This article is more than 5 years old. Information may no longer be current.

Meta-analysis reaffirms benefit of NADs in treating hepatic encephalopathy

A recent meta-analysis published in Hepatology reaffirmed the benefits of nonabsorbable disaccharides for treatment and prevention of both overt and minimal hepatic encephalopathy.

In 2014, nonabsorbable disaccharides had been recommended to treat overt but not minimal hepatic encephalopathy based on findings from a 2004 meta-analysis.

“This updated 2016 systematic Cochrane review on the efficacy and safety of [nonabsorbable disaccharides (NADs)] for the treatment and prevention of [hepatic encephalopathy (HE)] in patients with cirrhosis found sufficient evidence to reach conclusions and make recommendations for clinical practice,” Lise L. Gluud, in the gastrounit at Copenhagen University Hospital, and colleagues wrote. “Use of NADs had a significant beneficial treatment effect on HE, both minimal and overt, and an overall beneficial effect on liver-related morbidity and all-cause mortality. In addition, use of NADs provides effective prophylaxis against the development of HE in both primary and secondary settings.”

Since 1966, NADs, the first of which was lactulose, have been used as the primary treatment for HE, the researchers wrote. However, a Cochrane review published in 2004 found that NADs had no effect on mortality. As a result, EASL and AASLD published a joint recommendation of lactulose as the treatment of choice for overt HE, but not minimal HE. To better inform future guidelines, Gluud and colleagues published an updated systematic review.

The researchers found 38 randomized controlled trials assessing lactulose and lactitol as both treatment and prevention for HE in a total of 1,828 patients with cirrhosis.

Compared with placebo, NADs had a beneficial effect on HE (RR = 0.63; 95% CI, 0.53-0.74) and on liver failure, variceal bleeding, serious infections, spontaneous bacterial peritonitis and hepatorenal syndrome (RR = 0.42; 95% CI, 0.26-0.69). Treatment was associated with a reduction in mortality in patients with overt HE (RR = 0.36; 95% CI, 0.14-0.94), but not in patients with minimal HE. In addition, NADs prevented the development of HE (RR = 0.47; 95% CI, 0.33-0.68), the development of serious adverse events (RR = 0.48; 95% CI, 0.33-0.7) and was associated with reduced mortality (RR = 0.63; 95% CI, 0.4-0.98).

These findings support the EASL/AASLD recommendation of lactulose as the first-choice treatment for overt HE, the researchers wrote. However, the findings support a more proactive approach for patients with minimal HE.

“Patients with minimal HE benefit from NADs in relation to cognitive functioning and probably also quality of life,” the researchers wrote. “These results and their financial implications should be considered in the formulation of future versions of the EASL/AASLD guideline.” – by Will Offit

Disclosure: The researchers report no relevant financial disclosures.