• Korean Journal of Radiology
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• v.22 no.12
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• pp.1985-1995
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• 2021

Objective: Although the liver-to-spleen volume ratio (LSVR) based on CT reflects portal hypertension, its prognostic role in cirrhotic patients has not been proven. We evaluated the utility of LSVR, automatically measured from CT images using a deep learning algorithm, as a predictor of hepatic decompensation and transplantation-free survival in patients with hepatitis B viral (HBV)-compensated cirrhosis. Materials and Methods: A deep learning algorithm was used to measure the LSVR in a cohort of 1027 consecutive patients (mean age, 50.5 years; 675 male and 352 female) with HBV-compensated cirrhosis who underwent liver CT (2007-2010). Associations of LSVR with hepatic decompensation and transplantation-free survival were evaluated using multivariable Cox proportional hazards and competing risk analyses, accounting for either the Child-Pugh score (CPS) or Model for End Stage Liver Disease (MELD) score and other variables. The risk of the liver-related events was estimated using Kaplan-Meier analysis and the Aalen-Johansen estimator. Results: After adjustment for either CPS or MELD and other variables, LSVR was identified as a significant independent predictor of hepatic decompensation (hazard ratio for LSVR increase by 1, 0.71 and 0.68 for CPS and MELD models, respectively; p < 0.001) and transplantation-free survival (hazard ratio for LSVR increase by 1, 0.8 and 0.77, respectively; p < 0.001). Patients with an LSVR of < 2.9 (n = 381) had significantly higher 3-year risks of hepatic decompensation (16.7% vs. 2.5%, p < 0.001) and liver-related death or transplantation (10.0% vs. 1.1%, p < 0.001) than those with an LSVR ≥ 2.9 (n = 646). When patients were stratified according to CPS (Child-Pugh A vs. B-C) and MELD (< 10 vs. ≥ 10), an LSVR of < 2.9 was still associated with a higher risk of liver-related events than an LSVR of ≥ 2.9 for all Child-Pugh (p ≤ 0.045) and MELD (p ≤ 0.009) stratifications. Conclusion: The LSVR measured on CT can predict hepatic decompensation and transplantation-free survival in patients with HBV-compensated cirrhosis.

• Korean Journal of Veterinary Research
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• v.33 no.3
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• pp.407-417
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• 1993

Bupleurum falcatum has been used for treatment of inflammation, jaundice, influenza and hepatitis as a traditional orient folk medicine. This experiment was carried out to evaluate the effect of B falcatum extract on cellular immune responses in vivo and in vitro. Antigen binding cell(ABC) assay, antibody production, Arthus and delayed-type hypersensitivity(DTH) reaction against sheep erythrocytes(SRBC) were very depressed in B falcatum extract treated group in vivo. The growth of Staphylococcus aureus in brain heart infusion(BHI) broth containing B falcatum extract was remarkably inhibited. Otherwise, that of Salmonella typhyimurium was not significantly increased in vitro. When B falcatum extract pretreated mice were intraperitoneally(IP) injected S typhimurium and S aureus, respectively, the number of bacteria in peritoneal exudates were time dependent declination compared with those of control, and the weight of spleen and the number of macrophage migration into peritoneal cavity have no difference from those of untreated control. B falcatum extract gradually increased phagocytic activities of peritoneal macrophage against Candida albicans time and dose dependently, and was not significant production of migration inhibiotory factor(MIF). But migration abilities of normal leucocytes in B falcatum extract pretreated group were decreased dose dependently. When B falcatum extract was IP administered, these data indicate that B falcatum extract increases level of serum coticosterone. Therefore, B falcatum extract was indirectly mediated in immune system by serum coticosterone having relation to immunosuppression. These results lead to the conclusion that B falcatum extract acts as a trigger or regulator of cellular immune responses in immune system.

• Journal of Environmental Health Sciences
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• v.36 no.2
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• pp.155-162
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• 2010

Aflatoxin $B_1$, a known human carcinogen, is the member of aflatoxin subfamily that is most frequently found in contaminated foods. Epidemiological studies have suggested that aflatoxins may be associated with human liver cancer and acute hepatitis. Recently it was reported that the traditional medical herbs sold in domestic markets are contaminated with aflatoxins. Long-term administration of these contaminated medicines could result in adverse health effects. Therefore, it is important to evaluate the levels of exposure to aflatoxin in people who ingest traditional herbal medicines. Blood samples were collected, before and after the herbal medicine intake, from 151 subjects who visited the hospital. The metabolite of aflatoxin $B_1$ in blood, aflatoxin $B_1$-albumin (aflatoxin $B_1$-lysine), is reportedly an appropriate internal exposure indicator, and its levels in the collected bloods were therefore analyzed using a liquid chromatography-mass spectrometry. The analytical method of aflatoxin $B_1$-lysine in blood was firstly optimized in Korea and the levels were detected below quantification limits (2 pg/mg albumin) in this study population. Consequently, the exposure levels of aflatoxin $B_1$ by ingestion of herbal medicines were low but it is important to monitor routinely due to the possibility of risk on the aflatoxin exposure.

• BMB Reports
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• v.40 no.5
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• pp.814-824
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• 2007

Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1043-1047
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• 2013

Although there have been many studies investigating possible associations between the C1653T mutation and risk of HCC, the results have been inconsistent. We conducted searches of the published literature in Pubmed and Embase databases up to January 2013. Seventeen studies with a total of 1,085 HCC cases and 1,365 healthy controls were retrieved. We found a significant association between the C1653T mutation and HCC risk (OR = 2.01, 95%CI= 1.49-2.70). In the subgroup analysis by ethnicity, a significant association was also found in Asians (OR = 2.07, 95%CI= 1.71-2.51). In subgroup analysis by HBV genotype, B and C were linked with development of HCC (B:OR = 2.21, 95%CI= 1.13-4.34; C:OR = 2.26, 95%CI= 1.61-3.16). However, no significant association was found between the C1653T mutation and HCC risk in HBeAg positive cases. In conclusion, this meta-analysis suggests that the C1653T mutation may be associated with susceptibility to HCC.

• Herbal Formula Science
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• v.31 no.2
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• pp.99-109
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• 2023

Objectives : Sihosogan-tang (SST) is one of the traditional herbal formula and also one of the Korean medical insurance medicines. It commonly used in the treatment of hepatitis, chronic gastritis, intercostal neuralgia, pleurisy, and depression in East Asia. In the present study, we have demonstrated the anti-inflammatory effects of SST in macrophage cell line. Methods : To investigate mechanism of the anti-inflammatory effect of SST, we examined the productions of nitric oxide (NO) and pro-inflammatory cytokines, and the expressions of inducible NO synthase (iNOS), nuclear factor-κ B (NF-κB) and mitogen-activated protein kinase (MAPK) on RAW 264.7 cells activated by LPS. Results : SST significantly inhibited the expression of iNOS increased by LPS, and also significantly inhibited the production of NO. In addition, SST significantly inhibited pro-inflammatory cytokines such as TNF- α and interleukines. SST inhibited the expression of NF-κB and MAPK activation. Conclusions : These results suggest that SST ameliorates inflammatory response in LPS-activated RAW 264.7 cells through the inhibition of the NF-κB and MAPK pathway. Therefore, this study supplies objective evidence for the anti-inflammatory effect of SST.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7825-7829
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• 2015

Background: Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum B2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. Materials and Methods: In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. B2M levels were measured in serum with a fully-automated IMX system. Results: The mean serum B2M level of Group (1) was $4.25{\pm}1.48{\mu}g/ml$., Group (2) was $7.48{\pm}3.04$, Group (3) was $6.62{\pm}2.49$ and Group (4) was $1.62{\pm}0.63$. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis ($7.48{\pm}3.04$) and HCC groups ($6.62{\pm}2.49$) than the HCV group ($4.25{\pm}1.48$) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB andWBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%.The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Conclusions: Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.

• Korean Journal of Microbiology
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• v.28 no.1
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• pp.13-18
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• 1990

A DNA sequence encoding the adr subtype preS2 region of hepatitis B virus envelope protein was fused to 5' end of lacZ gene yielding a plasmid pTSZ, in order to produce a preS2-$\beta$-galactosidase fusion protein. Serial deletions from 3' and 5' end of preS2 were constructed in plasmids, which were expressed and their antigenicities were examined with the monoclonal antibody H8. Deletions from amino and carboxy terminal to certain points did not affect the antigenicity, but the longer deletions destroyed the antigenicity. End points of deleted preS2 sequence were determined by DNA sequencing. As a result, each end of preS2 epitope was located in the region of amino acid residue 130-132 and 140-142, respectively. Residue 143 may be supplementary for antigenic epitope since the deletion from carboxy terminal to residue 143 revealed partial defect of antigenicity. In the interval of antigenic epitope the amino acid differences between adr and adw2 subtype occurred ar residue 130, 132, and 141. This result indicated that one or more of the three residues are responsible for the binding specificity of monoclonal antibody H8 to adr subtype preS2 fusion protein.

• Korean Journal of Microbiology
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• v.45 no.4
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• pp.346-353
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• 2009

Viral, bacterial, and fungal infection can be transmitted from donor to recipient via transplantation of human amniotic membrane. Therefore human amniotic membrane for transplantation should be disinfected and sterilized before use. The purpose of this study was to examine the efficacy of the disinfection process and sterilization processes used at human tissue bank in the inactivation of viruses, bacteria, and fungi. A variety of experimental model viruses, bacteria, and fungus for human pathogens, including the human immunodeficiency virus type 1 (HIV-1), bovine herpes virus (BHV), bovine viral diarrhoea virus (BVDV), hepatitis A virus (HAV), porcine parvovirus (PPV), Escherichia coli, Bacillus subtilis, and Candida albicans were all selected for this study. Enveloped viruses such as HIV-1, BHV, and BVDV were effectively inactivated to undetectable levels by 70% ethanol treatment, gamma irradiation process, and ethylene oxide (EO) gas sterilization process. Also non-enveloped viruses such as HAV and PPV were effectively inactivated to undetectable levels by gamma irradiation and EO gas treatment. However HAV and PPV showed high resistance to 70% ethanol treatment. E. coli and C. albicans were effectively inactivated to undetectable levels by 70% ethanol treatment, gamma irradiation process, and EO gas treatment. Also B. subtilis was effectively inactivated to undetectable levels by gamma irradiation process and EO gas treatment. However it showed high resistance to 70% ethanol treatment.

• BMB Reports
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• v.42 no.12
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• pp.834-839
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• 2009

DNA methyltransferase (DNMT) 1 is the key enzyme responsible for DNA methylation, which often occurs in CpG islands located near the regulatory regions of genes and affects transcription of specific genes. In this study, we examined the possible association of DNMT1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Seven common polymorphic sites were selected by considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n = 1,100). Statistical analysis demonstrated that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, showed significant association with HBV clearance in a co-dominant model (OR = 1.30, $P^{corr}$ = 0.03) and co- dominant/recessive model (OR = 1.34-1.74, $P^{corr}$ = 0.01-0.03), respectively. These results suggest that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, might affect HBV clearance.