RESUMEN

Adefovir dipivoxil (ADV) has demonstrated clinical activity against both wild-type and lamivudine-resistant hepatitis B virus (HBV). We analyzed the evolution of viral load and the changes of polymerase and precore/core promoter sequences in lamivudine-resistant virus during ADV therapy. The authors studied 14 patients who had breakthrough hepatitis after lamivudine therapy. Serial sera were obtained prior to adefovir administration and at 3, 6 and 12 months after ADV therapy. Nucleotide sequences of polymerase and the precore/core promoter from the hepatitis B virus were analyzed. The median serum HBV DNA decrease with adefovir treatment was 4.35 log(10) copies/mL at 12 months. Tyrosine-methionine-aspartate-aspartate (YMDD) mutants were found in 12 patients among the 14 patients with lamivudine resistance. The YMDD mutant viruses reversed to the wild-type in 6 patients out of the 12 patients after 3-6 months of ADV after discontinuing lamivudine therapy. In the analysis of the nucleotide sequences of the precore/core promoter gene, core promoter mutants in 12 patients were replaced by wild-type virus in three patients (25%), while precore mutants in four patients were replaced by the wild-type in three patients (75%). The results demonstrate the patterns of polymerase and precore/core promoter mutations in lamivudine-resistant hepatitis B viruses and the reversion from the mutant to the wild-type in some patients. In addition, despite several mutations in the polymerase during ADV therapy, ADV effectively suppressed HBV replication without the emergence of resistant viral mutants.

Asunto(s)

Adenina/análogos & derivados , Antivirales/uso terapéutico , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Adulto , Secuencia de Bases , Análisis Mutacional de ADN , Cartilla de ADN/genética , ADN Viral/genética , Farmacorresistencia Viral/genética , Evolución Molecular , Femenino , Productos del Gen pol/genética , Genes Virales , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Lamivudine/farmacología , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Proteínas del Núcleo Viral/genética , Viremia/tratamiento farmacológico , Viremia/virología

RESUMEN

BACKGROUND AND AIM: Studies from hepatitis B virus endemic areas have shown less durable lamivudine-induced responses and have raised issues about the management of a post-treatment relapse. METHODS: From January 2000 to June 2004, all 51 patients (43 HBeAg-positive and eight HBeAg-negative) were retreated with lamivudine for at least 12 months. All had a post-treatment relapse after HBeAg responses (HBeAg loss/seroconversion) during the first therapy. RESULTS: During retreatment, HBeAg seroconversion occurred more frequently in those patients with HBeAg seroconversion than in those with HBeAg loss alone during prior lamivudine therapy (P = 0.001). On multivariate analysis, prior HBeAg seroconversion and early virological response (EVR) (< or = 2 months of retreatment) independently predicted HBeAg seroconversion (P = 0.012 and P = 0.004, respectively). With regard to virological breakthrough, only the time to virological response (> 2 months of retreatment) remained significant (P = 0.048). Among the HBeAg-negative patients, virological breakthrough occurred in only one patient with a late virological response. CONCLUSIONS: EVR is a major predictor in determining a favorable response to lamivudine retreatment. Our observations suggest that lamivudine retreatment will provide more therapeutic gains in those patients with a prior HBeAg seroconversion than in those with HBeAg loss alone.

Asunto(s)

Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , ADN Viral/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Retratamiento , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

BACKGROUND/AIMS: Protein-calorie malnutrition is a common complication in cirrhosis. Protein restriction for the treatment of hepatic encephalopathy (HE) may cause disease progression and poor prognosis. Therefore, we evaluated important clinical parameters for nutritional state in cirrhotic patients with or without HE to predict the development of HE. METHODS: Twenty-two cirrhotic patients were divided into two groups; group A-13 patients without HE and group B-9 patients with HE. Clinical and biochemical parameters, serum proteins {serum albumin, insulin-like growth factor-1 (IGF-1), transferrin, leptin, etc}, immunologic parameters and anthropometry were measured. RESULTS: Child-Pugh score and Model for End-stage Liver Disease (MELD) scale were higher in group B (p<0.01). After correction of various factors affecting nutritional assessment, especially of Child-Pugh score and MELD scale, leptin was higher in group B (p<0.05). There was no difference in anthropometric measurements. Transferrin correlated inversely with MELD scale in group A (p<0.01). IGF-1 correlated inversely with total lymphocyte count in group B (p<0.05). Leptin correlated with Child-Pugh scores, total lymphocyte count and mid-arm muscle circumference in group A (p<0.05, p<0.05 and p<0.05, respectively), and correlated inversely with CD8 in group B (p<0.05). CONCLUSIONS: Leptin level is higher in patients with HE, and further studies for parameters of nutrition to predict HE in many cirrhotic patients will be needed.

Asunto(s)

Biomarcadores/sangre , Encefalopatía Hepática/etiología , Cirrosis Hepática/complicaciones , Estado Nutricional , Anciano , Antropometría , Femenino , Encefalopatía Hepática/sangre , Encefalopatía Hepática/diagnóstico , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Leptina/sangre , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Transferrina/análisis

RESUMEN

BACKGROUND/AIMS: Apoptosis via Fas/FasL system is thought to be involved in the development of hepatocyte death in viral hepatitis B. In chronic hepatitis C, sFas/sFasL system was reported to control liver injury induced by Fas/FasL mediated apoptosis. To determine the role of sFas/sFasL system in chronic hepatitis B, we analyzed serum sFas/sFasL in 58 HBV patients and 29 healthy controls. METHODS: HBV patients were categorized into two groups; normal ALT (< or =40 IU/L) and elevated ALT (>40 IU/L). Serum sFas/sFasL levels in HBV patients were measured by ELISA and was compared with those in 29 healthy controls. Serum ALT levels, histological activity, and Fas/FasL expression of liver were compared. RESULTS: Chronic hepatitis B patients with elevated ALT had significantly higher serum sFas levels than those in healthy controls (P<0.01). Serum sFasL levels, however, were significantly lower than those in healthy controls (P<0.01). Patients with moderate to marked degree of inflammation and fibrosis had significantly higher serum sFas levels than those in healthy controls (P<0.05). Serum sFasL levels had no correlation with the hepatic histological activity. Serum sFas/sFasL levels also had no significant correlation with the Fas/FasL expression of liver. CONCLUSIONS: Serum sFas/sFasL levels play a possible role in the pathogenesis of chronic hepatitis B. These results suggest that serum sFas levels might serve as a marker for estimating the degree of hepatic histological activity.

Asunto(s)

Proteína Ligando Fas/sangre , Hepatitis B Crónica/diagnóstico , Receptor fas/sangre , Adulto , Proteína Ligando Fas/análisis , Femenino , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Receptor fas/análisis

RESUMEN

BACKGROUND/AIM: Recent data have shown that the clinical outcome of hepatitis C virus (HCV) infection may be influenced by the host genetic factor. The aim of this study was to investigate whether particular human leukocytes antigen (HLA) molecules are associated with the susceptibility to HCV infection in the Korean population. METHODS: One hundred and thirty-seven patients with chronic HCV infection and 206 normal individuals were examined for HLA class I and II molecules. RESULTS: In class I antigens, the frequencies of HLA-A3 (relative risk (RR)=3.5, P<0.04), HLA-B35 (RR=2.0, P<0.03), and HLA-B46 (RR=2.5, P<0.02) significantly increased in chronic HCV carriers compared with the controls. The frequencies of DRB1*0803, DQB1*0601 and DQB1*0604 were significantly higher in chronic HCV carriers than in controls (RR=2.5, P<0.005; RR=1.8, P<0.05; RR=1.9, P<0.04, respectively). On the other hand, the frequencies of DRB1*0301, DQA1*0501 and DQB1*0201 were significantly lower in chronic HCV carriers than in normal controls (RR=0.2, P<0.03; RR=0.4, P<0.004; RR=0.5, P<0.02, respectively). The haplotype DRB1*0803-DQB1*0601 significantly increased (RR=2.5, P<0.02) while the DQA1*0501-DQB1*0201 significantly decreased (RR=0.2, P<0.03) in chronic HCV carriers compared with normal controls. In stratification analysis to investigate the interrelationships among the associated alleles, DRB1*0803 and DQB1*0601 were associated with HLA-B46, particularly in patients with chronic HCV carriers. CONCLUSIONS: These results suggest that particular HLA alleles may have an influence on chronic HCV infection as a host genetic factor in the Korean population.

Asunto(s)

Antígenos HLA/genética , Hepatitis C Crónica/genética , Adulto , Anciano , Alelos , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Heterocigoto , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Fenotipo

RESUMEN

BACKGROUND: Few clinical trials have investigated the use of lamivudine (LAM) in patients with decompensated cirrhosis related to chronic hepatitis B. The aim of the present study was to evaluate the efficacy of extended LAM treatment and to determine the timing of LAM administration in patients with decompensated cirrhosis. METHODS: A total of 17 patients were treated with LAM 100 mg/day. The mean duration of follow up was 28 +/- 8.4 months (range: 14-42 months). All patients were evaluated for evidence of clinical, biochemical and serologic replication of hepatitis B virus (HBV) infection. There were 12 patients with Child class B and five with Child class C. RESULTS: Ten of 17 patients (58.2%) responded to LAM treatment. Of the breakthrough patients, six (86%) had YMDD motif variants. Clinical improvement was observed in nine out of 10 responders (90%), six of the seven breakthrough patients (86%) and five of six patients with YMDD variant DNA. Mean time to achieve a 2-point reduction in Child-Pugh-Turcotte score was 14 months in patients with Child class C, compared with 5.9 months in those with Child class B (P < 0.001). Mean time required to gain a 0.5 g/dL increment in albumin was 14 months in Child class C and 5.8 months in Child class B. Hepatitis B e antigen (HBeAg) seroconversion was achieved in five of 13 HBeAg-positive patients at the last follow up and during the follow-up period. CONCLUSION: Long-term administration of LAM for patients with decompensated cirrhosis is effective. Earlier LAM administration in Child class B patients led to improved clinical outcomes.

Asunto(s)

Lamivudine/administración & dosificación , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/fisiopatología , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adulto , ADN Viral/sangre , ADN Viral/genética , Esquema de Medicación , Femenino , Estudios de Seguimiento , Variación Genética , Hepatitis B/complicaciones , Hepatitis B/virología , Virus de la Hepatitis B/genética , Humanos , Lamivudine/uso terapéutico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

RESUMEN

BACKGROUND/AIMS: Barrett's esophagus is a premalignant lesion of the esophagus in which normal squamous epithelium is replaced by intestinalized columnar epithelium. In Korea, adenocarcinoma associated with Barrett's esophagus is rare compared with that of Western country. The purpose of this study was to investigate the immunohistochemical expression of p53 and Ki-67 in Barrett's esophagus which had predictive value for cancer risk in Korea. METHODS: Ninety five patients (43 male and 52 female, median age 44, range 21-75) who have been suspected to have Barrett's esophagus by endoscopic assessment were enrolled in this study. Alcian blue (pH 2.5) and high ion diamine stain for the evaluation of specialized intestinal metaplasia (SIM) and immunohistochemical stain for p53 and Ki-67 were done. RESULTS: 57.9% (55/95) of biopsies from the columnar lined esophagus showed SIM, but no dysplasia. 56.4% (31/55) of Barrett's esophagus showed sulfomucin positive colonic metaplasia. The p53 expression was observed in 10.9% (6/55) of the patients of Barrett's esophagus and all of them showed colonic metaplasia. Ki-67 labeling index showed no difference significantly. CONCLUSIONS: In Korea, 10.9% of Barrett's esophagus had p53 mutation and moreover all of them had colonic metaplasia. Consequently, we expect that these patients have high risk of developing dysplasia and adenocarcinoma and need careful follow-up.

Asunto(s)

Esófago de Barrett/metabolismo , Antígeno Ki-67/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adenocarcinoma/etiología , Adenocarcinoma/genética , Adulto , Anciano , Esófago de Barrett/complicaciones , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/genética , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Factores de Riesgo

RESUMEN

PURPOSE: The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute-on-chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT). PATIENTS AND METHODS: Between January and December 2001, 10 consecutive AoCLF patients (with progressive hyperbilirubinemia (>20 mg/dl) and hepatic encephalopathy grade > or =2) were studied. MARS was used in eight of these patients who were evaluated for LDLT during 2001. Three AoCLF patients who received LDLT before clinical use of MARS were used as historical controls. RESULTS: Because of a shortage of donors, only five out of 10 patients considered for LDLT could receive transplants. Three patients were treated with MARS for 8 h the day before receiving LDLT, and all three survived. The remaining two patients who received transplants, and who were not pretreated with MARS, died from sepsis and multi-organ failure within 2 weeks. Four of the patients who did not receive transplants because of donor shortage died despite 1 or 3 MARS treatments, however bilirubin levels and grade of encephalopathy were significantly reduced in these patients. CONCLUSIONS: Results of this small pilot study suggest that MARS, by reducing the severity of jaundice and encephalopathy, might be effective as a bridging option in AoCLF patients awaiting LDLT.

Asunto(s)

Cirrosis Hepática/terapia , Fallo Hepático/terapia , Trasplante de Hígado/métodos , Hígado Artificial , Diálisis Renal , Desintoxicación por Sorción/métodos , Acondicionamiento Pretrasplante , Adulto , Anciano , Femenino , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/patología , Fallo Hepático/mortalidad , Fallo Hepático/cirugía , Donadores Vivos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Efecto Placebo , Estudios Prospectivos , Resultado del Tratamiento

RESUMEN

Portal vein thrombosis is a rare complication accompanied with acute pancreatitis or cholangitis/cholecystitis. The main pathogenesis of portal vein thrombosis in pancreatitis or cholangitis/cholecystitis are suggested to be venous compression by pseudocyst and an imbalance between the blood coagulation and fibrinolysis. In this case report, we experienced a 63 year old male who developed portal vein thrombosis later in the course of the treatment of acute gallstone pancreatitis with cholangitis/cholecystitis without any symptom or sign. The diagnosis of portal vein thrombosis was given on follow up CT scan and serum protein S activity was decreased to 27% in laboratory study. Immediate anticoagulation therapy with heparin and thrombolytic therapy with urokinase and balloon dilatation were performed. Despite the aggressive treatment, complete reperfusion could not be obtained. With oral warfarin anticoagulation, the patient showed no disease progression and was discharged. We report a case of portal vein thrombosis as a complication of acute pancreatitis and cholangitis/cholecystitis with a review of literatures.

Asunto(s)

Colangitis/complicaciones , Pancreatitis/complicaciones , Vena Porta , Trombosis de la Vena/etiología , Enfermedad Aguda , Colangitis/diagnóstico , Colecistitis/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico , Tomografía Computarizada por Rayos X , Trombosis de la Vena/diagnóstico

RESUMEN

OBJECTIVE: The aim of this study was to evaluate retrospectively the long-term effects of lamivudine in 461 Korean patients with chronic hepatitis B who were treated for more than 12 months. METHODS: The annual rates of virological response and breakthrough were examined and the predictive factors for post-treatment relapse in 114 patients who achieved hepatitis B e antigen (HBeAg) loss or seroconversion after lamivudine therapy were also analyzed. RESULTS: During follow-up, the rates of HBeAg seroconversion after 1, 2, 3, 4 and 5 years of treatment were 22.9, 33.2, 47.6, 54.2 and 58.8%, respectively, while those for virological breakthrough at 1, 2, 3 and 4 years were 8.2, 41.7, 55.7 and 64.8%, respectively. Ninety-five patients (20.6%) had HBeAg seroconversion and 19 (4.1%) showed HBeAg loss alone with disappearance of hepatitis B virus DNA in serum. Seroconversion was higher with prolonged treatment in patients who had elevated serum alanine aminotransferase. The cumulative relapse rates in the seroconversion group were 52.0 and 55.7% 1 and 2 years after treatment, respectively. Age and the duration of additional treatment were significant predictive factors for post-treatment relapse. Patients aged 12 months after seroconversion had the lowest relapse rate (p < 0.001). CONCLUSIONS: These results suggest that additional treatment for over 12 months after HBeAg seroconversion in younger patients may produce a better long-term outcome.

Asunto(s)

Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Factores de Edad , Anciano , Alanina Transaminasa/sangre , ADN Viral/sangre , Femenino , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

BACKGROUND/AIMS: As a preliminary study to test the possibility of oral transmission of hepatitis C virus (HCV), many investigations in order to detect the extrahepatic localization of HCV have been performed. In this study, we examined the presence of HCV viral proteins in gastric mucosa. METHODS: Immunohistochemical staining to NS3 protein were done to detect the HCV virus in gastric mucosa. The results were compared with NS5a protein staining to confirm the NS3 protein staining. RESULTS: Total of 164 patient were included. 58 patients with anti-HCV (+) were designated to case group and 70 with anti-HCV (-) to control group. 36 were excluded in this study due to concomitant illness. Anti-HCV (+) group showed 50.0% (29/58) of positivity to NS3 protein staining and anti-HCV (-) group showed 12.6% (9/70) of positivity (p<0.001). Immunohistochemical staining to NS5a protein were done to validate the result of NS3 (+) staining in the anti-HCV (+) group (n=58). NS5a (+) staining were observed in 58.6% (34/58). The results of NS5a staining were consistent with that of NS3 in 70.7%. The reliability coefficients by Chronbach's Alpha for NS3 and NS5a stain test was 0.59. CONCLUSIONS: HCV can exist in gastric mucosal cell as an extrahepatic presence. In the future, this study may provide some fundamental data for the research of possible oral transmission route of HCV.

Asunto(s)

Mucosa Gástrica/virología , Hepacivirus/aislamiento & purificación , Antígenos de la Hepatitis C/análisis , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. This case of a 65-year-old Korean man with HCC and metastatic frontal bone mass that regressed after radiotherapy for frontal bone mass without any other therapeutic modalities is described. The clinical diagnosis of HCC was made because of the presence of a liver mass on abdominal computed tomography (CT) scan, high serum alpha-fetoprotein value and tissue diagnosis on frontal bone biopsy. The patient refused any other recommended treatments, but accepted the radiation therapy due to a painful frontal bone mass, and ingested mushroom called Phellinus linteus for one and a half years. Ten months after radiation therapy, he experienced a reduction in size of the frontal bone mass and improvement of lesions in the liver, sternum and ribs. The patient is alive and in good condition without any symptoms or tumor aggravation in August 2002. It was concluded that a rare case of spontaneous regression of HCC had occurred.

Asunto(s)

Carcinoma Hepatocelular/secundario , Neoplasias Hepáticas/patología , Regresión Neoplásica Espontánea , Neoplasias Craneales/secundario , Anciano , Biopsia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/radioterapia , Estudios de Seguimiento , Hueso Frontal/patología , Hueso Frontal/efectos de la radiación , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Neoplasias Craneales/patología , Neoplasias Craneales/radioterapia , Factores de Tiempo , Tomografía Computarizada por Rayos X

RESUMEN

BACKGROUND/AIMS: Reactivation of hepatitis B virus (HBV) replication is a well-known complication in cancer patients receiving chemotherapy. The aims of this study were to determine the incidence of HBV reactivation in hepatocellular carcinoma (HCC) patients undergoing transarterial chemo-lipiodolization, and to clarify factors contributing to HBV reactivation. METHODS: From April 2001 to September 2002, 146 HBsAg positive patients newly diagnosed as HCC were enrolled in the study. Among these, 83 patients underwent transarterial chemo-lipiodolization using epirubicin and/or cisplatin, and 63 received other treatments. RESULTS: In total, HBV reactivation occurred in 30 (20.5%) patients (28 with chemo-lipiodolization and 2 with other treatments), and of the 30 patients, 19 (13.0%) (18 with chemo-lipiodolization and 1 with other treatments) developed hepatitis. Chemo-lipiodolization was significantly correlated with a higher incidence of hepatitis attributed to HBV reactivation than other treatments (21.7% vs. 1.6%, P<0.001), irrespective of HBeAg or HBV DNA. Among 83 patients undergoing chemo-lipiodolization, HBV reactivation occurred in 28 (33.7%) patients, and HBeAg seropositivity was the only independent predictor of HBV reactivation (P=0.013). Three (10.7%) of them died of hepatic decompensation resulting from HBV reactivation. CONCLUSIONS: Transarterial chemo-lipiodolization can reactivate HBV, and HBeAg-positive HCC patients receiving chemo-lipiodolization should be closely monitored for HBV reactivation.

Asunto(s)

Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Hepatitis B Crónica/etiología , Neoplasias Hepáticas/terapia , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/complicaciones , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Humanos , Aceite Yodado/administración & dosificación , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Activación Viral/efectos de los fármacos

RESUMEN

Human cervical cancer oncogene (HCCR) was identified and appeared to function as a negative regulator of p53 gene. The objective of this study was to validate HCCR expression as a candidate marker for human hepatocellular carcinoma. HCCR epitope was identified as Y(355)LGTRR(360). According to immunofluorescence study, HCCR was predominantly localized in the plasma membrane and cytoplasm of hepatocellular carcinoma. HCCR proteins were overexpressed in the tumorous compared with the nontumorous cirrhosis tissues. However, HCCR was not detected in normal liver tissue. Concentration of HCCR protein in the serum was measured in a total of 570 subjects, and comparisons were made to alpha-fetoprotein. Serological studies revealed 78.2% sensitivity of HCCR (cutoff value, 15 microg/ml), which was significantly higher than 64.6% of alpha-fetoprotein (P = 0.0098) and 95.7% specificity for hepatocellular carcinoma. Forty of 52 (76.9%) patients with carcinoma negative for alpha-fetoprotein showed positive values for HCCR. A positive rate of 69.2% in carcinoma patients with tumor sizes <2 cm was found to be a higher rate than measurement of alpha-fetoprotein. Furthermore, HCCR expression was also detected in liver cirrhosis at an intermediate level between carcinoma and normal groups, which gave 88.1% sensitivity and 79.0% specificity using 8 microg/ml as a cutoff value. In summary, the HCCR assay may have an advantage over the alpha-fetoprotein assay in that it is elevated according to disease progression from liver cirrhosis to carcinoma, and it is more frequently positive in patients with early, small hepatocellular carcinoma.

Asunto(s)

Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/metabolismo , Proteínas Oncogénicas/metabolismo , Secuencia de Aminoácidos , Animales , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Mapeo Epitopo , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Estadificación de Neoplasias , Proteínas Oncogénicas/inmunología , Biblioteca de Péptidos , Pronóstico , Proteínas Proto-Oncogénicas , Sensibilidad y Especificidad , Fracciones Subcelulares , Neoplasias del Cuello Uterino/metabolismo , alfa-Fetoproteínas/metabolismo

RESUMEN

Although advances in imaging technology have allowed for earlier detection of disease, hepatocellular carcinoma is usually asymptomatic and discovered at an advanced stage with metastasis. The most common sites of metastasis include lung, peritoneum, adrenal gland, and bone, but rarely, the nasal cavity, orbit, gallbladder, and ovary can be metastatic sites. We experienced a case of metastatic hepatocellular carcinoma of the ovary in a living patient. The differential diagnosis includes hepatoid yolk sac tumor of the ovary, primary or metastatic hepatoid carcinoma and primary or metastatic oxyphil cell tumor of the ovary. To the best of our knowledge, there have been eight cases of metastatic hepatocellular carcinoma of the ovary in the English literature and only six cases discovered in living patients. This is the first report of a metastatic hepatocellular carcinoma of the ovary in Korea.

Asunto(s)

Carcinoma Hepatocelular/secundario , Neoplasias Hepáticas/patología , Neoplasias Ováricas/secundario , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Ováricas/diagnóstico

RESUMEN

BACKGROUND/AIMS: The extent of hepatic fibrosis is important in chronic liver disease. Liver biopsy is essential for diagnosis of fibrosis. However, biopsy is invasive and may not represent the whole liver state. Serum hyaluronic acid (HA), a major component of connective tissues, was introduced as a useful non-invasive index of hepatic fibrosis. The aim of this study was to evaluate the relationship among HA, the degree of fibrosis, several hematologic and biochemical parameters in patients with chronic liver diseases or post state liver transplantation (PSLT). METHODS: Total 102 cases were divided into 4 groups: 57 chronic hepatitis (CH), 12 cirrhosis, 21 hepatocellular carcinoma (HCC), 12 PSLT. HA was measured by enzyme-linked binding protein assay and evaluated in relation the degree of fibrosis, several hematologic and biochemical parameters. RESULTS: Among four groups, HCC showed the highest HA and HA of HCC significantly higher than that of CH. The degree of fibrosis were correlated with HA. HA was correlated with age, platelet count and albumin but, not with ALT and PT. There is no significant relation between HA and the presence of acute rejection in liver transplantation. CONCLUSIONS: In chronic liver diseases, HA is a useful non-invasive index of hepatic fibrosis and disease severity.

Asunto(s)

Ácido Hialurónico/sangre , Cirrosis Hepática/diagnóstico , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Carcinoma Hepatocelular/complicaciones , Enfermedad Crónica , Femenino , Rechazo de Injerto/diagnóstico , Hepatitis/complicaciones , Humanos , Hígado/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/complicaciones , Trasplante de Hígado , Masculino , Persona de Mediana Edad

RESUMEN

BACKGROUND/AIMS: Pyruvate kinase (PK) is a key enzyme of glycolysis. Different isoforms of this enzyme are tissue-specifically expressed (M2-PK, M1-PK, R-PK, L-PK). The concentration of the dimeric M2-PK is increased in a metabolic state of tumor cells. In this case, the dimeric M2-PK is termed Tumor M2-PK. We investigated EDTA-plasma of 73 patients with gastrointestinal (GI) cancer and 61 healthy controls to evaluate its significance in diagnosing GI cancer. METHODS: Plasma Tumor M2-PK was measured using an ELISA assay based on two monoclonal antibodies which specifically react with the dimeric Tumor M2-PK. RESULTS: The sensitivity of Tumor M2-PK was 67.1% for all GI cancers, that of CA 19-9 was 38.4% and that of CEA was 34.3%. The specificity of Tumor M2-PK was 91.8% (cutoff=20 U/mL). Tumor M2-PK showed a high sensitivity in gastric cancer (62.2%), colorectal cancer (66.7%) and bile duct cancer (75.0%). In colorectal cancer, the combination of Tumor M2-PK with CEA resulted in a remarkable increase in the sensitivity (86.2%). The average Tumor M2-PK levels were generally elevated in the metastatic GI cancer patients compared to nonmetastatic patients, especially in stomach cancer with statistical significance (p=0.005). CONCLUSIONS: Tumor M2-PK in EDTA-plasma seems to be a new valuable tumor marker in GI cancer.

Asunto(s)

Biomarcadores de Tumor/sangre , Neoplasias del Sistema Digestivo/diagnóstico , Piruvato Quinasa/sangre , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Neoplasias Gastrointestinales/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad

RESUMEN

BACKGROUND/AIMS: The study of liver fibrogenesis by hepatitis C virus (HCV) has been limited due to the lack of an efficiency in vitro culture systems. In the present study, we investigated whether or not HCV core protein is directly related to liver fibrogenesis through stimulation of hepatic stellate cells (HSC). METHODS: Human and rat HSC were isolated and we established an in vitro co-culture system of a stable HepG2-HCV core cell line which was transfected with HCV core gene and primary HSC. We performed immunocytochemical staining and Western and Northern blot analysis in the stimulated HSC by HCV core protein to identify the expression of transforming growth factor beta1 (TGF-beta1), transforming growth factor beta receptor II (TGFbeta R II), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF). The expression of matrix metalloproteinase-2 (MMP-2) and collagen type I (Col I) in the culture media were measured by zymogram and ELISA, respectively. RESULTS: The expression of TGF-beta1 and CTGF was significantly higher in the stable HepG2-HCV core cell line than in HepG2 cells. Furthermore, the makers related to fibrosis such as alpha-SMA, TGF-beta1, Col I, TGFRII and MMP-2 were highly expressed in the co-culture of stable HepG2-HCV core with HSC. CONCLUSIONS: HCV core protein may play a direct role in the fibrogenesis of chronic liver disease with HCV infection.

Asunto(s)

Antígenos de la Hepatitis C/fisiología , Hígado/patología , Proteínas del Núcleo Viral/fisiología , Actinas/metabolismo , Animales , Línea Celular Tumoral , Técnicas de Cocultivo , Factor de Crecimiento del Tejido Conjuntivo , Fibrosis , Humanos , Proteínas Inmediatas-Precoces/metabolismo , Immunoblotting , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Hígado/metabolismo , Proteínas Serina-Treonina Quinasas , Ratas , Ratas Sprague-Dawley , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1

RESUMEN

Budd-Chiari syndrome (BCS) is a disorder caused by occlusion of the hepatic vein or inferior vena cava. The clinical presentation include abdominal pain, hepatomegaly, ascites, leg edema, collateral venous dilatation of the body trunk, and portal hypertension. In addition, BCS can cause hepatocellular carcinoma (HCC) in some patients, although its pathogenesis is not yet completely understood. The average reported time lag from diagnosis of BCS to full-blown HCC ranges from several years to several decades. Hepatic carcinogenesis in patients with BCS perhaps reflects a prolonged and persistent liver injury in that it occurs in the primary inferior vena cava obstruction rather than the primary hepatic vein thrombosis. Among patients with BCS, membranous obstruction of the vena cava (MOVC) usually presents an insidious and chronic illness, whereas primary hepatic vein thrombosis presents an acute or subacute illness. We experienced a case of a patient with BCS, which progressed rapidly that HCC developed only nine months after the diagnosis of BCS. The factors causing this rapid progression are still unclear and remain to be investigated.

Asunto(s)

Síndrome de Budd-Chiari/complicaciones , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/etiología , Hígado/patología , Adulto , Síndrome de Budd-Chiari/diagnóstico por imagen , Síndrome de Budd-Chiari/patología , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos , Hígado/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Tomografía Computarizada por Rayos X

RESUMEN

BACKGROUND: Interindividual genetic differences in susceptibility to chemical carcinogens are among the most important host factors in human cancer. The present study was undertaken to reveal the association between the polymorphism of CYP2E1 (CYP2E1/PstI and CYP2E1/DraI) with genetic susceptibility to gastric cancer development in Koreans. METHODS: In the present study, 120 gastric cancer patients and 145 controls with no history of tumors were analyzed. CYP2E1 was determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP), or PCR and direct gel electrophoresis. RESULTS: The overall genotype distribution of CYP2E1 was not significantly different from that of controls. However, the genotype distribution of the patient subgroups with a history of heavy cigarette smoking (>30 pack/year) in the CYP2E1/PstI and CYP2E1/DraI polymorphisms were significantly different from those of non-smoking patients (P = 0.0122 and P = 0.0029, respectively). The difference was also noticeable in the younger patient subgroup (aged

Asunto(s)

Citocromo P-450 CYP2E1/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Citocromo P-450 CYP2E1/análisis , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Genotipo , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa/métodos , Factores de Riesgo , Neoplasias Gástricas/epidemiología