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Patterns of hepatitis B prevalence and seroconversion in hemodialysis units from three continents: the DOPPS.

BACKGROUND: Hepatitis B (HBV) historically has been a public health issue within hemodialysis units. This study estimates HBV prevalence and seroconversion rates across seven countries and investigates associations with facility level practice patterns. METHODS: The study sample was from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a cross-sectional, prospective, observational study of adult hemodialysis patients randomly selected from 308 dialysis facilities in France, Germany, Italy, Spain, the United Kingdom, Japan, and the United States. Logistic regression was used to model the odds ratio (OR) of HBV prevalence, and Cox regression was used to model time from entry into the study to HBV seroconversion. RESULTS: In this sample, mean HBV facility prevalence was 3.0% with a median of 1.9%. The percentage of facilities with an HBV prevalence 0% to 5% was 78.5%. Adjusted HBV prevalence was higher in France, Germany, and Italy and lower in Japan and the United Kingdom. The majority of facilities (78.1%) had a seroconversion rate of 0 conversions per 100 patient-years. Presence of a protocol for HBV-infected patients was significantly associated with HBV seroconversion in the separate practice pattern model [risk ratio (RR) = 0.52, P = 0.03] and in the combined practice pattern model (RR = 0.44, P = 0.01). CONCLUSION: There are differences in HBV prevalence and rate of seroconversion both at the country and the hemodialysis facility level. Presence of a protocol for HBV-infected patients was strongly and significantly associated with decreased risk for seroconversion. The observed variation suggests opportunities for improved HBV outcomes with further definition of optimal practice patterns at the facility level.

Adult↗

Quantitative detection of increasing HIV type 1 antibodies after seroconversion: a simple assay for detecting recent HIV infection and estimating incidence.

We have devised a simple enzyme immunoassay (EIA) that detects increasing levels of anti-HIV IgG after seroconversion and can be used for detecting recent HIV-1 infection. Use of a branched peptide that included gp41 immunodominant sequences from HIV-1 subtypes B, E, and D allowed similar detection of HIV-specific antibodies among various subtypes. Because of the competitive nature of the capture EIA, a gradual increase in the proportion of HIV-1-specific IgG in total IgG was observed for 2 years after seroconversion. This was in contrast to results obtained with the conventional EIA using the same antigen in solid phase, which plateaus soon after seroconversion. The assay was used to test 622 longitudinal specimens from 139 incident infections in the United States (subtype B) and in Thailand (subtypes B and E). The assay was also performed with an additional 8 M urea incubation step to assess the contribution of high-avidity antibodies. Normalized optical density (OD-n) was calculated (ODspecimen/ODcalibrator), using a calibrator specimen. An incremental analysis indicated that a cutoff of 1.0 OD-n and a seroconversion period of 160 days offered the best combination of sensitivity and specificity for classifying incident or long-term infections. The urea step increased the seroconversion period to 180 days with similar sensitivity and specificity. Separate analysis of B and E subtype specimens yielded the same optimal OD-n threshold and similar seroconversion periods. The assay was further validated in African specimens (subtypes A, C, and D) where the observed incidence was within 10% of the expected incidence. This assay should be useful for detecting recent HIV-1 infection and for estimating incidence among diverse HIV-1 subtypes worldwide.

AIDS Serodiagnosis↗

Temporal trends in human immunodeficiency virus type 1 seroconversion 1984-1989. A report from the Multicenter AIDS Cohort Study (MACS).

The 5-year temporal trends in human immunodeficiency virus type 1 (HIV-1) seroconversion between 1984 and 1989 among homosexual/bisexual men participating in the Multicenter AIDS Cohort Study (MACS) are reported. Of 3,262 initially seronegative men, 368 (11.3%) had seroconverted by December 31, 1989. Although the incidence of seroconversion declined precipitously during the first 3 years of follow-up (from 4.1% to 0.9% per 6 months), no evidence for a further substantial reduction was noted after mid-1987, since 6-month incidence rates ranged between 0.5% and 1.2%. The Chicago cohort experienced an increase in HIV-1 seroconversion during both semesters of 1989; 2.1% and 1.6% per 6 months, respectively, became newly infected. Other MACS centers did not report such an increase. Center-specific differences were observed by race; black men were at higher seroconversion risk than white men in Baltimore/Washington (relative risk (RR) = 3.4) and Chicago (RR = 2.4), while Hispanic men were at higher risk than white men in Chicago (RR = 3.3). Younger age (less than 35 years) was also associated with HIV-1 seroconversion (RR = 1.5). It is disturbing to report an overall annual seroconversion rate of 1.2% for the 2 years prior to December 31, 1989, as well as evidence for a sustained recent increase in Chicago during 1989. Long-term maintenance of safe-sex behaviors should be the cornerstone of acquired immunodeficiency syndrome prevention among homosexual/bisexual men.

Age Factors↗

Effects of age at seroconversion and baseline HIV RNA level on the loss of CD4+ cells among persons with hemophilia. Multicenter Hemophilia Cohort Study.

OBJECTIVE: To assess the impact of age at seroconversion and HIV RNA level in serum during early chronic infection on the initial values and subsequent trends (slopes) of CD4+ lymphocyte counts. DESIGN AND METHODS: In a cohort of 137 HIV-1-positive hemophiliacs with well-estimated dates of seroconversion, baseline HIV RNA level was measured by reverse transcription PCR in serum specimens collected 12-36 months after the estimated date of seroconversion. Baseline values, 24 months after seroconversion, and slopes of CD4+ lymphocyte counts by age and HIV RNA quartile were examined by fitting random effects models that allowed for intrasubject variability. RESULTS: Both age at seroconversion and HIV RNA level were associated with the CD4+ lymphocyte count at baseline and its subsequent slope. The baseline median CD4+ lymphocyte count was 620 x 10(6)/l. Within each HIV RNA quartile, the median CD4+ cell count of the oldest subjects (age 30-58 years) was about 200 x 10(6)/l lower and at least 350 x 10(6)/l lower than the median counts of the younger (age 11-29 years) and youngest (age 2-10 years) subjects, respectively. Within each age-group, the median CD4+ cell count differed by about 200 x 10(6)/l between subjects in the lowest compared with the highest HIV RNA quartiles. The mean slope of the CD4+ lymphocyte count after month 24 was linear on the square-root scale, steeper in children, and did not vary significantly by baseline HIV RNA quartile. There was large variation between subjects that was unexplained by differences in age and HIV RNA level. CONCLUSIONS: By 24 months after HIV seroconversion, the oldest subjects and those with the highest HIV RNA levels during early chronic infection had experienced the most severe depletion of CD4+ cells. Subsequent declines in CD4+ cells varied little by early chronic HIV RNA level or age.

Adolescent↗

Patterns of seroconversion to Aujeszky's disease virus in unvaccinated chronically infected Swedish weaner pig-producing herds.

This study was carried out in nine unvaccinated Swedish weaner pig-producing herds, ranging in size from 20 to 134 breeding animals, which had experienced a previous outbreak of Aujeszky's disease (AD) and in which seropositive sows were still present. The objective was to quantify the seroconversion rate to Aujeszky's disease virus (ADV) in breeding animals and to find out whether unvaccinated herds could become free from ADV by using only seronegative animals for replacement. Serum samples were initially obtained from all adult pigs in the herds. Animals testing negative, as well as replacement animals, were subsequently tested every second or third month and the herds were followed for 10-28 months. The herd owners were advised to keep seropositive and seronegative animals separate whenever possible and to implement sanitary measures against the reintroduction of the virus into the herds. All herds experienced long consecutive periods (> or = 4 months, median 9 months) without seroconversion. Three herds became free from ADV during the serological study; in two of these herds no seroconversion was observed. In those seven herds where seroconversion occurred, between 9 and 86% of the susceptible pigs became infected. The reinfection was indicative of the reactivation of latent virus in all herds but two, where the reintroduction of the virus was most likely. The pattern of seroconversion was either sporadic, involving not more than three animals at a time, or epidemic, involving a large proportion of the susceptible animals in the herd. Severe clinical outbreaks hit the two largest herds and these only became ADV-free after the conclusion of the study when vaccine was used, which reduced the incidence of seroconversion to zero. The results from the present study show that it is possible for smaller herds to achieve freedom from ADV without any radical control methods, provided that only ADV-free replacement animals are used and the virus is not reintroduced. Moreover, the finding that long periods can elapse without transmission suggests that when infection is discovered in a herd, the risk of massive spread is not necessarily imminent.

Animal Husbandry↗

Interleukin-10 promoter polymorphisms are associated with the mode and sequel of HBeAg seroconversion in patients with chronic hepatitis B virus infection.

BACKGROUND: The influence of interleukin-10 (IL-10) gene promoter polymorphisms on the mode and sequel of HBeAg seroconversion (a favorable event usually) in patients with chronic Hepatitis B virus (HBV) infection has not been clarified. PATIENTS AND METHODS: IL-10 genotyping and haplotype analyses of 340 HBsAg carriers and 100 volunteers with self-limiting HBV infection from southern China, a high prevalent area of HBV were performed according to the single nucleotide polymorphisms in its promoter (-1,082, -819 and -592) using a competitively differentiated PCR. RESULTS: High-producer genotype (GG at -1,082) or haplotype (GCC) was rarely found in patients from southern China (<1%). Intermediate-producer haplotype (ACC) was closely associated with chronic liver disease (P=0.004); compared with this, low-producer genotype (AA at -592) and haplotype (ATA) were closely associated with asymptomatic carriers (P=0.035 and 0.035). Intermediate-producer genotype (AC at -592) and haplotype (ACC) were closely associated with covert seroconversion of HBeAg (P=0.0086 and 0.0013) and progressive sequel after HBeAg seroconversion (P=0.013 and 0.0008), while, low-producer genotype (AA at -592) and haplotype (ATA) were closely associated with overt seroconversion of HBeAg (P=0.0023 and 0.0061) and silent sequel after HBeAg seroconversion (P=0.0009 and 0.001). CONCLUSIONS: IL-10 gene promoter polymorphisms significantly influence the mode and sequel of HBeAg seroconversion in patients with chronic HBV infection.

Adult↗

Spatial analysis of seroconversion of sentinel cattle to bluetongue viruses in Queensland.

OBJECTIVE: To assess quantitatively the spatial distribution of seroconversion of Queensland cattle to bluetongue viruses. DESIGN: A sentinel herd study. SAMPLE POPULATION: Sixty-nine sentinel herds at 30 locations. PROCEDURE: Spatial clustering of seroconversion to bluetongue viruses was investigated during the period from 1990 to 1994. RESULTS: Seroconversion to only two bluetongue virus serotypes, 1 and 21, was observed. The 14 herds, in which seroconversion to bluetongue virus serotype 1 was detected, were located only along the eastern coastal and subcoastal region of Queensland, and were significantly (P < 0.05) clustered. Locations at which seroconversion to serotype 21 was detected, were not significantly clustered. The results generally agree with field observations, except for the failure to detect seroconversion to bluetongue viruses in north-western Queensland. CONCLUSION: Bluetongue infection of cattle in north-western Queensland may be temporally sporadic. The dominance of serotype 1 in the Queensland cattle population may be the result of differential transmission by potential vector species. Long-term surveillance programs are important for defining disease status of animal populations.

Animals↗

HIV-1 seroconversion incidence following pregnancy and delivery among women seronegative at recruitment in Harare, Zimbabwe.

OBJECTIVE: To estimate the incidence of HIV seroconversion among women following pregnancy and delivery. DESIGN: A prospective cohort of women who were HIV negative at recruitment on first antenatal care visit. MATERIALS AND METHODS: Pregnant women were invited to undergo voluntary confidential HIV counselling and blood draw for HIV testing during the first antenatal care visit as part of a prospective study of mother-to-child transmission of HIV-1. Repeat tests were conducted at delivery, six weeks post partum and at three monthly intervals until 24 months or on termination due to subsequent pregnancy, death or loss to follow up. Logistic regression modelling was used to determine independent predictors of HIV seroconversion. RESULTS: Among 372 HIV negative pregnant women who were enrolled, 66 seroconverted during follow up, resulting in a sero-incidence of 4.8 per 100 person years (95% confidence interval [CI], 3.1 to 6.5). Women who did not seroconvert during the time of pregnancy or follow up were significantly more likely to have used a condom with their partners (OR = 0.68, 95% CI = 0.47 to 0.99). Women aged 17 years and below had the highest seroconversion incidence (6.25%) followed by those aged 18 to 19 years (5.42%). Women who seroconverted and those who were HIV positive at recruitment were more likely to be married. Lack of education by the partner of a pregnant woman constituted a significant risk factor for HIV seroconversion (OR = 2.8; 95% CI = 1.1 to 11.0). CONCLUSIONS: There is a high HIV seroconversion incidence among women during pregnancy and following delivery, especially those aged 19 years and below. Being married does not protect the women from the risk of HIV seroconversion. Strategies for HIV prevention should target pregnant women and their partners.

Adolescent↗

Longitudinal analysis of the 90K glycoprotein in the Italian HIV-seroconversion study: temporal trend and predictability of the maturity of HIV infection.

OBJECTIVES: To evaluate the level of 90K as a predictor of AIDS; to describe 90K levels over time after HIV serconversion; and to evaluate the 90K level as a marker of the maturity of infection. DESIGN: Prospective incident cohort of HIV-infected individuals with documented dates of seroconversion. METHODS: Cox models were applied to estimate the crude and adjusted relative hazards (RH) of AIDS by level of 90K. Regression models were applied to describe the temporal trend and the correlates of the level of 90K over time after HIV-seroconversion. Logistic models were applied to evaluate the probability of a sample of 90K having been taken within a certain time period after HIV-seroconversion. RESULTS: The study population consisted of 150 participants of the Italian Seroconversion Study. A total of 429 measurements of 90K were taken. Both early and later measurements of 90K were highly predictive of AIDS, also when adjusting for CD4 lymphocyte count and HIV load. The 90K level (U/ml) increased by 10% annually (95% CI: 7%-13%); the increase over time was linear. IDUs had higher 90K levels than heterosexuals and homosexuals over the course of HIV disease. High 90K levels were highly predictive of distant seroconversions (age-adjusted probability, 74%), whereas were poorly predictive of recent seroconversions (age-adjusted probability, 5%); the results were similar for the predictability of CD4 lymphocyte count. CONCLUSIONS: The level of 90K is a useful prognostic tool for clinical purposes. As a marker of the maturity of infection, 90K is similar to the CD4 lymphocyte count, with the advantage of being able to use serum instead of fresh whole blood. It has a good capacity to identify distant infections.

Acquired Immunodeficiency Syndrome↗

The Vancouver Lymphadenopathy-AIDS Study: 6. HIV seroconversion in a cohort of homosexual men.

In an ongoing prospective study of homosexual men conducted since November 1982 in Vancouver, we identified 345 men who did not have antibody to human immunodeficiency virus (HIV) at the time of enrolment and for whom results of follow-up serologic testing were available. A total of 66 cases of seroconversion were documented among the 345 men between November 1982 and October 1985. Methods of survival data analysis that take into account the varying durations of follow-up were used to study the epidemiologic features of seroconversion in this group. The probability of seroconversion during the entire observation period was 23.1%. The seroconversion rates remained stable, at 10.5% and 10.0% during the last 2 years of the observation period. Cox regression analysis revealed the following variables to be independently associated with risk of seroconversion: frequent receptive anal intercourse, elevated number of male sexual partners in the year before enrolment, use of illicit drugs, a history of gonorrhea and age less than 30 years in November 1982. Multivariate analysis failed to reveal any role of oral sexual activity in the transmission of HIV. Oral ingestion of semen was not associated with seroconversion in either univariate or multivariate analysis. The observation that younger men were more likely to seroconvert suggests that young homosexual men were less likely than older men to modify their sexual behaviour.

Acquired Immunodeficiency Syndrome↗

HIV-antibody seroconversions in Dutch haemophiliacs using heat-treated and non heat-treated coagulation factor concentrates.

A national multicentre study was performed to investigate the effects of donorselection and the use of heat-treated plasma products on seroconversion to HIV in 157 Dutch haemophiliacs. All patients included in the study were seronegative for HIV antibodies in 1983. Thirteen percent (20/157) seroconverted between 1983 and 1986. Nineteen of 20 seroconversions could be related to the use of non heat-treated products in the year preceding HIV antibody seroconversion. One seroconversion occurred in a person using heat-treated non donor screened product. Seroconversion rate decreased as a result of the policy to discourage high risk blood donors and no seroconversions were observed following the introduction of donor screening in 1985.

Blood Coagulation Factors↗

Changes in T and non-T lymphocyte subsets following seroconversion to HIV-1: stable CD3+ and declining CD3- populations suggest regulatory responses linked to loss of CD4 lymphocytes. The Multicenter AIDS Cohort Study.

We investigated changes in lymphocyte subsets (total, CD4+ and CD8+ T cells, as well as non-T cells) associated with human immunodeficiency virus type I (HIV-1) seroconversion in 321 homosexual or bisexual men in the Multicenter AIDS Cohort Study (MACS). These subjects had serial lymphocyte characterizations for up to 4 years before and 5 years after seroconversion. CD4+ lymphocyte levels declined rapidly in the first 18 months following seroconversion and less rapidly thereafter, while CD8 lymphocytes increased with similar kinetics. In contrast, total T (CD3+) lymphocytes declined only slightly in the first 18 months following seroconversion, and then remained stable. These results support the hypothesis of physiologic regulation of the total number of circulating T cells, such that lost CD4+ lymphocytes are replaced by newly generated CD4+ and CD8+ lymphocytes; over time, continued loss of CD4+ lymphocytes due to HIV-1 infection would result in net replacement of lost CD4+ lymphocytes with CD8+ lymphocytes. Non-T (CD3-) lymphocytes also declined after seroconversion, and this decline paralleled that of CD4+ lymphocytes. Thus, changes in both T and non-T lymphocytes after HIV-1 seroconversion may reflect the operation of homeostatic or regulatory mechanisms. Whether these mechanisms contribute to the development of immune deficiency requires further study.

CD3 Complex↗

Geographic variation in human immunodeficiency virus seroconversion rates in the U.S. Navy.

The Navy population is centered around 19 U.S. home ports and several inland duty stations. This is a study of variation in human immunodeficiency virus (HIV) seroconversions in Navy enlisted men by location in the United States, based on 949,570 enzyme-linked immunosorbent assays and 812 seroconversions during 1987-90. Seroconversion rates were higher in personnel in San Francisco (p = 0.0004), Washington, D.C. (p = 0.001), and Orlando, FL (p = 0.04) than in other areas. They were lower in Charleston, SC, New London, CT, Seattle; and Brunswick, ME (p < 0.05). Black men had triple the seroconversion rate of all other men (p < 0.0001). After adjustment for race, age, marital status, and occupation, risk of seroconversion remained high in San Francisco (p = 0.02) and Orlando (p = 0.03). The risk of seroconversion in San Francisco was twice that of other areas in a cohort that did not change location (p = 0.01). In contrast to declining trends overall in the Navy, rates did not decrease in Washington, D.C., a result consistent with previous calculations indicating a delayed second wave of HIV infection in the region.

Adolescent↗

Sex differences in risk factors for hiv seroconversion among injection drug users: a 10-year perspective.

BACKGROUND: Injection drug use directly or indirectly accounts for nearly half the annual human immunodeficiency virus (HIV) infections in the United States. Prospective studies that investigate both sexual and parenteral HIV risks among injection drug users (IDUs) are needed. We studied factors for HIV seroconversion among male and female IDUs in Baltimore, Md. METHODS: The HIV-negative IDUs (1447 male and 427 female) were recruited into a prospective study from 1988 to 1989 or in 1994. Participants underwent semiannual HIV tests and surveys through December 1998. Poisson regression was used to identify risk factors for HIV seroconversion, stratified by sex. Behaviors were treated as time-dependent covariates that varied at each semiannual period. RESULTS: Subjects were primarily African American (91%), and median age at enrollment was 35 years. Incidence of HIV was 3.14 per 100 person years (95% confidence interval, 2.78-3.53) and did not significantly differ by sex. Younger age independently predicted HIV seroconversion for both men and women. Among men, factors that independently predicted HIV seroconversion were the following: less than a high school education, recent needle sharing with multiple partners, daily injection, and shooting-gallery attendance. The incidence of HIV was double for men recently engaging in homosexual activity and cocaine injection. Among women, the incidence of HIV was more than double for those recently reporting sexually transmitted diseases. CONCLUSIONS: The incidence of HIV remained high among IDUs in Baltimore over the past decade. Risk factors for HIV seroconversion differed markedly by sex. Predominant risks among men included needle sharing and homosexual activity; among women, factors consistent with high-risk heterosexual activity were more significant than drug-related risks. Human immunodeficiency virus interventions aimed at IDUs should be sex-specific and incorporate sexual risks.

Adolescent↗

Genotypic differences in the hepatitis B virus core promoter and precore sequences during seroconversion from HBeAg to anti-HBe.

Hepatitis B virus (HBV) strains from anti-HBe positive patients often show specific mutations in the precore gene, the core promoter region, or both. The dynamics of seroconversion in relation to the appearance of these mutations has not been studied and compared between defined HBV genotypes. Samples from patients followed during seroconversion from HBeAg to anti-HBe were amplified by polymerase chain reaction (PCR), sequenced and genotyped. Among 16 sets of samples, 6 belonged to genotype A, 6 to genotype D, 2 to genotype B, 1 to genotype C, and 1 to genotype E. Whereas strains from genotypes B, C and E showed changes in the core promoter, precore codon 28 or both, genotype A and D strains displayed a different pattern. In 4 of 6 anti-HBe positive samples from genotype A, the precore had a wild-type sequence while the core promoter sequence showed a specific TGA mutation. In another genotype A strain a precore stop mutation was preceded by a mutation in codon 15, thus conserving base-pairing at the pregenomic RNA level in this region. In contrast, all genotype D strains showed wild-type sequences in both the core promoter and precore codon 28 in pre- and post-seroconversion samples. Thus, in 8 patients with a mean follow-up time of 17 months, wild-type sequences in both the core promoter and precore codon 28 were found after seroconversion to anti-HBe. This study also confirmed, for genotype D, that HBeAg seroconversion often occurs earlier than genomic conversion.

Adolescent↗

Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis.

Two types of clinical events, acute exacerbation and uneventful course, precede spontaneous HBeAg seroconversion to its antibody (anti-HBe) in chronic type B hepatitis. To examine the possible mechanism responsible for these two types of clinical events, serial serum specimens from 75 patients who underwent spontaneous HBeAg seroconversion were assayed for hepatitis B virus DNA by slot blot hybridization with 32P-labeled cloned hepatitis B virus DNA as probe. Of these 75 patients, 47 (62.7%) had episodes of acute exacerbation (ALT greater than 300 IU per liter) within 3 months prior to HBeAg seroconversion. All of these 47 patients had high hepatitis B virus DNA levels (greater than 1,000 pg per ml) at the onset of acute exacerbation. Their serum hepatitis B virus DNA disappears shortly before or simultaneously with the HBeAg clearance in 27 patients (57.4%) and persisted but with decreasing levels for 2 to 40 months in 20 patients. Most of these patients had high alpha-fetoprotein levels or evidence of bridging hepatic necrosis. In contrast, the serum hepatitis B virus DNA was undetectable for a minimum of 3 (3-17) months in the 28 patients who had an uneventful course before HBeAg seroconversion. Twenty of these 28 patients had well-documented episodes of acute exacerbation with high hepatitis B virus DNA levels, but with normal alpha-fetoprotein and little evidence of extensive necrosis as far back as 6 to 27 months before HBeAg seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Clinical and histological outcome after hepatitis B e antigen to antibody seroconversion in children with chronic hepatitis B.

Data regarding the outcome of children with chronic hepatitis B after seroconversion are scarce. We describe the long-term evolution of these patients. One hundred and three children with antibody against hepatitis B e antigen and normal alanine aminotransferase (ALT) levels were followed for 0.6 to 12.5 years (mean, 6.3 years). Paired liver biopsies (before and after seroconversion) were available in 83 cases. Final biopsies were obtained 0.5 to 12.5 years (mean, 4.5 years) after seroconversion. ALT levels remained normal in most of the children (79%) throughout the follow-up. All children, except five who lost hepatitis B surface antigen, had serum viral DNA detected by polymerase chain reaction. When comparing baseline and final liver biopsies, a significant improvement (P <.001) was found in the histological activity index and in the necrosis, cytolysis, inflammation, and fibrosis scores. The histological diagnosis improvement in the final biopsy was significantly related (P <.001) to the time from seroconversion to the biopsy performance. All children had viral DNA on their final liver biopsy. In summary, seroconversion and ALT normalization are quite stable findings in children, and no differences in the long-term outcome between treated and untreated children were found. In light of the histological outcome, it seems unnecessary to perform a follow-up liver biopsy in these cases.

Alanine Transaminase↗

Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriers.

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 < or =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.

Adolescent↗