Showing papers by "Kwang Hyub Han published in 2005"

Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma.

Abstract: Purpose: In order to determine the effect of additional radiotherapy (RT) after an incomplete transcatheter arterial chemoembolization (TACE) in an unresectable hepatocellular carcinoma (HCC), the treatment results of patients receiving TACE plus RT were analyzed and compared with those treated with TACE alone. Materials and methods: One hundred and five patients with an unresectable HCC were treated with TACE from January 1992 to December 2002. In 73 of these patients, the TACE was incomplete. Among them, TACE was repeatedly performed in 35 patients (TACE group), and the remaining 38 patients were also treated with local RT (TACERT group). The patients were either in stage III or IVa, Eastern Cooperative Oncology Group 2 or less, and Child–Pugh class A or B. The average frequency of TACE prior to RT was 2 and the RT was started within 7–10 days after the TACE. Results: The 2-year survival rate was significantly higher in the TACERT than in the TACE group (36.8 % vs. 14.3%, P=0.001). According to the tumor size, the 2-year survival rates in the TACERT and TACE groups were 63% vs. 42% in 5–7 cm (P=0.22), 50% vs. 0% in 8–10 cm (P=0.03), and 17% vs. 0% in larger than 10 cm (P=0.0002) respectively. Conclusion: There was a significantly improved survival rate in the TACERT group of unresectable HCC patients than in the TACE group, particularly in case of tumors ≥8 cm in diameter. Therefore, RT in addition to TACE is strongly recommended for patients with an unresectable HCC.

Comparison of Rifaximin and Lactulose for the Treatment of Hepatic Encephalopathy: A Prospective Randomized Study

Abstract: Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p = 0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0 --> 4.2, p = 0.000); lactulose group (11.3 --> 5.0, p = 0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

Different Glucose Uptake and Glycolytic Mechanisms Between Hepatocellular Carcinoma and Intrahepatic Mass-Forming Cholangiocarcinoma with Increased 18F-FDG Uptake

Abstract: 18F-FDG uptake in malignant tumors largely depends on the presence of facilitated glucose transporters, especially type 1 (Glut 1) and a rate-limiting glycolytic enzyme, hexokinase (HK) type II. Low expression of Glut 1 was reported in hepatocellular carcinoma (HCC), whereas high expression was found in cholangiocarcinoma. Immunohistochemistry and proteome analysis were performed to obtain a detailed evaluation of the mechanisms involved in glucose uptake and use in these tumors. Methods: Tumor tissues obtained from both HCC (n = 7) and mass-forming cholangiocarcinoma patients (n = 7) who showed increased 18F-FDG uptake on PET were used. Immunohistochemistry for Glut 1 and HK I–III was performed in all tumor tissues. To identify proteins that regulate carbohydrate metabolism, a proteome analysis with matrix-assisted laser desorption ionization–time of flight and enzymatic digestion in-gel were performed using 8 available tumor samples and 3 normal liver tissues. Of the 8 tumor samples, 4 were HCCs; one was an intermediate phenotype HCC, and 3 were cholangiocarcinomas. The spot intensity of the proteins was calculated using proteome data; the tissues then were divided into 2 groups on the basis of the protein expression pattern, because the protein expression pattern of the intermediate-phenotype HCC was close to that of the cholangiocarcinomas. Group A included the HCCs and group B included the intermediate-phenotype HCC as well as the cholangiocarcinomas. Results: Immunoreactivity for Glut 1 was positive in all cholangiocarcinomas, but was negative in all HCCs except the one intermediate phenotype. However, HK II was positive in HCCs but was negative in 6 of the 7 cholangiocarcinomas. A total of 331 protein spots with a P value of

Evaluation of methods for monitoring drug resistance in chronic hepatitis B patients during lamivudine therapy based on mass spectrometry and reverse hybridization.

Abstract: A matrix-assisted laser desorption/ionization time-offlight mass spectrometry-based genotyping assay, termed restriction fragment mass polymorphism (RFMP) has been recently developed for detecting hepatitis B virus (HBV) mutants. The assay is based on PCR amplification and mass measurement of oligonucleotides containing sites of mutations that confer resistance to lamivudine. We compared the efficacy and usefulness of the RFMP assay with a commercial assay using a reverse hybridization line probe technology, namely INNO-LiPA HBV DR (referred to henceforth as the LiPA assay), for the detection of lamivudine-resistant HBV mutants. A total of 60 patient samples were analysed for the presence of mutations at rtL180M and rtM204I/V of HBV polymerase by the LiPA and RFMP assays. The ability to detect mutations at rtM204I/V was compared with defined mixtures of wild-type and mutant HBV cloned in plasmids at relative concentrations ranging from 1‐25%. Concordance between methods was found to be 95.0% (57/60) when only the presence of resistance mutations was considered, regardless of quasispecies. In three cases, additional minor populations of resistant viruses were identified by RFMP. Defined mixtures were consistently successfully identified at a 1% relative concentration of mutant versus wild-type viruses by the RFMP assay and 4% by the LiPA assay. The RFMP assay proved to be an accurate and reliable tool for detection of lamivudine-resistant mutations and was more sensitive than the LiPA assay in detecting mixtures of mutant and wild-type viruses. The improved sensitivity of the RPMP assay can help monitor drug resistance as it develops, enabling early intervention and prevention.

How to predict HCC development in patients with chronic B viral liver disease

Abstract: Hepatocellular carcinoma (HCC) is one of the major malignant diseases in Asia. Although no randomized controlled studies have demonstrated decreased mortalities, screening for HCC has become an accepted procedure in the high-risk population. Since the incidence of HCC is strikingly different according to geographical distribution of risk factors, especially chronic hepatitis B virus (HBV) infection, a surveillance strategy in high endemic areas should be established according to national conditions. Chronic necro-inflammation by persistent HBV infection per se can progress to cirrhosis and the occurrence of HCC. As in other chronic liver diseases, the more risk factors the chronic B viral patients have, the higher occurrence of HCC was shown. Based on the risk factors of 4,339 Korean patients, the individual prediction model (IPM) was made by the calculation of relative weighs of risk factors and a self-exploited screening program for HCC was established accordingly. US screening at 6-month intervals was beneficial for the early detection of HCC, especially in the high-risk group, and prolonged survival. The usefulness of a tailored screening program with IPM for HCC was prospectively confirmed. The effective screening system for diagnosis of HCC limited to patients with chronic hepatitis B might be necessitated in high endemic area.

Usefulness of urine strip test in the rapid diagnosis of spontaneous bacterial peritonitis.

Abstract: Purpose: Rapid and accurate diagnosis of spontaneous bacterial peritonitis (SBP) is mandatory for timely treatment in cirrhotic patients. The purpose of this study was to assess the usefulness of two different reagent strips, the UriSCAN and the Multistix10SG, for the rapid bedside diagnosis of SBP. Methods: A total of 75 paracenteses in 53 cirrhotic patients with ascites were performed. All ascitic fluid was analyzed with the two reagent strips, and compared with the manual cell count with differential and ascitic fluid culture. SBP was defined as an ascitic polymorphonuclear cell count ≥250/mm3. Results: SBP was diagnosed in 18 of the 75 samples. If we considered the positive UriSCAN result of 2 or more, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. When we considered the positive UriSCAN result of 3, the sensitivity, specificity, PPV, and NPV were 67%, 100%, 100%, and 89%, respectively. When we considered the positive Multistix10SG result of 3, the sensitivity, specificity, PPV, and NPV were 50%, 100%, 100%, and 87%, respectively. Conclusion: Urine reagent strip might be useful for rapid and accurate diagnosis of SBP in cirrhotic patients with ascites.

Long‐term clinical outcome of large volume paracentesis with intravenous albumin in patients with spontaneous bacterial peritonitis: A randomized prospective study

Abstract: Background and Aim: Large volume paracentesis (LVP) with plasma volume expansion has been used for tense or refractory ascites. However, still in question is whether it is safe and effective for the treatment of spontaneous bacterial peritonitis (SBP). We addressed this issue and conducted a study to assess safety and long-term outcome of LVP in cirrhotic patients with SBP. Methods: Forty-two randomly assigned cirrhotic patients with SBP were classified into two groups; Group 1 included 21 patients who were treated with LVP and intravenous albumin; and Group 2 included 21 patients who were treated with diuretics and intravenous albumin. Results: The overall cumulative survival rate was poor in patients with SBP (42.5% and 22.5% at 6 and 12 months, respectively). At 7 days after treatment, the blood tests were similar between the two groups. In the ascitic fluid, the white blood cell counts decreased significantly and the protein concentrations tended to increase in both groups. In-hospital days, resolution rate of SBP, and in-hospital mortality rate were similar between the two groups. Although complication rates tended to be slightly higher in Group 1, long-term cumulative survivals were similar between Group 1 and Group 2. LVP was effective in removing abdominal discomfort in patients with tense ascites without serious complication. Conclusions: LVP with intravenous albumin was as effective as diuretics with intravenous albumin for the treatment of SBP with similar mortality. LVP with intravenous albumin might be feasible for the treatment of tense or refractory ascites in cirrhotic patients with SBP.

Association between CCR5 promoter polymorphisms and hepatitis B virus infection

Abstract: BACKGROUND/AIMS Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. CCR5 promoter polymorphisms are known to be associated with HIV infection. However, there has been no report on the association between CCR5 promoter polymorphism and HBV infection. Therefore, we investigated the relationship between the CCR5 promoter polymorphism and HBV infection. METHODS A total of 377 patients were classified into two groups according to their HBV infection status: (1) the spontaneous clearance group (SC); HBsAg (-), anti-HBc (+), anti-HBs (+) (2) the chronic HBsAg (+) carrier group (CC); HBsAg (+), anti-HBc (+), anti-HBs (-). CCR5 polymorphisms were detected by employing matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)- based SNP scoring assay, termed Restriction Fragment Mass Polymorphism (RFMP), which exploits the differences in molecular masses between the common allele and rare allele bases of interest. RESULTS We found that the genotype frequencies of CCR5 A59029G significantly differed between the SC group (n=138) and CC group (n=239) (P<0.05). The CCR5 59029A allelic genotype was associated with an increased risks of chronic infection rather than spontaneous clearance (P=0.002), and the presence of the CCR5 59029G allele was significantly associated with the spontaneous clearance of HBV (P=0.001). Strong linkage disequilibrium between the CCR5-59029 and the CCR5-59353 polymorphic variants was identified. None of the 377 subjects had the CCR5-32 bp deletion mutation. CONCLUSIONS The CCR5 promoter polymorphisms at position 59029 might play a role in the clearance of HBV infection. This primary experimental evidence needs further studies to clarify the clinical usefulness of CCR5 promoter polymorphisms as a target for the screening or treatment of HBV infection.

Risk factors of acute hepatic failure associated with transcatheter arterial chemoembolization for hepatocellular carcinoma

Abstract: Background : Transcatheter Arterial Chemoembolization (TACE) has been the most widely used treatment for advanced hepatocellular carcinoma (HCC) in Korea. However a number of complications associated with TACE have been reported in many studies. Acute hepatic failure is one of the most serious complications of TACE, because of its grave prognosis. The aim of this study was to investigate the risk factors associated with acute hepatic failure after TACE. Methods : A total of 263 TACE procedures performed in 163 patients with HCC were included in this study. We reviewed retrospectively the complications that occurred after TACE and analysed the risk factors associated with acute hepatic failure after TACE. Results : Complications included post-embolization syndrome (187 cases), temporary hepatic insufficiency (90 cases), acute hepatic failure (13 cases), hepatic arterial injury (9 cases), intrahepatic biloma (4 cases), liver infarction (2 cases), liver abscess (2 cases), tumor rupture (1 cases), gastrointestinal bleeding (14 cases), septicemia (3 cases), gall bladder infarction (2 cases), thrombocytopenia (2 cases), gastric perforation (1 cases), pneumonia (1 cases), urticaria (1 cases), sensorineural hearing loss (1 cases), femoral artery aneurysm (1 cases). According to univariate analysis, risk factors associated with acute hapatic failure after TACE were serum bilirubin and albumin, prothrombin time, dose of adriamycin, pre-TACE Child-Pugh class, tumor size, diffuse tumor type, portal vein thrombosis and TNM stage. Multivariate analysis revealed that serum bilirubin {odd ratio=3.86 (95% CI: 1.59-9.32)}, and diffuse tumor type {odd ratio=5.29 (95% CI: 1.46-23.86)} were statistically significant risk factors. Conclusions : It is recommended that above mentioned risk factors should be considered carefully before TACE to prevent the occurrence of acute hepatic failure after TACE in HCC patients.

Efficacy of repeated hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma with portal vein tumor thrombosis

Abstract: BACKGROUND/AIMS The aim of this study is to elucidate the efficacy of repeated hepatic arterial infusion chemotherapy (HAIC) and different chemotherapeutic regimens for treating patients having advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS From Jan. 1999 and Dec. 2003, a total of 103 patients diagnosed as having HCC with PVTT, but without extrahepatic spreading, were enrolled in this study. They were stratified into two groups. Group I (67 patients) received intraarterial cisplatin (CDDP, 80 mg/m2 for 2 hours on Day 1), Group II (36 patients) received intraarterial CDDP (60 mg/m2 for 2 hours on Day 2) and 5-fluorouracil (5-FU, 500 mg/m2 for 5 hours on Day 1-3). They were scheduled to receive at least three consecutive courses of the HAIC at 1 month intervals. RESULTS Among the 66 patients who completed the protocol, one (2.5%) and seven (17.5%) patients of group I, and one (3.8%) and four (15.4%) of group II, exhibited complete and partial responses, respectively. The median survival period of all the patients was 6 months. Group II showed a tendency to improve the median survival compared to group I (8.5 vs 5.0 months, respectively, P=0.45). The most common adverse reaction was nausea (58.2%). However, an elevation of the total bilirubin level was more frequent in Group I than in Group II (61.3% vs 20.7%, respectively, P<0.05). CONCLUSIONS Repeated HAIC using CDDP achieved favorable results in a few patients with HCC with PVTT, and additional 5-FU may be useful.

Clinical outcome of pulmonary resections in patients with pulmonary metastasis of hepatocellular carcinoma

Abstract: Background/aims Although the lung is the most common site of extrahepatic spread from hepatocellular carcinoma (HCC), the role of surgery for pulmonary metastasis remains unclear. The aim of this study was to evaluate the efficacy of pulmonary resection in patients with pulmonary metastasis from HCC. Methods Between July 2000 and July 2004, a total of 6 patients with pulmonary metastasis from HCC underwent curative pulmonary resections. The patients were divided into two groups (Surgery group and Non-surgery group) according to the primary treatment modality of HCC. Medical records, imaging studies, and pathologic reports of the surgical specimens were reviewed. Results Three patients in the surgery group underwent pulmonary resections for a solitary metastasis after hepatectomy for HCC, and they are all still alive. One of the 3 patients developed a tumor recurrence in the chest wall after pulmonary resection. The survival time after diagnosis of HCC were 79, 122, and 54 months, respectively. The survival time after pulmonary metastatectomy were 49, 39, and 20 months in the three patients. Another 3 patients in the non-surgery group, received a pulmonary metastatectomy; they had either a complete response HCC or partial radiologic response. These 3 patients developed recurrent disease in the liver. One of 3 patients died. The survival time after diagnosis of HCC were 153, 83, 12 months. The survival time after pulmonary metastatectomy were 51, 4, 2 months. Conclusions The surgical resections of a solitary pulmonary metastasis from HCC in highly selected patients might be an effective treatment modalities for prolonged survival.

[HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy].

Abstract: BACKGROUND/AIMS Viral suppression of the hepatitis B virus (HBV) can be induced by lamivudine, but the relapse seen in many patients after cessation of lamivudine therapy is troublesome. We thought that the host immune response is important to prevent viral relapse. We compared the frequency of HBV-specific CD8+ T cells in the peripheral blood and their expansion capacity after exposure to viral antigen between the patients showing sustained HBeAg seroconversion after use of lamivudine and those patients without sustained response. METHODS We analyzed HBV-specific CD8+ T cells that were isolated from the blood of 14 patients with HLA-A2 who showed lamivudine induced HBeAg seroconversion (HBV DNA < 0.5 pg/mL, and the cells were negative for HBeAg) at the end of lamivudine therapy. The purified T cells were directly stained ex vivo, after they had been stimulate with synthetic peptide, using the HBV core 18-27-specific HLA tetramer (Tc 18-27) and monoclonal antibody to CD8. The HBV viral load was quantified by the Amplicor HBV Monitor assay. RESULTS In patients with a sustained HBeAg response (the sustained group) for a duration of 15.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 49.5 (15-135). On the contrary, in patients who experienced relapse (the relapsed group) during a median of 7.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 13.5 (0-95). Especially, among patients with a viral load of HBV DNA < 1 X 10(3) copies at the end of treatment, the median number of Tc 18-27 cells out of 5 X 10(4) CD8+ T cells was 87 (45-135) in sustained group compared to 12 (6-50) in the relapsed group. All patients in the sustained group demonstrated a vigorous expansion of the core 18-27-specific CD8+ T cells after stimulation with viral peptide, in contrast to only 3 out of 8 patients in the relapsed group. CONCLUSIONS This study demonstrates that the frequency and functional responsiveness of the circulating HBV-specific CD8+ T cells may be important for obtaining a sustained HBeAg response to lamivudine.

Usefulness of PIVKA-II for diagnosis and evaluation of recurrence of hepatocellular carcinoma

Abstract: Background : Although alpha-fetoprotein (AFP) is most widely used tumor marker for hepatocellular carcinoma (HCC), the sensitivity is about 60˜0% in advanced HCC. Furthermore, the specificity of AFP is relatively low. The aim of this study was to evaluate the usefulness of prothrombin-induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HCC, and of recurrence after curative surgical resection. Methods : Between April 2001 and March 2004, a total of 245 patients with pathologically confirmed HCC and a total of 267 patients with non-HCC, chronic liver diseases were enrolled. Results : With cutoff-value 20 ng/mL for AFP and 40 mAU/mL for PIVKA-II, the sensitivity of AFP and PIVKA-II was 48.6% (119/245) and 75.1% (184/245), respectively. The specificity of them was 81.3% (217/267) and 94.8% (253/267), respectively. When AFP and PIVKA-II were combined, the sensitivity and specificity was 83.3% (204/245) and 77.2% (206/267), respectively. For HCC 3cm, the sensitivity of AFP, PIVKA-II and AFP+PIVKA-II was 42.5% (31/73), 50.7% (37/73), and 68.5% (50/73), respectively. Among the 42 patients with AFP less than 20 ng/mL, whose tumor size was equal to or less than 3 cm, PIVKA-II showed positivity in 19 patients (45.2%). Recurrent HCC developed after curative surgical resection in 27 patients, and the sensitivity of PIVKA-II was 74.1% (20/27). On the contrary, the sensitivity of AFP was 40.7% (16/27). Conclusion : PIVKA-II is a useful tumor marker for HCC, especially in small sized tumor and HCC without AFP elevation. Furthermore, serial measurement of PIVKA-II after surgical resection might be an early indicator for tumor recurrence.