A Randomized, Double-Blind, Controlled Trial Comparing Rifaximin Plus Lactulose With Lactulose Alone in Treatment of Overt Hepatic Encephalopathy

Sharma, Barjesh Chander; Sharma, Praveen; Lunia, Manish Kumar; Srivastava, Siddharth; Goyal, Rohit; Sarin, S. K.

doi:10.1038/ajg.2013.219

Cited by 275 publications

(217 citation statements)

References 23 publications

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“…As lactulose combined with antibiotic administration has often been suggested to improve liver performance, it is possible that combined treatment may also demonstrate positive effects with microemulsions (38)(39)(40). Other drugs that improve the metabolism and increase survival rates by reducing toxin absorption, thus protecting the brain and liver tissues, may also be beneficial when administered together with MBG-RCA (41,42).…”

Section: Discussionmentioning

confidence: 99%

pH-sensitive microemulsion-based gels for removal of colonic ammonia: A novel preventative oral preparation for hepatic encephalopathy in rats

Zhang

Duan

Tian

et al. 2015

Molecular Medicine Reports

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Abstract.Microemulsions with limited stability in mimetic gastrointestinal environments have previously demonstrated potential for the effective removal of ammonia from artificial colonic fluid. Specialized pH-sensitive microemulsion-based gels for the removal of colonic ammonia (MBG-RCA), however, possess relative stability in the gastrointestinal (GI) tract of normal rats, indicating potential use in in vivo applications. An investigation of the effects of oral MBG-RCA was conducted in order to evaluate the reduction of intestinal ammonia and the prevention of hepatic encephalopathy (HE) in rat models. Eighty rats were allocated into eight 4-day treatment groups: The HE model (intraperitoneal injection of thioacetamide) group; the high-, medium-and low-dose MBG-RCA therapeutic groups (15, 10 and 5 ml/kg MBG-RCA, respectively); and the normal, blank, lactulose and acetic acid control groups, each of which received daily treatment administration. Oral MBG-RCA effects were identified using behavioral monitoring observed by an infrared night vision supervisory control system, electroencephalograms, blood ammonia levels, intestinal ammonia levels, liver functionality and pathological observation. High-and medium-dose oral administrations of MBG-RCA significantly decreased the blood and intestinal ammonia levels (P<0.05), improved liver functionality and reduced the clinical manifestations of HE in rats. MBG-RCA demonstrated high clearance of rat colonic ammonia while maintaining sufficient stability in the GI tract, indicating the potential for the development of new clinically relevant oral preparations for the prevention of HE. Additionally, such preparations are advantageous in that ammonia is eliminated without the production of potentially harmful metabolic byproducts. IntroductionElimination of excess ammonia is the primary method of prevention and treatment of hepatic encephalopathy (HE), a progressive condition in which neurological function is impaired as the liver fails to remove toxic metabolites, particularly ammonia, from the bloodstream. The majority of intestinal ammonia is produced in the colon; however, no clinically viable oral treatment exists for the elimination of this excess ammonia, resulting in continuous low clearance levels due to poor ammonia elimination in the body.HE is a syndrome caused by serious hepatic diseases as a result of metabolic disturbance and dysfunction of the central nervous system. Its clinical manifestation includes deposition changes, ethological abnormalities and mental retardation. In severe cases, it may develop into a coma or even be life-threatening. A number of researchers have divided HE into three categories: Type A is associated with acute liver failure; type B is caused by severe portosystemic shunting without liver disease; and type C is associated with chronic liver disease and hepatic cirrhosis (1). Acute liver failure models are well recognized as a representative model of type A HE. These models may be used to examine the pathological response of HE to v...

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Section: Discussionmentioning

confidence: 99%

pH-sensitive microemulsion-based gels for removal of colonic ammonia: A novel preventative oral preparation for hepatic encephalopathy in rats

Zhang

Duan

Tian

et al. 2015

Molecular Medicine Reports

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“…On the other hand rifaxamin is an antibiotic which is not absorbed through the gut and it helps creating the balance between the gut flora. [16][17] While in another study done by Als-Nielsen B et al, the lactulose was compared with placebo and there was even no significant difference was seen as well. 18 The mortality was also better reduced by the combination therapy as compared to alone where it was seen in 29 (48.33%) cases with lactulose only and 18 (30%) cases with combination therapy with significant difference of 0.03.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Encephalopathy; To Compare the Efficacy of Lactulose Alone and Lactulose With Rifaxamin in Patients of Hepatic Encephalopathy

Hussain

Rehman

Akhtar

et al. 2017

TPMJ

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ABSTRACT… Background: Hepatic encephalopathy is one of the fatal complications of liver cirrhosis in clinical setting. A number of drugs with varied response have been tried up till now. Objectives: To compare the efficacy of lactulsoe alone and in combination with rifaxamin in cases with hepatic encephalopathy. Study Design: Randomized control trail. Setting: Sheikh Zayed Hospital (SZH) Rahim Yar Khan (RYK). Period: January 2015 to October 2015. Patients and Methods: 120 cases of liver cirrhosis with encephalopathy were randomized into different grades according to West Haven's criteria. These cases were then equally divided into group A and B. Group A was treated with lactulose alone while group B was treated with lactulose plus rifaxamin with their standard doses. The cases were assessed for their improvement in symptoms on West Haven's scale and the cases with complete resolution of symptoms were labeled as cured. The mortality benefit was also noted. Results: The mean age was 43.24± 8.34 years and mean duration of symptoms was 3.45± 0.8 days. There was no significant difference in terms of child pugh score in both groups with p= 0.69. There was also no significant difference in both groups in terms of grades of encephalopathy (p= 0.21). However there was significant better efficacy and decreased mortality in group B as compared to A with p values of 0.02 and 0.03 respectively. Conclusion: Lactulose combined with rifaxamin has significant improvement in encephalopathy as well as in reducing mortality in comparison with lactulsoe alone Key words:Hepatic encephalopathy, Lactulose, Rifaxamin. West Haven criteria.

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“…There was significant decrease in mortality after treatment with lactulose plus rifaximin versus lactulose and placebo (23.8% Vs 49.1%, P < 0.05). 46 Hence we recommend that combination of therapy should be practiced now for the treatment of HE.…”

Section: Combination Therapy For Overt Hepatic Encephalopathymentioning

confidence: 99%

Management of Overt Hepatic Encephalopathy

Sharma

2015

Journal of Clinical and Experimental Hepatology

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Hepatic encephalopathy (HE) is an important complication of cirrhosis with significant morbidity and mortality. Management of HE primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as non-absorbable disaccharides, antimicrobial agents like rifaximin and L-ornithine L-aspartate. The non-absorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and in primary and secondary prophylaxis of HE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Rifaximin is effective in treatment of HE and recent systemic reviews found it comparable to disaccharides and is effective in secondary prophylaxis of HE. H epatic encephalopathy (HE) is a complex neuropsychiatric syndrome, which may complicate acute, chronic liver failure or patients with portal-systemic shunting. It is characterized by changes in mental state including a wide range of neuropsychiatric symptoms ranging from minor signs of altered brain function to deep coma. 1,2 It is one of the commonest indications for admission in intensive care unit in patients with advanced cirrhosis. There were over 40 000 patients hospitalized in the United States alone for a primary diagnosis of HE, resulting in total charges of approximately $932 million. Data in other countries are lacking, hence it causes a huge burden financially to the patient and society. 3 The West Haven Criteria are most often used to grade HE, with scores ranging from I-IV (IV being coma). However, it is a challenge to diagnose patients with minimal hepatic encephalopathy (MHE) or grade 1 HE; so it might be practical to combine these entities and name them covert HE for clinical use and overt HE to patients with grade II to IV. 1,4,5 One of the major tenets of the pathophysiology of HE is hyperammonemia that results from an increased nitrogenous load from the gastrointestinal tract and reduced urea synthesis both due to portal-systemic shunting and decreased urea hepatic synthesis. Brain and skeletal muscle neither remove nor produce ammonium in normal conditions, but they are able to seize ammonium during hyperammonemia, releasing glutamine. Ammonia is produced both by bacterial degradation of amines, aminoacids, purines, and urea as well as enterocytic glutaminase activity that converts glutamine to glutamate and ammonia. 6,7 Astrocytes play an important role in the pathogenesis of HE with consequences for neuronal function. Astrocytes have the ability to eliminate ammonia by the synthesis of glutamine through amidation of glutamate by the enzyme glutamine synthetase Hyperammonemia leads to the accumulation of glutamine within astrocytes, which exerts an osmotic stress that causes astrocytes to take in water and swell. 8,9 This article reviewed the clinical impact, pathogenesis, and management of overt HE in patients with cirrhosis. Articles published between January 1960 and November 2013 were acquired through a MEDLINE search of different combi...

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A Randomized, Double-Blind, Controlled Trial Comparing Rifaximin Plus Lactulose With Lactulose Alone in Treatment of Overt Hepatic Encephalopathy

Abstract: Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.

Cited by 275 publications

References 23 publications

pH-sensitive microemulsion-based gels for removal of colonic ammonia: A novel preventative oral preparation for hepatic encephalopathy in rats

pH-sensitive microemulsion-based gels for removal of colonic ammonia: A novel preventative oral preparation for hepatic encephalopathy in rats

Hepatic Encephalopathy; To Compare the Efficacy of Lactulose Alone and Lactulose With Rifaxamin in Patients of Hepatic Encephalopathy

Management of Overt Hepatic Encephalopathy

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