Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure

AIM:To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acuteon-chronic liver failure(HBV-ACLF).METHODS:Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed.Their general conditions and survival were analyzed by survival analysis and Cox regression analysis.RESULTS:A total of 190 patients were included in this study.The overall 1-year survival rate was 57.6%.Patients not treated with antiviral drugs had a significantly higher mortality[relative risk(RR)=0.609,P=0.014].The highest risk of death in patients with ACLF was associated with hepatorenal syndrome(HRS)(RR=2.084,P=0.026),while other significant factors were electrolyte disturbances(RR=2.062,P=0.010),and hepatic encephalopathy(HE)(RR=1.879,P<0.001).CONCLUSION:Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate.HRS,electrolyte disturbances,and HE also affect patient survival.

Clinical characteristics and corticosteroid therapy in patients with autoimmune-hepatitis-induced liver failure

AIM:To investigate the clinical features,response to corticosteroids,and prognosis of autoimmune hepatitis(AIH)-induced liver failure in China.METHODS:A total of 22 patients(19 female and 3male;average age 51±15 years)with AIH-induced liver failure treated in our hospital from 2004 to 2012were retrospectively analyzed.Clinical,biochemical and pathological characteristics of the 22 patients and responses to corticosteroid treatment in seven patients were examined retrospectively.The patients were divided into survivor and non-survivor groups,and the clinical characteristics and prognosis were compared between the two groups.The t test was used for data analysis of all categorical variables,and overall survival was calculated by the Kaplan-Meier method.RESULTS:At the time of diagnosis,mean IgG was2473±983 mg/dL,with three(18.8%)patients showing normal levels.All of the patients had elevated serum levels of antinuclear antibody(≥1:640).Liver histology from one patient showed diagnostic pathological changes,including massive necrosis and plasma cell infiltration.Four patients survived(18.2%)and 18died(81.8%)without liver transplantation.The results showed that patients with low admission Model for End-Stage Liver Disease(MELD)scores(21.50±2.08vs 30.61±6.70,P<0.05)and corticosteroid therapy(100%vs 16.7%,P<0.05)had better prognosis.A total of seven patients received corticosteroid therapy,of whom,four responded and survived,and the other three died.Survivors showed young age,shorter duration from diagnosis to corticosteroid therapy,low MELD score,and absence of hepatic encephalopathy at the time of corticosteroid administration.Six patients who were administered corticosteroids acquired fungal infections but recovered after antifungal therapy.CONCLUSION:Early diagnosis and corticosteroid therapy are essential for improving the prognosis of patients with AIH-induced liver failure without liver transplantation.

Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure(ACLF),which includes hepatic and multiple extrahepatic organ failure,is a severe emergency condition that has high mortality.ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation.Bacterial infections(BIs)trigger ACLF and play pivotal roles in the deterioration of clinical course.AIM To investigate the clinical characteristics and 28-d outcomes of first BIs either at admission or during hospitalization in patients with hepatitis B virus(HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B(COSSH).METHODS A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016.The characteristics of BIs,the 28-d transplant-free survival rates,and the independent predictors of the 28-d outcomes were evaluated.RESULTS A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF.Among the episodes,13.4%were community-acquired,46.4%were healthcare-associated,and 40.2%belonged to nosocomial BIs.Pneumonia(40.7%),spontaneous bacterial peritonitis(SBP)(34.5%),and bloodstream infection(BSI)(13.4%)were the most prevalent.As the ACLF grade increased,the incidence of SBP showed a downward trend(P=0.021).Sixty-one strains of bacteria,including 83.6%Gramnegative bacteria and 29.5%multidrug-resistant organisms,were cultivated from 50 patients with ACLF.Escherichia coli(44.3%)and Klebsiella pneumoniae(23.0%)were the most common bacteria.As the ACLF grade increased,the 28-d transplant-free survival rates showed a downward trend(ACLF-1,55.7%;ACLF-2,29.3%;ACLF-3,5.4%;P<0.001).The independent predictors of the 28-d outcomes of patients with HBV-ACLF were COSSH-ACLF score(hazard ratio[HR]=1.371),acute kidney injury(HR=2.187),BSI(HR=2.339),prothrombin activity(HR=0.967),and invasive catheterization(HR=2.173).CONCLUSION For patients with HBV-ACLF combined with first BIs,pneumonia is the most common form,and the incidence of SBP decreases with increasing ACLF grade.COSSH-ACLF score,acute kidney injury,BSI,prothrombin activity,and invasive catheterization are the independent predictors of 28-d outcomes.

High-dependency units play a key role in the treatment of a Chinese military patient who developed liver failure while abroad

High-dependency units(HDUs)provide high-level care to patients who suffer from single organ failure,with the exception of respiratory failure requiring mechanical ventilation;HDUs serve as an intermediary between general wards and Intensive Care Units.Due to military and civilian needs,our hospital has established a unique HDU for patients with liver disease in China.A Chinese military officer in the United Nations Peacekeeping Forces in South Sudan was transferred to our HDU for liver failure treatment in 2018.The patient’s disease status,nutrition,sleep habits,and psychological behaviour were monitored on different scales.The patient was provided with vascular monitoring,telemetry,pulse oximetry,drug treatment,nutritional support,sleep intervention,psychological intervention,and humanistic care by a multidisciplinary treatment team.After treatment,the patient recovered and avoided liver transplantation.Based on the experience with this HDU,this new model may create an efficient treatment process for military and civilian patients with severe liver disease at home or abroad.

Granulocyte-colony stimulating factor therapy improves survival in patients with hepatitis B virus-associated acuteon-chronic liver failure

AIM:To evaluate the safety and efficacy of granulocyte-colony stimulating factor(G-CSF) therapy in patients with hepatitis B virus(HBV)-associated acuteon-chronic liver failure(ACLF).METHODS:Fifty-five patients with HBV-associated ACLF were randomized into two groups:the treatment group and the control group.Twenty-seven patients in the treatment group received G-CSF(5 μg/kg per day,six doses) treatment plus standard therapy,and 28 patients in the control group received standard therapy only.The peripheral CD34 + cell count was measured consecutively by flow cytometry.Circulating white blood cell count,biochemical parameters,and other clinical data of these patients were recorded and analyzed.All patients were followed up for a period of 3 mo to evaluate the changes in liver function and survival rate.RESULTS:The peripheral neutrophil and CD34 + cell counts in the G-CSF group increased on day 3 from the onset of therapy,continued to rise on day 7,and remained elevated on day 15 compared to those of the control group.Child-Turcotte-Pugh score of patients in the treatment group was improved on day 30 from the onset of G-CSF therapy,compared to that in the controls(P = 0.041).Model for End-Stage of Liver Disease score of patients in the treatment group was improved on day 7(P = 0.004) and remained high on day 30 from the onset of G-CSF therapy(P < 0.001) compared to that in controls.After 3 mo of follow-up observation,the survival rate in the treatment group(48.1%) was significantly higher than that in the control group(21.4%)(P = 0.0181).CONCLUSION:G-CSF therapy promoted CD34 + cell mobilization in patients with HBV-associated ACLF,and improved the liver function and the survival rate of these patients.

Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

AIM:To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF).METHODS:Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine(Cr)level(<1.2 mg/dL in men,or<1.1 mg/dL in women)were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012.Thirty patients with chronic hepatitis B(CHB)and 30 healthy controls in the same study period were also included.Measurement of serum cystatin C(CysC)was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system.The ACLF patients were followed during their hospitalization period.RESULTS:In the ACLF group,serum level of CysC was 1.1±0.4 mg/L,which was significantly higher(P<0.01)than those in the healthy controls(0.6±0.3mg/L)and CHB patients(0.7±0.2 mg/L).During the hospitalization period,eight ACLF patients developed AKI.Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development(odds ratio=1.8;95%CI:1.4-2.3,P=0.021).The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L.The baseline CysC-based estimated glomerular filtration rate(eGFR CysC)was significantly lower than the creatinine-based eGFR(eGFR CG and eGFR MDRD)in ACLF patients with AKI,suggesting that baseline eGFR CysC represented early renal function in ACLF patients while the Cr levels were still within the normal ranges.CONCLUSION:Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.

Hepatitis E virus-related acute liver failure associated with pure red cell aplasia

The Editor welcomes submissions for possible publication in the Letters to the Editor section. Letters commenting on an article published in the Journal or other interesting pieces will be considered if they are received within 6 weeks of the time the article was published. Authors of the article being commented on will be given an opportunity to offer a timely response to the letter. Authors of letters will be notified that the letter has been received. Unpublished letters cannot be returned.

Clinical Course and Outcome Patterns of Acute-on-chronic Liver Failure:A Multicenter Retrospective Cohort Study

Background and Aims:Acute-on-chronic liver failure(ACLF)is acute decompensation of liver function in the setting of chronic liver disease,and characterized by high short-term mortality.In this study,we sought to investigate the clinical course of patients at specific time points,and to propose dynamic prognostic criteria.Methods:We assessed the clinical course of 453 patients with ACLF during a 12-week follow-up period in this retrospective multicenter study.The clinical course of patients was defined as disease recovery,improvement,worsening or steady patterns based on the variation tendency in prothrombin activity(PTA)and total bilirubin(TB)at different time points.Results:Resolution of PTA was observed in 231 patients(51%)at 12 weeks after the diagnosis of ACLF.Among the remaining patients,66(14.6%)showed improvement and 156(34.4%)showed a steady or worsening course.In patients with resolved PTA,the clinical course of TB exhibited resolved pattern in 95.2%,improved in 3.9%,and steady or worse in 0.8%.Correspondingly,in patients with improved PTA,these values for TB were 28.8%,27.3%,and 43.9%,respectively.In patients with steady or worsening PTA,these values for TB were 5.7%,32.3%,and 65.6%,respectively.Dynamic prognostic criteria were developed by combining the clinical course of PTA/TB and the clinical outcomes at 4 and 12 weeks after diagnosis in ACLF patients.Conclusions:We propose the following dynamic prognostic criteria:rapid progression,slow progression,rapid recovery,slow recovery,and slow persistence,which lay the foundation for precise prediction of prognosis and the improvement of ACLF therapy.

Development of a Widely Applicable and Simple Prognostic Score for Patients with Acute-on-chronic Liver Failure

Background and Aims:Acute-on-chronic liver failure(ACLF)tends to progress rapidly with high short-term mortality.We aimed to create a widely applicable,simple prognostic(WASP)score for ACLF patients.Methods:A retrospective cohort of ACLF cases recruited from three centers in China were divided into training and validation sets to develop the new score.A prospective longitudinal cohort was recruited for further validation.Results:A total of 541 cases were included in the training set,and seven independent ACLF prognostic factors were screened to construct a new quantitative WASP-ACLF table.In the validation set of 671 cases,WASP-ACLF showed better predictive ability for 28-day and 90-day mortality than the currently used prognostic scores at baseline,day 3,week 1,and week 2.The predictive efficacy and clinical validity of the model improved over time.Patients were assigned to low-,intermediate-,and high-risk groups by their WASP-ACLF scores.Compared with the other two groups,intermediate-risk patients had a more uncertain prognosis,with a 90-day mortality of 44.4–50.6%.Sequential assessments at weeks 1 and 2 found the 90-day mortality of intermediate-risk groups was<20%forpatients with a≥2 point decrease in WASP-ACLF and was up to 56%for patients with a≥2 points increase.Similar results were observed in prospective data.Conclusions:The new ACLF prognostic score was simple,widely applicable,and had good predictive efficacy.Continuous assessments and trend of change in WASP-ACLF need to be considered,especially for intermediate-risk patients.

Expert Consensus on Diagnosis and Treatment of End-Stage Liver Disease Complicated with Infections

End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decompensation.Consequently,infections are among the most common complications of disease progression.There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus.This consensus assembled up-to-date knowledge and experience across Chinese colleagues,providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.

Predictive value of the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score in the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure

Background:As a large,prospective,multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF),the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score(COSSH-ACLFs),has been approved by some foreign scholars;however,its predictive value needs to be verified.This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF.Methods:This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014.Spearman method was used to assess the correlation of COSSHACLFs with classical scores.Different COX multivariate regression models were used to confirm the relationship between COSSHACLFs and short-term prognosis in patients with HBV-ACLF,and stratified analysis was used to further verify the stability of this relationship.We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve(AUROC)and Z-test.Results:A total of 975 patients with HBV-ACLF were screened,and 751 were analyzed(623 male and 128 female).COSSH-ACLFs was the highest in patients with end-stage ACLF,followed by those with middle-and early-stage ACLF(H=211.8,P<0.001).In the fully adjusted model,COX multivariate regression analysis revealed that COSSH-ACLFs(as a continuous variable)was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days(hazard ratio[HR]:1.37[1.22,1.53],P<0.001)and 90 days(HR:1.43[1.29,1.58],P<0.001).The same trend could be observed in the crude model and minimally adjusted model.The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792,respectively,indicating a stronger predictive accuracy than those of classic models.Conclusions:COSSH-ACLFs,with a superior predictive accuracy compared with other classical scores,can strongly predict shortterm prognosis in Chinese patients with HBV-ACLF.