Hypermethylation of thymosinβ4 predicts a poor prognosis for patients with acute-on-chronic hepatitis B liver failure

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.

Lymphocyte-to-white blood cell ratio is associated with outcome in patients with hepatitis B virus-related 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.

Hepatitis A virus-associated acute acalculous cholecystitis in an adult-onset Still’s disease patient:A case report and review of the literature

BACKGROUND Acute acalculous cholecystitis(AAC)is inflammation of the gallbladder without evidence of calculi.Although rarely reported,its etiologies include hepatitis virus infection(e.g.,hepatitis A virus,HAV)and adult-onset Still’s disease(AOSD).There are no reports of HAV-associated AAC in an AOSD patient.CASE SUMMARY Here we report a rare case of HAV infection-associated AAC in a 39-year-old woman who had a history of AOSD.The patient presented with an acute abdomen and hypotension.Elevated hepatobiliary enzymes and a thickened and distended gallbladder without gallstones on ultrasonography suggested AAC,but there were no signs of anemia nor thrombocytopenia.Serological screening revealed anti-HAV IgM antibodies.Steroid treatment did not alleviate her symptoms,and she was referred for laparoscopic cholecystectomy.The resected gallbladder was hydropic without perforation,and her clinical signs gradually improved after surgery.CONCLUSION AAC can be caused by HAV in AOSD patients.It is crucial to search for the underlying etiology for AAC,especially uncommon viral causes.

May 2022 acute hepatitis outbreak,is there a role for COVID-19 and other viruses?

There has been an increasing number of reported cases of acute hepatitis of unknown origin in previously healthy children since first reported on March 31,2022.This clinical syndrome is identified by jaundice and markedly elevated liver enzymes with increased aspartate transaminase and/or alanine aminotransa-minase(greater than 500 IU/L).We conducted an inclusive literature review with respect to acute hepatitis outbreaks in children using the search terms acute hepatitis,outbreak,children,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),coronavirus disease 2019(COVID-19),and adenovirus.According to the cumulative data presented in four main studies,the median age is 4 years,with a male predominance(1.3:1).Jaundice was the most common clinical manifestation(69%),followed by vomiting(63%),anorexia(52.9%),diarrhea(47.2%),abdominal pain(39%),pyrexia(33.3%),pale stool(30%),and dark urine(30%).Coryza and lethargy were reported in 16.6%,while pruritus was reported in 2%of cases.Acute liver failure was observed in 25%of cases.The exact mechanism of this acute hepatitis outbreak is still not entirely clear.Adenoviruses and SARS-CoV-2 were detected in a significant number of patients.Coinfection with adenovirus and SARS-CoV-2 could be a possible underlying mechanism.However,other possible infections and mechanisms must be considered in the pathogenesis of this condition.Acute hepatitis of unknown origin in children has been a serious problem since the start of the COVID-19 pandemic but has not yet been sufficiently addressed.Many questions remain regarding the underlying mechanisms leading to acute liver failure in children,and it is likely that extensive future research is needed.

Prognostic and diagnostic scoring models in acute alcoholassociated hepatitis:A review comparing the performance of different scoring systems

Alcohol-associated hepatitis(AAH)is a severe form of liver disease caused by alcohol consumption.In the absence of confounding factors,clinical features and laboratory markers are sufficient to diagnose AAH,rule out alternative causes of liver injury and assess disease severity.Due to the elevated mortality of AAH,assessing the prognosis is a radical step in management.The Maddrey discriminant function(MDF)is the first established clinical prognostic score for AAH and was commonly used in the earliest AAH clinical trials.A MDF>32 indicates a poor prognosis and a potential benefit of initiating corticosteroids.The model for end stage liver disease(MELD)score has been studied for AAH prognostication and new evidence suggests MELD may predict mortality more accurately than MDF.The Lille score is usually combined to MDF or MELD score after corticosteroid initiation and offers the advantage of assessing response to treatment a 4-7 d into the course.Other commonly used scores include the Glasgow Alcoholic Hepatitis Score and the Age Bilirubin international normalized ratio Creatinine model.Clinical AAH correlate adequately with histologic severity scores and leave little indication for liver biopsy in assessing AAH prognosis.AAH presenting as acute on chronic liver failure(ACLF)is so far prognosticated with ACLF-specific scoring systems.New artificial intelligence-generated prognostic models have emerged and are being studied for use in AAH.Acute kidney injury(AKI)is one possible complication of AAH and is significantly associated with increased AAH mortality.Predicting AKI and alcohol relapse are important steps in the management of AAH.The aim of this review is to discuss the performance and limitations of different scoring models for AAH mortality,emphasize the most useful tools in prognostication and review predictors of recurrence.

Influence of chronic HBV infection on superimposed acute hepatitis E

AIM:To investigate the influence of chronic hepatitis B virus(HBV)infection[based on the status of hepatitis B e antigen(HBeAg),HBV DNA,and cirrhosis]on superimposed acute hepatitis E.METHODS:A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital,Sun Yat-sen University,from January 2003 to January 2012.The patients were classified into two groups:an HBV+hepatitis E virus(HEV)group(a group with chronic HBV infection that was superinfected with acute hepatitis E,n=118)and an HEV group(a group with acute hepatitis E,n=176).We retrospectively analyzed and compared the clinical features of the two groups.Statistical analyses were performed using theχ2test or Fisher’s exact test for categorical variables and the Student’s t test forcontinuous variables.A P value<0.05 was considered statistically significant.RESULTS:The peak values of prothrombin time,serum total bilirubin,and Model for End-Stage Liver Disease scores were significantly higher in the HBV+HEV group.More patients in the HBV+HEV group had complications(39.8%vs 16.5%,P=0.000)and developed liver failure(35.6%vs 8.5%,P=0.000).Additionally,the mortality of the HBV+HEV group was significantly higher(20.3%vs 7.4%,P=0.002).Further analysis of the HBV+HEV group showed that there were no significant differences in complication occurrence,liver failure incidence,or mortality between patients with different HBeAg and HBV DNA statuses.However,in patients with underlying cirrhosis,complication occurrence and liver failure incidence significantly increased.In total,12.7%of the patients in the HBV+HEV group received anti-HBV treatment,but this therapy failed to reduce mortality in patients who developed liver failure.CONCLUSION:The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E.AntiHBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.

SOCS3 Expression Correlates with Severity of Inflammation in Mouse Hepatitis Virus Strain 3-induced Acute Liver Failure and HBV-ACLF

Summary： Recently, suppressor of cytokine signaling-3 （SOCS3） has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription （JAK/STAT） pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure （HBV-ACLF） have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 （MHV-3）-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells （PBMCs） of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immtmohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B （CHB）. Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin （IL）-1 β, IL-6, and tumor necrosis factor （TNF）-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.

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

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Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China:A large,multicenter,retrospective cohort study using a propensity score matching analysis

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.

Detection of anti-HAV and anti-HEV IgM in patients with sporadic acute hepatitis in Beijing between 1995-2000

Objective: To investigate the age range, liver functiondamage and prognosis of patients with sporadic acutehepatitis A and E in Beijing.Methods: Enzyme immunoassay (EIA) was used todetect anti-HAV and anti-HEV immunoglobulin M(IgM). Serum samples were collected from the pa-tients with sporadic acute viral hepatitis in Beijingfrom January 1995 to June 2000.Results: The total positive rate for anti-HAV and an-ti-HEV IgM was 55.2% (112)in 203 patients with a-cute hepatitis, of whom 22.2% (45 patients) and33.0% (67) were positive for anti-HAV and anti-HEV respectively. The duration of anti-HEV IgMwas 45-60 days and that of anti-HAV IgM was atleast 2-3 months. The patients with acute hepatitis Aand hepatitis E all experienced jaundice and a risingof liver enzyme, but did not develop chronic hepatitisor died.Conclusion: Acute hepatitis A as well as acute hepatitisE plays an important role in sporadic entericallytransmitted hepatitis in Beijing.

An Analysis of Epidemiological Characteristics and the Clinical Features of 394 Cases of Sporadic Acute Hepatitis E in Southwest China from 2008 to 2010

Background and Aims Recently, epidemiology studies of hepatitis E in different areas are attracted more attention. Extensive studies of prevalent status and clinical manifestations could help us to broaden our knowledge, so as to excellently prevent and treat hepatitis E. The study analyzed the epidemiological characteristics and clinical features of 394 cases of sporadic acute hepatitis E(AHE) in Southwest of China from 2008 to 2010. Methods The clinical data of 394 cases with sporadic AHE in Southwest of China from 2008 to 2010 were reviewed.Results In the 394 cases with sporadic AHE, the ratio of male/female was 1.432∶1, and the mean age was(31.53 ± 18.12) years. Totally, 94(23.86%) patients aged under 18, 271(68.78%) patients aged between 18 and 60, and 29(7.36%) patients aged above 60. The incidence rate was significantly increased in summer(P = 0.000), especially in May(14.72%) and July(13.71%). In addition, the characteristics of occupation and ethnic group distribution were migrant laborers(106/394, 26.90%) and Han people(365/394, 92.64%). The length of stay, incidence of jaundice, the peak value of total bilirubin and alanine aminotransferase in male patients were all higher than those in female patients significantly(P < 0.05). The prolonged length of stay, decreased levels of ALT/ALB/CHE, increased levels of TBil, and increased incidence of jaundice and fatigue were associated with older age significantly(P < 0.05). The differences in peak values of total bilirubin(TBil), total bile acid(TBA), glutamyltransferase(GGT), cholinesterase(CHE) between AHE group and the groups of AHE accompanied respectively by chronic hepatitis B(CHB), acute alcoholic fatty liver(AFL), nonalcoholic fatty liver disease(NAFLD) were significant(P < 0.05). In addition, no significant difference was found in length of stay and biochemical indexes among anti-HEV-Ig G positive group, anti-HEV-Ig M positive group and antiHEV-Ig M/Ig G both positive group(P > 0.05).Conclusions Four epidemiological characteristics, including aged between 18 and 60, male, summer and migrant laborers, are found to be associated with acute hepatitis E. The prognosis of AHE in the majority of patients was favorable, but aged above 60 years and coexistence with CHB, AFL and NAFLD could be considerede as the factors inducing the infaust prognosis.

Early warning and clinical outcome prediction of acute-onchronic hepatitis B liver failure

Hepatitis B virus(HBV) associated acute-on-chronic liver failure(ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B(CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field.

Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection

BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.

Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.

Is there a need for universal double reflex testing of HBsAg-positive individuals for hepatitis D infection?

Hepatitis D virus(HDV)can infect HBsAg-positive individuals,causing rapid fibrosis progression,early decompensation,increased hepatocellular carcinoma risk,and higher mortality than hepatitis B virus(HBV)mono-infection.Most countries lack high-quality HDV prevalence data,and the collection techniques employed often bias published data.In recent meta-analyses,HDV prevalence in HBsAg-positive patients reaches 5%-15%and is even significantly higher in endemic areas.Since HBV vaccination programs were implemented,HDV prevalence has decreased among younger populations.However,owing to immigrant influx,it has increased in some Western countries.The current practice of HDV screening in HBsAg-positive individuals is stepwise,based on physician’s discretion,and limited to at-risk populations and may require numerous visits.Double reflex testing,which includes anti-HDV testing in all HBsAg-positive individuals and then HDV RNA testing for anti-HDV-positive ones,is uncommon.Reflex testing can identify more HDV infection cases and link identified patients to further care and follow-up.Moreover,laboratory-based double reflex screening is less biased than physician-led testing.Therefore,health-care providers should learn about reflex testing,and federal and provincial hepatitis control programs should implement laboratory-based double reflex testing to obtain reliable HDV prevalence estimates.The test’s cost-effectiveness depends on the number of HBV-positive patients screened to identify one HDV-positive patient.Such testing may be viable in areas with low HBsAg but high HDV prevalence.However,its economic impact on areas with low HDV prevalence needs further study.

Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

The spread of hepatitis B virus(HBV)infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B,from 10/100000 inhabitants in1984 to 0.85/100000 in 2012,and by the reduced prevalence of hepatitis B surface antigen(HBsAg)-positive cases among chronic hepatitis patients with different etiologies,from 60%in 1975 to about 10%in 2001.The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3%in the 1980s to 1%in 2010.Linked to HBV by its characteristics of defective virus,the hepatitis delta virus(HDV)has shown a similar epidemiological impact on the Italian population over time.The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from24%in 1990 to 8.5%in 2006.Before the beneficial effects of HBV mass vaccination introduced in 1991,the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations,the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size.A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.

Entecavir vs lamivudine therapy for na?ve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure

AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.

Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients

AIM To investigate potential triggering factors leading to acute liver failure(ALF) as the initial presentation of autoimmune hepatitis(AIH).METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients(9.2%) fulfilled the criteria for ALF defined by the "American Association for the Study of the Liver(AASLD)". According to this definition, patients with "acute-on-chronic" or "acute-on-cirrhosis" liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients' demographics, causation of liver failure, laboratory data(liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.RESULTS The majority of patients with ALF were female(84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for antiliver kidney microsomal antibody(LKM). We could identify potential triggering factors in 26/52(50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF(57.7%), virus-induced ALF(30.8%), and preceding surgery in general anesthesia(11.5%), respectively. Unfortunately, 6 out of 52 patients(11.5%) did not survive ALF and 3 patients(5.7%) underwent liver transplantation(LT). Comparing data of survivors and patients with non-recovery following treatment, MELDscore(P < 0.001), age(P < 0.05), creatinine(P < 0.01), and finally, ALT-values(P < 0.05) reached statistical significance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.

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.

Corticosteroid and nucleoside analogue for hepatitis B virus-related acute liver failure

The early introduction of combination therapy of high-dose corticosteroid and nucleoside analogue is beneficial for the rescue of severe acute exacerbation of chronic hepatitis B.