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European Journal of Gastroenterology &... Apr 2019A consolidated overview of evidence for the effectiveness and safety/tolerability of hepatic encephalopathy (HE) treatment over the long term is currently lacking. We... (Review)
Review
A consolidated overview of evidence for the effectiveness and safety/tolerability of hepatic encephalopathy (HE) treatment over the long term is currently lacking. We identified and assessed published evidence for the long-term (≥6 months) pharmacological management of HE with lactulose and/or rifaximin. A literature search was conducted in PubMed (cutoff date 05 March 2018) using the search terms 'hepatic encephalopathy+rifaximin' and 'hepatic encephalopathy+lactulose'. All articles containing primary clinical data were manually assessed to identify studies in which long-term (≥6 months) effectiveness and/or safety/tolerability end points were reported for lactulose and/or rifaximin. Long-term effectiveness outcomes were reported in eight articles for treatment with lactulose alone and 19 articles for treatment with rifaximin, alone or in combination with lactulose. Long-term safety/tolerability outcomes were reported in six articles for treatment with lactulose alone and nine articles for treatment with rifaximin, alone or in combination with lactulose. These studies showed that lactulose is effective for the prevention of overt HE recurrence over the long term and that the addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization, compared with lactulose therapy alone, without compromising tolerability. Current evidence therefore supports recommendations for the use of lactulose therapy for the prevention of overt HE recurrence over the long term, and for the additional benefit of adding rifaximin to lactulose therapy. Addition of rifaximin to standard lactulose therapy may result in substantial reductions in healthcare resource utilization over the long term, by reducing overt HE recurrence and associated rehospitalization.
Topics: Drug Therapy, Combination; Evidence-Based Medicine; Gastrointestinal Agents; Hepatic Encephalopathy; Humans; Lactulose; Recurrence; Rifaximin; Secondary Prevention
PubMed: 30444745
DOI: 10.1097/MEG.0000000000001311 -
BMJ Open Gastroenterology May 2021Hepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity and mortality. Lactulose is the standard of care till this date; however, polyethylene glycol (PEG) has gained the attention of multiple investigators.
METHODS
We screened five databases namely PubMed, Scopus, Web of Science, Cochrane Library and Embase from inception to 10 February 2021. Dichotomous and continuous data were analysed using the Mantel-Haenszel and inverse variance methods, respectively, which yielded a meta-analysis comparing PEG versus lactulose in the treatment of HE.
RESULTS
Four trials with 229 patients were included. Compared with lactulose, the pooled effect size demonstrated a significantly lower average HE Scoring Algorithm (HESA) Score at 24 hours (Mean difference (MD)=-0.68, 95% CI (-1.05 to -0.31), p<0.001), a higher proportion of patients with reduction of HESA Score by ≥1 grade at 24 hours (risk ratio (RR)=1.40, 95% CI (1.17 to 1.67), p<0.001), a higher proportion of patients with a HESA Score of grade 0 at 24 hours (RR=4.33, 95% CI (2.27 to 8.28), p<0.0010) and a shorter time to resolution of HE group (MD=-1.45, 95% CI (-1.72 to -1.18), p<0.001) in favour of patients treated with PEG.
CONCLUSION
PEG leads to a higher drop in the HESA Score and thus leads to a faster resolution of HE compared with lactulose.
Topics: Hepatic Encephalopathy; Humans; Lactulose; Liver Cirrhosis; Polyethylene Glycols
PubMed: 34006606
DOI: 10.1136/bmjgast-2021-000648 -
PloS One 2022Rifaximin and lactulose are widely used in patients with hepatic encephalopathy (HE); however, data on whether the combined use of rifaximin and lactulose could yield... (Meta-Analysis)
Meta-Analysis
Rifaximin and lactulose are widely used in patients with hepatic encephalopathy (HE); however, data on whether the combined use of rifaximin and lactulose could yield additional benefits for patients with HE are limited and inconclusive. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the treatment effectiveness of rifaximin plus lactulose versus lactulose alone in patients with HE. Electronic databases (PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure) were searched for eligible RCTs from their inception until November 2020. Relative risks (RRs) with 95% confidence intervals (CIs) were applied to calculate pooled effect estimates for the treatment effectiveness of rifaximin plus lactulose versus lactulose alone by using the random-effects model. Sensitivity, subgroup, and publication bias analyses were also performed. We included 7 RCTs enrolling 843 patients with HE. We noted that the use of rifaximin plus lactulose was associated with an increased incidence of effective rate than lactulose alone (RR, 1.30; 95% CI, 1.10-1.53; P = 0.002). Moreover, the use of rifaximin plus lactulose was associated with a reduced risk of mortality as compared with lactulose alone (RR, 0.57; 95% CI, 0.41-0.80; P = 0.001). This study found that the use of rifaximin in combination with lactulose could provide additional benefits in terms of increased effective rate and decreased mortality than lactulose alone in patients with HE.
Topics: Combined Modality Therapy; Hepatic Encephalopathy; Humans; Lactulose; Rifaximin; Treatment Outcome
PubMed: 35471992
DOI: 10.1371/journal.pone.0267647 -
Anaerobe Oct 2019Lactulose is a disaccharide used in clinical practice since 1957 and has since been tested in the treatment of many human disorders, including chronic constipation,... (Review)
Review
Lactulose is a disaccharide used in clinical practice since 1957 and has since been tested in the treatment of many human disorders, including chronic constipation, hepatic encephalopathy, and chronic kidney disease. Its mode of action is based on the lactulose fermentation by intestinal microbiota. Based on in silico, in vitro and in vivo studies we comprehensively review here the impact of lactulose on human gut/fecal and vaginal microbiota composition and both fecal and blood metabolomes. However, both in vitro and in vivo studies summarized in this review have revealed that the effects of lactulose on human microbiota composition are both patient- and dose-dependent. This highlights the need of heterogeneity indication in clinical trials.
Topics: Feces; Female; Fermentation; Gastrointestinal Agents; Humans; Lactulose; Metabolome; Microbiota; Prebiotics; Vagina
PubMed: 31176002
DOI: 10.1016/j.anaerobe.2019.06.002 -
Biotechnology Advances Nov 2022Lactulose, a semisynthetic nondigestive disaccharide with versatile applications in the food and pharmaceutical industries, has received increasing interest due to its... (Review)
Review
Lactulose, a semisynthetic nondigestive disaccharide with versatile applications in the food and pharmaceutical industries, has received increasing interest due to its significant health-promoting effects. Currently, industrial lactulose production is exclusively carried out by chemical isomerization of lactose via the Lobry de Bruyn-Alberda van Ekenstein (LA) rearrangement, and much work has been directed toward improving the conversion efficiency in terms of lactulose yield and purity by using new chemo-catalysts and integrated catalytic-purification systems. Lactulose can also be produced by an enzymatic route offering a potentially greener alternative to chemo-catalysis with fewer side products. Compared to the controlled trans-galactosylation by β-galactosidase, directed isomerization of lactose with high isomerization efficiency catalyzed by the most efficient lactulose-producing enzyme, cellobiose 2-epimerase (CE), has gained much attention in recent decades. To further facilitate the industrial translation of CE-based lactulose biotransformation, numerous studies have been reported on improving biocatalytic performance through enzyme mediated molecular modification. This review summarizes recent developments in the chemical and enzymatic production of lactulose. Related catalytic mechanisms are also highlighted and described in detail. Emerging techniques that aimed at advancing lactulose production, such as the boronate affinity-based technique and molecular biological techniques, are reviewed. Finally, perspectives on challenges and opportunities in lactulose production and purification are also discussed.
Topics: Catalysis; Cellobiose; Isomerism; Lactose; Lactulose; Racemases and Epimerases; beta-Galactosidase
PubMed: 35901861
DOI: 10.1016/j.biotechadv.2022.108021 -
Zeitschrift Fur Gastroenterologie Oct 1997Lactulose is therapeutically used in hepatic encephalopathy, constipation, and salmonellosis. This semisynthetic disaccharide is neither metabolized nor absorbed in the... (Review)
Review
Lactulose is therapeutically used in hepatic encephalopathy, constipation, and salmonellosis. This semisynthetic disaccharide is neither metabolized nor absorbed in the normal small intestines. Comparable to plant-polysaccharides lactulose is bacterially fermented in the colon to short chain fatty acids and gases. Major consequences are a drop in pH and a change in composition and metabolic activity of the colonic flora. These and other potential effects suggest complex mechanisms of action of lactulose, with the potential for additional indications in diagnosis and therapy. The use of lactulose as substrate for the H2-breath-test is well known as a means for the measurement of oroeceal transit time and as test for small intestinal bacterial overgrowth. An extension of the diagnostic potential is given by the assessment of the permeability in diffuse intestinal disease with combined disaccharide/monosaccharide test solutions, especially in Crohn's disease. Explanations for positive effects in the prophylaxis of cholesterol-gallstones, in the therapy of hypercholesterolemia and in the prevention of colorectal adenoma and carcinoma can be found in changes in lipid- and bile acid metabolism found after lactulose ingestion. Lactulose may lead to an improved glucose-tolerance in parallel to fibre and acarbose effects which involve several mechanisms of carbohydrate metabolism. Lactulose presumably reduces pathogenic bacteria in favor of the health promoting bifidusflora; also, production and absorption of endotoxines may be reduced; this suggests that lactulose may have therapeutic effects on both infectious and idiopathic inflammatory bowel diseases. Numerous studies with interesting but not as yet convincingly documented clinical relevance suggest that the many effects of lactulose may be interesting subjects for future research.
Topics: Gastrointestinal Diseases; Humans; Intestinal Absorption; Lactulose
PubMed: 9370144
DOI: No ID Found -
Neurocritical Care Apr 2018Hepatic encephalopathy is a common encephalopathy and one of the very few that are treatable. Lactulose has remained a standard pharmaceutical intervention and is listed... (Review)
Review
Hepatic encephalopathy is a common encephalopathy and one of the very few that are treatable. Lactulose has remained a standard pharmaceutical intervention and is listed as one of the World Health Organization's Essential Medicines. The discovery of lactulose, the acid dialysis proof of concept, and the role of Bircher are not well known. This historical vignette reviews the gradual understanding of the complex liver-brain connection, the effective treatment of hepatic stupor with lactulose, and the immediate relevance of lactulose to the practice of consultative neurocritical care.
Topics: Gastrointestinal Agents; Hepatic Encephalopathy; History, 20th Century; Humans; Lactulose
PubMed: 29297141
DOI: 10.1007/s12028-017-0494-4 -
Frontiers in Endocrinology 2022The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy.... (Review)
Review
The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy. The mechanism of action of lactulose remains unclear, but it elicits more than osmotic laxative effects. As a prebiotic, lactulose may act as a bifidogenic factor with positive effects in preventing and controlling diabetes. In this review, we summarized the current evidence for the effect of lactulose on gut metabolism and type 2 diabetes (T2D) prevention. Similar to acarbose, lactulose can also increase the abundance of the short-chain fatty acid (SCFA)-producing bacteria and as well as suppress the potentially pathogenic bacteria . These bacterial activities have anti-inflammatory effects, nourishing the gut epithelial cells and providing a protective barrier from microorganism infection. Activation of peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP1) can influence secondary bile acids and reduce lipopolysaccharide (LPS) endotoxins. A low dose of lactulose with food delayed gastric emptying and increased the whole gut transit times, attenuating the hyperglycemic response without adverse gastrointestinal events. These findings suggest that lactulose may have a role as a pharmacotherapeutic agent in the management and prevention of type 2 diabetes actions on the gut microbiota.
Topics: Acarbose; Anti-Inflammatory Agents; Bacteria; Bile Acids and Salts; Diabetes Mellitus, Type 2; Fatty Acids, Volatile; Glucagon-Like Peptide 1; Humans; Lactulose; Laxatives; Lipopolysaccharides; Peptides; Tyrosine
PubMed: 36187096
DOI: 10.3389/fendo.2022.956203 -
The American Journal of Gastroenterology Sep 2013Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVES
Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE.
METHODS
In this prospective double-blind randomized controlled trial, 120 patients with overt HE were randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay.
RESULTS
A total of 120 patients (mean age 39.4±9.6 years; male/female ratio 89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7±2.8 and the MELD (model for end-stage liver disease) score was 24.6±4.2. At the time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and 58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29 (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8±3.4 vs. 8.2±4.6 days, P=0.001).
CONCLUSION
Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.
Topics: Adult; Double-Blind Method; Drug Therapy, Combination; Female; Gastrointestinal Agents; Hepatic Encephalopathy; Humans; Lactulose; Length of Stay; Male; Middle Aged; Rifamycins; Rifaximin; Severity of Illness Index; Treatment Outcome
PubMed: 23877348
DOI: 10.1038/ajg.2013.219 -
Nursing Times
Topics: Constipation; Gastrointestinal Agents; Humans; Lactulose; Patient Education as Topic
PubMed: 16475577
DOI: No ID Found