Zinc and other trace elements in liver cirrhosis.

Alterations in trace element concentrations may be observed in patients with chronic liver disease. Notably, selenium and zinc levels are reduced both in serum and in liver tissue of cirrhotic patients. Low selenium levels have been involved in the pathogenesis of liver damage as this element is important in controlling the levels of toxic oxygen radicals in the cells. Zinc deficiency has been involved in the pathogenesis of a number of clinical findings in chronic liver disease. These include the possible role of zinc deficiency in the pathogenesis of hepatic encephalopathy, by inducing alterations in urea metabolism. In CC14 cirrhotic rats oral zinc supplementation reduces ammonia levels and increases OCT activity in the liver. Oral zinc supplementation has been also proposed in the treatment of cirrhotic patients with chronic hepatic encephalopathy, the results however are not yet conclusive.     

Can zinc enhance response interferon therapy for patients with HCV-related liver disease?

Patients with liver disease may be at risk of zinc depletion. Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease. The standard of care for chronic HCV has improved markedly since the approval of interferon (IFN) therapy more than a decade ago. Over the past 20 years, IFN therapy has improved to more effectively eliminate the virus, progressing from single IFN therapy to combination therapy with ribavirin (RBV) and finally to pegylated IFN (PEG-IFN) therapy. However, even combined therapy with PEG-IFN and RBV for 48 wk is unable to eliminate the virus in some 40% of hepatitis C cases, particularly those with genotype 1b and high viral load. Treatment options for patients who have relapsed or are refractory to treatment with PEG-IFN and RBV therefore need to be critically assessed. This paper overviews the relationship between chronic liver disease and zinc metabolism.     

The efficacy of vitamin B12 supplementation for treating vitamin B12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review

Background and aimsMetformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B₁₂ deficiency and more severe neuropathy symptoms. There is still no guideline suggesting vitamin B₁₂ supplementation for this population. This study aimed to analyze the efficacy of vitamin B₁₂ supplementation in this population.MethodStudies reporting the efficacy of vitamin B₁₂ supplementation in metformin-treated T2DM patients were systematically searched in PubMed, Cochrane, EBSCOHost, and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Additional relevant studies were searched manually through citations. Study quality and risk of bias were assessed using suitable tools.ResultsSeven clinical trials with a total of 506 participants were included. Using the Cochrane's Risk of Bias 2 tools for clinical trials, 4 studies were assessed to have high risk of bias and 3 studies had low risk of bias. There were 5 studies that measured changes in serum vitamin B₁₂ level, all of which reported a statistically significant increase after supplementation. Significant reductions in homocysteine after supplementation were found in 2 studies. Its effect on neuropathy symptoms was still unclear, with 2 studies reporting a significant improvement and 1 study reporting no significant effect.ConclusionsThe results of this systematic review support the implementation of vitamin B₁₂ supplementation for metformin-treated T2DM to prevent or treat vitamin B₁₂ deficiency and neuropathy. More high-quality clinical studies are required to generate quantitative analysis and to encourage supplementation in available guidelines.     

Overt hepatic encephalopathy precipitated by zinc deficiency

Encephalopathy in liver disease may be unresponsive to protein restriction, lactulose, and neomycin. Zinc supplements have been reported to improve psychometric performance in liver cirrhosis, but the importance of zinc deficiency in overt hepatic encephalopathy has not yet been clearly established. A patient with severe recurrent hepatic encephalopathy was studied to determine the relation between her signs of encephalopathy and zinc deficiency. The study included a period in which zinc deficiency was artificially induced by oral histidine. An episode of overt encephalopathy occurred that was identical to earlier episodes and responded to oral zinc. The study showed an association between encephalopathy and zinc deficiency by successive zinc depletion and supplementation regimens. Long-term zinc supplementation improved severe recurrent hepatic encephalopathy and therefore the quality of life.     

Impacto da frequência posológica na adesão terapêutica em doenças cardiovasculares crónicas: revisão sistemática e meta‐análise

Introduction and ObjectiveNon‐adherence to drug treatment is a major health problem. In Europe, it has been estimated that 9% of cardiovascular events can be attributed to non‐adherence. The complexity of dosing regimens is one of the factors identified as contributing to non‐adherence. In this systematic review we aimed to assess the impact of dosing frequency on adherence to drug treatment in patients with chronic cardiovascular disease.MethodsMEDLINE and the Cochrane Library (November 2013) were searched for randomized controlled trials (RCTs) comparing different dosing regimens (once‐daily administration vs. two or more daily administrations) and assessing adherence to therapy in patients with chronic cardiovascular disease. Only trials with at least five months of follow‐up were included. The results of the studies were pooled through a random effects meta‐analysis. Relative risk (RR) and 95% confidence interval (CI) were derived. Statistical heterogeneity was calculated using the I² test.ResultsFour RCTs (a total of 2557 patients) were included. Dosing regimens with once‐daily administration were associated with a significant 56% reduction in risk of non‐adherence to drug therapy (RR: 0.44; 95% CI: 0.35‐0.54, I²=25%).ConclusionsFew clinical trials have assessed the long‐term impact of dosing frequency on medication adherence in chronic cardiovascular disease. The best available evidence suggests that taking medication once daily decreases the risk of non‐adherence to treatment by approximately 50%. The impact on clinical outcomes remains to be established.     

Prognostic value of hepatic encephalopathy for survival of patients with liver failure: A systematic review and meta-analysis

Introduction and ObjectivesThe aim of this paper was to evaluate the association of hepatic encephalopathy with survival of patients with liver failure.Materials and methodsWe retrieved the relevant articles from the PubMed, Embase and Cochrane Library, up to May 2017. The pooled odds ratio (OR) as well as their 95% confidence intervals (CI) was calculated by the software of R package version 3.12.ResultsTotal 13 studies with 2071 liver failure patients were included and reanalyzed in this meta-analysis. The results proved the prognostic value of hepatic encephalopathy for survival of patients with liver failure (OR = 5.62, 95%CI = 6.30–9.82, P < 0.001). The subgroup analyses showed that the type of liver failure and the follow up duration may be the factor influencing the association between hepatic encephalopathy and survival of patients with liver failure.ConclusionsThe results proved that hepatic encephalopathy was a prognostic factor of survival in patients with liver failure.     

Impact of chronic kidney disease on the prognosis of transcatheter aortic valve replacement in patients with aortic stenosis: A protocol for systematic review and meta-analysis

Background:The prognosis of patients with aortic stenosis, in conjunction with chronic kidney disease (CKD), after transcatheter aortic valve replacement (TAVR) remains unclear. This study assessed the impact of CKD, and different stages of CKD, on prognosis of patients undergoing TAVR.Methods:The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. As of June 2021, we performed a comprehensive literature search on studies related to CKD and TAVR, using databases such as PubMed, Embase, Cochrane Library, and Web of Science. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Then, Stata 15.0 software was used for meta-analysis.Results and Conclusion:The purpose of this study was to evaluate the effect of CKD and different stages of CKD on the prognosis of patients with TAVR. It is hoped to provide a comprehensive reference for clinical practice and related clinical trials in the future.     

Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure

BackgroundAcute-on-chronic liver failure (ACLF) is characterised by acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 weeks by ascites and/or encephalopathy in patients with previously diagnosed or undiagnosed chronic liver disease. We studied the clinical, biochemical and etiological profiles of ACLF patients investigating variables which could predict mortality.MethodsConsecutive ACLF patients were enrolled and given standard intensive care management. They were monitored for predictors of 90-day mortality.Results91 patients were included; besides jaundice (median bilirubin 23.1 mg/dL) and coagulopathy, acute onset ascites with or without encephalopathy was the presenting symptom in 92%. In all patients a first diagnosis of chronic liver disease was made, mainly due to hepatitis B (37%) or alcohol (34%). Reactivation of chronic hepatitis B and alcoholic hepatitis were the common acute insults. The 90-day mortality was 63%. On multivariate analysis, hepatic encephalopathy, low serum sodium, and high INR were found to be independent baseline predictors of mortality. Amongst all severity scores studied, MELD, SOFA and APACHE-II scores had AUROCs of >0.8 which was significantly higher than that of Child–Turcotte–Pugh.ConclusionsACLF has very high mortality. Hepatic encephalopathy, low serum sodium and high INR predict poor outcome. Mortality can also be predicted by baseline MELD, SOFA or APACHE-II scores.     

l-Ornithine-l-aspartate in the management of hepatic encephalopathy: A meta-analysis

Background and Aim:  Hepatic encephalopathy continues to be a major clinical problem and the current decade has not witnessed major therapeutic breakthroughs in this area. l -ornithine- l -aspartate (LOLA) is not frequently used as there are still some reservations about its benefits. The present study aimed to assess the effectiveness and safety of LOLA in the management of hepatic encephalopathy.
Methods:  We used the method recommended by the Cochrane Collaboration to perform a meta-analysis of randomized controlled trials of LOLA therapy for hepatic encephalopathy including three randomized controlled trials.
Results:  Three randomized trials randomizing 212 patients were included. LOLA versus placebo had a significant effect on improvement of hepatic encephalopathy (relative risk 1.89; 95% CI 1.32 to 2.71; P  = 0.0005). This comparison showed no statistical heterogeneity ( P  = 0.85 and χ² = 0.09). Subgroup analysis showed that LOLA could be effective versus placebo in trials with grade I or II overt hepatic encephalopathy patients (relative risk 1.87; 95% CI 1.30 to 2.68; P  = 0.0007) and had no significant effect in trials with subclinical hepatic encephalopathy patients (relative risk 1.69; 95% CI 0.72 to 3.94; P  = 0.23). Adverse effects were observed in only three patients treated with LOLA in one report.
Conclusions:  LOLA benefited patients with overt hepatic encephalopathy (I or II), whereas these data do not support the use of LOLA for patients with subclinical hepatic encephalopathy.     

Portal vein thrombosis,mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis

AIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations (variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis.METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI.RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality (OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites (OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy.CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed.     

Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy

Aim: The objective of this systematic review and meta‐analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy. Methods: Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation Index and Embase, abstract proceedings, reference lists and ongoing trial registers until 13 October 2010. We included randomized controlled trials comparing probiotics and synbiotics with no intervention, placebo or lactulose in patients with hepatic encephalopathy. The primary outcome measure was improvement in hepatic encephalopathy. Results were expressed as risk rates (RR) with confidence intervals (CI) and intertrial heterogeneity as I². Results: Seven trials with a total of 393 patients were analyzed. Compared to placebo or lactulose, treatment with probiotics or synbiotics significantly improved hepatic encephalopathy (RR = 1.40, 95% CI = 1.05–1.86, I² = 5%). Probiotics decreased arterial ammonia (weighted mean difference 15.95; 95% CI = 26.72–3.28; I² = 68%), but not venous ammonia (weighted mean difference 5.23; 95% CI = 21.77–11.30; I² = 89%). Treatment with probiotics or synbiotics did not significantly affect the psychometric tests. Overall adverse events were reported in four trials with no difference between probiotics and placebo groups (RR = 0.32, 95% CI = 0.04–2.57; I² = 59%). Regression analysis showed evidence of small‐study effects. Conclusion: The present meta‐analysis suggests that probiotics may be an effective treatment of hepatic encephalopathy, though rigorous evaluation in standardized, randomized, clinical trial with clinically relevant outcomes is still needed.     

Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy

The effect of short-term oral zinc supplementation (zinc sulfate 600 mg/day) on hepatic encephalopathy, was assessed in a double-blind, crossover trial. Fifteen cirrhotic patients with stable, chronic hepatic encephalopathy were randomized to receive either oral zinc or a placebo for 10 days. Following a two-week washout period, these were crossed over to the alternate treatment. Conn's index, which comprises the evaluation of the mental state, asterixis, number connection test, EEG record, and plasma ammonia, was used to score the degree of hepatic encephalopathy, both at the beginning and end of each treatment period. Serum zinc was significantly raised after oral zinc administration and reached the levels observed in cirrhotics without hepatic encephalopathy. Despite this, however, no modification in the parameters included in Conn's index were observed. In conclusion, this study failed to confirm that short-term oral zinc supplementation improves chronic hepatic encephalopathy.     

National trends and inpatient outcomes of inflammatory bowel disease patients with concomitant chronic liver disease

Abstract

Background. There is little information on the frequency of chronic liver disease among hospitalized patients with inflammatory bowel disease (IBD). In this study, we seek to define the common etiologies contributing to chronic liver disease among IBD patients and to identify potential risk factors predictive of increased mortality in this population. Methods. We analyzed the Nationwide Inpatient Sample from 1988 to 2006 to determine the frequency of chronic liver disease among patients with IBD and to determine their in-hospital outcomes. Results. From 1988 to 2006, the age-adjusted rate of chronic liver disease among hospitalized patients with IBD has increased from 4.35 per 100,000 persons in 1988–2001 to 7.45 per 100,000 persons in 2004–2006. The most common etiologies contributing to chronic liver disease among IBD patients were: primary sclerosing cholangitis, unspecified chronic hepatitis, chronic hepatitis C, and nonalcoholic fatty liver disease. Compared to IBD patients without liver disease, there was more than a twofold higher rate of inpatient morality among IBD patients with concomitant liver disease (2.7% vs. 1.3%, p < 0.01). The multivariate analysis showed that factors predictive of inpatient mortality include age >50, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy, presence of cirrhosis, malnutrition, Clostridium difficile colitis, and hospital-acquired pneumonia. Conclusion. There is a higher rate of inpatient mortality among patients with concomitant IBD and chronic liver disease compared to IBD alone. Early recognition and management of complications related to portal hypertension among patients with IBD and chronic liver disease is particularly important in order to reduce inpatient mortality and morbidity.     

Vitamin D as a therapy for colitis: A systematic review

Background and aimThe effect of vitamin D supplementation on immune disorders has been a topical research focus. The aim of this systematic review was to examine the current evidence of the effect of vitamin D supplementation as a therapy for colitis.MethodsThe following databases were searched: MEDLINE, Pubmed, Scopus, Web of Knowledge, Cinicaltrials.gov and the Cochrane Central Register of Controlled Trials using the terms ‘inflammatory bowel disease’ ‘Crohn's disease’ ‘ulcerative colitis’ ‘colitis’ [and] ‘vitamin D’. Both human and animal studies published in English language were examined. The reference lists of included studies and review articles were manually searched for any relevant studies.ResultsFour studies were included in this systematic review. All reported an improvement in disease activity with vitamin D supplementation. The only high quality human study reported a non-significant reduction of relapse rate for Crohn's disease. No major adverse effects of vitamin D supplementation were reported.ConclusionsAlthough there is some evidence that supplemental vitamin D, as an adjunctive treatment, may help in controlling colitis, this evidence is not enough to justify using vitamin D in treating inflammatory bowel disease (IBD). Large high quality placebo-controlled randomised controlled trials are needed to explore a possible benefit of using vitamin D in treating IBD.     

Increased Turnover of Gc-Globulin in Patients with Hepatic Encephalopathy

Background: A low serum level (_&lt;100 mg/L) of the actin-scavenger Gc-globulin is a prognostic marker of non-survival in fulminant hepatic failure (FHF). It is unknown whether decreased production or increased consumption (or both) is responsible for the low Gc-globulin levels. Methods: Ten patients with FHF and four patients with acute or chronic liver disease (AOCLD) with hepatic encephalopathy (HE) grades II-IV were included. Eight patients with cirrhosis (chronic liver disease, CLD) without HE served as controls. Total, free, and actin-bound Gc-globulin were measured in samples from an artery, a central vein, and a hepatic vein. In 12 patients (9 FHF, 3 AOCLD), concentrations were measured before and after high volume plasmapheresis (HVP). Results     

The effectiveness of iron supplementation for postpartum depression: A protocol for systematic review and meta-analysis

Background:Postpartum depression (PPD) is one of the most common postpartum psychiatric disorders. The prevalence of PPD ranges from approximately 10% to 30%. In recent years, iron supplementation has emerged as potential means to treat PPD, and an increasing number of studies have been published to support the effectiveness of iron supplementation for PPD. we will conduct a comprehensive systematic review and meta-analysis to evaluate the evidence of randomized controlled trials for iron supplementation treatment of PPD.Methods:PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Science, and Technology Journal Database, and Chinese Biomedical Literature Database will be searched from their inception of databases to December 31, 2020. Two reviewers will select articles, extract data and assess the risk of bias independently. Any disagreement will be resolved by discussion with the third reviewer. Review Manager 5.3 software will be used for data synthesis. The Cochrane risk of bias assessment tool will be used to assess the risk of bias.Results:This study will conduct a comprehensive literature search and provide a systematic synthesis of current published data to explore the effectiveness of iron supplementation for PPD.Conclusions:This systematic review and meta-analysis will provide clinical evidence for the effectiveness of iron supplementation for PPD, inform our understanding of the value of iron supplementation in improving PPD symptoms, and help clinicians to make better decisions regarding the appropriate role of iron supplementation as a part of prevention and treatment routines.Study registration number:INPLASY2020110007     

Efficacy of erythropoietin alone in treatment of neonates with hypoxic-ischemic encephalopathy: A protocol for systematic review and meta-analysis

Background:Multiple clinical trials have demonstrated the safety and efficacy of erythropoietin in improving neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy (HIE). It is undoubtedly urgent to include only randomized controlled trials (RCTs) for more standardized systematic reviews and meta-analyses. The purpose of this study is to examine whether erythropoietin reduces the risk of death and improve neurodevelopmental disorders in infants with HIE.Methods:The electronic databases of Cochrane Library, EMBASE, PubMed, and Web of Science were searched from the inception to June 2021 using the following key terms: “erythropoietin,” “hypoxic-ischemic encephalopathy,” and “prospective,” for all relevant RCTs. Only English publications were included. The primary outcome was mortality rate. Secondary outcomes included neurodevelopmental disorders, brain injury, and cognitive impairment. The Cochrane risk of bias tool was independently used to evaluate the risk of bias of included RCTs by 2 reviewers.Results:We hypothesized that group with erythropoietin would provide better therapeutic benefits compared with control group.OSF registration number:10.17605/OSF.IO/FERUS.     

Metabolic syndrome and hepatic resection: improving outcome

ObjectiveA review of the peri-operative risk associated with hepatic resection in patients with metabolic syndrome (MetS) and identification of measures for the improvement of cardiometabolic disturbances and liver-related mortality.BackgroundMetS and its hepatic manifestation non-alcoholic fatty liver disease (NAFLD) are associated with an increased operative mortality in spite of a significant improvement in peri-operative outcome after hepatic resection.MethodsA review of the English literature on MetS, liver resection and steatosis was performed from 1980 to 2011 using the MEDLINE and PubMed databases.ResultsMetS is a predictor of NAFLD and patients with multiple metabolic risk factors may harbour non-alcoholic steatohepatitis (NASH) predictive of operative and cardiovascular mortality. Pre-operative diagnosis of unsuspected NASH with the selective use of a liver biopsy can modify the operative strategy by limiting the extent of hepatic resection, avoiding or altering the pre-operative chemotherapy regimen and the utilization of portal vein embolization. Thiazolidinediones are therapeutic for MetS and NASH and Vitamin E for active NASH; however, their utility in improving the peri-operative outcome after hepatic resection is unknown. A short-term regimen for weight loss improves post-operative patient and liver-related outcomes in patients with >30% steatosis. Cardiovascular disease associated with MetS or NAFLD should be managed aggressively. Peri-operative measures to minimize thrombotic events and acute renal injury secondary to the pro-inflammatory, prothrombotic state of MetS may further improve the outcome.ConclusionPotential candidates for hepatic resection should be screened for MetS as the pre-operative identification of NASH, short-term treatment of significant steatosis, cardiovascular risk assessment and optimization of each component of MetS may improve the peri-operative outcome in this high-risk subset of patients.     

Effects of coenzyme Q10 on vascular endothelial function in humans: a meta-analysis of randomized controlled trials

ObjectiveThe purpose of this study was to quantify the effect of coenzyme Q10 on arterial endothelial function in patients with and without established cardiovascular disease.BackgroundEndothelial dysfunction has been implicated in the pathogenesis of atherosclerosis.Methods and resultsThe search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 July 2011. Eligible studies were randomized controlled trials on the effects of coenzyme Q10 compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Five eligible trials enrolled a total of 194 patients. Meta-analysis using random-effects model showed treatment with coenzyme Q10 significantly improvement in endothelial function assessed peripherally by flow-mediated dilatation (SMD 1.70, 95% CI: 1.00–2.4, p < 0.0001). However, the endothelial function assessed peripherally by nitrate-mediated arterial dilatation was not significantly improved by using fix-effects model (SMD ?0.19, 95% CI: ?1.75 to 1.38, p = 0.81).ConclusionCoenzyme Q10 supplementation is associated with significant improvement in endothelial function. The current study supports a role for CoQ10 supplementation in patients with endothelial dysfunction.