1.Outcomes of living donor liver transplantation using graft with multiple hepatic arteries on the graft: Propensity score-matched analysis
Minyu KANG ; Hwa-Hee KOH ; Deok-Gie KIM ; Seung Hyuk YIM ; Mun Chae CHOI ; Eun-Ki MIN ; Jae Geun LEE ; Dong Jin JOO ; Myoung Soo KIM
Annals of Liver Transplantation 2024;4(1):30-36
Background:
This study aims to analyze the outcomes of living donor liver transplantation (LDLT) using grafts with multiple hepatic arteries (HAs), compared to those with a single HA.
Methods:
A retrospective analysis was conducted on 1,059 LDLT patients from July 2005 to December 2022 at Severance Hospital, South Korea. Patients were categorized into multiple-HA and single-HA groups. Propensity score matching was employed to balance baseline characteristics, with primary outcomes being graft survival and secondary outcomes including HA, biliary, and total vascular complications.
Results:
The study included 27 patients in the multiple-HA group and 925 in the single-HA group before matching. After propensity score matching, no significant difference in 5-year graft survival rates was observed between the groups (60.4% for multiple-HA vs. 72.8% for single-HA, p=0.172). However, the multiple-HA group exhibited a higher incidence of bile duct complications (80.0% vs. 48.3%, p=0.038).Multivariable Cox regression analysis did not find multiple HAs to be a significant predictor of graft loss but confirmed their association with increased bile duct complications.
Conclusion
LDLT using grafts with multiple HAs does not adversely affect overall graft survival compared to single-HA grafts. Nevertheless, the increased risk of bile duct complications associated with multiple HAs necessitates careful surgical planning and postoperative management to mitigate this risk.
2.Carbapenem-resistant gram-negative rod bacteremia in the early postoperative period following liver transplantation
Eun-Ki MIN ; Deok-Gie KIM ; Minyu KANG ; Hwa-Hee KOH ; Jae Geun LEE ; Dong Jin JOO ; Myoung Soo KIM
Annals of Liver Transplantation 2024;4(1):16-22
Background:
Carbapenem-resistant gram-negative rod bacteremia (CRGNR-B) is emerging as a formidable challenge, complicating patient management and outcomes in liver transplantation (LT). This study aimed to investigate the incidence, mortality, and risk factors associated with CRGNR-B within 90 days following LT.
Methods:
A retrospective nested case-control study was conducted using single centric LT data (n=1,379). CRGNR-B cases were matched 1:5 with control patients for analyzing survival and risk factors for CRGNR-B.
Results:
The incidence of CRGNR-B within 90 days post-LT was 6.5% (n=87). The CRGNR-B group showed significantly lower 1-year post-LT survival compared to the control group (37.9% vs. 90.0%, p<0.001). CRGNR-B was significantly correlated with increased mortality after adjustment of covariates (adjusted hazard ratio, 5.66;95% confidence interval [CI], 3.89–8.24; p<0.001). Key risk factors identified include higher pretransplant model for end-stage liver disease scores (odds ratio [OR], 1.05;95% CI, 1.01–1.09; p=0.006), encephalopathy prior to transplant (OR, 2.79; 95% CI, 1.48–5.30; p=0.002), retransplantation (OR, 10.4; 95% CI, 2.79–42.1; p<0.001), each 60-minute increase in cold ischemic time (OR, 1.20; 95% CI, 1.01–1.42; p=0.037), and bile duct complications (OR, 6.16; 95% CI, 2.66–14.2; p<0.001).
Conclusion
The occurrence of CRGNR-B within 90 days post-LT poses a significant risk to patient survival, with identifiable pre- and peri-transplant risk factors. These findings underscore the importance of targeted preventive measures, early detection, and effective management strategies to enhance outcomes for LT recipients.
3.Graft-versus-host disease in liver transplantation: Experience in the Korean single center
Hwa-Hee KOH ; Deok-Gie KIM ; Minyu KANG ; Eun-Ki MIN ; Jae Geun LEE ; Dong Jin JOO ; Myoung Soo KIM
Annals of Liver Transplantation 2024;4(2):56-62
Background:
This investigation delves into the intricacies of graft-versus-host disease (GVHD) in the context of liver transplantation (LT), focusing on the experiences from a Korean single center. Despite GVHD’s relatively low incidence, its severe implications on patient mortality underscore the urgent need for advanced management and comprehension strategies.
Methods:
In a retrospective analysis at Severance Hospital, Korea, we reviewed 1,107 adult LT recipients from January 2009 to March 2023, excluding those who succumbed within 14 days post-transplantation, to scrutinize the manifestation, treatment, and outcomes of GVHD. Diagnostic approaches ranged from skin to colonoscopic biopsies, with interventions including high-dose corticosteroids and tailored immunosuppressive adjustments.
Results:
GVHD was diagnosed in 1.3% of the study cohort, predominantly identified through skin biopsies. Critical findings include the significant role of donor liver characteristics and recipient pre-transplant conditions in GVHD development. Notably, GVHD affected patients exhibited markedly lower survival rates at one year compared to their non-GVHD controls (21.4% vs. 90.2%, p<0.001), with deceased donor liver transplants and human leukocyte antigen one-way mismatches between donor and recipient identified as significant GVHD risk factors.
Conclusion
This study reaffirms the severe impact of GVHD on post-LT patient survival and highlights specific risk factors associated with its development. Enhanced understanding and targeted management of these risk factors are crucial for improving outcomes for LT recipients facing this complex complication.
4.Validation of risk factors for graft-torecipient weight ratio less than 0.8 graft in living donor liver transplantation with single center data
Young Jin YOO ; Minyu KANG ; Hwa-Hee KOH ; Eun-Ki MIN ; Jae Geun LEE ; Myoung Soo KIM ; Dong Jin JOO ; Deok-Gie KIM
Annals of Liver Transplantation 2024;4(2):80-85
Background:
The use of small grafts, defined by a graft-to-recipient weight ratio (GRWR) less than 0.8, is possibly associated with an increased risk of graft loss in living donor liver transplantation (LDLT). This study aims to validate risk factors for graft loss in LDLT with GRWR<0.8 using single-center data.
Methods:
LDLT recipients, who received GRWR<0.8 graft at Severance Hospital, between July 2007 and December 2022, were categorized based on the number of risk factors identified in previous Korean multicentric study: recipient age ≥60 years, model for end-stage liver disease (MELD) score ≥15, and male donor. Baseline characteristics and graft survival were compared among these groups.
Results:
The median GRWR was 0.74 (interquartile range 0.69–0.78) and minimum was 0.49. Recipients with more risk factors exhibited lower graft survival rates: 100% at 5 years in the Risk 0 group (n=18), 72.7% in the Risk 1 group (n=20), and 54.5% in the Risk≥2 group (n=18, p=0.015). This trend was similar in subgroups of right lobe graft and the others (left lobe plus right posterior lobe), although not statistically significant. Donor age did not significantly affect graft survival in GRWR<0.8 transplants (78.9% for donor age≥45 vs. 69.2% for donor age<45, p=0.25).
Conclusion
This study confirms that the number of risk factors, including recipient age, MELD score, and donor sex, significantly impacts graft survival in LDLT with GRWR<0.8. These findings highlight the need for careful recipient and donor selection to improve outcomes in LDLT.
5.Comparison of pharmacokinetics and safety characteristics between two olopatadine hydrochloride 5 mg tablet formulations in healthy Korean subjects
Jae Hoon KIM ; Minyu LEE ; Namsick KIM ; Tae-Young OH ; Seung-Kwan NAM ; Yoon Seok CHOI ; In Sun KWON ; Jin Gyu JUNG ; Jang Hee HONG
Translational and Clinical Pharmacology 2021;29(1):65-72
Histamine acts by binding to four histamine receptors (H1 to H4), of which the H1 is known to participate in dilate blood vessels, bronchoconstriction, and pruritus. Olopatadine hydrochloride blocks the release of histamine from mast cells and it inhibits H1 receptor activation. Olopatadine hydrochloride is anti-allergic agent that is effectively used. The object of this study had conducted to compare the pharmacokinetics (PKs) and safety characteristics between olopatadine hydrochloride 5 mg (test formulation) and olopatadine hydrochloride 5 mg (reference formulation; Alerac® ) in Korean subjects. This study had conducted an open-label, randomized, fasting condition, single-dose, 2-treatment, 2-period, 2-way crossover. Subjects received single-dosing of reference formulation or test formulation in each period and blood samples were collected over 24 hours after administration for PK analysis. A wash-out period of 7 days was placed between the doses. Plasma concentration of olopatadine were determined using liquid chromatography-tandem spectrometry mass (LC-MS/MS). A total of 32 subjects were enrolled and 28 subjects completed. There were not clinical significantly different in the safety between two treatment groups for 32 subjects who administered the study drug more than once. The geometric mean ratio of test formulation to reference formulation and its 90% confidence intervals for The peak plasma concentration (Cmax ) and the areas under the plasma concentration–time curve from 0 to the last concentration (AUClast ) were 1.0845 (1.0107–1.1637) and 1.0220 (1.0005–1.0439), respectively. Therefore, the test formulation was bioequivalent in PK characteristics and was equally safe as the reference formulation.
6.Pharmacokinetic comparison of two bazedoxifene acetate 20 mg tablet formulations in healthy Korean male volunteers
Ji-Sun YEUN ; Hye-Su KAN ; Minyu LEE ; Namsick KIM ; Tae-Young OH ; Seung-Kwan NAM ; Yoon Seok CHOI ; In Sun KWON ; Jang Hee HONG
Translational and Clinical Pharmacology 2020;28(2):102-108
Bazedoxifene, used as bazedoxifene acetate, is a selective estrogen receptor modulator that selectively affects the uterus, breast tissue, bone metabolism, and lipid metabolism by antagonizing or enhancing estrogens in the estrogen receptor in the tissue. This study was conducted as an open, randomized, two-period, two-treatment, crossover design to compare the pharmacokinetic (PK) characteristics and tolerability of two bazedoxifene tablets when administered to 50 healthy Korean male volunteers. Enrolled subjects were randomly allocated to 2 sequences of a single oral administration of a test drug and a reference drug, or vice versa with a 14-day washout period between the two doses. Serial blood samples were collected over 96 h for PK analysis. Plasma concentration of bazedoxifene was assayed using liquid chromatography-tandem spectrometry mass. Forty-five participants completed the study with no clinically relevant safety issues. The peak concentrations (Cmax, mean ± strandard deviation) of reference drug and test drug were 3.191 ± 1.080 and 3.231 ± 1.346 ng/mL, respectively, and the areas under the plasma concentration‐time curve from 0 to the last measurable concentration (AUClast) were 44.697 ± 21.168 ng∙h/mL and 45.902 ± 23.130 ng∙h/mL, respectively. The geometric mean ratios of test drug to reference drug and their 90% confidence intervals for Cmax and AUClast were 0.9913 (0.8828–1.1132) and 1.0106 (0.9345–1.0929), respectively. The incidence of adverse events between the two formulations was similar. The present study showed that PK and tolerability of two bazedoxifene tablet formulations were comparable when administered to healthy Korean male volunteers.

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