De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.

Effects of entecavir and lamivudine for hepatitis B decompensated cirrhosis: Meta-analysis

AIM:To compare the effects of entecavir(ETV)and lamivudine(LAM)for the treatment of hepatitis B decompensated cirrhosis using a meta-analysis.METHODS:We conducted a literature search for all eligible studies published prior to May 30,2013 using PUBMED,MEDLINE,EMBASE,the China National Knowledge Infrastructure(CNKI),the VIP database,the Wanfang database and the Cochrane Controlled Trial Register.Randomized controlled trials(RCTs)comparing ETV with LAM for the treatment of hepatitis B decompensated cirrhosis were included.The data were analyzed with Review Manager Software 5.0.2.We used RR as an effect measure,and reported its95%CI.The meta-analysis was performed using either a fixed-effect or random-effect model,based on the absence or presence of significant heterogeneity.Two reviewers assessed the risk of bias and extracted data independently and in duplicate.The analysis was executed using the main outcome parameters including hepatitis B virus(HBV)DNA undetectability,HBV DNA level,hepatitis B e antigen(HBeAg)seroconversion,alanine aminotransferase(ALT)level,albumin level,total bilirubin(TBIL)level,prothrombin time activity(PTA)level,Child-Turcotte-Pugh(CTP)score,mortality,drugresistance,and adverse reactions.Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics and the therapeutic effects of the two agents.RESULTS:Thirteen eligible trials(873 patients in total)were included and evaluated for methodological quality and heterogeneity.Of these studies,all had baseline comparability,12 of them reported baseline values of the two treatment groups in detail.Following various treatment durations(12,24,36,48 and>48 wk),both ETV and LAM significantly reduced HBV DNA level,however,reductions were greater in the ETV group(MD=-0.66,95%CI:-0.83-0.50,P<0.00001),(MD=-0.93,95%CI:-1.36-0.51,P<0.0001),(MD=-1.4,95%CI:-1.78-1.01,P<0.00001),(MD=-1.18,95%CI:-1.90-0.46,P=0.001),(MD=-0.14,95%CI:-0.17-0.11,P<0.00001,respectively).At 12,24 and48 wk of treatment,ETV had a significant effect on the rate of HBV DNA undetectability(RR=1.55,95%CI:1.22-1.99,P=0.0004),(RR=1.25,95%CI:1.13-1.38,P<0.0001),(RR=1.2,95%CI:1.10-1.32,P<0.0001,respectively).Although HBeAg seroconversion in the ETV group was more pronounced than that in the LAM group at 24 wk(27.90%vs 26.19%)and 48 wk(31.52%vs 25.00%)of treatment,there was no statistically significant difference between them(RR=1.49,95%CI:0.98-2.28,P=0.07),(RR=1.27,95%CI:0.98-1.65,P=0.07,respectively).Following various treatment durations,both the ETV group and the LAM group showed significantly improved liver function(ALT,AIB,TBIL,PTA and CTP levels)and reduced mortality(ETV 6.37%,LAM 7.89%).The effects in the ETV group(0.33%)were statistically lower than those in the LAM group(14.33%)regarding the rate of drug-resistance(RR=0.1,95%CI:0.04-0.24,P≤0.00001).In addition,no severe adverse reactions were observed in the two treatment groups.CONCLUSION:ETV and LAM significantly improved liver function and reduced mortality.Both drugs produced similar serological responses,and were safe and well tolerated.However,ETV resulted in a better virological response and lower drug-resistance,but is more expensive.

Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis

AIM To investigate survival rate and incidence of hepatocellular carcinoma(HCC) in patients with decompensated cirrhosis in the antiviral era.METHODS We used the Korean Health Insurance Review and Assessment. Korea's health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines.Overall, 48365 antiviral treatment-na?ve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1 st decompensated chronic hepatitis B(CHB) and treatment-na?ve patients(n = 7166). RESULTS The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1^(st) decompensated CHB treatment-na?ve subjects. But the annual mortality rates sharply decreased to 3.4%(2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5%(1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-na?ve patients was 3.4%(2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-na?ve patients.CONCLUSION Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.

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.

Danshao Huaxian capsule in treatment of decompensated cirrhosis resulting from chronic hepatitis B

BACKGROUND: The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are ourweight serious sideeffects and the risk of fatal exacerbation of disease. Danshao Huaxian capsule rapidly reduces hepatitis B virus(HBV)-DNA in serum to undetectable levels. METHODS: A total of 35 patients with chronic hepatitis B and decompensated cirrhosis were treated with Danshao Huaxian 1.2g. po. tid daily. Before the treatment, HBVDNA in serum was positive in all patients. Ten patients had Child-Pugh class B and 25, class C hepatitis B. Seven patients underwent liver transplantation within 6 months of initial treatment. Of the 10 patients of class B, 5 died within 6 months, and the other 5 did not complete the treatment for some reasons; the 25 patients of class C were treated for at least 6 months (mean =19 months). RESULTS: In most of the 25 patients, liver function was improved slowly but markedly after 9 months of treatment, showing a decreased level of serum bilirubin from 67±13 to 30±4μmol/L (P<0.05, baseline vs.6 months), an increased level of serum albumin from 27±1 to 34±1 g/L(P<0.05) and a decreased level of Child-Pugh score from 10.3±0.4 to 7.5+0.5 (P<0.05). Three patients developed resistance to Danshao Huaxian because of a mutation in the YMDD motif, but liver function was not deteriorated. Inhibition of viral replication with Danshao Huaxian resulted in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term results remain uncertain. CONCLUSION: Danshao Huaxian capsule is effective in inhibiting viral DNA replication in patients with decompensated cirrhosis and making clinical improvement.

Short Term Efficacy of Entecavir in the Treatment of Decompensated Chronic Hepatitis B Cirrhosis

Objective:To explore the effect of entecavir on patients with decompensated chronic hepatitis B cirrhosis.Methods:From October 2007 to December 2019,100 patients with decompensated chronic hepatitis B cirrhosis who were treated in our hospital were selected to carry out this study.The clinical data of the patients were analyzed.According to whether entecavir treatment was carried out,100 patients were divided into two groups,50 cases in the control group and 50 cases in the observation group.The control group was treated with conventional drugs,and the observation group was treated with entecavir.Liver function indexes,liver fibrosis indexes,HBV-DNA negative conversion rate and incidence of adverse reactions were compared between the two groups.Results:Compared with the control group,the liver function indexes of the observation group were lower,P<0.05;Compared with the control group,the observation group was better,P<0.05;The negative rate of HBV-DNA in the observation group was lower than that in the control group(P<0.05);There was no difference in the incidence of adverse reactions between the two groups,P>0.05.Conclusion:Entecavir can not only improve the liver function,but also enhance the shortterm treatment effect,without increasing adverse reactions,and has high safety,which is worthy of recommendation.

Lamivudine treatment enabling right hepatectomy for hepatocellular carcinoma in decompensated cirrhosis

A 69-year-old man was admitted to our hospital in October 2003,for further examination of two liver tumors.He was diagnosed with hepatocellular carcinoma(HCC) arising from decompensated hepatitis B virus(HBV)-related cirrhosis.Long-term lamivudine administration improved liver function dramatically despite repeated treatment for HCC.His Child-Pugh score was 9 points at start of lamivudine treatment,improving to 5 points after 1 year.His indocyanine green at 15 min after injection test score was 48%before lamivudine treat-ment,improving to 22%after 2 years and to 5%after 4 years.Radiofrequency ablation controlled the HCC foci and maintained his liver function.In April 2009,abdominal computed tomography revealed a tumor thrombus in the right portal vein.Since his indocyanine green test results had improved to less than 10%,we performed a right hepatectomy,which was successful.To our knowledge,there have been no documented reports of patients undergoing successful right hepatectomy for HCC arising from decompensated cirrhosis.The findings observed in our patient indicate the importance of nucleoside analogs for treating HBV-related HCC.

Collagen proportionate area of liver tissue determined by digital image analysis in patients with HBV-related decompensated cirrhosis

BACKGROUND: The accurate assessment of the degree of hepatic fibrosis plays a critical role in guiding the diagnosis, treatment and prognostic assessment of chronic liver diseases. Liver biopsy is currently the most reliable method to evaluate the severity of hepatic fibrosis. However, liver biopsy is an invasive procedure associated with morbidity and mortality, and has several limitations in patients with decompensated cirrhosis. There is no report on the collagen proportionate area (CPA) of liver tissue in the decompensated stage of cirrhosis. This study aimed to determine the CPA of resected liver tissue samples from patients with HBV-related decompensated cirrhosis using digital image analysis, and to analyze the relationship between the CPA and liver functional reserve. METHODS: Fifty-three resected liver tissue samples from liver transplant patients with chronic hepatitis B-induced decompensated cirrhosis were stained with Masson’s trichrome, and the CPA in these samples was quantitatively determined using digital image analysis. The values of relevant liver function just before liver transplantation, the CPA in liver tissue, and their correlation were analyzed. RESULTS: The mean CPA at the decompensated stage of cirrhosis was 35.93±14.42% (11.24%-63.41%). The correlation coefficients of the CPA with a model for end-stage liver disease score, serum total bilirubin and international standard ratio of prothrombin B were 0.553, 0.519 and 0.533, respectively (P<0.001). With increasing CPA values, the three indices reflecting liver functional reserve also changed significantly.CONCLUSIONS: The degree of fibrosis may be correlated with the functional reserve. With the advancement of fibrosis, the liver functional reserve is attenuated accordingly.

Antiviral drug resistance increases hepatocellular carcinoma:A prospective decompensated cirrhosis cohort study

AIM:To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.METHODS:Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort.With two years of follow-up,198patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed.RESULTS:Among the antiviral treatment patients,162had a complete virological response(CVR),and 36 were drug-resistant(DR).The two-year cumulative incidence of hepatocellular carcinoma(HCC)in the DR patients(30.6%)was significantly higher than that in both the CVR patients(4.3%)and the control group(10.3%)(P<0.001).Among the DR patients in particular,the incidence of HCC was 55.6%(5/9)in those who failed rescue therapy,which was extremely high.The rtA181T mutation was closely associated with rescue therapy failure(P=0.006).The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline(8.9±2.3 vs 6.0±1.3,P=0.043).CONCLUSION:This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients,especially in those who failed rescue therapy.

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.

Risk factors for hepatic decompensation in patients with primary biliary cirrhosis

AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) patients.METHODS:From 1995 to 2010,PBC patients without hepatic decompensation seen at the Peking Union Medical College Hospital were enrolled.Clinical signs and manifestations(pruritus,persistent fatigue,jaundice and pain in the right hypochondrium),laboratory parameters(auto-antibodies for autoimmune hepatic disease,biliary and hepatic enzymes,immunoglobulin,bilirubin,and albumin) and imaging findings were recorded at entry and at specific time points during follow-up.Cox regression and Kaplan-Meier analyses,respectively,assessed the risk factors for hepatic decompensation and survival.RESULTS:Two hundred and sixty-two PBC patients were enrolled with a median follow-up of 75.2 mo(range,21-201 mo).The 240 patients were aged 51.5 ± 10.2 years at diagnosis and 91.6% were female.Two hundred and forty-five(93.5%) were seropositive for anti-mitochondrial antibodies.At presentation,170 patients(64.9%) were symptomatic,while 96 patients(36.6%) had extra-hepatic autoimmune disease.During the follow-up period,62(23.7%) patients developed hepatic decompensation of whom four underwent liver transplantation and 17 died.The cumulative survival rate and median survival time were 83.9% and 181.7 mo,respectively.Cox regression analysis revealed that an incomplete ursodeoxycholic acid(UDCA) response or inconsistent treatment [P < 0.001;hazard risk(HR) 95%CI = 2.423-7.541],anti-centromere antibodies(ACA) positivity(P < 0.001;HR 95%CI = 2.516-7.137),alanine aminotransferase ratio(AAR) elevations(P < 0.001;HR 95%CI = 1.357-2.678),and histological advanced liver disease(P = 0.006;HR 95%CI = 1.481-10.847) were predictors of hepatic decompensation.The clinical features and survival of PBC in China are consistent with those described in Western countries.CONCLUSION:Incomplete UDCA response or inconsistent treatment,ACA positivity,AAR elevations,and advanced histological stage are predictors of decompensation.

HBV相关肝病患者外周血T细胞及细胞因子水平研究

背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关慢性肝病患者外周血T细胞亚群计数、细胞因子变化特点及关联性.方法本研究为一项观察性研究,共纳入慢性乙型肝炎(chronic hepatitis B,CHB)患者65例,肝硬化失代偿期(decompensated cirrhosis,DCC)患者122例,肝细胞癌(hepatocellular carcinoma,HCC)患者109例,收集患者一般信息、病史、治疗情况及实验室检查结果、Child-Paugh分级及HCC患者肿瘤巴塞罗那分期,分析各项指标,尤其是T细胞亚群计数及细胞因子的组间差异及特征.结果HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞水平与Child分级A到C呈负相关.HCC患者CD8^(+)T细胞绝对计数显著低于DCC[240(150-379)cells/μLvs 277(154-435)cells/μL,P<0.05]及CHB[240(150-379)cells/μL vs 452(269-706)cells/μL,P<0.001]患者.白细胞介素(interleukin,IL)-6、IL-8、肿瘤坏死因子(tumor necrosis factor,TNF)-α在HCC组均最高.DCC、HCC患者Child-Paugh分级越差,CD3^(+)、CD8^(+)T细胞水平越低,IL-6水平越高.HCC患者CD3^(+)、CD8^(+)T细胞水平随着肿瘤巴塞罗那分期由A到D呈下降趋势,IL-6呈上升趋势.且肝硬化、HCC患者CD3^(+)(r=-0.340,P<0.001)、CD8^(+)(r=-0.353,P<0.001)T细胞水平与IL-6升高水平呈显著负相关.结论HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞计数与Child分级(由A到C)呈负相关,且IL-6水平与CD8^(+)T细胞计数存在负相关关系.

De novo combination therapy with lamivudine and adefovir dipivoxil in chronic hepatitis B patients

AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function.

Clinical features of acute hepatitis E super-infections on chronic hepatitis B

AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B(CHB) superimposed with hepatitis E virus(HEV).METHODS This retrospective cohort study included 228 patients with acute HEV infection(showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB(confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus(HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases(defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.RESULTS The symptoms caused by superimposed acute hepatitis E(AHE) were much more severe in cirrhotic patients(n = 94) than in non-cirrhotic patients(n = 134), as evidenced by significantly higher liver complications(77.7% vs 28.4%, P < 0.001) and mortality rate(21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients(n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels(OR: 5.1, P = 0.012), alcohol consumption(OR: 6.4, P = 0.020), and underlying diabetes(OR: 7.5, P = 0.003) and kidney diseases(OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.

Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome

Hepatitis B virus(HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin(HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV(entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of "hepatitis B virus AND liver transplantation". We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.

Clinical factors associated with hepatitis B screening andvaccination in high-risk adults

BACKGROUND Hepatitis B virus is a viral infection that can lead to acute and/or chronic liver disease, and hepatocellular carcinoma(HCC). Hepatitis B vaccination is 95% effective in preventing infection and the development of chronic liver disease and HCC due to hepatitis B. In 2011, the Centers for Disease Control updated their guidelines recommending that adults at high-risk for hepatitis B infection be vaccinated against hepatitis B including those with diabetes mellitus(DM). We hypothesize that adults at high-risk for hepatitis B infection are not being adequately screened and/or vaccinated for hepatitis B in a large urban healthcare system.AIM To investigate clinical factors associated with Hepatitis B screening and vaccination in patients at high-risk for Hepatitis B infection.METHODS We conducted a retrospective review of 999 patients presenting at a large urban healthcare system from 2012-2017 at high-risk for hepatitis B infection. Patients were considered high-risk for hepatitis B infection based on hepatitis B practice recommendations from the Center for Disease Control. Medical history including hepatitis B serology, concomitant medical diagnoses, demographics, insurance status and social history were extracted from electronic health records.Multivariate logistic regression was used to identify clinical risk factors independently associated with hepatitis B screening and vaccination.RESULTS Among the 999 patients, 556(55.7%) patients were screened for hepatitis B. Of those who were screened, only 242(43.5%) patients were vaccinated against hepatitis B. Multivariate regression analysis revealed end-stage renal disease[odds ratio(OR): 5.122; 2.766-9.483], alcoholic hepatitis(OR: 3.064; 1.020-9.206),and cirrhosis or end-stage liver disease(OR: 1.909; 1.095-3.329); all P < 0.05 were associated with hepatitis B screening, while age(OR: 0.785; 0.680-0.906),insurance status(0.690; 0.558-0.854), history of DM(OR: 0.518; 0.364-0.737), and human immunodeficiency virus(OR: 0.443; 0.273-0.718); all P < 0.05 were instead not associated with hepatitis B screening. Of the adults vaccinated for hepatitis B,multivariate regression analysis revealed age(OR: 0.755; 0.650-0.878) and DM were not associated with hepatitis B vaccination(OR: 0.620; 0.409-0.941) both P <0.05.CONCLUSION Patients at high-risk for hepatitis B are not being adequately screened and/or vaccinated. Improvements in hepatitis B vaccination should be strongly encouraged by all healthcare systems.

失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与生化及凝血等指标相关性分析

目的分析失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与乙型肝炎病毒标志物、生化及凝血等指标的相关性。方法回顾性分析2018年1月至2020年12月我院收治的645例失代偿期乙型肝炎肝硬化患者的临床资料,根据HBV-DNA水平分为4组:阴性组、低病毒载量组(<2.0×10^(3)IU/mL)、中病毒载量组(2.0×10^(3)~2.0×10^(5)IU/mL)和高病毒载量组(>105IU/mL),测定所有患者乙型肝炎病毒血清学标志物(HBV-M)、肝功能相关生化指标(ALT、AST、TBIL、DBIL、ALB)、凝血相关指标(PT、INR、APTT、TT、D-D、PLT),比较4组患者各项指标的差异,并分析各项指标与HBV-DNA水平的相关性。结果在失代偿期乙型肝炎肝硬化患者中,HBsAg和HBeAg的定量数值随着HBV-DNA水平的升高而增高,HBsAg的明显升高主要体现在HBV-DNA阴性组和低病毒载量组之间(779.40 vs 5773.00IU/mL),而HBeAg的表达在中病毒载量组(0.19 COI)和高病毒载量组(7.96 COI)中才出现显著升高,低病毒载量组的HBeAg阳性表达率较低。随着病毒载量的升高,患者的ALT、AST、TBIL、DBIL、D/T、AFP指标均有所升高,而ALB的水平降低;除TT存在显著性差异外,PT、APTT、INR、Fib、D-D、PLT这6个指标差异均无统计学意义。经Pearson相关性分析检验,失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与ALT、AST、TBIL、DBIL、AFP、PT、APTT、TT、D-D、HBsAg、HBeAg水平呈正相关(r>0,P均<0.05),与ALB、Fib水平呈负相关(r<0,P均<0.05),与PLT、HBeAb水平不存在相关性。结论在失代偿期乙型肝炎肝硬化患者中,血清HBV-DNA载量与HBsAg、HBeAg表达水平密切相关,与ALT、AST、TBIL、DBIL、D/T、ALB等肝功能相关生化指标相关,与凝血相关指标存在关联,但在不同HBV-DNA载量组中无差异。HBV-DNA载量可作为HBeAg阴性患者肝脏损害程度的有效预测指标。

Does antiviral therapy reduce complications of cirrhosis?

Chronic hepatitis B infection is associated with the development of cirrhosis,hepatocellular carcinoma,and finally liver-related mortality.Each year,approximately,2%-5%of patients with hepatitis B virus(HBV)-related compensated cirrhosis develop decompensation,with additional clinical manifestations,such as ascites,jaundice,hepatic encephalopathy,and gastrointestinal bleeding.The outcome of decompensated HBV-related cirrhosis is poor,with a 5-year survival of 14%-35%compared to 84%in patients with compensated cirrhosis.Because the risk of disease progression is closely linked to a patient’s serum HBV DNA level,antiviral therapy may suppress viral replication,stabilize liver function and improve survival.This article briefly reviews the role that antiviral therapy plays in cirrhosis complications,particularly,in decompensation and acute-on-chronic liver failure.

Antiviral therapy of decompensated hepatitis B virus-related cirrhosis

Objective To review the development,mechanism,necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis.Data sources Most information was pulled from a literature search （Pubmed 2000 to 2011） using the keywords of antiviral and decompensated hepatitis B virus-related cirrhosis.Relevant book chapters were also reviewed.Study selection Well-controlled,prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected.Results Specific antiviral agents not only control viral replication,which permits liver transplantation,but also improve liver function so significantly that patients could be removed from the transplant waiting list.However,the emergence of drug-resistant mutants can result in treatment failure.Combination therapy is a save-strategy in drug-resistant.Conclusions Although the treatment of end-stage liver disease is still a challenge worldwide,antiviral therapy has altered the natural history of hepatitis B patients with decompensated cirrhosis.The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance.A combination of antivirals may be one of the future strategies for fulfilling these goals.

Prognosis of 153 patients with decompensated hepatitis B virus-related cirrhosis is improved after 3-year continuous lamivudine treatment

Background The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear. The present study attempted to describe the clinical outcomes of lamivudine therapy in these special patients over three years. Methods This study was a retrospective, controlled cohort study which involved 153 patients with decompensated hepatitis B virus-related cJrrhosJs. Of these, 86 patients received lamJvudJne 100 mg daily accompanied with general internal treatment, and the other 67 were given general internal treatment only. Significant clinical responses were recorded after years of antiviral treatment. Results The patients in both groups were matched in terms of age, sex and laboratory results at baseline. After years of therapy, the Child-Pugh-Turcotte scores and laboratory values of the patients receiving lamivudine were remarkably improved compared to the patients in the control group. The mortality rate and the incidence of cirrhosis-related complications were much lower in the lamivudine group than in the control group. Genotypic resistance tyrosine, methionine, aspartate, aspartate mutations developed in 26.7 percent of the patients during 3-year lamivudine treatment, and cirrhosis-related death and the hepatocellular carcinoma were more likely to occur in patients with these mutations than in the other patients who were treated with lamivudine. Conclusions Continuous long-term lamivudine treatment in patients with decompensated hepatitis B virus-related cirrhosis delays clinical progression, and significantly improves hepatic function and prognosis. However, the use of a retrospective control cohort precludes drawin（~ definitive conclusions.