Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Gluud LL
PROVIDER: S-EPMC7004252 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Publications
Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis.
Gluud Lise Lotte LL Vilstrup Hendrik H Morgan Marsha Y MY
The Cochrane database of systematic reviews 20160506 5
<h4>Background</h4>Non-absorbable disaccharides (lactulose and lactitol) are recommended as first-line treatment for hepatic encephalopathy. The previous (second) version of this review included 10 randomised clinical trials (RCTs) evaluating non-absorbable disaccharides versus placebo/no intervention and eight RCTs evaluating lactulose versus lactitol for people with cirrhosis and hepatic encephalopathy. The review found no evidence to either support or refute the use of the non-absorbable disa ...[more]
Similar Datasets
Project description:BackgroundHepatic encephalopathy (HE) is a major cause of mortality and morbidity in patients with cirrhosis. Lactulose non-adherence is one of the most frequently reported precipitants of hospital admission for HE.AimsWe aimed to identify which factors contribute most to lactulose non-adherence and propose strategies to promote greater adherence and utilization of lactulose.MethodsParticipants in this study consisted of patients with cirrhosis who were taking lactulose for prevention of HE. Subjects were administered the Morisky Adherence Scale 8 (MAS-8) and a customized 16-question survey that assessed barriers to lactulose adherence. Results from the MAS-8 were used to stratify subjects into "adherent" and "non-adherent" groups. Survey responses were compared between groups.ResultsWe enrolled 129 patients in our study, of whom 45 were categorized as "adherent and 72 were categorized as "non-adherent." Barriers to adherence included large volumes of lactulose, high frequency of dosing, difficulty remembering to take the medication, unpleasant taste, and medication side-effects. Most patients (97%) expressed understanding of the importance of lactulose, and 71% of patients felt that lactulose was working to manage their HE. Hospital admission rates for HE was higher in non-adherent patients, although this difference was not statistically significant.ConclusionWe identified several factors that contribute to lactulose non-adherence among patients treated for HE. Many of these factors are potentially modifiable. Patient and care-giver education are critical to assure adherence. Pharmacists and nurses are an essential but underutilized aspect of education regarding proper medication use.
| S-EPMC11380462 | biostudies-literature
Project description:ObjectivesDecreased magnetization transfer ratio (MTR) in the brain characterizes cerebral edema (CE) in patients with liver cirrhosis, but the role of treatment on its reversibility has not been studied in patients who have minimal hepatic encephalopathy (MHE). This study was carried to evaluate the reversibility of CE with lactulose and rifaximin treatment in patients with MHE and role of ammonia, pro-inflammatory interleukins (IL-1, IL-6) and tumor necrosis factor (TNF)-α in its pathogenesis.MethodsTwenty-three patients with cirrhosis (14 with MHE, 9 without MHE (NMHE)) and 6 healthy controls underwent ammonia, IL-1, IL-6, TNF-α estimation, and MTR in frontal white matter (FWM), parietal white matter (PWM), internal capsule (IC), and basal ganglia (BG).ResultsAmmonia was significantly higher in the cirrhosis group compared with controls and in MHE compared with the NMHE group. Ammonia correlated positively with IL-1 and IL-6. MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group. MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment. IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions.ConclusionsThis study, for the first time, demonstrated the reversibility of low-grade CE with treatment in patients with MHE. Negative correlation between ammonia, IL-6 levels, and MTR and positive correlation between PHES and MTR in MHE patients suggests the role of inflammation and ammonia in the genesis of low-grade CE.
| S-EPMC4816249 | biostudies-literature
Project description:Cirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common (20%-54%) and often severe complication. A prophylactic strategy is lacking. The Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a TIPS (PEARL) trial, is a multicentre randomised, double blind, placebo controlled trial. Patients undergoing covered TIPS placement are prescribed either rifaximin 550 mg two times per day and lactulose 25 mL two times per day (starting dose) or placebo 550 mg two times per day and lactulose 25 mL two times per day from 72 hours before and until 3 months after TIPS placement. Primary endpoint is the development of overt HE (OHE) within 3 months (according to West Haven criteria). Secondary endpoints include 90-day mortality; development of a second episode of OHE; time to development of episode(s) of OHE; development of minimal HE; molecular changes in peripheral and portal blood samples; quality of life and cost-effectiveness. The total sample size is 238 patients and recruitment period is 3 years in six hospitals in the Netherlands and one in Belgium. This study protocol was approved in the Netherlands by the Medical Research Ethics Committee of the Academic Medical Centre, Amsterdam (2018-332), in Belgium by the Ethics Committee Research UZ/KU Leuven (S62577) and competent authorities. This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Study results will be submitted for publication in a peer-reviewed journal. ClinicalTrials.gov (NCT04073290) and EudraCT database (2018-004323-37).
| S-EPMC7783616 | biostudies-literature
Project description:Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients' quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.
| S-EPMC10027066 | biostudies-literature
Project description:ObjectivesIdentify if lactulose administration is associated with hypercalcemia in dogs medically managed for hepatic encephalopathy due to a portosystemic shunt and measure any magnitude in change of ionized calcium (iCa) or total calcium.AnimalsSeventeen client-owned dogs diagnosed with a portosystemic shunt and medically managed with lactulose.ProcedureTotal calcium and iCa were measured at Time point 1 (T1), before starting medical management; and Time point 2 (T2), the time of a reassessment after > 3 wk of lactulose administration.ResultsThere were no statistically significant differences in iCa or total calcium between T1 and T2. Lactulose dose was positively correlated with change in iCa between T1 and T2.Conclusion and clinical relevanceThis study did not identify the development of hypercalcemia in a population of dogs treated with lactulose for the management of hepatic encephalopathy. A possible correlation was present between dose of lactulose and change in iCa, and this may represent a dose-dependent association.
| S-EPMC11618998 | biostudies-literature
Project description:Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA.
| S-EPMC8537523 | biostudies-literature
Project description: Not available
| S-EPMC6572872 | biostudies-literature
Project description:BackgroundHepatic encephalopathy (HE) is a complex neuropsychiatric syndrome associated with liver failure and/or portal systemic shunting. Polyethylene glycol (PEG) electrolyte solution is a commonly used for catharsis of gut, which has been demonstrated to relieve HE in a number of randomized controlled trials. The aim of this paper was to evaluate the comparative efficacy and safety of PEG with lactulose for current HE treatment.MethodsPEG electrolyte solution versus lactulose of HE was deeply studied by conducting a systematic search in electronic databases and other sources until December 31, 2020. The PRISMA statement recommended the use of meta-analysis with 95% confidence interval (CI), relative risk (RR), and weighted mean deviation (WMD) as the estimated effect size. A sensitivity analysis was performed comprehensively to present the risk of bias and the source of heterogeneity.ResultsA total of 434 patients were involved in 7 randomized studies. It is found that there was a significant advantage of PEG therapy in the increase of clinical efficacy (RR=1.46; 95% CI: 1.26-1.68; P=0.000; I2=0.0%) and the decrease of hospital stay (WMD=-1.78; 95% CI: -2.72 to 0.85; P=0.000; I2=90.1%). There was no significant difference in the incidence of adverse events (RR=0.75; 95% CI: 0.48-1.19; P=0.222>0.05; I2=7.2%) and the level of serum ammonia (WMD=9.02; 95% CI: -14.39 to 32.43; P=0.45>0.05; I2=84.9%) after 24 hours between the 2 groups.ConclusionsThe results prove that PEG has a beneficial effect on the treatment of HE. Compared with lactulose, PEG can lead to more rapid HE resolution during the first 24 hours and shorten the length of stay without increasing the rate of adverse effects.
| S-EPMC8647701 | biostudies-literature
Project description:Background & aimsHepatic encephalopathy (HE), one of the most serious prognostic factors for mortality in alcohol-related cirrhosis (ALD cirrhosis), is not recorded in Danish healthcare registries. However, treatment of HE with lactulose, the universal first-line treatment, can be identified through data on filled prescriptions. This study aimed to investigate if lactulose can be used as a surrogate marker of HE.MethodsWe used Danish healthcare registries to establish a cohort of patients with ALD cirrhosis diagnosed in 2000-2018. Lactulose users were identified using data on filled prescriptions. We computed the prevalence and cumulative incidence of lactulose use, and then matched lactulose users with cohort members who were not using lactulose. This matched dataset was used to identify predictors of lactulose initiation, and to examine the association between lactulose use and all-cause mortality.ResultsWe included 23,089 patients, among whom we identified 4,789 first-time lactulose users. The prevalence of lactulose usage rose to 11% within the first 6 months after ALD diagnosis and reached 19% 5 years after inclusion. The 1-year cumulative incidence of lactulose use was 31%, and predictors of initiating lactulose use were history of severe liver disease (ascites, portal hypertension, spontaneous bacterial peritonitis or gastrointestinal bleeding) or hepatocellular carcinoma. Lactulose use was associated with higher mortality (adjusted hazard ratio 1.61 [95% confidence interval 1.53; 1.69]).ConclusionsLactulose is used by 10-20% of patients with ALD cirrhosis, primarily those with severe cirrhosis, and lactulose users have a markedly higher mortality than nonusers. We conclude that lactulose use can be used to estimate the prevalence of HE and to reduce confounding from HE, but it should not be used as a surrogate for HE in studies with HE as an outcome.
| S-EPMC11742859 | biostudies-literature
Project description:Hepatic encephalopathy (HE) is one of the main complications of liver cirrhosis (LC) and is classified into minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy (overt HE). S100B is expressed mainly in astrocytes and other glial cells, and S100B has been reported to be associated with various neurological disorders. The present study aimed to investigate the diagnostic ability of serum S100B to discriminate the grade of HE and the parameters correlated with serum S100B levels. Additionally, we investigated whether serum S100B levels can be used to predict 1-year mortality in cirrhotic patients. In total, 95 cirrhotic patients were consecutively enrolled and divided into the following three groups: (i) without any types of HEs; (ii) with MHE; and (iii) with overt HE. The diagnosis of MHE was made by the Mini-Mental State Examination (MMSE) and Psychometric Hepatic Encephalopathy Score (PHES). Among the three groups, there were no significant differences in serum S100B levels regardless of HE severity. The clinical parameters correlated with serum S100B levels were age, serum bilirubin, and creatinine levels. The Model for End-Stage Liver Disease (MELD) score showed a significant positive correlation with serum S100B levels. The relationship between serum S100B levels and MELD score was maintained in 48 patients without any type of HE. Additionally, hyperammonemia, low cholesterol levels, and the combination of serum S100B levels ≥ 35 pg/mL with MELD score ≥ 13 were factors for predicting 1- year mortality. In conclusion, serum S100B level was not useful for differentiating the severity of HE. However, we found that serum S100B levels can be affected by age, serum bilirubin, and creatinine in cirrhotic patients and are associated with MELD scores. Additionally, serum S100B levels showed the possibility of predicting 1-year mortality in cirrhotic patients. These findings suggest that serum S100B levels may reflect liver dysfunction and prognosis in liver disease.
| S-EPMC9914222 | biostudies-literature