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Sexual risk behaviors and implications for secondary HIV transmission during and after HIV seroconversion.

OBJECTIVES: To determine the potential for secondary HIV transmission among newly HIV-infected men who have sex with men (MSM) during their HIV antibody seroconversion period, and for the 12 months after seroconversion. DESIGN: A cohort study. METHODS: Risk assessment questionnaires administered before receipt of the first positive HIV antibody result, plasma and seminal viral load measurements, and risk assessments one month and quarterly after receipt of the first HIV-positive test, and generalized estimating equation modelling techniques to analyse behavioral trends. RESULTS: Of 66 seroconverters, more than half reported unprotected anal intercourse (UAI) with HIV-negative or unknown-serostatus partners during seroconversion, with 27% reporting insertive UAI with an HIV-negative partner. The initial median plasma viral load was 4.6 log/ml, the median seminal viral load was 2.7 log/ml, suggesting a high level of infectiousness. Compared with risk behavior during seroconversion, UAI with HIV-negative or unknown-serostatus partners was reduced after the receipt of positive antibody results; however, a substantial proportion of participants reported high-risk behaviors for transmission for 12 months of follow-up. After learning of their HIV infection, recent seroconverters did not reduce the risk of secondary transmission by engaging in proportionally more high-risk practices with HIV-infected partners (compared with HIV-negative or unknown-serostatus partners), or engaging in proportionally more receptive compared with insertive UAI. CONCLUSION: Substantial potential exists for secondary HIV transmission during and for one year after HIV seroconversion. Receipt of an HIV-positive test is associated with a significant reduction in risk behavior, reinforcing the need to identify and counsel recently HIV-infected MSM.

Adult↗

Age at time of hepatitis Be antibody seroconversion in childhood chronic hepatitis B infection and mutant viral strain detection rates.

BACKGROUND: Investigations of adult patients have demonstrated that with seroconversion, changes occur from wild-type strains of the infecting virus to mutant strains. However, to date, there have been few reports and insufficient investigation of this issue in children. METHODS: The presence or absence of nucleotide base and amino acid sequence mutations in a portion of the X region containing the core promoter region, the pre-C region, and the C region of HBV genomic DNA were investigated using a polymerase chain reaction-direct sequencing method on serum samples collected from 14 children who were hepatitis Be antibody (HBeAb)-positive carriers. Samples from three children who were HBe antigen (HBeAg)-positive carriers served as the control subjects. RESULTS: When patients were grouped based on whether they had had documented seroconversion before age 6 or at age 6 or older, differences in mutant viral detection rates involving the core promoter region and the pre-C region were apparent. Specifically, a mutant strain showing a G-to-A substitution at nucleotide 83 in the pre-C region, or a mutant strain showing an A-to-T substitution at nucleotide 1762 and a G-to-A substitution at nucleotide 1764, was detected in only two of eight cases (25%) from the HBeAb-positive carriers with documented seroconversion before age 6. In contrast, these findings were present in six of six patients (100%) with documented seroconversion at age 6 or older. CONCLUSIONS: The results of the present study suggest that the mechanism of onset of HBeAb seroconversion differs between children aged less than 6 years and those who are aged 6 or more.

Adolescent↗

Cytomegalovirus infections in Toronto child-care centers: a prospective study of viral excretion in children and seroconversion among day-care providers.

OBJECTIVES: To prospectively determine the rate of cytomegalovirus shedding in children and the rate of seroconversion to cytomegalovirus in providers at 38 infant-toddler day care centers in Toronto, Canada. METHODS: Urine was collected for shell vial assay in 471 children between the ages of 3 and 42 months. Providers (n = 206) were tested for the presence of cytomegalovirus antibody by latex agglutination. Of the 68 providers who were seronegative, 56 were retested approximately 1 year later. RESULTS: Viruria was documented in 79 (17%) children and antibody in 67% of providers. Seropositivity was significantly related to country of birth outside Canada, presence of children at home < 5 years of age and increased household size. Seroconversion was documented in 12.5% (n = 7). Of these providers 71% worked at centers where workers never wore gloves for diaper changing vs. 33% of those who did not seroconvert (P = 0.06), and all were younger than 30 years vs. 59% of those who did not seroconvert (P = 0.04). In centers with viruria the association of seroconversion with lack of glove use was enhanced (P = 0.04). Seroconversion was marginally more likely in providers working with infants only than with infants and toddlers or with toddlers alone. Logistic regression confirmed that seroprevalence was more likely in providers who were born outside Canada, had children younger than age 5 years in the household and with an increased number of people in the household. Seroconversion was more likely if the provider worked at centers not using gloves for diaper changes, worked with infants only rather than with toddlers and infants and was < 30 years old, with each factor contributing independently to the model. CONCLUSIONS: Cytomegalovirus infection is common in children and providers in Toronto day-care centers.

Adolescent↗

Human immunodeficiency virus type-1 seroconversion trends among young adults serving in the United States Army, 1985-1993. United States Military Medical Consortium for Applied Retroviral Research.

The direct measurement of the incidence of new infections with the human immunodeficiency virus type 1 (HIV-1) can be made among soldiers because of the routine and periodic nature of HIV-1 testing in the United States Army. Between November 1985 and October 1993, 978 HIV-1 seroconversions were seen among 1,061,768 soldiers, contributing over 3.6 million person-years of follow-up [seroconversion rate (95% confidence interval) = 0.27/1,000 person-years (0.25-0.29)]. A significant decreasing trend in HIV-1 seroconversion rates was seen over the analysis period. The rate of new infections declined significantly from the first interval, 1985-1987, (0.43/1,000 person-years) to the second interval, 1987-1988, (0.28/1,000 person-years), but stabilized at approximately 0.22/1,000 person-years after 1988, representing new infections in approximately 100-150 soldiers annually. The risk of seroconversion among active duty soldiers was significantly associated with racial/ethnic group, age, gender, and marital status. Surveillance of HIV-1 seroconversion rates in the U.S. Army continues to offer a unique opportunity to assess temporal trends in the evolving HIV-1 infection epidemic. Monitoring the rate of new HIV-1 infections allows for identification of subgroups in need of intervention, refocusing of intervention strategies, and evaluation of their effectiveness.

Adult↗

Continuous cytomegalovirus seroconversion in a large group of healthy blood donors.

BACKGROUND AND OBJECTIVES: Transmission of cytomegalovirus (CMV) to seronegative, immunocompromised recipients can cause serious and fatal complications. Although the seroprevalence of CMV is high, the risk of primary CMV infection among healthy blood donors has not yet been analysed in a large population. MATERIALS AND METHODS: We developed an algorithm to determine the rate of CMV seroconversion in an overall cohort of 24,260 subjects who donated 176,474 blood units during an 11-year observation period. RESULTS: We detected CMV seroconversion in all relevant age groups (18-60 years) with an overall seroconversion rate of 0.55% per year. Both CMV seroconversion and seroprevalence occurred more frequently in female donors (P = 0.02 and P < 0.001, respectively). We identified 30-35-year-old blood donors as the group with the highest rate of CMV seroconversion per year (1.33% vs. 0.46%; P < 0.0001). CONCLUSIONS: We conclude that the risk of primary CMV infection is a continuous lifelong event and correlates with age and female gender.

Adolescent↗

Seroconversion and seroreversion of Helicobacter pylori antibodies over a 9-year period and related factors in Japanese adults.

BACKGROUND: There are still insufficient data on the frequency of seroconversion and seroreversion of Helicobacter pylori antibodies. The frequency of serochange and related factors were investigated in this study over 9 years. SUBJECTS AND METHODS: Using sera from 3104 workers who underwent health checks in 1989 and again in 1998, H. pylori antibodies were measured. Those with intermediate serology were excluded from the study. Information on past history was collected using a questionnaire. RESULTS: Of the 912 seronegative and 1286 seropositive subjects in 1989, seroconversion was observed in 57 and seroreversion in 91 subjects. Seroconversion and seroreversion rates over the 9-year period were 6.3% and 7.1%, respectively, giving rates per 1000 person-years (with 95% confidence interval) of 7.0 (5.2-8.7) and 7.9 (6.3-9.4), respectively. Subjects that reported abdominal symptoms or gastric fiberscope use showed significantly higher seroconversion rates than controls (8.7 vs. 4.5 and 9.2 vs. 1.6, respectively), which remained significant after adjustment for age and gender. Those with a history of duodenal ulcers, a smoking habit or a drinking habit showed significantly lower seroreversion rates than controls (3.5 vs. 8.9, 5.4 vs. 9.2 and 5.9 vs. 13.3, respectively). After adjustment, the association between seroreversion and smoking habit disappeared, while the associations with history of duodenal ulcers and drinking habit remained. CONCLUSIONS: Those with a history of nonspecific abdominal symptoms and those with a history of gastric fiberscope use showed higher seroconversion rates. Alcohol consumption and duodenal ulcers may inhibit the autoeradication of H. pylori, possibly through increased acid secretion.

Adult↗

Modification of rapid human immunodeficiency virus (HIV) antibody assay protocols for detecting recent HIV seroconversion.

Assay protocols of three rapid human immunodeficiency virus (HIV) assays, OraQuick-1/2, SeroStrip-1/2, and Determine-1/2, were modified to detect recent HIV seroconversion using a higher dilution of serum specimens. Optimal predilution of specimens resulted in negative test results during early periods of seroconversion (about 6 months), when antibody levels were low. A total of 269 seropositive specimens from routine HIV type 1 testing and from commercial sources (low-titer and seroconversion panels) were tested, and results were recorded as negative (score=0) or positive using intensity scores from 0.5 (weak positive) to 4 (strongly positive). The same specimens were previously tested by a less sensitive (LS) enzyme immunoassay (EIA), Abbott 3A 11-LS, and were classified as recent or long-term infections based on the standardized optical density (SOD) cutoff of 0.75. Overall concordance of >94% was observed between 3A 11-LS and modified rapid tests (RT-LSs) for detecting and distinguishing recent HIV seroconversion from long-term HIV infection (kappa statistics=0.894 to 0.901). Moreover, intensity scores on RT-LSs correlated well with median 3A 11-LS SOD values (R(2)>0.98). Our results indicate that rapid HIV tests can be modified to detect recent seroconversion with results comparable to those from less sensitive EIA.

Antibodies, Viral↗

Prospective multicenter study on isolation of human immunodeficiency virus type 1 from homosexual men after seroconversion.

A prospective multicenter study was undertaken to isolate human immunodeficiency virus type 1 (HIV-1) from 45 homosexual men for a period of 30 months after seroconversion. Efficiency of HIV-1 isolation from peripheral blood mononuclear cells was relatively stable over time, ranging from 64% at the time of seroconversion to more than 82% after 18 months of seroconversion. However, Kaplan-Meier analysis of HIV-1 culture data indicates that the cumulative proportion of HIV-1 culture positivity at 3, 6, 12, and 18 months after seroconversion was 62, 65, 84, and 92%, respectively. No significant correlation was observed between the presence of HIV-1 p24 antigen in serum, or numbers of CD4+ and CD8+ blood lymphocytes, and HIV-1 isolation within this period of time. These data suggest that HIV-1 viremia in homosexual men gradually increases to almost 100% culture positivity by 18 months after seroconversion.

HIV Seropositivity↗

Relation between humoral responses to HIV gag and env proteins at seroconversion and clinical outcome of HIV infection.

OBJECTIVE: To study the contribution of the humoral response to HIV-I at seroconversion to disease outcome after 84 months. DESIGN: A retrospective longitudinal study. SETTING: Two haemophilia centres in the United Kingdom. PATIENTS: 88 Haemophiliac patients infected with HIV-I for whom sera were available from before seroconversion and in whom clinical follow up data were available. RESULTS: Kaplan-Meier survival analysis showed a significant difference between a high titre (greater than 1600) p24 antibody response at seroconversion and prolonged time before the development of HIV related disease (p = 0.0008). In contrast, higher titres of antibody to gp120 at seroconversion (greater than 25,600) correlated with more rapid clinical deterioration (p = 0.025). CONCLUSIONS: The first humoral response to HIV proteins at seroconversion is associated with clinical outcome; patients with an initial low titre antibody response to the gagp24 protein have a significantly faster rate of progression to CDC stage IV disease. Patients with a high titre p24 antibody response progress to AIDS more slowly, and these data provide an explanation why p24 antigenaemia is not universally detected in patients with AIDS. It is unclear whether the association between a strong initial p24 antibody response and slower progression of HIV disease is causal and if so whether it is due to viral or host factors.

Gene Products, gag↗

Incidence of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England, 1993-5.

OBJECTIVE: To estimate the rate of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England and to describe the probable routes of infection in these donors. DESIGN: Retrospective survey of blood donors becoming positive for hepatitis C antibody and of the results of donation testing. SETTING: The 14 blood centres in England. SUBJECTS: All repeat donors giving blood between January 1993 and December 1995. MAIN OUTCOME MEASURES: Number of donors developing hepatitis C between donations during the three years of testing for hepatitis C antibody at English blood centres and the rate of seroconversion among repeat blood donors. Probable routes of infection. RESULTS: 14 donors during 1993-5 fulfilled the case definition for seroconversion to positivity for hepatitis C antibody. The estimated seroconversion rate for infection with hepatitis C in repeat donors was 0.26 per 100 000 person years (95% confidence interval 0.15 to 0.43). Counselling after diagnosis found that four of these donors had risk factors specified in the criteria excluding people from giving blood but these factors had not come to light before donation. Another of the donors who seroconverted had a risk factor that has since been included in the exclusion criteria. Heterosexual intercourse was considered to be the most likely route of infection for five of the 14 donors. CONCLUSIONS: The rate of seroconversion for positivity to hepatitis C antibody in repeat blood donors in England was extremely low. During 1993-5 fewer than 1 in 450 000 donations were estimated to have come from repeat donors who had become positive for hepatitis C antibody since the previous donation.

Adolescent↗

Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase.

BACKGROUND AND AIMS: Interferon (IFN) induced hepatitis B e antigen (HBeAg) seroconversion is durable in 80-90% of chronic hepatitis B patients. Preliminary reports on the durability of HBeAg seroconversion following lamivudine are contradictory. We investigated the durability of response following IFN, lamivudine, or IFN-lamivudine combination therapy in a meta-analysis of individual patient data. PATIENTS AND METHODS: Twenty four centres included 130 patients in total with an HBeAg seroconversion (HBeAg negative, antibodies to hepatitis B e antigen positive) at the end of antiviral therapy: 59 with lamivudine, 49 with interferon, and 22 with combination therapy. Relapse was defined as confirmed reappearance of HBeAg. RESULTS: The three year cumulative HBeAg relapse rate by the Kaplan-Meier method was 54% for lamivudine, 32% for IFN, and 23% for combination therapy (p=0.01). Cox regression analysis identified pretreatment hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), sex, and therapy as independent predictive factors of post-treatment relapse; Asian race, previous therapy, centre, and type of study were not predictive of relapse. The relative HBeAg relapse risk of lamivudine compared with IFN therapy was 4.6 and that of combination therapy to IFN therapy 0.7 (p(overall)=0.01). CONCLUSIONS: The durability of HBeAg seroconversion following lamivudine treatment was significantly lower than that following IFN or IFN-lamivudine combination therapy. The risk of relapse after HBeAg seroconversion was also related to pretreatment levels of serum ALT and HBV DNA, but independent of Asian race.

Adult↗

Seroconversion of hepatitis B vaccine in infants related to the mother's serostatus in a community of São José dos Campos, state of São Paulo, Brazil.

PURPOSE: To detect seroconversion of hepatitis B vaccine and antibody waning 3 years after vaccination in children immunized according to the World Health Organization schedule and its relationship to the mother's serostatus during pregnancy. METHODS: A serological study was carried out in São José dos Campos. Blood samples from pregnant women were taken for hepatitis B marker serology. To evaluate seroconversion in infants born to these women, serology was performed 1 month after they were vaccinated with recombinant vaccine. Another group of children was evaluated 3 years after being immunized. RESULTS: Among 224 pregnant women, 0.9% were positive for hepatitis B surface antigen, 8.0% for antibodies to the surface antigen, and 4.5% for antibodies to the virus core. Seroconversion among 174 infants was as follows: absent in 18 children (10.35%), low level in 15 (8.62%), intermediate level in 26 (14.94%), and a high level (good response) in 115 (66.09%). Antibody positivity after 3 years was as follows: absent in 8 children (7.92%), low level in 51 (50.5%), intermediate level in 20 (19.8%), and high level in 22 (21.78%). Considering the age that the vaccine was administered, a significant proportion of non-seroconverters was found among children who had received the complete 3-dose schedule before 9 months (P = 0.023). Another factor that significantly contributed to the lack of seroconversion was the presence of any serological marker for hepatitis B during pregnancy (P = 0.044). CONCLUSIONS: Data gathered in this work show that the immunization schedule for hepatitis B in low or moderate prevalence areas should be revised in order to optimize seroconversion.

Adolescent↗

Relative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection.

AIM: To determine the predictive factors for hepatocellular carcinoma (HCC) development in patients after spontaneous or therapeutic HBeAg seroconversion. METHODS: In 48 patients who seroconverted to anti-HBe positive during follow-up, the background factors for HCC development were analyzed. RESULTS: HCC was developed in six patients during follow-up (average follow-up after HBeAg seroconversion: 10.9+/-5.4 years). The incidence of HCC evaluated by Kaplan-Meier analysis was significantly higher in patients with abnormal aspartate aminotransferase (AST>40 IU/L) level, lower platelet counts (PLT< 10 x 10(4)/microL), lower albumin level (Alb<30 g/L), positive HBV-DNA or older age at seroconversion (>40 years). However, lower platelet count was the only predictive factor for HCC development shown by multivariate proportional-hazard analysis. CONCLUSION: Active hepatitis or advanced hepatitis at HBeAg seroconversion or progressive hepatitis even after HBeAg seroconversion would be the risk factors for HCC development. These predictive factors should be taken into account in determining the frequency of biochemical study or imaging studies for HCC surveillance.

Adolescent↗

Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion after lamivudine treatment.

AIM: To investigate the association of hepatitis B virus (HBV) genotype and HBeAg seroconversion after nucleotide analogue treatment. METHODS: Chronic hepatitis B patients receiving lamivudine followed up for at least 6 months post-treatment were studied. Consecutive treatment-naïve patients who were prospectively followed up in the clinic for at least 18 months were studied as controls. HBeAg seroconversion was defined as loss of HBeAg, appearance of anti-HBe and normalization of alanine aminotransferase for at least 6 months. RESULTS: Thirty-five patients on lamivudine and 96 control patients followed up for 39 (18-49) months were studied. Lamivudine was given for 12 (10-18) months, and patients were followed up for 15 (6-34) months after drug cessation. Genotype B and C HBV were found in 43 and 88 patients and HBeAg seroconversion occurred in 12 (28%) and 16 (18%) patients, respectively (P=0.30). There was no difference in HBeAg seroconversion between patients infected by genotype B and C HBV in the control (35% vs 21%, P=0.25) and lamivudine-treated (14% vs 10%, P=1.00) groups. CONCLUSION: HBeAg seroconversion after treatment by lamivudine was not influenced by the HBV genotype.

Adolescent↗

How soon after HIV seroconversion is antiretroviral therapy initiated? The UK Register of HIV Seroconverters Steering Committee.

OBJECTIVE: To estimate the time from HIV seroconversion to initiating antiretroviral therapy (ART) and whether this has changed over calendar time, and to estimate the CD4 cell count at which ART is initiated. DESIGN: Data from a cohort of HIV seroconverters in the UK were analysed with the initiation of ART as the outcome variable. METHOD: The association of the time from seroconversion to initiating ART with age, sex, exposure category, calendar time, CD4 cell count and acute infection at diagnosis was examined using Kaplan-Meier plots and Cox proportional hazards models. The CD4 level at which therapy was initiated was examined. Results Of 1308 seroconverters, 710 (54%) had started ART by 30 September 1998. Median interval from seroconversion to initiating ART was estimated to be 59.5 months [95% confidence interval (CI), 54.7-63.6]. Compared with 1989-1994 (after adjusting for CD4 cell count), time to initiation of ART was significantly shorter in 1997-1998 with relative rates of initiating ART of 1.02 (95% CI, 0.67-1.55), 1.07 (95% CI, 0.88-1.31) and 3.16 (95% CI, 2.56-3.90) pre-1989, 1995-1996, and 1997-1998, respectively. Median CD4 cell count at initiation of treatment was 73 (95% CI, 30-109), 136 (95% CI, 118-161), 110 (95% CI, 84-140) and 221 (95% CI, 200-250) x 10(6) cells/I for the periods pre-1989, 1989-1994, 1995-1996 and 1997-1998, respectively. Of persons seroconverting in 1997-1998, 19.5% initiated ART within 6 months of seroconversion compared with 8.4% and 2.0% in 1995-1996 and 1989-1994, respectively. CONCLUSIONS: ART is being initiated closer to HIV seroconversion than in previous years. Whether the improvements in survival reported from recent observational studies result solely from increased efficacy of the regimens or also from the timing of their initiation is difficult to determine. No clinical trial has yet addressed the optimum timing of initiating ART in the era of potent therapies.

Adolescent↗

[A long-term observation and follow-up for patients with HBeAg/Anti-HBe seroconversion after lamivudine treatment].

OBJECTIVE: To observe the resulting change in patients who achieved HBeAg/Anti-HBe seroconversion after lamivudine treatment. METHODS: 68 patients were observed for over 24 months. They were HBeAg/Anti-HBe with a seroconversion time > or = 6 months and the course of lamivudine treatment was > or = 18 months. RESULTS: After lamivudine treatment, the rate of HBeAg/Anti-HBe seroconversion was 25.19%, the rate of YMDD mutations was 20.59%, and the rate of relapse was 27.94% for these patients that achieved HBeAg/Anti-HBe seroconversion in observation and in the follow-up period. Lamivudine was still an effective drug for these patients with relapses. The rate of relapse was in correlation to the patients' age and the ALT level before treatment. The rate of relapse was not correlated to the HBV DNA level before the course of treatment. YMDD mutations were not correlated to the relapses. CONCLUSION: Even with a HBeAg/Anti-HBe seroconversion time > or = 6 months, the rate of relapse was still higher in patients with chronic hepatitis B that received lamivudine. The patients with long-term lamivudine treatment should be observed and have frequent follow-up visits.

Adult↗

Trends of HIV seroconversion among young adults in the US Army, 1985 to 1989. US Army Retrovirus Research Group.

Because soldiers in the US Army are recurrently tested for the presence of antibody to the human immunodeficiency virus (HIV), HIV seroconversion rates can be directly measured. From November 1985 through October 1989, 429 HIV seroconversions were detected among 718,780 soldiers who contributed 1,088,447 person-years of follow-up time (HIV seroconversion rate, 0.39 per 1000 person-years). Period-specific seroconversion rates declined significantly from 0.49 per 1000 person-years (November 1985 through October 1987) to 0.33 per 1000 person-years (November 1987 through October 1988) to 0.29 per 1000 person-years (November 1988 through October 1989). The HIV seroconversion risk among active-duty soldiers was significantly associated with race/ethnic group, age, gender, and marital status. Based on these trends, we estimate that approximately 220 soldiers (95% confidence interval, 160 to 297 soldiers) were infected with HIV during 1989 and 1990, with potentially fewer in future years.

Adolescent↗

[Morphologic findings in liver tissue in chronic active hepatitis B after seroconversion from HBeAg to anti-HBe].

Replication of the virus is in the majority of patients with chronic hepatitis B associated with permanent activity and progression of the inflammatory process. The change of the virus to the latent stage expressed by seroconversion of HBeAg to anti-HBe leads to a significant repression of inflammatory changes and has a favourable impact on the course of the disease. The morphological changes in the hepatic tissue after spontaneous seroconversion or after interferon treatment were investigated in specimens of needle biopsy in 18 patients with active chronic hepatitis B. In 10 of them the diagnosis of chronic hepatitis was confirmed by biopsy in the stage of replication of the virus. During the subsequent time interval after seroconversion of HBeAg, incl. two instances where interferon was administered, in the tissue of 14 HBsAg positive patients regression of inflammatory changes was apparent, in particular a lower incidence of piecemeal necroses. The regular finding of periportal and septal fibrosis in these patients is probably associated with a longer course of chronic active hepatitis and late spontaneous or therapeutically induced seroconversion of HBeAg. In one man, treated with interferon, morphological examination revealed one month after seroconversion of HBeAg an acute exacerbation of the disease. In another three patients, who at the time of the bioptic examination were HBsAg negative, in the hepatic tissue minor silent periportal and septal fibrosis persisted.

Adolescent↗