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Predictive Factors for Beneficial Response to Interferon-alfa Therapy in Chronic Hepatitis C
( Seung Kew Yoon ),( Sung Soo Kim ),( Young Min Park ),( Kyu Sik Shim ),( Chang Don Lee ),( Hee Sik Sun ),( Doo Ho Park ),( Boo Sung Kim ),( Wang Shick Ryu ),( Joong Myung Cho ) 대한내과학회 1995 The Korean Journal of Internal Medicine Vol.10 No.2
(Seung Kew Yoon),(Young Min Park),(Byung Hoon Byun),(Si Hyun Bae),(Jin Mo Yang),(Byung Min Ahn),(Young Sok Lee),(Chang Don Lee),(Hee Sik Sun),(Boo Sung Kim) 대한내과학회 2000 The Korean Journal of Internal Medicine Vol.15 No.2
N/A Background : Although the polyproteins of hepatitis C virus(HCV) are processed and formed in nearly equimolar amounts, individual functional proteins have a discrepancy in their time of appearance following HCV infection and eliciting immune response. This study was conducted to compare the reactivity toward regional specific HCV protein in relation to virological characteristics, including HCV genotype and HCV replication. Methods : Sera from forty-five patients with chronic HCV infection were analyzed through the experiments of the recombinant immunoblot assay(RIBA-2), HCV genotyping and HCV RNA quantitation. Results : The frequencies of seropositivity to C22-3, C33C, C100-3 and 5-1-1 proteins were 91.1%, 91.1%, 64.4% and 53.3%, respectively, of all the patients, and thus the antibodies to C22-3 and C33C proteins were found more frequently (p <0.05). The antibody responses between core or NS3 proteins and NS4 proteins showed more discrepancy in the HCC group than that in the CH group, implying a possibility of oncogenic potential of core or NS3 gene in hepatocarcinogenesis. The detection rate of antibodies to C22-3 and C33C, in accordance with serum HCV RNA levels, was significantly higher in highly viremic patients than that in low viremic patients (p <0.05). Antibodies to C22-3, C33C, C100-3 and 5-1-1 were also found more frequently in patients with HCV genotype 1b, compared to those with HCV genotype 2a (p <0.05). Conclusion : These results suggest that antibody detection of HCV may depend on the virological characteristics of HCV, the levels of HCV replication and HCV genotype and, therefore, HCV RNA detection using RT-PCR technique is essential for confirmatory diagnosis for HCV infection. Furthermore, the HCV core or NS3 Protein may play important role in hepatocarcinogenesis.
( Seung Kew Yoon ),( Maurizia Brunetto ),( Young Suk Lim ),( Ed Gane ),( Wai Kay Seto ),( Marina Osipenko ),( Sang Hoon Ahn ),( Harry L. Janssen ),( Akash Shukla ),( Wan Long Chuang ),( Huy Trinh ),( 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: In this randomized, double blind study in HBeAg- negative patients comparing TAF to TDF, the efficacy of TAF was demonstrated to be noninferior to that of TDF at Week 48 in the proportion with HBV DNA <29 IU/mL with improved bone and renal effects. Here we present the results after two years of treatment. Methods: 425 patients were randomized to receive TAF 25 mg QD (n=285) or TDF 300 mg QD (n=140) and treated for 144 weeks.. Efficacy analyses at Week 96 included virologic (HBV DNA <29 IU/mL), and biochemical (ALT normalization) responses; key secondary safety endpoints were changes in hip and spine bone mineral density (BMD), and changes in serum creatinine and estimated GFR by Cockcroft- Gault method (eGFRCG). Serum markers of bone turnover and urine markers of renal tubular function were also assessed. Results: Baseline characteristics included: mean age 46 years, 61% males, 72% Asians, genotypes A through D (5%, 24%, 38%, 31%); 19% had HBV DNA ≥ 7 log10 IU/mL, and 21% were previously treated with nucleos(t)ides. Efficacy and safety results are summarized in the Table. At Week 96, virologic response rates were similar in the TAF and TDF groups.A greater percentage of TAF patients achieved normalization of serum ALT valuesPatients receiving TAF showed smaller declines in hip and spine BMD compared with TDF patients through Week 96. The smaller decline in eGFRCG and smaller changes in renal tubular markers observed with TAF. The rates of treatment discontinuations for adverse events (<2%) and serious adverse events were (≤11%) were similar. Conclusions: At Week 96, high rates of virologic suppression were maintained with a higher rate of ALT normalization seen in TAF patients relative to TDF and continued improved bone and renal safety with TAF compared with TDF.
Review : The Biology of Cancer Stem Cells and Its Clinical Implication in Hepatocellular Carcinoma
( Seung Kew Yoon ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.1
Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options in its advanced state. The molecular mechanisms underlying HCC remain unclear because of the complexity of its multi-step development process. Cancer stem cells (CSCs) are defi ned as a small population of cells within a tumor that possess the capability for selfrenewal and the generation of heterogeneous lineages of cancer cells. To date, there have been two theories concerning the mechanism of carcinogenesis, i.e., the stochastic (clonal evolution) model and the hierarchical (cancer stem cell-driven) model. The concept of the CSC has been established over the past decade, and the roles of CSCs in the carcinogenic processes of various cancers, including HCC, have been emphasized. Previous experimental and clinical evidence indicated the existence of liver CSCs; however, the potential mechanistic links between liver CSCs and the development of HCC in humans are not fully understood. Although defi nitive cell surface markers for liver CSCs have not yet been found, several putative markers have been identifi ed, which allow the prospective isolation of CSCs from HCC. The identifi cation and characterization of CSCs in HCC is essential for a better understanding of tumor initiation or progression in relation to signaling pathways. These markers could be used along with clinical parameters for the prediction of chemoresistance, radioresistance, metastasis and survival and may represent potential targets for the development of new molecular therapies against HCC. This review describes the current evidence for the existence and function of liver CSCs and discuss the clinical implications of CSCs in patients demonstrating resistance to conventional anticancer therapies, as well as clinical outcomes. Such data may provide a future perspective for targeted therapy in HCC. (Gut Liver 2012;6:29-40)