Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials

Als‐Nielsen, Bodil; Gluud, Lise Lotte; Gluud, Christian

doi:10.1136/bmj.38048.506134.ee

Cited by 342 publications

(209 citation statements)

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“…Lactulose was chosen as a modality of intervention in this study because the drug is cost effective, easily available, and effective in reducing blood ammonia. 47,48 In a recent systematic review, Als-Nielsen et al 49 concluded there is insufficient evidence to support or refute use of nonabsorbable diasaccharides for HE. However, the inconclusive results of these studies could be related to confounding factors, such as precipitating events, degree of hepatic failure, and extent of portosystemic shunting.…”

Section: Discussionmentioning

confidence: 99%

Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy

et al. 2007

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Minimal hepatic encephalopathy (MHE) has a negative effect on patients' daily functioning. Thus far, no study has investigated the effect of treatment-related improvement in cognitive functions on health-related quality of life (HRQOL). We measured psychometric performance by number and figure connection tests parts A and B, picture completion, and block design tests and HRQOL by the Sickness Impact Profile (SIP) of 90 patients with cirrhosis on inclusion into the study and 3 months later. A Z score less than ؊2 on the neuropsychological (NP) tests was considered abnormal. Sixty-one (67.7%) patients had MHE. They were randomly assigned in a 1:1 ratio to receive treatment (lactulose) for 3 months (n ‫؍‬ 31) or no treatment (n ‫؍‬ 30) in a nonblinded design. H epatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction diagnosed after exclusion of other known brain diseases. The Working Party at the 11th World Congress of Gastroenterology, Vienna, under the Organization Mondiale de Gastroentrologie proposed a multiaxial definition of HE that defined both the type of hepatic abnormality (type A, B, or C) and the duration and characteristics of neurological manifestations (episodic, persistent, or minimal HE) in chronic liver disease. 1 HE has been considered a continuous dimension that could be measured with 1 index to summarize several neurological domains, such as cognition, emotion, behavior, and biologic rhythms. Minimal hepatic encephalopathy (MHE) represents a portion of this dimension and is the mildest form of HE. Whereas patients with HE have impaired intellectual functioning, personality changes, altered level of consciousness, and neuromuscular dysfunction, patients with MHE have no recognizable clinical symptoms of HE but do have mild cognitive and psychomotor deficits. In the absence of a "gold standard" for determining MHE, neuropsychological (NP) and neurophysiological methods have been the most trusted and widely used tests to diagnose this condition. 1,2 MHE is considered clinically relevant for at least 3 reasons. First, it impairs patients' daily functioning and

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Section: Discussionmentioning

confidence: 99%

Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy

et al. 2007

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“…In a recent meta-analysis, only few high quality studies have shown any beneficial effect with lactulose and its popularity stems from a long clinical experience rather than strong objective evidence. 46 Antibiotics have their inherent adverse effects, especially on prolonged use. Concepts on protein restriction are being revised.…”

Section: Ammonia Lowering Strategiesmentioning

confidence: 99%

Management in Acute Liver Failure

Shalimar

Acharya

2015

Journal of Clinical and Experimental Hepatology

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Acute liver failure (ALF) is a rare, potentially fatal complication of severe hepatic illness resulting from various causes. In a clinical setting, severe hepatic injury is usually recognised by the appearance of jaundice, encephalopathy and coagulopathy. The central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a central role in the pathogenesis. The role of newer ammonia lowering agents is still evolving. Liver transplant is the only effective therapy that has been identified to be of promise in those with poor prognostic factors, whereas in the others, aggressive intensive medical management has been documented to salvage a substantial proportion of patients. A small fraction of patients undergo liver transplant and the remaining are usually treated with medical therapy. Therefore, identification of the complications and causes of death in such patients, and use of appropriate prognostic models to identify those who need liver transplant and those who can be managed with medical treatment is a vital component of therapeutic strategy. In this review, we discuss the various pathogenetic mechanisms and treatment options available. ( J CLIN EXP HEPATOL 2015;5:S104-S115)A cute liver failure (ALF) can be a fatal complication of acute hepatic injury and occurs unpredictably. It is a rare clinical entity marked by the sudden loss of hepatic function and a severe life-threatening course in a person with no prior history of liver disease. ALF represents a syndrome rather than a specific disease, having multiple causes that vary in course and outcome. ALF is difficult to identify in its early stages, resulting in frequent delays in initiation of treatment. The causes of ALF include viral hepatitis, drug induced and toxin-induced liver damage, metabolic errors, ischemia, and miscellaneous rare causes.ALF is defined by three criteria: (1) rapid development of hepatocellular dysfunction (jaundice, coagulopathy), (2) encephalopathy, and (3) absence of a prior history of liver disease. 1 However, the interval between onset of acute hepatic injury (jaundice) and onset of liver failure (encephalopathy with or without coagulopathy) in such patients (icterus-encephalopathy interval; IEI) has been described to be between 4 weeks (Indian definition) 2-4 to 24 weeks (AASLD-ALF study group). 5 Further, due to the diverse natural course, ALF has been sub-classified as hyperacute (IEI # 7 day), acute (IEI # 4 weeks) and sub-acute ALF (IEI $ 5 week to #12 weeks) by British authors. 6 Despite these differences in definitions, the central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique an...

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“…However high quality trials found no significant effect of lactulose or lactitol on the risk of no improvement (0.92, 0.42-2.04), whereas low quality trials found a significant beneficial effect of lactulose or lactitol (0.57, 0.40-0.83). 20 Most of the studies were carried out in adults however lactulose has shown to be effective in the treatment of HE in children also. 21 At present time, however, there is a lack of sufficient evidence to thoroughly refute the use of non-absorbable disaccharides for the treatment of HE.…”

Section: Clinical Efficacy Of Non-absorbable Disaccharidesmentioning

confidence: 99%

“…26 Many studies have demonstrated the efficacy of rifaximin in the treatment of overt HE (grade $1) 27-32 ( Table 2). In a meta-analysis by Nielsen et al 20 compared with antibiotics, patients taking rifaximin had a significant lower risk of no improvement of HE than those taking lactulose or lactitol alone. However in another two recent meta-analysis including more trials and higher number of patients rifaximin is not superior to non-absorbable disaccharides for acute or chronic hepatic encephalopathy in the long-term or short-term treatment except that it may be better tolerated.…”

Section: Rifaximin For 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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Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials

Abstract: Objective To assess the effects of non-absorbable disaccharides (lactulose and lactitol) in patients with hepatic encephalopathy.

Cited by 342 publications

References 33 publications

Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy

Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy

Management in Acute Liver Failure

Management of Overt Hepatic Encephalopathy

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