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Results for “seroconversion”

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PubMed2004

Longitudinal study of hepatitis activity and viral replication before and after HBeAg seroconversion in chronic hepatitis B patients infected with genotypes B and C.

The aims of this study were to compare chronic hepatitis B (CHB) patients with genotypes B and C for the probability of HBeAg seroconversion, hepatitis activity, and viral replication before and after HBeAg seroconversion and to compare the prevalence of core promoter and precore mutations. A total of 180 asymptomatic Chinese patients with CHB were monitored for a median of 53.8 months, and 38 patients with cirrhosis-related complications were studied. Hepatitis B virus (HBV) DNA levels were measured in 16 patients with HBeAg seroconversion at 3 months before, during, and 3 months after HBeAg seroconversion and in all patients at the last follow-up. Hepatitis B genotypes and core promoter and precore mutations were determined. Compared to patients with genotype C (n = 109), patients with subtype Ba (n = 69) had a higher rate of anti-HBe positivity on presentation (P = 0.05). HBeAg-positive patients with subtype Ba had a higher cumulative rate of HBeAg seroconversion than patients with genotype C (P = 0.02). However, there were no differences between the two groups with regard to the median HBV DNA levels before, during, and after HBeAg seroconversion; the probability of having persistently normal or elevated aminotransferase levels; and the median HBV DNA levels and liver biochemistry at the last follow-up. There was no difference in the prevalence of genotypes and core promoter and precore mutations between patients with and without cirrhosis-related complications. Though patients with subtype Ba had earlier HBeAg seroconversion, the liver biochemistry, HBV DNA levels in different phases of the disease, and the probability of development of cirrhosis-related complications were the same with genotypes Ba and C.

Adolescent↗

PubMed1999

Variants from the diverse virus population identified at seroconversion of a clade A human immunodeficiency virus type 1-infected woman have distinct biological properties.

Development of effective therapeutics to prevent new infections with human immunodeficiency type 1 (HIV-1) is predicated on an understanding of the properties that provide a selective advantage to a transmitted viral population. In contrast to the homogeneous virus population that typifies early HIV-1 infection of men, the viral population in women recently infected with clade A HIV-1 is genetically diverse, based on evaluation of the envelope gene. A longitudinal study of viral envelope evolution in several women suggested that representative envelope variants detected at seroconversion had distinct biological properties that affected viral fitness. To test this hypothesis, a full-length, infectious molecular clone, Q23-17, was obtained from an infected woman 1 year following seroconversion, and chimeric viruses containing envelope genes representative of seroconversion and 27-month-postseroconversion populations were constructed. Dendritic cells (DC) could transfer infection of seroconversion variant Q23ScA, which dominated the viral population in the year following seroconversion, and the closely related 1-year isolate Q23-17 to resting peripheral blood mononuclear cells (PBMC). In contrast, resting PBMC exposed to DC pulsed with Q23ScB, which was detected infrequently in samples after seroconversion, or the 27-month chimeras were inconsistently infected. Additionally, quiescent PBMC infected with Q23ScA or Q23-17 proliferated more robustly than uninfected cells or cells infected with the other envelope chimeras in response to immobilized anti-CD3. Stimulation with tetanus toxoid led to an increased proportion of CD45RA+ cells and a decreased expression of CD28 on CD45RO+ cells in cultures of Q23-17-infected PBMC. These data demonstrate that variants from the heterogeneous seroconversion clade A HIV-1 population in a Kenyan woman have distinct biological features that may influence viral pathogenesis.

Amino Acid Sequence↗

PubMed2005

Long-term results of lamivudine monotherapy in Korean patients with HBeAg-positive chronic hepatitis B: response and relapse rates, and factors related to durability of HBeAg seroconversion.

OBJECTIVE: The aim of this study was to evaluate retrospectively the long-term effects of lamivudine in 461 Korean patients with chronic hepatitis B who were treated for more than 12 months. METHODS: The annual rates of virological response and breakthrough were examined and the predictive factors for post-treatment relapse in 114 patients who achieved hepatitis B e antigen (HBeAg) loss or seroconversion after lamivudine therapy were also analyzed. RESULTS: During follow-up, the rates of HBeAg seroconversion after 1, 2, 3, 4 and 5 years of treatment were 22.9, 33.2, 47.6, 54.2 and 58.8%, respectively, while those for virological breakthrough at 1, 2, 3 and 4 years were 8.2, 41.7, 55.7 and 64.8%, respectively. Ninety-five patients (20.6%) had HBeAg seroconversion and 19 (4.1%) showed HBeAg loss alone with disappearance of hepatitis B virus DNA in serum. Seroconversion was higher with prolonged treatment in patients who had elevated serum alanine aminotransferase. The cumulative relapse rates in the seroconversion group were 52.0 and 55.7% 1 and 2 years after treatment, respectively. Age and the duration of additional treatment were significant predictive factors for post-treatment relapse. Patients aged </=40 who had additional treatment for >12 months after seroconversion had the lowest relapse rate (p < 0.001). CONCLUSIONS: These results suggest that additional treatment for over 12 months after HBeAg seroconversion in younger patients may produce a better long-term outcome.

Adult↗

PubMed1995

The significance of spontaneous hepatitis B e antigen seroconversion in childhood: with special emphasis on the clearance of hepatitis B e antigen before 3 years of age.

To investigate the significance of spontaneous hepatitis B e antigen (HBeAg) seroconversion during childhood, 415 hepatitis B surface antigen (HBsAg) carrier children (ages 0 to 15 years) were prospectively followed for 7.1 +/- 2.9 years. Hepatitis B virus (HBV) markers and liver function profiles of each child were tested at least once every 6 months. Among them, 50 were initially anti-HBe positive and 140 seroconverted from HBeAg to anti-HBe during follow-up. Before HBeAg seroconversion, jaundice occurred in 9 and alanine transaminase (ALT) activities elevated in 99 of the 140 seroconverters. Serum ALT returned to normal in all patients within 1 to 5 years of seroconversion. Six had reelevated ALT later after seroconversion. Only 7 (9.7%) of the 72 carrier infants seroconverted before 3 years of age. The peak ALT levels in five of them exceeded 100 IU/L, and two had jaundice before HBeAg seroconversion. One of the early seroconverters developed hepatocellular carcinoma (HCC) at 11 years of age, although his liver function profiles remained normal after HBeAg seroconversion. Liver biopsy specimens from 30 children during the anti-HBe-positive stag e showed inactive cirrhosis in 2 (including one with HCC), chronic hepatitis with marked fibrosis in 1, mild activity and moderate fibrosis in 2, mild activity and mild fibrosis in 9, and minimal histologic changes in the remaining 16. Although most will achieve a normalization of ALT and inactive liver histologic changes, the seroconversion of HBsAg carrier children from HBeAg to anti-HBe is not necessarily an indicator of favorable prognosis; a small proportion of children will develop cirrhosis or even HCC.

Adolescent↗

PubMedDate not supplied

Incidence and consequences of pregnancy in women with known duration of HIV infection. Italian Seroconversion Study Group.

BACKGROUND: The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease. OBJECTIVES: To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women. PATIENTS: All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years. RESULTS: A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24). CONCLUSION: Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.

CD4 Lymphocyte Count↗

PubMed1992

A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion.

To evaluate the risk of transfusion-related transmission of HTLV-I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV-I serological screening assay. This information would prove useful in formulating strategies for blood-donor screening. We followed 118 pre-transfusion HTLV-I-negative transfusion recipients at monthly intervals post-transfusion for 1 year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV-I seroconversion was estimated and risk-factor data associated with seroconversion among 66 HTLV-I-exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44%) of recipients of HTLV-I-positive cellular blood components, 0/12 recipients of positive non-cellular donor units and 0/52 recipients of HTLV-I-negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week [odds ratio (OR) = 6.34, 95% confidence interval (CI) = 1.83 to 21.92], male sex (OR = 4.79, 95% CI = 1.15 to 20.0) or use of immuno-suppressive therapy at time of transfusion (OR = 12.20, 95% CI = 0.95 to 156). Risk of blood-borne infection per person per year in Jamaica was estimated to be 0.009%. Our results confirm that blood transfusion carries a significant risk of HTLV-I transmission and that screening of donor blood effectively prevents HTLV-I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood-donor screening for HTLV-I is not possible.

Blood Donors↗

PubMed1992

Effects of different parametric estimates of seroconversion time on analysis of progression to AIDS among Italian HIV-positive haemophiliacs.

The purpose of this study was to estimate seroconversion time using different parametric methods and to assess their influence on the estimation of the incubation time between HIV infection and onset of AIDS. Study subjects were 712 HIV-positive haemophiliacs enrolled in the Italian National Registry of patients with congenital coagulation disorders. Seroconversion time was estimated using the mid-point of each seroconversion interval (MID), the median of each interval under an estimated uniform distribution with cutpoints at December 1981 and December 1985 (MUU), the median of each interval under an estimated Weibull distribution (MUW), and the median of three random values drawn from each interval under the Weibull distribution (RUW). Kaplan-Meier survival analysis showed that the cumulative incidence of AIDS over a 7-year period was 11.6 per cent (SE 1.3 per cent) when using the MID estimate of seroconversion time, 10.8 per cent (1.2 per cent) with the MUU estimate, and 13.4 per cent (1.3 per cent) and 12.3 per cent (1.3 per cent) when using MUW and RUW estimates, respectively. This study demonstrates that the estimate of seroconversion time does not seem to be a major factor affecting estimates of AIDS incidence since the different techniques for estimating HIV seroconversion time yielded very similar results.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Median time from seroconversion to AIDS in Italian HIV-positive haemophiliacs: different parametric estimates.

The purpose of this study was to estimate the median incubation time between human immunodeficiency virus (HIV) infection and onset of acquired immunodeficiency syndrome (AIDS), using three parametric models and six estimates of seroconversion time. Study subjects were 732 HIV-positive haemophiliacs enrolled in the Italian Registry of patients with congenital coagulation disorders. Seroconversion time was estimated for each subject according to six different criteria, based on three distributions of seroconversion (uniform, uniform on three sub-intervals and truncated Weibull) and two indices synthesizing each distribution (median and median of three random values). The estimated seroconversion times were subsequently used as starting points in the analysis of incubation. This was performed applying Kaplan-Meier non-parametric survival analysis, and fitting to incubation data three probability density functions, representing three different situations with respect to the hazard of developing AIDS following seroconversion (namely Weibull (WE), generalized exponential (GE) and log-logistic (LL)). The cumulative incidence over an 8-year period ranged from 14.9 to 17.8 per cent when applying the Kaplan-Meier method, from 14.1 to 17.2 per cent when using the WE function, from 14.5 to 17.3 per cent when using the GE function and from 14.4 to 17.3 per cent when using the LL function, depending on the estimate of seroconversion time used. Similarly, the median incubation times ranged from 12.6 to 15.0 years with the WE function, from 14.0 to 16.5 years with the GE function, and from 13.4 to 16.1 years with the LL function. The presence of a bound on the increase of the hazard function seems to affect the incubation more strongly than the eventual decrease following the attainment of the maximum risk. This may be due to the decrease in the hazard beginning when most of the seropositive subjects have already developed AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Risk of hepatitis C seroconversion after occupational exposures in health care workers. Italian Study Group on Occupational Risk of HIV and Other Bloodborne Infections.

BACKGROUND: To determine the incidence of hepatitis C virus (HCV) seroconversion, health care workers reporting an occupational exposure with blood or other risk-prone body materials from a patient known to be seropositive for HCV antibody were enrolled. METHODS: HCV seroconversion within 6 months of a reported exposure was assessed by second-generation enzyme immunoassay and immunoblot assay. RESULTS: From January 1992 through December 1993, 331 (51%) hollow-bore needlesticks, 105 (16.5%) suture needle or sharp object injuries, 85 (13%) mucous membrane contaminations, and 125 (19.5%) skin contaminations were reported. Four HCV seroconversions were observed after hollow-bore needlesticks (1.2%; 95% CI 0.3% to 3.0%); no seroconversions occurred after other routes of exposure. Blood-filled needlesticks and source patient coinfection with HIV appeared to be associated with a higher risk of seroconversion. CONCLUSIONS: The risk of HCV seroconversion after occupational exposure appears to be low but is not negligible. Aggressive implementation of universal precautions is important for preventing risk-prone exposure, but safer devices are also needed.

Adolescent↗

PubMed2004

Human herpesvirus 8 seroconversion in Kenyan women by enzyme-linked immunosorbent assay and immunofluorescence assay.

BACKGROUND: Human herpesvirus 8 (HHV-8) antibody tests vary in reported sensitivity and specificity, depending on the population tested and the assay. OBJECTIVE: The purpose of this study was to compare the ability to detect seroconversion to HHV-8 in a cohort of HHV-8 seronegative female commercial sex workers in Kenya using three tests: HHV-8 viral lysate-based enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay for HHV-8 lytic antigens (IFA-lytic) and IFA for latent nuclear antigens (IFA-LANA). STUDY DESIGN: By ELISA, 16 women from a prospective cohort of commercial sex workers were identified as seroconverting to HHV-8. A total of 124 post-enrollment samples from these 16 women as well as the enrollment samples were tested for HHV-8 antibodies by all three assays to monitor seroconversion. RESULTS: Of 16 women with apparent seroconversion by ELISA, 8 had a rise in IFA-lytic titers either concomitant with or prior to the first positive ELISA sample and no initial LANA by IFA. Five of the 16 women were IFA-LANA positive at entry, indicating prior infection with HHV-8. Three women had no evidence of seroconversion by either IFA-lytic or IFA-LANA and two of these three had increased ELISA reactivity concomitant with HIV-1 infection. CONCLUSIONS: Conversion from a negative to a positive ELISA result for HHV-8 antibody indicated seroconversion in only half of the study cohort of 16 women when IFA-lytic and IFA-LANA results were considered. The IFA-lytic assay was more sensitive than ELISA for early antibody responses. The IFA-LANA was positive in some women who had neither IFA-lytic nor ELISA antibodies suggesting it may be a marker for latent infections. Presumptive identification of incident HHV-8 infection by ELISA screening followed by IFA-lytic testing to confirm the positive test and IFA-LANA to rule out prior infection provides the most accurate documentation of HHV-8 seroconversion.

Antibodies, Viral↗

PubMed2004

Intra-unit correlations in seroconversion to Actinobacillus pleuropneumoniae and Mycoplasma hyopneumoniae at different levels in Danish multi-site pig production facilities.

In this paper, multilevel logistic models which take into account the multilevel structure of multi-site pig production were used to estimate the variances between pigs produced in Danish multi-site pig production facilities regarding seroconversion to Actinobacillus pleuropneumoniae serotype 2 (Ap2) and Mycoplasma hyopneumoniae (Mh). Based on the estimated variances, three newly described computational methods (model linearisation, simulation and linear modelling) and the standard method (latent-variable approach) were used to estimate the correlations (intra-class correlation components, ICCs) between pigs in the same production unit regarding seroconversion. Substantially different values of ICCs were obtained from the four methods. However, ICCs obtained by the simulation and the model linearisation were quite consistent. Data used for estimation were collected from 1161 pigs from 429 litters reared in 36 batches at six Danish multi-site farms chronically infected with the agents. At the farms, weaning age was 3-4.5 weeks, after which batches of pigs were reared using all-in/all-out management by room. Blood samples were collected shortly before: weaning, transfer from weaning-site to finishing-site, and sending the first pigs in the batch for slaughter (third sampling). Few pigs seroconverted at the weaning-sites, whereas considerable variation in seroconversion was observed at the finishing-sites. Multilevel logistic models (initially including four levels: farm, batch, litter, pig) were used to decompose the variation in seroconversion at the finishing-site. However, there was essentially no clustering at the litter level-leading to the use of three-level models. In the case of Ap2, clustering within batch was so high that the data eventually were reduced to two levels (farm, batch). For seroconversion to Ap2, ICC between pigs within batches was approximately 90%, whereas the ICC between pigs within batches for Mh was approximately 40%. This indicates that the possibility for Mh to spread between pigs within batches is lower than for Ap2. The diversity in seroconversion between batches within the same farm was large for Ap2 (ICC approximately 10%), whereas there was a relative strongly ICC (approximately 50%) between batches for Mh. This indicates that the transmission of Mh is more consistent within a farm, whereas the presence of Ap2 varies between batches within a farm.

Actinobacillus Infections↗

PubMed1997

Time course of viremia and antibody seroconversion following human immunodeficiency virus exposure.

Rational application of diagnostic assays in the management of healthcare workers (HCWs) following occupational exposure is needed to rule out pre-existing human immunodeficiency virus (HIV) infection, detect HIV infection or seroconversion as early as possible in the small proportion individuals who become infected, and to rule out infection in the high proportion of individuals who remain uninfected following occupational exposure to HIV. An understanding of the time course of viremia and seroconversion following HIV exposure is essential in developing recommendations for management of occupational exposure among HCWs. Several data sources that address the timing and dynamics of HIV viremia and seroconversion following primary infection are reviewed. The implications of each data source for management of occupational exposure among HCWs is assessed. Although the majority of infected HCWs seroconvert within 2 months of exposure, the possibility of delayed seroconversion is well established, with approximately 5% of infected HCWs estimated to seroconvert >6 months after exposure. In contrast, the period of viremia (detectable by p24 antigen or RNA assays) preceding antibody seroconversion is consistently brief (1-3 weeks). Animal inoculation studies indicate that a variable period of localized viral replication in lymphoid tissue draining inoculation sites exists prior to systemic viremia and subsequent seroconversion.

Animals↗

PubMed2003

Human herpesvirus-6 in renal transplant recipients: potential risk factors for the development of human herpesvirus-6 seroconversion.

Herpesviruses, including human herpesvirus-6 (HHV-6), reactivate and have the potential to be pathogenic in immunocompromised patients. Little information is available regarding the correlation between immunosuppressive therapy and HHV-6 seroconversion after organ transplantation. Serum samples obtained from 120 kidney and kidney/pancreas transplant recipients were tested to explore the potential risk factors for developing HHV-6 infection including types of immunosuppression and induction/rejection therapy. Stored serum samples obtained prior to and at the 2nd, 4th, 12th and 48th weeks after transplantation were tested for anti-HHV-6 immunoglobulin (Ig)M antibodies using indirect immunofluorescence assay. Prior to transplantation and 48 weeks after transplantation the sera were additionally tested for anti-HHV-6 IgG using enzyme-linked immunoassay. Ninety-one percent of 120 recipients were HHV-6 IgG-positive before transplantation. One hundred seven of 120 patients were anti-HHV-6 IgM-negative before transplantation. Primary/secondary HHV-6 seroconversion occurred in sera of 46.6% of these 107 patients. HHV-6 seroconversion most frequently occurred 2 to 4 weeks after transplantation. There was no significant relationship between HHV-6 seroconversion and the treatment with methylprednisolone (MP). The incidence of HHV-6 seroconversion was significantly higher in subjects who were treated with the regimens including Daclizumab or Sirolimus as compared with those who were on other protocols. HHV-6 seropositivity in the Polish population of organ transplant recipients is very high. We demonstrated a trend toward association of HHV-6 seroconversion with type of immunosuppressive therapy.

Adolescent↗

PubMed1999

Improved performance of seroconversion with a 4th generation HIV antigen/antibody assay.

Recently a new fourth generation microELISA for large scale blood screening has been described in which HIV p24 Ag detection was integrated in an anti-HIV-1/-2 and anti-HIV-1 group O assay based on a direct assay format: (Vironostika HIV Uni-Form II Ag/Ab (Van Binsbergen et al., (1998)). When compared to the third generation a-HIV assay (Vironostika HIV Uni-Form II plus O), the seroconversion window was narrowed with more than one week. A more precise window estimation based on seroconversion series with short sampling time intervals of up to 7 days, is described in parallel with that for the single HIV p24 Ag assay. It was found with 10 relevant seroconversion series that the HIV p24 Ag assay closes the seroconversion window with 6.2 days as compared to the 3rd generation a-HIV assay, while a window reduction of 4 days was found with Vironostika HIV Uni-Form II Ag/Ab. These seroconversion data show that with the new assay two-thirds of the current p24 Ag window is closed. There was no statistical difference in seroconversion sensitivity between the HIV p24 Ag and the new assay format. An extended evaluation of the new assay with subtype HIV-1 M and group O p24 Ag strains and with anti-HIV antibodies obtained from individuals infected with different HIV-1 subtypes showed that all subtypes of HIV-1 M and HIV-1 group O p24 antigen were detected as well as of HIV antibody.

Enzyme-Linked Immunosorbent Assay↗

PubMed1997

Age-related hepatitis B seroconversion rates in health care workers.

BACKGROUND: Protective hepatitis titers are reported for more than 90% of healthy adults who received three intradeltoid injections of vaccine. Some factors that influence seroconversion rates include age, sex, and presence of chronic diseases. METHODS: Because of work-related factors that placed them at risk of acquiring hepatitis B, 112 employees, who ranged in age from 20 to 70 years with a mean age of 39.2 years, completed the hepatitis B vaccination series between 1986 and 1993. All participants received three vaccinations. RESULTS: Hepatitis B surface antibody did not develop in 16 of 112 recipients (14.2%, 95% CI, 7.6% to 20.8%). Race, sex, and duration to antibody titer did not affect rates of seroconversion. Age greater than 50 years was associated with significantly decreased seroconversion rates (64.7%, 95% CI, 42.0% to 87.4%) compared with seroconversion rates of those younger than 50 years of age (89.5%, 95% CI 83.3% to 95.7%, p = 0.02). CONCLUSIONS: Our results indicate that when a hepatitis B immunization program is implemented, seroconversion rates are lower than published rates for healthy adults and adolescents. We recommend that seroconversion data from immunization programs for employees at risk for hepatitis B be reviewed and that postimmunization testing be considered to ensure adequate protection for those employees at highest risk for nonconversion.

Adult↗

PubMed2001

HBe seroconversion and HBs mutation among Japanese hepatitis B virus carriers.

It has been reported in Germany that seroconversion to anti-HBe or anti-HBs is frequently associated with genotype changes of hepatitis B virus (HBV) from genotype A to genotype D. We previously reported that the HBeAg-negative state in Japan was significantly more common in patients infected with genotype B HBV than those infected with genotype C HBV. To determine whether the high prevalence of genotype B in the HBeAg-negative state is due to a change from genotype C to genotype B, 72 pairs of serum samples before and after HBe seroconversion were examined for nucleotide sequences in the S gene (amino acids 42-164) among Japanese HBV carriers. No one was identified to have undergone genotype change during HBe seroconversion. A total of 71 codon mutations were observed. Sixty-two of these 71 codon mutations (87.3%) were non-synonymous. Genotype B HBV had no mutational hot spots. In genotype C, there was a mutational hot spot at amino acid 126 of the S protein, and it was suggested that Thr126 before HBe seroconversion was more susceptible to becoming an asymptomatic carrier after HBe seroconversion than Ile126. In conclusion, genotype changes during HBe seroconversion were not found to be common in Japan.

Journal Article↗

PubMed1998

Spontaneous seroconversion in chronic hepatitis B: role of mutations in the precore/core gene.

The mechanism underlying spontaneous clearance of hepatitis B e antigen (HBeAg) and the appearance of antibodies (anti-HBe seroconversion) in chronic hepatitis B is not known. Previous studies have demonstrated mutations within the precore/core gene before, during, and after seroconversion, suggesting that the emergence of mutations in the core gene may abrogate tolerance and that this event may act as a general principle for the initiation of the clearance of HBeAg. To investigate this hypothesis, we studied three patients with adult-acquired chronic hepatitis B virus (HBV) infection before spontaneous seroconversion by sequential sequencing and single-stranded conformation polymorphism (SSCP) analysis of the entire precore/core genome. In one patient, a new viral strain appeared six months before seroconversion, but no mutations or new viral strains could be detected in the other two patients. SSCP analysis confirmed the sequencing results and revealed no evidence for the emergence of new viral subpopulations before seroconversion. These results suggest that the appearance of nucleotide changes within the precore/core region of the dominant viral strain is not a prerequisite for the induction of seroconversion in patients with chronic hepatitis B virus infection acquired during adulthood.

Adult↗

PubMed2002

Effect of virological response on post-treatment durability of lamivudine-induced HBeAg seroconversion.

Lamivudine-induced HBeAg seroconversion may not be durable in Korean patients with hepatitis B virus (HBV) infection. It is unknown whether virological response during lamivudine treatment affects the post-treatment outcome. We retrospectively analysed 124 consecutive HBeAg-positive chronic hepatitis B (CHB) patients treated with lamivudine. Lamivudine was given at a dose of 100 mg per day. HBV DNA levels in sera obtained before and during therapy were measured by the Digene Hybrid Capture II assay and Digene Ultrasensitive Hybrid Capture II assay, respectively. HBeAg seroconversion was achieved in 42 of the 124 patients (33.8%) treated with lamivudine. Mean duration of treatment in HBeAg seroconverters was 12.86 +/- 4.44 months. During the follow-up period, the cumulative relapse rates at 3 months and 6 months post-treatment in 42 patients with HBeAg seroconversion were 40.5% and 57.4%, respectively. Among 31 seroconverted patients whose sera were available at the second month of treatment, HBV DNA remained at > 4.7 x 103 genomes/mL in 15 patients and decreased to < 4.7 x 103 genomes/mL in the remaining 16 patients. HBV DNA levels at the second month of treatment was not related with relapse after discontinuation of treatment (66.7% vs. 43.8%, P= 0.2). At the time of HBeAg seroconversion, HBV DNA remained at > 4.7 x 103 genomes/mL in five patients and decreased to < 4.7 x 103 genomes/mL in the remaining 37 patients. Relapse rates were increased in patients who remained at > 4.7 x 103 genomes/mL compared with patients with HBV DNA levels < 4.7 x 103 genomes/mL (100% vs. 51.4%, P < 0.001). Thus, monitoring of serum HBV DNA at the time of HBeAg seroconversion may be helpful for predicting relapse in patients with lamivudine-induced HBeAg seroconversion.

Antiviral Agents↗