Influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

AIM. To investigate the influence of HLA-DRB1 alleles and HBV genotypes on inberferon-α therapy for chronic hepatitis B. METHODS： HLA-DRBI＊03, ＊07, ＊09,＊12, ＊15 alleles were determined using polymerase chain reaction/sequence specific primer （PCR/SSP） technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. RESULTS： The positivity of HLA-DRB1＊07 allele in chronic hepatitis B group was significantly higher than that in normal control group （X^2 = 6.33, P〈0.025, RR = 2.37）. Among the 126 patients, genotype B was found in 38 （30.2%）, genotype C in 69 （54.8%）, and mixed genotype （B＋C） in 19 （15.0%）, genotypes D-F were not found. Among the 46 DRB1＊07（＋） patients, 7 were responders and 39 were non-responders among them （X^2 = 6.71, P〈0.05）. The positivity of HLADRB1＊07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. CONCLUSION： High positivities of HLA-DRB1 ＊07 allele and HBV genotype C are closely associated with the lower response to interferon-α therapy for chronic hepatitis B.

Correlation of the occurrence of YMDD mutations with HBV genotypes,HBV-DNA levels,and HBeAg status in Chinese patients with chronic hepatitis B during lamivudine treatment

BACKGROUND:Continuous lamivudine therapy is associated with high rates of YMDD mutations,which are the main causes of drug resistance.The current study explores the association of the emergence of YMDD mutations with pretherapy HBV genotype,HBV-DNA levels,HBeAg status,and serum alanine aminotransferase(ALT) levels in Chinese patients receiving lamivudine therapy for chronic hepatitis B.METHODS:A total of 319 chronic hepatitis B patients who received lamivudine therapy for more than a year were enrolled in this study.YMDD mutations,HBV genotype,HBV-DNA levels,HBeAg status,and ALT levels were determined prior to their lamivudine treatment and every three months for a year of this therapy.RESULTS:Among the 319 patients,137(42.95%) were infected with genotype B and 182(57.05%) with genotype C.Up to 94 patients(29.47%) developed YMDD mutations within one year of lamivudine therapy.Furthermore,50 patients with HBV genotype B and 44 patients with genotype C developed YMDD mutations(36.50% vs 24.18%,P<0.05).Logistic regression analysis showed that pretherapy HBV genotype,HBV-DNA levels,and HBeAg status are independent factors for the emergence of YMDD mutations(HBV genotype:OR=2.159,95% CI 1.291-3.609,P=0.003;HBV-DNA:OR=1.653,95% CI 1.231-2.218,P=0.001;HBeAg:OR=2.021,95% CI 1.201-3.399,P=0.008).CONCLUSIONS:HBV genotype,HBV-DNA levels,and HBeAg status at baseline are the independent factors associated with the emergence of YMDD mutations among Chinese patients receiving lamivudine therapy for chronic hepatitis B.These findings are helpful to the development of therapeutic strategies for these patients.

Distribution of HBV genotypes among HBV carriers in Benin:phylogenetic analysis and virological characteristics of HBV genotype E

AIM: To determine the distribution of Hepatitis B virus (HBV) genotypes in Benin, and to clarify the virological characteristics of the dominant genotype.METHODS: Among 500 blood donors in Benin, 21 HBsAg-positive donors were enrolled in the study. HBV genotypes were determined by enzyme immunoassay and restriction fragment length polymorphism. Complete genome sequences were determined by PCR and direct sequencing.RESULTS: HBV genotype E (HBV/E) was detected in 20/21 (95.2%), and HBV/A in 1/21 (4.8%). From the age-specific prevalence of HBeAg to anti-HBe seroconversion (SC) in 19 HBV/E subjects, SC was estimated to occur frequently in late teens in HBV/E.The comparison of four complete HBV/E genomes from HBeAg-positive subjects in this study and five HBV/E sequences recruited from the database revealed that HBV/E was distributed throughout West Africa with very low genetic divers ity (nucleotide homology 96.7-99.2%).Based on the sequences in the basic core promoter (BCP)to precore region of the nine HBV/E isolates compared to those of the other genotypes, a nucleotide substitution in the BCP, G1757A, was observed in HBV/E.CONCLUSION: HBV/E is predominant in the Republic of Benin, and SC is estimated to occur in late teens in HBV/E. The specific nucleotide substitution G1757A in BCP, which might influence the virological characteristics,is observed in HBV/E.

Distribution of hepatitis B virus genotypes:Phylogenetic analysis and virological characteristics of Genotype C circulating among HBV carriers in Kolkata,Eastern India

AIM: To evaluate the genotype distribution of hepatitis B virus (HBV) in Eastern India and to clarify the phyloge- netic origin and virological characteristics of the recently identifi ed genotype C in this region. METHODS: Genotype determination, T1762/A1764 mutation in the basal core promoter (BCP) and A1896 mutation in the precore region of 230 subjects were de- termined by restriction fragment length polymorphism method (RFLP) and the result was confi rmed by direct sequencing. RESULTS: The predominant genotypes D (HBV/D) and A (HBV/A) were detected in 131/230 (57%) and 57/230 (25%) samples. In addition, genotype C (HBV/C) was detected in 42/230 (18%) isolates. Surface gene region was sequenced from 45 isolates (27 HBV/C, 9 HBV/A and 9 HBV/D). Phylogenetic analysis revealed that all of the HBV/C sequences clustered with South East Asian subgenotype (HBV/Cs). The sequence data showed re- markable similarity with a Thai strain (AF068756) (99.5% ± 0.4% nucleotide identities) in 90% of the genotype C strains analyzed. T1762/A1764 mutation in BCP re- gion, associated with high ALT was signifi cantly higher in HBeAg negative isolates than HBeAg positive isolates. Frequency of A1896 mutation leading to HBeAg negativ- ity was low.CONCLUSION: The present study reports the genotypic distribution and the characteristics of partial genome sequences of HBV/C isolates from Eastern India. Low genetic diversity and confi nement of HBV/C in Eastern India possibly indicate a recent, limited, spread in this region. Genotype C with T1762/A1764 mutation has been reported to increase the risk for hepatocellular car- cinoma; therefore genotype C carriers in Eastern India should be carefully monitored.

Intrahepatic HBV DNA as a predictor of antivirus treatment efficacy in HBeAg-positive chronic hepatitis B patients

AIM： To evaluate the effect of antiviral agents on intrahepatic HBV DNA in HBeAg-positive chronic hepatitis B patients. METHODS： Seventy-one patients received treatment with lamivudine, interferon alpha （IFN-α2b） or sequential therapy with lamivudine-IFN-α2b for 48 wk. All subjects were followed up for 24 wk. Serum and intrahepatic HBV DNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP. RESULTS： At the end of treatment, the intrahepatic HBV DNA level in 71 patients decreased from a mean of （6.1 ± 1.0） Iog10 to （4.9± 1.4） Iog10. Further, a larger decrease was seen in the intrahepatic HBV DNA level in patients with HBeAg seroconversion. Intrahepatic HBV DNA level （before and after treatment） was not significantly affected by the patients＇ HBV genotype, or by the probability of virological flare after treatment. CONCLUSION： Intrahepatic HBV DNA can be effectively lowered by antiviral agents and is a significant marker for monitoring antivirus treatment. Low intrahepatic HBV DNA level may achieve better efficacy of antivirus treatment.

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong,China

Background:Hepatitis B surface antigen(HBsAg)clearance is vital for a functional cure of hepatitis B virus(HBV)infection.However,the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus(HIV)remain largely unknown in Guangdong,China.Methods:Between 2009 and 2019,patients co-infected with HBV/HIV undergoing antiretroviral therapy(ART)in Guangzhou Eighth People’s Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31,2020.The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses.Results:A total of 1550 HBV/HIV co-infected patients were included in the study,with the median age of 42 years and 86.0%(1333/1550)males.Further,98.3%(1524/1550)received ART containing tenofovir disoproxil fumarate(TDF)plus lamivudine(3TC).HBV DNA was examined in 1283 cases at the last follow-up.Over the median 4.7 years of follow-up,8.1%(126/1550)patients achieved HBsAg seroclearance,among whom 50.8%(64/126)obtained hepatitis B surface antibody,28.1%(137/488)acquired hepatitis B e antigen seroconversion,and 95.9%(1231/1283)undetectable HBV DNA.Compared with patients who maintained HBsAg positive,cases achieving HBsAg seroclearance showed no differences in age,gender,CD4+T cell count,alanine aminotransferase(ALT)level,or fibrosis status;however,they presented lower HBV DNA levels,lower HBsAg levels,and higher rates of HBV genotype B at the baseline.Multivariate analysis showed that baseline HBsAg<1500 cutoff index(COI)(adjusted hazard ratio[aHR],2.74,95%confidence interval[95%CI]:1.48-5.09),ALT elevation>2×upper limit of normal during the first six months after receiving ART(aHR,2.96,95%CI:1.53-5.77),and HBV genotype B(aHR,3.73,95%CI:1.46-9.59)were independent predictors for HBsAg seroclearance(all P<0.01).Conclusions:Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients.Lower baseline HBsAg levels,HBV genotype B,and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.