ABSTRACT: The impact of oral nutritional supplements (ONS) on patients with complications (disease related morbidity) requires further exploration. This systematic review included 44 randomised controlled trials (RCT) (29 RCT surgical, 15 RCT medical patients) examining the effect of ONS in community settings on the incidence of complications (n5716, mean age 67 years, range 35-87). ONS (mean intake 588kcal/day, range 125-1750; protein 22g/day, range 0-54; mean energy from protein 22%, range 0-54) were prescribed for a mean 74 days, range 5-365. Most RCT (77%) reported fewer complications in the ONS group versus control. Meta-analysis (39 RCT) showed ONS consumption reduced complications including infections, pressure ulcers, wound and fracture healing (OR 0.68, 95% CI 0.59,0.79; p<0.001). Results showed reductions when ONS were used in hospital and community settings (OR 0.72, 95% CI 0.59,0.87; p=0.001) or just in the community (OR 0.65, 95% CI 0.52, 0.80; p<0.001). Reductions in complications were only seen with high ONS adherence ≥80% (OR 0.63, 95% CI 0.48,0.83; p=0.001) and ready-to-drink ONS (OR 0.69, 95% CI 0.60,0.81; p<0.001). This systematic review and meta-analysis show community-based use of ONS in addition to the diet substantially reduces the incidence of complications. The diversity of ONS, patient populations and complication outcomes within the trials included in this review mean further research is warranted.
Hepatic encephalopathy (HE) is a challenging complication of liver disease that is associated with substantial morbidity and mortality. Branched-chain amino acid (BCAA) supplementation in the management of HE is a debated topic. This narrative review aims to provide an up-to-date review of the topic and includes studies featuring patients with hepatocellular carcinoma. A review of the literature was performed using the online databases MEDLINE and EMBASE for studies between 2002 and December 2022. Keywords 'branched-chain amino acids', 'liver cirrhosis' and 'hepatic encephalopathy' were used. Studies were assessed for inclusion and exclusion criteria. Of 1045 citations, 8 studies met the inclusion criteria. The main outcomes reported for HE was changed in minimal HE (MHE) (n = 4) and/or incidence of overt HE (OHE) (n = 7). Two of the 4 studies reporting on MHE had improvement in psychometric testing in the BCAA group, but there was no change in the incidence of OHE in any of the 7 papers in the BCAA group. There were few adverse effects of BCAA supplementation. This review found weak evidence for BCAA supplementation for MHE, and no evidence for BCAAs for OHE. However, given the relative paucity and methodological heterogeneity of the current research, there is scope for future studies to examine the effects of varying timing, dosage, and frequency of BCAAs on outcomes such as HE. Importantly, research is also needed to examine BCAAs in conjunction with standard therapies for HE such as rifaximin and/or lactulose.
BACKGROUND: Branched chain amino acids' (BCAAs) beneficial role in the management of hepatic encephalopathy is already well established, whereas a number of randomized clinical trials (RCTs) have showed promising results examining BCAA supplementation in the management of other aspects of liver cirrhosis. Current results in the light of BCAAs' biochemical properties make them an attractive supplementation option, in addition to standard pharmaceutical treatment of cirrhosis.
AIM: The aim of this systematic review is to summarize the current literature and assess the efficacy of BCAA supplementation in patients with liver cirrhosis.
METHODS: Major electronic databases and grey literature sources were searched up to October 4th, 2021 for RCTs assessing the supplementation of BCAA against an active comparator, diet or placebo in patients with liver cirrhosis.
RESULTS: Twenty RCTs fulfilled selection criteria. Relative to other interventions BCAAs showed beneficial effect regarding muscle mass (SMD 0.21, 95% CI 0.01 to 0.4, I2 0%), but no effect regarding fat mass. Furthermore, BCAAs were associated with significant increase in plasma albumin concentration (SMD 0.52, CI 95% 0.18 to 0.86, I2 84.99%), reduction in occurrence of serious cirrhotic complications (logOR -046, CI 95% -0.78 to -0.13, I2 0%) and increase in body mass index (WMD 0.24, CI 95% 0.08 to 0.40, I2 0%). On the other hand, no significant effect was noted concerning the incidence of mortality.
CONCLUSION: Supplementation with BCAA seems to improve significant prognostic factors for patients with cirrhosis, with potential positive impact in mortality. Heterogeneity of study findings attributed to many factors limit overall conclusion and results require further assessment.
PURPOSE OF REVIEW: Ascites is a common, morbid complication of cirrhosis. Nutritional interventions such as sodium-restriction and high-protein diet are considered standard of care. However, their evidence base is limited. We performed a systematic review of randomized trials of nutritional interventions for ascites.
RECENT FINDINGS: Increasing consumption of calories and protein alone was ineffective. Studies reached contradictory conclusions regarding sodium restriction in patients taking combination diuretics. Intravenous amino acid infusion alone did not improve outcomes, peripheral parenteral nutrition did not improve outcomes except alone but reduced mortality in conjunction with branched-chain amino acid evening snack.
SUMMARY: Patients may benefit from sodium restriction and a protein-rich evening snack. Future trials should prioritize standardizing nutritional targets and tailoring interventions to the specific needs of patients including the socioeconomic factors impacting adherence.
BACKGROUND: Sarcopenia, i.e., muscle loss is now a well-recognized complication of cirrhosis and in cases of non-alcoholic fatty liver disease can contribute to accelerate liver fibrosis leading to cirrhosis. Hence, it is imperative to study interventions which targets to improve sarcopenia in cirrhosis.
AIM: To examine the relationship between interventions such nutritional supplementation, exercise, combined life style intervention, testosterone replacement and trans jugular intrahepatic portosystemic shunt (TIPS) to improve muscle mass in cirrhosis.
METHODS: We search PubMed, EMBASE and Cochrane between June-August 2018, without a limiting period and the types of articles (RCTs, clinical trial, comparative study) in adult patients with sarcopenia and cirrhosis. The primary outcome of interest was improvement in muscle mass, strength and physical function interventions mentioned above. In the screening process, 154 full text articles were included in the review and 129 studies were excluded.
RESULTS: We identified 24 studies that met review inclusion criteria. The studies were diverse in terms of the design, setting, interventions, and outcome measurements. We performed only qualitative synthesis of evidence due to heterogeneity amongst studies. Risk of bias was medium in most of the included studies and low quality of evidence showed improvement in the muscle mass, strength and physical function following aerobic exercise. 60% of the included studies on the nutritional intervention, 100% of the studies on testosterone replacement in hypogonadal men and trans-jugular portosystemic shunt were proved to be effective in improving sarcopenia in cirrhosis.
CONCLUSION: Although the quality of evidence is low, the findings of our systematic review suggest improvement in the sarcopenia in cirrhosis with exercise, nutritional interventions, hormonal and TIPS interventions. High quality randomized controlled trials needed to further strengthen these findings.
BACKGROUND AND AIM: Reduce post-absorptive (fasting) phase by eating late-evening snacks (LES) is a potential intervention to improve substrate utilization and reverse sarcopenia. This study analyzed the results of published randomized control and controlled clinical trials to evaluate the effects of LES on liver function of patients with cirrhosis.
METHODS: A meta-analysis was conducted. The search strategy included electronic database searches and 300 articles were searched. Eight of these articles provided qualified data for pooling and analysis. Outcomes assessments included serum albumin, total bilirubin, alanine aminotransferase, prothrombin time and aspartate aminotransferase, complications of cirrhosis, severity of liver disease, and blood glucose levels.
RESULTS: Our analysis included eight studies comprising 341 patients (167 in LES groups and 174 in control groups). The results showed LES intervention helped to maintain liver reserves. These eight studies demonstrated that LES intervention had significant effects for liver biochemical parameters on albumin, ammonia and PT, with respective effect sizes of 0.233, -0.425, and -0.589; liver enzymes include AST and ALT, with respective effect sizes of -0.320 and -0.284. Studies on clinical signs of liver dysfunction showed lower occurrence rates of ascites and HE than in the control group. LES had no significant effect on CPS.
CONCLUSIONS: The overall results of the meta-analysis indicated that having LES can improve liver function reserve for patients with LC, with or without HCC. LES is a promising intervention for reversing anabolic resistance and the sarcopenia of cirrhosis, resulting in an improved quality of life for patients with cirrhosis.
AIMS AND OBJECTIVES: To evaluate the effects of preoperative nutritional support using a regular diet for undernourished surgical patients at the outpatient clinic.
BACKGROUND: Undernutrition (or malnutrition) in surgical patients has severe consequences i.e. more complications, longer hospital stay, and decreased quality of life. While systematic reviews show the effects of oral nutritional supplements (ONS), enteral and parenteral nutrition in surgical patients, the effects of normal foods and regular diets remain unclear.
DESIGN: A systematic review.
METHODS: PubMed, CINAHL, Web of Science, PsycInfo, Cochrane Library, and Embase were searched up to July 24th , 2017. Studies on undernourished patients receiving nutritional support using regular or therapeutic diet, performed preoperatively at the outpatient clinic, were considered eligible. Risk of bias was assessed using the Cochrane Risk of Bias tool. Two reviewers independently performed study selection, quality assessment, and data extraction.
RESULTS: Six studies with moderate risk of bias were included. Interventions were preoperatively performed in mainly oncological outpatients by dieticians and aimed to reach nutrient requirements. Interventions included consults for counselling and advice, follow-up meetings and encouragements, and ONS. Nutritional status, nutrient intake, and quality of life improved in supported patients. Improvements were better in counselled patients compared to patients using supplements. Unsupported patients experienced worse outcomes.
CONCLUSION: Frequent consults with counselling and advice as nutritional support for undernourished patients before surgery result in improvements to nutritional status, intake, and quality of life. This statement is supported by weak evidence due to few studies and inadequate methods.
RELEVANCE TO CLINICAL PRACTISE: Nutritional support should be provided to all undernourished surgical patients during preoperative course. Nurses are in key position to provide nutritional support during outpatient preoperative evaluations. This article is protected by copyright. All rights reserved.
MINI: This meta-analysis of 16 randomized controlled trials reporting on 1387 patients has shown that preoperative immune-enhancing nutrition significantly reduces infectious complications, but not noninfectious complications, in patients undergoing surgery for gastrointestinal cancer.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 OBJECTIVE:: To define the influence of preoperative immune modulating nutrition (IMN) on postoperative outcomes in patients undergoing surgery for gastrointestinal cancer.
BACKGROUND: Although studies have shown that perioperative IMN may reduce postoperative infectious complications, many of these have included patients with benign and malignant disease, and the optimal timing of such an intervention is not clear.
METHODS: The Embase, Medline, and Cochrane databases were searched from 2000 to 2018, for prospective randomized controlled trials evaluating preoperative oral or enteral IMN in patients undergoing surgery for gastrointestinal cancer. The primary endpoint was the development of postoperative infectious complications. Secondary endpoints included postoperative noninfectious complications, length of stay, and up to 30-day mortality. The analysis was performed using RevMan v5.3 software.
RESULTS: Sixteen studies reporting on 1387 patients (715 IMN group, 672 control group) were included. Six of the included studies reported on a mixed population of patients undergoing all gastrointestinal cancer surgery. Of the remaining, 4 investigated IMN in colorectal cancer surgery, 2 in pancreatic surgery, and another 2 in patients undergoing surgery for gastric cancer. There was 1 study each on liver and esophageal cancer. The formulation of nutrition used in all studies in the treated patients was Impact (Novartis/Nestlé), which contains ω-3 fatty acids, arginine, and nucleotides. Preoperative IMN in patients undergoing surgery for gastrointestinal cancer reduced infectious complications [odds ratio (OR) 0.52, 95% confidence interval (CI) 0.38-0.71, P < 0.0001, I = 16%, n = 1387] and length of hospital stay (weighted mean difference -1.57 days, 95% CI -2.48 to -0.66, P = 0.0007, I = 34%, n = 995) when compared with control (isocaloric isonitrogeneous feed or normal diet). It, however, did not affect noninfectious complications (OR 0.98, 95% CI 0.73-1.33, P = 0.91, I = 0%, n = 1303) or mortality (OR 0.55, 95% CI 0.18-1.68, P = 0.29, I = 0%, n = 955).
CONCLUSION: Given the significant impact on infectious complications and a tendency to shorten length of stay, preoperative IMN should be encouraged in routine practice in patients undergoing surgery for gastrointestinal cancer.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.
BACKGROUND: Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy.
OBJECTIVES: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy.
SEARCH METHODS: We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index – Science, and LILACS (May 2017).
SELECTION CRITERIA: We included randomised clinical trials, irrespective of the bias control, language, or publication status.
DATA COLLECTION AND ANALYSIS: The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach.
MAIN RESULTS: We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30).
AUTHORS' CONCLUSIONS: In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.
BACKGROUND & AIMS: Patients with cirrhosis and alcoholic hepatitis are often malnourished and have a superimposed stress metabolism, which increases nutritional demands. We performed a systematic review on the effects of nutritional therapy versus no intervention for patients with cirrhosis or alcoholic hepatitis.
METHODS: We included trials on nutritional therapy designed to fulfill at least 75 % of daily nutritional demand. Authors extracted data in an independent manner. Random-effects and fixed-effect meta-analyses were performed and the results expressed as risk ratios (RR) with 95% confidence intervals (CI). Sequential analyses were performed to evaluate the risk of spurious findings due to random and systematic errors. Subgroup and sensitivity analyses were performed to evaluate the risk of bias and sources of between trial heterogeneity.
RESULTS: Thirteen randomized controlled trials with 329 allocated to enteral (9 trials) or intravenous (4 trials) nutrition and 334 controls. All trials were classed as having a high risk of bias. Random-effects meta-analysis showed that nutritional therapy reduced mortality 0.80 (95% CI, 0.64-0.99). The result was not confirmed in sequential analysis. Fixed-effect analysis suggested that nutrition prevented overt hepatic encephalopathy (0.73; 95% CI, 0.55-0.96) and infection (0.66; 95% CI, 0.45-0.98, respectively), but the results were not confirmed in random-effects analyses.
CONCLUSION: Our review suggests that nutritional therapy may have beneficial effects on clinical outcomes in cirrhosis and alcoholic hepatitis. High quality trials are needed to verify our findings. This article is protected by copyright. All rights reserved.
The impact of oral nutritional supplements (ONS) on patients with complications (disease related morbidity) requires further exploration. This systematic review included 44 randomised controlled trials (RCT) (29 RCT surgical, 15 RCT medical patients) examining the effect of ONS in community settings on the incidence of complications (n5716, mean age 67 years, range 35-87). ONS (mean intake 588kcal/day, range 125-1750; protein 22g/day, range 0-54; mean energy from protein 22%, range 0-54) were prescribed for a mean 74 days, range 5-365. Most RCT (77%) reported fewer complications in the ONS group versus control. Meta-analysis (39 RCT) showed ONS consumption reduced complications including infections, pressure ulcers, wound and fracture healing (OR 0.68, 95% CI 0.59,0.79; p<0.001). Results showed reductions when ONS were used in hospital and community settings (OR 0.72, 95% CI 0.59,0.87; p=0.001) or just in the community (OR 0.65, 95% CI 0.52, 0.80; p<0.001). Reductions in complications were only seen with high ONS adherence ≥80% (OR 0.63, 95% CI 0.48,0.83; p=0.001) and ready-to-drink ONS (OR 0.69, 95% CI 0.60,0.81; p<0.001). This systematic review and meta-analysis show community-based use of ONS in addition to the diet substantially reduces the incidence of complications. The diversity of ONS, patient populations and complication outcomes within the trials included in this review mean further research is warranted.