BACKGROUND Long-term abdominal drains(LTAD)are a cost-effective palliative measure to manage malignant ascites in the community,but their use in patients with end-stage chronic liver disease and refractory ascites is ...BACKGROUND Long-term abdominal drains(LTAD)are a cost-effective palliative measure to manage malignant ascites in the community,but their use in patients with end-stage chronic liver disease and refractory ascites is not routine practice.The safety and cost-effectiveness of LTAD are currently being studied in this setting,with preliminary positive results.We hypothesised that palliative LTAD are as effective and safe as repeat palliative large volume paracentesis(LVP)in patients with cirrhosis and refractory ascites and may offer advantages in patients’quality of life.AIM To compare the effectiveness and safety of palliative LTAD and LVP in refractory ascites secondary to end-stage chronic liver disease.METHODS A retrospective,observational cohort study comparing the effectiveness and safety outcomes of palliative LTAD and regular palliative LVP as a treatment for refractory ascites in consecutive patients with end-stage chronic liver disease followed-up at our United Kingdom tertiary centre between 2018 and 2022 was conducted.Fisher’s exact tests and the Mann-Whitney U test were used to compare qualitative and quantitative variables,respectively.Kaplan-Meier survival estimates were generated to stratify time-related outcomes according to the type of drain.RESULTS Thirty patients had a total of 35 indwelling abdominal drains and nineteen patients underwent regular LVP.The baseline characteristics were similar between the groups.Prophylactic antibiotics were more frequently prescribed in patients with LTAD(P=0.012),while the incidence of peritonitis did not differ between the two groups(P=0.46).The incidence of acute kidney injury(P=0.014)and ascites/drain-related hospital admissions(P=0.004)were significantly higher in the LVP group.The overall survival was similar in the two groups(log-rank P=0.26),but the endpoint-free survival was significantly shorter in the LVP group(P=0.003,P<0.001,P=0.018 for first ascites/drain-related admission,acute kidney injury and drain-related complications,respectively).CONCLUSION The use of LTAD in the management of refractory ascites in palliated end-stage liver disease is effective,safe,and may reduce hospital admissions and utilisation of healthcare resources compared to LVP.展开更多
The application of machine learning(ML)algorithms in various fields of hepatology is an issue of interest.However,we must be cautious with the results.In this letter,based on a published ML prediction model for acute ...The application of machine learning(ML)algorithms in various fields of hepatology is an issue of interest.However,we must be cautious with the results.In this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the future.Although the future faces significant challenges,it also holds a great potential.展开更多
Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is sti...Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.展开更多
The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiologic...The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.展开更多
There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonistssuch as semaglutide worldwide for weight loss and management of non-alcoholicsteatohepatitis (NASH). remains a paucity of safety data in th...There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonistssuch as semaglutide worldwide for weight loss and management of non-alcoholicsteatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASHcirrhotic population. We report herein the first documented case of liver decompensationand need for liver transplant waitlisting in a patient with NASHcirrhosistreated with semaglutide. Rapid weight loss led to the development ofascites and hepatic encephalopathy and an increase in the patients Model forEndstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritionalsupplementation was commenced and the semaglutide was stopped. Overthe following months she regained her weight and her liver recompensated andher MELD-Na decreased to 13, allowing her to be delisted from the transplantwaitlist. This case serves as a cautionary tale to clinicians using semaglutide in thecirrhotic population and highlights the need for more safety data in this patientgroup.展开更多
The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or earl...The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.展开更多
BACKGROUND Liver disease incidence and hence demand on hepatology services is increasing.AIM To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology s...BACKGROUND Liver disease incidence and hence demand on hepatology services is increasing.AIM To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology services.METHODS The registry is populated by International Classification of Diseases-10(ICD-10)code diagnoses for residents derived from mortality data and inpatient/day case activity between 1999-2019.Pseudo-anonymised linkage of:(1)Causative diagnoses;(2)Cirrhosis;(3)Portal hypertension;(4)Decompensation;and(5)Liver cancer diagnoses enabled tracking liver disease progression.RESULTS The population of Wales in 2019 was 3.1 million.Between 1999 and 201973054 individuals were diagnosed with a hepatic disorder,including 18633 diagnosed with cirrhosis,10965 with liver decompensation and 2316 with hepatocellular carcinoma(HCC).Over 21 years the incidence of liver diseases increased 3.6 fold,predominantly driven by a 10 fold increase in non-alcoholic fatty liver disease(NAFLD);the leading cause of liver disease from 2014.The incidence of cirrhosis,decompensation,HCC,and allcause mortality tripled.Liver-related mortality doubled.Alcohol-related liver disease(ArLD),autoimmune liver disease and congestive hepatopathy were associated with the highest rates of decompensation and all-cause mortality.CONCLUSION A 10 fold increase in NAFLD incidence is driving a 3.6 fold increase in liver disease in Wales over 21 years.Liver-related morbidity and mortality rose more slowly reflecting the lower progression rate in NAFLD.Incidence of ArLD remained stable but was associated with the highest rates of liver-related and all-cause mortality.展开更多
BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in...BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in elderly patients(>70 years old)treated with laparoscopic liver resection for hepatocellular carcinoma(HCC).METHODS Retrospective multicenter study including 224 elderly patients(>70 years old)operated by laparoscopy for HCC(196 with a BMI<30 and 28 with BMI≥30),observed from January 2009 to January 2019.RESULTS After propensity score matching,patients in two groups presented comparable results,in terms of operative time(median range:200 min vs 205 min,P=0.7 respectively in non-obese and obese patients),complications rate(22%vs 26%,P=1.0),length of hospital stay(median range:4.5 d vs 6.0 d,P=0.1).There are no significant differences in terms of short-and long-term postoperative results.CONCLUSION The present study showed that BMI did not impact perioperative and oncologic outcomes in elderly patients treated by laparoscopic resection for HCC.展开更多
The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic ...The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.展开更多
Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and aff...Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population.Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated assessments.We believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.展开更多
In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular carcinoma.Hepatocellular ca...In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular carcinoma.Hepatocellular carcinoma(HCC),which is characterized by high incidence and mortality rates,remains a major global health challenge primarily due to the critical issue of postoperative recurrence.Early recurrence,defined as recurrence that occurs within 2 years posttreatment,is linked to the hidden spread of the primary tumor and significantly impacts patient survival.Traditional predictive factors,including both patient-and treatment-related factors,have limited predictive ability with respect to HCC recurrence.The integration of machine learning algorithms is fueled by the exponential growth of computational power and has revolutionized HCC research.The study by Zhang et al demonstrated the use of a groundbreaking preoperative prediction model for early postoperative HCC recurrence.Challenges persist,including sample size constraints,issues with handling data,and the need for further validation and interpretability.This study emphasizes the need for collaborative efforts,multicenter studies and comparative analyses to validate and refine the model.Overcoming these challenges and exploring innovative approaches,such as multi-omics integration,will enhance personalized oncology care.This study marks a significant stride toward precise,efficient,and personalized oncology practices,thus offering hope for improved patient outcomes in the field of HCC treatment.展开更多
Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to...Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.展开更多
Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial transloc...Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.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
Introduction: This paper provides a review of the practice of liver transplantation with the main emphasis on UK practice and indications for transplantation.``Referral and Assessment: This section reviews the process...Introduction: This paper provides a review of the practice of liver transplantation with the main emphasis on UK practice and indications for transplantation.``Referral and Assessment: This section reviews the process of referral and assessment of patients with liver disease with reference to UK practice.``Donor Organs: The practice of brainstem death and cadaveric organ donation is peculiar to individual countries and rates of donation and potential areas of improvement are addressed.``Operative Technique: The technical innovations that have led to liver transplantation becoming a semi-elective procedure are reviewed. Specific emphasis is made to the role of liver reduction and splitting and living related liver transplantation and how this impacts on UK practice are reviewed. The complications of liver transplantation are also reviewed with reference to our own unit.``Imrnunosuppression: The evolution of immunosuppression and its impact on liver transplantation are reviewed with some reference to future protocols.Retransplantation: The role of retransplantation is reviewed.``Outcome and Survival: The results of liver transplantation are reviewed with specific emphasis on our own experience.``Future: The future of liver transplantation is addressed.展开更多
Liver transplantation(LT)is the best treatment for endstage hepatic failure,with an excellent survival rates over the last decade.Biliary complications after LT pose a major challenge especially with the increasing nu...Liver transplantation(LT)is the best treatment for endstage 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 com-pared 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 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
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
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 bac...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
文摘BACKGROUND Long-term abdominal drains(LTAD)are a cost-effective palliative measure to manage malignant ascites in the community,but their use in patients with end-stage chronic liver disease and refractory ascites is not routine practice.The safety and cost-effectiveness of LTAD are currently being studied in this setting,with preliminary positive results.We hypothesised that palliative LTAD are as effective and safe as repeat palliative large volume paracentesis(LVP)in patients with cirrhosis and refractory ascites and may offer advantages in patients’quality of life.AIM To compare the effectiveness and safety of palliative LTAD and LVP in refractory ascites secondary to end-stage chronic liver disease.METHODS A retrospective,observational cohort study comparing the effectiveness and safety outcomes of palliative LTAD and regular palliative LVP as a treatment for refractory ascites in consecutive patients with end-stage chronic liver disease followed-up at our United Kingdom tertiary centre between 2018 and 2022 was conducted.Fisher’s exact tests and the Mann-Whitney U test were used to compare qualitative and quantitative variables,respectively.Kaplan-Meier survival estimates were generated to stratify time-related outcomes according to the type of drain.RESULTS Thirty patients had a total of 35 indwelling abdominal drains and nineteen patients underwent regular LVP.The baseline characteristics were similar between the groups.Prophylactic antibiotics were more frequently prescribed in patients with LTAD(P=0.012),while the incidence of peritonitis did not differ between the two groups(P=0.46).The incidence of acute kidney injury(P=0.014)and ascites/drain-related hospital admissions(P=0.004)were significantly higher in the LVP group.The overall survival was similar in the two groups(log-rank P=0.26),but the endpoint-free survival was significantly shorter in the LVP group(P=0.003,P<0.001,P=0.018 for first ascites/drain-related admission,acute kidney injury and drain-related complications,respectively).CONCLUSION The use of LTAD in the management of refractory ascites in palliated end-stage liver disease is effective,safe,and may reduce hospital admissions and utilisation of healthcare resources compared to LVP.
文摘The application of machine learning(ML)algorithms in various fields of hepatology is an issue of interest.However,we must be cautious with the results.In this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the future.Although the future faces significant challenges,it also holds a great potential.
基金Supported by PIP-CONICET 2021-2023 grant,No.11220200100875COPICT-2020-Serie,No.A-00788and“Florencio Fiorini Foundation”grants.
文摘Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.
文摘The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.
文摘There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonistssuch as semaglutide worldwide for weight loss and management of non-alcoholicsteatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASHcirrhotic population. We report herein the first documented case of liver decompensationand need for liver transplant waitlisting in a patient with NASHcirrhosistreated with semaglutide. Rapid weight loss led to the development ofascites and hepatic encephalopathy and an increase in the patients Model forEndstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritionalsupplementation was commenced and the semaglutide was stopped. Overthe following months she regained her weight and her liver recompensated andher MELD-Na decreased to 13, allowing her to be delisted from the transplantwaitlist. This case serves as a cautionary tale to clinicians using semaglutide in thecirrhotic population and highlights the need for more safety data in this patientgroup.
基金funding received in the form of the Catherine Marie Enright research scholarship from the Royal Australasian College of Surgeons to support his program of research
文摘The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.
文摘BACKGROUND Liver disease incidence and hence demand on hepatology services is increasing.AIM To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology services.METHODS The registry is populated by International Classification of Diseases-10(ICD-10)code diagnoses for residents derived from mortality data and inpatient/day case activity between 1999-2019.Pseudo-anonymised linkage of:(1)Causative diagnoses;(2)Cirrhosis;(3)Portal hypertension;(4)Decompensation;and(5)Liver cancer diagnoses enabled tracking liver disease progression.RESULTS The population of Wales in 2019 was 3.1 million.Between 1999 and 201973054 individuals were diagnosed with a hepatic disorder,including 18633 diagnosed with cirrhosis,10965 with liver decompensation and 2316 with hepatocellular carcinoma(HCC).Over 21 years the incidence of liver diseases increased 3.6 fold,predominantly driven by a 10 fold increase in non-alcoholic fatty liver disease(NAFLD);the leading cause of liver disease from 2014.The incidence of cirrhosis,decompensation,HCC,and allcause mortality tripled.Liver-related mortality doubled.Alcohol-related liver disease(ArLD),autoimmune liver disease and congestive hepatopathy were associated with the highest rates of decompensation and all-cause mortality.CONCLUSION A 10 fold increase in NAFLD incidence is driving a 3.6 fold increase in liver disease in Wales over 21 years.Liver-related morbidity and mortality rose more slowly reflecting the lower progression rate in NAFLD.Incidence of ArLD remained stable but was associated with the highest rates of liver-related and all-cause mortality.
文摘BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in elderly patients(>70 years old)treated with laparoscopic liver resection for hepatocellular carcinoma(HCC).METHODS Retrospective multicenter study including 224 elderly patients(>70 years old)operated by laparoscopy for HCC(196 with a BMI<30 and 28 with BMI≥30),observed from January 2009 to January 2019.RESULTS After propensity score matching,patients in two groups presented comparable results,in terms of operative time(median range:200 min vs 205 min,P=0.7 respectively in non-obese and obese patients),complications rate(22%vs 26%,P=1.0),length of hospital stay(median range:4.5 d vs 6.0 d,P=0.1).There are no significant differences in terms of short-and long-term postoperative results.CONCLUSION The present study showed that BMI did not impact perioperative and oncologic outcomes in elderly patients treated by laparoscopic resection for HCC.
文摘The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.
文摘Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population.Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated assessments.We believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.
文摘In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular carcinoma.Hepatocellular carcinoma(HCC),which is characterized by high incidence and mortality rates,remains a major global health challenge primarily due to the critical issue of postoperative recurrence.Early recurrence,defined as recurrence that occurs within 2 years posttreatment,is linked to the hidden spread of the primary tumor and significantly impacts patient survival.Traditional predictive factors,including both patient-and treatment-related factors,have limited predictive ability with respect to HCC recurrence.The integration of machine learning algorithms is fueled by the exponential growth of computational power and has revolutionized HCC research.The study by Zhang et al demonstrated the use of a groundbreaking preoperative prediction model for early postoperative HCC recurrence.Challenges persist,including sample size constraints,issues with handling data,and the need for further validation and interpretability.This study emphasizes the need for collaborative efforts,multicenter studies and comparative analyses to validate and refine the model.Overcoming these challenges and exploring innovative approaches,such as multi-omics integration,will enhance personalized oncology care.This study marks a significant stride toward precise,efficient,and personalized oncology practices,thus offering hope for improved patient outcomes in the field of HCC treatment.
基金Supported by Rumah Program 2024 of Research Organization for Health,National Research and Innovation Agency of Indonesia2023 Grant of The Fondazione Veronesi,Milan,Italy(Caecilia H C Sukowati)2023/2024 Postdoctoral Fellowship of The Manajemen Talenta,Badan Riset dan Inovasi Nasional,Indonesia(Sri Jayanti).
文摘Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.
基金Supported by Immuron, Nasvax, Plantylight, Desert Labs,Teva Pharmaceutical and ENZO Biochem
文摘Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.
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Introduction: This paper provides a review of the practice of liver transplantation with the main emphasis on UK practice and indications for transplantation.``Referral and Assessment: This section reviews the process of referral and assessment of patients with liver disease with reference to UK practice.``Donor Organs: The practice of brainstem death and cadaveric organ donation is peculiar to individual countries and rates of donation and potential areas of improvement are addressed.``Operative Technique: The technical innovations that have led to liver transplantation becoming a semi-elective procedure are reviewed. Specific emphasis is made to the role of liver reduction and splitting and living related liver transplantation and how this impacts on UK practice are reviewed. The complications of liver transplantation are also reviewed with reference to our own unit.``Imrnunosuppression: The evolution of immunosuppression and its impact on liver transplantation are reviewed with some reference to future protocols.Retransplantation: The role of retransplantation is reviewed.``Outcome and Survival: The results of liver transplantation are reviewed with specific emphasis on our own experience.``Future: The future of liver transplantation is addressed.
文摘Liver transplantation(LT)is the best treatment for endstage 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 com-pared 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 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.
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.
