Several studies that looked at the frequency of development of overt HE in cirrhotic

patients found that those with MHE developed overt HE more often during follow up than those without MHE (Table 4).4,15,17,20,48,88,89 In addition, some studies have shown an increased risk of death in patients with liver cirrhosis and MHE compared to those without MHE (Table 4).20,22,88 However, patients with MHE had poorer liver function Midostaurin solubility dmso than those without MHE in these studies, making it difficult to ascribe the poor outcome to the presence of MHE. Das et al.4 studied the relationship of progression of MHE to overt HE in relation to the severity of liver dysfunction and found that the rate of progression to overt HE was much higher in patients with MHE and a CTP score > 6 than in those with MHE and a CTP score ≤ 6. Amodio et al.88 found that the presence of MHE and that of liver dysfunction were both associated with mortality on univariate analysis; however, on multivariate analysis, liver functional status was the only independent predictor of mortality. In another study, progression of MHE to overt HE was associated with abnormal response to oral glutamine challenge, which in turn CCI-779 mouse was associated with poor liver function.90 Furthermore, MHE in patients with preserved liver function but large portal-systemic shunts (congenital

shunts, non-cirrhotic portal hypertension and cirrhosis with preserved liver function) appears to have a good outcome, even though these data are based on a small number of patients.10 Thus, it appears that the higher risk of overt HE or death in patients with MHE may not be related to MHE per se but to the poorer liver

function in patients with MHE. 42 Patients with liver cirrhosis and MHE have a higher rate of subsequent development of HE than those with cirrhosis but no MHE. (1b) Treatment of MHE is primarily directed towards reduction of ammonia and includes non-absorbable disaccharides, prebiotics/probiotics and LOLA. Treatment of MHE improves psychometric performance and quality of life (Table 5). However, several issues regarding therapy remain unsettled. The effects of treating MHE on driving, complex occupational tasks, development MCE公司 of overt HE, and on survival have not been studied. Duration of therapy for achieving these end-points, choice of therapeutic agents and the role of combinations of therapies have also not been adequately studied and further research is needed to clarify these issues. Lactulose decreases blood ammonia levels, and improves psychometric performance and HRQOL (Table 5).3,59,62,64,67,91–95 Using cerebral diffusion tensor imaging, Kale et al.59 showed that interstitial brain edema observed in patients with MHE resolves after treatment for 3 weeks with lactulose in parallel with improvements in neuropsychiatric performance. Prasad et al.