Publications by authors named "Gi-Won Song"

301 Publications

Cervicocerebral atherosclerosis and its hepatic and coronary risk factors in patients with liver cirrhosis.

Clin Mol Hepatol 2021 Oct 12. Epub 2021 Oct 12.

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

Background/aims: This study aimed to investigate the silent atherosclerotic burden of cervicocephalic vessels in cirrhotic patients compared with the general population, and the relevant risk factors including coronary parameters.

Methods: The study population consisted of 993 stroke-free subjects with LC who were screened by magnetic resonance angiography (MRA) of the head and neck as a pre-liver transplant workup, and 6,099 health checkup participants who underwent MRA examination. The two cohorts were matched for cerebrovascular risk factors, and the prevalence rates of atherosclerosis in the major intracranial and extracranial arteries were compared in 755 matched pairs. Also, traditional, hepatic and coronary variables related to the cerebral atherosclerosis were assessed in cirrhotics.

Results: Overall, intracranial atherosclerosis was significantly less prevalent in the LC samples than the matched controls (2.3% vs. 5.4%; P=0.002), whereas the prevalence of extracranial atherosclerosis were similar (4.4% vs. 5.8%; P=0.242). These results were maintained in multivariate analyses in the pooled samples, with the corresponding adjusted odds ratios (ORs) for LC of 0.56 and 0.77 (95% CIs, 0.36-0.88 and 0.55-1.09), respectively. In the cirrhotic series, lower platelet count was inversely correlated with intracranial atherosclerosis (adjusted OR, 0.31; 95% CI, 0.13-0.76). Coronary artery calcium (CAC) score ≥100 was the only factor predicting both intra- and extra-cranial atherosclerosis (adjusted ORs, 4.06 and 5.43; 95% CIs, 1.45-11.41 and 2.68-11.00, respectively).

Conclusions: Our data suggest that LC confers protection against intracranial atherosclerosis, and that thrombocytopenia may be involved in this protection. High CAC score could serve as a potential surrogate for cervicocerebral vascular screening in asymptomatic cirrhotics.
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http://dx.doi.org/10.3350/cmh.2021.0202DOI Listing
October 2021

Feasibility of modified endarterectomized aortic allograft for middle hepatic vein reconstruction in living donor liver transplantation: A retrospective cohort study.

Int J Surg 2021 Sep 27;94:106124. Epub 2021 Sep 27.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: Cryopreserved allografts and artificial vascular grafts were introduced to meet the increasing demand for adequate vascular substitutes for middle hepatic vein (MHV) reconstruction during living donor liver transplantation (LDLT). This study evaluated patency outcomes after engraftment of a modified endarterectomized aortic allograft (MEAA) without any additional patches.

Methods: This retrospective double-arm study was conducted in single tertiary referral center between January 2015 and July 2018. Of 1,047 adult patients who underwent single-graft LDLT with a modified right lobe (MRL), 111 patients who received grafts with MHV reconstruction using MEAA were selected. The control group comprised 434 patients who underwent MHV reconstruction using iliac vein allografts. The main outcome measure was the short-term patency of the MEAA. The secondary outcome was the incidence of graft-associated complications.

Results: Clinically significant MHV stenoses requiring stenting occurred in 3 patients (2.7%) in the MEAA group and in 17 patients (3.9%) in the iliac vein group (P = 0.778). Three-month and one-year patency rates on Doppler ultrasonography and computed tomography were 88.5% and 54.0%, respectively, in the MEAA group and 84.0% and 42.2%, respectively, in the iliac vein group, indicating the superior patency outcomes with MEAA (P = 0.017).

Conclusions: MHV reconstruction using MEAA during LDLT of a MRL graft is technically simple, achieves clinical outcomes comparable to iliac vein grafts, and is effective in expanding the allograft vessel pool for LDLT.
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http://dx.doi.org/10.1016/j.ijsu.2021.106124DOI Listing
September 2021

Recent Improvement in Survival Outcomes and Reappraisal of Prognostic Factors in Pediatric Living Donor Liver Transplantation.

Liver Transpl 2021 Sep 18. Epub 2021 Sep 18.

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Living donor liver transplantation (LDLT) is a significant advancement for the treatment of children with end-stage liver disease given the shortage of deceased donors. The ultimate goal of pediatric LDLT is to achieve complete donor safety and zero recipient mortality. We conducted a retrospective, single-center assessment of the outcomes as well as the clinical factors that may influence graft and patient survival after primary LDLTs performed between 1994 and 2020. A Cox proportional hazards model was used for multivariate analyses. The trends for independent prognostic factors were analyzed according to the following treatment eras: 1, 1994 to 2002; 2, 2003 to 2011; and 3, 2012 to 2020. Primary LDLTs were performed on 287 children during the study period. Biliary atresia (BA; 52%), acute liver failure (ALF; 26%), and monogenic liver disease (11%) were the leading indications. There were 45 graft losses (16%) and 27 patient deaths (7%) in this population during the study period. During era 1 (n = 81), the cumulative survival rates at 1 and 5 years after LDLT were 90.1% and 81.5% for patients and 86.4% and 77.8% for grafts, respectively. During era 2 (n = 113), the corresponding rates were 92.9% and 92% for patients and 89.4% and 86.7% for grafts, respectively. During era 3 (n = 93), the corresponding rates were 100% and 98.6% for patients and 98.9% and 95.4% for grafts, respectively. In the multivariate analyses, primary diagnosis ALF, bloodstream infection, posttransplant lymphoproliferative disease, and chronic rejection were found to be negative prognostic indicators for patient survival. Based on generalized care guidelines and center-oriented experiences, comprehensive advances in appropriate donor selection, refinement of surgical techniques, and meticulous medical management may eventually realize a zero-mortality rate in pediatric LDLT.
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http://dx.doi.org/10.1002/lt.26308DOI Listing
September 2021

Comprehensive characterization of viral integrations and genomic aberrations in HBV-infected intrahepatic cholangiocarcinomas.

Hepatology 2021 Sep 3. Epub 2021 Sep 3.

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

Background And Aims: Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic effects. We sought to identify the landscape and mechanism of HBV integration, along with the genomic architecture of HBV-infected iCCA tumors.

Approach And Results: We profiled a cohort of 108 HBV-infected iCCAs using whole-genome sequencing, deep sequencing, and RNA sequencing, together with pre-constructed datasets of HBV-infected hepatocellular carcinoma (HBV-HCC; n=167) and combined hepatocellular cholangiocarcinoma (HBV-cHCC/CCA; n=59), and conventional (n=154) and fluke-related iCCAs (n=16). Platforms based on primary iCCA cell lines to evaluate the functional effects of chimeric transcripts were also used. We found that HBV had inserted at multiple sites in the iCCA genomes in 45 (41.7%) of the tumors. Recurrent viral integration breakpoints were found at 9 different sites. The most common insertional hotspot (7 tumors) was in the TERT promoter, where insertions and mutations (11 tumors) were mutually exclusive, and were accompanied by promoter hyperactivity. Recurrent HBV integration events (5 tumors) were also detected in FAT2, and were associated with enrichment of epithelial-mesenchymal transition-related genes. A distinctive intergenic insertion, between DMRTA1 and LINC01239 (chr9p21.3), had oncogenic effects through activation of the mTOR/4EBP/S6K pathway. Regarding the mutational profiles of primary liver cancers, the overall landscape of HBV-iCCA was closer to that of nonviral conventional iCCA, than to HBV-HCC and HBV-cHCC/CCA.

Conclusions: Our findings provide insight into the behavior of iCCAs driven by various pathogenic mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.
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http://dx.doi.org/10.1002/hep.32135DOI Listing
September 2021

Pediatric deceased donor liver transplantation with size reduction for recipient-graft size matching.

Ann Hepatobiliary Pancreat Surg 2021 Aug;25(3):431-435

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

We present a case of pediatric deceased donor liver transplantation using a reduced whole liver graft in a 25-month-old boy weighing 12.7 kg. After he had undergone Kasai portoenterostomy for biliary atresia, his general condition deteriorated progressively. He was enrolled on the waiting list for liver transplantation with Pediatric End-stage Liver Disease score of 15. The donor was a 51-monthold boy with body weight of 20 kg. The donor-to-recipient body weight ratio was 158%. The liver graft appeared to be larger than the recipient's abdominal cavity. Thus, we planned to do size reduction. Recipient surgery was performed following standard procedures. We performed graft outflow vein reconstruction using a modified piggyback technique like the double inferior vena cava method. Since the portal vein was hypoplastic, a side-to-side anastomosis technique was used. We also performed intraoperative portogram to embolize venous collaterals. After completing the graft implantation, we found that the liver graft was too large to be accommodated within the abdomen. After resection of the left lateral section parenchyma, we successfully performed primary closure of the abdominal wound. This patient experienced episodes of acute rejection. He has been doing well for four years after the transplantation.
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http://dx.doi.org/10.14701/ahbps.2021.25.3.431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382866PMC
August 2021

Controlled attenuation parameter measured using transient elastography for the noninvasive assessment of macrovesicular steatosis in potential living liver donors.

Ultrasonography 2021 Jun 6. Epub 2021 Jun 6.

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

Purpose: This study aimed to determine the diagnostic performance of the controlled attenuation parameter (CAP) measured using transient elastography (TE) for assessing macrovesicular steatosis (MaS) in potential living liver donors using same-day biopsy as a reference standard.

Methods: This retrospective study included 204 living liver donor candidates who underwent TE and liver biopsy on the same day between July 2013 and June 2014. The histologic degree of MaS was determined. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of CAP for diagnosing MaS of >10%, and the optimal cutoff value was identified using the maximal Youden index.

Results: Based on liver biopsy, 185 subjects had MaS of ≤10% and 19 had MaS of >10%. The CAP value was significantly correlated with the percentage of MaS on liver biopsy (r=0.635, P<0.001), and the median CAP value was significantly higher in subjects with MaS of >10% than in those with MaS of ≤10% (300 dB/m vs. 209 dB/m, P<0.001). The AUROC for diagnosing MaS of >10% by CAP was 0.938 (95% confidence interval, 0.896 to 0.967), and a CAP of >259 dB/m yielded a sensitivity of 84.2% and a specificity of 92.4%.

Conclusion: The CAP measured using TE was significantly correlated with MaS and accurately detected substantial MaS in potential living liver donors. The CAP is a promising tool for the noninvasive diagnosis of MaS and may be used to screen unsuitable living liver donor candidates.
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http://dx.doi.org/10.14366/usg.21071DOI Listing
June 2021

Salvage living donor liver transplantation versus repeat liver resection for patients with recurrent hepatocellular carcinoma and Child-Pugh class A liver cirrhosis: A propensity score-matched comparison.

Am J Transplant 2021 Aug 12. Epub 2021 Aug 12.

Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

Following curative liver resection (LR), resectable tumor recurrence in patients with preserved liver function leads to deciding between a repeat LR and a salvage liver transplantation (LT), if a donor's liver is available. This retrospective study compared survival outcomes and recurrence pattern following salvage living donor LT (LDLT) and repeat LR in patients with recurrent hepatocellular carcinoma (HCC). We reviewed the medical records of patients who underwent repeat LR (n = 163) or LDLT (n = 84) for recurrent HCC following curative resections, between January 2005 and December 2017 at a single institution. A 1:1 propensity score matching led to 42 patients per group. Disease-specific and recurrence-free survival were significantly better in the salvage LDLT group than in the repeat LR group (p = .042; HR = 2.40; 95% CI, 0.69-6.00 and p < .001; HR = 4.23; 95% CI, 2.05-8.71, respectively). Despite significant differences in recurrence patterns between the two groups (p = .019), the patient death rates, after recurrence, were similar for both groups (p = .760). This study indicates that salvage LDLT is superior to repeat LR for treating patients with transplantable, intrahepatic HCC recurrence, even in patients with Child-Pugh class A liver cirrhosis.
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http://dx.doi.org/10.1111/ajt.16790DOI Listing
August 2021

Fates of retained hepatic segment IV and its prognostic impact in adult split liver transplantation using an extended right liver graft.

Ann Surg Treat Res 2021 Jul 30;101(1):37-48. Epub 2021 Jun 30.

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

Purpose: When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft.

Methods: This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts.

Results: The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes.

Conclusion: The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.
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http://dx.doi.org/10.4174/astr.2021.101.1.37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255581PMC
July 2021

Visceral adiposity as a risk factor for lean non-alcoholic fatty liver disease in potential living liver donors.

J Gastroenterol Hepatol 2021 Jun 24. Epub 2021 Jun 24.

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

Background And Aim: This study aimed to investigate the relationship between hepatic steatosis (HS) evaluated by biopsy and visceral adiposity assessed by computed tomography in lean living liver donor candidates and to determine the risk factors for lean non-alcoholic fatty liver disease (NAFLD).

Methods: This retrospective study included 250 lean (body mass index, < 23 kg/m ) potential living liver donors (mean age, 31.1 ± 8.6 years; 141 men) who had undergone liver biopsy and abdominal computed tomography between 2017 and 2018. Anthropometry, laboratory parameters, body composition, and the degree of HS were evaluated. Logistic regression was used to identify independent predictors of lean NAFLD.

Results: The visceral fat area (VFA) was significantly correlated with the degree of HS in men (r = 0.408; P < 0.001) and women (r = 0.360; P < 0.001). The subcutaneous fat area was significantly correlated with the degree of HS in men (r = 0.398; P < 0.001), but not in women. The skeletal muscle area did not correlate with the degree of HS in either men or women. In the multivariable logistic regression analysis, the VFA (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.013-1.044; P < 0.001) and subcutaneous fat area (OR, 1.016; 95% CI, 1.004-1.028; P = 0.009) were independent risk factors for lean NAFLD in men, and the VFA (OR, 1.036; 95% CI, 1.013-1.059; P = 0.002) was an independent risk factor for lean NAFLD in women.

Conclusions: The severity of non-alcoholic fatty liver was positively correlated with visceral fat accumulation in a lean Asian population. Visceral adiposity may be a risk factor for lean NAFLD in potential living liver donors.
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http://dx.doi.org/10.1111/jgh.15597DOI Listing
June 2021

Clinicopathological correlation and post-resection outcomes of hepatic angiomyolipoma.

Ann Hepatobiliary Pancreat Surg 2021 May;25(2):215-220

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

Backgrounds/aims: Angiomyolipoma is a rare neoplasm of mesenchymal origin derived from perivascular epithelioid cells. Due to rarity, hepatic angiomyolipoma (HAML) has been often misdiagnosed as hepatocellular carcinoma (HCC) or other hypervascular liver tumors based on imaging studies. This study investigated the clinicopathological correlation and post-resection outcomes of HAML.

Methods: This retrospective observational study included 40 patients who underwent hepatic resection (HR) for HAML between 2008 and 2018.

Results: Mean age of the patients was 42.6±11.4 years and there were 30 (75.0%) females. Hepatitis B and C virus infection was present in 8 patients (20.0%) and 1 patient (2.5%), respectively. Preoperative diagnoses on imaging studies were HCC in 23 (57.5%) patients, HAML in 14 (35.0%) patients, focal nodular hyperplasia in 2 (5.0%) patients, and hepatic adenoma in 1 (2.5%) patient. Percutaneous liver biopsy was performed in 10 (25.0%) patients and HAML was diagnosed in all patients. Only 3 patients (7.5%) showed a slight elevation in the level of liver tumor markers. Major HR was performed in 10 (25.0%). Laparoscopic HR was performed in 9 (22.5%). The mean tumor size was 4.8±3.9 cm and single tumor was present in 38 (95.0%) patients. Currently, all the patients are alive without tumor recurrence during the follow-up observation period of 75.7±37.3 months.

Conclusions: HAML is a rare form of primary liver tumor and is often misdiagnosed as HCC or other hypervascular tumors. Although HAML is benign in nature, it has malignant potential, thus resection is indicated if the tumor grows or malignancy cannot be excluded.
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http://dx.doi.org/10.14701/ahbps.2021.25.2.215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180398PMC
May 2021

Comparison of skeletal muscle index-based formula and body surface area-based formula for calculating standard liver volume.

Ann Hepatobiliary Pancreat Surg 2021 May;25(2):192-197

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Backgrounds/aims: Formula-derived standard liver volume (SLV) has been clinically used for living donor liver transplantation and hepatic resection. The majority of currently available SLV formulae are based on body surface are (BSA). However, they often show a wide range of error. Skeletal muscle index measured at the third lumbar vertebra level (L3SMI) appears to reflect lean body mass. The objective of this study was to compare the accuracy of L3SMI-based formula and BSA-based formula for calculating SLV.

Methods: The study cohort was 500 hundred living liver donors who underwent surgery between January 2010 and December 2013. Computed tomography images were used for liver volumetry and skeletal muscle area measurement.

Results: The study cohort included 250 male and 250 female donors. Their age, BSA, L3SMI, and body mass index were 26.8±8.7 years, 1.68±0.16 m, 45.6±9.0 cm/m, and 21.7±2.5 kg/m, respectively. The BSA-based SLV formula was "SLV (ml)=-362.3+901.5×BSA (m) (r=0.71, r=0.50, <0.001)". The L3SMI-based SLV formula was "SLV (ml)=471.9+14.9×L3SMI (cm/m) (r=0.65, r=0.42, <0.001)". Correlation coefficients were similar in subgroup analyses with 250 male donors and 250 female donors. There was a crude correlation between L3SMI and body mass index (r=0.51, r=0.27, <0.001).

Conclusions: The results of this study suggest that SLV calculation with L3SMI-based formula does not appear to be superior to the currently available BSA-based formulae.
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http://dx.doi.org/10.14701/ahbps.2021.25.2.192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180406PMC
May 2021

Efficacy of Living Donor Liver Transplantation in Patients with Methylmalonic Acidemia.

Pediatr Gastroenterol Hepatol Nutr 2021 May 4;24(3):288-294. Epub 2021 May 4.

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Despite aggressive medical and nutritional management, patients with methylmalonic acidemia (MMA) often suffer from multi-organ damage. Early deceased donor liver transplantation (DDLT) has emerged as an intervention to prevent disease progression. We investigated the efficacy of living donor LT (LDLT) with a potential carrier of MMA and a small volume of graft in patients with MMA as an alternative to DDLT.

Methods: Of five patients (three male, two female; median age 5.7 years; range, 1.3-13.7 years), four underwent carrier LDLT, while one underwent non-carrier auxiliary LDLT. All patients received pre- and post-LT continuous renal replacement therapy and were provided with minimal restriction diet according to serum MMA level after LT. MMA levels in the serum and urine, the incidence of metabolic crisis, and clinical findings before and after LT were compared.

Results: The survival rate was 100% during 2.2 years of follow up period after LT. In all five cases, MMA titer in the serum after transplantation decreased with less restrictive diet. Metabolic crisis was not observed during the follow-up period. In addition, no patient showed progression of severe renal impairment requiring hemodialysis. Progression of delayed cognitive development was not observed. Social functioning with improved neuropsychiatric development was observed.

Conclusion: This study showed that LDLT achieved improved quality of life with less restrictive diet, therefore it could be a feasible alternative option to DDLT for the treatment of patients with MMA, even with an auxiliary LT.
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http://dx.doi.org/10.5223/pghn.2021.24.3.288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128783PMC
May 2021

Postresection prognosis of combined hepatocellular carcinoma-cholangiocarcinoma according to the 2010 World Health Organization classification: single-center experience of 168 patients.

Ann Surg Treat Res 2021 May 29;100(5):260-269. Epub 2021 Apr 29.

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

Purpose: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis.

Methods: The medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated.

Results: During the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes.

Conclusion: Postresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.
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http://dx.doi.org/10.4174/astr.2021.100.5.260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103158PMC
May 2021

Absence of association between pretransplant serum soluble programmed death protein-1 level and prognosis following living donor liver transplantation in patients with hepatocellular carcinoma.

Medicine (Baltimore) 2021 Apr;100(17):e25640

Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation.

Abstract: Programmed death protein 1 (PD-1) pathway is one of the most critical mechanisms in tumor biology of hepatocellular carcinoma (HCC). The study aimed to assess the prognostic influence of pretransplant serum soluble PD-1 (sPD-1) in patients undergoing liver transplantation for treatment of HCC.Data from 229 patients with HCC who underwent living donor liver transplantation between January 2010 and December 2015 were retrospectively evaluated. Stored serum samples were used to measure sPD-1 concentrations.Overall survival (OS) and disease-free survival (DFS) rates were 94.3% and 74.5% at 1 year; 78.2% and 59.2% at 3 years; and 75.4% and 55.5% at 5 years, respectively. Prognostic analysis using pretransplant serum sPD-1 with a cut-off of 93.6 μg/mL (median value of the study cohort) did not have significant prognostic influence on OS (P = .69) and DFS (P = .26). Prognostic analysis using sPD-1 with a cut-off of 300 μg/mL showed similar OS (P = .46) and marginally lower DFS (P = .070). Combination of Milan criteria and sPD-1 with a cutoff of 300 μg/mL showed similar outcomes of OS and DFS in patients within and beyond Milan criteria. Multivariate analysis revealed that only Milan criteria was an independent prognostic for OS and DFS, but pretransplant sPD1 with a cut-off of 300 μg/mL did not become a prognostic factor.The results of this study demonstrate that pretransplant serum sPD-1 did not show significant influences on post-transplant outcomes in patients with HCC. Further large-scale, multicenter studies are necessary to clarify the role of serum sPD-1 in liver transplantation recipients.
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http://dx.doi.org/10.1097/MD.0000000000025640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084037PMC
April 2021

Reduction of Visceral Adiposity as a Predictor for Resolution of Nonalcoholic Fatty Liver in Potential Living Liver Donors.

Liver Transpl 2021 Oct 26;27(10):1424-1431. Epub 2021 Jul 26.

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

This study aimed to determine the factors associated with resolution of nonalcoholic fatty liver (NAFL) after lifestyle intervention in potential living liver donors as assessed by the gold standards in a longitudinal setting. This retrospective study included 115 potential living liver donors (mean age, 30.5 ± 7.5 years; 101 men) with NAFL who underwent paired liver biopsies and abdominal computed tomography (CT) examinations before and after lifestyle intervention between January 2011 and December 2018. Anthropometry, laboratory parameters, body composition, and hepatic steatosis (HS) were evaluated before and after lifestyle intervention. Anthropometry, laboratory parameters, body composition, and HS were significantly decreased after lifestyle intervention (all, P < 0.001). Relative changes in HS were weakly correlated with relative changes in the visceral fat area (VFA; r = 0.278; P = 0.003) and subcutaneous fat area (r = 0.382; P < 0.001), but not with body weight, body mass index, or skeletal muscle area. Patients with resolved NAFL after lifestyle intervention had significantly lower VFA at follow-up than those with persistent NAFL (mean ± standard deviation, 69.8 ± 39.1 versus 91.5 ± 41.4 cm ; P = 0.01). Multivariable logistic regression analysis demonstrated that the relative reduction of VFA (odds ratio per percent, 1.031; 95% confidence interval, 1.010-1.053; P = 0.004) was a significant independent factor associated with resolved NAFL after lifestyle intervention. In potential living liver donors with NAFL, the reduction of VFA is a significant factor associated with the resolution of NAFL after lifestyle intervention.
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http://dx.doi.org/10.1002/lt.26071DOI Listing
October 2021

Clinical impact of mild to moderate pulmonary hypertension in living-donor liver transplantation.

Transpl Int 2021 06 22;34(6):1150-1160. Epub 2021 Apr 22.

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

Severe pulmonary hypertension (PHT) is a contraindication to liver transplantation (LT); however, the prognostic implication of mild to moderate PHT in living-donor LT (LDLT) is unknown. The study cohort retrospectively included 1307 patients with liver cirrhosis who underwent LDLT. PHT was defined as a mean pulmonary artery pressure (PAP) of ≥25 mmHg, measured intraoperatively just before surgery. The primary endpoint was graft failure within 1 year after LDLT, including retransplantation or death from any cause. The secondary endpoints were in-hospital adverse events. In the overall cohort, the median Model for End-stage Liver Disease-Sodium (MELD-Na) score was 19, and 100 patients (7.7%) showed PHT. During 1-year follow-up, graft failure occurred in 94 patients (7.2%). Patients with PHT had lower 1-year graft survival (86% vs. 93.4%, P = 0.005) and survival rates (87% vs. 93.6%, P = 0.011). Mean PAP was associated with a high risk of in-hospital adverse events and 1-year graft failure. Adding the mean PAP to the clinical risk model improved the risk prediction. In conclusion, mild to moderate PHT was associated with higher risks of 1-year graft failure and in-hospital events, including mortality after LDLT in patients with liver cirrhosis. Intraoperative mean PAP can help predict the early clinical outcomes after LDLT.
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http://dx.doi.org/10.1111/tri.13875DOI Listing
June 2021

Post-resection prognosis of combined hepatocellular carcinoma-cholangiocarcinoma cannot be predicted by the 2019 World Health Organization classification.

Asian J Surg 2021 Mar 22. Epub 2021 Mar 22.

Department of Surgery and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

Background: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) has wide histologic diversity. This study investigated the prognostic impacts of cHCC-CCA histology according to the 2019 World Health Organization (WHO) classification.

Methods: This retrospective observational study included 153 patients who underwent surgical resection for cHCC-CCA at Asan Medical Center between August 2012 and July 2019.

Results: During the study period, 153 patients, 112 (73.2%) men and 41 (26.8%) women with a mean age of 56.4 ± 10.8 years, underwent R0 resection for cHCC-CCA. Mean tumor diameter was 4.2 ± 2.6 cm, and 147 (96.1%) patients had solitary tumors. According to 2019 WHO classification, 111 (72.5%) patients had cHCC-CCA alone, and 29 of them (26.1%) showed stem cell features. cHCC-CCA-intermediate cell carcinoma and cHCC-CCA-cholangiolocellular carcinoma were identified in 27 (17.6%) and 15 (9.8%), respectively. The 1-, 3-, and 5-year tumor recurrence and patient survival rates were 31.8% and 92.1%, 49.8% and 70.9%, and 59.0% and 61.7%, respectively. Univariate analyses revealed that significant prognostic factors were tumor size >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th American Joint Committee on Cancer (AJCC) tumor stage, and status of stem cell features. Multivariate analysis revealed 8th AJCC tumor stage and status of stem cell features as independent prognostic factors. 2019 WHO classification was not associated with post-resection prognosis.

Conclusions: 2019 WHO classification was not associated with post-resection prognosis, thus was considered as simplified histologic classification requiring prognostic validation. We suggest that stem cell features should be included as an essential component of the pathology report for cHCC-CCA.
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http://dx.doi.org/10.1016/j.asjsur.2021.03.002DOI Listing
March 2021

Change in hepatic volume profile in potential live liver donors after lifestyle modification for reduction of hepatic steatosis.

Abdom Radiol (NY) 2021 08 25;46(8):3877-3888. Epub 2021 Mar 25.

Division of Liver Transplantation and Hepatobiliary Surgery, Departments of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

Purpose: We aimed to evaluate changes in hepatic volume and hemiliver volume percentage in potential liver donors after hepatic steatosis (HS) reduction through lifestyle modification.

Methods: Fifty liver donor candidates with HS (macrovesicular fat [MaF] ≥ 20%) underwent abdominal computed tomography (CT) and liver biopsy before (baseline) and after (follow-up) lifestyle modification. According to the change in MaF, subjects were classified as group A (MaF reduction ≥ 20%, n = 25), and group B (MaF reduction < 20%, n = 25). The hepatic volume and hemiliver volume percentage were measured using CT volumetric analysis.

Results: Volume percentage of the left hemiliver + S1 (over the whole liver) significantly increased at follow-up in group A (P < 0.001) but not in group B (P = 0.598). The absolute volume change of the right hemiliver and its percentage change from the baseline were significantly greater than those of the left hemiliver + S1 in group A (P < 0.007). There were no significant differences in these values in group B (P = 0.064 and 0.507, respectively). The percentage of subjects that earned the benefit of becoming suitable donors from the change in hepatic volume distribution caused by HS improvement was 52.0% (13/25) and 40.0% (10/25) in group A and group B, respectively. Regarding posthepatectomy liver failure, none was identified in group A after donation, whereas 12% (3/25) was identified in group B.

Conclusion: Hepatic volume profile may change considerably in potential liver donors with HS (MaF ≥ 20%) after HS reduction through lifestyle modification. Reevaluation of the hepatic volume is required before liver procurement after lifestyle modification in these subjects.
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http://dx.doi.org/10.1007/s00261-021-03058-zDOI Listing
August 2021

Post-resection prognosis of patients with hepatic epithelioid hemangioendothelioma.

Ann Surg Treat Res 2021 Mar 26;100(3):137-143. Epub 2021 Feb 26.

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

Purpose: Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. This retrospective, single-center study evaluated the outcomes of hepatic resection (HR) in patients with hepatic EHE.

Methods: Over the 10-year period from 2009 to 2018, 11 patients with hepatic EHE underwent HR, accounting for 0.1% of the 11,979 adults who underwent HR at our center. Diagnosis of hepatic EHE was confirmed by immunohistochemical staining for CD34, CD31, and factor VIII-related antigen.

Results: The 11 patients included 9 females (81.8%) and 2 males (18.2%) with mean age of 43.5 ± 13.6 years. Preoperative imaging resulted in a preliminary diagnosis of suspected liver metastasis or EHE, with 9 patients (81.8%) undergoing liver biopsy. No patient presented with abnormally elevated concentrations of liver tumor markers. The extents of HR were determined by tumor size and location from trisectionectomy to partial hepatectomy. All patients recovered uneventfully from HR. Five patients showed tumor recurrence, with 4 receiving locoregional treatments for recurrent lesions. The 1-, 3- and 5-year disease-free survival rates were 90.9%, 54.5%, and 54.5%, respectively. Currently, all patients remain alive and are doing well. Univariate analysis on tumor recurrence showed that tumor size ≥ 4 cm was significantly associated with tumor recurrence (P = 0.032), but tumor number ≥ 4 was not related to (P = 0.24).

Conclusion: Hepatic EHE is a rare form of primary liver tumor often misdiagnosed as a metastatic tumor. Because of its malignant potential, HR is indicated if possible. HR plus, when necessary, treatment of recurrence yields favorable overall survival rates in patients with hepatic EHE.
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http://dx.doi.org/10.4174/astr.2021.100.3.137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943284PMC
March 2021

Renal Recovery After Liver Transplantation Alone in Patients With Liver Cirrhosis and Severe Chronic Kidney Disease With Normal Kidney Size.

Transplant Proc 2021 Jun 23;53(5):1719-1725. Epub 2021 Mar 23.

Division of Liver Transplantation and Hepato-Biliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Background: Most guidelines recommend simultaneous liver-kidney transplantation (SLKT) in patients with liver cirrhosis (LC) and severe chronic kidney disease (CKD) over liver transplantation alone (LTA). CKD, however, is not irreversible. This study evaluates the reversibility of kidney disease after LTA based on kidney size.

Materials And Methods: In this single-center retrospective study, we classified 90 patients with LC and severe CKD into 3 groups: the normal kidney (NK)-LTA group (n=39), small kidney (SK)-LTA group (both kidneys <9 cm at the time of LTA, n=40), and SK-SLKT group (n=11).

Results: The NK-LTA group had a lower percentage of hepatocellular carcinoma and a higher pre-liver transplantation (LT) estimated glomerular filtration rate. This group, however, was older, received livers from a higher percentage of deceased donors, and had a higher Child-Pugh score. Renal recovery, defined as the return of creatinine to their baseline, or a persistent change from baseline but not persistent (≥3 months) need for renal replacement therapy after LT, was found in 79% in the NK-LTA group, which was higher than 7.5% in the SK-LTA group. Renal and patient survival was found in 56% of the NK-LTA group, which was higher than 2.5% of the SK-LTA group.

Conclusions: There is a high percentage of renal recovery in the NK-LTA group, and accordingly, this does not justify SLKT, since this would result in a "waste" of kidneys. Therefore, KT after LT is recommended over SLKT for the LC patients with NK size.
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http://dx.doi.org/10.1016/j.transproceed.2021.01.016DOI Listing
June 2021

Safe use of right lobe living donor livers with moderate steatosis in adult-to-adult living donor liver transplantation: a retrospective study.

Transpl Int 2021 05 30;34(5):872-881. Epub 2021 Mar 30.

Division of Transplantation, Department of Surgery, and Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN, USA.

Hepatic steatosis (HS) beyond a certain degree can jeopardize living donor (LD) safety, particularly in right lobe (RL) donors, making it a major obstacle for donor pool expansion in adult-to-adult living donor liver transplantation (ALDLT). From July 2004 to June 2016, 58 LDs donated their RLs despite having moderate HS (30%-50% steatosis) determined by intraoperative biopsy at a single center. We performed greedy matching to compare the outcomes of the donors and recipients of this group with those of LDs with no HS. The mean left lobe (LL) HS value in the 58 cases was 20.9 ± 12.4%, which was significantly lower than the mean RL HS value (38.8 ± 6.7%, P < 0.001). The mean ratio of the remnant LL to the total liver volume was 37.8 ± 2.2. No differences were observed in the postoperative liver function and donor and recipient morbidity and mortality rates. The liver regeneration rates in recipients and donors at 1 month, 6 months, and 1 year postoperatively did not differ significantly. The patient and graft survival rates of the recipients showed no differences. The use of well-selected RL grafts with moderate steatosis does not impair graft function, recipient outcomes, or donor safety.
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http://dx.doi.org/10.1111/tri.13859DOI Listing
May 2021

Patency of Hemashield grafts versus ringed Gore-Tex grafts in middle hepatic vein reconstruction for living donor liver transplantation.

Ann Hepatobiliary Pancreat Surg 2021 Feb;25(1):46-53

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Backgrounds/aims: Owing to the short supply of homologous vein allografts, we previously used ringed Gore-Tex vascular grafts for middle hepatic vein (MHV) reconstruction in living donor liver transplantation. When ringed Gore-Tex grafts became unavailable, we used Hemashield vascular grafts. This study aimed to compare the patency and complication rates of Hemashield and ringed Gore-Tex grafts.

Methods: This retrospective two-arm study compared the study group that received Hemashield grafts (n=157) and the propensity score-matched control group that received ringed Gore-Tex grafts (n=157).

Results: In the Hemashield and Gore-Tex groups, the recipient age was 54.7±9.4 and 53.3±6.3 years; Model for End-stage Liver Disease scores were 15.9±9.2 and 16.9±8.3; and graft-recipient weight ratios were 1.07±0.24 and 1.10±0.23, respectively. In the Hemashield group, V5 reconstruction was performed using single (n=113, 72.0%), double (n=39, 24.8%), and triple (n=3, 1.9%) anastomoses. The proportion of double and triple anastomoses for V5 and V8 was higher in the Hemashield group than in the Gore-Tex group. Two (1.3%) patients required MHV conduit stenting owing to early thrombosis of the Hemashield graft. There was no difference in conduit occlusion- free patient survival rates between groups (=0.91). The incidence of accidental conduit migration in the Hemashield and Gore-Tex groups was 0 (0%) and 2 (1.3%), respectively.

Conclusions: Hemashield grafts used in MHV reconstruction demonstrated acceptably high short- and mid-term patency rates, no incidences of conduit migration, easy handling, and good flexibility for length adjustment. Therefore, we suggest that the Hemashield graft is the preferentially suitable prosthetic material for MHV reconstruction.
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http://dx.doi.org/10.14701/ahbps.2021.25.1.46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952673PMC
February 2021

Clinicopathological features and post-resection outcomes of inflammatory pseudotumor of the liver.

Ann Hepatobiliary Pancreat Surg 2021 Feb;25(1):34-38

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

Backgrounds/aims: Hepatic inflammatory pseudotumor (HIPT) is a rare disease characterized by chronic infiltration of inflammatory cells and area of fibrosis. The objective of this retrospective observational study was to investigate clinicopathological features and outcomes of patients who underwent hepatic resection (HR) for HIPT.

Methods: From 2009 to 2018, seven patients with HIPT underwent HR, accounting for 0.06% of 11,979 adults who underwent HR at our center.

Results: These seven patients included five men and two women. Their mean age was 62.3±11.6 years. In four patients with hepatitis B virus (HBV)-associated liver cirrhosis or chronic hepatitis, liver masses were suspected of hepatocellular carcinoma (HCC) or combined HCC-cholangiocarcinoma based on imaging studies. In three patients without HBV infection, two patients were suspected of HCC, for whom liver biopsy was not performed. One patient was suspected of liver abscess or HIPT, for whom percutaneous liver biopsy was performed and the mass was diagnosed with HIPT. However, this patient underwent HR owing to abdominal pain. No patient presented with abnormally elevated levels of alpha-fetoprotein, protein induced by vitamin K absence or antagonist-II, or CA19-9. During a mean follow-up period of 76.4±34.8 months, no patient experienced recurrence of HIPT.

Conclusions: HIPT, a rare form of liver disease, is often misdiagnosed as malignant liver tumor. Active histological diagnosis is warranted for patients with suspected HIPT to avoid unnecessary operation. HR can be indicated in case of diagnostic ambiguity of HIPT or under a clinical diagnosis of malignant liver tumor.
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http://dx.doi.org/10.14701/ahbps.2021.25.1.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952659PMC
February 2021

Clinicopathological features and post-resection outcomes of hepatocellular adenoma.

Ann Hepatobiliary Pancreat Surg 2021 Feb;25(1):25-33

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

Backgrounds/aims: Hepatocellular adenomas (HCA) are rare benign liver tumors with the potential of malignant transformation and risk of bleeding. We investigated the clinicopathological features and outcomes of HCA in 19 patients who underwent surgical resection.

Methods: This retrospective observational study included 19 patients who underwent hepatic resection during a 9-year period from 2011 to 2019.

Results: The incidence of HCA was 0.18% of all hepatic resection cases during the study period. The mean age of the patients was 34.3±9.6 years, and 12 patients (63.2%) were female. Abdominal pain was present as initial clinical manifestation in 5 patients and the other 14 patients had no specific symptoms. HCA was diagnosed in 7 out of 8 patients who underwent liver biopsy. R0 resection was performed in 18 patients (94.7%) and laparoscopic liver resection was performed in 11 patients (57.9%). The mean tumor size was 5.6±3.6 cm and 17 patients had a single tumor. Immunohistochemical analysis of the resected tumor specimens revealed hepatocyte-nuclear-factor-1 mutated HCA in 2 (10.5%), -catenin-mutated HCA in 2 (10.5%), inflammatory HCA in 12 (63.2%) and unclassified HCA in 3 (15.8%). There were no pathognomonic findings in the preoperative liver imaging studies among these four groups. Currently, all patients are alive with a mean follow-up period of 40.1±26.3 months. One patient showed residual tumors after incomplete resection.

Conclusions: Surgical resection may be indicated if imaging studies show diagnostic ambiguity, growing tumor or symptomatic mass. Because of the risk of tumor recurrence and malignant transformation, long-term follow-up is necessary.
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http://dx.doi.org/10.14701/ahbps.2021.25.1.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952660PMC
February 2021

Implication of CD69 CD103 tissue-resident-like CD8 T cells as a potential immunotherapeutic target for cholangiocarcinoma.

Liver Int 2021 04 23;41(4):764-776. Epub 2021 Feb 23.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.

Background: The heterogeneous immune landscapes of intrahepatic cholangiocarcinoma (ICC) remain largely unknown. Here we aimed to investigate the implications of tissue-resident memory (TRM)-related features of tumour-infiltrating CD8 T cells (CD8 TILs) from ICC patients.

Methods: From ICC patients, we obtained blood samples and ICC surgical specimens (n = 33). We performed multicolour flow cytometry, multiplexed immunohistochemistry and RNA sequencing.

Results: When compared to peripheral CD8 T cells, the CD8 TILs included significantly higher proportions of the CD69 CD103 and CD69 CD103 TRM-like subsets (P < .001 for both). Relative to CD69 and CD69 CD103 cells, the CD69 CD103 CD8 TILs harboured higher levels of T-cell markers representing tumour specificity (ie CD39), proliferation (ie Ki-67) and T-cell activation (ie HLA-DR and CD38) (all P < .001). Moreover, compared to the stroma, the tumour margin and core density each had a significantly higher density of CD103 CD8 TILs (P < .001 for both). ICCs with high proportions of CD69 CD103 cells displayed higher levels of parameters associated with response to immune checkpoint inhibitors (ICIs)-including number of CD8 TIL infiltrates (P = .019), PD-L1 expression in the tumour (P = .046) and expression of the T cell-inflamed gene signature (P < .001). ICCs with lower proportions of CD69 CD103 CD8 TILs exhibited significant enrichment of genes related to the Wnt/β-catenin (P < .001) and TGF-β pathways (P = .002).

Conclusion: CD69 CD103 TRM-like CD8 TILs represent prominent tumour-specific immune responses and hold promise as a potential therapeutic target in ICC patients. Differential TRM-related features of ICCs may help develop future immunotherapeutic strategies such as maximizing TRM responses or inhibiting pathways contributing to immune evasion.
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http://dx.doi.org/10.1111/liv.14814DOI Listing
April 2021

Quantitative Prognostic Prediction Using ADV Score for Hepatocellular Carcinoma Following Living Donor Liver Transplantation.

J Gastrointest Surg 2021 Oct 2;25(10):2503-2515. Epub 2021 Feb 2.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea.

Background: We assessed the prognostic impact of the ADV score (α-fetoprotein [AFP]-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score) for predicting hepatocellular carcinoma (HCC) recurrence and patient survival after living donor liver transplantation (LDLT).

Methods: This study included 843 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. These cases were divided into treatment-naïve (TN, n = 256]) and pretransplant-treated (PT, n = 587 [69.6%]) groups.

Results: There were weak or nearly no correlations among AFP, DCP, and TV. There existed high correlations between the pretransplant and explant findings regarding tumor number, size, and ADV score. Right lobe grafts were implanted in 760 (90.2%) patients. HCC recurrence and all-cause patient death occurred in 182 (15.9%) and 126 (15.0%) respectively during the follow-up period for 75.6 ± 35.5 months. The 5-year tumor recurrence (TR) and overall patient survival (OS) rates were 21.5% and 86.2%, respectively. The PT group showed higher TR (p < 0.001) and lower OS rates (p < 0.001). TR and OS were closely correlated with both pretransplant and explant ADV scores in the TN and PT groups. The ADV score enabled further prognostic stratification of the patients within and beyond the Milan, UCSF, and Asan Medical Center criteria. Compared with the 7 pre-existing selection criteria, ADV score with a cutoff of 5log showed the highest prognostic contrast regarding TR and OS.

Conclusions: Our prognostic prediction model using ADV scores is an integrated quantitative surrogate biomarker for posttransplant prognosis in HCC patients and can provide reliable information that assists the decision-making for LDLT.
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http://dx.doi.org/10.1007/s11605-021-04939-wDOI Listing
October 2021

The Real Impact of Bridging or Downstaging on Survival Outcomes after Liver Transplantation for Hepatocellular Carcinoma.

Liver Cancer 2020 Dec 28;9(6):721-733. Epub 2020 Oct 28.

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

Introduction: There is no consensus regarding selection criteria on liver transplantation (LT) for hepatocellular carcinoma (HCC), especially for living donor liver transplantation, although emerging evidence has been found for the effectiveness of bridging or downstaging.

Objective: We evaluated the long-term outcomes of patients who underwent LT with or without bridging or downstaging for HCC.

Methods: This retrospective study included 896 LT recipients with HCC between June 2005 and May 2015. Recurrence-free survival (RFS), overall survival (OS), and their associated factors were evaluated.

Results: The 5-year RFS in the full cohort of 896 patients was 82.4%, and the OS was 85.3%. In patients with initial Organ Procurement and Transplantation Network (OPTN) T1 and T2, the 5-year RFS and OS did not significantly differ between LT groups with and without bridging (all ≥ 0.05). The 5-year RFS and OS of OPTN T3 patients with successful downstaging were not significantly different from those of patients with OPTN T2 with primary LT ( = 0.070 and = 0.185), but were significantly higher than in patients with OPTN T3 with downstaging failure and initial OPTN T1 or T2 with progression (all < 0.001). In the multivariate analysis, last alpha-fetoprotein before LT ≥70 ng/mL (hazard ratio [HR]: 1.77, = 0.001; HR: 1.72, = 0.004), pretransplant HCC status exceeding the Milan criteria (HR: 5.12, < 0.001; HR: 3.31, < 0.001), and positron emission tomography positivity (HR: 2.57, < 0.001; HR: 2.57, < 0.001) were independent predictors for worse RFS and OS.

Conclusions: The impact of bridging therapy on survival outcomes is limited in patients with early-stage HCC, whereas OPTN T1 or T2 with progression provides worse prognosis. OPTN T3 should undergo LT after successful downstaging, and OPTN T3 with successful downstaging allows for acceptable long-term posttransplant outcomes.
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http://dx.doi.org/10.1159/000507887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768098PMC
December 2020

Single-Center Experience of Living Donor Liver Transplantation for Patients With Secondary Biliary Cirrhosis.

Transplant Proc 2021 Jan-Feb;53(1):98-103. Epub 2020 Dec 16.

Department of Surgery, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea.

Background: Secondary biliary cirrhosis (SBC) represents a unique form of cirrhosis that develops in the liver secondary to persistent biliary obstruction. This study aimed to review the living donor liver transplants (LDLTs) performed at our center for patients with SBC and end-stage liver disease and to share the perioperative strategies undertaken to achieve satisfactory outcomes.

Methods: The medical records of 29 patients who underwent LDLT for SBC between December 1994 and July 2018 at the Asan Medical Center (Seoul, South Korea) were retrospectively reviewed. Their clinical data were extracted and statistically analyzed. Survival curves were computed.

Results: The perioperative and in-hospital morbidity rates were 72.4% and 10.3%, respectively. The overall mean recipient follow-up was 80.0 (SD, 66.4) months (range, 0.8-246.8 months). Patient survival rates after 1, 3, 5, and 10 years after transplant were 82.8%, 79.3%, 79.3%, and 79.3%, respectively. For liver grafts, the survival rates were 82.8%, 75.8%, 75.8%, and 75.8% at 1, 3, 5, and 10 years, respectively.

Conclusions: LDLT is potentially a final lifesaving resort for patients with SBC with portal hypertension. However, considering the difficulty of surgery and perioperative management, LDLT should be performed by experienced transplant surgeons in a center where a multidisciplinary approach is possible.
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http://dx.doi.org/10.1016/j.transproceed.2020.10.044DOI Listing
April 2021

Living Donor Liver Transplantation Versus Deceased Donor Liver Transplantation for Hepatocellular Carcinoma Within or Beyond the Milan Criteria: Comparable Long-Term Outcomes.

Transplant Proc 2021 Jan-Feb;53(1):92-97. Epub 2020 Dec 5.

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

Background: The long-term outcomes after living donor liver transplantation (LDLT) vs deceased donor liver transplantation (DDLT) for hepatocellular carcinoma (HCC) remain controversial. We compared the long-term outcomes between LDLT and DDLT in patients with HCCs within or beyond the Milan criteria.

Methods: This retrospective study included 896 patients who underwent liver transplantation (829 LDLTs and 67 DDLTs) for HCC from June 2005 to May 2015. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method with log-rank test.

Results: RFS at 1, 3, 5, and 10 years after LDLT was 89.6%, 84.6%, 82.4%, and 79.6%, respectively, and, after DDLT, was 92.4%, 86.2%, 82.4%, and 82.4%, respectively, and OS at 1, 3, 5, and 10 years after LDLT was 96.1%, 88.1%, 85.6%, and 82.7%, respectively, and, after DDLT, was 97.0%, 83.6%, 82.1%, and 77.3%, respectively, with no significant differences in RFS (P = .838) or OS (P = .293) between groups. No statistically significant differences after LDLT or DDLT were identified in RFS (89.8% vs 98.1%, respectively, at 5 years; P = .053) or OS (90.4% vs 90.6% , respectively, at 5 years; P = .583) for HCCs meeting the Milan criteria as well as for those beyond the Milan criteria (RFS, 37.8% vs 28.6%, respectively, at 5 years; P = .560 and OS, 57.3% vs 50.0%, respectively, at 5 years; P = .743).

Conclusions: Patients who underwent LDLT for HCCs showed comparable long-term outcomes to patients who underwent DDLT. Patients with HCCs within the Milan criteria demonstrated acceptable long-term outcomes after both LDLT and DDLT.
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http://dx.doi.org/10.1016/j.transproceed.2020.10.012DOI Listing
April 2021

Pediatric liver transplantation with hyperreduced left lateral segment graft.

Ann Hepatobiliary Pancreat Surg 2020 Nov;24(4):503-512

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

Backgrounds/aims: To prevent large-for-size graft-related complications in small infant patients, the size of a left lateral segment (LLS) graft can be reduced to be a hyperreduced LLS (HRLLS) graft.

Methods: This study was intended to describe the detailed techniques for harvesting and implanting HRLLS grafts developed in a high-volume liver transplantation (LT) center.

Results: The mean recipient age was 4.0±1.7 months (range: 3-6) and body weight was 5.3±1.4 kg (range: 4.1-6.9). Primary diagnoses of the recipients were progressive familial intrahepatic cholestasis in 2 and biliary atresia in 1. The types of LT were living donor LT in 1 and split deceased donor LT in 2. Non-anatomical size reduction was performed to the transected LLS grafts. The mean weight of the HRLLS grafts was 191.7±62.1 g (range: 120-230) and graft-recipient weight ratio was 3.75±1.57% (range: 2.45-5.49). Widening venoplasty was applied to the graft left hepatic vein outflow orifice. Vein homograft interposition was used in a case with portal vein hypoplasia. Types of the abdomen wound closure were one case of primary repair, one of two-staged closure with a mesh, and one of three-staged repair with a silo and a mesh. All three patients recovered uneventfully from the LT operation and are doing well to date for more than 6 years after transplantation.

Conclusions: Making a HRLLS graft through non-anatomical resection during living donor LT and split deceased donor LT can be a useful option for treating small infant patients.
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http://dx.doi.org/10.14701/ahbps.2020.24.4.503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691208PMC
November 2020
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