BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatm...BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatments.NLR has emer-ged as an indicator of systemic inflammation and physiological stress.NPR has emerged as a potential indicator of inflammation and thrombotic risk in the context of surgical and radiological procedures.AIM To analyze the correlation of NLR and NPR with the development of post-liver transplantation(LT)early complications after stratification for hepatocellular carcinoma diagnosis.METHODS Consecutive patients undergone LT between January 2019 and December 2023 were enrolled.Data regarding the concentration of hemoglobin and the differ-ential leukocyte count on postoperative days(POD)0,1,3,and 5 were collected.RESULTS The dataset included 161 consecutive patients undergone LT.Clavien-Dindo IV-V complications had a good correlation with NLR POD 1(P=0.05),NLR POD 3(P<0.001),NLR POD 7(P<0.001),NPR POD 3(P<0.001).In addition,the NPR ratio on POD 3 correlated with the onset of 30-day hemorrhage(P=0.009).Finally,30-day mortality had a significant association with the NLR POD 1(P=0.03)and with NLR POD 7(P=0.004),while NPR had a significant correlation with 30-day mortality in NPR POD 7(P=0.004).CONCLUSION The analysis of NLR and NPR are strictly correlated with Clavien-Dindo IV-V complications and 30-day post-LT death.展开更多
This manuscript is based on a recent study by Pillay et al that was published in recently.Liver abscesses can be caused by rare potentially life-threatening infections of either bacterial or parasitic origin.The incid...This manuscript is based on a recent study by Pillay et al that was published in recently.Liver abscesses can be caused by rare potentially life-threatening infections of either bacterial or parasitic origin.The incidence rate in Europe is lower than in developing countries,but it is a major complication with high morbidity,particularly in immunocompromised patients.They are most frequently caused by Enterobacterales infections,but hypervirulent Klebsiella strains are an emerging problem in Western countries.Amoebiasis has been a public health problem in Europe,primarily imported from other endemic foci.At the same time,this infection is becoming an emerging disease,as the number of infected patients who have not traveled to endemic areas is rising.Treatment options for hydatid liver cyst include chemotherapy,open or laparoscopic surgery,percutaneous treatment(percutaneous aspiration,re-aspiration and injection and its modification)and“wait and watch”strategy.Most hydatid liver cyst patients in Pillay et al’s study received surgical treatment,but several studies have confirmed the safety and efficacy of percutaneous aspiration,re-aspiration and injection.展开更多
BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHOD...BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.展开更多
Targeting the gut-liver axis has emerged as a promising strategy in the treatment of metabolic dysfunction-associated steatotic liver disease(MASLD),a condition that currently represents the most common cause of chron...Targeting the gut-liver axis has emerged as a promising strategy in the treatment of metabolic dysfunction-associated steatotic liver disease(MASLD),a condition that currently represents the most common cause of chronic liver disease worldwide.Within this axis,the duodenum serves not only as a site of nutrient absorption but also as a metabolic sensor capable of influencing systemic and hepatic homeostasis.We have read with great interest the recent study by Yu et al,investigating the effects of duodenal mucosal ablation(DMA)by irreversible electroporation in a rat model of MASLD.The authors reported remarkable reductions in hepatic lipid content,improvements in serum lipid profiles,and both structural and functional changes in the intestinal mucosa,including alterations in enteroendocrine signaling.These results corroborate the pivotal role of the gut-liver axis in the pathogenesis of MASLD and highlight the potential of minimally invasive approaches targeting the proximal intestine.In this letter,we discuss the broader implications of these findings,emphasizing the translational relevance of intestinal modulation strategies in the comprehensive treatment of MASLD.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation.Post-transplant MASLD manifests a...Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation.Post-transplant MASLD manifests as recurrent disease in nearly all recipients by five years post-transplantation,while de novo MASLD shows variable incidence(18%-78%).Although histologically similar,recurrent MASLD follows a more aggressive trajectory,with accelerated fibrosis and cirrhosis.Metabolic disturbances,immunosuppression regimens,donorrelated factors,and chronic inflammation synergistically contribute to disease pathogenesis.The disorder not only compromises graft function but is also associated with elevated cardiovascular and overall morbidity,and malignancy risk.Despite advancements in noninvasive diagnostics,histopathology remains essential for definitive diagnosis and prognostic stratification.Management should prioritize metabolic optimization,lifestyle intervention,and tailored immunosuppressive regimens.Glucagon-like peptide-1 receptor agonists represent a promising therapeutic avenue.However,the absence of standardized,transplant-specific guidelines is a significant limitation.Further research is necessary to define diagnostic criteria,risk stratification,and targeted therapy to improve graft survival and patient outcomes.展开更多
BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive...BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive strategy to expand the donor pool and reduce waitlist times.Given increased risk of cold ischemia time with SLT,machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes.The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion(NMP)closed circuit device.CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor.The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients.After a mixed in-situ and ex-situ split,in order to improve logistics,the right trisectional graft was placed on a closed circuit NMP device,following an appropriate vascular reconstruction.Both grafts were implanted with excellent short-term outcomes.CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics.We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.展开更多
The trial by Cano Contreras et al examined a proprietary formulation containing Silybum marianum and alpha-lipoic acid(SM-ALA),combined with a Mediter-ranean diet,in patients with metabolic dysfunction-associated stea...The trial by Cano Contreras et al examined a proprietary formulation containing Silybum marianum and alpha-lipoic acid(SM-ALA),combined with a Mediter-ranean diet,in patients with metabolic dysfunction-associated steatotic liver disease.While some metabolic benefits were observed,limitations such as the absence of an SM-ALA-only group,the lack of histological data,and a small sam-ple size reduce the validity of the findings.Future research should follow clinical trial standards for pharmacological studies,including phase 1/2 testing,validated outcomes,and transparency.展开更多
In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two ...In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two major contributors to the global burden of liver disease.By analyzing clinical characteristics,metabolic parameters,immune profiles,and liver pathology,Zhao et al comprehensively explored how MASLD influences the presentation,severity,and prognosis of DILI.Additionally,this study underscores the importance of structured diagnostic tools,such as the Roussel Uclaf Causality Assessment Method,to accurately assess the causality of DILI within the MASLD population.Although this study provides valuable insights,limitations such as its retrospective design and cohort heterogeneity underscore the need for future prospective research to refine diagnostic approaches and therapeutic strategies.展开更多
BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury...BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.展开更多
BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver disease.Liver transplantation(LT)is the most impactful treatment...BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver disease.Liver transplantation(LT)is the most impactful treatment.Yellow fever(YF)is an infectious disease that primarily affects the liver and has a high mortality rate.However,LT can be a viable option for treating rare cases with extensive liver involvement.However,the criteria for assessing the severity of ALF and determining the indications for transplantation have not been specifically validated for cases caused by YF.AIM To present necessary adjustments to established scoring systems for ALF secondary to YF.METHODS This was an observational,retrospective,single-center study.Fourteen consecutive patients with confirmed ALF due to YF were monitored in the intensive care unit by a specialized liver transplant team during a three-month epidemic outbreak in Brazil.During hospitalization,general supportive therapeutic measures were implemented,and the patients were regularly assessed using the King's College criteria and the Clichy-Villejuif criteria to determine the severity of liver failure.LT is considered a viable measure for patients with signs of end-stage liver failure.RESULTS Eight of 14(57%)patients developed severe neurological alterations within the first 96 hours after hospital admission.Four patients underwent emergency LT,and despite a moderate viral infection of the graft after transplantation,the 5-year survival rate was 50%.Although the King's College criteria and the Clichy-Villejuif criteria are the main scoring systems for ALF,they are insufficient for predicting the risk of mortality in this context,primarily because of low serum bilirubin levels in the final stage of the disease and significant disparities between coagulation abnormalities and patient severity.CONCLUSION To ensure good applicability in cases of YF-induced ALF,the authors suggest adaptations to the King's College and Clichy-Villejuif criteria.展开更多
BACKGROUND Shear wave elastography(SWE)is a non-invasive ultrasound-based technique used to assess tissue stiffness,which reflects underlying pathological changes.While SWE has been widely applied for liver fibrosis e...BACKGROUND Shear wave elastography(SWE)is a non-invasive ultrasound-based technique used to assess tissue stiffness,which reflects underlying pathological changes.While SWE has been widely applied for liver fibrosis evaluation,its application to other abdominal organs,such as the spleen and pancreas,is gaining interest.However,normal stiffness values and inter-system agreement remain poorly defined.AIM To assess the feasibility and agreement of liver,spleen,and pancreas stiffness using three SWE methods.METHODS This single-center observational study enrolled 50 healthy adult volunteers.Liver,spleen,and pancreas stiffness were assessed using three SWE methods:Point-SWE(p-QElaXto)and 2-Dimensional-SWE(2D-QElaXto)with Esaote MyLab 9,and 2D-SWE with SuperSonic Imagine.Feasibility,inter-operator reproducibility,and concordance among systems were evaluated.Stiffness was expressed as median kPa values,and technical reliability was assessed using the interquartile range/median ratio and stability index thresholds.RESULTS Liver and spleen stiffness assessment was feasible in>98%of patients,while pancreas stiffness was measurable in 84%-88%depending on the SWE technique.Mean liver stiffness ranged between 3.9-4.7 kPa across techniques,spleen stiffness ranged from 19.4-23.0 kPa,and pancreas stiffness from 5.2-7.6 kPa.Inter-operator agreement was excellent for liver(intraclass correlation coefficient>0.90)and good to moderate for spleen and pancreas(intraclass correlation coefficient from 0.43 to 0.90).Bland-Altman analysis confirmed good correlation but also systematic differences among devices,especially in pancreas measurements.CONCLUSION This is the first study to establish normal liver,spleen,and pancreas stiffness using MyLab 9 SWE integrated methods as compared to SuperSonic Imagine,with acceptable inter-technique agreement.Liver and spleen values matched existing guidelines;pancreas SWE showed more variability and reduced reproducibility.展开更多
In this article,we discuss the recently published article by Soni et al.This study explores the effectiveness of a comprehensive digital health program,RESET care,which integrates personalized dietary plans,structured...In this article,we discuss the recently published article by Soni et al.This study explores the effectiveness of a comprehensive digital health program,RESET care,which integrates personalized dietary plans,structured exercise,and cognitive behavioral therapy delivered through a mobile app equipped with Internet of Things devices such as body composition analyzers and smartwatches.Metabolic dysfunction-associated liver disease(MASLD),a global health burden affecting approximately 25%of the population,demands sustainable lifestyle modifications as its primary management strategy.The study reports that 100%of participants in the comprehensive intervention group(diet+exercise+cognitive behavioral therapy)achieved a weight reduction≥7%(6.99±2.98 kg,7.00%±3.39%;P=0.002),a clinically significant threshold for MASLD improvement.In addition,participants showed a mean weight reduction of 6.99 kg(101.10±17.85 vs 94.11±17.38,P<0.001)and a body mass index reduction of 2.18 kg/m²(32.90±3.02 vs 30.72±3.41,P<0.001).These results underscore the potential of digital health platforms to provide scalable,evidence-based solutions for the treatment of MASLD.While these results highlight the potential of digital platforms in the scalable and personalized management of MASLD,the small study sample size and short duration of follow-up limit the generalizability of the results.Future large-scale,long-term trials are needed to confirm sustained benefits,cost-effectiveness,and broader applicability.This letter contextualizes the study within the evolving landscape of MASLD management and emphasizes the clinical implications of integrating digital technologies into standard care.展开更多
BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly lead...BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly leads to infections or adversely impacts clinical outcomes remains unclear.Clarifying this relationship may help deter-mine the prognostic significance of colonization in these patients.AIM To evaluate the clinical relevance of MDRO colonization and infection at ICU admission in patients with cirrhosis.METHODS This retrospective single-center cohort study included 107 ICU admissions of patients with liver cirrhosis at a tertiary care center(2018-2024).Colonization was assessed by rectal and nasal/pharyngeal swabs within 48 hours of ICU admission.Outcomes analyzed included MDRO infection during ICU stay,concordance between colonizing and infecting strains,organ support requirements,and 28-day transplant free survival.Multivariable logistic regression and Kaplan-Meier analyses were used to evaluate predictors of infection and mortality.RESULTS Nearly one-third(29.9%)of patients were colonized with MDROs on admission,more commonly in the acute-onchronic liver failure phenotype than those with acute decompensation(34.5 vs 10.0%,P=0.033).Although infections were established in the majority(85%)of cases,of which 17.6%due to MDROs,colonization alone did not independently predict these infections[odds ratio(OR)=2.18,P=0.383]nor influenced short-term mortality(OR=1.14,P=0.813).However,once MDRO infection occurred,an 82%concordance was observed between colonizing and infecting strains.MDRO infections,unlike colonization,significantly increased the need for organsupport interventions,including mechanical ventilation and vasopressor therapy and prolonged ICU stays.Only severity of organ dysfunction,quantified by the Sequential Organ Failure Assessment score,independently predicted 28-day mortality(OR=1.38,P=0.024).CONCLUSION MDRO colonization at ICU admission is frequent among critically ill patients with cirrhosis,particularly those with acute-on-chronic liver failure.While colonization alone does not predict infection or early mortality,its clinical value emerges in guiding empirical antibiotic treatment once infection is suspected.Ultimately,short-term survival appears to be more strongly influenced by the severity of organ failure than by either MDRO colonization or infection.展开更多
BACKGROUND Chylous ascites(CA),which is characterized by lymphatic leakage into the peritoneal cavity,is a rare but significant complication of liver transplantation.Although dietary and pharmacological strategies hav...BACKGROUND Chylous ascites(CA),which is characterized by lymphatic leakage into the peritoneal cavity,is a rare but significant complication of liver transplantation.Although dietary and pharmacological strategies have shown effectiveness in managing CA,standardized treatment protocols have yet to be established.AIMTo evaluate the comparative effectiveness of low-fat diet (LFD) enriched with medium-chain triglycerides (MCTs)vs octreotide therapy in managing post-liver transplantation CA.METHODSA comprehensive literature review was conducted to analyze the outcomes of dietary interventions and octreotidetherapy. The key parameters examined included resolution rates, treatment duration, and recurrence.RESULTSA comprehensive literature search yielded 13 studies that met the inclusion criteria, comprising 4 retrospectivecohort studies and 8 case studies. The incidence of CA following liver transplantation ranges from 0.6% to 4.7%.The onset varied, with a median time to diagnosis of 10 days after transplantation. A LFD with MCT supplementationwas used as the first-line therapy in 83.3% of the studies, with resolution rates ranging from 62.5% to100%. Octreotide therapy was utilized in 66.7% of the studies, primarily as a second-line therapy, with resolutionrates of 83.3% to 100%. Combination therapy showed a significantly higher resolution rate than did dietarymanagement alone (97.8% vs 78.9%, P = 0.02). The time to resolution was significantly shorter with octreotidecontainingregimens than with dietary management alone (median, 7 days vs 14 days;P = 0.03).CONCLUSIONA stepwise approach to CA management is recommended, initiating dietary interventions and escalating tooctreotide when necessary. Further research through well-designed randomized controlled trials is essential toestablish standardized treatment protocols for optimizing patient outcomes.展开更多
Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic ba...Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.展开更多
Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasi...Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.展开更多
The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect...The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.展开更多
Increasing evidence suggests that derangement of gut flora is of substantial dinical relevance to patients with cirrhosis. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the in...Increasing evidence suggests that derangement of gut flora is of substantial dinical relevance to patients with cirrhosis. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen, in particular, predispose to an increased potential for bacterial infection in this group. Recent studies suggest that, in addition to their role in the pathogenesis of overt infective episodes and the clinical consequences of sepsis, gut flora contributes to the pro-inflammatory state of cirrhosis even in the absence of overt infection. Furthermore, manipulation of gut flora to augment the intestinal content of lactic acid-type bacteria at the expense of other gut flora species with more pathogenic potential may favourably influence liver function in cirrhotic patients. Here we review current concepts of the various inter-relationships between gut flora, bacterial translocation, bacterial infection, pro-inflammatory cytokine production and liver function in this group.展开更多
The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistan...The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.展开更多
The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from ...The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.展开更多
文摘BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatments.NLR has emer-ged as an indicator of systemic inflammation and physiological stress.NPR has emerged as a potential indicator of inflammation and thrombotic risk in the context of surgical and radiological procedures.AIM To analyze the correlation of NLR and NPR with the development of post-liver transplantation(LT)early complications after stratification for hepatocellular carcinoma diagnosis.METHODS Consecutive patients undergone LT between January 2019 and December 2023 were enrolled.Data regarding the concentration of hemoglobin and the differ-ential leukocyte count on postoperative days(POD)0,1,3,and 5 were collected.RESULTS The dataset included 161 consecutive patients undergone LT.Clavien-Dindo IV-V complications had a good correlation with NLR POD 1(P=0.05),NLR POD 3(P<0.001),NLR POD 7(P<0.001),NPR POD 3(P<0.001).In addition,the NPR ratio on POD 3 correlated with the onset of 30-day hemorrhage(P=0.009).Finally,30-day mortality had a significant association with the NLR POD 1(P=0.03)and with NLR POD 7(P=0.004),while NPR had a significant correlation with 30-day mortality in NPR POD 7(P=0.004).CONCLUSION The analysis of NLR and NPR are strictly correlated with Clavien-Dindo IV-V complications and 30-day post-LT death.
文摘This manuscript is based on a recent study by Pillay et al that was published in recently.Liver abscesses can be caused by rare potentially life-threatening infections of either bacterial or parasitic origin.The incidence rate in Europe is lower than in developing countries,but it is a major complication with high morbidity,particularly in immunocompromised patients.They are most frequently caused by Enterobacterales infections,but hypervirulent Klebsiella strains are an emerging problem in Western countries.Amoebiasis has been a public health problem in Europe,primarily imported from other endemic foci.At the same time,this infection is becoming an emerging disease,as the number of infected patients who have not traveled to endemic areas is rising.Treatment options for hydatid liver cyst include chemotherapy,open or laparoscopic surgery,percutaneous treatment(percutaneous aspiration,re-aspiration and injection and its modification)and“wait and watch”strategy.Most hydatid liver cyst patients in Pillay et al’s study received surgical treatment,but several studies have confirmed the safety and efficacy of percutaneous aspiration,re-aspiration and injection.
文摘BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.
文摘Targeting the gut-liver axis has emerged as a promising strategy in the treatment of metabolic dysfunction-associated steatotic liver disease(MASLD),a condition that currently represents the most common cause of chronic liver disease worldwide.Within this axis,the duodenum serves not only as a site of nutrient absorption but also as a metabolic sensor capable of influencing systemic and hepatic homeostasis.We have read with great interest the recent study by Yu et al,investigating the effects of duodenal mucosal ablation(DMA)by irreversible electroporation in a rat model of MASLD.The authors reported remarkable reductions in hepatic lipid content,improvements in serum lipid profiles,and both structural and functional changes in the intestinal mucosa,including alterations in enteroendocrine signaling.These results corroborate the pivotal role of the gut-liver axis in the pathogenesis of MASLD and highlight the potential of minimally invasive approaches targeting the proximal intestine.In this letter,we discuss the broader implications of these findings,emphasizing the translational relevance of intestinal modulation strategies in the comprehensive treatment of MASLD.
基金Supported by The LTx Unit at Hospital Israelita Albert Einstein is financed by the Programa de Apoio ao Desenvolvimento Insitucional do SUS(PROADI-SUS)a partnership with the Brazilian Ministry of Health,No.25000.171086/2023-80.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation.Post-transplant MASLD manifests as recurrent disease in nearly all recipients by five years post-transplantation,while de novo MASLD shows variable incidence(18%-78%).Although histologically similar,recurrent MASLD follows a more aggressive trajectory,with accelerated fibrosis and cirrhosis.Metabolic disturbances,immunosuppression regimens,donorrelated factors,and chronic inflammation synergistically contribute to disease pathogenesis.The disorder not only compromises graft function but is also associated with elevated cardiovascular and overall morbidity,and malignancy risk.Despite advancements in noninvasive diagnostics,histopathology remains essential for definitive diagnosis and prognostic stratification.Management should prioritize metabolic optimization,lifestyle intervention,and tailored immunosuppressive regimens.Glucagon-like peptide-1 receptor agonists represent a promising therapeutic avenue.However,the absence of standardized,transplant-specific guidelines is a significant limitation.Further research is necessary to define diagnostic criteria,risk stratification,and targeted therapy to improve graft survival and patient outcomes.
文摘BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive strategy to expand the donor pool and reduce waitlist times.Given increased risk of cold ischemia time with SLT,machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes.The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion(NMP)closed circuit device.CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor.The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients.After a mixed in-situ and ex-situ split,in order to improve logistics,the right trisectional graft was placed on a closed circuit NMP device,following an appropriate vascular reconstruction.Both grafts were implanted with excellent short-term outcomes.CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics.We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.
文摘The trial by Cano Contreras et al examined a proprietary formulation containing Silybum marianum and alpha-lipoic acid(SM-ALA),combined with a Mediter-ranean diet,in patients with metabolic dysfunction-associated steatotic liver disease.While some metabolic benefits were observed,limitations such as the absence of an SM-ALA-only group,the lack of histological data,and a small sam-ple size reduce the validity of the findings.Future research should follow clinical trial standards for pharmacological studies,including phase 1/2 testing,validated outcomes,and transparency.
文摘In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two major contributors to the global burden of liver disease.By analyzing clinical characteristics,metabolic parameters,immune profiles,and liver pathology,Zhao et al comprehensively explored how MASLD influences the presentation,severity,and prognosis of DILI.Additionally,this study underscores the importance of structured diagnostic tools,such as the Roussel Uclaf Causality Assessment Method,to accurately assess the causality of DILI within the MASLD population.Although this study provides valuable insights,limitations such as its retrospective design and cohort heterogeneity underscore the need for future prospective research to refine diagnostic approaches and therapeutic strategies.
文摘BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.
基金Supported by The INCT-CNPq Program,No.465425/2014-3.
文摘BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver disease.Liver transplantation(LT)is the most impactful treatment.Yellow fever(YF)is an infectious disease that primarily affects the liver and has a high mortality rate.However,LT can be a viable option for treating rare cases with extensive liver involvement.However,the criteria for assessing the severity of ALF and determining the indications for transplantation have not been specifically validated for cases caused by YF.AIM To present necessary adjustments to established scoring systems for ALF secondary to YF.METHODS This was an observational,retrospective,single-center study.Fourteen consecutive patients with confirmed ALF due to YF were monitored in the intensive care unit by a specialized liver transplant team during a three-month epidemic outbreak in Brazil.During hospitalization,general supportive therapeutic measures were implemented,and the patients were regularly assessed using the King's College criteria and the Clichy-Villejuif criteria to determine the severity of liver failure.LT is considered a viable measure for patients with signs of end-stage liver failure.RESULTS Eight of 14(57%)patients developed severe neurological alterations within the first 96 hours after hospital admission.Four patients underwent emergency LT,and despite a moderate viral infection of the graft after transplantation,the 5-year survival rate was 50%.Although the King's College criteria and the Clichy-Villejuif criteria are the main scoring systems for ALF,they are insufficient for predicting the risk of mortality in this context,primarily because of low serum bilirubin levels in the final stage of the disease and significant disparities between coagulation abnormalities and patient severity.CONCLUSION To ensure good applicability in cases of YF-induced ALF,the authors suggest adaptations to the King's College and Clichy-Villejuif criteria.
文摘BACKGROUND Shear wave elastography(SWE)is a non-invasive ultrasound-based technique used to assess tissue stiffness,which reflects underlying pathological changes.While SWE has been widely applied for liver fibrosis evaluation,its application to other abdominal organs,such as the spleen and pancreas,is gaining interest.However,normal stiffness values and inter-system agreement remain poorly defined.AIM To assess the feasibility and agreement of liver,spleen,and pancreas stiffness using three SWE methods.METHODS This single-center observational study enrolled 50 healthy adult volunteers.Liver,spleen,and pancreas stiffness were assessed using three SWE methods:Point-SWE(p-QElaXto)and 2-Dimensional-SWE(2D-QElaXto)with Esaote MyLab 9,and 2D-SWE with SuperSonic Imagine.Feasibility,inter-operator reproducibility,and concordance among systems were evaluated.Stiffness was expressed as median kPa values,and technical reliability was assessed using the interquartile range/median ratio and stability index thresholds.RESULTS Liver and spleen stiffness assessment was feasible in>98%of patients,while pancreas stiffness was measurable in 84%-88%depending on the SWE technique.Mean liver stiffness ranged between 3.9-4.7 kPa across techniques,spleen stiffness ranged from 19.4-23.0 kPa,and pancreas stiffness from 5.2-7.6 kPa.Inter-operator agreement was excellent for liver(intraclass correlation coefficient>0.90)and good to moderate for spleen and pancreas(intraclass correlation coefficient from 0.43 to 0.90).Bland-Altman analysis confirmed good correlation but also systematic differences among devices,especially in pancreas measurements.CONCLUSION This is the first study to establish normal liver,spleen,and pancreas stiffness using MyLab 9 SWE integrated methods as compared to SuperSonic Imagine,with acceptable inter-technique agreement.Liver and spleen values matched existing guidelines;pancreas SWE showed more variability and reduced reproducibility.
文摘In this article,we discuss the recently published article by Soni et al.This study explores the effectiveness of a comprehensive digital health program,RESET care,which integrates personalized dietary plans,structured exercise,and cognitive behavioral therapy delivered through a mobile app equipped with Internet of Things devices such as body composition analyzers and smartwatches.Metabolic dysfunction-associated liver disease(MASLD),a global health burden affecting approximately 25%of the population,demands sustainable lifestyle modifications as its primary management strategy.The study reports that 100%of participants in the comprehensive intervention group(diet+exercise+cognitive behavioral therapy)achieved a weight reduction≥7%(6.99±2.98 kg,7.00%±3.39%;P=0.002),a clinically significant threshold for MASLD improvement.In addition,participants showed a mean weight reduction of 6.99 kg(101.10±17.85 vs 94.11±17.38,P<0.001)and a body mass index reduction of 2.18 kg/m²(32.90±3.02 vs 30.72±3.41,P<0.001).These results underscore the potential of digital health platforms to provide scalable,evidence-based solutions for the treatment of MASLD.While these results highlight the potential of digital platforms in the scalable and personalized management of MASLD,the small study sample size and short duration of follow-up limit the generalizability of the results.Future large-scale,long-term trials are needed to confirm sustained benefits,cost-effectiveness,and broader applicability.This letter contextualizes the study within the evolving landscape of MASLD management and emphasizes the clinical implications of integrating digital technologies into standard care.
基金approved by the Institutional Review Board of the University Hospital Centre Zagreb(Approval No:02/013 AG).
文摘BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly leads to infections or adversely impacts clinical outcomes remains unclear.Clarifying this relationship may help deter-mine the prognostic significance of colonization in these patients.AIM To evaluate the clinical relevance of MDRO colonization and infection at ICU admission in patients with cirrhosis.METHODS This retrospective single-center cohort study included 107 ICU admissions of patients with liver cirrhosis at a tertiary care center(2018-2024).Colonization was assessed by rectal and nasal/pharyngeal swabs within 48 hours of ICU admission.Outcomes analyzed included MDRO infection during ICU stay,concordance between colonizing and infecting strains,organ support requirements,and 28-day transplant free survival.Multivariable logistic regression and Kaplan-Meier analyses were used to evaluate predictors of infection and mortality.RESULTS Nearly one-third(29.9%)of patients were colonized with MDROs on admission,more commonly in the acute-onchronic liver failure phenotype than those with acute decompensation(34.5 vs 10.0%,P=0.033).Although infections were established in the majority(85%)of cases,of which 17.6%due to MDROs,colonization alone did not independently predict these infections[odds ratio(OR)=2.18,P=0.383]nor influenced short-term mortality(OR=1.14,P=0.813).However,once MDRO infection occurred,an 82%concordance was observed between colonizing and infecting strains.MDRO infections,unlike colonization,significantly increased the need for organsupport interventions,including mechanical ventilation and vasopressor therapy and prolonged ICU stays.Only severity of organ dysfunction,quantified by the Sequential Organ Failure Assessment score,independently predicted 28-day mortality(OR=1.38,P=0.024).CONCLUSION MDRO colonization at ICU admission is frequent among critically ill patients with cirrhosis,particularly those with acute-on-chronic liver failure.While colonization alone does not predict infection or early mortality,its clinical value emerges in guiding empirical antibiotic treatment once infection is suspected.Ultimately,short-term survival appears to be more strongly influenced by the severity of organ failure than by either MDRO colonization or infection.
文摘BACKGROUND Chylous ascites(CA),which is characterized by lymphatic leakage into the peritoneal cavity,is a rare but significant complication of liver transplantation.Although dietary and pharmacological strategies have shown effectiveness in managing CA,standardized treatment protocols have yet to be established.AIMTo evaluate the comparative effectiveness of low-fat diet (LFD) enriched with medium-chain triglycerides (MCTs)vs octreotide therapy in managing post-liver transplantation CA.METHODSA comprehensive literature review was conducted to analyze the outcomes of dietary interventions and octreotidetherapy. The key parameters examined included resolution rates, treatment duration, and recurrence.RESULTSA comprehensive literature search yielded 13 studies that met the inclusion criteria, comprising 4 retrospectivecohort studies and 8 case studies. The incidence of CA following liver transplantation ranges from 0.6% to 4.7%.The onset varied, with a median time to diagnosis of 10 days after transplantation. A LFD with MCT supplementationwas used as the first-line therapy in 83.3% of the studies, with resolution rates ranging from 62.5% to100%. Octreotide therapy was utilized in 66.7% of the studies, primarily as a second-line therapy, with resolutionrates of 83.3% to 100%. Combination therapy showed a significantly higher resolution rate than did dietarymanagement alone (97.8% vs 78.9%, P = 0.02). The time to resolution was significantly shorter with octreotidecontainingregimens than with dietary management alone (median, 7 days vs 14 days;P = 0.03).CONCLUSIONA stepwise approach to CA management is recommended, initiating dietary interventions and escalating tooctreotide when necessary. Further research through well-designed randomized controlled trials is essential toestablish standardized treatment protocols for optimizing patient outcomes.
文摘Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.
文摘Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.
文摘The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.
文摘Increasing evidence suggests that derangement of gut flora is of substantial dinical relevance to patients with cirrhosis. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen, in particular, predispose to an increased potential for bacterial infection in this group. Recent studies suggest that, in addition to their role in the pathogenesis of overt infective episodes and the clinical consequences of sepsis, gut flora contributes to the pro-inflammatory state of cirrhosis even in the absence of overt infection. Furthermore, manipulation of gut flora to augment the intestinal content of lactic acid-type bacteria at the expense of other gut flora species with more pathogenic potential may favourably influence liver function in cirrhotic patients. Here we review current concepts of the various inter-relationships between gut flora, bacterial translocation, bacterial infection, pro-inflammatory cytokine production and liver function in this group.
文摘The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.
文摘The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.
