A study on patients with cirrhosis who had minimal hepatic encephalopathy (MHE), a condition in which behavioral, psychological and neurological changes are associated with advanced liver disease, found that cognitive function and health related quality-of-life improved when they took lactulose. Lactulose is a drug used to help eliminate toxins such as ammonia that are normally cleared by the liver.

The results of this study appear in the March 2007 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD).

MHE is the mildest form of hepatic encephalopathy (HE), a condition marked by impaired intellectual functioning, personality changes, altered levels of consciousness, and neuromuscular dysfunction. Although MHE has no recognizable symptoms, patients who have it show mild cognitive and psychomotor deficits. These can impair their daily functioning and health related quality-of-life (HRQOL) to the extent that they may not be able to work or drive a car. MHE can also lead to the development of more severe HE, and can be associated with a poor prognosis.

Led by Radha K. Dhiman, MD, DM, MNAMS, FACG, of the Department of Hepatology, Postgraduate Institute of Medical Education and Research in Chandigarh, India, researchers conducted a study involving 61 patients who had MHE. The patients were diagnosed with MHE if they had abnormal scores on two or more neuropsychological tests that were used to assess their mental state. The patients were also given a Sickness Impact Profile (SIP) questionnaire to determine the impact of the

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disease on daily activities such as sleep/rest, eating, work, home management, mobility, social interaction and emotional behavior and communication. They were then divided into two groups: 31 patients received lactulose treatment for 3 months, while 30 patients received no treatment.

The results showed that the number of abnormal neuropsychological tests decreased among patients who took lactulose compared to those who did not. Changes in these tests indicating significant improvement in cognitive function were also seen in the lactulose group. In addition, the lactulose group also showed improvement in their quality of life as measured by SIP scores, with significant improvement in emotional behavior, movement, mobility, sleep/rest, and recreational activities.

The study also confirms the negative impact of MHE on HRQOL: patients showed impairment in perception, memory, learning, expression, mental activity and executive function. Other studies have shown that half of MHE patients do not have regular employment and that it has a negative effect on the ability to drive. «These observations strongly suggest that MHE should be considered a medical condition that might warrant treatment in order to improve psychomotor impairment and HRQOL,» the authors state.

Ammonia is the key factor in HE and although the study did not measure ammonia levels, the authors

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believe that this is also the case with MHE. They chose lactulose since it is inexpensive, easily

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available and is effective at reducing ammonia levels in the blood. The authors conclude that cirrhosis patients with MHE may benefit from treatment with lactulose, adding: «Whether treatment also prevents or delays progression to overt HE and improves prognosis, remains to be determined in prospective studies.»

In an accompanying editorial in the same issue, Asif Qadri and colleagues from MetroHealth Medical Center affiliated with Case Western Reserve University in Cleveland, OH state that the current study «may potentially change the overall management of hepatic encephalopathy (HE),» adding that the results strongly suggest that MHE is the cause of reduced quality-of-life in patients with cirrhosis. While studies need to be done to confirm these findings, Dhiman et al. also note that the study highlights some interesting questions that could be answered in future studies, such as whether early treatment of HE can postpone worsening symptoms for longer periods of time, and whether it impacts survival. Although the results support the ability of lactulose as a treatment for HE, there are significant barriers to widespread diagnosis of MHE, the authors point out. They suggest that measures need to be taken to simplify the diagnosis of MHE, or alternatively, it may emerge that all cirrhotic patients will eventually develop MHE, making its treatment the standard of care and eliminating the need to determine if it is actually present. «In any event,» they conclude, «it appears that we cannot ignore minimal hepatic encephalopathy any longer.»