Prophylaxis of Hepatic Encephalopathy in Cirrhosis Patients
Background and Aim: Development of overt hepatic encephalopathy (HE) is associated with poor prognosis in patients with cirrhosis. Lactulose is used for the treatment of HE. There is no study on the prevention of overt HE using lactulose in patients who never had HE earlier.
Methods: Consecutive cirrhotic patients who never had an episode of overt HE were randomized to receive lactulose (Gp-L) or no lactulose (Gp-NL). All patients were assessed by psychometry (number connection test [NCT-A and B], figure connection test if illiterate [FCT-A and B], digit symbol test [DST], serial dot test [SDT], line tracing test [LTT]) and critical flicker frequency test (CFF) at inclusion and after 3 months. These patients were followed every month for 12 months for development of overt HE.
Results: Of 250 patients screened, 120 (48%) meeting the inclusion criteria were randomized to Gp-L (n = 60) and Gp-NL (n = 60). Twenty (19%) of 105 patients followed for 12 months developed an episode of overt HE. Six (11%) of 55 in the lactulose (Gp-L) group and 14 (28%) of 50 in the Gp-NL (P = 0.02) developed overt HE. Ten (20%) of 50 patients in Gp-NL and five (9%) of 55 patients in the Gp-L group died, P = 0.16. Number of patients with minimal hepatic encephalopathy (MHE) were comparable in two groups at baseline (Gp-L vs Gp-NL, 32:36, P = 0.29). Lactulose improved MHE in 66% of patients in Gp-L. Taking a cutoff < 38 Hz sensitivity and specificity of CFF in predicting HE were 52% and 77% at baseline and 52% and 82% at 3 months of treatment. On multivariate analysis, Child's score and presence of MHE at baseline were significantly associated with development of overt HE.
Conclusions: Lactulose is effective for primary prevention of overt hepatic encephalopathy in patients with cirrhosis.
Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain. HE is a common complication in cirrhotic patients and its development is associated with a poor prognosis and economic burden to hospital. The majority of the drugs used in the treatment of HE are primarily directed at the reduction or elimination of the increased neurotoxic ammonia. Management of overt HE primarily involves avoidance of precipitating factors, dietary protein restriction and administration of various ammonia-lowering therapies such as non-absorbable disaccharides and antimicrobial agents. Non-absorbable disaccharides, such as lactulose, have traditionally been regarded as first-line pharmacotherapy for patients with HE. Lactulose serves as a "prebiotic" ingredient, encouraging the growth of endogenous bacteria that resemble those found in many probiotics. Lactulose has been shown to be useful in the treatment of acute as well as chronic recurrent porto-systemic HE and the secondary prophylaxis of overt HE. Minimal hepatic encephalopathy (MHE) predicts future episodes of overt HE and lactulose is effective in the treatment of MHE. Treating patients to prevent development of a first episode of overt HE is classified as primary prophylaxis of HE and preventing recurrence of overt HE in patients who had previous episodes of HE is secondary prophylaxis of HE. We assessed the effects of lactulose for the prevention of first episode of overt HE (primary prophylaxis) in patients with cirrhosis.
Abstract and Introduction
Abstract
Background and Aim: Development of overt hepatic encephalopathy (HE) is associated with poor prognosis in patients with cirrhosis. Lactulose is used for the treatment of HE. There is no study on the prevention of overt HE using lactulose in patients who never had HE earlier.
Methods: Consecutive cirrhotic patients who never had an episode of overt HE were randomized to receive lactulose (Gp-L) or no lactulose (Gp-NL). All patients were assessed by psychometry (number connection test [NCT-A and B], figure connection test if illiterate [FCT-A and B], digit symbol test [DST], serial dot test [SDT], line tracing test [LTT]) and critical flicker frequency test (CFF) at inclusion and after 3 months. These patients were followed every month for 12 months for development of overt HE.
Results: Of 250 patients screened, 120 (48%) meeting the inclusion criteria were randomized to Gp-L (n = 60) and Gp-NL (n = 60). Twenty (19%) of 105 patients followed for 12 months developed an episode of overt HE. Six (11%) of 55 in the lactulose (Gp-L) group and 14 (28%) of 50 in the Gp-NL (P = 0.02) developed overt HE. Ten (20%) of 50 patients in Gp-NL and five (9%) of 55 patients in the Gp-L group died, P = 0.16. Number of patients with minimal hepatic encephalopathy (MHE) were comparable in two groups at baseline (Gp-L vs Gp-NL, 32:36, P = 0.29). Lactulose improved MHE in 66% of patients in Gp-L. Taking a cutoff < 38 Hz sensitivity and specificity of CFF in predicting HE were 52% and 77% at baseline and 52% and 82% at 3 months of treatment. On multivariate analysis, Child's score and presence of MHE at baseline were significantly associated with development of overt HE.
Conclusions: Lactulose is effective for primary prevention of overt hepatic encephalopathy in patients with cirrhosis.
Introduction
Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain. HE is a common complication in cirrhotic patients and its development is associated with a poor prognosis and economic burden to hospital. The majority of the drugs used in the treatment of HE are primarily directed at the reduction or elimination of the increased neurotoxic ammonia. Management of overt HE primarily involves avoidance of precipitating factors, dietary protein restriction and administration of various ammonia-lowering therapies such as non-absorbable disaccharides and antimicrobial agents. Non-absorbable disaccharides, such as lactulose, have traditionally been regarded as first-line pharmacotherapy for patients with HE. Lactulose serves as a "prebiotic" ingredient, encouraging the growth of endogenous bacteria that resemble those found in many probiotics. Lactulose has been shown to be useful in the treatment of acute as well as chronic recurrent porto-systemic HE and the secondary prophylaxis of overt HE. Minimal hepatic encephalopathy (MHE) predicts future episodes of overt HE and lactulose is effective in the treatment of MHE. Treating patients to prevent development of a first episode of overt HE is classified as primary prophylaxis of HE and preventing recurrence of overt HE in patients who had previous episodes of HE is secondary prophylaxis of HE. We assessed the effects of lactulose for the prevention of first episode of overt HE (primary prophylaxis) in patients with cirrhosis.
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