Home About us Contact
|
Home About us Contact | ||
|
|
||
HBV Genotypes (hbv + genotype)
Terms modified by HBV Genotypes Selected AbstractsSerum hepatitis B surface antigen and hepatitis B e antigen titers: Disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers,,HEPATOLOGY, Issue 6 2010Alexander J.V. Thompson Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication in vivo. In all, 149 treatment-naïve CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA (r = 0.69, 0.71, 0.76, P < 0.01). HBeAg correlated with serum HBV DNA (r = 0.60, P < 0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA (r = 0.28, P = 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients. Conclusion: The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker. (HEPATOLOGY 2010) [source] Prediction of response to treatment of chronic hepatitis B with pegylated interferon in the PhilippinesJOURNAL OF MEDICAL VIROLOGY, Issue 2 2010Dorothy M. Agdamag Abstract The response marker for interferon has not been investigated fully for hepatitis B viruses (HBVs) in the Philippines where novel subtypes B5 and C5 were recognized recently. The prediction parameters for interferon treatment were assessed, with emphasis on the mutation patterns in the basal core promoter and precore regions in patients with chronic hepatitis B. Seventeen HBeAg-positive patients were stratified according to response to treatment with pegylated interferon based on HBe seroconversion and HBV load. Intra-patient distributions of wild-type strains (A1762, G1764) and variants (T1762, A1764) were analyzed using HBV-DNA amplification and subsequent molecular cloning. The rate of variants (T1762, A1764) harbored by a patient was higher among responders (41.2% and 31% per person on average) than among non-responders (2.4% and 2.4%) to treatment with pegylated interferon at the baseline, respectively (P,<,0.05). The rate of variants (T1762, A1764) harbored by responders (41.2% and 31%) decreased to 1.7% and 1.7%, and wild-type strains (A1762, G1764) conversely became majority (98.3% and 98.3%) after treatment with pegylated interferon, respectively. HBV strains harbored by two of six responders and a patient with lower baseline load (1.0,×,104,copies/ml) showed genotype shift from A to other genotypes, where genotype A disappeared preferentially after the loss of HBeAg and genotypes B and C formed a major population. These results suggest that the HBV variants (T1762, A1764) and HBV genotype A in the Philippines have an advantage in the response to pegylated interferon. These results warrant a large-scale examination for further precise prediction of the response to treatment with interferon. J. Med. Virol. 82:213,219, 2010. © 2009 Wiley-Liss, Inc. [source] A serological and molecular survey of hepatitis B in children 15 years after inception of the national hepatitis B vaccination program in eastern China,JOURNAL OF MEDICAL VIROLOGY, Issue 9 2009Ying Dong Abstract The emergence of mutations in the hepatitis B virus (HBV) S gene has threatened the long-term success of vaccination programs since the worldwide introduction of effective vaccines against hepatitis B. This study was conducted on 5,407 children (0,8 years old) in eastern China in 2007. We analyzed the prevalence of HBsAg, anti-HBs, and "a"-determinant mutations in the HBV S gene by microparticle enzyme immunoassays, PCR, and DNASTAR software. The total HBsAg prevalence was 1.52% (82/5,407) in the children and increased with age. In contrast, the positive rate (65.42%, 2,374/3,629) and the titers of anti-HBs decreased with age. The predominant infection was HBV of genotype C and serotype adr (45/51; 88% of cases). Mutations of I126T, amino acid 137 (nt553T deletion mutation), G145A, G145R, and F158S were found in the children; the mutations of amino acid 137 and F158S have not been reported previously. The total prevalence of mutant strains was 14% (7/51). To investigate whether the infection resulted from maternal transmission, we compared the S gene sequences in 16 mother,child pairs. Fourteen mother,child pairs exhibited the same HBV genotype, with 99.5,100% sequence homology in the S gene, while two pairs exhibited different genotypes. This study suggested that the hepatitis B vaccination strategies in eastern China have been successful. Although the emergence of "a"-determinant mutations in the HBV S gene have resulted in HBV infection in immunized children, this does not pose a threat to the vaccination strategies. The HBV-infected children had contracted the infection via vertical transmission. J. Med. Virol. 81:1517,1524, 2009. © 2009 Wiley-Liss, Inc. [source] Effect of HIV co-infection on mutation patterns of HBV in patients with lamivudine-resistant chronic hepatitis B,,§JOURNAL OF MEDICAL VIROLOGY, Issue 7 2009Fabio Iacomi Abstract A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125,213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co-infected with HIV/HBV. In this latter group, the prevalence of the rtV173L,+,rtL180M,+,rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D,+,sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0,61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5,34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat. J. Med. Virol. 81:1151,1156, 2009. © 2009 Wiley-Liss, Inc. [source] Prevalence of HBV genotypes in Central and Eastern EuropeJOURNAL OF MEDICAL VIROLOGY, Issue 10 2008Katja Deterding Abstract The importance of hepatitis B virus (HBV) genotypes for disease progression and response to interferon-alpha-based treatment is well established. While almost all patients in the Mediterranean area are infected with HBV genotype D, HBV genotype A is dominant in Northern Europe. However, the distribution of HBV genotypes is unknown for several Central and Eastern European countries. Data are described of 1313 HBsAg-positive patients recruited at 14 referral centers in eight countries. There were only very few cases of HBV genotype B, C, E, F, and H infection while HBV genotypes A and D were found in 42% and 48% of patients, respectively. Eight percent of patients had positive bands for more than one genotype using the hybridization assay. The frequency of genotype A was higher in Poland (77%) and the Czech Republic (67%) as compared to Hungary (47%), Lithuania (41%), Croatia (8%), and Germany (32%). In contrast, HBV genotype D was most frequent in Croatian, Romanian, and Russian patients with 80%, 67%, and 93% of cases, respectively. In conclusion, HBV genotype A versus D showed significantly different distribution patterns in Central and Eastern Europe which deserves consideration for national guidelines and treatment decisions. J. Med. Virol. 80:1707,1711, 2008. © 2008 Wiley-Liss, Inc. [source] Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearanceJOURNAL OF MEDICAL VIROLOGY, Issue 8 2007Jinlin Hou Abstract The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon-alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO-LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16-weeks interferon-alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P,=,0.014), or genotype D alone (P,=,0.05). The HBV genome analysis revealed that: (i) after 16-weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P,<,0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P,=,0.001; odds ratio 6.19, 95 confidence interval 1.94,19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon-alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon-based therapies in chronic hepatitis B may vary between different HBV genotypes. J. Med. Virol. 79: 1055,1063, 2007. © 2007 Wiley-Liss, Inc. [source] Molecular epidemiology of hepatitis B virus in Dakar, SénégalJOURNAL OF MEDICAL VIROLOGY, Issue 3 2006Muriel Vray Abstract Using DNA chip technology and real-time quantitative PCR, molecular profile of HBV strains infecting blood donors and patients in Dakar, Sénégal was studied. All HBsAg-positive blood donors (n,=,175) and all patients who presented with chronic hepatitis B (n,=,29) between 1st June 2003 and 31st July 2003 were studied. One patient, a blood donor, was coinfected by HCV, and nine patients had anti-HDV antibodies. Few persons in either group were HBeAg-positive. Viral load values were relatively low but correlated with biochemical abnormalities. Patients were infected mainly by genotype E (72%). Patients infected by genotype A (28%) tended to be younger than other patients. There was no significant difference between the blood donors and the patients with hepatitis B as regards virological markers, including viral load, when the HBV genotype was taken into account. The BCP A1762T and G1764A mutations were found in four patients and one patient, respectively; the two mutations were never found in the same patient. The W28* mutation at position 1896 of the core was detected in 19 of the 32 genotyped patients, 18 (83%) of whom had genotype E infection. ALT levels were not influenced by HBV mutations. This study shows a low frequency of clinical signs in HBsAg-positive blood donors, a relatively low level of viral replication, and a high frequency of pre-core mutants in this West African population. These results underline the importance of molecular characterization of HBV infection as specific treatments become available in this region. J. Med. Virol. 78:329,334, 2006. © 2006 Wiley-Liss, Inc. [source] Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriersJOURNAL OF MEDICAL VIROLOGY, Issue 3 2004Jia-Horng Kao MD Abstract Hepatitis B virus (HBV) is classified into eight genotypes (A,H), and genotype C is associated with more aggressive liver disease compared to genotype B. However, the mechanisms responsible for the clinical differences remain unclear. To test whether genotype C patients had with lower rates of spontaneous hepatitis B ge antigen (HBeAg) seroconversion than genotype B patients, stored serum samples from 146 Taiwanese adult HBeAg-positive hepatitis B carriers followed-up for a mean of 52 months (range, 12,120 months) were tested for HBV genotype by a molecular method. Genotype C patients were significantly older than genotype B patients (mean age, 37,±,12 vs. 29,±,10 years, P,<,0.001). During the follow-up period, genotype C patients had a significantly lower rate of spontaneous HBeAg seroconversion than genotype B patients (27 vs. 47%, P,<,0.025). Spontaneous HBeAg seroconversion occurred one decade later in genotype C patients compared with genotype B patients. Multivariate analyses identified age ,35 years (odds ratio: 2.08; 95% confidence interval [CI], 1.07,4.0; P,<,0.05), high baseline serum alanine aminotransferase level (odds ratio: 2.34; 95%CI, 1.39,4.09; P,<,0.005), and HBV genotype B (odds ratio: 1.94; 95%CI, 1.03,3.63; P,<,0.05) as independent factors associated with spontaneous HBeAg seroconversion. In conclusion, genotype C patients, compared to genotype B patients, have a delayed HBeAg seroconversion in the immune clearance phase of chronic HBV infection, which may contribute to a more progressive liver disease and more refractory to antiviral therapy. J. Med. Virol. 72:363,369, 2004. © 2004 Wiley-Liss, Inc. [source] Difference in prognosis between patients infected with hepatitis B virus with genotype B and those with genotype C in the Okinawa Islands: A prospective studyJOURNAL OF MEDICAL VIROLOGY, Issue 3 2003Tomokuni Nakayoshi Abstract The factors contributing to the prognosis of hepatitis B virus (HBV)- related chronic liver disease were assessed prospectively in 72 patients with chronic hepatitis B confirmed clinically and pathologically. A comparative study was undertaken between patients infected with genotype B and those with genotype C. During the follow-up period, 13 (81.3%) of 16 patients with genotype B who were initially hepatitis B e antigen (HBeAg) positive became HBeAg negative and 14 (51.9%) of 27 with genotype C became HBeAg negative. HBeAg had been cleared in 8 (61.5%) of 13 patients with genotype B within the first 2 years of the follow-up, but in only one (7.1%) of 14 with genotype C (P,<,0.05). Four (11.4%) of 35 patients with genotype B had progressed to cirrhosis, whereas, 12 (32.4%) of 37 patients with genotype C progressed to cirrhosis, including two patients with hepatocellular carcinoma. Multivariate analysis showed that difference in HBV genotype influenced significantly either the clearance of HBeAg or the development of cirrhosis. In conclusion, HBeAg was cleared from sera more frequently and earlier in patients with genotype B compared with those with genotype C, and development of cirrhosis occurred less frequently in patients with genotype B compared with those with genotype C. Thus, HBV genotypes may influence the prognosis of HBV-related chronic liver disease. J. Med. Virol. 70:350,354, 2003. © 2003 Wiley-Liss, Inc. [source] Hepatitis B virus genotypes and serotypes in western India: Lack of clinical significanceJOURNAL OF MEDICAL VIROLOGY, Issue 3 2003Swati S. Gandhe Abstract To determine hepatitis B virus genotype and subtype distribution among HBV infected individuals with different clinical manifestations in western India, serum samples from 19 asymptomatic hepatitis B surface antigen carriers, 30 chronic hepatitis B patients, 8 acute hepatitis B patients, 5 fulminant hepatitis B patients, and with circulating HBV DNA were genotyped and subtyped on the basis of the nucleotide sequence analysis of S region of the HBV genome. Genotype D was the predominant genotype circulating in western India (57/62; 91.93%). All 19 asymptomatic hepatitis B surface antigen carriers, 8 acute hepatitis B patients, 5 fulminant hepatic failure patients and 25/30 chronic hepatitis B patients were circulating genotype D and ayw3/ayw2 subtypes. HBV genotype A was prevalent in 8% (5/62) of the total number of patients and all belonged to chronic hepatitis B category. Subtyping analysis showed that all genotype A isolates were of subtype adw2. As most of the patients from different clinical categories were infected with HBV genotype D, it is concluded that this genotype did not influence the outcome of HBV infection. J. Med. Virol. 69:324,330, 2003. © 2003 Wiley-Liss, Inc. [source] Hepatitis B virus genotypes and HBsAg subtypes in refugees and injection drug users in the United States determined by LiPA and monoclonal EIAJOURNAL OF MEDICAL VIROLOGY, Issue 3 2001Paul D. Swenson Abstract Hepatitis B virus (HBV) genotyping and hepatitis B surface antigen (HBsAg) subtyping were carried out on sera from 196 HBsAg-positive patients, including 151 refugees entering the United States and 45 injection drug users in Seattle. HBsAg subtyping was performed by enzyme immunoassay (EIA) using a panel of monoclonal antibodies and the HBV genotype was determined by polymerase chain reaction (PCR) followed by detection of amplified HBV DNA by a reverse-phase hybridization line probe assay (LiPA) using genotype-specific probes. HBV DNA was detected by PCR in 155 (79%) of the 196 sera and all 155 were genotyped by LiPA. Samples from Southeast Asia were predominantly genotype B/subtype ayw1 and genotype C/adr; samples from the former Soviet Union and eastern Europe were mostly genotype D/ayw2 and genotype D/ayw3; samples from east Africa were mainly genotype A/adw2 and genotype D/ayw2; and samples from injection drug users were mostly genotype D/ayw3 and genotype A/adw2. Some strains of ayw3 gave atypical monoclonal antibody reactivity patterns in the subtyping assay due to a Val/Ala instead of a Thr at amino acid residue 118 and a Thr instead of a Met at residue 125. A strain of ayw2 also gave an atypical monoclonal antibody reactivity pattern due to an Ala instead of a Thr at amino acid residue 123. LiPA genotyping and monoclonal EIA subtyping can provide useful information for epidemiological studies. J. Med. Virol. 64:305,311, 2001. © 2001 Wiley-Liss, Inc. [source] Main mutations in the hepatitis B virus basic core promoter (A1762T/G1764A) before HBeAg loss are markers that identify patients who will require long-term treatmentALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010D. Tabernero Aliment Pharmacol Ther 2010; 32: 97,104 Summary Background, Some patients continue to have detectable HBV-DNA levels with liver disease progression after hepatitis B e antigen (HBeAg) loss. It is important to identify these patients, candidates for long-term treatment. Aims, To evaluate hepatitis B virus (HBV) genotype and the main mutations in the basic core promoter (BCP, A1762T/G1764A) and precore (G1896A) sequences as markers of persistent HBV-DNA after HBeAg loss. Methods, We analysed 60 serum samples from 20 Caucasian, HBeAg-positive, chronic hepatitis B patients, who lost HBeAg and were followed-up longitudinally. HBV genotype and precore and BCP mutations were determined before, at the time of, and after HBeAg loss. Results, After HBeAg loss, eight (40%) patients continued to have undetectable HBV-DNA and 12 (60%) had persistent HBV-DNA (median level 4.7 log10 copies/mL). The presence of BCP mutations prior to therapy was the only variable associated with persistently detectable viraemia (P = 0.017). Four patients with genotype A and no mutations in the BCP region experienced hepatitis B surface antigen (HBsAg) loss after a mean period of 35 months from baseline. Conclusions, Main BCP mutations in HBeAg-positive patients are useful markers to identify patients who will not have sustained virological suppression after HBeAg loss and therapy discontinuation and could benefit from long-term treatment. [source] Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B,JOURNAL OF VIRAL HEPATITIS, Issue 1 2010R. G. Gish Summary., This retrospective analysis was conducted to describe the characteristics of nucleoside-naïve hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B, who achieved hepatitis B surface antigen (HBsAg) loss during entecavir or lamivudine therapy. HBeAg-positive adults with chronic hepatitis B, elevated serum alanine aminotransferase, and compensated liver disease were randomized to double-blind treatment for up to 96 weeks with entecavir 0.5 mg/day or lamivudine 100 mg/day. HBsAg and hepatitis B virus (HBV) DNA were measured at regular intervals during and off-treatment follow-up. Through a maximum duration of 96 weeks on-treatment and 24 weeks off-treatment, HBsAg loss was confirmed in 18/354 (5.1%) patients treated with entecavir and 10/355 (2.8%) patients treated with lamivudine. Among the 28 patients with confirmed HBsAg loss, 27 (96%) achieved HBV DNA <300 copies/mL, and 27 (96%) achieved confirmed HBeAg loss. All entecavir recipients with HBsAg loss had HBV DNA <300 copies/mL. Caucasian patients, and those infected with HBV genotype A or D, were significantly more likely to lose HBsAg. This retrospective analysis of data from a randomized, global phase three trial shows that confirmed loss of HBsAg occurred in 5% of nucleoside-naïve HBeAg-positive patients treated with entecavir, and that HBsAg loss is associated with sustained off-treatment suppression of HBV DNA. [source] Hepatitis B viral DNA is methylated in liver tissuesJOURNAL OF VIRAL HEPATITIS, Issue 2 2008P. Vivekanandan Summary., The mechanisms that regulate hepatitis B virus (HBV) replication within the liver are poorly understood. Given that methylation of CpG islands regulates gene expression in human tissues, we sought to identify CpG islands in HBV-DNA and to determine if they are methylated in human tissues. In silico analysis demonstrated three CpG islands in HBV genotype A sequences, two of which were of particular interest because of their proximity to the HBV surface gene start codon (island 1) and to the enhancer 1/X gene promoter region (island 2). Human sera with intact virions that were largely unmethylated were used to transfect HepG2 cells and HBV-DNA became partially methylated at both islands 1 and 2 by day 6 following exposure of HepG2 to virus. Examination of three additional human sera and 10 liver tissues showed no methylation in sera but tissues showed methylation of island 1 in six of 10 cases and of island 2 in five of 10 cases. The cell line Hep3B, with integrated HBV, showed complete methylation of island 1 but no methylation of island 2. In conclusion, HBV-DNA can be methylated in human tissues and methylation may play an important role in regulation of HBV gene expression. [source] Differences of YMDD mutational patterns, precore/core promoter mutations, serum HBV DNA levels in lamivudine-resistant hepatitis B genotypes B and CJOURNAL OF VIRAL HEPATITIS, Issue 11 2007X. P. Pan Summary., The aims of this study were to investigate the viral differences among lamivudine-resistant hepatitis B virus (HBV) genotypes B and C in vivo. Fifty-three patients carrying lamivudine-resistant HBV were enrolled in this study. HBV genotypes, Levels of alanine aminotransferase (ALT), HBV DNA levels were monitored during therapy. The polymerase and precore/core promoter genes were amplified by polymerase chain reaction and their products were sequenced directly. Among 53 patients resistant HBV genotypes B and C accounted for 41.50% and 58.50%, respectively. The occurrence of reverse transcriptase rt204I mutants was lower in genotype B (36.36%) than that in genotype C (87.10%), whereas rt204V mutants was higher in genotype B (63.64%) than that in genotype C (12.90%). The occurrence of precore mutation (nt1896A) was higher in genotype B (77.27%) than that in genotype C (32.26%). Serum HBV DNA levels after emergence of lamivudine resistance were higher in genotype C (7.71 ± 0.80 Log copies/mL) compared with genotype B (6.97 ± 0.77 Log copies/mL). Multivariate analysis identified pretreatment HBV DNA levels, HBeAg status and HBV genotype as independent factors associated with a shorter time to lamivudine resistance(P = 0.035, P = 0.006 and P = 0.001, respectively). Multivariate analysis showed that HBV genotype (P = 0.004) and pretreatment ALT levels (P = 0.01) was independently associated with YMDD mutational patterns. The results showed that the YMDD mutational patterns, precore mutation and serum HBV DNA levels differ between lamivudine-resistant HBV genotypes B and C in vivo. It is valuable for treatment of lamivudine-resistant HBV in clinic. [source] Characterization of Hepatitis B Virus Surface Antigen and Polymerase Mutations in Liver Transplant Recipients Pre- and Post-TransplantAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2003Jeffrey J. Germer We evaluated serum samples from 18 chronic hepatitis B virus (HBV) patients who underwent liver transplantation for the presence of HBV polymerase and S gene mutations and HBV genotype using a new commercially available sequencing assay. All three patients with hepatitis B immune globulin (HBIG) treatment failure followed by nucleoside analogue treatment failure were infected with HBV genotype C; a pre-existing HBV S antigen (HBsAg) mutation (sD144A) was identified in one patient pretransplant, while sG145R mutations emerged in the other two patients post-transplant. These HBsAg mutations persisted for the duration of the study (5,6 years), despite the absence of HBIG administration for a 4,5-year period. Significant viral polymerase mutations (rtL180M and rtM204I/V) also emerged in all of these patients following treatment with lamivudine and/or famciclovir. Four of six patients with HBIG breakthrough without nucleoside analogue treatment failure yielded potentially significant HBsAg mutations post transplant. These data do not support previous reports highlighting the disappearance of HBsAg mutants in liver transplant recipients after discontinuation of HBIG. Determination of HBV genotype, as well as identification of HBV polymerase and S gene mutations in liver transplant candidates may be warranted to optimize HBV management strategies post transplant. [source] Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam,HEPATOLOGY, Issue 6 2006Nguyen L. Toan Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A-G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication-phenotype of single genotypes compared to genotype-mixtures suggest that co-infection with different HBV-genotypes is associated with altered pathogenesis and clinical outcome. (HEPATOLOGY 2006;43:1375,1384.) [source] HBV genotypes and outcome of HBV infection,HEPATOLOGY, Issue 1 2005Jia-Horng Kao No abstract is available for this article. [source] Efficacy of granulocyte-macrophage colony-stimulating factor or lamivudine combination with recombinant interferon in non-responders to interferon in hepatitis B virus-related chronic liver disease patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2002RAJKUMAR C GUPTAN AbstractBackground and Aims : Non-response to interferon (IFN) monotherapy is a major therapeutic problem in the management of chronic hepatitis B infection. The efficacy of combination therapy to enhance the immunomodulatory effect of IFN by combining granulocyte-macrophage colony-stimulating factor (GMCSF) or decreasing viral load by adding an antiviral agent such as lamivudine was evaluated prospectively. Methods : Twenty-four patients with chronic hepatitis B who were non-responders to previous IFN therapy were randomized to receive an IFN and GMCSF (group A, n = 10) or IFN and lamivudine (group B, n = 14) combination for 6 months. The end-of-treatment response was assessed by hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg) determination. Results : All patients successfully completed both the treatment schedules. The mean age, alanine aminotransferase (ALT) levels, liver histology, HBV-DNA levels and distribution of HBV genotypes were comparable between the two groups. At the end of treatment there was a significant decrease in mean ALT levels. The HBV-DNA and HBeAg loss was seen in six of 10 (60%) patients in group A and in seven of 14 (50%) patients in group B. During a mean follow-up of 15 ± 3 months, two of six (33%) patients in group A and three of seven (43%) patients in group B relapsed with HBV-DNA and HBeAg positivity, which meant an overall sustained response of 40% and 28%, respectively. None of the factors such as HBV viral load, ALT levels or liver histology could predict the non-response to combination therapy or occurrence of relapse. There was a trend in patients with genotype A compared with genotype D towards non-response to therapy, although the difference was not significant. Conclusions : The combination of IFN plus GMCSF or lamivudine was effective in non-responders to IFN monotherapy. Larger studies using such combination therapies would be helpful in improving treatment strategies for chronic hepatitis B. © 2002 Blackwell Publishing Asia Pty Ltd [source] Hepatitis B virus BCP, precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in IndiaJOURNAL OF MEDICAL VIROLOGY, Issue 7 2010Mohammad Asim Abstract The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient's age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P,<,0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India. J. Med. Virol. 82: 1115,1125, 2010. © 2010 Wiley-Liss, Inc. [source] Molecular evolutionary analysis and mutational pattern of full-length genomes of hepatitis B virus isolated from Belgian patients with different clinical manifestationsJOURNAL OF MEDICAL VIROLOGY, Issue 3 2010Mahmoud Reza Pourkarim Abstract Molecular evolutionary patterns of 62 HBV full-length genomes obtained from Belgian patients were characterized. Phylogenetic analysis revealed diverse HBV subgenotypes including A2 and A6 (46.8%), D1,D4 (38.8%), E (9.7%), C1 (1.6%), and B2 (1.6%). The study population consisted of patients with different ethnic origin (Caucasian, Turkish, Asian, Arab, and African). One HBV D/C recombinant isolate was identified, which encoded subtype adw2. An HBV subgenotype D4 with an aberrant subtype ayw4 was detected. Although none of the genotypes was associated with a specific disease outcome, several nucleotide substitutions, deletions and insertions were observed within the HBV preS1/S and X genes, particularly among patients with active chronic hepatitis B infection and patients with cirrhosis. Within the immunological domain of the HBsAg gene, the most frequent substitutions were sT125M and sT118A. High rates of precore and basal core promoter mutations were detected in patients infected with genotype D of HBV. Almost half of the patients who received lamivudine therapy for at least 1 year had HBV variants associated with lamivudine drug resistance. In conclusion, the most common HBV genotypes in West Europe (A and D) also prevail in Belgium. The highest degree of genetic diversity was detected in HBV genotype D. In addition, this study reveals the circulation of exotic HBV genotypes B, C, and E in Belgium. J. Med. Virol. 82:379,389, 2010. © 2010 Wiley-Liss, Inc. [source] Change of hepatitis B virus genotypes in acute and chronic infections in JapanJOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Mariko Kobayashi Abstract During 35 years from 1971 to 2005, 153 patients with acute and 4,277 with chronic HBV infection visited the Toranomon Hospital in Tokyo, Japan. They were grouped into seven 5-year periods, and HBV genotypes/subgenotypes were determined. Patients with acute HBV infection were younger (P,=,0.046), predominantly male (P,=,0.004), possessed higher alanine aminotransferase levels (P,<,0.001), positive more frequently for HBeAg (P,<,0.001), and had lower HBV DNA loads (P,=,0.014) than those with chronic infection. Sexual transmission was more frequent in patients with acute than chronic HBV infection (67% vs. 3%, P,<,0.001). The number of patients with acute infection increased throughout 1971,2005. Patients with chronic infection increased since 1971, peaked in 1986,1990 and then decreased. The number of patients increased since 1990,2000 again, however, reflecting recent boost of acute HBV infection. The distribution of HBV genotypes was considerably different between patients with acute and chronic infections (A, B, and C: 28.6%, 10.3%, and 59.5% vs. 3.0%, 12.3%, and 84.5%, respectively, P,<,0.001). Since 1991, genotype A foreign to Japan started to increase sharply in patients with acute infection, and gradually in those with chronic infection. There was a trend for the foreign subgenotype B2/Ba to increase recently (P,<,0.05). Despite immunoprophylaxis of high-risk babies born to carrier mothers with hepatitis B e antigen, implemented nationally since 1986, acute and chronic infections with HBV have been increasing in Japan. Based on genotypes/subgenotypes changing with time, the resurgence of hepatitis B could be attributed to infections, with foreign HBV genotypes/subgenotypes, spreading swiftly by sexual contact. J. Med. Virol. 80:1880,1884, 2008. © 2008 Wiley-Liss, Inc. [source] Prevalence of HBV genotypes in Central and Eastern EuropeJOURNAL OF MEDICAL VIROLOGY, Issue 10 2008Katja Deterding Abstract The importance of hepatitis B virus (HBV) genotypes for disease progression and response to interferon-alpha-based treatment is well established. While almost all patients in the Mediterranean area are infected with HBV genotype D, HBV genotype A is dominant in Northern Europe. However, the distribution of HBV genotypes is unknown for several Central and Eastern European countries. Data are described of 1313 HBsAg-positive patients recruited at 14 referral centers in eight countries. There were only very few cases of HBV genotype B, C, E, F, and H infection while HBV genotypes A and D were found in 42% and 48% of patients, respectively. Eight percent of patients had positive bands for more than one genotype using the hybridization assay. The frequency of genotype A was higher in Poland (77%) and the Czech Republic (67%) as compared to Hungary (47%), Lithuania (41%), Croatia (8%), and Germany (32%). In contrast, HBV genotype D was most frequent in Croatian, Romanian, and Russian patients with 80%, 67%, and 93% of cases, respectively. In conclusion, HBV genotype A versus D showed significantly different distribution patterns in Central and Eastern Europe which deserves consideration for national guidelines and treatment decisions. J. Med. Virol. 80:1707,1711, 2008. © 2008 Wiley-Liss, Inc. [source] Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinomaJOURNAL OF MEDICAL VIROLOGY, Issue 4 2008Yuehua Huang Abstract Identification of risk factors for recurrence and metastasis of HCC is important for the prognosis of HCC surveillance in chronic HBV infection. In this article, 125 HCC patients recruited were followed up prospectively for tumor metastasis and recurrence for a median of 104 (10,130) weeks. HBV DNA level was detected by LightCycler-based real-time fluorescence quantitative polymerase chain reaction-restriction system. HBV genotypes were determined by using PCR restriction-fragment length polymorphism. BCP and PC mutations were performed by PCR and direct sequencing of amplified products. Among 125 HCC patients, 19 patients were excluded because of the lack of follow-up data and the remaining 106 patients were followed up of 2 years and entered into analysis. Sixty-nine patients had tumor metastasis or recurrence during the follow-up and the cumulative probability of HCC metastasis or recurrence was 65.1%. On multivariate analysis, genotype C and HBV DNA level were the risk factors for HCC recurrence or metastasis. The incidence of recurrence or metastasis increased with baseline HBV DNA level in a dose-response relationship ranging from 22% for HBV DNA level of less than 3 log10 copies/ml to 80% for HBV DNA level of 5 log10 copies/ml or greater (P,=,0.012). Fifty-seven (74.0%) and 12 (41.4%) patients had metastasis or recurrence in patients with genotype C and B, respectively. The adjusted OR of recurrence or metastasis for genotype C compared with genotype B was 9.755 (P,=,0.009). In conclusion, elevated HBV DNA level and genotype C are strong risk predictors of HCC metastasis or recurrence. J. Med. Virol. 80:591,597, 2008. © 2008 Wiley-Liss, Inc. [source] Transmission routes of hepatitis B virus infection in chronic hepatitis B patients in The NetherlandsJOURNAL OF MEDICAL VIROLOGY, Issue 3 2008M. Toy Abstract The Netherlands is a low endemic country for hepatitis B virus (HBV). Rotterdam, a city in The Netherlands harbors a large group of chronic hepatitis B (CHB) patients of which most are born abroad. The study included 464 consecutive CHB patients who were reported to the Municipal Public Health Service in Rotterdam from January 1, 2002 to September 15, 2005. The HBV genotypes, possible transmission routes of infection and travel history of CHB patients born in The Netherlands, were compared with those CHB patients living in The Netherlands but who were foreign-born, taking into account the ethnicity of the mother. Of the 464 patients with CHB infection, 14% were Dutch-born and 86% were foreign-born. The CHB patients in the Dutch-born group had genotypes A (35%), B (15%), C (11%), D (37%), and G (2%). In the foreign-born group, the distribution of genotypes was A (20%), B (15%), C (11%), D (40%), and E (15%). In the Dutch-born group, sexual transmission accounted for a larger proportion of infections (P,<,0.0001) compared to the foreign-born group, whereas perinatal transmission is reported to be higher in the foreign-born group and in the Dutch-born group with a foreign mother. The genotypes of the chronic HBV strains determined corresponded well with the HBV genotypes expected from the countries of origin of the patients or their mothers. Genotypes A and D are predominant in CHB patients in The Netherlands. J. Med. Virol. 80:399,404, 2008. © 2008 Wiley-Liss, Inc. [source] Genetic characteristics of hepatitis B virus genotypes as a factor for interferon-induced HBeAg clearanceJOURNAL OF MEDICAL VIROLOGY, Issue 8 2007Jinlin Hou Abstract The factors determining the responsiveness of different hepatitis B virus (HBV) genotypes to interferon treatment are not fully understood. We investigated the relationship between HBV genetic characteristics and the outcome of short (16 weeks) or prolonged (32 weeks) treatment with standard interferon-alpha in a prospectively followed cohort of 103 patients across Europe with HBeAg positive chronic hepatitis B. INNO-LiPA assays and HBV DNA sequencing were used to determine HBV genotypes, mutations in the core promoter and precore/core regions. After 16-weeks interferon-alpha treatment, the rate of HBeAg clearance was higher in genotype A versus all other genotypes (P,=,0.014), or genotype D alone (P,=,0.05). The HBV genome analysis revealed that: (i) after 16-weeks treatment, an HBV subpopulation with core promoter mutations emerged or increased (P,<,0.001) only in genotype A; (ii) the core gene of genotype A has the lowest number of amino acid variations in comparison with genotypes B, C, or D. Logistic regression analysis identified genotype A as a positive predictor of short (16 weeks) treatment response (P,=,0.001; odds ratio 6.19, 95 confidence interval 1.94,19.8), having a greater impact than baseline HBV DNA or alanine aminotransferase (ALT) levels. In contrast, the response to prolonged interferon-alpha treatment was not different between HBV genotypes. These results suggest that HBV genotype A responds earlier to interferon treatment than other genotypes, which is associated with its molecular characteristics. The optimal duration of interferon-based therapies in chronic hepatitis B may vary between different HBV genotypes. J. Med. Virol. 79: 1055,1063, 2007. © 2007 Wiley-Liss, Inc. [source] Hepatitis B virus genotypes in children and adolescents in Japan: Before and after immunization for the prevention of mother to infant transmission of hepatitis B virusJOURNAL OF MEDICAL VIROLOGY, Issue 6 2007Ayano Inui Abstract The genotype distribution of hepatitis B virus (HBV) was investigated in 118 children in Japan. One hundred and sixteen children (98%) had chronic HBV infection, and the remainder had acute hepatitis. Genotyping of HBV was determined by PCR and sequencing analysis in the S gene. Genotype C (86%) was the most frequent, followed by genotype B (9%), D (2.5%), and A (1.0%). Transmission routes of HBV to children were from mothers in 91 patients (77%), fathers in 8 (6.5%), mother or father in 1 (1%), family members other than the parents in 5 (4%), and unknown in 13 (11.5%). The relationship between routes of HBV transmission and HBV genotypes was studied. Eighty-eight (97%) of 91 children of mother-to-infant transmission were genotype C, while 13 (49%) of 27 children of the routes other than the mother to infant transmission were genotype C. The number of children with genotype C who were infected from their mothers was significantly higher than those with genotype B, D, or A (P,<,0.01). In conclusion, HBV genotypes influence not only clinical characteristics but also the mechanisms of inter-personal HBV transmission. J. Med. Virol. 79: 670,675, 2007. © 2007 Wiley-Liss, Inc. [source] Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia,JOURNAL OF MEDICAL VIROLOGY, Issue 5 2006Bira Tsatsralt-Od Abstract One hundred ten consecutive patients (60 males and 50 females; age, mean,±,standard deviation [SD], 22.6,±,6.4 years; range 16,48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B,+,D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n,=,1) and D (98.5%, n,=,66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia. J. Med. Virol. 78:542,550, 2006. © 2006 Wiley-Liss, Inc. [source] Characterization of seven genotypes (A to E, G and H) of Hepatitis B virus recovered from Japanese patients infected with human immunodeficiency virus type 1,JOURNAL OF MEDICAL VIROLOGY, Issue 1 2005Takao Shibayama Abstract To investigate the prevalence of hepatitis B virus (HBV) genotypes and characteristics of HBV isolates among Japanese patients infected with human immunodeficiency virus type 1 (HIV), serum samples collected between September 1990 and March 2002 from 471 HIV-infected patients (age, 38.8,±,11.4 [mean,±,standard deviation] years; male, 90%) were tested for hepatitis B surface antigen (HBsAg) and HBV DNA. Positivity for HBsAg and HBV DNA was seen in 42 patients (8.9%), 41 of whom had contracted HIV infection through sexual activity and 1 had hemophilia. Genotypes of HBV were determined by comparative and phylogenetic analyses of the S gene sequence (396 nucleotides [nt]). The distribution of HBV genotypes among the 42 HBV-viremic patients was: A (50%), B (5%), C (24%), D (5%), E (2%), H (10%), A plus D (2%), A plus G (2%). The hemophilia patient had HBV genotype D. Genotypes E, G, and H which had not been reported in Japan, were found in one patient each who had traveled to Zambia, the US, and South America, respectively. Genotypes A and D, which are rare in Japan, were found in patients who had no history of traveling abroad. The entire genome of the HB-JI411 (genotype E [3,212 nt]), HB-JI444G (genotype G [3,248 nt]), and HB-JI260 (genotype H [3,218 nt]) isolates had the highest identity of 98.3%, 99.9%, and 98.5%, respectively, with reported HBV isolates of the same genotype. Most Japanese patients coinfected with HIV and HBV had HBV genotypes that are found rarely or had not been reported in Japan. J. Med. Virol. 76:24,32, 2005. © 2005 Wiley-Liss, Inc. [source] Difference in prognosis between patients infected with hepatitis B virus with genotype B and those with genotype C in the Okinawa Islands: A prospective studyJOURNAL OF MEDICAL VIROLOGY, Issue 3 2003Tomokuni Nakayoshi Abstract The factors contributing to the prognosis of hepatitis B virus (HBV)- related chronic liver disease were assessed prospectively in 72 patients with chronic hepatitis B confirmed clinically and pathologically. A comparative study was undertaken between patients infected with genotype B and those with genotype C. During the follow-up period, 13 (81.3%) of 16 patients with genotype B who were initially hepatitis B e antigen (HBeAg) positive became HBeAg negative and 14 (51.9%) of 27 with genotype C became HBeAg negative. HBeAg had been cleared in 8 (61.5%) of 13 patients with genotype B within the first 2 years of the follow-up, but in only one (7.1%) of 14 with genotype C (P,<,0.05). Four (11.4%) of 35 patients with genotype B had progressed to cirrhosis, whereas, 12 (32.4%) of 37 patients with genotype C progressed to cirrhosis, including two patients with hepatocellular carcinoma. Multivariate analysis showed that difference in HBV genotype influenced significantly either the clearance of HBeAg or the development of cirrhosis. In conclusion, HBeAg was cleared from sera more frequently and earlier in patients with genotype B compared with those with genotype C, and development of cirrhosis occurred less frequently in patients with genotype B compared with those with genotype C. Thus, HBV genotypes may influence the prognosis of HBV-related chronic liver disease. J. Med. Virol. 70:350,354, 2003. © 2003 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||