Lamivudine-Resistance in Patients with Chronic Hepatitis B and/or Cirrhosis and Detection of Mutations in YMDD Motif of Hepatitis B Virus Genome / 대한간학회지

BACKGROUND/AIMS: Lamivudine is an antiviral nucleoside analogue effective for the treatment of hepatitis B virus (HBV) infection via the inhibition of DNA polymerase activity. The mutations, however, in YMDD motif, such as YVDD and YIDD, have been found to interfere with the therapeutic efficacy of lamivudine. This study was performed to identify the role of such mutant-type HBV among Korean hepatitis B patients with chronic hepatitis or cirrhosis receiving lamivudine treatment. METHODS: Serum samples were collected from four groups of patients; patients with breakthrough (group I, n = 8); patients who showed no response after the treatment (group II, n = 6); patients who showed good response (group III, n = 6); patients with chronic hepatitis B without any treatment (group IV, n = 4). Mutations were detected by PCR-cloning and automated sequencing. RESULTS: Mutations in YMDD were found in only 4 (50%) in group I and were negative in group II. No mutations could be identified in the serum samples collected before treatment and from groups III and IV. YVDD mutation was found to be associated with two additional mutations, 'L-to-M' in 528th amino acid and 'L-to-V' in 577th amino acid. CONCLUSIONS: Lamivudine resistance appeared in three different patterns: (1) breakthrough related to the mutations in YMDD motif; (2) breakthrough not related to the YMDD mutations; and (3) primary non-responder not related to the YMDD mutations.

Liver Abscess Formation in Non-Tumorous Parenchyma after Transcatheter Arterial Chemoembolization (TACE) for the Treatment of Hepatocellular Carcinoma Associated with Pneumobilia / 대한간학회지

Transcatheter arterial chemoembolization (TACE) is widely used to treat inoperable hepatocellular carcinoma and metastatic tumor of the liver. Among the complications occurring after TACE, liver abscess formation in HCC is a fatal complication. The reported incidence of this complication ranges from 0% to 3.3%. Moreover, liver abscess formation in non-tumorous parenchyma is very rare. The pathogenic mechanism of this complication has been linked to several factors but retrograde enteric bacterial contamination of the biliary tract appears to be the most commonly implicated cause. The major risk factors of the biliary tract infection are pneumobilia, portal vein thrombosis, bilo-enteric anastomosis and biliary obstruction. We report a rare case of liver abscess formation in non-tumorous liver parenchyma after TACE for the treatment of hepatocellular carcinoma in a patient with pneumobilia.

Mutations of hepatitis C virus 1b NS5A 2209-2248 amino acid sequence is not a edictive factor for response to interferon-alpha therapy and development of patocellular carcinoma

Genetic changes between codons 2209 and 2248 of NS5A of genotype 1b hepatitis C virus (HCV-1b) have been reported to be associated with the sensitivity to interferon-alpha (IFN-alpha). The present study was performed to analyze such relationship in Korean patients with chronic hepatitis C and HCV-1b (n=19), including 12 chronic hepatitis C patients treated with IFN-alpha, 3 chronic hepatitis C patients without treatment as controls, and 4 patients with hepatocellular carcinoma (HCC). Two serum samples, before and after the treatment, were analyzed for the mutations by reverse transcription-polymerase chain reaction, cloning and sequencing. The mutations were identified in 32% (6/19), including five intermediate type (1-3 mutations) and one mutant type (4 or more). In 12 patients treated with IFN-alpha, the number of amino acid substitutions in NS5A2209-2248 was not associated with outcome of the treatment.

A Case of Pulmonary Embolism Induced by Complication of Histoacryl Injection Therapy in Gastric Varix Bleeding / 대한소화기내시경학회지

N-Butyl-2-cyanoacrylate (Histoacryl) has been used successfully to control bleeding from esophagogastric varices since the first report in 1986 by Soehendra. Complications of Histoacryl injection include local sloughing with ulcer formation, rebleeding, sepsis, mediastinitis, esophageal strictures and fever. Systemic embolization, including pulmonary and cerebral embolization, has been reported. We describe here the presentation of an un-usual complication of Histoacryl injection. A 42-year-old woman presented with an attack of massive hematemesis. Endoscopy revealed bleeding evidence of gastric varices. Sclero-therapy was carried out using Histoacryl mixed with Lipiodol (ratio 1 : 1), with complete solidification of the varix. Next morning she complained of dyspnea and tachycardia. The chest x-ray showed multiple metallic densities, consistent with cyanoacrylate mixed with lipoidol, located at central portion. She was diagnosed as having pulmonary embolism by convential precontrast chest CT. She was treated conservatively using oxygen and analge-sics. She recovered soon and was discharged without significant problems.

Two cases of common bile duct stone after liver transplantation

Biliary complications after orthotopic liver transplants are a continuing cause of morbidity and mortality. Biliary stones and sludge are less well known complications of hepatic transplantation, although they have long been recognized. Recently we experienced two cases of biliary stones developed after liver transplantation. One 32-year-old male, who frequently admitted due to recurrent cholangitis, was treated with percutaneous transhepatic biliary drainage and choledochojejunostomy with cholecystectomy. The other 58-year-old male, who had stones in commone bile duct, was treated by endoscopic manipulation. They are in good condition without recurrent bile duct stones or its accompanying complications. Although stones and sludge are relatively infrequent after liver transplantation, surgical or interventional radiologic treatments are usually performed for treatment.

Monitoring antibody titers to recombinant Core-NS3 fusion polypeptide is useful for evaluating hepatitis C virus infection and responses to interferon-alpha therapy

To evaluate the clinical feasibility of the antibody titer against a chimeric polypeptide (named Core 518), in which a domain of Core and NS3 of hepatitis C virus (HCV) was fused, ELISA was performed in a total of 76 serum samples. Each serum was serially diluted using two-fold dilution method with distilled water into 10 concentrations. They were all positive for second generation anti-HCV assay (HCV EIA II; Abbott Laboratories). Genotyping RT-PCR, quantitative competitive RT-PCR, and RIBA (Lucky Confirm; LG Biotech) were also assayed. Anti-Core 518 antibody was detected in x 12800 or higher dilutions of sera from 35 of 43 chronic hepatitis C (81.4%) and nine of 16 hepatocellular carcinoma sera (56.3%), one of four cirrhosis (25%), 0 of four acute hepatitis C, and one of nine healthy isolated anti-HCV-positive subjects (p=0.0000). The anti-Core 518 antibody titers were well correlated with the presence of HCV RNA in serum (p=0.002). The anti-Core 518 antibody titers decreased significantly in nine of ten responders to IFN-alpha treatment. Monitoring anti-Core 518 titers may be helpful not only for differentiating the status of HCV infection among patients with various type C viral liver diseases, but also for predicting responses to IFN-alpha treatment.

The Incidence and Clinical Significance of GB Virus C/hepatitis G Virus Infection in Hemodialysis Patients / 대한신장학회잡지

The incidence and clinical significance of GB virus C/hepatitis G virus(GBV-C/HGV) infection were evaluated in 68 patients on maintenance hemodialysis. GBV-C/HGV RNA was identified in serum by a reverse transcription-polymerase chain reaction assay with nested primers deduced from a nonstructural region. Hepatitis B surface antigen(by RIA) and anti-hepatitis C(by ELISA) were checked simultaneously. Out of 68 patients, GBV-C/HGV RNA was detected in 5(7.4%), HBsAg in 4 patients(5.9%) and anti-HCV in 15 patients(22%). All 5 patients with positive GBV-C/HGV RNA had a history of blood transfusion. Out of 5 patients with positive GBV-C/HGV RNA, 2 patients were coinfected with hepatitis C virus, who showed chronic hepatitis clinically. Three patients with isolated GBV-C/HGV infection showed normal liver function during last 18 months' period. Between the patients with positive GBV-C/HGV RNA and those with negative GBV- C/HGV RNA, there was no difference in age, sex, duration of hemodialysis and amount of transfusion. Our data suggest that GBV-C/HGV infection may be present, with or without hepatitis C virus infection, in maintenance hemodialysis patients. Although the liver function of patients with isolated GBV-C/ HGV infection was normal, the clinical significance of this new virus remains to be determined.

Telomerase is strongly activated in hepatocellular carcinoma but not in chronic hepatitis and cirrhosis

Telomerase is highly activated in human immortal cell lines and tumor tissues, whereas it is not activated in primary cell strains and many tumor-adjacent tissues. It is suggested that telomerase activation is one of the critical steps in malignant transformation. In the present study, the telomerase activity was investigated in hepatocellular carcinoma tissues and non-tumor liver tissues from Korean patients with chronic hepatitis and cirrhosis. Eighty two liver tissues (24 chronic hepatitis specimens, 34 cirrhosis specimens, and 24 hepatocellular carcinomas) were obtained from 23 chronic viral hepatitis patients, 19 cirrhosis patients (including 7 liver transplants), and 24 patients with hepatocellular carcinoma, of which the surrounding non-tumor liver tissues were available in 16 patients (1 chronic hepatitis and 15 cirrhosis). As negative controls, 3 normal liver tissues were included. Protein from liver specimens was purified by a detergent lysis method as described elsewhere, and telomerase activity was measured in 2 diluents of each sample (1:1 and 1:100) by a telomeric repeat amplification protocol (TRAP). Telomerase was strongly activated in 79% (19/24) of the hepatocellular carcinomas, while weakly in 8% (2/24) of the chronic hepatitis tissues and in 24% (8/34) of the cirrhosis tissues. All of 3 normal control livers showed no telomerase activation. No relationship could be observed between the enhancement of telomerase activity and tumor nature. None of the chronic heaptitis or cirrhosis patients with mild telomerase activation in the liver have developed hepatocellular carcinoma for at least 2 years of follow-up period. These results suggest that the strong enhancement of telomerase activity may be a critical part of hepatocarcinogenesis, although the exact mechanism of such high activation in hepatocellular carcinoma is not clear. In addition, further study will be necessary to clarify the reason why no telomerase activity detectable by a conventional TRAP can be seen in some hepatocellular carcinoma.

Overestimation of the Depth of Invasion in Early Gastric Cancer due to Eosinophilic Abscess by Endoscopic Ultrasonography / 대한소화기내시경학회지

Eosinophilic abscess is a rare disease of stomach that consists of many eosinophils in submucosa and muscle layers of stomach. Eosinophilic abscess is usually observed in liver after parasite infestation such as hepatic fascioliasis or in intradermal lesion of pemphigus. A 67-year-old female was admitted due to epigastric pain and indigestion. Endoscopic finding suggested early gastric cancer type IIc with the depth of invasion to mucosal layer at the lesser curvature of lower body. Histologic examination of endoscopic biopsy proved to be signet ring cell type adenocarcinoma. On endoscopic ultrasonography, the tumor was imaged as a slightly elevated mass with 15 mm in diameter. The lesion was localized from the first layer to the fourth layer which correspond to the mucosa and the proper muscle layer, The lesion consisted of low echoic and isoechoic densities. The lower echoic lesion ranging from the third layer to the fourth layer was thought to be necrotic or hemorrhagic portion within the tumor. Subtotal gasterectomy was performed. We compared the endoscopic and endosonographic features with the histologic findings of the resected stomach. Histologic examination showed signet ring cell carcinoma in mucosal layer and eosinophilic abscess in submucosal and proper muscle layer. We concluded that the endosonographic depth of invasion was overestimated because of the eosinophilic abscess.