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<p><b>OBJECTIVE</b>To investigate the effect of different nucleoside analogues on the long-term survival rate of patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV) infection.</p><p><b>METHODS</b>One hundred and eighty patients with HBV-related ACLF were enrolled in this prospective cohort study and divided into a basic treatment group (n=30) and an antiviral treatment group, the latter of which was further subdivided into the lamivudine treatment group (n=66), telbivudine treatment group (n=38) and entecavir treatment group (n=46) according to voluntary choice by the patient.All study participants were followed-up for 24 months. The Kaplan-Meier method was applied for survival analysis.</p><p><b>RESULTS</b>The patients in the four antiviral treatment groups had statistically similar baseline clinical characteristics and 1-month survival rates (Breslow =4.475, P=0.215).However, the basic treatment group had a significantly lower survival rate than the antiviral treatment groups that received lamivudine, telbivudine, or entecavir (all P less than 0.05) at the treatment periods of 2, 3, 6, 12 and 18-months; however, these three treatment groups showed no significant differences in survival rates. At the time point of 24 months of treatment, the basic treatment group retained its lower rate of survival than the three antiviral treated groups (lamivudine:Breslow =5.604, P=0.018; telbivudine:Breslow =5.621, P=0.018; entecavir:Breslow =14.701, P less than 0.001); while the survival rates were similar for the lamivudine treatment group and the telbivudine treatment group at this time point, their survival rates were significantly lower than that of the entecavir treatment group (Breslow =4.010, P=0.045; Breslow =4.307, P=0.038).Stratification analysis showed that when the baseline was 30 less than PTA less than or equal to 40 or MELD less than or equal to 29 or HBV DNA more than or equal to 5 log10 IU/mL, the cumulative survival rates of the basic treatment group and antiviral treatment group were statistically similar even though the patients had completed 1 month of treatment After being treated for 2, 3, 6, 12, 18 and 24 months, the cumulative survival rates of the basic treatment group were consistently below those of the overall antiviral treatment group (P less than 0.05). The cumulative survival rate of the basic treatment group followed-up for 1 to 24 months, with PTA values between 20 and 30, was lower than that of the overall antiviral treatment group (P less than 0.05); two groups of patients with PTA less than or equal to 20 or MELD more than or equal to 30 were followed-up for 1 months to 24 months, and their cumulative survival rates showed no significant difference (P more than 0.05). Among the patients whose baseline was HBV DNA less than 5 log10 IU/mL, the comparison of survival rates between the basic treatment group and the overall antiviral treatment group showed no significant differences after treatment for 1, 2, 3, 6, 12 or 18 months, and the survival rate was lower than that of the overall antiviral treatment group (Breslow =4.055, P=0.044) after 24 months.</p><p><b>CONCLUSION</b>Nucleoside analogues can improve the long-term survival rate of HBV-related ACLF patients.Entecavir is preferred for the long-term treatment of these patients.Patients in the early and middle stages of this disease and HBV DNA-positive patients should adopt antiviral treatment as early as possible.</p>
Subject(s)
Humans , Acute-On-Chronic Liver Failure , Antiviral Agents , Cohort Studies , Guanine , Hepatitis B virus , Hepatitis B, Chronic , Lamivudine , Prospective Studies , Survival Analysis , Survival Rate , Thymidine , Time FactorsABSTRACT
Objective To investigate the risk factors for the presence of hepatic encephalopathy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) in the midphase.Methods A total of 287 patients with HBV-related ACLF in the mid-phase were recruited.Clinical data (age,gender,diabetes,liver cirrhosis,upper gastrointestinal hemorrhage,spontaneous bacterial peritonitis,and pulmonary infection) and laboratory findings [albumin,globulin,total bilirubin (TBil),alanine transaminase (ALT),aspartate aminotransferase (AST),glutamyl transpeptidase (γ-GT),alkaline phosphatase,total cholesterol,cholinesterase,creatinine,prothrombin activity (PTA),international normalized ratio,alpha-fetoprotein (AFP),loads of HBV DNA,serum potassium,serum sodium,white blood cell,and platelet count] were included as potential risk factors and analyzed with univariate and multivariate Logistic regressions.Results Multiple Logistic regression analysis indicated that serum potassium(B =-2.006,P =0.000,OR =0.135,95％CI:0.051-0.353),serum sodium(B=-0.096,P=0.014,OR=0.908,95％CI..0.841-0.981),pulmonary infection (B =1.648,P =0.018,OR =5.199,95 ％ CI:1.326-20.386),AFP (B=-0.010,P =0.024,OR =0.990,95％ CI:0.982-0.999) were correlated with hepatic encephalopathy.Conclusion Hypokalemia,hyponatremia,pulmonary infection and low levels of AFP are independent risk factors of the presence of hepatic encephalopathy in patients with HBV-related ACLF in the mid-phase.
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Objective The aim of this study was to analyze risk factors which may affect prognosis of patients with hepatits B virus (HBV)-related liver failure,and to construct a model for prognostic evaluation and further assess its predictive ability.Methods In this retrospective cohort study,569 hospitalized patients who were diagnosed with HBV-related liver failure from January 2007 to December 2010 were enrolled.All the patients were followed up and survival analysis was performed using the Kaplan-Meier method.Univariate and multivariate COX proportional hazards regression analyses were applied to variables such as age,sex,complications,biochemical markers,coagulation markers,and HBV DNA levels to construct a model for prognostic evaluation,and 79 independent cases of HBV-related liver failure were used to confirm the model's predictive ability.Accuracy of the constructed model and model for end-stage liver disease (MELD) was evaluated by receiver operating characteristic (ROC) curves.Results The median survival time for all the patients was 59 days.The survival rates at 1,3,6 months were 58.9％,46.2％ and 45.5％,respectively;and survival rates at 1 and 3 years were 44.9％ and 44.5％,respectively.Hepatic encephalopathy,pulmonary infection,upper gastrointestinal bleeding (UGIB),albumin (Alb),aspartate aminotransferase (AST),creatinine (Cr),international normalized ratio (INR) were determined to be independent risk factors (all P＜0.01) which may affect survival of patients with HBV related liver failure.Accordingly,the prognostic index (PI) of the constructed model for prognostic evaluation 4.98 × assignment of hepatic encephalopathy + 4.57 × assignment of pulmonary infection + 4.41 ×assignment of UGIB-9.69 ×lm[Alb (g/L)]+2.46 ×ln[AST (U/L)]+5.18×ln[Cr (mmol/L)]+3.35×ln (INR) 15.36.The area under receiver operating characteristic curve was 0.838 for the constructed model assessing 90-d survival of the patients,and was 0.751 for model for end-stage liver disease,with no significant difference between the two models (Z=1.085,P =0.278).Conclusions Prognosis of patients with HBV-related liver failure can be accurately predicted by the constructed prognostic assessment model,which is consisted of hepatic encephalopathy,pulmonary infection,UGIB,Alb,AST,Cr,and INR as independent risk factors,and is able to predict the 90 d survival.
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Objective To investigate the predictive factors of virological response in HBeAg-positive chronic hepatitis B (CHB)patients treated with adefovir dipivoxil (ADV).Methods A total of 203 HBeAg-positive CHB patients treated with ADV (Mingzheng)10 mg once daily for 48 weeks were recruited.The gene polymorphisms at positions-238 and-308 in tumor necrosis factor (TNF)-α promoter region were determined by the restriction fragment length polymorphism assay of products amplified using polymerase chain reaction (PCR-RFLP).The serum levels of TNF-a at baseline were measured by enzyme linked immunosorbent assay (ELISA).Hepatitis B virus (HBV)genotypes were tested by real-time fluorescent quantitative PCR and HBV subgenotypes were tested by HBV S gene sequencing.Factors related to ADV response were determined by Logistic regression analysis.Results The HBV DNA negative rate,alanine aminotransferase (ALT)normalization rate,HBeAg loss rate and seroconversion rate,and combined response rate at week 24 and 48 of treatment in 203 patients were 31.5% (64/203),59.1% (120/203),15.8% (32/203),8.9% (18/203),13.3% (27/203)and 58.6% (119/203),78.3% (159/203),29.6% (60/203),16.7% (34/203),25.6% (52/203),respectively.HBV DNA negative rate at week 24 was higher in patients with HBV genotype B,that was higher in patients with TNF-α-308G/A genotype,and that was higher in patients with higher baseline ALT level or lower baseline HBV DNA level [OR = 0.405,95 % CI (0.191 - 0.859),P =0.019;OR=0.292,95%CI(0.132-0.643),P=0.002;OR=0.933,95%CI(0.989-0.997),P＜0.01 ;OR=2.089,95%CI (1.412-3.092),P＜0.01].Meanwhile,HBV DNA negative rate at week 48 were higher in patients with higher HBV DNA negative rate at week 24 or higher baseline ALT level [OR=0.029,95%CI(0.007-0.126),P＜0.01;OR= 0.995,95%CI(0.991-0.999),P=0.016].Conclusions HBV genotype,TNF-α-308 genotype,baseline levels of ALT and HBV DNA are predictors of virological response at week 24 in HBeAg-positive CHB patients treated with ADV.And the HBV DNA negative rate at week 24 and baseline ALT level are predictors of virological response at week 48.
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Objective To investigate the predictive value of TNFα,ALT,HBV DNA loads and HBV serological markers in response to adefovir dipivoxil (ADV) treatment for patients with chronic hepatitis B(CHB).Methods Two hundred and three HBeAg.positive CHB patients were administered with ADV 10 mg/d for 48 weeks.HBV serological markers and TNFα at the baseline were determined by enzyme linked immunosorbent assay(EUSA),and HBV DNA loads were detected by PCR.Logistic regression was used to identify predictive factors for serological response at 48th week after the treatment.Results The rates of HBV DNA clearance,ALT normalization,HBeAg lOSS,HBeAg seroconversion and response at 24th week were 31.5%(64/203),59.1%(120/203),15.8%(32/203).8.9%(18/203)and 13.3%(27/203)respectively,while those at 48th week were 58.6%(119/203),78.3%(159/203),29.6%(60/203),16.7%(34/203)and 25.6%(52/203),respectively.Patients who achieved HBeAS loss at 48th week were found to have higher rates of HBV DNA clearance.HBeAg loss and seroconversion at 24th week and higher TNFα at baseline(P=0.017,0.ooI,0.029 and 0.040),while those who achieved HBeAg seroconversion at 48th week were found to have higher rate of HBeAg seroconversion at 24th week.and lower baseline HBV DNA loads(P=0.000 and 0.004).Conclusion For HBeAg.positive CHBpatients with ADV treatment,the rate of HBV DNA clearanee,HBeAg loss and seroeonversion at 24th week and TNFα at baseline may be used to predict the rate of HBeAg 1088 at 48th week:the rate of HBeAgseroconversion at 24th week and baseline HBV DNA loads may be used to predict the rate of HBeAgseroeonversion at 48th week.