• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.1
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• pp.23-29
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• 2009

Purpose: To provide the primary data for reaching a consensus on the adequate duration of treatment of lamivudine in children with HBeAg negative chronic hepatitis B. Methods: Seven of 83 children/adolescents with chronic hepatitis B were diagnosed with HBeAg-negative and HBV DNA-positive chronic hepatitis B and treated with lamivudine. Six children/adolescents were enrolled among 7 patients, who had been treated with lamivudine over 2 years. The primary goal of treatment was HBV DNA clearance and normalization of the serum ALT level; the final goal of treatment was the durability of the complete response after discontinuation of lamivudine. It was planned to continue lamivudine for more than two additional years after HBV DNA negativity and normalization of ALT. Results: The mean duration of lamivudine treatment was 32.2 months (range, 26~40 months) and the mean duration of follow-up was 59.5 months (range, 26~110 months). HBV DNA levels became undetectable (<0.5 pg/mL) in 6 patients within 3 months of treatment. ALT levels were normalized in 3.5 months (range, 2~7 months) in all 6 patients. Biochemical breakthrough developed in 1 patient 18 months after the initiation of lamivudine treatment. No evidence of relapse could be found in 4 patients with a mean follow-up of 23.8 months (range, 4~75 months) after cessation of lamivudine treatment. Conclusion: Suppression of HBV replication and normalization of serum ALT levels were effectively achieved with long-term lamivudine treatment in children/adolescents with HBeAg-negative chronic hepatitis B. Two additional years of lamivudine may be needed after HBV DNA clearance and ALT normalization in HBeAg-negative chronic hepatitis B in order to decrease the relapse rate.

• Biomedical Science Letters
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• v.18 no.3
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• pp.283-290
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• 2012

In this study, we investigated the virological characteristics, HBV DNA levels and presence of mutations of "a" determinant in the HBsAg S gene in chronic hepatitis B patients with coexisting HBsAg and anti-HBs. The 18 patients who were diagnosed with chronic hepatitis B were both positive for HBsAg and anti-HBs. HBV Among them, 15 patients were DNA positive. The median of HBV DNA levels in serum was $2.18{\times}10^7$ copies/mL with the HBsAg+/anti-HBsAb+ patients. Also, 4 of 8 HBeAg negative patients had HBV DNA levels higher than $10^4$ copies/mL and the median of HBV DNA levels was $2.03{\times}10^6$ copies/mL, which were significantly high. These results showed that viral replication still existed in most of the patients of the concomitant HBsAg and anti-HBs, and even in the some HBeAg negative patients. Furthermore, mutation within the "a" determinant of HBV were found in 7 of 15 patients. The most frequent changes were located at positions aa126. In addition, one mutation observed for HBsAg only positive.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.7 no.2
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• pp.197-207
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• 2004

Purpose: To evaluate the long-term therapeutic efficacy and durability of lamivudine in Korean children with chronic hepatitis B. Methods: A total of 48 children (31 male and 17 female; age, 1~18 years, mean, 8 years) with chronic hepatitis B who received lamivudine for at least six months from March 1999 to September 2004 were followed for a mean period of 29 months (8~66 months) at Department of Pediatrics, Kyungpook National University Hospital in Korea. Response to treatment was defined as the normalization of ALT and HBV DNA levels, and HBeAg seroconversion after the initiation of treatment. Results: Twenty nine (60%) among the 48 children treated with lamivudine responded and nine (19%) children lost HBsAg during therapy. ALT and HBV DNA level had normalized in 94% one year after the initiation of treatment. Kaplan-Meier estimates of cumulative HBeAg seroconversion rates over the years were 13% (0.5 year), 34% (1 year), 50% (1.5 years), 68% (2 years), 79% (2.5 years) and 90% at 3 years respectively. Above all, among the 22 children treated before the age of seven, loss of HBsAg occurred in eight (36%), which showed superior rate of HBsAg loss (p=0.002 vs age >7). Conclusion: Long-term treatment of lamivudine improved the rate of HBeAg seroconversion in Korean children with chronic hepatitis B. After three years' observation, most of treated children have sustained HBeAg clearance. We believe that lamivudine should be tried as the first therapeutic option for children with chronic hepatitis B in immune clearance phase.

• Journal of Microbiology and Biotechnology
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• v.18 no.10
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• pp.1722-1728
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• 2008

The natural course of chronic hepatitis B (CH-B) virus infection is reportedly variable, and the long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection are distinct from HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in the south Indian setting remain largely unclear. We prospectively studied 679 consecutive patients for HBsAg, HBeAg, anti-HBe, and HBV DNA by qualitative PCR. Randomly selected samples were subjected to bidirectional sequencing to reveal core/precore variants. Of the total 679 chronic HBV cases investigated, 23% (154/679) were replicative HBV carriers. Furthermore, amongst the 560 HBV DNA samples analyzed, 26% (146/560) were viremic. Among the 154 HBeAg positive cases, HBV DNA was positive in 118 cases (77%), significantly (p<0.001) higher than the anti-HBe positive (7%) (28/406) cases. Significant increase in liver disease (p<0.01) with ALT enzyme elevation (p<0.001) was observed in both HBe and anti-HBe viremic cases. Interestingly, low frequencies of mutations were seen in the precore region of the HBV strains studied. HBV precore and core promoter variants were less often detected in subjects with "e" negative chronic HBV infection and, therefore, may not have a prognostic role in determining liver disease sequelae in this part of tropical India.

• Clinical and Experimental Pediatrics
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• v.48 no.1
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• pp.55-62
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• 2005

Purpose : We compared the therapeutic efficacy of lamivudine and alpha-interferon in children with chronic hepatitis B two years after the initiation of treatment, so that we could verify the safety and long term efficacy of lamivudine in children. Methods : We prospectively studied 44 children(32 male and 12 female; age, 1-18 years, mean, 9 years) treated for chronic hepatitis B from September 1996 to June 2004 in Kyungpook National University Hospital in Korea. Twenty three children were treated with interferon, and 21 with lamivudine. Treatment efficacy was defined as the normalization of ALT and hepatitis B virus(HBV) DNA levels, loss of HBsAg and HBeAg seroconversion at two years after the initiation of treatment. Results : Among the 23 children treated with interferon, the ALT level normalized in 10 children(43 %) and HBV DNA was undetectable in 12 children(52%). HBsAg was undetectable in one child (4 %) and HBeAg seroconversion occurred in nine children(39%) two years after the initiation of treatment. In comparison, among the 21 children treated with lamivudine, ALT normalized in 20 children (95%), HBV DNA in 19(90%), HBsAg in 5(24%), and HBeAg seroconversion occurred in 13(62%). Above all, in the lamivudine treated group under the age of seven, HBeAg and HBsAg seroconversion occurred in six(75%) and five(63%) out of the eight children respectively, which showed superior HBsAg seroconversion rate if treated in preschool aged children. Conclusion : We believe that the therapeutic efficacy of lamivudine in children with chronic hepatitis B could be better than interferon with fewer side effects, especially in preschool aged children.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.90-99
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• 1998

Purpose: The aim of this study was to clarify the serum cytokine pattern in patients with chronic HBV infection in terms of their clinical state. Methods: Intravenous blood samples were taken from 35 patients who were seropositive for HBsAg for at least 6 months and 7 healthy controls. Samples were initially tested for serum aminotransferases and serologic markers for hepatitis B virus by EIA. Serum levels of interleukin(IL)-2, tumor necrosis factor-alpha (TNF-${\alpha}$), interferon-gamma (IFN-${\gamma}$), IL-4, and IL-10 were measured by ELISA. Results: Among 35 patients, seropositive for HBeAg was 20 and for anti-HBe was 15. The histologic diagnosis of 19 patients underwent liver biopsy were chronic persistent hepatitis (CPH) in 10 and chronic active hepatitis (CAH) in 9. Serum IL-10 level in patients seropositive for HBeAg was significantly higher than that in patients seropositive for anti-HBe (p<0.05). All measured cytokine levels in patients with CAH were higher than those of patients with CPH. High values of all measured cytokines except IL-4 were seen in patients with AST and ALT > 100 U/L. High level of IL-4 was seen in patients with normal aminotransferase levels. Conclusion: These results were thought to indicate that anti-inflammatory Th2-like cytokine (IL-10) production in chronic HBV infection is related to circulating HBeAg rather than activity of hepatitis and that Th1 cytokines seem to be associated with the increasing activity of hepatitis.

• Clinical and Experimental Pediatrics
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• v.50 no.4
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• pp.348-354
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• 2007

Purpose : Perinatal hepatitis B viral infection is decreasing; however, 10% of babies to HBeAg positive mothers still become chronic carriers despite perinatal prophylaxis. Although, the cause of prophylaxis failure is still unclear, an importance of maternal HBV-DNA level at the delivery time has been suggested. This study was established to certify if it would be a useful predictable factor for the outcome of perinatal prophylaxis. Methods : Twenty-nine HBeAg positive mothers whose babies had known outcomes of prophylaxis were selected. To determine the amount of maternal HBV-DNA, a quantitative PCR was performed with the WHO International Standard for HBV DNA NAT assays. Results : The mean logarithm HBV-DNA level of mothers with failed outcomes was significantly higher than that of mothers with succeessful outcomes (7.99 vs. 6.72, P=0.015). The predictable maternal HBV-DNA cut-off level to prophylaxis outcome was $2.83{\times}10^7copies/mL$ (100 pg/mL). None out of the case 16 (0%) who had below this level, and 5 out of 13 (38.5%) who had above this level of maternal HBV-DNA failed in perinatal prophylaxis. Conclusion : Mothers with higher levels of HBV-DNA at delivery time would be prone to a worse outcome of prophylaxis using the conventional approach. Perinatal prophylaxis failure rate can be reduced, if we try to introduce more potent prophylactic treatment into the cases with this risk factor.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1165-1171
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• 2008

Purpose : This study aimed to identify the true extent of non-responsiveness in full-term infants born from HBsAg-negative or HBsAg-positive mothers and vaccinated against hepatitis B virus (HBV) at 0, 1, and 6 months of age and to evaluate the effect of revaccination among non-responders. Methods : The study included 716 full-term infants born in 2004-2007. Of 716, 662 infants (A group) were born to HBsAg-negative mothers and 54 infants (B group: 50, except HBsAg-positive infants) were born to HBsAg-positive mothers. All infants were administered DNA recombinant vaccines at 0, 1, and 6 months of age. B group infants received hepatitis B immunoglobulin at birth. Anti-HBs titers were tested at 7-12 and 9-15 months in A and B groups, respectively. Three revaccination doses were administered to non-responders whose anti-HBs titers were under 10 mIU/ml; revaccinated infants were retested at 1-3 months after last vaccination. The association between HBeAg seropositivity of mother and the failure of HBV immunoprophylaxis was evaluated. Results : The seroconversion rates after primary hepatitis B vaccination were higher in A group (94.1%) than in B group (78%, P<0.001). The seroconversion rates were high in revaccinated infants (A group non-responders: 96.9%, B group non-responders: 87.5%). The failure of HBV immunoprophylaxis was significantly associated with maternal HBeAg seropositivity (P<0.001). Conclusion : The seroconversion rates after primary hepatitis B vaccination were low in B group infants. Revaccination of non-responders in B group was very effective. Therefore, anti-HBs testing and revaccination of B group is very important. Revaccination of non-responders in A group was also very effective. Thus, testing the immune status of infants born to HBsAg-negative mothers even after primary hepatitis B vaccination should be considered. However, to realize this, further studies on the cost-effectiveness of anti-HBs testing in healthy full-term infants are necessary.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.2
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• pp.130-136
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• 2008

Purpose: Lamivudine is known to be effective for the treatment of chronic hepatitis B in adults. However, data on lamivudine therapy in pediatrics is limited. The aim of this study was to evaluate the efficacy and durability of lamivudine therapy for chronic hepatitis B in Korean children. Methods: A total of 44 children (27 males and 17 females, ages 6 months to 14.8 years, mean age 6.7 years) with chronic hepatitis B who received lamivudine (3 mg/kg/day, max 100 mg) for at least 12 months were enrolled. We evaluated the serum AST, ALT and serological HBV markers (HBsAg and anti-HBs, HBeAg and anti HBe, and HBV DNA) periodically. Predictive three year cumulative seroconversion rates were obtained using the Kaplan-Meier method. Results: Twenty one (48%) of 44 children achieved seroconversion of HBeAg by three years, while 23 (42%) children did not. HBV DNA was cleared in 34 (77%) children and the serum ALT levels were normalized in 41 children (93%). The three year cumulative seroconversion rates were 60% for HBeAg, and the clearance rates were 76% for HBV DNA. Eighteen children who discontinued lamivudine after HBeAg seroconversion maintained the therapeutic response for three years (treatment duration 13~58 months mean 24 months). Viral breakthrough developed in 12 children (27%) during the therapy and the YMDD mutation was documented in 11 children (25%). The mean duration for the development of a mutation was 22.7 months. Loss of HBsAg occurred in 6 children (14%). The pretreatment ALT levels were higher in responders; however, the differences were not statistically significant (p>0.05). Conclusion: The results of this study showed that lamivudine treatment had a favorable effect and durable therapeutic response in children with chronic hepatitis B. Long term follow-up and alternative therapy are warranted for those patients who do not respond to this treatment.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.209-214
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• 2006

Objective : Report on a hepatitis B patient with abnormal AST/ALT, HBeAg(+), and habitual diarrhea stemming from irritable colon. Methods : Lab-evaluation of intervals of herb medicine treatment for a patient with hepatitis B with HBeAg and irritable colon. Result & Conclusion : AST/ALT level was normalized and did not rise again. Seroconversion to HBeAb repeatedly appeared just druing the time of the treatment, but typically repeated seroconversion between treatment period and no treatment period confirmed that the treatment was effective for the immune system against hepatitis B. The exact mechanism is not clear but the result provides an indication that oriental herbal medicine has potential capacity to treat liver diseases.