Joon Yeol Han

Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation -- a pilot study.

Abstract: 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).

Association between human leukocytes antigen alleles and chronic hepatitis C virus infection in the Korean population.

Abstract: 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.

Clevudine therapy for 24 weeks further reduced serum hepatitis B virus DNA levels and increased ALT normalization rates without emergence of viral breakthrough than 12 weeks of clevudine therapy

Objectives: The objectives of the study were to evaluate the safety and antiviral activity of 24-week treatment with clevudine 30 mg in HBeAg(+) chronic hepatitis B patients. Biochemical and serological responses were also assessed. Method: Twenty-one patients received clevudine 30 mg for 24 weeks and were followed up for another 24 weeks off therapy. Results: Median decreases from baseline in HBV DNA were 4.65 and 1.96 log10 copies/ml at week 24 (end of treatment) and week 48 (24 weeks off therapy), respectively. Analysis of individual data showed that HBV DNA levels were below the lower limit of detection (300 copies/ml) by Amplicor PCR assay in 19, 57, 19 and 0% at week 12, 24, 34 and 48, respectively. The proportion of patients with normal ALT were 67, 81 and 75% at week 24 (end of treatment), 34 and 48 (24 weeks off therapy), respectively. The rates of HBeAg loss were 24 and 20% at week 24 and 48, respectively. No viral breakthrough during treatment was observed. Conclusion: Clevudine 30 mg treatment for 24 weeks was well tolerated and exhibited more potent antiviral activity and a higher ALT normalization rate than 12-week treatment with durable efficacy at week 24 off therapy.

Clinical Outcomes of Delayed Clearance of Serum HBsAg in Patients with Chronic HBV Infection

Background Spontaneous delayed clearance of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection is a rare event. The aim of this study was to investigate the incidence of delayed clearance of serum HBsAg in chronic HBV infection and to determine the characteristics and clinical outcomes of HBsAg delayed clearance in Korean patients. Methods From April 1981 to June 2003, 4,061 patients who were positive for HBsAg were evaluated retrospectively. The following assessments were undertaken in 47 patients who had spontaneous delayed clearance: liver biochemistry, viral markers, α-fetoprotein levels, and radiographic examinations including ultrasonography every three to six months for 6-264 months (median 87.9 months). Results Twenty-four of 47 patients were asymptomatic carriers. The others included seven patients with chronic hepatitis, seven with liver cirrhosis and nine with hepatocellular carcinoma. The estimated annual incidence of HBsAg seroclearance was 0.4%. The time span from positive HBsAg to HBsAg seroclearance in the AHC, CH, LC, and HCC was 62.9, 141, 63, and 95.3 months during follow up. Twenty-four of 24 AHC remained normal, 5 of 7 CH remained as CH and 2 patients remained normal, 1 of 7 with LC developed HCC and 6 of the LC remained as LC, and 4 of 9 HCC patients died. Conclusion The clinical course following delayed clearance of HBsAg had diverse outcomes from AHC to HCC. Therefore, these patients require close follow up for the possible development of hepatocellular carcinoma following HBsAg clearance.

Pharmacokinetics of oltipraz and its major metabolite (RM) in patients with liver fibrosis or cirrhosis: Relationship with suppression of circulating TGF-Β1

Oltipraz is a potential candidate drug for the treatment of liver fibrosis (LF) and liver cirrhosis (LC). The pharmacokinetics of oltipraz and its major rearranged metabolite (7‐methyl‐6,8‐bis(methylthio)H‐pyrrolo[1,2‐a]pyrazine (RM)) were evaluated after single‐dose (30−90 mg) and multiple‐dose (60 mg b.i.d. or 90 mg q.d. for 24 weeks) oral administration of oltipraz to patients with LF or LC. Oltipraz was safe and well tolerated in both studies. In the single‐dose study, the area under the plasma concentration–time curve (AUC), peak plasma concentration (Cmax), and terminal half‐life (t1/2) of oltipraz as well as the AUC of its RM were dose dependent. Oltipraz was rapidly absorbed; the time to reach Cmax (Tmax) was 2–4 h. The conversion of oltipraz to RM was also rapid and substantial (AUC of RM from time 0 to the last measured concentration (AUClast, RM)/AUClast, oltipraz, 42−61%). In the multiple‐dose study, the level of transforming growth factor‐β1 (TGF‐β1) (a blood fibrosis marker) was suppressed at steady‐state plasma concentrations of _20−60 ng/ml of oltipraz or of _60−140 ng/ml of oltipraz plus RM. Overall, the pharmacokinetics, safety, and efficacy of oltipraz suggest that it may be helpful in the treatment of patients with LF or LC, at an optimal dosing regimen.

Oltipraz therapy in patients with liver fibrosis or cirrhosis: a randomized, double-blind, placebo-controlled phase II trial

Objectives  Oltipraz, a cancer chemopreventive agent, has an anticirrhotic effect in animals. A phase II trial was designed to investigate the preliminary efficacy of oltipraz therapy in liver fibrosis or cirrhosis.

Adult Living Donor Liver Transplantation Using Hepatitis B Core Antibody-Positive Grafts in Korea, a Hepatitis B-endemic Region

Background/Aims The exclusion of hepatitis B core antibody (HBcAb)-positive donors from liver transplants (LTs) due to the risk of transmitting hepatitis B virus (HBV) does not appear to be practical in Korea, where hepatitis B is endemic. This study assessed the risk of de novo HBV infection in hepatitis B surface antigen (HBsAg)-negative LT recipients receiving a liver from HBcAb-positive donors. Methods Of 341 adult living donor LTs conducted at our institution between March 2001 and September 2008, 176 donors (51.6%) were HBcAb-positive, and 26 HBcAb-positive grafts were transplanted to HBsAg-negative recipients. The median follow-up time after LT was 41.9 months. Results Without anti-HBV prophylaxis, 2 out of 26 (7.7%) HBsAg-negative recipients who received grafts from HBcAb-positive donors developed de novo HBV infection 20 and 85 months after LT. These patients had been negative for all HBV serologic markers before transplantation. In both cases, there were no abnormalities in liver function tests upon diagnosis of de novo HBV infection. Conclusions De novo HBV infection from HBcAb-positive donors after LT does not appear to be of great concern in terms of the number of cases in Korea because high risk patients who are HBV-negative comprise only a small proportion of the recipients. However, HBV-naïve LT recipients still carry the risk of developing de novo HBV infection as in non-HBV endemic areas.

Congenital Hemidiaphragmatic Agenesis Presenting as Reversible Mesenteroaxial Gastric Volvulus and Diaphragmatic Hernia: A Case Report

A 70-yr-old woman complained of left sided chest pain and non-bilious vomiting for four days after taking a gastric bloating agent for an upper gastrointestinal study. The chest radiography revealed gastric air-fluid levels and bowel loops in the left thoracic cavity. An emergency thoracotomy was performed. The abdominal organs (stomach, spleen, splenic flexure of the colon) were in the left thorax and the entire left hemidiaphragm was absent. There were no diaphragmatic remnants visible for reconstruction of the left diaphragm. We provided warm saline irrigation and performed a left lower lobe adhesiotomy. Thirteen days after surgery, the chest radiography showed improvement in the herniation but mild haziness remained at the left lower lung field. Here we present the oldest case of congenital diaphragmatic agenesis presenting with transient gastric volvulus and diaphragmatic hernia.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct‐acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct‐acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct‐acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct‐acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child‐Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha‐fetoprotein level >9.5 ng/mL at the time of end‐of‐treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768‐2882.473) and in patients treated with direct‐acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417‐1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct‐acting antivirals and was associated with the serum alpha‐fetoprotein level at the time of end‐of‐treatment response.

R&D Project Selection Methodology for Green Technology : Focused on Developing Country-Oriented Technology Commercialization

This paper proposes an R&D project selection methodology for green technology centered on developing country-oriented technology commercialization. Eight selection criteria are derived from the R&BD logic model: technology needs of developing countries, effectiveness of green technology, technological potentials, domestic technological capability, commercialization feasibility, economic benefits, business feasibility, and spillover effects of developing countries. 21 qualitative and quantitative indicators are then defined for each criterion. The analytic hierarchy process is then conducted to produce relative importance of evaluation indicators and to set final priority scores of R&D project candidates. The working of the proposed methodology is provided with the help of a case study example of Green Technology Center. The proposed methodology is expected to be effectively utilized for policy practices of R&D project selection in the field of green technology.