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Objective To investigate the baseline independent prognostic factors for 24 months survival of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) patients treated with telbivudine.Methods The prospective cohort study was conducted in HBV-associated ACLF patients who were hospitalized in Mengchao Hepatobiliary Hospital of Fujian Medical University and volunteered to be treated with telbivudine for more than 24 months.The patients were observed for survival at month 1,3,6,12,and 24 after treatment.The baseline biochemical index,coagulant function,model for end-stage liver disease (MELD) score,HBV DNA level as well as comorbidities were analyzed in this study.The count data were compared with kappa test or Fisher's exact test.For the normal distributed measurement data,the homogeneity test of variances (Levene test) was firstly used for comparison between groups.Further,the group t test was applied for variance homogeneity,while the approximate t test was applied for variance non-homogeneity and the Mann-Whitney U test was applied for the non-distributed measurement data.Results A total of 41 patients were enrolled,including 3 drop-outs and 38 accomplishments.Among these 38 patients,there were 3 females (7.9 ％) and 35 males (92.1％),with ages (38.5 ± 11.1) years.There were 32 patients alive and 6 dead during 1 month's follow-up,while baseline MELD score was the independent prognostic factor (RR=1.864,95％CI:1.151-3.019) for survival.There were 31 patients alive and 7 dead during 3 months' follow-up,while baseline MELD score and upper gastrointestinal hemorrhage (UGH) were the independent prognostic factors (RR =2.053,95％CI:1.163-3.625;RR=394.939,95％CI:1.880-82 948.817).There were both 26 patients alive and 12 dead during 6 and 12 months' follow-up,while baseline MELD score was the independent prognostic factor (RR=1.761,95％ CI:1.230-2.523).At the end of 24 months' follow-up,there were 15 patients alive and 23 dead.Viral rebounds were observed in 6 patients and 3 of them were dead.Baseline HBV DNA level,MELD score and electrolyte imbalance were the independent prognostic factors (RR-9.722,95％ CI:1.607-58.821;RR=l.518,95％ CI:1.066-2.162;RR=87.505,95％ CI:2.263-3 384.232) for 24 months'survival.Conclusions Although telbivudine is not recommended as the first-line treatment,ACLF patients with low MELD score and low HBV DNA level at baseline,individualized treatment may improve patient's survival rate.UGH and electrolyte imbalance may affect the efficacy of telbivudine and reduce the survival rate of ACLF patient.
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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 whether the clinical outcomes of HBV infection are associated with single nucleotide polymorphisms of Toll-like receptor (TLR) 9 gene promoter region.Methods The polymorphisms of three positions at TLR9 gene promoter region including A-1923C, T-1486C and T-1237C were detected using real-time fluorescence quantitative polymerase chain reaction in 96 patients with severe chronic hepatitis B, 156 patients with chronic hepatitis B and 151 cases of HBV spontaneous clearance, then the differences between the groups were analyzed.Analysis of variance was performed for measurement data,and χ2 test or Fisher exact probability test were used for enumeration data.Results The frequency of AC genotype at TLR9 gene A-1923C site in chronic hepatitis B group was 3.8%, which was significantly lower than that in HBV spontaneous clearance group (11.3%) (χ2=6.082, P ＜ 0.05), but no significant difference was found between severe chronic hepatitis B group (8.3%) and HBV spontaneous clearance group (χ2=0.552, P ＞0.05).No significant differences of genotype distribution were found between chronic severe hepatitis B group and HBV spontaneous clearance group , chronic hepatitis B group and HBV spontaneous clearance group at polymorphism sites of T-1486C and T-1237C (χ2=1.534 and 0.745, P ＞ 0.05).Conclusions Genotype AC at TLR9 gene A-1923C site is associated with HBV spontaneous clearance, but not correlated with chronic HBV infection and liver failure; there is no correlation of polymorphisms in T-1486C and T-1237C at TLR9 gene promoter region with the clinical outcomes of HBV infection.
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Objective To investigate the association between promoter polymorphisms of interferon-alpha receptor-1 (IFNAR1) gene and the treatment response to interferon-alpha (IFN-α) in patients with chronic hepatitis B (CHB). Methods Sixty-one CHB patients who consented to receive IFN-a therapy were enrolled in this study. The subjects were treated with recombinant IFN-α2b 500 MU intramuscular injection qod for 48 weeks. The treatment responses were monitored.Meanwhile, the promoters of IFNAR1 gene in these patients were sequenced. Measurement data were analyzed by t test and enumeration data were analyzed by Chi square test. Results Twenty-two treated patients achieved complete response. Eight patients achieved partial response and 31 had no response. Polymorphisms were identified in the promoter of IFNAR1 gene, which included C/T substitution at locus -408, C/T substitution at locus-3 and GT microsatellite repeat sequence at locus-77 [-77(GT)n]. The three polymorphisms were in linkage and composed some haplotypes,such as - 408C/-77(GT)5/-3C. The response rate to IFN-α in CHB patients with genotypes -408C/-77(GT)5/-3C, -408C/-77(GT)5/-3C, and-408C/-77(GT)5/-3C, non -408C/ - 77(GT)5/-3C in IFNAR1 gene promoter was higher than that in patients with genotype non -408C/-77(GT)5/-3C, non-408C/- 77(GT)5/- 3C (61. 0% vs 25. 0%, x2=6. 961, P =0.008). Conclusions CHB patients with genotype-408C/ - 77(GT)5/ - 3C, -408C/-77(GT)5/-3C and -408C/ -77(GT)5/ -3C, non -408C/ -77(GT)5/-3C in the promoter of the IFNAR1 gene are prone to have better response to IFN-a treatment. Polymorphisms in the promoter of IFN-αgene are associated with the treatment response to IFN-α in CHB patients.
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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.