Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Stromal cell derived factor-1(SDF-1)plays a pivotal role in the recruitment of stem cells to injured livers.However,the changes of SDF-l in patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF)have yet to be elucidated.AIM To study the SDF-1 changes in patients with HBV-related ACLF.METHODS 30 patients with HBV-related ACLF,27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study.The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction.Immunohistochemical staining was performed to illustrate the expression of SDFl,CXC receptor 4(CXCR4)and Ki67.The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays.RESULTS The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients(both P<0.05).The expression of SDF-l,CXCR4 and Ki67 from ACLF were the highest among the three groups(all P<0.01).The serum SDF-l levels in ACLF patients were significantly lower than that in other patients(both P<0.01).Moreover,in ACLF patients,the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio.In addition,the serum SDF-l levels in survival were significantly lower compared with the non-survivals(P<0.05).The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722(P<0.05).CONCLUSION This study provides the SDF-1 changes in patients with HBV-related ACLF.The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term 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.

Bacterial infection triggers and complicates acute-on-chronic liver failure in patients with hepatitis B virus-decompensated cirrhosis: A retrospective cohort study

BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatitis B virus decompensated cirrhosis(HBV-DC)remains to be investigated.AIM To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF.METHODS This retrospective study included patients with HBV-DC admitted to two tertiary centers in China.In-hospital overall survival,90-d transplant-free survival,5-year post-discharge survival,and cumulative incidence of ACLF were evaluated.Risk factors for death were analyzed considering liver transplantation as a competing event.RESULTS A total of 1281 hospitalized HBV-DC patients were included;284 had ACLF at admission.The overall prevalence of BI was 28.1%.The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without,in both the patients admitted with and without ACLF.The presence of BI significantly increased the risk of developing ACLF[subdistribution hazard ratio(sHR)=2.52,95%CI:1.75-3.61,P<0.001]in the patients without ACLF.In the patients discharged alive,those who had an episode of BI had a significantly lower 5-year transplant-free survival.BI was an independent risk factor for death in the patients admitted without ACLF(sHR=3.28,95%CI:1.93-5.57),while in ACLF admissions,the presence of pneumonia,but not other type of BI,independently increased the risk of death(sHR=1.87,95%CI:1.24-2.82).CONCLUSION BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival.HBV-DC patients should be monitored carefully for the development of BI,especially pneumonia,to avoid an adverse outcome.

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 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 To were community-acquired,46.4 To 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-doutcomes 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.

Role of nutritional status and nutritional support in outcome of hepatitis B virus-associated acute-on-chronic liver failure

BACKGROUNDHepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is animportant type of liver failure in Asia. There is a direct relationship between HBVACLFand gastrointestinal barrier function. However, the nutritional status ofHBV-ACLF patients has been poorly studied.AIMTo investigate the nutritional risk and nutritional status of HBV-ACLF patientsand evaluated the impact of nutritional support on the gastrointestinal barrier and28-d mortality.METHODSNutritional risk screening assessment and gastrointestinal barrier biomarkers ofpatients with HBV-ACLF (n = 234) and patients in the compensatory period ofliver cirrhosis (the control group) (n = 234) were compared during the periodbetween 2016 and 2018. Changes were analyzed after nutritional support in HBVACLFpatients. Valuable biomarkers have been explored to predict 28-d death.The 28-d survival between HBV-ACLF patients with nutritional support (n = 234)or no nutritional support (2014-2016) (n = 207) was compared.RESULTSThe nutritional risk of the HBV-ACLF patients was significantly higher than thatof the control group. The nutritional intake of the patients with HBV-ACLF waslower than that of the control group. The decrease in skeletal muscle and fatcontent and the deficiency of fat intake were more obvious (P < 0.001). Thecoccus-bacillus ratio, secretory immunoglobulin A, and serum D-lactate weresignificantly increased in HBV-ACLF patients. The survival group had a lowernutritional risk, lower D-lactate, and cytokine levels (endotoxin, tumor necrosisfactor alpha, interleukin-10, and interleukin-1). Interleukin-10 may be a potentialpredictor of death in HBV-ACLF patients. The 28-d survival of the nutritionalsupport group was better than that of the non-nutritional support group (P =0.016).CONCLUSIONPatients with HBV-ACLF have insufficient nutritional intake and high nutritionalrisk, and their intestinal barrier function is impaired. Individualized and dynamicnutritional support is associated with a better prognosis of 28-d mortality in HBVACLFpatients.

Chronic hepatitis B virus infection in Eastern Ethiopia:Clinical characteristics and determinants of cirrhosis

BACKGROUND Chronic hepatitis B(CHB)virus infection is a major cause of liver-associated morbidity and mortality,particularly in low-income countries.A better understanding of the epidemiological,clinical,and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia.AIM To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment.METHODS This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019.Baseline assessments included chemistry,serologic,and viral markers.χ^(2) tests,Mann-Whitney U tests,and logistic regression analyses were used to identify the determinants of cirrhosis.Tenofovir disoproxil fumarate(TDF)was initiated using treatment criteria from the Ethiopian CHB pilot program.RESULTS A total of 132 patients(68.4%)were men,with a median age of 30 years[interquartile range(IQR):24-38].At enrollment,60(31.1%)patients had cirrhosis,of whom 35(58.3%)had decompensated cirrhosis.Khat use,hepatitis B envelope antigen positivity,and a high viral load were independently associated with cirrhosis.Additionally,66 patients(33.4%)fulfilled the treatment criteria and 59(30.6%)started TDF.Among 29 patients who completed 24 months of treatment,the median aspartate aminotransferase to platelet ratio index declined from 1.54(IQR:0.66-2.91)to 1.10(IQR:0.75-2.53)(P=0.002),and viral suppression was achieved in 80.9%and 100%of patients after 12 months and 24 months of treatment,respectively.Among the treated patients,12(20.3%)died within the first 6 months of treatment,of whom 8 had decompensated cirrhosis.CONCLUSION This study highlights the high prevalence of cirrhosis,initial mortality,and the efficacy of TDF treatment.Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients

This letter to the editor relates to the study entitled“Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study”,which was recently published by Peng et al.Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer.The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects,so it is crucial to identify safe and effective drugs to inhibit viral replication.

Chronic Hepatitis B in Indian Americans: Lack of Screening and Poor Linkage to Care

Background: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality in the United States (US) and globally. CHB disproportionately affects Asian Americans and many other immigrant minority populations, primarily owing to the high prevalence of CHB in their countries of origin. India is a country with a medium-to-high prevalence of hepatitis B (HB) (>2%) and has over 40 million people infected with hepatitis B virus (HBV), with more than 115,000 deaths annually from HBV-related complications. Indian Americans are one of the largest immigrant populations in the US but remain underdiagnosed and poorly linked to clinical care. We, therefore, assessed the HBV prevalence and evaluated the linkage-to-care (LTC) among Indian Americans to develop strategic plans to reduce the impact of HBV in the US. Methods: Between April 2022 and January 2024, serologic screening and surveys were provided to 328 Indian American adults (age 20 - 80) in New York City. All participants were tested for a triple panel consisting of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core IgG antibody (anti-HBc). A survey was conducted on the subjects chronically infected with HBV regarding their histories of infection. Self-administered questionnaires were employed to evaluate demographic and epidemiologic characteristics. Results: Of 328 screened and evaluated (246 males and 82 females), 10 (3.0%) were HBV-infected, 222 (67.7%) were susceptible to HBV, and 96 (29.3%) were immune. The prevalence of chronic HBV varied between the age groups: 4.6% (age 20 - 40), 3.4% (age 41 - 60), and 1.7% (age 61 - 80). Of 10 chronically infected, only two subjects had been previously diagnosed but were not engaged in care. Conclusion: HBV disproportionately affects Asian Americans, primarily owing to immigration from parts of the world where the disease is endemic. Indian Americans belong to an intermediate-risk group, with an HBV prevalence of >2%, but remain underdiagnosed and poorly linked to care. Our pilot study on Indian American populations, the first of its kind, demonstrates a 3% prevalence of CHB, none of whom are linked to care. In addition, this population has a high percentage of unimmune subjects, creating a large reservoir for future infection. With the growing population of Indian Americans, our findings can be used to develop community-based strategies for HBV screenings and LTC that target high-risk groups.

Chronic hepatitis B:Prevent,diagnose,and treat before the point of no return

Hepatitis B remains a significant global health challenge,contributing to substantial morbidity and mortality.Approximately 254 million people world-wide live with Chronic hepatitis B(CHB),with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions.Alarmingly,only about 13.4%of the individuals infected with this disease have been diagnosed,and awareness of hepatitis B virus(HBV)infection status is as low as 1%in sub-Saharan Africa.In 2022,CHB led to 1.1 million deaths globally.The World Health Organization(WHO)has set a target of eliminating hepatitis B as a public health concern by 2030;however,this goal appears increasingly unattainable due to multiple challenges.These challenges include low vaccination coverage;a large number of undiagnosed cases;a low proportion of patients eligible for treatment under current guidelines;limited access to healthcare;and the costs associated with lifelong treatment.Treatment of HBV can yield significant clinical benefits within a long window of opportunity.However,the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage.This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients:Hepatitis B virus infection and transaminases should be considered

BACKGROUND Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma(HCC),but a convenient and comprehensive method to assess liver condition is lacking.Liver stiffness(LS)measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition.Chronic hepatitis B(CHB)is an important risk factor for HCC progression,but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication.We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition.AIM To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB.METHODS A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus(HBV)-DNA levels[HBV-DNA≥100.00 IU/mL as Pos group(n=200)and<100.00 IU/mL as Neg group(n=84)].Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition.RESULTS A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition(P<0.05).When alanine aminotransferase(ALT)concentrations were normal(≤40 U/L),LS was correlated with liver condition indices(P<0.05),but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group(9.30 kPa)than the Pos group(7.40 kPa).When ALT levels were elevated(>40 U/L),the correlations between LS and liver condition indices were not significant(P>0.05).CONCLUSION LS was significantly correlated with most liver condition indices in patients with CHB and HCC.However,these correlations varied according to differences in HBV-DNA and transaminase concentrations.

Chronic hepatitis B and occult infection in chemotherapy patients-evaluation in oncology and hemato-oncology settings:The CHOICE study

BACKGROUND Reactivation of hepatitis B virus(HBV)infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies,including cancer chemotherapy.HBV reactivation can cause significant morbidity and even mortality,which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis.AIM To determine the prevalence of chronic HBV(CHB)and occult HBV infection(OBI)among oncology and hematology-oncology patients undergoing chemo-therapy.METHODS In this observational study,the prevalence of CHB and OBI was assessed among patients receiving chemotherapy.Serological markers of HBV infection[hepatitis B surface antigen(HBsAg)/anti-hepatitis B core antigen(HBc)]were evaluated for all patients.HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc.RESULTS The prevalence of CHB in the study cohort was determined to be 2.3%[95%confidence interval(95%CI):1.0-4.2].Additionally,the prevalence of OBI among the study participants was found to be 0.8%(95%CI:0.2-2.3).CONCLUSION The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy.Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection,which can lead to increased morbidity and mortality.

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.

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.

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.

Incidence of infectious complications is associated with a high mortality in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND In China,hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is the most common liver failure characterized by serious clinical syndromes of liver decompensation with a very high mortality.Bacterial and/or fungal infections are the most common complications that are associated with high short-term mortality.Bacterial translocation from the intestine,impaired hepatic clearance,and immune paralysis of circulating immune cells are thought to contribute to infectious complications in liver failure.The control of bacterial and fungal infections is the key to improving HBV-ACLF outcomes.Active prevention,early diagnosis,and timely treatment of bacterial and fungal infections are essential for treating HBV-ACLF.AIM To investigate the frequency and role of bacterial and fungal infections in patients with HBV-ACLF.METHODS Patients with HBV-ACLF hospitalized at Taihe Hospital,Hubei University of Medicine from January 2014 to December 2017 were retrospectively enrolled.Patient-related information was retrieved from the hospital case database,including general information,blood biochemistry,complications,etc.According to the occurrence of secondary infection or not,the patients were divided into an infection group and a non-infection group.The sites,types,and incidences of bacterial and fungal infections and the influence of infections on the prognosis of HBV-ACLF were statistically analyzed.The risk factors for infections were assessed by unconditional logistic regression.RESULTS There were 174 cases of HBV-ACLF that met the enrollment criteria,of which 114 (65.52%) were diagnosed with infectious complications.Infections occurred in the abdominal cavity (87 cases),respiratory tract (51 cases),urinary tract (18 cases),and biliary tract (10 cases).Patients with infectious complications had a significantly higher 28-d mortality (70.18%,80/114) than those without (40.00%,24/60)(70.18% vs 40.00%,P < 0.05).And patients with infectious complications had a much higher incidence of non-infectious complications (54.39%,62/114)(54.39% vs 15.00%,P < 0.05),leading to an extremely high 28-d mortality of 88.71%(55/62)(P < 0.05).The grade of liver failure,period of hospital stay ≥ 30 d,age ≥ 45 years,and percentage of neutrophils > 70% were identified as risk factors for infectious complications.CONCLUSION The high incidence of infectious complications in patients with HBV-ACLF is associated with severity and deterioration of the disease and may contribute to the extremely high mortality of these patients.

Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure

AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC >= 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Changes in circulating Foxp3^+ regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure

AIM: To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells, to observe T-cell phenotypes during hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACHBLF) and to analyze changes in Th17 and Treg phenotypes during disease progression.