) in the treatment of hepatic encephalopathy (HE) have been published recently. Our purpose was to update the meta-analysis to reevaluate the safety and efficacy of LOLA on HE in patients with cirrhosis. METHODS: The following databases were searched from inception to June 2012: Medline, Embase, and the Cochrane Central Register of Controlled Trials (Issue 6). Differences between groups were assessed by the pooled risk ratio (RR) or mean difference (MD). Possible sources of heterogeneity were assessed by sensitivity analyses. RESULTS: Eight randomized controlled trials with 646 patients were included. When comparing placebo/no-intervention control, LOLA was significantly more effective in the improvement of HE in the total (RR: 1.49, 95% CI: 1.10 to 2.01), overt HE (RR: 1.33, 95% CI: 1.04 to 1.69), and minimal HE patients (RR: 2.25, 95% CI: 1.33 to 3.82). Furthermore, the reduction of fasting ammonia significantly favored LOLA (post-treatment value, MD: -18.26, 95% CI: -26.96 to -9.56; change, MD: 8.59, 95% CI: 5.22 to 11.96). The tolerance ratio, incidence of adverse events, and mortality were not significantly different between LOLA and the placebo/no-intervention control. LOLA and lactulose demonstrated similar effectiveness in the improvement of HE (RR: 0.88, 95% CI: 0.57 to 1.35). CONCLUSIONS: LOLA benefits both overt and minimal HE patients in the improvement of HE by reducing the serum ammonia concentration compared to the placebo/no-intervention control. Further, evaluations between LOLA and other effective treatments are needed.Journal of Gastroenterology and Hepatology 02/2013; · 3.33 Impact Factor