Addition of Rifaximin to Lactulose Reduces Mortality in Patients with Overt Hepatic Encephalopathy

EBM Focus - Volume 8, Issue 41

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Reference: (Am J Gastroenterol 2013 Sep;108(9):1458) (level 1 [likely reliable] evidence)

Hepatic encephalopathy is a common complication of liver failure with manifestations ranging from minor cognitive and motor dysfunction to stupor or coma. The clinical course may be lethal, but the condition may also be reversible. Lactulose is a widely used treatment directed at reducing blood ammonia levels, but evidence for its efficacy is limited (Cochrane Database Syst Rev 2004;(2):CD003044). Rifaximin has been shown to be at least as effective as lactulose (Pharmacotherapy 2008 Aug;28(8):1019), and to improve cognitive function in patients with minimal hepatic encephalopathy (Am J Gastroenterol 2011 Feb;106(2):307). A recent randomized trial compared the combination of rifaximin plus lactulose to lactulose alone in 120 patients with overt hepatic encephalopathy.

Inpatients (mean age 39 years, 74% men) with overt hepatic encephalopathy were randomized to rifaximin 1,200 mg/day orally vs. placebo for up to 10 days and followed until death or hospital discharge. All patients received lactulose 30-60 mL 3 times daily (targeting 2-3 semisoft stools per day). Grade 3 disease was present in 33% of patients (gross disorientation, confusion, bizarre behavior, asterixis usually absent, somnolence or stupor), and 48% had grade 4 disease (coma).

At the end of treatment, 76% in the rifaximin plus lactulose group had complete reversal of symptoms compared to 44% receiving lactulose alone (p = 0.004, NNT 4). Mortality was 23.8% with rifaximin vs. 49.1% without rifaximin (p < 0.05, NNT 4). Rifaximin plus lactulose was also associated with reduced risk of sepsis (11% vs. 29%, p = 0.01, NNT 6) and shorter mean hospital stay (5.8 days vs. 8.2 days, p = 0.001). There were no significant differences in rates of gastrointestinal bleeding or hepatorenal syndrome, and no treatment-related serious adverse events occurred in either group.

For more information, see the Hepatic encephalopathy and Rifaximin topics in DynaMed.


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