• Pediatric Infection and Vaccine
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• v.25 no.2
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• pp.72-81
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• 2018

Purpose: This prospective study aimed to investigate the therapeutic efficacy of lamivudine in children with chronic hepatitis B virus (HBV) infection. Methods: During July 2003 through October 2015, children with chronic hepatitis B who visited our institution were included in this study. Fifty-five patients, who received first-line treatment of lamivudine (3 mg/kg, 100 mg maximum) for over three months, were enrolled. After initiating lamivudine, alanine aminotransferase (ALT), HBV-DNA, and HBV markers were followed up at 1 month, 3 months, and every 3 months, thereafter. The treatment endpoint was determined as 1) normalization of ALT, 2) HBeAg seroconversion, and 3) anti-HBe positivity for twelve consecutive months. Results: Thirty-one male (56.4%) and 24 female (43.6%) patients were included. The mean age at treatment initiation was 8.1 years. The mean duration of treatment was 23.4 months. ALT normalization was found in 98.2% (54 of 55). Anti-HBe seroconversion was found in 70.6% (36/51). Loss of HBsAg was found in 10.9% (6/55). All biochemical responses occurred under age seven. The rate of virologic response (defined as HBV-DNA <2,000 IU/mL) at six months after treatment initiation was 78.7% (37/47). At twelve months after reaching treatment endpoint, 87.2% (34/39) maintained their virologic response. Resistance to lamivudine was found in 16.4% (9/55). Conclusions: Lamivudine treatment in Korean pediatric patients with chronic hepatitis B showed better outcomes compared with other studies that implemented similar protocols in foreign populations. Further studies are needed to investigate the efficacy of newly recommended antiviral drugs on the Korean pediatric population.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.16 no.2
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• pp.80-88
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• 2013

Purpose: To identify the predictive factors of long-term therapeutic response or resistance to lamivudine treatment in children and adolescents with chronic hepatitis B. Methods: Eighty one children and adolescents with chronic hepatitis B were included, who received lamivudine treatment for at least 6 months. Their condition was monitored for at least 12 months (12-88 months) thereafter. Twenty one (25.9%) were preschool children ($age{\leq}6$). For patients who had developed HBeAg seroconversion or breakthrough, univariate and multivariate analyses were used to identify the effects of age, gender, pretreatment alanine aminotransferase (ALT) and hepatitis B virus DNA levels. Results: HBeAg seroconversion occurred in 49 (60.5%) of the 81 patients after the initiation of the lamivudine therapy. In 65 patients whom were monitored for over 24 months, the seroconversion rate was significantly higher in younger patients (p=0.040), especially in those patients of preschool age ($age{\leq}6$, p=0.031). The seroconversion rate was significantly higher in higher pretreatment ALT (p=0.003). The breakthrough occurred in 21 (25.9%) of the 81. The breakthrough rate was lower in younger aged patients ($age{\leq}6$), and with higher pretreatment ALT levels, but no significant difference. Conclusion: Younger age is a good predictor of HBeAg seroconversion in children with long-term lamivudine treatment as well as high pretreatment ALT levels.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.17 no.1
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• pp.41-46
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• 2014

Purpose: The spontaneous seroconversion rate of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) virus infection in children is lower than that in adults. However, few studies have investigated the rate of transition from the immune-tolerant to the early immune-clearance phase in children. Methods: From February 2000 to August 2011, we enrolled 133 children aged <18 years who had visited the Department of Pediatrics, Kyungpook National University Hospital. All subjects were in the immune-tolerant phase of HBeAg-positive CHB virus infection. The estimated transition rate into the early immune-clearance phase was calculated using the Kaplan-Meier method. Results: Among the 133 enrolled pediatric CHB virus infection patients in the HBeAg-positive immune-tolerant phase, only 21 children (15.8%) had converted to the early immune-clearance phase. The average age at entry into active hepatitis was $10.6{\pm}4.8$ years. The incidence of transition from the immune-tolerant to the early immune-clearance phase in these children was 1.7 episodes/100 patient-years. When analyzed by age, the estimated transition rate was 4.6%, 7.1%, and 28.0% for patients aged <6, 6-12, >12 years, respectively. Conclusion: In children with CHB virus infection, the estimated rate of entry into the early immune-clearance phase was 28.0% for patients aged 12-18 years, which was significantly higher than that observed for children aged <12 years (11.7%; p=0.001).

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.79-89
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• 1998

Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

• Journal of Yeungnam Medical Science
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• v.14 no.2
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• pp.483-496
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• 1997

만성 B형 간염의 경과중 흔히 볼 수 있는 간기능의 이상은 대부분 심한 황달의 동반없이 혈청 AST와 ALT의 증가만 보이면서 악화되는 것이다. 저자는 심한 황달을 동반한 16명의 만성 B형 간염 악화 환자(연구군)와 심한 황달없이 AST와 ALT치만 증가된 13명의 환자(비교군)를 비교관찰하였다. PMC 제재를 복용했던 환자는 연구군에서 11명(68.8%), 대조군에서 1명(7.7.%)으로 나타났으며 PMC를 포함하여 각종 약제 및 알콜 섭취가 저명했던 환자가 연구군에서 15명(93.8%), 대조군에서는 2명(15.4%)이었다. 혈청 HBeAg 양성율은 급성 악화전에는 연구군에서 14명 중 7명(50.0%), 비교군에서는 13명 모두 (100%)에서 양성이었으며, 급성 악화 경과후에는 연구군에서는 변함없었고 비교군에서는 13명중 3명(23.1%)에만 양성이었다. 연구군 중 anti-HBe 양성화는 한 사람도 생기지 않았고 6명이 사망하였으며 대조군에서는 8명의 환자에서 anti-HBe 양성화가 생겼고 아무도 간기능 부전으로 사망하지 않았다. 만성 B형 간질환에서 심한 황달을 동반한 급성 악화와 관련있는 요인은 진행된 만성 활동성 간염, 간경변 등 근본적으로 진행된 간기능 저하와 동반된 부적절한 약제나 알콜 복용이 확실히 관계있을 것으로 사료되며 간기능 부전도 그리 드물지 않다. 반면에 간경변으로 진행되기 전 상대적으로 진행이 덜 된 비교군의 만성 B형 간염 환자에서는 황달의 저명한 증가없이 간기능이 갑자기 악화될 때는 자연적인 혈청 anti-HBe 양성전환의 동반이 흔한 것으로 나타났다.

• Journal of Yeungnam Medical Science
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• v.14 no.2
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• pp.329-336
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• 1997

만성 B형 간염의 경과중 흔히 볼 수 있는 간기능의 이상은 대부분 심한 황달의 동반없이 혈청 AST와 ALT의 증가만 보이면서 악화되는 것이다. 저자는 심한 황달을 동반한 16명의 만성 B형 간염 악화 환자(연구군)와 심한 황달없이 AST와 ALT치만 증가된 13명의 환자(비교군)를 비교관찰하였다. PMC 제재를 복용했던 환자는 연구군에서 11명(68.8%), 대조군에서 1명(7.7%)으로 나타났으며 PMC를 포함하여 각종 약제 및 알콜 섭취가 저명했던 환자가 연구군에서 15명(93.8%), 대조군에서는 2명(15.4%)이었다. 혈청 HBeAg 양성율은 급성 악화전에는 연구군에서 14명 중 7명(50.0%), 비교군에서는 13명 모두(100%)에서 양성이었으며, 급성 악화 경과후에는 연구군에서는 변함없었고 비교군에서는 13명 중 3명(23.1%)에서만 양성이었다. 연구군 중 anti-HBe 양성화는 한 사람도 생기지 않았고 6명이 사망하였으며 대조군에서는 8명의 환자에서 anti-HBe 양성화가 생겼고 아무도 간기능 부전으로 사망하지 않았다. 만성 B형 간질환에서 심한 황달을 동반한 급성 악화와 관련있는 요인은 진행된 만성 활동성 간염, 간경변 등 근본적으로 진행된 간기능 저하와 동반된 부적절한 약제나 알콜 복용이 확실히 관계있을 것으로 사료되면 간기능 부전도 그리 드물지 않다. 반면에 간경변으로 진행되기 전 상대적으로 진행이 덜 된 비교군의 만성 B형 간염 환자에서는 황달의 저명한 증가없이 간기능이 갑자기 악화될 때는 자연적인 혈청 anti-HBe 양성 전환의 동반이 흔한 것으로 나타났다.

• Korean Journal of Clinical Laboratory Science
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• v.44 no.3
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• pp.142-146
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• 2012

Hepatitis B surface antigen (HBsAg) seroclearance is a rare event in chronic hepatitis B virus (HBV) infection which acquires the disease early in life. A case study have examined with asymptomatic chronic hepatitis B carrier who exhibits HBsAg seroclearance in anti-HBe positive. We comprehensively studied the biochemical, virological and clinical aspects of a patient with HBsAg seroclearance. Liver biochemistry, serological markers, serum HBV DNA levels, and development of clinical complications were monitored. Mutation of hepatitis B virus is suspected serum HBsAg detected by the HBsAg assay systems of VITROS (OrthoClinical Diagnostics, USA), AxSYM (Abbott Laboratories, USA), Elecsys (Roche Diagnostics, Germany) and ADVIA Centaur (Bayer Diagnostics, USA). These four immunoassays showed negative results. Also, the patient had undetectable serum HBV DNA. Therefore, no mutation within the "a" determinant of HBsAg, which might escape detection from HBsAg immunoassay were found. Natural seroclearance was confirmed.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.959-962
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• 2013

Objective: HBV infection may cause damage to the immune system and induce lymphomas as a result. Some scholars have indicated that HBsAg(+) reflecting HBV infection may have a relationship with lymphoma development. This study was designed to find out the specific stage of HBV infection which may be related to lymphoma. Methods: HBV serum markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb were tested among 100 lymphoma patients and 100 other patients who were diagnosed with non-lymphoma diseases in the First Hospital of Jilin University from 2010.1.1 to 2012.12.31. Three subgroups were established depending on different combinations of HBV serum markers. Subgroup 1 was HBsAg(+) representing the early stage of HBV infection. Subgroup 2 was HbsAb(+) representing convalescence and Subgroup 3 was "HbsAg and HbsAb negative combined with other positive markers" representing the intermediate stage of HBV infection. Chi square tests were used to compare the rates of three subgroups in lymphoma and control groups. Results: The rates of Subgroup were 13% and 5% respectively, an association between HBsAg and lymphoma being found (P<0.05). There was no difference between rate of Subgroup 2 of lymphoma group (15%) and that of control group (16%). In lymphoma group and control group, the rate of Subgroup 3 was different (12% vs 4%). This evidence was not specific to T cell lymphoma, B cell lymphoma or Hodgkin's lymphoma. Conclusions: Among serum markers of HBV, the combination of serum markers representing the early stage and intermediate stage of HBV infection have a relationship with lymphoma. Convalescence from HBV infection appears to have no relationship with lymphoma.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.4
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• pp.311-318
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• 2020

Chronic hepatitis B viral (HBV) infection remains a major health threat, especially in high-prevalence areas. Most infants infected by mother-to-infant HBV transmission become chronic carriers. In Taiwan, many important preventive interventions have been implemented to block the perinatal transmission of HBV in the past 35 years. The first nationwide universal HBV vaccination program was launched in Taiwan in July 1984. The three-dose HBV vaccine completion rate reached 98.1% in 2018. The prevalence of Hepatitis B surface antigen (HBsAg) decreased from 9.8% in pre-vaccinated period in 1984 to 0.5% in the vaccinated cohort in 2014. The incidence of hepatocellular carcinoma in children aged 6-9 years significantly declined from 0.52 to 0.13 per 100,000 children born before and after 1984, respectively. Furthermore, we have performed a maternal HBV screening program during pregnancy since 1984, with the screening rate peaked at 93% in 2012. The HBsAg- and HBeAg-seropositive rate in pregnant women declined from 13.4% and 6.4% in 1984-1985 to 5.9% and 1.0% in 2016, respectively. To closely control perinatal HBV infection, we have administered hepatitis B immunoglobulin immediately after birth and checked the serum level of HBsAg and anti-HBs in high-risk babies born to HBsAg-seropositive mothers, irrespective of their HBeAg status, since July 2019. We have also adopted short-term antiviral treatments such as tenofovir 300 mg daily in the third trimester for highly viremic mothers and reduced the perinatal infection rates from 10.7 to 1.5%. Through all these efforts, we expect to meet the global goal of eliminating HBV infection by 2030.

• Korean Journal of Microbiology
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• v.27 no.3
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• pp.169-175
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• 1989

To study the role of mutant precore region in expression and secretion of hapatitis B viral core antigen, we have cloned core antigen gene(HBc) with or without precore region in geterologous expression vectors containing SV40 promoter, yeast promoter, and lambda $P_{L}$ promoter. In COS cells transfected with plasmid containing C-gene with precore region, antigens were detected in both cell extract and cultured medium. However, in the cells transfected with plasmids containing C-gene without precore or with mutated precore region by one nucleotide (T) addition at the nucleotide 1,821, HBcAg was detected only in cell extracts. These results support that the mutation by one nucleotide addition shifted the initiation codon of precore region to 53 nucleotides upward and the elongated precore region also played a major role in the secretion of HBcAg in mammalian cells. In the case of yeast and E. coli, HBcAg was detected only in cell extracts in spite of the presence of precore region, which suggest that precore region could not affect HBcAg secretion in these system.