Publications by authors named "Youn Jae Lee"

63 Publications

Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in South Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID.

Epidemiol Health 2021 Oct 6:e2021077. Epub 2021 Oct 6.

Seoul National University Bundang Hospital , Seongnam, Korea.

Objectives: Injection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data are available in South Korea. Thus, this study aimed to investigate the epidemiological and clinical characteristics, treatment uptake, and outcomes of HCV infection among people who inject drugs (PWID).

Methods: We used the data from the Korea HCV cohort, which prospectively enrolled patients with HCV infection between 2007 and 2019. Clinical data and results of the questionnaire survey focused on the lifetime risk factors for HCV infection were analyzed based on the self-reported history of injection drug use.

Results: Among the 2,468 patients, 166 (6.7%) had a history of injection drug use (PWID group). In the PWID group, the patients were younger (50.68.2 vs. 58.213.1 years) and the proportion of males was higher (81.9% vs. 48.8%) than in the non-PWID group. The distribution of PWID showed significant regional variations. Exposure to other risk factors for HCV infection was different between the groups. The proportion of patients with genotype non-2 infection was higher in the PWID group. Treatment uptake was higher in the PWID group in the interferon era; however, it was comparable between the groups in the direct-acting antiviral era. The rate of sustained virological response did not differ between the groups.

Conclusion: By 2019, PWID were a minority among the HCV-infected people in Korea. The epidemiological characteristics were different between the groups, but not the treatment uptake and outcomes. Therefore, active screening and treatment should be offered to PWID in Korea.
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http://dx.doi.org/10.4178/epih.e2021077DOI Listing
October 2021

Efficacy and Safety of Glecaprevir/Pibrentasvir in Korean Patients with Chronic Hepatitis C: A Pooled Analysis of Five Phase II/III Trials.

Gut Liver 2021 11;15(6):895-903

Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.

Background/aims: Glecaprevir/pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral combination therapy approved in Korea. An integrated analysis of five phase II and III trials was conducted to evaluate the efficacy and safety of G/P in Korean patients with chronic hepatitis C virus (HCV) infection.

Methods: The study analyzed pooled data on Korean patients with HCV infection enrolled in the ENDURANCE 1 and 2, SURVEYOR II part 4 and VOYAGE I and II trials, which evaluated the efficacy and safety of 8 or 12 weeks of G/P treatment. The patients were either treatment-naïve or had received sofosbuvir or interferon-based treatment. Efficacy was evaluated by assessing the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Safety was evaluated by monitoring adverse events (AEs) and laboratory assessments.

Results: The analysis included 265 patients; 179 (67.5%) were HCV treatment-naïve, and most patients were either subgenotype 1B (48.7%) or 2A (44.5%). In the intention-to-treat population, 262 patients (98.9%) achieved SVR12. Three patients did not achieve SVR12: one had virologic failure and two had non-virologic failures. Most AEs were grade 1/2; eight patients (3.0%) experienced at least one grade ≥3 AE. No serious AEs related to G/P treatment were reported, and grade ≥3 hepatic laboratory abnormalities were rare (0.8%).

Conclusions: G/P therapy was highly efficacious and well tolerated in Korean patients with HCV infection, with most patients achieving SVR12. The safety profile was comparable to that observed in a pooled analysis of a global pan-genotypic population of patients with HCV infection who received G/P.
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http://dx.doi.org/10.5009/gnl20321DOI Listing
November 2021

Percutaneous Trans-splenic Obliteration for Duodenal Variceal bleeding: A Case Report.

Korean J Gastroenterol 2020 12;76(6):331-336

Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Kore.

Duodenal varices are a serious complication of portal hypertension. Bleeding from duodenal varices is rare, but when bleeding does occur, it is massive and can be fatal. Unfortunately, the optimal therapeutic modality for duodenal variceal bleeding is unclear. This paper presents a patient with duodenal variceal bleeding that was managed successfully using percutaneous trans-splenic variceal obliteration (PTVO). A 56-year-old man with a history of alcoholic cirrhosis presented with a 6-day history of melena. Emergency esophagogastroduodenoscopy revealed a large, bluish mass with a nipple sign in the second portion of the duodenum. Coil embolization of the duodenal varix was performed via a trans-splenic approach (i.e., PTVO). The patient no longer complained of melena after treatment. The duodenal varix was no longer visible at the follow-up esophagogastroduodenoscopy performed three months after PTVO. The use of PTVO might be a viable option for the treatment of duodenal variceal bleeding.
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http://dx.doi.org/10.4166/kjg.2020.123DOI Listing
December 2020

Effectiveness and safety of elbasvir/grazoprevir in Korean patients with hepatitis C virus infection: a nationwide real-world study.

Korean J Intern Med 2021 03 17;36(Suppl 1):S1-S8. Epub 2020 Jun 17.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background/aim: This study aimed to establish the real-world effectiveness and safety of grazoprevir/elbasvir (EBR/GZR) therapy in South Korea.

Methods: A total of 242 patients with chronic hepatitis C virus (HCV) genotype 1 or 4 infection who started EBR/GZR were consecutively enrolled from seven tertiary hospitals. Retrospective analysis of the fractions of patients that achieved sustained virological response (SVR) was performed, and the incidence of adverse events was noted.

Results: The mean age of enrolled patients was 59.0 ± 12.6 years and 47.5% were males. Patients with HCV genotype 1b accounted for 93.8% (n = 227), and patients with HCV of unspecified genotype 1 accounted for 5.8% (n = 14). Hypertension was the most common comorbid disease (29.8%) followed by diabetes (22.7%) and chronic kidney disease (CKD, 12.4%). SVR rates of treatment-naïve and treatment-experienced patients were 85.5% (182/213) and 93.1% (27/29), respectively, in the intention-to-treat analyses, whereas in the per-protocol analyses, those were 97.8% (179/183) and 100% (28/28), respectively. Fewer patients with HCV genotype 1 of unspecified subtype achieved SVR (81.8%, n = 11) compared to the patients with SVR infected with genotype 1b (99%, n = 198, p < 0.001). All patients with CKD showed SVR. Itching (12%) and dyspepsia (4.1%) were common adverse events. Of the four patients who discontinued the antiviral therapy, one experienced mild fatigue but neither treatment withdrawal was because of an adverse event.

Conclusion: EBR/GZR showed high real-world effectiveness and safety in Korean patients with chronic HCV infection regardless of the previous antiviral treatment, liver cirrhosis, or CKD status.
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http://dx.doi.org/10.3904/kjim.2019.357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009154PMC
March 2021

Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose.

Gut Liver 2020 11;14(6):775-782

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to investigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection.

Methods: From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecutively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by intention- to-treat (ITT) and per-protocol (PP) analyses.

Results: The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/ mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber's discretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were observed in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea.

Conclusions: SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.
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http://dx.doi.org/10.5009/gnl19260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667937PMC
November 2020

Real-life effectiveness and safety of the daclatasvir/asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: An emphasis on the pretreatment NS5A resistance-associated substitution test.

J Med Virol 2019 12 9;91(12):2158-2165. Epub 2019 Sep 9.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.

This study aimed to investigate the real-life effectiveness and safety of daclatasvir (DCV) and asunaprevir (ASV) combination therapy in Korean patients. We consecutively enrolled patients with genotype 1b hepatitis C virus (HCV) infection treated with at least one dose of DCV/ASV combination therapy in seven tertiary hospitals of South Korea. The sustained virologic response (SVR) rates and safety according to intention-to-treat (ITT) and per-protocol (PP) analyses were evaluated. Among the 526 enrolled patients, 91% showed negative (87%) or "undetermined" (4%) resistance-associated substitution (RAS); 9% did not undergo RAS testing. The SVR rates for ITT and PP were 89.3% and 95.0% in treatment-naive patients and 93.2% and 95.6% in treatment-experienced patients, respectively. In PP analysis, negative RAS was associated with higher SVR (96.3%) than with "undetermined RAS" (85.7%) or "not tested for RAS" (84.4%). Adverse events were reported in 185 (35.4%) patients, and events leading to discontinuation were observed in 4.3% of the study population. Forty-two (8.0%) patients developed transaminase elevation (≥2 × upper normal limit), resulting in treatment discontinuation in six (1.1%) patients. DCV/ASV combination therapy showed acceptable efficacy in genotype 1b compensated HCV-infected patients with negative pretreatment RAS. Although most adverse events were tolerable to continue antiviral treatment, adequate monitoring for transaminase elevation is warranted.
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http://dx.doi.org/10.1002/jmv.25575DOI Listing
December 2019

Epidemiological and Clinical Characteristics of Hepatitis C Virus Infection in South Korea from 2007 to 2017: A Prospective Multicenter Cohort Study.

Gut Liver 2020 03;14(2):207-217

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: This study aimed to elucidate the epidemiological and clinical characteristics of chronic hepatitis C (CHC) patients in South Korea from 2007 to 2017 and to compare the treatment patterns between two periods before and after the first approval of direct-acting antivirals (DAA) in South Korea in 2015.

Methods: This prospective, multicenter cohort enrolled 2,758 patients with hepatitis C virus (HCV) viremia at seven tertiary centers, and clinical data were prospectively collected with questionnaire surveys focused on lifetime risk factors related to HCV infection.

Results: The HCV patients had a mean age of 57.3 years (50.8% male). Among them, 14.3% showed a positive history of transfusion before HCV screening and 5.6% reported intravenous drug use (IVDU), with significant differences in these risk factors between men and women. The proportions of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) were 69.5%, 18.9%, and 11.5%, respectively. The mean alanine aminotransaminase level was within the upper normal limit at 49.9%, and the major genotypes were 1b (48.2%) and 2 (46.4%). The overall treatment rate was 53.8%, showing a rapid transition from interferon-based therapy to DAA therapy. In the post-DAA-approval era, the untreated group was older, had a higher prevalence of HCC, and had less education than the treated group.

Conclusions: More than 90% of CHC patients were over 40 years old, the major genotypes were 1b and 2, and IVDU was observed in less than 6% of CHC patients. Approximately half of the patients underwent antiviral therapy even in the DAA era, showing an unmet need with regard to HCV elimination.
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http://dx.doi.org/10.5009/gnl19005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096238PMC
March 2020

An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection.

Clin Mol Hepatol 2019 12 28;25(4):400-407. Epub 2019 May 28.

Merck & Co., Inc., Kenilworth, NJ, USA.

Background/aims: In the Republic of Korea, an estimated 231,000 individuals have chronic hepatitis C virus (HCV) infection. The aim of the present analysis was to evaluate the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) administered for 12 weeks in Korean patients who were enrolled in international clinical trial phase 3 studies.

Methods: This was a retrospective, integrated analysis of data from patients with HCV genotype (GT) 1b infection enrolled at Korean study sites in four EBR/GZR phase 3 clinical trials. Patients were treatment-naive or had previously failed interferon-based HCV therapy, and included those with human immunodeficiency virus coinfection or ChildPugh class A cirrhosis. All patients received EBR 50 mg/GZR 100 mg once daily for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12, HCV RNA <15 IU/mL).

Results: SVR12 was achieved by 73 of 74 (98.6%) patients. No patients had virologic failure and one discontinued from the study after withdrawing consent. SVR12 rates were uniformly high across all patient subgroups. A total of 16 patients had nonstructural protein 5A resistance-associated substitutions at baseline (16/73, 22%), all of whom achieved SVR12. Adverse events (AEs) reported in >5% of patients were fatigue (6.8%), upper respiratory tract infection (5.4%), headache (5.4%), and nausea (5.4%). Thirteen patients (17.6%) reported drug-related AEs, two serious AEs occurred, and two patients discontinued treatment owing to an AEs.

Conclusion: In this retrospective analysis, EBR/GZR administered for 12 weeks was well-tolerated and highly effective in Korean patients with HCV GT1b infection.
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http://dx.doi.org/10.3350/cmh.2019.0006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933128PMC
December 2019

Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial.

J Hepatol 2019 04 6;70(4):684-691. Epub 2018 Dec 6.

Keimyung University Dongsan Medical Center, South Korea.

Background & Aims: Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC.

Methods: In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS).

Results: For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006).

Conclusion: Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC.

Lay Summary: For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.
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http://dx.doi.org/10.1016/j.jhep.2018.11.029DOI Listing
April 2019

Concomitant food intake does not affect the efficacy of entecavir in chronic hepatitis B patients with virological response: a randomized, multicenter, noninferiority trial.

Drug Des Devel Ther 2018 2;12:3767-3774. Epub 2018 Nov 2.

Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea,

Background: Little clinical data are available about the effect of food on the antiviral efficacy of entecavir for chronic hepatitis B virus (HBV) infection. The present study evaluated whether entecavir administration in the fed state had comparable efficacy to the fasted condition for maintenance of viral suppression in HBV-infected patients with virological response on entecavir therapy.

Methods: In this multicenter, randomized, open-label, noninferiority study, patients who were currently receiving entecavir and showed a serum HBV DNA level of <20 IU/mL were randomized to take entecavir either under the fasted or fed condition for 48 weeks.

Results: We randomly assigned 50 patients to the fasted group and 46 patients to the fed group. The full analysis set consisted of 49 patients in the fasted group and 44 patients in the fed group. At week 48, the proportion of patients with HBV DNA <20 IU/mL was not significantly different between the fasted and fed groups (98% vs 100%, =1.00). The mean log HBV DNA changes from baseline were similar between the two groups (-0.004 vs -0.012 log IU/mL, =0.43). There were no significant differences in the proportions of patients with normal alanine aminotransferase (87.8% vs 95.5%, =0.27) and hepatitis B e-antigen seroconversion (0% vs 6.7%, =0.47) between the two groups. None of the patients showed viral breakthrough. In pharmacokinetic analysis, the maximum concentration and the area under the concentration- time curve to the last quantifiable concentration decreased by 26.4% and 9.3%, respectively, in the fed group compared with the fasted group. However, the differences between two groups were not statistically significant (=0.28 and 0.83, respectively).

Conclusion: In patients with virological response under entecavir therapy, concomitant food intake did not affect the antiviral efficacy. For patients with adherence problem, taking entecavir with food may be considered to improve compliance.
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http://dx.doi.org/10.2147/DDDT.S181561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223329PMC
March 2019

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study.

J Korean Med Sci 2018 Oct 12;33(42):e264. Epub 2018 Sep 12.

Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

Background: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study.

Methods: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m or proteinuria as at least grade 2+ of urine protein.

Results: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, < 0.001, and 14.1%, < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m.

Conclusion: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.
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http://dx.doi.org/10.3346/jkms.2018.33.e264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179986PMC
October 2018

Factors Associated with Health-Related Quality of Life in Korean Patients with Chronic Hepatitis C Infection Using the SF-36 and EQ-5D.

Gut Liver 2018 07;12(4):440-448

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: This study aimed to describe the health-related quality of life (HRQoL) outcomes for Korean chronic hepatitis C patients and to investigate the impact of patient and virus-related factors on HRQoL.

Methods: HRQoL was assessed in 235 hepatitis C virus (HCV)-infected patients from seven nationwide tertiary hospital, including those with liver cirrhosis and hepatocellular carcinoma (HCC), using the Shor-Form 36 (SF-36) version 2 and the European quality of life questionnaire-5 dimensions (EQ-5D-3L).

Results: The SF-36 physical (48.8±8.3) and mental (46.2±11.7) component summary scores of the HCV-infected patients were below normal limits. Of the eight domains, general health, vitality, and mental health tended to show low scores. Patients with decompensated cirrhosis had the lowest HRQoL, while HCC and chronic hepatitis patients had similar HRQoL results. The EQ-5D index was low (0.848±0.145) in the HCV infected patients. Multivariable analysis showed age ≤65 years, high monthly family income (>$2,641), low comorbidity score, and sustained virologic response (SVR) were independently associated with favorable HRQoL.

Conclusions: HRQoL in Korean patients with chronic HCV infection was low and was affected by cirrhosis severity, SVR, and comorbidity as well as income, which had the strongest effect. Therefore, HRQoL may be improved by antiviral therapy with reasonable costs to prevent cirrhosis progression.
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http://dx.doi.org/10.5009/gnl17322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027832PMC
July 2018

Baracle vs Baraclude for 48 weeks in patients with treatment-naïve chronic hepatitis B: a comparison of efficacy and safety.

Drug Des Devel Ther 2017 31;11:3145-3152. Epub 2017 Oct 31.

Department of Internal Medicine, Asan Medical Center, Ulsan University, Seoul, Republic of Korea.

Background And Objective: Entecavir (ETV) is a standard of care for chronic hepatitis B (CHB). In a bioequivalence study, ETV from Dong-A ST (Baracle) was found to have a pharmacokinetic profile equivalent to ETV from Bristol-Myers Squibb (BMS) (Baraclude). The present study was conducted to evaluate the antiviral activity and safety of ETV from Dong-A ST in comparison to ETV from BMS in patients with CHB.

Methods: In this multicenter, double-blind, active-controlled, stratified-randomized, parallel group, comparative trial, 118 treatment-naïve patients with CHB were randomly assigned to receive either 0.5 mg of ETV from Dong-A ST or ETV from BMS once daily for 48 weeks. The primary efficacy endpoint was virologic improvement (a mean reduction from baseline in serum HBV DNA levels) at 24 weeks. Secondary efficacy endpoints included a mean reduction in serum HBV DNA levels at 48 weeks, proportion of patients with undetectable levels of serum HBV DNA, rates of hepatitis B e antigen (HBeAg) loss and seroconversion, rates of HBsAg loss and seroconversion, and rates of normalization of alanine aminotransferase (ALT) levels.

Results: From baseline to week 24, HBV DNA levels (log) decreased by 4.81 and 4.63 with ETV from Dong-A ST and with ETV from BMS, respectively. The upper limit of two-sided 95% confidence intervals (CI) (equivalent to one-sided 97.5% CIs) for the difference between the treatment groups was 0.208, which was below the noninferiority margin of 1, thus supporting the noninferiority of ETV from Dong-A ST in comparison to ETV from BMS. No statistically significant differences were noted between the treatment groups in all secondary and tertiary efficacy endpoints. Safety profiles were also similar between the two groups.

Conclusion: In patients with previously untreated HBeAg-positive or negative HBV infection, the efficacy of ETV from Dong-A ST was noninferior to that of ETV from BMS, and there were no significant differences in efficacy or safety between two groups.
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http://dx.doi.org/10.2147/DDDT.S149199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673034PMC
July 2018

Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study.

Lancet Gastroenterol Hepatol 2018 01 4;3(1):37-46. Epub 2017 Oct 4.

Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan.

Background: Orantinib is an oral multi-kinase inhibitor. This study was done to evaluate the efficacy of orantinib combined with conventional transcatheter arterial chemoembolisation (cTACE) in patients with unresectable hepatocellular carcinoma.

Methods: This randomised, double-blind, placebo-controlled, phase 3 study was done at 75 sites in Japan, South Korea, and Taiwan. Patients with unresectable hepatocellular carcinoma, no extra-hepatic tumour spread, and Child-Pugh score of 6 or less were randomly assigned (1:1) by interactive web response system using a computer-generated sequence to receive orantinib or placebo, within 28 days of cTACE. Randomisation was stratified by region, Child-Pugh score (5 vs 6), alpha fetoprotein concentrations (<400 ng/mL vs ≥400 ng/mL), and size of the largest lesion (≤50 mm vs >50 mm). Orantinib at 200 mg, twice per day, or placebo was given orally until TACE failure or unacceptable toxicity. The patients, investigators, and study personnel were masked to treatment assignment. The primary endpoint was overall survival, analysed in the full analysis set (patients who had received at least one dose of study drug). This study is registered at ClinicalTrials.gov, number NCT01465464, and has been terminated.

Findings: Between Dec 10, 2010, and Nov 21, 2013, 889 patients were randomly assigned to receive either orantinib (445 patients; 444 treated) or placebo (444 patients; all treated). The study was ended at interim analysis for futility evaluation. Median follow-up was 17·3 months (IQR 11·3-26·4). There was no improvement in overall survival with orantinib compared with placebo (median 31·1 months [95% CI 26·5-34·5] vs 32·3 months [28·4-not reached]; hazard ratio 1·090, 95% CI 0·878-1·352; p=0·435). The main adverse events in the orantinib group were oedema, ascites, and elevation of aspartate and alanine aminotransferases. The most frequent adverse events of grade 3 or worse in the orantinib group included elevated aspartate aminotransferase (189 [43%] patients in the oratinib group, 161 [36%] patients in the placebo group), elevated alanine aminotransferase (150 [34%] patients in the oratinib group, 132 (30%) patients in the placebo group), and hypertension (47 [11%] patients in the oratinib group, 39 [9%] patients in the placebo group). Serious adverse events were reported in 200 (45%) patients in the orantinib group and 134 (30%) patients in the placebo group.

Interpretation: Orantinib combined with cTACE did not improve overall survival in patients with unresectable hepatocellular carcinoma.

Funding: Taiho Pharmaceutical.
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http://dx.doi.org/10.1016/S2468-1253(17)30290-XDOI Listing
January 2018

Final Report of Unmet Needs of Interferon-Based Therapy for Chronic Hepatitis C in Korea: Basis for Moving into the Direct-Acting Antiviral Era.

Gut Liver 2017 Jul;11(4):543-550

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: To evaluate the era of direct acting antivirals (DAAs), we must understand the treatment patterns and outcomes of interferon-based therapy for hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate, factors affecting treatment decisions, and efficacy of interferon- based therapy in a real-world setting.

Methods: This nationwide cohort study included 1,191 newly diagnosed patients with chronic HCV infection at seven tertiary hospitals in South Korea. Subjects were followed retrospectively until March 2015, which was just before the approval of DAA therapy.

Results: In total, 48.2% and 49.3% of the patients had HCV genotypes 1 and 2, respectively. Interferon-based therapy was initiated in 541 patients (45.4%). The major reasons for no treatment included ineligibility (18.9%), concern about adverse events (22.3%), cost (21.5%), and an age >75 years (19.5%). Interferon-based therapy was discontinued (18.5%) mainly due to adverse events (n=66). The intent-to-treat analysis found that the sustained virologic response (SVR) rate was 58.3% in genotype 1 patients and 74.7% in nongenotype 1 patients.

Conclusions: Approximately one-third of newly diagnosed HCV patients in South Korea received interferon-based therapy and showed a suboptimal SVR rate. Diagnosis of patients at younger ages and with a less advanced liver status and reducing the DAA therapy cost may fulfill unmet needs.
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http://dx.doi.org/10.5009/gnl16530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491090PMC
July 2017

Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1.

J Gastroenterol Hepatol 2017 Dec;32(12):1998-2005

Bristol-Myers Squibb, Princeton, New Jersey, USA.

Background And Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis.

Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients.

Results: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9-99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8-100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths.

Conclusions: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.
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http://dx.doi.org/10.1111/jgh.13796DOI Listing
December 2017

A phase IIIb study of ledipasvir/sofosbuvir fixed-dose combination tablet in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 hepatitis C virus.

Hepatol Int 2016 Nov 20;10(6):947-955. Epub 2016 May 20.

Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.

Background: The standard-of-care regimen for chronic hepatitis C virus (HCV) infection in Korea, pegylated-interferon-alpha plus ribavirin, is poorly tolerated. Ledipasvir/sofosbuvir is a two-drug, fixed-dose combination tablet approved in the USA, European Union, and Japan for chronic genotype 1 HCV infection.

Methods: This single-arm, phase IIIb study (NCT02021656) investigated the efficacy and safety of ledipasvir/sofosbuvir fixed-dose combination tablet for 12 weeks in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 HCV with or without compensated cirrhosis.

Results: The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 99 % (92/93), with rates of 100 % (46/46) and 98 % (46/47) in treatment-naïve and treatment-experienced patients, respectively. There were no on-treatment failures. One patient relapsed after the end of treatment. The most common treatment-emergent adverse events were headache (8 %, 7/93) and fatigue (6 %, 6/93). There were no grade 3 or 4 adverse events, seven grade 3 laboratory abnormalities, and one premature discontinuation of study treatment (due to nonserious mouth ulceration). None of the three reported serious adverse events were related to treatment.

Conclusions: These data suggest that 12 weeks of ledipasvir/sofosbuvir is effective and well tolerated in treatment-naïve and treatment-experienced Korean patients with chronic genotype 1 HCV infection.
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http://dx.doi.org/10.1007/s12072-016-9726-5DOI Listing
November 2016

The clinical outcomes of chronic hepatitis C in South Korea: A prospective, multicenter cohort study.

Medicine (Baltimore) 2016 Aug;95(35):e4594

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan Departement of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University College of Medicine, Jeonju Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun Department of Internal Medicine, The Catholic University of Korea, Seoul Saint Mary's Hospital Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

This prospective cohort study aimed to elucidate the clinical outcome and its related factors of chronic hepatitis C in a hepatitis B-dominant Asian region.From January 2007 to October 2012, 382 patients with chronic hepatitis C without liver cirrhosis were prospectively enrolled at 6 university hospitals, and regularly followed until Apr 2014 to identify the development of liver cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), and overall survival.During the median follow-up of 39.0 months (range 18.0-81.0 months), liver cirrhosis, hepatic decompensation, and HCC developed in 42 patients (11.0%), 4 patients (1.0%), and 12 patients (3.1%), respectively. The cumulative probability of development of cirrhosis at 3 years and at 5 years was 9.6% and 16.7%, respectively. That of HCC at 3 and 5 years was 1.6% and 4.5%, respectively. The 3-year and 5-year overall survival rate was 99.7% and 96.0%, respectively. Pegylated interferon-based antiviral therapy was undertaken in 237 patients (62.0%) with a sustained virologic response (SVR) rate of 74.3%. The factors related to the overall clinical outcomes were age ≥55 years (HR 2.924, P = 0.016), platelet counts <150  × 10/L (HR 3.195, P = 0.007), and the achievement of SVR (HR 0.254, P = 0.002).The clinical outcomes of this Korean chronic hepatitis C cohort were modest with minimal mortality, but significant disease progression occurred in the patients with old age, low platelet, and non-SVR after interferon-based antiviral treatment or no treatment, suggesting priority for direct acting antiviral therapy.
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http://dx.doi.org/10.1097/MD.0000000000004594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008558PMC
August 2016

All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study.

Liver Int 2016 10 28;36(10):1433-41. Epub 2016 Apr 28.

Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.

Background & Aims: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b (GT-1b) infection in the HALLMARK DUAL trial. This post hoc analysis was conducted to determine the efficacy and safety of this treatment in Asian patients.

Methods: Treatment-naive patients were randomly assigned (2:1; double-blinded) to receive DCV (60 mg once daily) plus ASV (100 mg twice daily) or placebo for 12 weeks. Subsequently, placebo patients entered another study, and the remaining patients continued treatment for an additional 12 weeks. Non-responders to peginterferon/ribavirin and ineligible/intolerant patients received dual therapy for 24 weeks. Sustained virological response at post-treatment Week 12 [sustained virological response (SVR)12] and safety outcomes were evaluated.

Results: This post hoc analysis included 186 Asian patients (Korean, 78; Taiwanese, 85; others, 23), of whom 32.3% were cirrhotic. SVR12 was observed in 92.3, 78.6 and 80.0% of treatment-naive, ineligible/intolerant and non-responder patients, respectively, and was comparable with non-Asian patients. SVR12 by baseline factors including age, viral load, interleukin-28B genotype and cirrhosis status was similar between the Asian sub-cohorts. Among 18 Asian patients with NS5A-Y93H or NS5A-L31M/V resistance-associated variants (RAVs), seven patients achieved SVR12. Multivariate regression analysis showed a significant influence of NS5A RAVs in both Asian and non-Asian cohorts. The incidence of serious adverse events in Asian patients was low (7.2%). Two Taiwanese patients had elevated alanine aminotransferase (≥5.1 × ULN); both achieved SVR12.

Conclusions: All-oral dual therapy with DCV + ASV resulted in high SVR rates and was well tolerated in Asian patients with HCV GT-1b infection.
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http://dx.doi.org/10.1111/liv.13128DOI Listing
October 2016

Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: a pooled analysis.

Liver Int 2016 07 24;36(7):954-62. Epub 2016 Jan 24.

Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.

Background & Aims: We compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV).

Methods: Outcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes.

Results: In the Japanese phase 3 study, SVR12 was achieved by 91% of patients with cirrhosis (n = 22) and 84% of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84% of patients with cirrhosis (n = 206) and by 85% of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10%) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2%, respectively) compared with those without cirrhosis (both 0.6%). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8%) compared with those without cirrhosis (3.5-4.7%). Alanine aminotransferase elevations were not associated with hepatic decompensation.

Conclusions: The safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: Clinicaltrials.gov identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834.
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http://dx.doi.org/10.1111/liv.13049DOI Listing
July 2016

Comparison and analysis of the prevalence of hepatitis C virus infection by region in the Republic of Korea during 2005-2012.

Clin Mol Hepatol 2015 Sep 30;21(3):249-56. Epub 2015 Sep 30.

Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

Background/aims: This study compared the prevalence of hepatitis C virus (HCV) infection in the Republic of Korea and estimated the high-risk regions and towns.

Methods: National Health Insurance Service data for 8 years from 2005 to 2012 were used. The subjects of the study had visited medical facilities and been diagnosed with or received treatment for acute or chronic HCV as a primary or secondary disease according to ICD-10 codes of B17.1 or B18.2, respectively. Any patient who received treatment for the same disease multiple times during 1 year was counted as one patient in that year. To correct for the effect of the age structure of the population by year and region, the age-adjusted prevalence was calculated using the direct method based on the registered population in 2010.

Results: The overall prevalence of HCV infection among Korean adults (>20 years old) increased from 0.14% in 2005 to 0.18% in 2012. The sex-, age-, and region-adjusted prevalence in 2012 was 0.18%. The prevalence was highest in Busan, Jeonnam, and Gyeongnam, and there were towns with noticeably higher prevalences within these regions: Jindo (0.97%) in Jeonnam, Namhae (0.90%) in Gyeongnam, and Seo-gu (0.86%) in Busan.

Conclusions: The prevalence of HCV infection differs by regions as well as towns in the Republic of Korea, and is highest in Busan, Jeonnam, and Gyeongnam. The reasons for the high prevalence in these specific regions should be identified, since this could help prevent HCV infections in the future. In addition, active surveillance and treatment policies should be introduced to stop any further spread of infection in these high-prevalence regions.
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http://dx.doi.org/10.3350/cmh.2015.21.3.249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612286PMC
September 2015

Pre-stimulation of CD81 expression by resting B cells increases proliferation following EBV infection, but the overexpression of CD81 induces the apoptosis of EBV-transformed B cells.

Int J Mol Med 2015 Dec 13;36(6):1464-78. Epub 2015 Oct 13.

Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.

Hepatitis C virus (HCV) E2 protein binds to CD81, which is a component of the B cell co-stimulatory complex. The E2-CD81 interaction leads to B cell proliferation, protein tyrosine phosphorylation and to the hypermutation of immunoglobulin genes. Epidemiological studies have reported a high prevalence of B cell non-Hodgkin lymphoma (NHL) in HCV-positive patients, suggesting a potential association between HCV and Epstein-Barr virus (EBV) in the genesis of B lymphocyte proliferative disorders. In the present study, in order to investigate the association between EBV and HCV in B cells, we created an in vitro EBV-induced B cell transformation model. CD81 was gradually overexpressed during transformation by EBV. B cells isolated from HCV-positive patients grew more rapidly and clumped together earlier than B cells isolated from healthy donors following EBV infection. Pre-stimulation of CD81 expressed by resting B cells with anti-CD81 monoclonal antibody (mAb) or HCV E2 accelerated the generation of lymphoblastoid cell lines (LCLs) by EBV infection. These cells proliferated prominently through the early expression of interleukin-10 and intracellular latent membrane protein (LMP)-l. By contrast, the overexpression of CD81 on EBV-transformed B cells by anti-CD81 mAb or HCV E2 protein induced apoptosis through reactive oxygen species (ROS)-mediated mitochondrial dysfunction. These results suggest that the engagement of CD81 expressed by B cells has differential effects on B cell fate (proliferation or apoptosis) according to EBV infection and the expression level of CD81.
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http://dx.doi.org/10.3892/ijmm.2015.2372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678167PMC
December 2015

Risk Factors for Hepatitis C Virus (HCV) Infection in Areas with a High Prevalence of HCV in the Republic of Korea in 2013.

Gut Liver 2016 Jan;10(1):126-32

Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

Background/aims: The prevalence of hepatitis C virus (HCV) infection in Busan, Gyeongnam, and Jeonnam Provinces in Korea is more than twice the national average. This study aimed to examine whether demographic and lifestyle characteristics are associated with HCV infection in these areas.

Methods: A case control study was performed at three study hospitals. HCV cases were matched with two controls for sex and age. Patient controls were selected from non-HCV patients at the same hospital. Healthy controls were subjects participating in medical checkups. Conditional logistic regression models were used.

Results: A total of 234 matched-case and patient- and healthy-control pairs were analyzed. The significant risk factors for both controls were sharing razors (adjusted odds ratio [aOR], 2.39 and 3.29, respectively) and having more than four lifetime sexual partners (aOR, 2.15 and 6.89, respectively). Contact dockworkers (aOR, 1.91) and tattoos (aOR, 2.20) were significant risk factors for the patient controls. Transfusion (aOR, 5.38), a bloody operation (aOR, 5.02), acupuncture (aOR, 2.08), and piercing (aOR, 5.95) were significant risk factors for the healthy controls. Needle stick injuries and intravenous drug abuse were significant in the univariate analysis.

Conclusions: More education concerning the dangers of sharing razors, tattoos and piercings is required to prevent HCV infection. More attention should be paid to needle stick injuries in hospitals and the community.
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http://dx.doi.org/10.5009/gnl14403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694744PMC
January 2016

Treatment rate and factors related to interferon-based treatment initiation for chronic hepatitis C in South Korea.

J Med Virol 2016 Feb 4;88(2):275-81. Epub 2015 Aug 4.

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Under-recognition and under-treatment of chronic hepatitis C virus (HCV) infection is an important determinant of the disease outcome. The aim of this study was to investigate the treatment rate and factor of initiation of interferon-based antiviral treatment for chronic hepatitis C patients in a prospective, multicenter Korean HCV cohort. Treatment-naïve 759 patients with chronic HCV infection were prospectively followed from January 2007-2013 at six university hospitals during a median (interquartile range) follow-up of 769 (76-1,427) days. The subjects consisted of patients with chronic hepatitis C (n = 553, 72.9%), liver cirrhosis (n = 127, 16.7%), and hepatocellular carcinoma (n = 79, 10.4%), and were treated usually using pegylated interferon alpha and ribavirin. Treatment initiation rate and its related factors were analysed. The initiation rate of antiviral treatment was 37.3% (n = 273), and the cumulative probability of treatment initiation over 5 years was 39.4%. Multivariate analysis showed that age <58 years (hazard ratio [HR] = 1.588, 95% CI = 1.151-2.193), job employment (HR = 1.737, 95% CI = 1.279-2.363), absence of HCC (chronic hepatitis, HR = 2.534, 95% CI = 1.003-6.400; liver cirrhosis, HR = 2.873, 95% CI = 1.101-7.494), alanine transaminase (ALT) >40 IU/L (HR = 1.682, 95% CI = 1.228-2.303), and genotype 2 (HR = 1.364, 95% CI = 1.034-1.798) were independent factors related to treatment initiation. Interferon-based antiviral treatment was initiated in more than one third of chronic HCV infected patients visiting university hospitals, who were young, employed, HCV genotype 2, and with abnormal ALT without HCC, in Korea.
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http://dx.doi.org/10.1002/jmv.24335DOI Listing
February 2016

Highly effective peginterferon α-2a plus ribavirin combination therapy for chronic hepatitis C in hemophilia in Korea.

Clin Mol Hepatol 2015 Jun 26;21(2):125-30. Epub 2015 Jun 26.

Department of Gastrohepatology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.

Background/aims: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon α-2a plus ribavirin for CHC in hemophilia.

Methods: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests.

Results: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naïve patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis.

Conclusions: Peginterferon α-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.
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http://dx.doi.org/10.3350/cmh.2015.21.2.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493355PMC
June 2015

A review of the burden of hepatitis C virus infection in China, Japan, South Korea and Taiwan.

Hepatol Int 2015 Jul 13;9(3):378-90. Epub 2015 Jun 13.

ICON Epidemiology, ICON plc, Toronto, Canada,

Hepatitis C virus (HCV) infection is associated with substantial clinical and economic burden and is an important public health issue in Asia. The objective of this review was to characterize HCV epidemiology and related complications in China, Japan, South Korea and Taiwan. A search of electronic databases and conference abstracts identified 71 potentially relevant articles. Of those, 55 were included in the epidemiology review and 9 in the review of HCV-related complications. HCV prevalence in the general population was 1.6% in China, 0.6-0.9% in Japan, 0.6-1.1% in South Korea and 1.8-5.5% in Taiwan. Prevalence was higher for injecting drug users (48-90%) and those with human immunodeficiency virus coinfection (32-85%) and was lower for blood donors (<1%). Annual incidence of HCV in China was 6.01 per 100,000. HCV genotype 1b was associated with the highest incidence of hepatocellular carcinoma (HCC). Five-year survival for patients with liver cirrhosis was 73.8%, decreasing to 39.2% following liver transplantation; the majority of deaths were attributable to HCC. Limitations were that the majority of studies included in the epidemiology review were small, regional studies conducted in specific populations, and there was an absence of large population-based studies. Thus, estimates may not be representative of the epidemiology of HCV for each country. The prevalence HCV in China and HCV incidence in the Asian region remain largely unknown, and they are likely underestimated. Further epidemiologic and clinical data are needed to provide more precise estimates for use by public health agencies.
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http://dx.doi.org/10.1007/s12072-015-9629-xDOI Listing
July 2015

Prospective cohort study on the outcomes of hepatitis C virus-related cirrhosis in South Korea.

J Gastroenterol Hepatol 2015 Aug;30(8):1281-7

Division of AIDS, Korea National Institute of Health, Osong, South Korea.

Background And Aims: The outcomes of hepatitis C virus (HCV)-related liver cirrhosis was limitedly studied in a hepatitis B virus-endemic area. This multicenter, prospective cohort study was conducted to elucidate the incidence of hepatocellular carcinoma (HCC) and mortality in the Korean patients with HCV-related cirrhosis.

Methods: From January 2007 through June 2012, 196 patients with HCV-related cirrhosis were prospectively enrolled and regularly followed at six university hospitals to determine HCC occurrence and mortality. A multivariable analysis using Cox proportional hazards regression was performed to clarify the related factors to the outcomes.

Results: During a mean follow-up period of 39.2 months, 31 (15.8%) patients developed HCC, and 33 (16.8%) patients died or underwent liver transplantation. The estimated HCC incidence was 5.8 per 100 person-years, and the independent factors for HCC were absence of anti-HBV surface antibody (HBs hazard ratio [HR], 5.018; 95% confidence interval [CI], 1.710-14.726; P = 0.003) and serum albumin < 3.8 g/dL (HR, 3.051; 95% CI, 1.318-7.067; P = 0.009). The overall mortality rate was 5.1 per 100 person-years, and the related independent factors were the presence of ascites (HR, 2.448; 95% CI, 1.142-5.210; P = 0.022), serum albumin < 3.8 g/dL (HR, 3.067; 95% CI, 1.254-8.139, P = 0.014), and nonachievement of sustained virologic response (SVR) (HR, 0.066; 95% CI, 0.001-0.484, P = 0.002).

Conclusion: The incidence of HCC in HCV-related cirrhosis seems to be high in Korea, and advanced liver disease and no achievement of SVR were associated with mortality. The absence of anti-HBs in hepatocarcinogenesis related to HCV warrants further study.
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http://dx.doi.org/10.1111/jgh.12950DOI Listing
August 2015

Accuracy of transient elastography in assessing liver fibrosis in chronic viral hepatitis: A multicentre, retrospective study.

Liver Int 2015 Oct 26;35(10):2246-55. Epub 2015 Feb 26.

Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea.

Background/aims: Transient elastography (TE) has become an alternative to liver biopsy (LB). This study investigated the diagnostic performance of liver stiffness (LS) measurement using TE in Korean patients with chronic hepatitis B and C (CHB and CHC).

Methods: From April 2006 to June 2014, 916 patients (567 CHB and 349 CHC) who underwent LB and TE at 15 centres were analyzed. The Batts and Ludwig scoring system was used for histologic assessment. Aspartate aminotransferase (AST)-to-platelet ratio indexes (APRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used.

Results: The median age, LS value, and APRI score were 45 years, 8.8 kPa, and 0.61, respectively, in CHB patients vs. 51 years, 6.8 kPa and 0.55, respectively, in CHC patients. TE was significantly superior to APRI in CHB patients (AUROC 0.774 vs. 0.72 for ≥F2, 0.849 vs. 0.812 for ≥F3, and 0.902 vs. 0.707 for F4, respectively; all P < 0.05). Furthermore, TE was significantly superior for predicting ≥ F3 stage (AUROC 0.865 vs. 0.840, P = 0.009) whereas it was similar for predicting ≥ F2 and F4 stage (AUROC 0.822 vs. 0.796; 0.910 vs. 0.884; all P > 0.05) in CHC patients. In CHB patients, optimal cut-off LS values were 7.8 kPa for ≥F2, 8.2 kPa for ≥ F3, and 11.6 kPa for F4, vs. 6.8 kPa, 8.6 kPa, and 14.5 kPa, respectively, in CHC patients.

Conclusions: TE can accurately assess the degree of liver fibrosis in Korean patients with CVH. TE was superior to APRI for predicting each fibrosis stage.
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http://dx.doi.org/10.1111/liv.12808DOI Listing
October 2015

Geographic differences in the epidemiological features of HCV infection in Korea.

Clin Mol Hepatol 2014 Dec 24;20(4):361-7. Epub 2014 Dec 24.

Division of AIDS, Korea National Institute of Health, Osong, Korea.

Background/aims: The prevalence of hepatitis C virus (HCV) infection in Korea exhibits significant geographic variation, with it being higher in Busan and Jeonam than in other areas. The reason for this intranational geographic difference was investigated in this study by conducting a comparative analysis of the risk factors related to HCV infection among three geographic areas: the capital (Seoul), Busan, and the province of Jeolla.

Methods: In total, 990 patients with chronic HCV infection were prospectively enrolled at 5 university hospitals located in Seoul (n=374), Busan (n=264), and Jeolla (n=352). A standardized questionnaire survey on the risk factors for HCV infection was administered to these three groups of patients, and a comparative analysis of the findings was performed.

Results: The analysis revealed significant regional differences in exposure to the risk factors of HCV infection. By comparison with patients in Seoul as a control group in the multivariate analysis, patients in Busan had significantly more experience of invasive medical procedures, acupuncture, cosmetic procedures, and multiple sex partners. In contrast, patients in Jeolla were significantly older, and they had a higher prevalence of hepatocellular carcinoma, a lower prevalence of multiple sex partners, and had experienced fewer invasive procedures.

Conclusions: There was a significant geographic difference in the exposure to potential risk factors of HCV infection between patients from the three studied regions. This may explain the regional variation of the prevalence of HCV infection in Korea, and should be taken into account when planning strategies for the prevention and management of HCV infection.
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http://dx.doi.org/10.3350/cmh.2014.20.4.361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278067PMC
December 2014

Tenofovir monotherapy versus tenofovir plus lamivudine or telbivudine combination therapy in treatment of lamivudine-resistant chronic hepatitis B.

Antimicrob Agents Chemother 2015 Feb 24;59(2):972-8. Epub 2014 Nov 24.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

Tenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated the antiviral efficacy and safety of TDF alone compared to those of TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (P=0.562 and P=0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has antiviral efficacy comparable to that of TDF plus LAM or LdT combination therapy, with a favorable safety profile in CHB patients with LAM-resistant HBV variants.
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http://dx.doi.org/10.1128/AAC.04454-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335865PMC
February 2015
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