In Reply We appreciate the interest by Drs Cutler and Mints regarding our randomized clinical trial comparing lactulose vs polyethylene glycol (PEG) for the treatment of acute hepatic encephalopathy (HE).1 The lack of correlation between ammonia levels and HE improvement as measured by the Hepatic Encephalopathy Scoring Algorithm (HESA) was likely explained by several factors, as discussed in the article.1 Although such a lack of correlation might challenge the “ammonia hypothesis” basis for HE, it is noteworthy that complex and poorly understood mechanisms that may lead to neuronal cell impairment and dysfunction are likely at play in HE.2 Of note, other than PEG, patients received no therapy for HE for a total of 24 hours (PEG was given soon after admission); thus, it is possible that ammonia levels increased during this time in the PEG group. In contrast, those assigned to lactulose continued to receive treatment during that entire 24 hours. Thus, in aggregate, we do not believe that the lack of correlation between ammonia and change in HESA in this study is of great concern.
Rahimi RS, Cuthbert JA, Rockey DC. Lactulose vs Polyethylene Glycol for Treatment of Hepatic Encephalopathy—Reply. JAMA Intern Med. 2015;175(5):868-869. doi:10.1001/jamainternmed.2015.0334