Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease:A meta-analysis

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,some studies have contested the prognostic value of NLR in ESLD.AIM To investigate the ability of NLR to predict ESLD.METHODS Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD.Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1.RESULTS A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the evaluation.Among the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced effect.CONCLUSION Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian patients.NLR is a useful prognostic biomarker in patients with ESLD.

Frailty in end-stage liver disease:Understanding pathophysiology,tools for assessment,and strategies for management

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease.Frailty is a complex condition that arises from deteriorations across various physiological systems,including the musculoskeletal,cardiovascular,and immune systems,resulting in a reduced ability of the body to withstand stressors.This condition is associated with declined resilience and increased vulnerability to negative outcomes,including disability,hospitalization,and mortality.In cirrhotic patients,frailty is influenced by multiple factors,such as hyperammonemia,hormonal imbalance,malnutrition,ascites,hepatic encephalopathy,and alcohol intake.Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients.It can aid in making critical decisions regarding patients’eligibility for critical care and transplantation.This,in turn,can guide the development of an individualized treatment plan for each patient with cirrhosis,with a focus on prioritizing exercise,proper nutrition,and appropriate treatment of hepatic complications as the primary lines of treatment.In this review,we aim to explore the topic of frailty in liver diseases,with a particular emphasis on pathophysiology,clinical assessment,and discuss strategies for preventing frailty through effective treatment of hepatic complications.Furthermore,we explore novel assessment and management strategies that have emerged in recent years,including the use of wearable technology and telemedicine.

Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus

BACKGROUND Human immunodeficiency virus(HIV)-positive patients coinfected with hepatitis B virus(HBV)are eligible for liver transplantation(LT)in Africa and Southeast Asia,particularly China.However,the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT(ABOi-LT)is unknown.AIM To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with endstage liver disease(ESLD).METHODS We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT.The pretransplantation HIV viral load was undetectable,with no active opportunistic infections.Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses,followed by an intraoperative regimen of intravenous immunoglobulin,methylprednisolone,and basiliximab.Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil,and prednisone.RESULTS At the intermediate-term follow-up,patients showed undetectable HIV viral load,CD4(+)T cell counts greater than 150 cells/μL,no HBV recurrence,and stable liver function.A liver allograft biopsy showed no evidence of acute cellular rejection.Both patients survived at 36-42 mo of follow-up.CONCLUSION This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes,suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.

Modified model for end-stage liver disease improves shortterm prognosis of hepatitis B virus-related acute-on-chronic liver failure

AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.

Comparative study of indocyanine green-R15,Child-Pugh score,and model for end-stage liver disease score for prediction of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt

BACKGROUND Hepatic encephalopathy(HE)remains an enormous challenge in patients who undergo transjugular intrahepatic portosystemic shunt(TIPS)implantation.The preoperative indocyanine green retention rate at 15 min(ICG-R15),as one of the liver function assessment tools,has been developed as a prognostic indicator in patients undergoing surgery,but there are limited data on its role in TIPS.AIM To determine whether the ICG-R15 can be used for prediction of post-TIPS HE in decompensated cirrhosis patients with portal hypertension(PHT)and compare the clinical value of ICG-R15,Child-Pugh score(CPS),and model for end-stage liver disease(MELD)score in predicting post-TIPS HE with PHT.METHODS This retrospective study included 195 patients with PHT who underwent elective TIPS at Beijing Shijitan Hospital from January 2018 to June 2019.All patients underwent the ICG-R15 test,CPS evaluation,and MELD scoring 1 wk before TIPS.According to whether they developed HE or not,the patients were divided into two groups:HE group and non-HE group.The prediction of one-year post-TIPS HE by ICG-R15,CPS and MELD score was evaluated by the areas under the receiver operating characteristic curves(AUCs).RESULTS A total of 195 patients with portal hypertension were included and 23%(45/195)of the patients developed post-TIPS HE.The ICG-R15 was identified as an independent predictor of post-TIPS HE.The AUCs for the ICG-R15,CPS,and MELD score for predicting post-TIPS HE were 0.664(95%confidence interval[CI]:0.557-0.743,P=0.0046),0.596(95%CI:0.508-0.679,P=0.087),and 0.641(95%CI:0.554-0.721,P=0.021),respectively.The non-parametric approach(Delong-Delong&Clarke-Pearson)showed that there was statistical significance in pairwise comparison between AUCs of ICG-R15 and MELD score(P=0.0229).CONCLUSION The ICG-R15 has appreciated clinical value for predicting the occurrence of post-TIPS HE and is a choice for evaluating the prognosis of patients undergoing TIPS.

Safety and efficacy of dual antiplatelet therapy after percutaneous coronary interventions in patients with end-stage liver disease

The prevalence of coronary artery disease(CAD)increases in patients with endstage liver disease,with part of them receiving the percutaneous coronary intervention(PCI)as a treatment option.Dual antiplatelet therapy(DAPT),a standard of care after PCI,could result in catastrophic consequences in this population.Before PCI and the start of DAPT,it is recommended to assess patient bleeding risk.Based on novel findings,liver cirrhosis does not necessarily lead to a significant increase in bleeding complications.Furthermore,conventional methods,such as the international normalized ratio,might not be appropriate in assessing individual bleeding risk.The highest bleeding risk among cirrhotic patients has a subgroup with severe thrombocytopenia(<50×10^(9)/L)and elevated portal pressure.Therefore,every effort should be made to maintain thrombocyte count above>50×10^(9)/L and prevent variceal bleeding.There is no solid evidence for DAPT in patients with cirrhosis.However,randomized trials investigating short(one month)DAPT duration after PCI with new drug-eluting stents(DES)in a high bleeding risk patient population can be implemented in patients with cirrhosis.Based on retrospective studies(with older stents and protocols),PCI and DAPT appear to be safe but with a higher risk of bleeding complications with longer DAPT usage.Finally,novel methods in assessing CAD severity should be performed to avoid unnecessary PCI and potential risks associated with DAPT.When indicated,PCI should be performed over radial artery using contemporary DES.Complementary medical therapy,such as proton pump inhibitors and beta-blockers,should be prescribed for lower bleeding risk patients.Novel approaches,such as thromboelastography and“preventive”upper endoscopies in PCI circumstances,warn clinical confirmation.

Individual immunosuppressive protocol after liver transplantation in benign end-stage liver disease:a single-center experience of 645 cases

Objective To analyze individual immunosuppressive protocol ( IP) after liver transplantation ( LT) in benign end - stage liver disease. Methods The clinical data of 645 patients with benign end - stage liver disease undergoing LT in our institute from April 2002 to Aug 2010 were analyzed retrospectively. 146 cases from Apr.

Modified upper abdominal cluster transplantation in patients with end-stage liver diseases associated with insulin dependent type 2 diabetes mellitus

Objective Modified upper abdominal cluster transplantation ( MCT) ,which was inspired by classical cluster transplant technique,has been proven more effective and feasible in the treatment of patients with end stage liver diseases associated with insulin - dependent

Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis

BACKGROUND:The indocyanine green(ICG)clearance test(clearance rate(K)and retention rate at 15 minutes (R15))is a sensitive indicator to evaluate liver function. The model for end-stage liver disease(MELD)score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity.In this study,we investigated the correlation between the ICG clearance test and MELD score of patients with liver cirrhosis. METHODS:From June 2007 to March 2008,52 patients with liver cirrhosis admitted to our center were classified into Child-Pugh class A(8 patients),B(14)and C(30).The ICG clearance test(K value and R15)was performed by ICG pulse spectrophotometry(DDG-3300K),and the MELD scores of patients were calculated. RESULTS:As the Child-Pugh classification of liver function gradually deteriorated,the K value decreased, while R15 and MELD score increased.There were significant statistical differences in K value,R15 and MELD score in patients with different Child-Pugh classifications. Significant correlations were found between the parameters of the ICG clearance test(K value and R15)and MELD score.A negative correlation was observed between K value and MELD score(r=-0.892,P<0.05),while a positive correlation was observed between R15 and MELD score(r=0.804,P<0.05).CONCLUSIONS:The ICG clearance test and MELD score are good parameters for evaluating liver function.Moreover, K value and R15 have significant correlations with MELD score,especially the K value,which may be a convenient and appropriate indicator to evaluate liver function of patients with liver cirrhosis.

End-stage liver disease score and future liver remnant volume predict post-hepatectomy liver failure in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is the world’s sixth most common malignant tumor and the third cause of cancer death.Although great progress has been made in hepatectomy,it is still associated with a certain degree of risk of posthepatectomy liver failure(PHLF),which extends the length of hospital stay and remains the leading cause of postoperative death.Studies have shown that assessment of hepatic functional reserve before hepatectomy is beneficial for reducing the incidence of PHLF.AIM To assess the value of model for end-stage liver disease(MELD)score combined with standardized future liver remnant(sFLR)volume in predicting PHLF in patients undergoing hepatectomy for HCC.METHODS This study was attended by 238 patients with HCC who underwent hepatectomy between January 2015 and January 2018.Discrimination of sFLR volume,MELD score,and sFLR/MELD ratio to predict PHLF was evaluated according to the area under the receiver operating characteristic curve.RESULTS The patients were divided into two groups according to whether PHLF occurred after hepatectomy.The incidence of PHLF was 8.4%in our research.The incidence of PHLF increased with the decrease in sFLR volume and the increase in MELD score.Both sFLR volume and MELD score were considered independent predictive factors for PHLF.Moreover,the cut-off value of the sFLR/MELD score to predict PHLF was 0.078(P<0.001).This suggests that an sFLR/MELD≥0.078 indicates a higher incidence of PHLF than an sFLR/MELD<0.078.CONCLUSION MELD combined with sFLR is a reliable and effective PHLF predictor,which is superior to MELD score or sFLR volume alone.

Relationship between model for end-stage liver disease score and left ventricular function in patients with end-stage liver disease

BACKGROUND:Decreased cardiac contractility has been observed in cirrhosis,suggesting a latent cardiomyopathy in these patients.This study was designed to evaluate left ventricular structure and function in patients with end-stage liver disease by the model for end-stage liver disease(MELD) scoring system. METHODS:We recruited 82 patients(72 male,10 female; mean age 50.3±8.9 years)with end-stage liver disease who underwent orthotopic liver transplantation between January 2002 and May 2008.Seventy-eight patients had cirrhosis and 4 had primary liver cancer.Patients were categorized into three groups on the basis of MELD score:≤9(27 patients, 33%);10-19(40,49%);and≥20(15,18%).The relationship between MELD score and cardiac structure and function was determined.Preoperative assessments of blood biochemistry, blood coagulation,serum virology,echocardiography and electrocardiography were performed. RESULTS:MELD score was positively correlated with enlarged left atrial diameter,increased interventricular septum thickness(IVST),increased aortic flow,corrected QT interval (QTc)extension and cardiac output(P=0.033,0.002,0.000, 0.000 and 0.009,respectively).International normalized ratio also had a correlation with the above parameters and enlarged left ventricular end-diastolic diameter(P=0.043,0.010,0.000, 0.001,0.016 and 0.008,respectively).Serum creatinine was positively correlated with IVST(r=0.257,P=0.020),but negatively correlated with early maximal ventricular filling velocity/late diastolic or atrial velocity ratio(r=-0.300, P=0.006).A difference of QTc>440 ms among the three groups was statistically significant(χ2=9.791,P=0.007).CONCLUSIONS:Abnormalities in cardiac structure and function are common in patients with end-stage liver disease. MELD score is a practically useful approach for the assessment of cardiac function in such patients.

Survival outcomes of right-lobe living donor liver transplantation for patients with high Model for End-stage Liver Disease scores

BACKGROUND: Controversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a high MELD score would result in inferior outcomes of right-lobe LDLT. METHODS: Among 411 consecutive patients who received right-lobe LDLT at our center, 143 were included in this study. The patients were divided into two groups according to their MELD scores: a high-score group (MELD score ≥25; n=75) and a low-score group (MELD score <25; n=68). Their demographic data and perioperative conditions were compared. Univariable and multivariable analyses were performed to identify risk factors affecting patient survival. RESULTS: In the high-score group, more patients required preoperative intensive care unit admission (49.3% vs 2.9%; P<0.001), mechanical ventilation (21.3% vs 0%; P<0.001), or hemodialysis (13.3% vs 0%; P=0.005); the waiting time before LDLT was shorter (4 vs 66 days; P<0.001); more blood was transfused during operation (7 vs 2 units; P<0.001); patients stayed longer in the intensive care unit (6 vs 3 days; P<0.001) and hospital (21 vs 15 days; P=0.015) after transplantation;more patients developed early postoperative complications (69.3% vs 50.0%; P=0.018); and values of postoperative peak blood parameters were higher. However, the two groups had comparable hospital mortality. Graft survival and patient overall survival at one year (94.7% vs 95.6%; 95.9% vs 96.9%), three years (91.9% vs 92.6%; 93.2% vs 95.3%), and five years (90.2% vs 90.2%; 93.2% vs 95.3%) were also similar between the groups. CONCLUSIONS: Although the high-score group had signifi-cantly more early postoperative complications, the two groups had comparable hospital mortality and similar satisfactory rates of graft survival and patient overall survival. Therefore, a high MELD score should not be a contraindication to right-lobe LDLT if donor risk and recipient benefit are taken into full account.

Outcomes of liver transplantation for end-stage biliary disease: A comparative study with end-stage liver disease

AIM: To evaluate the outcomes of patients with endstage biliary disease(ESBD) who underwent liver transplantation, to define the concept of ESBD, the criteria for patient selection and the optimal operation for decision-making.METHODS: Between June 2002 and June 2014, 43 patients with ESBD from two Chinese organ transplantation centres were evaluated for liver transplantation. The causes of liver disease were primary biliary cirrhosis(n = 8), cholelithiasis(n = 8), congenital biliary atresia(n = 2), graft-related cholangiopathy(n = 18), Caroli's disease(n = 2), iatrogenic bile duct injury(n = 2), primary sclerosing cholangitis(n = 1), intrahepatic bile duct paucity(n = 1) and Alagille's syndrome(n = 1). The patients with ESBD were compared with an end-stage liver disease(ESLD) case control group during the same period, and the potential prognostic values of multiple demographic and clinical variables were assessed. The examined variables included recipient age, sex, pre-transplant clinical status, pre-transplant laboratory values, operation condition and postoperative complications, as well as patient and allograft survival rates. Survival analysis was performed using Kaplan-Meier curves, and the rates were compared using log-rank tests. All variables identified by univariate analysis with P values < 0.100 were subjected to multivariate analysis. A Cox proportional hazard regression model was used to determine the effect of the study variables on outcomes in the study group.RESULTS: Patients in the ESBD group had lower model for end-stage liver disease(MELD)/paediatric end-stage liver disease(PELD) scores and a higher frequency of previous abdominal surgery compared to patients in the ESLD group(19.2 ± 6.6 vs 22.0 ± 6.5, P = 0.023 and 1.8 ± 1.3 vs 0.1 ± 0.2, P = 0.000). Moreover, theoperation time and the time spent in intensive care were significantly higher in the ESBD group than in the ESLD group(527.4 ± 98.8 vs 443.0 ± 101.0, P = 0.000, and 12.74 ± 6.6 vs 10.0 ± 7.5, P = 0.000). The patient survival rate in the ESBD group was not significantly different from that of the ESBD group at 1, 3 and 5 years(ESBD: 90.7%, 88.4%, 79.4% vs ESLD: 84.9%, 80.92%, 79.0%, χ2 = 0.194, P = 0.660). The graftsurvival rates were also similar between the two groups at 1, 3 and 5 years(ESBD: 90.7%, 85.2%, 72.7% vs ESLD: 84.9%, 81.0%, 77.5%, χ2 = 0.003, P = 0.958). Univariate analysis identified MELD/PELD score(HR = 1.213, 95%CI: 1.081-1.362, P = 0.001) and bleeding volume(HR = 0.103, 95%CI: 0.020-0.538, P = 0.007) as significant factors affecting the outcomes of patients in the ESBD group. However, multivariate analysis revealed that MELD/PELD score(HR = 1.132, 95%CI: 1.005-1.275, P = 0.041) was the only negative factor that was associated with short survival time.CONCLUSION: MELD/PELD criteria do not adequately measure the clinical characteristics and staging of ESBD. The allocation system based on MELD/PELD criteria should be re-evaluated for patients with ESBD.

Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease

AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.

Stem cell transplantation for the treatment of end-stage liver disease

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer,liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety,mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.

Compromised nutritional status in patients with end-stage liver disease:Role of gut microbiota

Background: Patients with end-stage liver disease(ESLD) have a compromised nutritional status because of the liver crucial role in regulating metabolic homeostasis and energy balance.Data sources: A systematic review of literature based on extensive relevant articles published from 2001 to 2017 in English in Pub Med database was performed by searching keywords such as liver disease, nonalcoholic liver disease, alcoholic liver disease, malnutrition, epigenetics, gut microbiota, and probiotics.Results: Liver transplantation would be one eligible therapy for ESLD patients, even if, the clinical outcome is negatively influenced by malnutrition and/or infections. The malnutrition is a condition of nutrient imbalance with a high incidence in ESLD patients. An accurate evaluation of nutritional status could be fundamental for reducing complications and prolonging the survival of ESLD patients including those undergoing liver transplantation. In addition, the interaction among nutrients, diet and genes via epigenetics has emerged as a potential target to reduce the morbidity and mortality in ESLD patients. The malnutrition induces changes in gut microbiota causing dysbiosis with a probable translocation of bacteria and/or pathogen-derived factors from the intestine to the liver. Gut microbiota contribute to the progression of chronic liver diseases as well as hepatocellular carcinoma. The administration of probiotics modulating gut microbiota could improve all chronic liver diseases.Conclusions: This review provides an update on malnutrition status linked to epigenetics and the potential benefit of some probiotics on the management of ESLD patients. In support of this view and to reveal the constant and growing interest in this field, some clinical trials are reported.

Markers of bacterial translocation in end-stage liver disease

Bacterial translocation(BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence.BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT.

Bone marrow derived stem cells for the treatment of end-stage liver disease

End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell(BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups.

Beyond the Pediatric end-stage liver disease system: Solutions for infants with biliary atresia requiring liver transplant

Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.

Clinical Outcome of Autologous Hematopoietic Stem Cell Infusion via Hepatic Artery or Portal Vein in Patients with End-stage Liver Diseases

Objective To investigate the efficacy of hematopoietic stem cell(HSC) transplantation via the hepatic artery vs.the portal vein for end-stage liver disease(ESLD).Methods Patients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein.Liver function was examined at 3,6,and 12 months after transplantation.Liver biopsy results were analyzed using the Knodell score.Results Eighty patients(58 males and 22 females) were enrolled in the study.The Child-Pugh score was grade B in 69 cases,and grade C in the remaining 11 cases.HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients.ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation(P<0.05 compared with pre-transplantation levels).Total bilirubin levels decreased significantly in both groups at 3,6,and 12 months after HSC transplantation(P<0.05 compared with pre-transplantation levels).Additionally,prothrombin time decreased in both groups at 12 months after HSC transplantation(P<0.05 compared with pre-transplantation level).There were no significant differences in ALT,total bilirubin and prothrombin time between the two groups either before or after transplantation.Moreover,Knodell score decreased significantly at 6 and 12 months.Histological examination showed that liver cell edema,degeneration,necrosis,and inflammation were significantly relieved at 3,6,and 12 months after transplantation.The incidence of portal vein thrombosis,upper gastrointestinal bleeding,and hepatic encephalopathy were 1.25%,3.75%,and 2.5% respectively.The one-year survival rate was 100%.Conclusions Autologous HSC transplantation improves liver function and histology in ESLD patients.The administration route of HSC has no significant impact on the efficacy of transplantation.