• Childhood Kidney Diseases
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• v.2 no.1
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• pp.50-59
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• 1998

Purpose : Hepatitis B virus (HBV) infection has been involved in several forms of immune-related glomerulopathy but the pathogenic role of HBV infection is not clear. To evaluate the clinicopathological features of HBV-associated glomerulopathy, a clinicopathological analysis and immunohistochemical stain for HBs Ag and HBe Ag were done. Methods : Clinicopathological features of HBV-associated glomerulopathy were analyzed with renal biopsies in 28 HBsAg seropositive patients from April 1990 to February 1997 at Pusan Paik Hospital, and immunohistochemical evaluation for HBsAg and HBeAg was done in renal tissues. Light microscopic, immunofluorescent and electron microscopic examination and immunohistochemical staining for HBsAg (DAKO) and HBeAg (BIONIKE) of renal tissue were performed. Result ; 1. The age distribution was 6 to 73 years old, and eight were children and 20 were adults. Male : female ratio was 3:1. Nineteen (67.9%) and 21 (75.0%) of 28 cases showed hematuria and proteinuria, respectively at the time of biopsy. Sixteen (57.2%) of them had nephrotic syndrome. 2. Liver function test was performed in 11 patients and seven (63.6%) of them showed increased AST and ALT levels. Liver biopsy was done in three patients and revealed findings of chronic active hepatitis. 3. HBV-associated glomerulopathy was membranous glomerulonephritis (MGN) in 10 (35.7%), mesangiopathy in 8 (28.6%), membranoproliferative glomerulonephritis (MPGN) in 7 (25.0%) and minimal change disease in 3 (10.7%) out of 28 cases. 4. Ultrastructurally HBV-associated MGN showed conspicuous subepithelial deposits with intramembranous, mesangial and subendothelial deposits and proliferation of mesangial cells and matrix, which were suggestive of MPGN. In HBV-associated MPGN, intramembranous and subepithelial deposits were scattered. 5. Immunohistochemical staining revealed no expression for HBsAg, but positive reaction for HBeAg along capillary wall in 8 cases (28.6%), of which 3 cases were checked for serum HBeAg, all showed positivity. Conclusion : HBV-associated glomerulopathy showed a wide morphologic spectrum and overlapping ultrastructural features in MGN and MPGN, and the activity of hepatitis B virus may be related to the development of HBV-associated glomerulopathy but further studies are recommended to confirm this relationship.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.823-834
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• 2007

Interferon (IFN) alpha has been the first line therapy of chronic hepatitis B in children, but HBeAg seroconversion occurred in 26% of treated children compared to 11% of controls in multinational randomized controlled study. Recently, lamivudine was shown to be a potent inhibitor of Hepatitis B virus (HBV) reproduction both in HBeAg positive and in HBeAg negative (the pre-core mutant form) chronic hepatitis in randomized studies worldwide. Lamivudine therapy led to considerable improvement in the seroconversion rate of HBeAg in children with chronic hepatitis B, though long-term therapy resulted in the expansion of lamivudine-resistant mutant viruses. Combination therapy with lamivudine plus alpha-IFN does not seem to improve HBe Ag seroconversion. Above all, the most effective way to prevent hepatitis B is universal HBV vaccination.

• Pediatric Infection and Vaccine
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• v.5 no.1
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• pp.96-103
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• 1998

Purpose : We performed this study to evaluate the immune responses and protective efficacies of the HBV vaccine in infants born from hepatitis B virus(HBV) carrier mothers. Methods : Seventy eight infants born from HBV carrier mothers, who were able to follow up for 12months in the Catholic University St. Vincents hospital, were involved in this study from July 1995 to December 1996. Samples were collected at birth, 4, 8 and 12months after injection of HBIG and HBV heat-inactivated plasma derived vaccines. We evaluated the changes and relationships of viral markers detecting by enzyme immunoassay and radioimmunoassay between HBV carrier mothers and their infants. Results : 1) A total of 5.0%(106/2,117) of pregnant women were found to be a HBV carrier. The rates of HBeAg positive and negative were 38.5%(37/96) and 61.5%(59/96), respectively. 2) The seroconversion rates of anti-HBs with infants of HBV carrier mothers at 4, 8 and 12 months were 85.9%(67/78), 75.6%(59/78) and 73.1%(57/78), respectively. Although these were statistically significant differences(P<0.05), they were not related to HBeAg status of the mothers. The geometric mean titers of anti-HBs at 8 and 12 months were significantly higher than at 4 months, statistically(P<0.05). The protective efficacy of the HBV vaccine and HBIG at 12 months in infants from HBeAg positive and negative mothers were 89.8% and 100%, respectively. 3) Five of 78(6.4%) infants became infected by HBV from only HBeAg positive mothers during the follow up period of 12 months. Three of 5 infected infants became HBV carriers. HBsAg positive at birth from HBeAg positive and negative mother were 4 infants, respectively. Three of 4 infants became infected by HBV from only HBeAg positive mothers. Conclusion : We confirmed that the seroconversion rate of HBV heat-inactivated plasma derived vaccine which was one of other vaccines manufacturing in Korea was 85.9%. The protective efficacy of this HBV vaccine and HBIG at 12 months in infants from HBeAg positive and negative mothers were 89.8% and 100%, respectively.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.2
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• pp.143-149
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• 2008

Purpose: To estimate the long-term therapeutic efficacy and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B who have developed lamivudine resistance. Methods: Sixteen patients (12 boys and 4 girls; ages 4.3~20.9 years; mean age 14.2 years) with chronic hepatitis B infection resistant to lamivudine therapy received adefovir (0.3 mg/kg/day, maximal dose 10 mg) orally for at least 9 months between March 2004 and April 2008. Each patient was followed up for a mean period of 27 months (range 9~49 months) until April 2008 at Kyungpook National University Hospital in Korea. Therapeutic responses to adefovir were evaluated at 12, 24, 36, and 48 months from the initiation of therapy using the Kaplan-Meier method. Response measurements included ALT normalization, HBV DNA negativization, 2 $log_{10}$ IU/mL decrement of HBeAg titer, HBeAg loss, and HBeAg/Ab seroconversion rate. Results: Three (18.8%) of the 16 patients treated with adefovir showed HBeAg/Ab seroconversion. Kaplan-Meier estimates of cumulative ALT normalization were 12.5% (12 months), 43.8% (24 months), 63.5% (36 months), and 92.7% (48 months), respectively. Cumulative HBV DNA negativization was 6.7%, 30.0%, 45.6%, and 78.2% at 12, 24, 36, and 48 months, respectively. Cumulative 2 $log_{10}$ copies/mL decrement of HBeAg titer was 12.5%, 43.8%, 56.3%, and 86.9% at 12, 24, 36, and 48 months, respectively. Cumulative HBeAg loss and HBeAg/Ab seroconversion were 6.7% (12 months) and 22.2% (24 months), respectively. Conclusion: The long-term therapeutic efficacy of adefovir dipivoxil was favorable in children and adolescents with chronic hepatitis B who had developed lamivudine resistance. The long-term use of adefovir should be safe in children.

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.209-213
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• 1986

To study the therapeutic effect of ribavirin, a broad spectrum antiviral agent, for chronic hepatitis B in pediatric patients, 24 patients who were diagnosed as chronic hepatitis B (elevated SGOT and SGPT and positive HBsAg and HBeAg for more than 6 months) at the pediatric department of Yeungnam University Hospital from Mar. 1, 1985 to Sep. 30, 1986 were randomly divided into two groups. Ribavirin was administered to 11 patients in dose of 15mg/kg/day and 13 patients were control group and both groups were followed for 12 months. Serum HBsAg and HBeAg were measured with RIA(Ausria-1I and Abbott-HBe, respectively) and compared in PIN ratio (counts per minute of patient's sample/counts per minute of normal serum). There were no statistically significant reductions in PIN ratios of HBsAg and HBeAg in both groups between prior to the therapy and 12 months follow-up period. It seems that ribavirin does not have the therapeutic effect on chronic hepatis B in children. Also, there were no noticeable side effects from ribavirin therapy.

• The Journal of Internal Korean Medicine
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• v.20 no.1
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• pp.122-132
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• 1999

Purpose : Hepatitis B virus DNA transfected cell line(HepG2.2.15) was cultured to evaluate the effect of herbs on the expression of HBeAg and the replication of HBV. HepG2.2.15 produces HBV particles as well as viral proteins into cell culture media. Methods : Extracts of herbs were adminitered to the cells on the proper concentration. Culture media was collected 48 hours after the herbal administration and HBeAg level in the media was examined by ELISA method. To confirm that the anti-viral effect was not due to direct cytotocixity of the extracts, normal cell proliferation was shown by cell counting. And as of the interference in protein synthesis of HepG2.2.15 by herb-extracts, we used the result of study that we performed before by ${\alpha}FP$ assay using EIA method. Results& Conclusion : Herb medicines like 地楡(Sanguisorbae Radix) and 覆盆子(Rubi Frusctus) showed significant inhibitory effect on HBeAg expression at p<0.01 and 五味子(Acanthopanacis Cortex) at p<0.05. Whereas, though some herbs such as ?草根(Rubiae Radix), 山査(Crataegii Fructus), 白芍藥(Paeoniae Radix Alba), and 大黃(Rhei Radix et Rhizoma) showed the tendecy to suppress HBeAg. most of them were not significant statistically. From the above, we could conclude that those herb medicines can be applied to patients effectively and further studies on effective fraction of some herbs are thought to be needed.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.6 no.2
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• pp.140-151
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• 2003

Purpose: We tried to evaluate the long term efficacy and positive predictive factors of interferon-alpha treatment in children with chronic hepatitis B. Methods: The study population included 113 children who received interferon therapy between May 1982 and July 2002 (20 years) for chronic hepatitis B in Department of Pediatrics, Yonsei University College of Medicine. Male to female ratio was 2.3 : 1 and the mean age at diagnosis was $11.1{\pm}4.1$ years old. Response to treatment was defined as normalization of alanine aminotransferase (ALT), disappearance of HBeAg and HBV-DNA Eighty two children responded while 32 did not. Interferon-alpha was given intramuscularly for 6 months at a dosage of $3{\times}10^6$ unit, 3 times weekly. In relapsed cases, lamivudine or interferon retreatment was done. Results: Seroconversion rate was 77.0% in terms of HBeAg, 74.3% in terms of HBV-DNA, and 80.5% in terms of ALT normalization after treatment. Seroconversion rate of both HBeAg and HBV-DNA was 72.6%. Analyzed by life table method, the effect of the treatment had been maintained over 10 years after cessation of therapy. Pre-treatment ALT level was the only significant positive predictive factor of response. Eleven cases (13.4%) relapsed, and 2 out of 3 showed response when treated with lamivudine and 1 out of 3 with interferon retreatment. Conclusion: Interferon-alpha showed significant efficacy in the treatment of chronic hepatitis B in our study. Further studies about the effect of interferon therapy on complications of hepatitis such as hepatocarcinoma, cirrhosis are warranted.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.131-139
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• 2001

Lamivudine, an oral nucleoside analogue, effectively inhibits hepatitis B virus replication and reduces hepatic necroinflammation in patients with chronic hepatitis B. Although lamivudine has shown a promise in patients with chronic hepatitis B, a long-term data on Korean patients with hepatitis B are lacking. The purpose of this study is to evaluate the effects and safety of 52-week lamivudine therapy in Korean patients with chronic hepatitis B, A total of twenty-nine patients (27 male and 2 female) who had received 100 mg of oral lamivudine daily for 52 weeks were evaluated, retrospectively. The mean age of 29 patients in the study group was 37.7 $\pm$ 8.9 years (range 19-54). Pretreatment HBV PCR and HBsAg were positive in all 29 patients, and HBeAg were positive in 25 patients (86%). The serum HBV DNA of 28 patients (97%) significantly fell to undetectable levels (<5 pg/ml) within 12 weeks of therapy and it remained undetectable in 24 patients (83%) by the end of 52-week therapy (p<0.001). Mean serum ALT levels of 29 patients declined to the normal range within 12 weeks and remained within the normal range during the evaluative period (p<0.05). The proportions of patients with HBeAg seroconversion (loss of HBeAg, development of antibody to HBeAg, and undetectable HBV DNA) were 42% after 52-week therapy. The differences of response to lamivudine therapy in HBeAg- positive and HBeAg-negative patients were negligible (p>0.05). Furthermore, the study showed that pretreatment serum HBV DNA and ALT levels have no effect to the efficacy of lamivudine therapy (p>0.05). Further comparison of lamivudine's efficacy showed that lamivudine is just as efficacious in patients with cirrhosis as without cirrhosis (p>0.05). In conclusion, lamivudine is an effective and safe therapy for the treatment of chronic hepatitis B in Korean patients.

• The Korean Journal of Nuclear Medicine Technology
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• v.23 no.1
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• pp.35-39
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• 2019

Purpose Hepatitis B virus (hepatitis B virus, HBV) infection is a worldwide major public health problem and it is known as a major cause of chronic hepatitis, liver cirrhosis and liver cancer. And serologic tests of hepatitis B virus is essential for diagnosing and treating these diseases. In addition, with the development of molecular diagnostics, the detection of HBV DNA in serum diagnoses HBV infection and is recognized as an important indicator for the antiviral agent treatment response assessment. We performed HBeAg assay using Immunoradiometric assay (IRMA) and Chemiluminescent Microparticle Immunoassay (CMIA) in hepatitis B patients treated with antiviral agents. The detection rate of HBV DNA in serum was measured and compared by RT-PCR (Real Time - Polymerase Chain Reaction) method Materials and Methods HBeAg serum examination and HBV DNA quantification test were conducted on 270 hepatitis B patients undergoing anti-virus treatment after diagnosis of hepatitis B virus infection. Two serologic tests (IRMA, CMIA) with different detection principles were applied for the HBeAg serum test. Serum HBV DNA was quantitatively measured by real-time polymerase chain reaction (RT-PCR) using the Abbott m2000 System. Results The detection rate of HBeAg was 24.1% (65/270) for IRMA and 82.2% (222/270) for CMIA. Detection rate of serum HBV DNA by real-time RT-PCR is 29.3% (79/270). The measured amount of serum HBV DNA concentration is $4.8{\times}10^7{\pm}1.9{\times}10^8IU/mL$($mean{\pm}SD$). The minimum value is 16IU/mL, the maximum value is $1.0{\times}10^9IU/mL$, and the reference value for quantitative detection limit is 15IU/mL. The detection rates and concentrations of HBV DNA by group according to the results of HBeAg serological (IRMA, CMIA)tests were as follows. 1) Group I (IRMA negative, CMIA positive, N = 169), HBV DNA detection rate of 17.7% (30/169), $6.8{\times}10^5{\pm}1.9{\times}10^6IU/mL$ 2) Group II (IRMA positive, CMIA positive, N = 53), HBV DNA detection rate 62.3% (33/53), $1.1{\times}10^8{\pm}2.8{\times}10^8IU/mL$ 3) Group III (IRMA negative, CMIA negative, N = 36), HBV DNA detection rate 36.1% (13/36), $3.0{\times}10^5{\pm}1.1{\times}10^6IU/mL$ 4) Group IV(IRMA positive, CMIA negative, N = 12), HBV DNA detection rate 25% (3/12), $1.3{\times}10^3{\pm}1.1{\times}10^3IU/mL$ Conclusion HBeAg detection rate according to the serological test showed a large difference. This difference is considered for a number of reasons such as characteristics of the Ab used for assay kit and epitope, HBV of genotype. Detection rate and the concentration of the group-specific HBV DNA classified serologic results confirmed the high detection rate and the concentration in Group II (IRMA-positive, CMIA positive, N = 53).

• The Journal of Korean Medicine
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• v.21 no.4
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• pp.112-121
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• 2000

Objectives : The purpose of this study was to examine the efficacy of Gamichunggan-tang(Jiaweiqinggan-tang) on 57 patients who have suffered from chronic liver disease. Methods : Gamichunggan-tang(Jiaweiqinggan-tang) was administered to patients for over 2 months continuously. We checked improvement of clinical symptoms, changes of Hepatitis B markers and lymphocyte count. Results : Gamichunggan-tang(Jiaweiqinggan-tang) has significant effect on the improvement of clinical symptoms. And the ratio of seroconversion from HBeAg positive to HBeAg negative was 42.9%. Lymphocyte increased in 83.3% of patients converted to HBeAg negative. Conclusions : It is suggested that Gamichunggan-tang(Jiaweiqinggan-tang) has significant effects on the recovery of weakened liver function and immune modulation. This treatment could be recommened as a prescription for Chronic liver disease.