Hyo-Sin Kim

Telbivudine protects renal function in patients with chronic hepatitis B infection in conjunction with adefovir-based combination therapy

Previous studies have demonstrated that the treatment of chronic hepatitis B (CHB) infection with adefovir (ADV) can impair renal function. In contrast, treatment with telbivudine (LdT) improves renal function in CHB patients. The aim of this study was to evaluate the renoprotective effect of LdT in CHB patients receiving ADV‐based combination therapy. The effects of treatment with ADV + LdT on renal function were compared to those resulting from treatment with ADV + entecavir (ETV), ADV + lamivudine (LAM), ADV alone and ETV alone. The consecutive cohort analysis included 831 CHB patients who received ADV + LdT, ADV + LAM, ADV + ETV, ADV alone or ETV alone for 96 weeks. Alterations in estimated glomerular filtration rate (eGFR) were compared between the five groups using a linear mixed‐effects model. HBV DNA levels were also compared between the five groups during the 96‐week period. Among the five treatment groups, significant improvements in eGFR were observed in the ADV + LdT and ADV + LAM groups over time (P < 0.001 for each group compared with baseline eGFR). In patients with a baseline eGFR between 50 and 90 mL/min, the change in eGFR was the most significant in the ADV + LdT group (+0.641 mL/min; P < 0.001). Age, gender, baseline eGFR and treatment option were significant predictive factors for eGFR changes. In conclusion, our results suggest that the combination therapy of LdT and ADV is significantly associated with renoprotective effects in CHB patients when compared with other ADV‐based combination or single therapies.

Living donor liver transplantation for hepatocellular carcinoma in Seoul National University

BACKGROUND Liver transplantation is an effective treatment modality for hepatocellular carcinoma (HCC). Due to deceased organ shortage, living donor liver transplantation (LDLT) accounts for the majority of liver transplants in Korea. The aim of this study is to evaluate the recent trend of LDLT for HCC, and to suggest guidelines and criteria for selecting the appropriate candidates for LDLT. METHODS Between January 2000 and December 2015, 532 patients underwent LDLT for HCC. Clinicopathologic data were analyzed as well as overall survival rate (SR) and disease-free survival rate (DFSR) according to the Milan criteria based on explant pathology, positron emission tomography (PET) positivity, and serum alpha-fetoprotein (AFP) level. RESULTS The 5-year overall SR and DFSR were 81.5% and 75.5% respectively. According to our previously reported combination of AFP and PET [Seoul National University Hospital (SNUH) criteria]; low risk group [AFP <200 ng/mL, PET (-)], intermediate risk group [AFP >200 ng/mL, PET (-) or AFP <200 ng/mL, PET (+)], and high risk group [AFP >200 ng/mL, PET (+)], the 5-year DFSR of low risk group was 86.1%, intermediate risk group was 79.0%, and high risk group was 18.5% (P<0.001). Within the Milan criteria, the 5-year DFSR of low risk group was 88.4%, intermediate risk group was 79.9%, and high risk group was 60.0% (P=0.016). Beyond the Milan criteria, the 5-year DFSR of low, intermediate, and high risk group was 80.3%, 77.7%, and 9.1%, respectively (P<0.001). CONCLUSIONS In conclusion, our data and experience suggest that a continued paradigm shift from a conventional size based criteria to a biological marker based criteria is indicated when evaluating LDLT candidates with HCC.

Effect of PNPLA3 I148M polymorphism on histologically proven non-alcoholic fatty liver disease in liver transplant recipients: Effect of PNPLA3 polymorphism on post-LT NAFLD

PNPLA3 I148M polymorphism (rs738409 C>G) is the most important and best‐known polymorphism for non‐alcoholic fatty liver disease (NAFLD). However, little is known about the effect of this polymorphism on NAFLD after liver transplantation (LT). We aimed to evaluate the association between this polymorphism and post‐LT NAFLD.

Tips and pitfalls in direct ligation of large spontaneous splenorenal shunt during liver transplantation

Patients with large spontaneous splenorenal shunts (SRSs) prove challenging during liver transplantation (LT), regardless of organizing portal vein (PV) thrombosis. Here, we detail the clinical outcomes of 26 patients who underwent direct ligation of large SRSs during LT. Direct ligation of large SRS was applied in poor portal flow during LT. We performed temporary test clamping of the SRS before direct ligation and applied PV pressure monitoring in patients who showed signs of portal hypertension, such as bowel edema. We retrospectively reviewed and evaluated their clinical outcomes. Among 843 patients who underwent LT between 2010 and 2015, 26 (3.1%) underwent direct ligation of SRS without any intraoperative event. Mean preoperative Model for End‐Stage Liver Disease score was 16.7 ± 9.0. The main PV diameter on preoperative computed tomography was 8.3 ± 3.4 mm (range, 3.0‐14.0 mm). SRS was easily identified at just below the distal pancreas and beside the inferior mesenteric vein in all patients. Accompanying PV thrombectomy was done in 42.3% of patients. Among 26 patients, massive and prolonged ascites was evident in 15.4% (n = 4) postoperatively. They were all living donor LT recipients with a small PV diameter (4.0‐6.7 mm). Except for 1 patient who underwent splenic artery embolization, ascites was tolerable and well controlled by conservative management. There was a 7.7% rate of major complications related to direct ligation, including reoperation due to combined ligation of SRS along with a left renal vein at the confluence. Except for 1 hospital mortality due to sepsis, 25 patients (96.2%) are alive with no evidence of further PV complications. In conclusion, direct ligation of large SRS during LT is a safe and feasible method to overcome the effects of a large SRS. Liver Transplantation 23 899–906 2017 AASLD.

Pretransplantation fetal-maternal microchimerism in pediatric liver transplantation from mother

AIM To investigate the rates of pretransplantation fetal-maternal microchimerism (MC) and its effect on rejection in children receiving maternal liver grafts. METHODS DNA or blood samples before liver transplantation (LT) were available in 45 pediatric patients and their mothers. The presence of pretransplantation MC to non-inherited maternal antigens (NIMAs) (NIMA-MC) in the peripheral blood was tested using nested PCR-single-strand conformation polymorphism analysis for the human leukocyte antigen (HLA)-DRB1 alleles. NIMA-MC was successfully evaluated in 26 of the 45 children. Among these 45 pediatric LT recipients, 23 children (51.1%) received transplants from maternal donors and the other 22 from non-maternal donors. RESULTS Among these 26 children, pretransplantation NIMA-MC was detected in 23.1% (n = 6), 6.1 (range, 0.8-14) years after birth. Among the children with a maternal donor, the rate of biopsy-proven cellular rejection (BPCR) was 0% in patients with NIMA-MC positivity (0/3) and those with HLA-DR identity with the mother (0/4), but it was 50% in those with NIMA-MC negativity (5/10). Patients with NIMA-MC positivity or HLA-DR identity with the mother showed significantly lower BPCR rate compared with NIMA-MC-negative patients (0% vs 50%, P = 0.04). NIMA-MC-positive patients tended to show lower BPCR rate compared with NIMA-MC-negative patients (P = 0.23). CONCLUSION The presence of pretransplantation NIMA-MC or HLA-DR identity with the mother could be associated with BPCR-free survival in pediatric recipients of LT from maternal donors.

Evaluation of donor workups and exclusions in a single‐center experience of living donor liver transplantation

The process of evaluating potential donors in liver transplantation is important to ensure donor safety and provide optimal recipient outcomes. However, there has been no report about donor exclusion rates and reasons for such exclusion in Korea. In this study, we aimed to elucidate the outcomes of potential living liver donor evaluation in a major living donor liver transplantation center. From July 2011 to June 2015, prospectively collected data of 726 potential donors for 588 matched recipients were subsequently evaluated. Among 726 potential donors, 374 potential donors (51.5%) finally reached donation; 352 potential donors (48.5%) were excluded for various reasons. Donor reasons were 29.8%, including medical problems, withdrawal of consent, graft volume issues, and identification of a better suitable donor. Recipient reasons were 20.7%, including recipient death or recovery, allocation to deceased donor, and progressions of hepatocellular carcinoma. A total of 38 (5.2%) potential donors had a fatty liver. Among them, 15 (39.5%) potential donors tried short‐term weight reduction and eventually were able to donate. In conclusion, the main reasons for donor exclusion were medical problems and withdrawal of consent. Therefore, thorough medical screening and careful examination for donor voluntarism are important in the donor evaluation process. Liver Transplantation 23 614–624 2017 AASLD.

Living donor liver transplantation using a right anterior section of the liver

The foremost obstacle of adult-to-adult living donor liver transplantation (LDLT) is the adequacy of the graft size for balancing demand of the recipient and safety of the donor. To overcome this issue, various novel approaches have been attempted, such as using the right posterior section graft and left trisection graft. In the same manner, a right anterior section (RAS) graft can make up the balance of the recipient’s demand and safety of the donor although it is technically complex and elaborate. In this case report, we describe our experience of an adult-to-adult LDLT using a RAS graft and suggest the possible use of 3 liver grafts from 1 cadaveric liver. Case Report

The correlation between preoperative volumetry and real graft weight: comparison of two volumetry programs

Purpose Liver volumetry is a vital component in living donor liver transplantation to determine an adequate graft volume that meets the metabolic demands of the recipient and at the same time ensures donor safety. Most institutions use preoperative contrast-enhanced CT image-based software programs to estimate graft volume. The objective of this study was to evaluate the accuracy of 2 liver volumetry programs (Rapidia vs. Dr. Liver) in preoperative right liver graft estimation compared with real graft weight. Methods Data from 215 consecutive right lobe living donors between October 2013 and August 2015 were retrospectively reviewed. One hundred seven patients were enrolled in Rapidia group and 108 patients were included in the Dr. Liver group. Estimated graft volumes generated by both software programs were compared with real graft weight measured during surgery, and further classified into minimal difference (≤15%) and big difference (>15%). Correlation coefficients and degree of difference were determined. Linear regressions were calculated and results depicted as scatterplots. Results Minimal difference was observed in 69.4% of cases from Dr. Liver group and big difference was seen in 44.9% of cases from Rapidia group (P = 0.035). Linear regression analysis showed positive correlation in both groups (P < 0.01). However, the correlation coefficient was better for the Dr. Liver group (R2 = 0.719), than for the Rapidia group (R2 = 0.688). Conclusion Dr. Liver can accurately predict right liver graft size better and faster than Rapidia, and can facilitate preoperative planning in living donor liver transplantation.

Sirolimus and Metformin Synergistically Inhibits Colon Cancer In Vitro and In Vivo

We estimated the effect of various immunosuppressants (ISs) and metformin (M) to provide theoretical background of optimal therapeutic strategy for de novo colon cancer after liver transplantation (LT). Three colon cancer cell lines (HT29, SW620, and HCT116) were used in in vitro studies. HT29 was also used in BALB/c-nude mice animal models. Following groups were used in both in vitro and in vivo studies: sirolimus (S), tacrolimus (T), cyclosporin A (CsA), M, metformin/sirolimus (Met/S), metformin/tacrolimus (Met/T), and metformin/cyclosporin A (Met/CsA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed and western blot analyses were performed for mTOR pathway proteins, apoptosis proteins, and epithelial-mesenchymal-transition (EMT) proteins. Tumor volume was measured for 4 weeks after inoculation. MTT-assay revealed significant cell viability inhibition in all 3 colon cancer cell lines in groups of S, M, and Met/S. Of note, group Met/S showed synergistic effect compare to M or S group. Western blot analysis showed significant low levels of all investigated proteins in groups of S and Met/S in both in vitro and in vivo experiment. Tumor growth was significantly inhibited only in the Met/S group. Combination of Met and S showed the most potent inhibition in all colon cancer cell lines. This finding might have application for de novo colon cancer.

Korean Patients Undergoing Deceased Donor Liver Transplantation for Alcoholic Liver Disease Have Non-Inferior Survival Outcomes than for Hepatitis B Virus: a Real-World Experience without Minimum Abstinence before Transplantation

Few studies have compared outcomes in patients undergoing liver transplantation (LT) for hepatitis B virus (HBV) and alcoholic liver disease (ALD) in Asian countries in which living donor LT (LDLT) is dominant, where HBV is endemic and where there are no strict regulations on pre-transplant abstinence for ALD. This study compared post-LT outcomes of deceased donor LT (DDLT) in patients with ALD and HBV. Data from 220 patients who underwent primary DDLT at Seoul National University Hospital from January 2010 to December 2014, including 107 with HBV and 38 with ALD, were retrospectively analyzed. Seventy-four patients (69.2%) in the HBV group and 30 (78.9%) in the ALD group had United Network for Organ Sharing (UNOS) status 2A (P = 0.250). There were no significant differences in their 1-year (90.7% vs. 92.1%) and 3-year (82.1% vs. 82.3%) overall survival rates (P = 1.000). Multivariate analysis showed that high serum gamma glutamyltransferase concentration (≥ 70 IU/L) was independently prognostic of 1-year post-LT overall survival. Survival outcomes following DDLT were similar in Korean patients with ALD and HBV, even in the absence of strict pre-transplant abstinence from alcohol as a selection criterion.