Biomedical subjects

Chae Yoon Chon

Publications and source records attributed to Chae Yoon Chon.

31 records · Page 2Linked to original sources

PubMed2004

Hepatitis B virus infection after renal transplantation in the presence of antibody to hepatitis B surface antigen immunity.

BACKGROUND AND AIM: Hepatitis B virus (HBV) infection has been known to be hampered by immunity against hepatitis B surface antigen (HBsAg). However, HBV with mutations within the common antigenic epitope of HBsAg, the "a" determinant region, can escape from humoral immunity. Moreover, HBV infection by "a" determinant mutants in chronic HBV patients has been reported after renal transplantation. In the present study, the authors investigated HBV infection after renal transplantation despite passive immunization or resolved HBV infection. METHODS: A total of 1682 patients who underwent a renal transplant between 1979 and 1998 at the Severance Hospital, Yonsei University College of Medicine, Korea, were enrolled. The sequence of the HBV genome was analyzed from two patients with antibody to HBsAg (anti-HBs) immunity. RESULTS: Of 1682 patients who were HBsAg negative before transplantation, 21 patients were found to be HBsAg positive, with elevated aspartate aminotransferase and alanine aminotransferase levels after transplantation. Interestingly, six of 21 (28.6%) patients were anti-HBs positive before the transplantation. Sequence analysis of the cloned HBV from two of six patients with anti-HBs immunity showed no evidence of significant mutations within the "a" determinant region, suggesting a wild-type of HBV. Their donors were not exposed to HBV before transplantation (all HBV markers were negative). Seven deaths of 21 patients were ascribed to HBV-related complications. CONCLUSIONS: Regardless of anti-HBs immunity, HBV infection occurred in immunosuppressed patients in a high endemic area. The molecular mechanism and clinical impact of HBV infection after renal transplantation in patients with anti-HBs immunity should be further reappraised.

Adult↗

PubMed2004

[Changes of ascites nitric oxide according to the treatment course in cirrhotic patients with spontaneous bacterial peritonitis].

BACKGROUND/AIMS: Nitric oxide (NO) is a molecule involved in vascular dilatation and pathogen suppression. It also has immunologic and regulatory functions. Liver cirrhosis is characterized by an increased risk for bacterial infections, including spontaneous bacterial peritonitis (SBP). The role of NO in SBP which develops in cirrhosis has not been clearly established. The aim of this study was to investigate the role of NO in the pathogenesis of SBP and its clinical usefulness for prediction of disease prognosis. METHODS: This study was designed to investigate the changes of ascites NO in the course of treatment. Nitric oxide metabolite (nitrites+nitrates [NOx]) was measured by chemiluminescence in 84 ascites samples obtained from 84 cirrhotic patients. Among them, the 38 patients with SBP were treated with cefotaxime 2.0 g, q 12hr for 7 days. In 24 of SBP patients, ascites was obtained consecutively before treatment (day 0), during treatment (day 2), and after treatment (day 7). RESULTS: Ascites NO levels in the patients with SBP (n=38; 82.3 +/- 14.4 microM) were not different from those in patients with sterile ascites (n=46; 54.6 +/- 13.0 microM). There was no significant change of NO levels in sequential ascites samples during antibiotic treatment. Ascites NO level before treatment was significantly higher in SBP patients who responded to antibiotics (n=26; 101.86 microM/L) than that in SBP patients who did not respond to antibiotics (n=12; 40.03 microM/L, P=0.044). A significant direct correlation was found between ascites and serum NO levels before treatment (Pearson correlation, r2=0.86, P=0.001). Among the SBP patients, treatment response rate to antibiotics were significantly higher in those patients with pretreatment NO level > or = 80 microM/L in multivariate analysis. CONCLUSIONS: Ascites NO level was not different between ascites from SBP patients and ascites from cirrhotic patients with sterile ascites. There were no changes of ascites NO in SBP patients during treatment. Therefore ascites NO was not useful to predict the progress of SBP. Ascites NO levels reflect serum NO levels, and the patients with higher NO level may have better response to antibiotics.

Adult↗

PubMed2004

[Reappraisal of HBV genotypes and clinical significance in Koreans using MALDI-TOF mass spectrometry].

BACKGROUND/AIMS: Recent studies have shown that the genotype of hepatitis B virus (HBV) may correlate with the disease natural history and treatment outcome. However, several of these studies used low sensitivity assays in a small number of patients, and this has precluded an accurate evaluation of Korean HBV genotypes. We analyzed Korean HBV genotypes in a large population by employing a new technology, restriction fragment mass polymorphism (RFMP) using MALDI-TOF mass spectrometry, in a sensitive and specific manner. METHODS: Between February 1995 and December 2003, a total of 475 patients with chronic HBV infection were enrolled. The assay is based on the mass measurement of oligonucleotides having genotypic variations of the S gene. Clinical features including the virologic status and disease progression were also evaluated. RESULTS: The median age of the total patients was 35.5 years. Out of 475 patients, there were 162 (34.1%) inactive carriers, 172 (36.2%) had chronic hepatitis, 77 (16.2%) had liver cirrhosis and 64 (13.5%) had hepatocellular carcinoma (HCC). There were 454 patients (95.6%) with genotype C, 4 patients (0.8%) with genotype A, 16 patients (3.4%) with the mixed A and C genotype [7 patients (1.4%) with A A], and 1 patient (0.2%) with B genotype. Comparing genotype A and C, genotype A patients were all inactive carriers without HCC, whereas genotype C patients included those with chronic hepatitis, liver cirrhosis and HCC. CONCLUSIONS: HBV genotype C is highly prevalent in Korea. Although it is a small percentage, genotype A also exists and it seems to take a more benign clinical course than genotype C. Further studies are necessitated to assess the relationship between HBV genotypes and the various aspects of the diseases' clinical course.

Adolescent↗

PubMed2004

[Clinical features and prognostic factors of fulminant hepatic failure in Koreans].

BACKGROUND/AIMS: There have been scant reports on the prognostic factors of fulminant hepatic failure for selecting the patients who need liver transplantation. We investigated the clinical features and prognostic factors throughout the clinical course of the disease in Korean patients with fulminant hepatic failure. METHODS: Between 1992 and 2003, a total of 60 patients with fulminant hepatic failure were divided into the survival group and the non-survival group, and these groups were compared according to gender, age, etiology, values of the laboratory tests, grade of the encephalopathy that was obtained at the time of admission and the worst clinical status (hepatic encephalopathy). RESULTS: The mean age of the total patients was 40.9 years (M:F=31:29) and the survival rate was 28.3% (n=17). Drugs (n=25, 12 herbal medicines) and viral infection (n=24, 18 HBV infection) were most common causes. On univariate analysis, the WBC, AST, ALT, total bilirubin and HE IV stage at the time of admission were the significant factors for a poor prognosis. Total bilirubin, albumin and HE IV stage also remained as significant factors at the time of the worst clinical status. On multivariate analysis, total bilirubin (P=0.033) and ALT (P=0.042) at admission were the prognostic factors, and the progression to HE IV stage (P=0.019) or hypoalbuminemia (P=0.028) during hospitalization represented the significant factors for a poor prognosis. CONCLUSIONS: In contrast to Western countries, HBV infection and herbal medicines were major causes of fulminant hepatic failure in Korea. The total serum bilirubin level and progressive hyperbilirubinemia with HE (stage IV) during hospitalization seemed to be the most important prognostic factors, and liver transplantation should be considered before the patient reaches this status.

Adult↗

PubMed2003

Clinical results and prognostic factors in radiotherapy for unresectable hepatocellular carcinoma: a retrospective study of 158 patients.

PURPOSE: To analyze the treatment results and prognostic factors affecting survival in patients with unresectable hepatocellular carcinoma treated with local radiotherapy (RT). METHODS AND MATERIALS: Between 1992 and 2000, 158 patients with unresectable hepatocellular carcinoma received local RT. Sixty-seven patients had an advanced UICC Stage III lesion and 91 patients had Stage IVA. The mean tumor size was 9.0 +/- 3.0 cm, and liver cirrhosis was present in 142 patients. Local RT was combined with transarterial chemoembolization as primary treatment (107 patients) or as salvage after failure of repeated transarterial chemoembolization (51 patients). The mean radiation dose was 48.2 +/- 7.9 Gy in daily 1.8-Gy fractions. RESULTS: The mean follow-up was 21.6 months after diagnosis and 14.6 months after RT. The response rate was 67.1%. The overall survival rate at 2 and 5 years was 30.5% and 9%, respectively, from the time of diagnosis (median survival time 16 months) and 19.9% and 4.7%, respectively, after RT (median survival time 10 months). On univariate analysis, tumor size (p = 0.047), the presence of portal vein thrombosis (p = 0.007), and RT dose (p = 0.001) were significant factors for survival. However, on multivariate analysis, RT dose was the only significant factor (p = 0.01). CONCLUSION: Local RT achieved substantial tumor regression and survival. The radiation dose was found to be a significant prognostic factor in the RT of hepatocellular carcinoma. Additional efforts for dose escalation are warranted to improve the treatment results in parallel with better protecting the nontumorous liver.

Adult↗

PubMed2003

Apoptosis of hepatic stellate cells in carbon tetrachloride induced acute liver injury of the rat: analysis of isolated hepatic stellate cells.

BACKGROUND/AIMS: Analysis of isolated hepatic stellate cells (HSCs) from the injured liver may provide direct information on HSC apoptosis. However, it has not been established whether apoptotic HSCs would be isolated using the usual density gradient centrifugation method. The aim of this study was to observe the serial pattern of proliferation and apoptosis in isolated HSCs in comparison with that of liver tissue sections in CCl4 induced acute liver injury. METHODS: Male Sprague-Dawley rats were treated with a single intraperitoneal injection of carbon tetrachloride (CCl4) and were killed at various time points after the treatment. RESULTS: HSC proliferation showed a maximal increase at 32 h after CCl4 injection. Apoptosis of HSC, examined by quantitative analysis of annexin-V-fluorescein isothiocyanate (FITC)staining, showed the maximal increase at 64 h. Apoptosis of HSC in liver tissue sections examined by counting desmin and Tdt-mediated-dUTP biotin nick end labeling (TUNEL) double staining cells, peaked at 64 h. The number of TUNEL positive HSCs in liver tissue sections correlated significantly with annexin-V-FITC binding of isolated HSC. CONCLUSIONS: Studying apoptosis using apoptotic HSCs isolated by a usual density gradient centrifugation method from injured tissue sections would be feasible since it correlated with in vivo apoptosis of HSC.

Acute Disease↗

PubMed2003

Clinical results of 3-dimensional conformal radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma in the cirrhotic patients.

PURPOSE: Recent reports have shown that a portion of the liver can tolerate higher radiation doses, which can be further accomplished by the application of 3-dimensional conformal radiotherapy (3-DCRT). The purpose of this study was to investigate the efficacy and toxicity of 3-DCRT combined with transcatheter arterial chemoembolization (TACE) for HCC in the cirrhotic patients. METHODS AND MATERIALS: From 1994 to 2000, 50 HCC patients with liver cirrhosis (LC) were included in this study. The degree of LC was Child A in 38 and Child B in 12. The UICC stages were II in 12, III in 16, and IVa in 22. The mean tumor size was 8.3+/-3.5 cm. Patients were treated with TACE and then followed by 3-DCRT within 7-14 days. 3-DCRT planning was used to define both the target and normal liver volumes. The total dose of radiation (mean 50.1+/-8.3 Gy) was determined by the fractional volume of normal liver receiving 50% of the isocenter dose. RESULTS: A partial response (PR) was observed in 33 patients (66%). A subsequent surgical resection was successful in three patients, showing complete necrosis in one and near total necrosis in two. Most common acute toxicity was alteration in liver function test (13 patients) and none of the patients showed an acute toxicity more than grade 3. Subacute and chronic toxicity involved radiation induced liver disease (RILD) (six patients) and gastrointestinal toxicity (seven patients; ulcer in five and hemorrhagic mucositis in two). The actuarial survival rate at 3 years was 43% from the commencement of radiotherapy. CONCLUSIONS: Radiotherapy using 3-DCRT combined with TACE can achieve a substantial tumor response and survival rate for HCC in the cirrhotic patients.

Journal Article↗

PubMed2002

Dose-response relationship in local radiotherapy for hepatocellular carcinoma.

PURPOSE: Dose escalation using three-dimensional conformal radiotherapy (3D-CRT) is based on the hypothesis that increasing the dose can enhance tumor control. This study aimed to determine whether a dose-response relationship exists in local radiotherapy for primary hepatocellular carcinoma (HCC). METHODS AND MATERIALS: One hundred fifty-eight patients were enrolled in the present study between January 1992 and March 2000. The exclusion criteria included the presence of an extrahepatic metastasis, liver cirrhosis of Child class C, tumors occupying more than two-thirds of the entire liver, and a performance status on the Eastern Cooperative Oncology Group scale of more than 3. Radiotherapy was given to the field, including the tumor, with generous margin using 6- or 10-MV X-rays. The mean radiation dose was 48.2 +/- 7.9 Gy in daily 1.8-Gy fractions. The tumor response was assessed based on diagnostic radiologic examinations, including a computed tomography scan, magnetic resonance imaging, and hepatic artery angiography 4-8 weeks after the completion of treatment. Liver toxicity and gastrointestinal complications were evaluated. RESULTS: An objective response was observed in 106 of 158 (67.1%) patients. Statistical analysis revealed that the total dose was the most significant factor associated with the tumor response. The response rates in patients treated with doses <40 Gy, 40-50 Gy, and >50 Gy were 29.2%, 68.6%, and 77.1%, respectively. Survivals at 1 and 2 years after radiotherapy were 41.8% and 19.9%, respectively, with a median survival time of 10 months. The rate of liver toxicity according to the doses <40 Gy, 40-50 Gy, and >50 Gy was 4.2%, 5.9%, and 8.4%, respectively, and the rate of gastrointestinal complications was 4.2%, 9.9%, and 13.2%, respectively. CONCLUSIONS: The present study showed the existence of a dose-response relationship in local radiotherapy for primary HCC. Only the radiation dose was a significant factor for predicting an objective response. The results of this study showed that 3D-CRT can theoretically be used for treating primary HCC.

Carcinoma, Hepatocellular↗

PubMed2002

[Direct analysis of HBV-specific CD8+ lymphocyte by tetrameric HLA-A2/core 18-27 complex in chronic Hepatitis B].

BACKGROUND/AIMS: Hepatitis B virus(HBV) specific cytotoxic T lymphocyte (CTL) response is believed to play a major role in virus control and liver damage in chronic hepatitis B(CHB). We performed this study to evaluate whether HBV specific CTL could be visualized directly by tetrameric HLA-A2/core 18-27 complex(T c18-27) in the peripheral blood and liver of patients with CHB. On the basis of our results we clarified patients intrahepatic compartmentalization and correlation with HBV specific CTL and viral replication or liver damage. METHODS: We stained peripheral blood mononuclear cells of 33 HLA-A2 + and 8 HLA-A2 patients with CHB with cytochrome conjugated anti-CD8 mAb and phycoerythrin conjugated T c18-27. Among these we analysed intrahepatic lymphocyte of 11 HLA-A2 + patients. We compared the frequency of T c18-27 specific CD8+ cells with serum HBV-DNA levels or alanine aminotransferase(ALT) levels. RESULTS: The frequency of circulating T c18-27 specific CD8+ cell was higher(9-101 cells per 50,000 CD8+ cells) than background level in 14 among 33 patients. The frequency of intrahepatic T c18-27 specific CD8+ cells was 12-2100 cells per 50,000 CD8+ cells in 8 out of 11 patients whose liver was obtained This was 17.4-150 times higher than circulating T c18-27 specific CD8+ cells. The frequency of circulating T c18-27 specific CD8+ cells was increased in 10 out of 18 patients with serum HBV DNA level <0.5 pg/mL and ALT < 40 IU/L. It was increased in just 4 out of 15 patients with HBV DNA level > 800 pg/mL and ALT > 70 IU/L. The frequency of intrahepatic T c18-27 CTL tended to be lower in high levels of serum HBV DNA and was not correlated with liver inflammation. CONCLUSION: This study proves that if HBV-specific CTLs are barely detectable in the peripheral blood of CHB, much more HBV-specific CTLs are in the liver and most HBV-specific CTLs are infiltrated in the liver. Also, in the presence of an effective HBV specific CD8 response the inhibition of viral replication can be independent of liver damage.

CD8-Positive T-Lymphocytes↗

PubMed2002

[Efficacy and safety of large volume paracentesis in cirrhotic patients with spontaneous bacterial peritonitis: a randomized prospective study].

BACKGROUND/AIMS: Large volume paracentesis (LVP) associated with plasma volume expansion is known to be an effective and safe therapy for tense or refractory ascites in cirrhosis. Spontaneous bacterial peritonitis (SBP) is one of the frequent infections in patients with cirrhosis. We conducted a study to assess the efficacy and safety of large volume paracentesis in cirrhotic patients with SBP. METHODS: We randomly assigned 40 patients with cirrhosis and SBP to either treatment with LVP (21 patients) or general management (19 patients). LVP was defined as drainage of ascitic fluid of more than 4 liters in a single tap or loss of shifting dullness after paracentesis. LVP was performed within 48 hours after the diagnosis of SBP in the LVP group. Cefotaxime was given daily in doses that varied according to the serum creatinine level in both groups. Albumin was given at a dose of 6-8 g per 1 liter of removed ascites in the LVP group. RESULTS: After seven days of treatments, the blood chemistry test, and WBC (PMN) counts and protein concentration in the ascitic fluid were not different between the two groups. Among them, the WBC (PMN) counts were decreased significantly in both groups and protein concentrations tended to increase. Durations of abdominal tenderness and pain were shorter in the LVP group but the differences were statistically not significant. Admission periods, resolution rates of SBP after seven days of treatment, complication rates and in-hospital mortality rates were not different between the two groups. CONCLUSIONS: The two treatment methods demonstrated almost the same effectiveness and safety. The symptoms were improved slightly faster in the LVP group. We concluded that large volume paracentesis is not an absolute contraindication and can be a tolerable and safe therapy in some selected cirrhotic patients with tense ascites and SBP.

Adult↗

PubMed2002

[Concurrent chemo-radiation therapy for advanced hepatocellular carcinoma with portal vein thrombosis].

BACKGROUND/AIMS: Advanced hepatocellular carcinoma with portal vein thrombosis has a poor prognosis. This study was undertaken to evaluate the therapeutic effects of concurrent chemo-radiation therapy in advanced hepatocellular carcinoma with portal vein thrombosis. METHODS: A total of 54 patients with advanced hepatocellular carcinoma (TNM stage IVa) were enrolled. Nineteen patients were treated with external beam radiotherapy (4,500 cGy/ 5 weeks) and intrahepatic arterial 5-FU infusion (500 mg on 1-5 day and 30-35 day, respectively) via implanted chemoport. The others were treated with intrahepatic arterial cisplatin infusion (80 mg/m(2)). RESULTS: In patients treated with concurrent chemo-radiation therapy, response rates at 2nd and 6th months were 42.1% and 26.3%, respectively. In patients treated with intrahepatic arterial cisplatin therapy, response rates at 2nd and 6th months were 2.9% and 0%, respectively. The median survival time was 11.6 months in concurrent chemo-radiation therapy and 4.8 months in intrahepatic arterial cisplatin infusion therapy. Concurrent chemo-radiation therapy produced better response rates and longer survival time than those of intrahepatic arterial cisplatin infusion therapy (p<0.05). CONCLUSIONS: Concurrent chemo-radiation therapy achieved favorable results in advanced hepatocellular carcinoma with portal vein thrombosis and can be considered as a treatment option for the management of advanced hepatocellular carcinoma.

Antineoplastic Agents↗

PubMed2002

[Chemokine receptor expression of hepatitis B virus-specific CD8+ lymphocyte in chronic B viral infection].

BACKGROUND/AIMS: The protective role of HBV-specific CD8+ cells is dependent on their ability to efficiently migrate to the infected liver, where they may exert an effector function. The migratory behavior of CD8+ cells is influenced by their expression of different chemokine receptors. This study was intended to analyse the pattern of chemokine receptor expression of HBV specific CD 8+ cells in chronic B viral infection. METHODS: We analysed the CCR5 and CCR3 profile of HBV-specific CD8+ cells isolated from the blood and liver of patients with different patterns of HBV infection. Purified T cells were stained directly ex vivo, or after antigen-specific stimulation, using HBV peptide-specific HLA tetramers and monoclonal antibodies to CD8, CCR5 and CCR3, with analysis by flow cytometry. RESULTS: In patients with chronic hepatitis B characterised by low levels of virus (serum HBV DNA <0.5 pg/mL) and minimal liver inflammation, analysis of circulating and intrahepatic CD8+ cells demonstrated that liver infiltrating Tc18-27-specific cells were preferentially CCR5+ (up to 80% of HBV-specific CD8+ cells), in contrast to cells of the same specificity within the circulating compartment (up to 35% of HBV-specific CD8+ cells). Furthermore, CCR3 was expressed by about 10% of Tc18-27+ cells infiltrating the liver, but was absent from circulating cells. Following HBV-specific stimulation in vitro the CCR5 expression of circulating Tc18-27-specific cells was up-regulated, to levels found in liver infiltrating cells, whereas CCR3 expression was unchanged. CONCLUSIONS: The chemokine receptor profile of HBV-specific CD8+ cells is influenced by the anatomical site of these cells, and the clinical pattern of disease. The ability of circulating HBV-specific CD8+ cells of patients with low replicating virus to upregulate CCR5 suggests that these cells may respond to increases in virus replication by efficiently migrating into the infected liver.

CD8-Positive T-Lymphocytes↗

PubMed2002

[Clinical efficacy of serum PIVKA-II in the diagnosis and follow up after treatment of hepatocellular carcinoma].

BACKGROUND/AIMS: Protein induced by vitamin K absence or antagonist II (PIVKA-II) appears to be a useful tumor marker for the evaluation of patients with hepatocellular carcinoma (HCC). But the usefulness of PIVKA-II was not yet clear in Korea where hepatitis B-virus is endemic. We investigated the usefulness of PIVKA-II in the diagnosis and follow-up after treatment of HCC. METHODS: We studied patients with HCC which was pathologically confirmed. PIVKA-II was measured by enzyme immunoassay. PIVKA- levels before and after treatment, in correlation with imaging studies, were analyzed for the comparison of treatment responses. Kappa index was obtained. RESULTS: A total of 129 patients were included. 93 patients (72%) were HBsAg positive. 86 patients (67%) were PIVKA-II >40 mAU/mL. 52 patients (40%) were AFP >20 ng/mL and 77 patients (60%) were AFP < or = 20 ng/mL. Of 77 patients, 40 patients (52%) showed PIVKA-II >40 mAU/mL. 68 of 129 patients were evaluated treatment response. On the basis of radiologic response, CR was 33, PR 17, SD 12, and PD 6. Of the 33 radiologic CR patients, 30 patients were CR and 3 patients were PR by means of PIVKA-II response. Of the 17 radiologic PR patients, 6 patients were CR and 7 patients were PR. Therefore, tumor responses by radiologic and PIVKA-II were well correlated (Kappa index was 0.59). CONCLUSIONS: PIVKA-II can be used as a useful tumor marker for patients with HCC, especially those with low levels of AFP, before and after treatment in Korea.

Biomarkers↗