Lactulose treatment for hepatic encephalopathy, gastrointestinal symptoms, and health-related quality of life
Authors: Evangelos Kalaitzakis, Einar Björnsson
Journal: Hepatology (2007)

We read with great interest the article by Prasad et al.1 regarding the effect of lactulose therapy on cognitive function and health-related quality of life (HRQOL) in patients with cirrhosis and minimal hepatic encephalopathy. The authors randomly assigned 61 patients with minimal hepatic encephalopathy to receive lactulose treatment or no treatment in a nonblinded fashion. After 3 months of therapy, the lactulose-treated group exhibited significant improvement in cognitive function (measured by means of 6 neuropsychiatric tests) and HRQOL (measured by means of the Sickness Impact profile) compared with the untreated group of patients with minimal hepatic encephalopathy. Thus, this study provides important data supporting the concept that hepatic encephalopathy per se is linked to HRQOL impairment in cirrhosis and that lactulose treatment may help improve both cognition and HRQOL in this group of patients. Several factors have been reported to influence HRQOL in patients with cirrhosis, including cirrhosis severity,2 cirrhosis-specific symptoms such as muscle cramps and pruritus,2 hepatic encephalopathy (overt or minimal),2, 3 and psychological factors.4 Recently, we performed a prospective study evaluating gastrointestinal symptom severity and HRQOL in 128 consecutive patients with liver cirrhosis using validated questionnaires.5 We found that patients with liver cirrhosis showed increased severity of gastrointestinal symptoms compared with a control population, which was associated with impaired HRQOL. Twenty-nine percent of patients with cirrhosis included in our study were taking lactulose as a treatment for hepatic encephalopathy, and, interestingly, lactulose treatment was found to be independently related to gastrointestinal symptom severity. Daily lactulose use was also negatively related to HRQOL expressed as the physical SF-36 component summary score (biseral correlation coefficient r = −0.27; P < 0.005).5 Lactulose is known to accelerate colonic transit,6 and, due to a narrow therapeutic window, it can lead to diarrhea. Colonic lactulose fermentation can also induce bloating and abdominal distension.7 Although lactulose is known to induce gastrointestinal symptoms,8 this has only rarely resulted in withdrawal of therapy.9 However, gastrointestinal side effects have only vaguely been reported in clinical trials evaluating the effect of lactulose on hepatic encephalopathy.10 In the article by Prasad et al., it is mentioned that none of the patients reported side effects related to lactulose therapy1 but it is unclear whether patients included were actively evaluated for the occurrence and severity of gastrointestinal symptoms. Although it is unlikely that gastrointestinal symptoms due to lactulose had any significant effect on HRQOL in the patients included in this study,1 it should be noted that lactulose use as a treatment of hepatic encephalopathy in everyday clinical practice (that is, outside the controlled conditions of a clinical trial) may be implicated in increased gastrointestinal symptom severity and, consequently, reduced HRQOL. Improved physician and patient awareness about the actions of lactulose could potentially help decrease its side effects. Evangelos Kalaitzakis M.D., Ph.D.*, Einar Björnsson M.D., Ph.D.*, * Section of Gastroenterology and Hepatology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.