BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accu...BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.展开更多
BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver ...BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.展开更多
BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(...BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF)remains unclear.AIM To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients.METHODS This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital.Patients were divided into survivor and non-survivor groups according to their 28-d prognosis.The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses.Patients were divided into low-and high-LWR groups according to the cutoff values.Kaplan-Meier analysis was performed according to the level of LWR.RESULTS During the 28-d follow-up time,135 patients died,and the mortality rate was 40.90%.The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients.A lower LWR level was an independent risk factor for poor 28-d outcomes(hazard ratio=0.052,95%confidence interval:0.005-0.535).The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh,model for end-stage liver disease,and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores.In addition,the 28-d mortality was higher for patients with LWR<0.11 than for those with LWR≥0.11.CONCLUSION LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBVACLF patients.展开更多
Acute-on-chronic liver failure(ACLF)is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease.Consequences include high short-term morbidity,mortality,and health...Acute-on-chronic liver failure(ACLF)is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease.Consequences include high short-term morbidity,mortality,and healthcare resource utilisation.ACLF encompasses a dysregulated,systemic inflammatory response,which can precipitate extra hepatic organ failures.Common precipitants include infection,alcoholic hepatitis,and reactivation of viral hepatitis although frequently no cause is identified.Heterogenous definitions,diagnostic criteria,and treatment guidelines,have been proposed by international hepatology societies.This can result in delayed or missed diagnoses of ACLF,significant variability in clinical management,and under-estimation of disease burden.Liver transplantation may be considered but the mainstay of treatment is organ support,often in the intensive care unit.This review will provide clarity around where are the controversies and consensus in ACLF including:Epidemiology and resource utilisation,key clinical and diagnostic features,strategies for management,and research gaps.展开更多
Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to...Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF.Methods:This was an observational cohort study conducted between January 2018 and December 2020.Clinical characteristics,cirrhosis-related complications at LT and patient survival post-LT were collected.All liver recipients with ACLF were followed for 1 year post-LT.Results:A total of 212 LT recipients with ACLF were enrolled,including 75(35.4%)patients with ACLF-1,64(30.2%)with ACLF-2,and 73(34.4%)with ACLF-3.The median waiting time for LT was 11(4-24)days.The most prevalent cirrhosis-related complication was ascites(78.8%),followed by hepatic encephalopathy(57.1%),bacterial infections(48.1%),hepatorenal syndrome(22.2%)and gastrointestinal bleeding(11.3%).Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications(all P<0.05).A simplified model was developed by assigning one point to each complication:transplantation for ACLF with cirrhosis-related complication(TACC)model.Risk stratification of TACC model identified 3 strata(≥4,=3,and≤2)with high,median and low risk of death after LT(P<0.001).Moreover,the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic models(chronic liver failure-consortium ACLF score,Chinese Group on the Study of Severe Hepatitis B-ACLF score,model for end-stage liver disease score and Child-Turcotte-Pugh score).Conclusions:The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF.The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival,which might help to determine transplant timing for ACLF.展开更多
Background:Cirrhosis with acute decompensation(AD)and acute-on-chronic liver failure(ACLF)are characterized by high morbidity and mortality.Cytolysin,a toxin from Enterococcus faecalis(E.faecalis),is associated with m...Background:Cirrhosis with acute decompensation(AD)and acute-on-chronic liver failure(ACLF)are characterized by high morbidity and mortality.Cytolysin,a toxin from Enterococcus faecalis(E.faecalis),is associated with mortality in alcohol-associated hepatitis(AH).It is unclear whether cytolysin also contributes to disease severity in AD and ACLF.Methods:We studied the role of fecal cytolysin in 78 cirrhotic patients with AD/ACLF.Bacterial DNA from fecal samples was extracted and real-time quantitative polymerase chain reaction(PCR)was performed.The association between fecal cytolysin and liver disease severity in cirrhosis with AD or ACLF was analyzed.Results:Fecal cytolysin and E.faecalis abundance did not predict chronic liver failure(CLIF-C)AD and ACLF scores.Presence of fecal cytolysin was not associated with other liver disease markers,including Fibrosis-4(FIB-4)index,‘Age,serum Bilirubin,INR,and serum Creatinine(ABIC)’score,Child-Pugh score,model for end-stage liver disease(MELD)nor MELD-Na scores in AD or ACLF patients.Conclusions:Fecal cytolysin does not predict disease severity in AD and ACLF patients.The predictive value of fecal cytolysin positivity for mortality appears to be restricted to AH.展开更多
BACKGROUND There is no consensus on the usage of extended criteria donor(ECD)grafts in liver transplantation(LT)for acute-on-chronic liver failure(ACLF)patients.AIM To summarize the experience of using ECD livers in A...BACKGROUND There is no consensus on the usage of extended criteria donor(ECD)grafts in liver transplantation(LT)for acute-on-chronic liver failure(ACLF)patients.AIM To summarize the experience of using ECD livers in ACLF-LT.METHODS A retrospective cohort study was conducted,enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021.The patients were divided into ECD and non-ECD groups for analysis.RESULTS A total of 145 recipients were enrolled in this study,of which ECD and non-ECD recipients accounted for 53.8%and 46.2%,respectively.Donation after cardiac death(DCD)recipients accounted for the minority compared with donation after brain death(DBD)recipients(16.6%vs 83.4%).Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients.ECD grafts were associated with a significantly higher incidence of early allograft dysfunction(EAD)than non-ECD grafts(67.9%vs 41.8%,P=0.002).Postoperative outcomes between DCD and DBD recipients were comparable(P>0.05).ECD graft(P=0.009),anhepatic phase(P=0.034)and recipient gamma glutamyltransferase(P=0.016)were independent risk factors for EAD.Recipient preoperative number of extrahepatic organ failures>2(P=0.015)and intraoperative blood loss(P=0.000)were independent predictors of poor post-LT survival.CONCLUSION Although related to a higher risk of EAD,ECD grafts can be safely used in ACLF-LT.The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.展开更多
The coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a significant impact on the lives of millions of people,especially those with other conco...The coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a significant impact on the lives of millions of people,especially those with other concomitant diseases,such as chronic liver diseases.To date,seven coronaviruses have been identified to infect humans.The main site of pathological action of these viruses is lung tissue.However,a substantial number of studies have proven that SARSCoV-2 shows affinity towards several organs,including the gastrointestinal tract and the liver.The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination.Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells,a systemic reaction consisting of inflammation,hypoxia and cytokine storm,drug-induced liver injury,with the possible contribution of a perturbed gut-liver axis.Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection.Acute-onchronic liver failure(ACLF)is a relatively new syndrome that occurs in 10%–30%of all hospitalized patients with chronic liver disease.It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases.Several published studies have reported virus infection as a trigger factor for ACLF.However,to date,there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection.In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.展开更多
BACKGROUND There have been no reports of acute-on-chronic liver failure(ACLF)during treatment of chronic hepatitis C(CHC)with direct-acting antivirals(DAAs).CASE SUMMARY We report a 50-year-old male patient with CHC.T...BACKGROUND There have been no reports of acute-on-chronic liver failure(ACLF)during treatment of chronic hepatitis C(CHC)with direct-acting antivirals(DAAs).CASE SUMMARY We report a 50-year-old male patient with CHC.The patient sought medical attention from the Department of Infectious Diseases at our hospital due to severe yellowing of the skin and sclera,which developed 3 mo previously and attended two consecutive hospitals without finding the cause of liver damage.It was not until 1 mo ago that he was diagnosed with CHC at our hospital.After discharge,he was treated with DAAs.During treatment,ACLF occurred,and timely measures such as liver protection,enzyme lowering,anti-infective treatment,and suppression of inflammatory storms were implemented to control the condition.CONCLUSION DAA drugs significantly improve the cure rate of CHC.However,when patients have factors such as autoimmune attack,coinfection,or unclear hepatitis C virus genotype,close monitoring is required during DAA treatment.展开更多
BACKGROUND Acute liver failure(ALF)and acute-on-chronic liver(ACLF)carry high short-term mortality rate,and may result from a wide variety of causes.Plasma exchange has been shown in a randomized control trial to impr...BACKGROUND Acute liver failure(ALF)and acute-on-chronic liver(ACLF)carry high short-term mortality rate,and may result from a wide variety of causes.Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant.Other cohort studies demonstrated potential improvement in survival in patients with ACLF.AIM To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.METHODS Databases MEDLINE via PubMed,and EMBASE were searched and relevant publications up to 30 March,2019 were assessed.Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange,with or without another alternative non-bioartificial liver assist device.RESULTS Three hundred twenty four records were reviewed,of which 62 studies were found to be duplicates.Of the 262 records screened,211 studies were excluded.Fifty-one articles were assessed for eligibility,for which 7 were excluded.Twenty-nine studies were included for ALF only,and 9 studies for ACLF only.Six studies included both ALF and ACLF patients.A total of 44 publications were included.Of the included publications,2 were randomized controlled trials,14 cohort studies,12 case series,16 case reports.All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange.In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment(SMT)for ACLF,a biochemical improvement was seen.Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT.Using the aforementioned studies,plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60(95%CI 0.46-0.77,P<0.01).CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high.Plasma exchange in ACLF improves survival at 30-and 90-d in nontransplanted patients.Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.展开更多
AIM To explore the applicability of the Asia-Pacific Association for the Study of the Liver(APASL) and European Association for the Study of the Liver(EASL) guidelines for acute-on-chronic liver failure(ACLF) in profi...AIM To explore the applicability of the Asia-Pacific Association for the Study of the Liver(APASL) and European Association for the Study of the Liver(EASL) guidelines for acute-on-chronic liver failure(ACLF) in profiling patients and determining the outcome.METHODS Patients admitted to a tertiary hospital in Singapore with acute decompensation of liver disease from January 2004to July 2014 are screened for ACLF according to the APASL and EASL criteria. The patients' data(including basic demographics, information about existing chronic liver disease, information about the acute decompensation, relevant laboratory values during admission, treatment, and outcome) are retrospectively analyzed to determine the background, precipitating factors and outcome.RESULTS A total of 458 liver patients is analyzed, and 78 patients with ACLF are identified. Sixty-three patients(80.8%) meet the APASL criteria, 64 patients(82.1%) meet the EASL criteria, and 49 patients(62.8%) fulfilled both criteria. The most common causes of acute liver injury are bacterial infections(59.0%), hepatitis B flare(29.5%), and variceal bleeding(24.4%). The common aetiologies of the underlying chronic disease included hepatitis B(43.6%), alcoholic(20.5%) and cryptogenic(11.5%) liver disease. The overall mortality rate is 61.5%. Increased age, the number of organ failures(as per CLIF-SOFA score), peak creatinine, INR, and amylase levels are associated with increased mortality or the need for liver transplantation. 14.3% of patients undergo liver transplantation with a 100% 1-year survival rate. CONCLUSION Both APASL and EASL criteria have identified ACLF patients with high three-month mortality, but those who fulfill APASL criteria alone have a better survival.展开更多
Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.T...Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.展开更多
AIM To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.METHODS This is a prospective cohort study designed to assess the prognostic performance...AIM To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.METHODS This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium(CLIF-C) acute decompensation score(CLIF-C AD) and CLIF-C acute-on-chronic liver failure score(CLIF-C ACLF),regarding 28-d and 90-d mortality,as well as to compare them to other prognostic models,such as Model for End-Stage Liver Disease(MELD),MELD Sodium(MELD-Na),ChildPugh(CP) score,and the CLIF-C Organ Failure score(CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic(ROC) curves,area under the curves(AUC) and 95%CI.RESULTS One hundred and thirteen cirrhotic patients were included. At admission,18 patients had acute-onchronic liver failure(ACLF) and 95 individuals had acute decompensation(AD) without ACLF,of which 24 eventually developed ACLF during the course of hospitalization(AD evolving to ACLF group). The AD group had significantly lower 28-d(9.0%) and 90-d(18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group(both P < 0.001). On the other hand,28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group(P = 0.542 and P = 0.708,respectively). Among patients with ACLF,at 28 d from the diagnosis,CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line,with an AUC(95%CI) of 0.71(95%CI: 0.54-0.88,P = 0.021). Among patients with AD,all prognostic scores performed significantly better than the reference line regarding 28-d mortality,presenting with similar AUCs: CLIF-C AD score 0.75(95%CI: 0.63-0.88),CP score 0.72(95%CI: 0.59-0.85),MELD score 0.75(95%CI: 0.61-0.90),MELD-Na score 0.76(95%CI: 0.61-0.90),and CLIF-C OF score 0.74(95%CI: 0.60-0.88). The same occurred concerning AUCs for 90-d mortality: CLIF-C AD score 0.70(95%CI: 0.57-0.82),CP score 0.73(95%CI: 0.62-0.84),MELD score 0.71(95%CI: 0.59-0.83),MELD-Na score 0.73(95%CI: 0.62-0.84),and CLIF-C OF score 0.65(95%CI: 0.52-0.78).CONCLUSION This study demonstrated that CLIF-C ACLF is the best available score for the prediction of 28-d mortality among patients with ACLF. CLIF-C AD score is also useful for the prediction of mortality among cirrhotic patients with AD not fulfilling diagnostic criteria for ACLF,but it was not superior to other well-established prognostic scores.展开更多
BACKGROUND Liver transplantation for the most critically ill remains controversial;however,it is currently the only curative treatment option.AIM To assess immediate posttransplant outcomes and compare the short(1 yea...BACKGROUND Liver transplantation for the most critically ill remains controversial;however,it is currently the only curative treatment option.AIM To assess immediate posttransplant outcomes and compare the short(1 year)and long-term(6 years)posttransplant survival among cirrhotic patients stratified by disease severity.METHODS We included cirrhotic patients undergoing liver transplantation between 2015 and 2019 and categorized them into compensated cirrhosis(CC),decompensated cirrhosis(DC),and acute-on-chronic liver failure(ACLF).ACLF was further divided into severity grades.Our primary outcomes of interest were total days of intensive care unit(ICU)and hospital stay,development of complications and posttransplant survival at 1 and 6 years.RESULTS 235 patients underwent liver transplantation(CC=11,DC=129 and ACLF=95).Patients with ACLF had a significantly longer hospital stay[8.0(6.0-13.0)vs CC,6.0(3.0-7.0),and DC 7.0(4.5-10.0);P=0.01]and developed more infection-related complications[47(49.5%),vs CC,1(9.1%)and DC,38(29.5%);P<0.01].Posttransplant survival at 1-and 6-years was similar among groups(P=0.60 and P=0.90,respectively).ACLF patients stratified according to ACLF grade[ACLF-1 n=40(42.1%),ACLF-2 n=33(34.7%)and ACLF-3 n=22(23.2%)],had similar ICU and hospital stay length(P=0.68,P=0.54),as well as comparable frequencies of overall and infectious posttransplant complications(P=0.58,P=0.80).There was no survival difference between ACLF grades at 1 year and 6 years(P=0.40 and P=0.15).CONCLUSION Patients may benefit from liver transplantation regardless of the cirrhosis stage.ACLF patients have a longer hospital stay and frequency of infectious complications;however,excellent,and comparable 1 and 6-year survival rates support their enlisting and transplantation including those with ACLF-3.展开更多
Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack o...Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack of universal diagnostic criteria,the actual ACLF prevalence remains unclear;nevertheless,it is expected to be a highly prevalent condition worldwide.Earlier transplantation is an effective protective measure for selected ACLF patients.Besides liver transplantation,diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy.Although new clinical specific therapies have been researched,more studies are necessary to assess safety and efficacy.Therefore,future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow.Thus,an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality.In addition,while donor organ quality is meant to be a prognostic factor in the ACLF setting,recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.展开更多
The liver is a multifaceted organ;its location and detoxifying function expose this organ to countless injuries.Acute-on-chronic failure liver(ACLF)is a severe syndrome that affects the liver due to acute decompensati...The liver is a multifaceted organ;its location and detoxifying function expose this organ to countless injuries.Acute-on-chronic failure liver(ACLF)is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease.An infection environment,ascites,increased liver enzymes and prothrombin time,encephalopathy and fast-evolving multiorgan failure,leading to death,usually accompany this.The pathophysiology remains poorly understand.In this context,animal models become a very useful tool in this regard,as understanding;the disease may be helpful in developing novel therapeutic methodologies for ACLF.However,although animal models display several similarities to the human condition,they do not represent all ACLF manifestations,resulting in significant challenges.An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-Ga IN,potentiating liver damage supports the methodologies applied to induce experimental ACLF.The entire methodology has been described mostly for rats.Nevertheless,a quick Pub Med database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models.These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.展开更多
Background and Aims:To investigate the safety and efficacy of double plasma molecular adsorption system(DPMAS)with sequential low-dose plasma exchange(LPE)in treating early hepatitis B virus-related acute-on-chronic l...Background and Aims:To investigate the safety and efficacy of double plasma molecular adsorption system(DPMAS)with sequential low-dose plasma exchange(LPE)in treating early hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).Methods:Clinical data of patients with HBVACLF were prospectively collected,including patients in a DPMAS with sequential LPE(DPMAS+LPE)group and those in a standard medical treatment(SMT)group.The primary endpoint was death or liver transplantation(LT)at 12 weeks of follow-up.Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups.Results:After 2 weeks,total bilirubin,alanine aminotransferase,blood urea nitrogen levels,and Chinese Group on the Study of Severe Hepatitis B score,were significantly lower in the DPMAS+LPE group than those in the SMT group(p<0.05).After 4 weeks,laboratory parameters of the two groups were similar.The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks(97.9%vs.85.4%,p=0.027),but not at 12 weeks(85.4%vs.83.3%,p=0.687).Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group(p<0.05).Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes,regulation of immune effect response,regulation of endotoxin response,and glial cell proliferation.Conclusion:DPMAS+LPE significantly improved the 4-week cumulative survival rate,and ameliorated the inflammatory response in patients.DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.展开更多
The concept of acute-on-chronic liver failure(ACLF)has gained increasing awareness during the last decade.It considers liver cirrhosis as a systemic disease where precipitating events lead to a sudden deterioration,de...The concept of acute-on-chronic liver failure(ACLF)has gained increasing awareness during the last decade.It considers liver cirrhosis as a systemic disease where precipitating events lead to a sudden deterioration,decompensation and extrahepatic organ failures.Disease severity is determined by the number and types of organ failures and patients with ACLF have a distinct and worse prognosis than patients with acute decompensation but not fulfilling ACLF criteria(1-3).展开更多
BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mecha...BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines.CONCLUSION The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling,leading to advanced HBV-ACLF.These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.展开更多
Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver...Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).Tβ4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of Tβ4 mRNA showed the opposite trend.In patients with ACHBLF,Tβ4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,Tβ4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,Tβ4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.展开更多
基金National Natural Science Foundation of China,No.81970550,No.82070613 and No.82370638Natural Science Foundation of Hunan Province,China,No.2021JJ31067 and No.2021JJ41048+1 种基金Hunan innovative province construction project,No.2023JJ10095Innovative Talented Project of Hunan province,China,No.2022RC1212.
文摘BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.
文摘BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.
基金Supported by the National Natural Science Foundation of China,No.81960120 and 81660110the Postgraduate Innovation Special Foundation of Jiangxi Province,No.YC2022-B052“Gan-Po Talent 555”Project of Jiangxi Province,No.GCZ(2012)-1.
文摘BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF)remains unclear.AIM To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients.METHODS This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital.Patients were divided into survivor and non-survivor groups according to their 28-d prognosis.The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses.Patients were divided into low-and high-LWR groups according to the cutoff values.Kaplan-Meier analysis was performed according to the level of LWR.RESULTS During the 28-d follow-up time,135 patients died,and the mortality rate was 40.90%.The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients.A lower LWR level was an independent risk factor for poor 28-d outcomes(hazard ratio=0.052,95%confidence interval:0.005-0.535).The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh,model for end-stage liver disease,and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores.In addition,the 28-d mortality was higher for patients with LWR<0.11 than for those with LWR≥0.11.CONCLUSION LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBVACLF patients.
文摘Acute-on-chronic liver failure(ACLF)is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease.Consequences include high short-term morbidity,mortality,and healthcare resource utilisation.ACLF encompasses a dysregulated,systemic inflammatory response,which can precipitate extra hepatic organ failures.Common precipitants include infection,alcoholic hepatitis,and reactivation of viral hepatitis although frequently no cause is identified.Heterogenous definitions,diagnostic criteria,and treatment guidelines,have been proposed by international hepatology societies.This can result in delayed or missed diagnoses of ACLF,significant variability in clinical management,and under-estimation of disease burden.Liver transplantation may be considered but the mainstay of treatment is organ support,often in the intensive care unit.This review will provide clarity around where are the controversies and consensus in ACLF including:Epidemiology and resource utilisation,key clinical and diagnostic features,strategies for management,and research gaps.
基金supported by grants from the National Key R&D Program of China(2021YFC2301800)Zhejiang Basic Public Welfare Research Program(LGF20H030008)the National Natural Sci-ence Foundation of China(81874038)。
文摘Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF.Methods:This was an observational cohort study conducted between January 2018 and December 2020.Clinical characteristics,cirrhosis-related complications at LT and patient survival post-LT were collected.All liver recipients with ACLF were followed for 1 year post-LT.Results:A total of 212 LT recipients with ACLF were enrolled,including 75(35.4%)patients with ACLF-1,64(30.2%)with ACLF-2,and 73(34.4%)with ACLF-3.The median waiting time for LT was 11(4-24)days.The most prevalent cirrhosis-related complication was ascites(78.8%),followed by hepatic encephalopathy(57.1%),bacterial infections(48.1%),hepatorenal syndrome(22.2%)and gastrointestinal bleeding(11.3%).Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications(all P<0.05).A simplified model was developed by assigning one point to each complication:transplantation for ACLF with cirrhosis-related complication(TACC)model.Risk stratification of TACC model identified 3 strata(≥4,=3,and≤2)with high,median and low risk of death after LT(P<0.001).Moreover,the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic models(chronic liver failure-consortium ACLF score,Chinese Group on the Study of Severe Hepatitis B-ACLF score,model for end-stage liver disease score and Child-Turcotte-Pugh score).Conclusions:The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF.The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival,which might help to determine transplant timing for ACLF.
基金This study was supported in part by National Institutes of Health(NIH)grant(K12 HD85036)University of California San Diego Altman Clinical and Translational Research Institute(ACTRI)/NIH grant(KL2TR001444)+14 种基金Pinnacle Research Award in Liver Diseases Grant(PNC22-159963)from the American Association for the Study of Liver Diseases Foundation(to Hartmann P)Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)fellowship(LA 4286/1-1)the“Clinical and Translational Research Fellowship in Liver Disease”by the American Association for the Study of Liver Diseases(AASLD)Foundation(to Lang S)National Institutes of Health grants(R01 AA24726,R01 AA020703,U01 AA026939)Award Number BX004594 from the Biomedical Laboratory Research&Development Service of the VA Office of Research and DevelopmentBiocodex Microbiota Foundation Grant(to Schnabl B)services provided by NIH centers(P30 DK120515 and P50 AA011999)This study was also supported by the German Research Foundation(DFG)project(403224013-SFB 1382)(to Trebicka J)the German Federal Ministry of Education and Research(BMBF)for the DEEP-HCC project(to Trebicka J)the Hessian Ministry of Higher Education,Research and the Arts(HMWK)for the ENABLE and ACLF-I cluster projects(to Trebicka J)The MICROB-PREDICT(825694)DECISION(847949)GALAXY(668031)LIVERHOPE(731875)IHMCSA(964590)projects(all to Trebicka J)have received funding from the European Union’s Horizon 2020 research and innovation program.
文摘Background:Cirrhosis with acute decompensation(AD)and acute-on-chronic liver failure(ACLF)are characterized by high morbidity and mortality.Cytolysin,a toxin from Enterococcus faecalis(E.faecalis),is associated with mortality in alcohol-associated hepatitis(AH).It is unclear whether cytolysin also contributes to disease severity in AD and ACLF.Methods:We studied the role of fecal cytolysin in 78 cirrhotic patients with AD/ACLF.Bacterial DNA from fecal samples was extracted and real-time quantitative polymerase chain reaction(PCR)was performed.The association between fecal cytolysin and liver disease severity in cirrhosis with AD or ACLF was analyzed.Results:Fecal cytolysin and E.faecalis abundance did not predict chronic liver failure(CLIF-C)AD and ACLF scores.Presence of fecal cytolysin was not associated with other liver disease markers,including Fibrosis-4(FIB-4)index,‘Age,serum Bilirubin,INR,and serum Creatinine(ABIC)’score,Child-Pugh score,model for end-stage liver disease(MELD)nor MELD-Na scores in AD or ACLF patients.Conclusions:Fecal cytolysin does not predict disease severity in AD and ACLF patients.The predictive value of fecal cytolysin positivity for mortality appears to be restricted to AH.
文摘BACKGROUND There is no consensus on the usage of extended criteria donor(ECD)grafts in liver transplantation(LT)for acute-on-chronic liver failure(ACLF)patients.AIM To summarize the experience of using ECD livers in ACLF-LT.METHODS A retrospective cohort study was conducted,enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021.The patients were divided into ECD and non-ECD groups for analysis.RESULTS A total of 145 recipients were enrolled in this study,of which ECD and non-ECD recipients accounted for 53.8%and 46.2%,respectively.Donation after cardiac death(DCD)recipients accounted for the minority compared with donation after brain death(DBD)recipients(16.6%vs 83.4%).Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients.ECD grafts were associated with a significantly higher incidence of early allograft dysfunction(EAD)than non-ECD grafts(67.9%vs 41.8%,P=0.002).Postoperative outcomes between DCD and DBD recipients were comparable(P>0.05).ECD graft(P=0.009),anhepatic phase(P=0.034)and recipient gamma glutamyltransferase(P=0.016)were independent risk factors for EAD.Recipient preoperative number of extrahepatic organ failures>2(P=0.015)and intraoperative blood loss(P=0.000)were independent predictors of poor post-LT survival.CONCLUSION Although related to a higher risk of EAD,ECD grafts can be safely used in ACLF-LT.The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.
基金Research and Development of a Telemedicine System to Support the Monitoring of the Possible Spread of COVID-19 in Order to Develop Analytical Tools Used to Reduce the Risk of Infection,No.ITMS:313011ASX4.
文摘The coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a significant impact on the lives of millions of people,especially those with other concomitant diseases,such as chronic liver diseases.To date,seven coronaviruses have been identified to infect humans.The main site of pathological action of these viruses is lung tissue.However,a substantial number of studies have proven that SARSCoV-2 shows affinity towards several organs,including the gastrointestinal tract and the liver.The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination.Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells,a systemic reaction consisting of inflammation,hypoxia and cytokine storm,drug-induced liver injury,with the possible contribution of a perturbed gut-liver axis.Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection.Acute-onchronic liver failure(ACLF)is a relatively new syndrome that occurs in 10%–30%of all hospitalized patients with chronic liver disease.It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases.Several published studies have reported virus infection as a trigger factor for ACLF.However,to date,there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection.In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.
基金Supported by the National Natural Science Foundation of China,No.82160558and Zunyi Science and Technology Fund.
文摘BACKGROUND There have been no reports of acute-on-chronic liver failure(ACLF)during treatment of chronic hepatitis C(CHC)with direct-acting antivirals(DAAs).CASE SUMMARY We report a 50-year-old male patient with CHC.The patient sought medical attention from the Department of Infectious Diseases at our hospital due to severe yellowing of the skin and sclera,which developed 3 mo previously and attended two consecutive hospitals without finding the cause of liver damage.It was not until 1 mo ago that he was diagnosed with CHC at our hospital.After discharge,he was treated with DAAs.During treatment,ACLF occurred,and timely measures such as liver protection,enzyme lowering,anti-infective treatment,and suppression of inflammatory storms were implemented to control the condition.CONCLUSION DAA drugs significantly improve the cure rate of CHC.However,when patients have factors such as autoimmune attack,coinfection,or unclear hepatitis C virus genotype,close monitoring is required during DAA treatment.
文摘BACKGROUND Acute liver failure(ALF)and acute-on-chronic liver(ACLF)carry high short-term mortality rate,and may result from a wide variety of causes.Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant.Other cohort studies demonstrated potential improvement in survival in patients with ACLF.AIM To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.METHODS Databases MEDLINE via PubMed,and EMBASE were searched and relevant publications up to 30 March,2019 were assessed.Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange,with or without another alternative non-bioartificial liver assist device.RESULTS Three hundred twenty four records were reviewed,of which 62 studies were found to be duplicates.Of the 262 records screened,211 studies were excluded.Fifty-one articles were assessed for eligibility,for which 7 were excluded.Twenty-nine studies were included for ALF only,and 9 studies for ACLF only.Six studies included both ALF and ACLF patients.A total of 44 publications were included.Of the included publications,2 were randomized controlled trials,14 cohort studies,12 case series,16 case reports.All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange.In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment(SMT)for ACLF,a biochemical improvement was seen.Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT.Using the aforementioned studies,plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60(95%CI 0.46-0.77,P<0.01).CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high.Plasma exchange in ACLF improves survival at 30-and 90-d in nontransplanted patients.Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.
文摘AIM To explore the applicability of the Asia-Pacific Association for the Study of the Liver(APASL) and European Association for the Study of the Liver(EASL) guidelines for acute-on-chronic liver failure(ACLF) in profiling patients and determining the outcome.METHODS Patients admitted to a tertiary hospital in Singapore with acute decompensation of liver disease from January 2004to July 2014 are screened for ACLF according to the APASL and EASL criteria. The patients' data(including basic demographics, information about existing chronic liver disease, information about the acute decompensation, relevant laboratory values during admission, treatment, and outcome) are retrospectively analyzed to determine the background, precipitating factors and outcome.RESULTS A total of 458 liver patients is analyzed, and 78 patients with ACLF are identified. Sixty-three patients(80.8%) meet the APASL criteria, 64 patients(82.1%) meet the EASL criteria, and 49 patients(62.8%) fulfilled both criteria. The most common causes of acute liver injury are bacterial infections(59.0%), hepatitis B flare(29.5%), and variceal bleeding(24.4%). The common aetiologies of the underlying chronic disease included hepatitis B(43.6%), alcoholic(20.5%) and cryptogenic(11.5%) liver disease. The overall mortality rate is 61.5%. Increased age, the number of organ failures(as per CLIF-SOFA score), peak creatinine, INR, and amylase levels are associated with increased mortality or the need for liver transplantation. 14.3% of patients undergo liver transplantation with a 100% 1-year survival rate. CONCLUSION Both APASL and EASL criteria have identified ACLF patients with high three-month mortality, but those who fulfill APASL criteria alone have a better survival.
基金supported by grants from the Science&Technology Key Program of Zhejiang China(2017C03051)the National Science&Technology Major Project of China(2017ZX10203201)。
文摘Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.
文摘AIM To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.METHODS This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium(CLIF-C) acute decompensation score(CLIF-C AD) and CLIF-C acute-on-chronic liver failure score(CLIF-C ACLF),regarding 28-d and 90-d mortality,as well as to compare them to other prognostic models,such as Model for End-Stage Liver Disease(MELD),MELD Sodium(MELD-Na),ChildPugh(CP) score,and the CLIF-C Organ Failure score(CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic(ROC) curves,area under the curves(AUC) and 95%CI.RESULTS One hundred and thirteen cirrhotic patients were included. At admission,18 patients had acute-onchronic liver failure(ACLF) and 95 individuals had acute decompensation(AD) without ACLF,of which 24 eventually developed ACLF during the course of hospitalization(AD evolving to ACLF group). The AD group had significantly lower 28-d(9.0%) and 90-d(18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group(both P < 0.001). On the other hand,28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group(P = 0.542 and P = 0.708,respectively). Among patients with ACLF,at 28 d from the diagnosis,CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line,with an AUC(95%CI) of 0.71(95%CI: 0.54-0.88,P = 0.021). Among patients with AD,all prognostic scores performed significantly better than the reference line regarding 28-d mortality,presenting with similar AUCs: CLIF-C AD score 0.75(95%CI: 0.63-0.88),CP score 0.72(95%CI: 0.59-0.85),MELD score 0.75(95%CI: 0.61-0.90),MELD-Na score 0.76(95%CI: 0.61-0.90),and CLIF-C OF score 0.74(95%CI: 0.60-0.88). The same occurred concerning AUCs for 90-d mortality: CLIF-C AD score 0.70(95%CI: 0.57-0.82),CP score 0.73(95%CI: 0.62-0.84),MELD score 0.71(95%CI: 0.59-0.83),MELD-Na score 0.73(95%CI: 0.62-0.84),and CLIF-C OF score 0.65(95%CI: 0.52-0.78).CONCLUSION This study demonstrated that CLIF-C ACLF is the best available score for the prediction of 28-d mortality among patients with ACLF. CLIF-C AD score is also useful for the prediction of mortality among cirrhotic patients with AD not fulfilling diagnostic criteria for ACLF,but it was not superior to other well-established prognostic scores.
基金This study was reviewed and approved by the Research Ethics Committee of Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán(GAS-2368-17-20).
文摘BACKGROUND Liver transplantation for the most critically ill remains controversial;however,it is currently the only curative treatment option.AIM To assess immediate posttransplant outcomes and compare the short(1 year)and long-term(6 years)posttransplant survival among cirrhotic patients stratified by disease severity.METHODS We included cirrhotic patients undergoing liver transplantation between 2015 and 2019 and categorized them into compensated cirrhosis(CC),decompensated cirrhosis(DC),and acute-on-chronic liver failure(ACLF).ACLF was further divided into severity grades.Our primary outcomes of interest were total days of intensive care unit(ICU)and hospital stay,development of complications and posttransplant survival at 1 and 6 years.RESULTS 235 patients underwent liver transplantation(CC=11,DC=129 and ACLF=95).Patients with ACLF had a significantly longer hospital stay[8.0(6.0-13.0)vs CC,6.0(3.0-7.0),and DC 7.0(4.5-10.0);P=0.01]and developed more infection-related complications[47(49.5%),vs CC,1(9.1%)and DC,38(29.5%);P<0.01].Posttransplant survival at 1-and 6-years was similar among groups(P=0.60 and P=0.90,respectively).ACLF patients stratified according to ACLF grade[ACLF-1 n=40(42.1%),ACLF-2 n=33(34.7%)and ACLF-3 n=22(23.2%)],had similar ICU and hospital stay length(P=0.68,P=0.54),as well as comparable frequencies of overall and infectious posttransplant complications(P=0.58,P=0.80).There was no survival difference between ACLF grades at 1 year and 6 years(P=0.40 and P=0.15).CONCLUSION Patients may benefit from liver transplantation regardless of the cirrhosis stage.ACLF patients have a longer hospital stay and frequency of infectious complications;however,excellent,and comparable 1 and 6-year survival rates support their enlisting and transplantation including those with ACLF-3.
文摘Acute-on-chronic liver failure(ACLF)is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation,organ failure and high short-term mortality.Partially due to the lack of universal diagnostic criteria,the actual ACLF prevalence remains unclear;nevertheless,it is expected to be a highly prevalent condition worldwide.Earlier transplantation is an effective protective measure for selected ACLF patients.Besides liver transplantation,diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy.Although new clinical specific therapies have been researched,more studies are necessary to assess safety and efficacy.Therefore,future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow.Thus,an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality.In addition,while donor organ quality is meant to be a prognostic factor in the ACLF setting,recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.
基金Supported by FIOCRUZ and FAPERJ Fundacao Carlos Chagas Filho de Amparo à Pesquisa do Rio de Janeiro-"Redes de Pesquisa em Saúde no Estado do Rio de Janeiro"No. E-26/010.002422/2019
文摘The liver is a multifaceted organ;its location and detoxifying function expose this organ to countless injuries.Acute-on-chronic failure liver(ACLF)is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease.An infection environment,ascites,increased liver enzymes and prothrombin time,encephalopathy and fast-evolving multiorgan failure,leading to death,usually accompany this.The pathophysiology remains poorly understand.In this context,animal models become a very useful tool in this regard,as understanding;the disease may be helpful in developing novel therapeutic methodologies for ACLF.However,although animal models display several similarities to the human condition,they do not represent all ACLF manifestations,resulting in significant challenges.An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-Ga IN,potentiating liver damage supports the methodologies applied to induce experimental ACLF.The entire methodology has been described mostly for rats.Nevertheless,a quick Pub Med database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models.These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.
基金This study was supported by grants from the National major science and technology project for the prevention and treatment of AIDS and viral hepatitis(2018ZX10302204-002-002 to LP,2018ZX10302205-002 to CX)Natural Science Foundation of China(No.81873572 to LP,82070611 to LP)+3 种基金Guangzhou Science and Technology Plan Projects(201904010442 to CX,202102010204 to LP)Guangdong Science and Technology Plan Projects(2020A1515010317 to CX)Sun Yat-Sen University Clinical Research 5010 Program(2018009 to CX,2020007 to LP)the Five-Year Plan of Third Affiliated Hospital of Sun Yat-Sen University(K00006 to LP).
文摘Background and Aims:To investigate the safety and efficacy of double plasma molecular adsorption system(DPMAS)with sequential low-dose plasma exchange(LPE)in treating early hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).Methods:Clinical data of patients with HBVACLF were prospectively collected,including patients in a DPMAS with sequential LPE(DPMAS+LPE)group and those in a standard medical treatment(SMT)group.The primary endpoint was death or liver transplantation(LT)at 12 weeks of follow-up.Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups.Results:After 2 weeks,total bilirubin,alanine aminotransferase,blood urea nitrogen levels,and Chinese Group on the Study of Severe Hepatitis B score,were significantly lower in the DPMAS+LPE group than those in the SMT group(p<0.05).After 4 weeks,laboratory parameters of the two groups were similar.The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks(97.9%vs.85.4%,p=0.027),but not at 12 weeks(85.4%vs.83.3%,p=0.687).Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group(p<0.05).Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes,regulation of immune effect response,regulation of endotoxin response,and glial cell proliferation.Conclusion:DPMAS+LPE significantly improved the 4-week cumulative survival rate,and ameliorated the inflammatory response in patients.DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.
文摘The concept of acute-on-chronic liver failure(ACLF)has gained increasing awareness during the last decade.It considers liver cirrhosis as a systemic disease where precipitating events lead to a sudden deterioration,decompensation and extrahepatic organ failures.Disease severity is determined by the number and types of organ failures and patients with ACLF have a distinct and worse prognosis than patients with acute decompensation but not fulfilling ACLF criteria(1-3).
基金the Domestic First-class Construction Disciplines of the Hunan University of Chinese MedicinePostgraduate Research Innovation Program of Hunan Province,No.CX20220771Clinical MedTech Innovation Project of Hunan Province,No.2021SK51415.
文摘BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.The correlation analysis revealed that hepatic organic acid metabolites were closely associated with macrophage-derived cytokines/chemokines.CONCLUSION The results indicated that bioenergetic alteration driven by hypoxia and mitochondrial dysfunction affects hepatic immune and metabolic remodeling,leading to advanced HBV-ACLF.These findings highlight a new therapeutic target for improving the treatment of HBV-ACLF.
基金supported by grants from the Key Project of the Chinese Ministry of Science and Technology(2017ZX102022022)the National Natural Science Foundation of China(81970522)the Key Research and Development Project of Shandong Province(2019GSF108023).
文摘Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).Tβ4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of Tβ4 mRNA showed the opposite trend.In patients with ACHBLF,Tβ4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,Tβ4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,Tβ4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.
