• Toxicological Research
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• v.2 no.1
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• pp.23-30
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• 1986

Acute toxicity study was conducted on a Hepatitis B vaccine (Hepaccine-B-inj.) with mice, guinea pigs, and rabbits, in accordance with the norms suggested by the F.D.A. in U.S.A. Dose ranges were 2 doses/mouse, 5 doses/guinea pig, 10 doses/rabbit. They received the vaccine subcutaneously and intraperitoneally. Thereafter, all animals injected were observed of general signsdaily, and of body weight for two weeks. At the end of the observation period (or at the time of death), all animals received the highest dose group were autopsied and gross observation was made on various organs and tissues. No significant toxicity was noted.

• Korean Journal of Family Medicine
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• v.39 no.6
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• pp.360-363
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• 2018

Background: Acute alcoholic intoxication patients (AAIP) are a common public health problem. The aim of this study was to perform a comprehensive laboratory analysis for these patients to investigate the co-morbid medical problem. Methods: We retrospectively reviewed laboratory findings of AAIP who were transferred to the emergency department (ED) from January 2017 to June 2017. Results: A total of 160 male patients were enrolled. Sixteen patients (16/160, 10.0%) and three patients (3/160, 1.9%) had macrocytic anemia and microcytic anemia, respectively. A total of 33 patients (33/160, 20.6%) showed thrombocytopenia ($<150{\times}10^9/L$). Twelve patients (12/159, 7.5%) showed low serum albumin level (<3.5 g/dL). Three patients (3/160, 1.9%) had chronic kidney disease stages 3-4 based on estimated glomerular filtration rate. Six patients (6/27, 22.2%) had high hemoglobin A1c (HbA1c) level (>7.0%). Positive rates of hepatitis B surface antigen and antiHBs antibody (anti-HBs Ab) were 3.5% (5/141) and 49.0% (68/141), respectively. Conclusion: Patients with AAIP who were transferred to ED had various laboratory abnormalities (anemia, thrombocytopenia, high HbA1c). They had low positive rate of anti-HBs Ab. This might be a public health problem, suggesting the need of hepatitis B virus vaccination program for AAIP. Our data suggest the need of further nationwide studies.

• The Journal of Korean Medicine
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• v.18 no.1
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• pp.411-429
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• 1997

Recent survey shows that chronic liver disease such as chronic hepatitis, liver cirrhosis and hepatoma is the third leading causes for death in Korea. In oriental medicine, viral hepatitis is related to Hwangdal(黃疸) and alcoholic liver disease is related to Joosang(酒傷). ARTEMISIAE HERBA and PUERARIAE RADIX have long been used in treating those symptoms. This study was done to evaluate the effect of AR1EMISIAE HERBA and PUERARIAE RADIX on viral and alcoholic hepatitis. ARTEMISIAE HERBA and PUERARIAE RADIX were decocted respectively with water and followed by vaccum evaporation. The solution was diluted to adequate concentration. Sprague-Dawley rats were used in this experiment. Each group was given PUERARIAE RADIX or ARTEMISIAE HERBA solution orally and CCl4, d-galactosamine or alcohol was given orally 30 minutes later. After 24 hours of starvation, blood samples were taken to check serum GOT, GPT, LDH and ALP activities, TC, TG, glucose and BUN levels. These results show that ARTEMISIAE HERBA has better effect on liver injury induced by d-Galactosamine than PUERARIAE RADIX and that both ARTEMISIAE HERBA and PUERARlAE RADIX have good effect on acute alcoholic liver disease while in the liver injury induced by $CCl_{4}$, PUERARIAE RADIX has better inhibitory effect on serum AST, ALT and ALP levels and ARTEMISIAE HERBA has better inhibitory effect on serum total cholesterol and triglyceride. And the result that high concentration group has better effect shows these effects are concentration-dependent. Further study on the mechanism of these herbs is still required.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.3 no.2
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• pp.169-174
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• 2000

Purpose: Previously reported ocular complications of interferon alfa administration are extremely rare. We experienced a 15-year-old boy with chronic hepatitis B who developed glaucoma after interferon alfa therapy. The purpose of this prospective study was to evaluate the possible development of glaucoma after interferon alfa therapy for chronic hepatitis B. Methods: Nine patients with chronic hepatitis B who visited Inha university hospital between February 1998 and July 1999 received interferon alfa therapy. We measured visual acuity, intraocular pressure, C/D ratio, and visual field examination at pre-interferon therapy, three and six months after therapy, respectively. Results: The total number of patients was 9 (4 boys and 5 girls). Mean age was $11.7{\pm}4.1$ years. The duration of therapy was 6 months and mean dosage of interferon was 5 million units. Compared with visual acuity, intraocular pressure, and C/D ratio at pre-therapy, those parameters at 3 months and 6 months after therapy showed no significant differences and none showed visual field defect after therapy. Conclusion: Our prospective study showed no evidence of development of glaucoma after interferon therapy. However, it is necessary to be concerned about the possibility of developing glaucoma or other ophthalmologic diseases after interferon therapy in chronic hepatitis B.

• Journal of Microbiology and Biotechnology
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• v.28 no.8
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• pp.1376-1383
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• 2018

The hepatitis B virus (HBV) envelope contains small (S), middle (M), and large (L) proteins. PreS1 of the L protein contains a receptor-binding motif crucial for HBV infection. This motif is highly conserved among 10 HBV genotypes (A-J), making it a potential target for the prevention of HBV infection. In this study, we successfully generated a neutralizing human monoclonal antibody (mAb), 1A8 (IgG1), that recognizes the receptor-binding motif of preS1 using a phage-displayed human synthetic Fab library. Analysis of the antigen-binding activity of 1A8 for different genotypes indicated that it can specifically bind to the preS1 of major HBV genotypes (A-D). Based on Bio-Layer interferometry, the affinity ($K_D$) of 1A8 for the preS1 of genotype C was 3.55 nM. 1A8 immunoprecipitated the hepatitis B virions of genotypes C and D. In an in vitro neutralization assay using HepG2 cells overexpressing the cellular receptor sodium taurocholate cotransporting polypeptide, 1A8 effectively neutralized HBV infection with genotype D. Taken together, the results suggest that 1A8 may neutralize the four HBV genotypes. Considering that genotypes A-D are most prevalent, 1A8 may be a neutralizing human mAb with promising potential in the prevention and treatment of HBV infection.

• Toxicological Research
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• v.33 no.4
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• pp.343-350
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• 2017

Lamivudine belongs to the set of antiviral agents effective against hepatitis B virus infection. Given case reports on liver injuries after certain antiviral agent treatments, this study examined the effects of lamivudine on alanine aminotransferase (ALT) and total bilirubin (TB) using a medical system database. A total of 1,321 patients taking lamivudine alone or with others were evaluated using laboratory hits in an electronic medical system at Seoul National University Hospital from 2005 through 2011. The patients were grouped according to prior ALT results: G#1, ALT < 40 IU/L; G#2, 40 IU/L ${\leq}$ ALT < 120 IU/L; G#3, 120 IU/L ${\leq}$ ALT < 240 IU/L; and G#4, ALT ${\geq}$ 240 IU/L. In G#1 and G#2 patients, lamivudine or adefovir treatment decreased ALT and TB compared to prior values. In G#3 and G#4 patients with three times the upper limit of normal (ULN) ${\leq}$ ALT < 15 times the ULN, both ALT and TB were decreased after treatment with lamivudine alone, or adefovir following lamivudine therapy, indicating that lamivudine therapy ameliorated liver functions. However, in G#4 patients who experienced severely advanced hepatitis (ALT ${\geq}$ 15 times the ULN, or ${\geq}$ 600 IU/L), lamivudine augmented TBmax ($6.3{\rightarrow}13.3mg/dL$) despite a slight improvement in ALT ($839{\rightarrow}783IU/L$), indicative of exacerbation of bilirubinemia. Patients who used adefovir after lamivudine also showed a high incidence of hyperbilirubinemia when they experienced severely advanced hepatitis. Treatment with adefovir alone did not show the effect. In conclusion, lamivudine may increase the risk of hyperbilirubinemia in patients with severely advanced hepatitis, implying that caution should be exercised when using lamivudine therapy in certain patient populations.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.9 no.2
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• pp.242-248
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• 2006

Purpose: Neonatal hepatitis is the major cause of neonatal cholestasis and may be divided into infectious, metabolic, genetic, and idiopathic neonatal hepatitis. Non-familial, non-metabolic, and non-A, B, C viral neonatal hepatitis is known to have made satisfactory progress, but little is known about its chronic clinical features. Methods: Clinical and histological assessments were carried out in 34 cases with chronic neonatal hepatitis [elevated serum alanine aminotrasferase (ALT) level for more than 6 months] except for A, B, C viral hepatitis, metabolic, or genetic neonatal hepatitis, who were admitted to the Department of Pediatrics, Pusan National University Hospital, from January 1998 to January 2004. Results: Males were more common (70%). Jaundice (100%) and hepatomegaly (44%) were frequent manifestations. Peak serum ALT levels were most commonly below 300 IU/L in 41.2% of patients and peak serum direct bilirubin levels were most commonly between 1.0~5.0 mg/dL in 50% of patients. Ten cases (34%) of 29 patients had positive serum cytomegalovirus (CMV) IgM or urine CMV polymerase chain reaction. Serum ALT level was normalized within 1 year in 11 (37.9%) of 29 cases, and within 2 years in 9 (69.2%) of 13 cases. Serum ALT level was elevated persistently over 2 years in four (30.7%) of 13 cases. Histologic findings such as portal or periportal activity, lobular necrosis, portal or periportal fibrosis were more severe in patients with persistent ALT elevation over 2 years than in those showing normalization of ALT within 2 years (p>0.05). Conclusion: When the elevation of ALT level sustains over 1 year in non-familiar, non-metabolic, non-A, B, C viral neonatal hepatitis, an assessment of the severity of liver injury and a careful monitoring about chronic liver disease may be required.

• Journal of Microbiology and Biotechnology
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• v.27 no.7
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• pp.1336-1344
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• 2017

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma. With recent identification of HBV receptor, inhibition of virus entry has become a promising concept in the development of new antiviral drugs. To date, 10 HBV genotypes (A-J) have been defined. We previously generated two murine anti-preS1 monoclonal antibodies (mAbs), KR359 and KR127, that recognize amino acids (aa) 19-26 and 37-45, respectively, in the receptor binding site (aa 13-58, genotype C). Each mAb exhibited virus neutralizing activity in vitro, and a humanized version of KR127 effectively neutralized HBV infection in chimpanzees. In the present study, we constructed a humanized version (HzKR359-1) of KR359 whose antigen binding activity is 4.4-fold higher than that of KR359, as assessed by competitive ELISA, and produced recombinant preS1 antigens (aa 1-60) of different genotypes to investigate the binding capacities of HzKR359-1 and a humanized version (HzKR127-3.2) of KR127 to the 10 HBV genotypes. The results indicate that HzKR359-1 can bind to five genotypes (A, B, C, H, and J), and HzKR127-3.2 can also bind to five genotypes (A, C, D, G, and I). The combination of these two antibodies can bind to eight genotypes (A-D, G-J), and to genotype C additively. Considering that genotypes A-D are common, whereas genotypes E and F are occasionally represented in small patient population, the combination of these two antibodies might block the entry of most virus genotypes and thus broadly neutralize HBV infection.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.277-282
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• 2000

Purpose : Though It has been known that the to tolerance of the liver to external beam irradiation depends on the irradiated volume and dose, few data exist which Quantify this dependence. However, recently, with the development of three dimensional (3-D) treatment planning, have the tools to Quantify the relationships between dose, volume, and normal tissue complications become available. The objective of this study is to investigate the relationships between normal tissue complication probabili쇼 (WCP) and the risk of radiation hepatitis for patients who received variant dose partial liver irradiation. Materials and Methods : From March 1992 to December 1994, 10 patients with hepatoma and 10 patients with bile duct cancer were included in this study. Eighteen patients had normal hepatic function, but 2 patients (prothrombin time 73$\%$, 68$\%$) had mild liver cirrhosis before irradiation. Radiation therapy was delivered with 10MV linear accelerator, 180$\~$200 cGy fraction per day. The total dose ranged from 3,960 cGy to 6,000 cGy (median dose 5,040 cGy). The normal tissue complication probability was calculated by using Lyman's model. Radiation hepatitis was defined as the development of anicteric elevation of alkaline phosphatase of at least two fold and non-malignant ascites in the absence of documented progressive. Results: The calculated NTCP ranged from 0.001 to 0.840 (median 0.05). Three of the 20 patients developed radiation hepatitis. The NTCP of the patients with radiation hepatitis were 0.390, 0.528, 0.844(median : 0.58$\pm$0.23), but that of the patients without radiation hepatitis ranged fro 0.001 to 0.308 (median .0.09$\pm$0.09). When the NTCP was calculated by using the volume factor of 0.32, a radiation hepatitis was observed only in patients with the NTCP value more than 0.39. By contrast, clinical results of evolving radiation hepatitis were not well correlated with NTCP value calculated when the volume factor of 0.69 was applied. On the basis of these observations, the volume factor of 0.32 was more correlated to predict a radiation hepatitis. Conclusion : The risk of radiation hepatitis was increased above the cut-off value. Therefore the NTCP seems to be used for predicting the radiation hepatitis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.2
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• pp.177-183
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• 2008

This study aimed to investigate the protective effect of dandelion water extract (DWE) on liver injury induced by D-galactosamine (GalN) in Sprague-Dawley rats. Fifty rats were divided into 5 groups; normal control (C), DWE-control (DWE-C: saline injection after feeding 3% DWE diet), GalN-control (GalN-C: GalN injection after normal diet), DWE I (GalN injection after feeding 1.5% DWE diet), and DWE II (GalN injection after feeding 3% DWE diet). After 2 weeks, the acute hepatitis was induced by GalN (650 mg/kg, i.p.) and 24 hrs later, all rats were sacrificed. The DWE supplement ameliorated the serum alanine and aspartate aminotransferase (AST, ALT) as well as alkaline phosphatase (ALP) and tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$. Hepatic antioxidative enzyme activities, such as catalase, GSH peroxidase, GSH reductase, and Mn-superoxide dismutase (SOD) were slightly or significantly elevated by the treatment of DWE. Moreover, the histological examination corresponded with these biochemical observations. According to these findings, dandelion could be used as a potential therapeutic material for treating chemically induced acute hepatitis.