Publications by authors named "Jae-Won Joh"

276 Publications

Cost-effectiveness and long-term outcomes of liver transplantation using hepatitis B core antibody-positive grafts with hepatitis B immunoglobulin prophylaxis in Korea.

Clin Mol Hepatol 2021 Sep 8. Epub 2021 Sep 8.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background/aims: Hepatitis B core antibody (anti-HBc)-positive donors are used as an extended donor pool, and current guidelines recommend the usage of nucleos(t)ide analogues (NAs) as prophylaxis for preventing de novo hepatitis B virus infection (DNH). We analyzed the long-term outcomes of a large cohort of liver transplantation (LT) patients receiving anti-HBc-positive grafts and evaluated the risk of DNH when hepatitis B immunoglobulin (HBIG) monotherapy was used as prophylaxis. We also compared the cost-effectiveness of HBIG and NAs.

Methods: We retrospectively reviewed 457 patients with anti-HBc-positive grafts and 898 patients with anti-HBc-negative grafts who underwent LT between January 2001 and December 2018. We compared recipient characteristics according to the anti-HBc status of the donor, and compared the costs of using NAs for the rest of the patient's life and using HBIG to maintain hepatitis B surface antibody titers above 200 IU/L.

Results: The 1-, 5-, and 10-year patient survival rates were 87.7%, 73.5%, and 67.7%, respectively, in patients with anti-HBc-positive grafts, and 88.5%, 77.4%, and 70.3%, respectively, in patients with anti-HBc-negative grafts (P=0.113). Among 457 recipients with anti-HBc-positive grafts, 117 (25.6%) were non-HBV recipients. The overall incidence of DNH was 0.9%. When using HBIG under insurance coverage, the cumulative cost was lower compared with using NA continuously without insurance coverage in Korea.

Conclusions: Anti-HBc-positive grafts alone do not affect patient survival or graft survival. HBIG monoprophylaxis has good outcomes for preventing DNH, and the patient's long-term cost burden is low in Korea because of the national insurance system in this cohort.
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http://dx.doi.org/10.3350/cmh.2021.0137DOI Listing
September 2021

Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma.

J Cancer Res Clin Oncol 2021 Aug 30. Epub 2021 Aug 30.

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Background: ZMYND8 (Zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8) has been known to play an important role in tumor regulation in various types of cancer. However, the results of ZMYND8 expression and their clinical significance in hepatocellular carcinoma (HCC) have not yet been published. In the present study, we investigate the expression of ZMYND8 protein and mRNA in HCC and elucidate its prognostic significance.

Methods: ZMYND8 protein and mRNA expression in 283 and 234 HCCs were investigated using immunohistochemistry and microarray gene expression profiling data. The relationships between ZMYND8 expression with clinicopathologic features and prognosis of HCC patients were evaluated. Furthermore, we performed the invasion, migration, apoptosis, soft agar formation assay and sphere formation assay in HCC cell lines, and evaluated tumorigenicity in a nude mouse model, after ZMYND8 knockdown.

Results: Overexpression of ZMYND8 protein and mRNA was observed in 20.5% and 26.9% of HCC cases, respectively. High ZMYND8 expression showed significant correlations with microvascular invasion, high Edmondson grade, advanced American Joint Committee on Cancer, and increased alpha-fetoprotein level. ZMYND8 mRNA overexpression was an independent prognostic factor for predicting early recurrence as well as short recurrence-free survival (RFS). Downregulation of ZMYND8 reduced migration and invasion of HCC cells, and promoted apoptosis of HCC cells in an in vitro model. In a xenograft nude mouse model, knockdown of ZMYND8 significantly reduced tumor growth.

Conclusion: ZMYND8 mRNA overexpression could be a prognostic marker of shorter RFS in HCC patients after curative resection. ZMYND8 might play an important role in the proliferation and progression of HCC and could be a promising candidate for targeted therapy.
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http://dx.doi.org/10.1007/s00432-021-03768-3DOI Listing
August 2021

Clinical impact of the treatment modality on small, solitary, recurrent intrahepatic hepatocellular carcinomas after primary liver resection.

Ann Surg Treat Res 2021 Aug 29;101(2):85-92. Epub 2021 Jul 29.

Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

Purpose: The aim of this study was to determine the survival benefit based on different treatment strategies in patients with small, solitary, recurring intrahepatic hepatocellular carcinomas (HCCs) that were defined as recurred Barcelona Clinic Liver Cancer stage O (reBCLC-O).

Methods: Among the 917 patients with HCC recurrence after primary hepatic resection, 394 patients with reBCLC-O were selected. Of these, 150 patients underwent curative treatment (re-resection, radiofrequency ablation, and liver transplantation) and 203 underwent transarterial chemoembolization (TACE) group for recurrent HCC. After propensity score matching (PSM), both the groups were well balanced (89 patients in each group).

Results: Before PSM, the 1-, 3-, and 5-year overall survival (OS) rates of patients in the curative treatment group (96.7%, 78.6%, and 70.5%, respectively) were significantly better than those in the TACE treatment group (95.6%, 53.7%, and 44.2%, respectively) (P < 0.001). After PSM, the 1-, 3-, and 5-year OS rates also differed significantly (92.0%, 79.6%, and 71.1% in the curative treatment group vs. 88.8%, 65.6%, and 57.9% in the TACE group) (P = 0.005). The independent predictors of worse OS were tumor number at the time of resection and treatment modality for the recurrence, time interval to recurrence, and prothrombin time international normalized ratio and alpha-fetoprotein levels at the time of recurrence.

Conclusion: The OS of patients in the curative treatment group was better than that in the non-curative treatment group after PSM. Based on our results, curative treatment should be strongly recommended in the patients with reBCLC-O recurrence for better survival.
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http://dx.doi.org/10.4174/astr.2021.101.2.85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331554PMC
August 2021

Risk factors for poor survival after recurrence of hepatocellular carcinoma after liver transplantation.

Ann Surg Treat Res 2021 Jul 30;101(1):28-36. Epub 2021 Jun 30.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: This study was designed to analyze the risk factors for poor survival after recurrence of hepatocellular carcinoma after liver transplantation.

Methods: Patients who underwent liver transplantation for hepatocellular carcinoma during the period of 2007 to 2018 were reviewed and patients who experienced recurrence were included. Multivariable Cox proportional hazard ratios were performed for potential risk factors for survival after recurrence.

Results: A total of 151 recipients experienced hepatocellular carcinoma recurrence after liver transplantation. The median of the recurrence-free period was 9.3 months (0.89-97.25 months). The median follow-up after recurrence was 13.4 months (0.59-118.28 months). One-, 3-, and 5-year survival after recurrence were 65.2%, 34.0% and 20.5%, respectively. Multivariable Cox analysis showed that, graft from living donor (hazard ratio [HR], 0.430; 95% confidence interval [CI], 0.210-0.882; P = 0.021), recurrence-free interval of ≥9 months (HR, 0.257; 95% CI, 0.164-0.403; P < 0.001), alphafetoprotein of ≥100 ng/mL at the time of recurrence (HR, 1.689; 95% CI, 1.059-2.695; P = 0.028), and recurrence in bone (HR, 2.304; 95% CI, 1.399-3.794; P = 0.001) and everolimus within 3 months after recurrence (HR, 0.354; 95% CI, 0.141-0.889; P = 0.027) were related to survival after recurrence.

Conclusion: Although survival was generally poor after recurrence of hepatocellular carcinoma in liver transplantation recipients, prolonged survival can be achieved in certain patients with better prognostic factors.
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http://dx.doi.org/10.4174/astr.2021.101.1.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255579PMC
July 2021

Tailored Prediction Model of Survival after Liver Transplantation for Hepatocellular Carcinoma.

J Clin Med 2021 Jun 28;10(13). Epub 2021 Jun 28.

Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea.

This study aimed to create a tailored prediction model of hepatocellular carcinoma (HCC)-specific survival after transplantation based on pre-transplant parameters. Data collected from June 2006 to July 2018 were used as a derivation dataset and analyzed to create an HCC-specific survival prediction model by combining significant risk factors. Separate data were collected from January 2014 to June 2018 for validation. The prediction model was validated internally and externally. The data were divided into three groups based on risk scores derived from the hazard ratio. A combination of patient demographic, laboratory, radiological data, and tumor-specific characteristics that showed a good prediction of HCC-specific death at a specific time (t) were chosen. Internal and external validations with Uno's C-index were 0.79 and 0.75 (95% confidence interval (CI) 0.65-0.86), respectively. The predicted survival after liver transplantation for HCC (SALT) at a time "t" was calculated using the formula: [1 - (HCC-specific death(t'))] × 100. The 5-year HCC-specific death and recurrence rates in the low-risk group were 2% and 5%; the intermediate-risk group was 12% and 14%, and in the high-risk group were 71% and 82%. Our HCC-specific survival predictor named "SALT calculator" could provide accurate information about expected survival tailored for patients undergoing transplantation for HCC.
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http://dx.doi.org/10.3390/jcm10132869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268829PMC
June 2021

Prediction model for early graft failure after liver transplantation using aspartate aminotransferase, total bilirubin and coagulation factor.

Sci Rep 2021 06 18;11(1):12909. Epub 2021 Jun 18.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.

This study was designed to build models predicting early graft failure after liver transplantation. Cox regression model for predicting early graft failure after liver transplantation using post-transplantation aspartate aminotransferase, total bilirubin, and international normalized ratio of prothrombin time was constructed based on data from both living donor (n = 1153) and deceased donor (n = 359) liver transplantation performed during 2004 to 2018. The model was compared with Model for Early Allograft Function Scoring (MEAF) and early allograft dysfunction (EAD) with their C-index and time-dependent area-under-curve (AUC). The C-index of the model for living donor (0.73, CI = 0.67-0.79) was significantly higher compared to those of both MEAF (0.69, P = 0.03) and EAD (0.66, P = 0.001) while C-index for deceased donor (0.74, CI = 0.65-0.83) was only significantly higher compared to C-index of EAD. (0.66, P = 0.002) Time-dependent AUC at 2 weeks of living donor (0.96, CI = 0.91-1.00) and deceased donor (0.98, CI = 0.96-1.00) were significantly higher compared to those of EAD. (both 0.83, P < 0.001 for living donor and deceased donor) Time-dependent AUC at 4 weeks of living donor (0.93, CI = 0.86-0.99) was significantly higher compared to those of both MEAF (0.87, P = 0.02) and EAD. (0.84, P = 0.02) Time-dependent AUC at 4 weeks of deceased donor (0.94, CI = 0.89-1.00) was significantly higher compared to both MEAF (0.82, P = 0.02) and EAD. (0.81, P < 0.001). The prediction model for early graft failure after liver transplantation showed high predictability and validity with higher predictability compared to traditional models for both living donor and deceased donor liver transplantation.
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http://dx.doi.org/10.1038/s41598-021-92298-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213713PMC
June 2021

Surgical treatment outcomes of primary hepatic sarcomas: A single-center experience.

World J Hepatol 2021 May;13(5):584-594

Department of Surgery, Samsung Medical Center, Seoul 06351, South Korea.

Background: Primary hepatic sarcoma is a rare tumor originated from mesenchymal tissue. There are various pathologic types of primary hepatic sarcoma and the treatment outcome of this tumor was usually disappointing. Unlike hepatocellular carcinoma, outcome of primary hepatic sarcoma is not well-known due to it's rarity. However, with development of medical technology, surgical treatment may lead to better survival.

Aim: To investigate the surgical outcomes of primary hepatic sarcoma, we gathered and analyzed the cases of a single institute.

Methods: From August 2001 to September 2016, a total of nine patients were surgically treated for primary hepatic sarcoma after exclusion of cases with open and closure, early loss to follow-up and sarcomatoid hepatocellular carcinoma and sarcomatoid cholangiocellular carcinoma. Baseline characteristics, tumor characteristics such as tumor pathology, size and number, surgical and adjuvant treatments were reviewed. Tumor recurrence, and patient survival were analyzed with retrospective approach.

Results: The enrolled participants included five patients with angiosarcoma and four patients with undifferentiated sarcoma. All patients experienced tumor recurrence at a median of 52 post-operative days. Only two patients survived and the 5-year survival rate was 29.6%. One patient with angiosarcoma who received central hepatectomy for primary tumor and received radiofrequency ablation for recurrent tumor still lives for 11 years. One patient with undifferentiated sarcoma received Rt. lobectomy for primary tumor followed by chemotherapy and radiation therapy still lives around 30 mo even though she got additional operation for recurrent tumor. Two patients who received living donor liver transplantation due to angiosarcoma died. Only adjuvant therapy was associated with survival gain ( = 0.002).

Conclusion: Patients with primary hepatic sarcoma may gain survival benefit with surgical resection followed by adjuvant therapy, even though the outcome remains relatively poor.
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http://dx.doi.org/10.4254/wjh.v13.i5.584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173340PMC
May 2021

Application of three-dimensional printing for intraoperative guidance during liver resection of a hepatocellular carcinoma with sophisticated location.

Ann Hepatobiliary Pancreat Surg 2021 May;25(2):265-269

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

While 3D printing is adapted usefully in certain field of surgery, its application in liver surgery was limited. Here, we introduce our experience for using 3D printing for intraoperative guidance during liver resection in a case for HCC with an intrahepatic metastasis at a sophisticated location. A 50 years old male patient was diagnosed 4.7 cm-sized hepatocellular carcinoma located on segment 3 with and an intrahepatic metastasis located on segment 8 which was between right anterior portal vein, middle hepatic vein and right hepatic vein. Since radiofrequency ablation appeared to be inappropriate, surgical resection was planned. However, the patient had a cirrhotic liver and left liver was estimated to be 47% according to volume measurement. Therefore, we planned a two-step procedure by performing left hemihepatectomy preserving the middle hepatic vein and additionally removing the intrahepatic metastasis by tumorectomy. For better guidance, we made a 3D printed model tailored for using it as a guidance during operation, and the accuracy of 3D-printed model helped the surgical team perform a safe operation. The patient underwent adjuvant proton beam therapy on the site of tumorectomy and did not experience recurrence.
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http://dx.doi.org/10.14701/ahbps.2021.25.2.265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180396PMC
May 2021

Adjuvant therapy using -expanded allogenic natural killer cells in hepatectomy patients with hepatitis B virus related solitary hepatocellular carcinoma: MG4101 study.

Ann Hepatobiliary Pancreat Surg 2021 May;25(2):206-214

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Backgrounds/aims: Fewer reports have been published regarding hepatectomy patients with solitary hepatocellular carcinoma (HCC) who received immunotherapeutic agents as adjuvant therapy. We evaluated the safety and efficacy of -expanded allogenic natural killer (NK) cells in those patients with modified International Union Against Cancer (UICC) stage T3.

Methods: From August 2014 to October 2015, five patients who underwent hepatic resection received -expanded allogenic NK cells. Patients received five rounds of NK cells (2-3×10 cells/kg) at postoperative 4, 6, 8, 12, and 16 weeks. This study is registered with ClinicalTrials.gov, number NCT02008929.

Results: The median age of the five patients (three men and two women) was 44.8 years (range, 36-54 years). All had hepatitis B virus-related HCC, and the median tumor size was 2.2 cm (range, 2.1-8.2 cm). None of the patients had any adverse events. HCC recurrence developed in two patients at one year after hepatic resection, but four patients were alive at 3 years. The two recurrence-free patients showed a higher ratio of CD8+ T lymphocyte populations before and after administration of -expanded allogenic NK cells compared with the three patients who experienced recurrence.

Conclusions: Immunotherapy using -expanded allogenic NK cells in hepatectomy patients can be used safely. Further studies should be investigated for efficacy.
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http://dx.doi.org/10.14701/ahbps.2021.25.2.206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180393PMC
May 2021

Quantitative analysis of contrast-enhanced ultrasonography following living donor liver transplantation: early diagnosis of middle hepatic venous occlusion.

Med Ultrason 2021 May 20. Epub 2021 May 20.

Department of Surgery, Samsung Medical Center.

Aim: This study aimed to evaluate whether a quantitative contrast-enhanced ultrasonography (CEUS) study is feasible to diagnose middle hepatic venous occlusion after living donor liver transplantation (LDLT).

Materials And Methods: From December 2018 to July 2019, the CEUS study on the first postoperative day had been conducted in patients who underwent LDLT. 46 patients were finally included in the study. To obtain CEUS parameters from time-intensity curves (TICs) on the hepaticparenchyma, the two regions of interests (ROIs) were located in the right hepatic vein (RHV) territory and middle hepatic vein (MHV) territory of the right hepatic graft. The measured CEUS parameters were wash-in slope (WIS), peak intensity (PI), time to peak (TTP), and area under the curve (AUC). The subjects were classified into the occlusion and non-occlusion groups. In each group, the parameters measured in the RHV and MHV territories were compared with paired-sample Student'st-tests.

Results: Hepatic venous occlusion was diagnosed in 25 patients (54%). The WIS, TTP, and AUC of the MHV territory (2.95 dB/sec; 22.39 sec; 204.27 dB·sec, respectively) were significantly different from those of the RHV territory (2.16 dB/sec; 25.81 sec; 165.66 dB·sec; all p<0.05). There were no statistically significant differences in PI between the MHV and RHV territories (19.08 dB vs. 18.27 dB, respectively; p=0.259). In the non-occlusion group, there was no parameter which was significantly different between MHV and RHV territories (p>0.05).

Conclusion: The parametric analysis of CEUS can help diagnose middle hepatic venous occlusion after LDLT.
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http://dx.doi.org/10.11152/mu-2906DOI Listing
May 2021

Sex difference in the tolerance of hepatic ischemia-reperfusion injury and hepatic estrogen receptor expression according to age and macrosteatosis in healthy living liver donors.

Transplantation 2021 Feb 22. Epub 2021 Feb 22.

1From the Department of Anesthesiology and Pain Medicine 2 Department of Surgery Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3From the Department of Obstetrics and Gynecology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea 4Statistics and Data Center, Samsung Medical Center, Seoul, Korea 5 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Hepatic estrogen signaling, which is important in liver injury/recovery, is determined by the level of systemic estrogen and hepatic estrogen receptor. We aimed to evaluate whether female's advantage in the tolerance of hepatic ischemia-reperfusion injury decreases according to the age of 40 y (systemic estrogen decrease) and macrosteatosis (hepatic estrogen receptor decrease).

Methods: We included 358 living liver donors (128 females and 230 males). The tolerance of hepatic ischemia-reperfusion injury was determined by the slope of the linear regression line modeling the relationship between the duration of intraoperative hepatic ischemia and the peak postoperative transaminase level. Estrogen receptor content was measured in the biopsied liver samples using immunohistochemistry.

Results: In the whole cohort, the regression slope for aspartate transaminase was comparable between females and males (P=0.940). Within the subgroup of ≤40 y donors, the regression slope was significantly smaller in females (P=0.031), whereas it was comparable within >40 y donors (P=0.867). Within the subgroup of ≤40 y non-macrosteatotic donors, the regression slope was significantly smaller in females in univariable (P=0.002) and multivariable analysis (P=0.006), whereas the sex difference was not found within ≤40 y macrosteatotic donors (P=0.685). Estrogen receptor content was significantly greater in females within ≤40 y non-macrosteatotic donors (P=0.021), whereas it was not different in others of >40 y or with macrosteatosis (P=0.450).

Conclusions: The tolerance of hepatic ischemia-reperfusion injury was greater in females than in males only when they were <40 y and without macrosteatosis. The results were in agreement with hepatic estrogen receptor immunohistochemistry study.
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http://dx.doi.org/10.1097/TP.0000000000003705DOI Listing
February 2021

Predictors and outcome of emergent Liver transplantation for patients with acute-on-chronic liver failure.

Dig Liver Dis 2021 Aug 27;53(8):1004-1010. Epub 2021 Apr 27.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background And Aims: Controversy exists over whether emergent liver transplantation (LT) should be performed for patients with acute-on-chronic liver failure (ACLF), especially for patients with multiple organ failure.

Methods: A total of 110 ACLF patients, defined by the European Association for the Study of the Liver (EASL) Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) criteria were analyzed. The primary outcome was overall survival after ACLF diagnosis.

Results: During follow-up, 76 patients received LT (59 received deceased-donor LT and 17 patients received living-donor LT). The overall survival was better for patients who received LT than patients who did not (82.9% vs. 17.6%, P < 0.001). Among the 76 patients who received LT, the overall survival was not different according to ACLF grade at diagnosis (70.0%, 85.3%, and 84.4% at one-year for ACLF grades 1, 2, and 3, respectively, P = 0.45). The baseline model for end-stage liver disease (MELD) score and progression of the ACLF grade during the pre-transplant period were independent factors for survival after LT. The one-year survival rate was 92.3% for patients with baseline MELD scores of ≤ 32 without ACLF grade progression, whereas it was 33.3% for those with baseline MELD scores of > 32 and ACLF grade progression.

Conclusions: Emergent LT provided a significant survival benefit to ACLF patients, regardless of the baseline ACLF grade. Post-LT outcomes were associated with baseline MELD scores and ACLF progression during the pre-transplant period, which might be used in the emergent LT plan for patients presenting with ACLF.
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http://dx.doi.org/10.1016/j.dld.2021.03.030DOI Listing
August 2021

Blood Salvage and Autotransfusion Does Not Increase the Risk of Tumor Recurrence After Liver Transplantation for Advanced Hepatocellular Carcinoma.

Ann Surg 2021 Mar 18. Epub 2021 Mar 18.

*Department of Anesthesiology and Pain Medicine and †Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea ‡Statistics and Data Center, Samsung Medical Center, Seoul, Korea; †Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA §XXXX ¶Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.

Objective: To determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC).

Background: Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC.

Methods: Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74/129 without autotransfusion were matched with 74/220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence.

Results: Recipients in autotransfusion group received 811 (497-1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/38.3%/39.7% for non-autotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the two groups in overall recurrence (hazard ratio [HR] = 0.72 [0.43-1.21]), intrahepatic recurrence (HR = 0.70 [0.35-1.40]), and extrahepatic recurrence (HR = 0.82 [0.46-1.47]). Also, there were no significant differences in overall death (HR = 0.57 [0.29-1.12]), HCC-related death (HR = 0.59 [0.29-1.20]), and HCC-unrelated death (HR = 0.48 [0.09-2.65]).

Conclusion: When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.
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http://dx.doi.org/10.1097/SLA.0000000000004866DOI Listing
March 2021

Postoperative outcomes of purely laparoscopic donor hepatectomy compared to open living donor hepatectomy: a preliminary observational study.

Ann Surg Treat Res 2021 Apr 30;100(4):235-245. Epub 2021 Mar 30.

Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: To lessen the physical, cosmetic, and psychological burden of donors, purely laparoscopic donor hepatectomy (PLDH) has been proposed as an ideal method for living donors. Our study aimed to prospectively compare the effect of PLDH and 2 other types of open living donor hepatectomy (OLDH) on postoperative pain and recovery.

Methods: Sixty donors scheduled to undergo donor hepatectomy between March 2015 and November 2017 were included. Donors were divided into 3 groups by surgical technique: OLDH with a subcostal incision (n = 20), group S; OLDH with an upper midline incision (n = 20), group M; and PLDH (n = 20), group L. The primary outcomes were postoperative pain and analgesic requirement during postoperative day (POD) 3. Other variables regarding postoperative recovery were also analyzed.

Results: Although pain relief during POD 3, assessed by visual analog scale (VAS) score and analgesic requirement, was similar among the 3 groups, group L showed lower VAS scores and opioid requirements than group M. Moreover, group L was associated with a rapid postoperative recovery evidenced by the shorter hospital length of stay and more frequent return to normal activity on POD 30.

Conclusion: This pilot study failed to verify the hypothesis that PLDH reduces postoperative pain. PLDH did not reduce postoperative pain but showed faster recovery than OLDH.
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http://dx.doi.org/10.4174/astr.2021.100.4.235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019986PMC
April 2021

Liver Imaging Reporting and Data System Category on Magnetic Resonance Imaging Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation Within the Milan Criteria: A Multicenter Study.

Ann Surg Oncol 2021 Oct 9;28(11):6782-6789. Epub 2021 Mar 9.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: This study was designed to investigate the association between Liver Imaging Reporting and Data System (LI-RADS) category and recurrence of hepatocellular carcinoma (HCC) after primary liver transplantation (LT) within the Milan criteria.

Methods: This multicenter, retrospective study included 140 recipients who underwent living donor LT (LDLT) for treatment-naïve HCC and pretransplant contrast-enhanced magnetic resonance imaging (MRI) between 2009 and 2013. LI-RADS categories were assigned using LI-RADS version 2018. Recurrence-free survival (RFS) and associated factors were evaluated using Cox proportional hazards regression analysis, Kaplan-Meier analysis, and log-rank test. Histological grading and microvascular invasion (MVI) were analyzed on the pathologic examinations of explanted livers.

Results: The overall 1-, 3-, 5-, and 7-year RFS rates were 95.6%, 92.6%, 90.2%, and 89.3%, respectively. In the multivariable analysis, independent predictors of recurrence included HCCs categorized as LR-M (hazard ratio [HR], 18.68; 95% confidence interval [CI], 5.79-60.23; P < 0.001) and the largest tumor size of ≥ 3 cm on MRI (HR, 4.18; 95% CI, 1.42-12.37; P = 0.010). The 5-year RFS rate was significantly lower in patients with HCCs categorized as LR-M than in those with HCCs categorized as LR-5 or 4 (LR-5/4) (36.9% vs. 95.8%, respectively; P < 0.001). HCCs categorized as LR-M exhibited significantly more MVI than HCCs categorized as LR-5/4 (57.1% vs. 17.5%, respectively; P = 0.002).

Conclusions: Patients with HCCs categorized as LR-M using LI-RADS version 2018 may have a worse prognosis after primary LT within the Milan criteria than those with HCCs categorized as LR-5/4.
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http://dx.doi.org/10.1245/s10434-021-09772-8DOI Listing
October 2021

Efficacy and Safety of Everolimus With Reduced Tacrolimus in Liver Transplant Recipients: 24-month Results From the Pooled Analysis of 2 Randomized Controlled Trials.

Transplantation 2021 07;105(7):1564-1575

University of Toronto, Toronto, Canada.

Background And Methods: Data from 2 randomized liver transplant trials (N = 772; H2304 [deceased donor, n = 488], H2307 [living donor, n = 284]) were pooled to further evaluate the efficacy and safety of everolimus with reduced tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) regimen at month 24.

Results: EVR + rTAC was comparable to sTAC for composite efficacy failure of treated biopsy-proven acute rejection, graft loss, or death (9.8% versus 10.8%; difference, -1.0%; 95% confidence interval, -5.4 to 3.4; P = 0.641) at month 24. EVR + rTAC was superior to sTAC for the mean change in estimated glomerular filtration rate (eGFR) from randomization to month 24 (-8.37 versus -13.40 mL/min/1.73 m2; P = 0.001). A subanalysis of renal function by chronic kidney disease (CKD) stage at randomization showed significantly lower decline in eGFR from randomization to month 24 for patients with CKD stage 1/2 (eGFR ≥ 60 mL/min/1.73 m2) in EVR + rTAC group versus sTAC (-12.82 versus -17.67 mL/min/1.73 m2, P = 0.009). In patients transplanted for hepatocellular carcinoma (HCC) beyond Milan criteria, HCC recurrence was numerically lower although not statistically significant with EVR + rTAC versus sTAC group (5.9% [1 of 17] versus 23.1% [6 of 26], P = 0.215), while comparable in patients within Milan criteria (2.9% [3 of 102] versus 2.1% [2 of 96], P = 1.000), irrespective of pretransplant alpha-fetoprotein levels.

Conclusions: EVR + rTAC versus sTAC showed comparable efficacy and safety with significantly better renal function, particularly in patients with normal/mildly decreased renal function (CKD stage 1/2) at randomization and a trend toward lower HCC recurrence in patients transplanted with HCC beyond Milan at month 24. Further long-term data would be required to confirm these results.
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http://dx.doi.org/10.1097/TP.0000000000003394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221719PMC
July 2021

Impact of Graft Weight Change During Perfusion on Hepatocellular Carcinoma Recurrence After Living Donor Liver Transplantation.

Front Oncol 2020 24;10:609844. Epub 2021 Feb 24.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Backgrounds: Inadequate liver volume and weight is a major source of morbidity and mortality after adult living donor liver transplantation (LDLT). The purpose of our study was to investigate HCC recurrence, graft failure, and patient survival according to change in right liver graft weight after histidine-tryptophan-ketoglutarate (HTK) solution perfusion in LDLT.

Methods: Two hundred twenty-eight patients underwent LDLT between 2013 and 2017. We calculated the change in graft weight by subtracting pre-perfusion graft weight from post-perfusion graft weight. Patients with increased graft weight were defined as the positive group, and patients with decreased graft weight were defined as the negative group.

Results: After excluding patients who did not meet study criteria, 148 patients underwent right or extended right hepatectomy. The negative group included 89 patients (60.1%), and the positive group included 59 patients (39.9%). Median graft weight change was -28 g (range; -132-0 g) in the negative group and 21 g (range; 1-63 g) in the positive group (P<0.001). Median hospitalization time was longer for the positive group than the negative group (27 days vs. 23 days; P=0.048). There were no statistical differences in tumor characteristics, postoperative complications, early allograft dysfunction, or acute rejection between the two groups. Disease-free survival, death-censored graft survival, and patient survival were lower in the positive group than the negative group. Additionally, the positive group showed strong association with HCC recurrence, death-censored graft survival, and patient survival in multivariate analysis.

Conclusion: This study suggests that positive graft weight change during HTK solution perfusion indicates poor prognosis in LDLT.
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http://dx.doi.org/10.3389/fonc.2020.609844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945034PMC
February 2021

Laparoscopic Living Donor Right Hepatectomy Regarding the Anatomical Variation of the Portal Vein: A Propensity Score-Matched Analysis.

Liver Transpl 2021 07 24;27(7):984-996. Epub 2021 Jun 24.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

This study is designed to analyze the feasibility of laparoscopic living donor right hemihepatectomy in living donors with portal vein variation. Living donor liver transplantation cases using a right liver graft during the period of January 2014 to September 2019 were included. Computed tomographic angiographies of the donor were 3-dimensionally reconstructed, and the anatomical variation of the portal vein was classified. To reduce selection bias, a 1:1 ratio propensity score-matched analysis between the laparoscopy group and the open group was performed. Surgical and recovery-related outcomes as well as portal vein complication-free survival, graft survival, and overall survival rates were analyzed. After matching, 171 cases in each group from 444 original cases were compared. The laparoscopy group had a shorter operation time (P < 0.001), a smaller number of additional opioids required by the donor (P < 0.001), and a shorter hospital stay (P < 0.001). There were no differences in the portal vein complication-free survival (P = 0.16), graft survival (P = 0.26), or overall survival rates (P = 0.53). Although portal vein complication-free survival was inferior in portal veins other than type I (P = 0.01), the laparoscopy group showed similar portal vein complication-free survival regardless of the anatomical variation of portal vein (P = 0.35 in type I and P = 0.30 in other types). Laparoscopic living donor right hemihepatectomy can be performed as safely as open surgery regardless of the anatomical variation of the portal vein.
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http://dx.doi.org/10.1002/lt.26050DOI Listing
July 2021

Association between neutrophil-lymphocyte ratio change during living donor liver transplantation and graft survival.

Sci Rep 2021 Feb 18;11(1):4199. Epub 2021 Feb 18.

Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.

Preoperative neutrophil-lymphocyte ratio (NLR), has shown a predictive value in living donor liver transplantation (LDLT). However, the change in the NLR during LDLT has not been fully investigated. We aimed to compare graft survival between the NLR increase and decrease during LDLT. From June 1997 to April 2019, we identified 1292 adult LDLT recipients with intraoperative NLR change. The recipients were divided according to NLR change: 103 (8.0%) in the decrease group and 1189 (92.0%) in the increase group. The primary outcome was graft failure in the first year. In addition, variables associated with NLR change during LDLT were evaluated. During 1-year follow-up, graft failure was significantly higher in the decrease group (22.3% vs. 9.1%; hazard ratio 1.87; 95% confidence interval 1.10-3.18; p = 0.02), but postoperative complications did not differ between two groups. This finding was consistent for the overall follow-up. Variables associated with NLR decrease included preoperative NLR > 4, model for end-stage liver disease score, intraoperative inotropic infusion and red blood cell transfusion, and operative duration. The least absolute shrinkage and selection operator model yielded similar results. NLR decrease during LDLT appeared to be independently associated with graft survival. Further studies are needed to confirm our findings.
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http://dx.doi.org/10.1038/s41598-021-83814-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892541PMC
February 2021

Initial experience with high-volume plasma exchange in patients with acute liver failure.

J Clin Apher 2021 Jun 5;36(3):379-389. Epub 2021 Jan 5.

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background/aims: High-volume plasma exchange (HVPE), defined as an exchange of 8 to 12 L per day per procedure or 15% of the ideal body weight with fresh frozen plasma, has shown promising results in improving the survival of patients with acute liver failure (ALF). However, clinical evidence is limited. The aim of this study was to report our initial experience using HVPE as a bridge treatment in patients with ALF.

Methods: We retrospectively reviewed 32 consecutive patients awaiting liver transplantation (LT) due to ALF between 2013 and 2020 at Samsung Medical Center in Korea. HVPE has been used for patients with ALF since May 2016 at our institution.

Results: During the study period, 16 patients received HVPE. After HVPE, coagulopathies (INR, 4.46 [2.32-6.02] vs 1.48 [1.33-1.76], P < .05), total bilirubin (22.6 [9.1-26.4] vs 8.9 [5.6-11.3], P < .05), alanine aminotransferase (506 [341-1963] vs 120 [88-315], P < .05), and ammonia levels (130.6 [123.7-143.8] vs 98.2 [84.2-116.5], P < .05) were improved. Improvement in the hepatic encephalopathy grade was observed in four patients. Among 16 patients who received HVPE, 12 patients were bridged to LT, and three patients recovered spontaneously. The overall survival was 94% and 69%, respectively at 30 days in patients who received and did not receive HVPE (P = .068). Among 18 patients with high chronic liver failure-sequential organ failure assessment scores (≥13), the overall survival was significantly better for those who received HVPE than for those who did not (91% vs 29%, respectively, at 30 days, P < .05).

Conclusions: Our initial clinical experience with HVPE suggests that HVPE can be a viable option in improving the outcomes of patients presenting with ALF.
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http://dx.doi.org/10.1002/jca.21873DOI Listing
June 2021

Liver transplantation in an adult patient with hepatocellular carcinoma following liver cirrhosis as a complication of the Fontan procedure -A case report.

Anesth Pain Med (Seoul) 2020 Oct 21;15(4):466-471. Epub 2020 Oct 21.

Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Fontan-associated liver disease (FALD) is a hepatic disorder caused by hemodynamic changes and systemic venous congestion following the Fontan procedure. FALD includes liver cirrhosis and hepatocellular carcinoma (HCC), both of which may require liver transplantation (LT). However, the Fontan circulation, characterized by elevated central venous pressure and reduced cardiac output, is a challenging issue for surgeons and anesthesiologists.

Case: We report a living-donor LT for the treatment of HCC. The patient was a 24-year-old male who underwent the Fontan procedure for pulmonary atresia and right ventricle hypoplasia. We focused on maintaining enough blood volume for cardiac output without causing pulmonary edema, as the patient is not well adapted to changes in volume. Owing to a multidisciplinary approach, the surgery was successfully performed without fatal adverse events.

Conclusions: To our knowledge, this is the first case of isolated LT in a recipient who became an adult after having undergone the Fontan procedure.
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http://dx.doi.org/10.17085/apm.20037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724127PMC
October 2020

Clinical impact of anatomical resection on long-term outcomes after hepatectomy for primary solitary hepatocellular carcinoma with or without preoperative positron emission tomography positivity.

Ann Transl Med 2020 Nov;8(21):1377

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: There is little evidence indicating that anatomical resection (AR) is associated with improved survival in patients with solitary hepatocellular carcinoma (HCC) who were preoperatively evaluated by positron emission tomography (PET). The aim of our study was to compare the oncologic outcomes of AR in PET-positive versus PET-negative patients with HCC.

Methods: From January 2007 to September 2015, 259 patients with preoperative PET underwent hepatectomy as the primary treatment for solitary HCC. Patients were divided into four groups according to PET uptake and hepatectomy type [AR or non-anatomical resection (NAR)]: Group 1 (PET-negative and AR, n=62); Group 2 (PET-negative and NAR, n= 46); Group 3 (PET-positive and AR, n=100); Group 4 (PET-positive and NAR, n=51).

Results: PET positivity was associated with higher protein induced by vitamin K antagonist-II (P=0.025), lager tumor size (P=0.05), microvascular invasion (MVI) (P=0.012), and portal vein invasion (P=0.031). In Kaplan-Meier analysis for RFS, Group 1 showed remarkable difference from Group 3 and Group 4 (P=0.045, P=0.023, respectively). In the PET-positive subgroup with HCC under 3 cm, AR was associated with better RFS than NAR (P=0.016).

Conclusions: A combination of AR and PET negativity showed good prognosis in long-term outcomes. Finally, AR can decrease the risk of tumor recurrence in patients with a solitary PET-positive HCC less than 3 cm.
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http://dx.doi.org/10.21037/atm-20-1583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723622PMC
November 2020

Venous outflow congestion is related to poor recurrence-free survival of living donor liver transplantation recipients with hepatocellular carcinoma - a retrospective study.

Transpl Int 2021 02 12;34(2):272-280. Epub 2020 Dec 12.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

This study analyzed the impact of venous outflow congestion in the liver graft on hepatocellular carcinoma recurrence in liver transplantation recipients. Hepatocellular carcinoma patients who underwent living donor liver transplantation at Samsung Medical Center between 2007 and 2018 were included. The congested volume was calculated based on 2-week post-transplantation computed tomography. Recurrence-free survival and overall survival were analyzed using the multivariable Cox proportional hazard model including the degree of venous congestion. A total of 582 patients were included. There were 232 patients (39.9%) with certain degree of congestion volume. Kaplan-Meier survival analyses showed 1-, 5-, and 10-year recurrence-free survivals of 86.0%, 72.2%, and 70.7%, respectively, and overall survivals of 91.5%, 73.4%, and 68.9%, respectively. While congestion volume per 10 cm was a significant risk factor for recurrence-free survival (HR = 1.024, CI: 1.002-1.047, P = 0.034), there was no significant relationship with overall survival. (HR = 1.015, CI: 0.992-1.039, P = 0.213). Venous outflow congestion in the liver after living donor liver transplantation was related to the poor recurrence-free survival of hepatocellular carcinoma patients.
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http://dx.doi.org/10.1111/tri.13792DOI Listing
February 2021

Serial Observations of Muscle and Fat Mass as Prognostic Factors for Deceased Donor Liver Transplantation.

Korean J Radiol 2021 02 3;22(2):189-197. Epub 2020 Nov 3.

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

Objective: Muscle depletion in patients undergoing liver transplantation affects the recipients' prognosis and therefore cannot be overlooked. We aimed to evaluate whether changes in muscle and fat mass during the preoperative period are associated with prognosis after deceased donor liver transplantation (DDLT).

Materials And Methods: This study included 72 patients who underwent DDLT and serial computed tomography (CT) scans. Skeletal muscle index (SMI) and fat mass index (FMI) were calculated using the muscle and fat area in CT performed 1 year prior to surgery (1 yr Pre-LT), just before surgery (Pre-LT), and after transplantation (Post-LT). Simple aspects of serial changes in muscle and fat mass were analyzed during three measurement time points. The rate of preoperative changes in body composition parameters were calculated (preoperative ΔSMI [%] = [SMI at Pre-LT - SMI at 1 yr Pre-LT] / SMI at Pre-LT × 100; preoperative ΔFMI [%] = [FMI at Pre-LT - FMI at 1 yr Pre-LT] / FMI at Pre-LT × 100) and assessed for correlation with patient survival.

Results: SMI significantly decreased during the preoperative period (mean preoperative ΔSMI, -13.04%, < 0.001). In the multivariable analysis, preoperative ΔSMI ( = 0.016) and model for end-stage liver disease score ( = 0.011) were independent prognostic factors for overall survival. The mean survival time for patients with a threshold decrease in the preoperative ΔSMI (≤ -30%) was significantly shorter than for other patients ( = 0.007). Preoperative ΔFMI was not a prognostic factor but FMI increased during the postoperative period ( = 0.009) in all patients.

Conclusion: A large reduction in preoperative SMI was significantly associated with reduced survival after DDLT. Therefore, changes in muscle mass during the preoperative period can be considered as a prognostic factor for survival after DDLT.
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http://dx.doi.org/10.3348/kjr.2019.0750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817639PMC
February 2021

Image guidance using two-dimensional illustrations and three-dimensional modeling of donor anatomy during living donor hepatectomy.

Clin Transplant 2021 01 12;35(1):e14164. Epub 2020 Dec 12.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: For living donor liver transplantation, preoperative imaging is required for the safety of both the donor and the recipient. We previously initiated our image-guidance program using two-dimensional illustrations and three-dimensional modeling in September 2018; herein, we analyzed the resultant changes in the clinical outcomes.

Methods: Living donors and recipients who underwent liver transplantation between September 2017 and August 2019 were included. Cases with image guidance were compared to those without image guidance regarding the operative outcome, especially bile-duct opening in the graft as well as surgical complications.

Results: Among 200 living donor transplantation, 90 transplantations were completed with image guidance. The image-guidance group had a higher rate of laparoscopy (80.9% vs. 97.8%; p < .001) as compared with the group without image guidance. Although there was no difference in the type of bile duct (p = .144), more grafts with single bile-duct openings were found in the image-guidance group (52.7% vs. 80.0%; p = .001). Consequently, achievements in bile-duct openings were superior in the image-guidance group (p = .022). There were no differences in bile leakage, graft failure, or number of deaths during the first month post-transplantation.

Conclusion: As we initiated our image-guidance program for living donor liver transplantation, clinical outcomes, especially bile-duct division, were improved relative to before implementation.
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http://dx.doi.org/10.1111/ctr.14164DOI Listing
January 2021

Poor outcomes of early recurrent post-transplant bloodstream infection in living-donor liver transplant recipients.

Eur J Clin Microbiol Infect Dis 2021 Apr 21;40(4):771-778. Epub 2020 Oct 21.

Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Bloodstream infection (BSI) is a common complication after living-donor liver transplantation (LDLT). Some patients develop recurrent BSIs. We evaluated the impacts of early recurrent BSIs (ER-BSIs) on outcomes in LDLT recipients. LDLT cases between 2008 and 2016 were included. Early BSI (E-BSI) was defined as a BSI event that occurred within 2 months after LDLT. ER-BSIs were defined as new-onset BSIs within 2 months due to another pathogen at a ≥ 48-h interval or a relapse of BSIs by the same pathogen at a ≥ 1-week interval, with negative cultures in between. The primary objective was evaluating the all-cause mortality of each group of LDLT recipients (90 days and 1 year). The secondary objectives were analyzing associated factors of each all-cause mortality and risk factors for early single BSI and ER-BSI. Among 727 LDLT recipients, 108 patients experienced 149 events of E-BSI with 170 isolated pathogens. Twenty-eight patients (25.9%, 28/108) experienced ER-BSI. The 1-year survival rates of patients without BSI, with early single BSI event, and with ER-BSIs were 92.4%, 81.3%, and 28.6%, respectively. ER-BSI was the most significant risk factor for 1-year mortality (adjusted HR = 5.31; 95% CI = 2.27-12.40). Intra-abdominal and/or biliary complications and early allograft dysfunction were risk factors for both early single BSI and ER-BSI. Interestingly, longer cold ischemic time and recipient operative time were associated with ER-BSI. LDLT recipients with ER-BSI showed very low survival rates accompanied by intra-abdominal complications. Clinicians should prevent BSI recurrence by being aware of intra-abdominal complications.
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http://dx.doi.org/10.1007/s10096-020-04074-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577647PMC
April 2021

Comparison of outcome between liver resection, radiofrequency ablation, and transarterial therapy for multiple small hepatocellular carcinoma within the Milan criteria.

Ann Surg Treat Res 2020 Oct 24;99(4):238-246. Epub 2020 Sep 24.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Although surgical resection is usually considered for a single tumor, several reports have suggested that resection can be considered for multiple tumors. The objective of this study was to determine whether resection could provide better long-term outcome for patients with multiple hepatocellular carcinomas (HCCs) within Milan criteria.

Methods: A total of 276 patients with multiple HCCs within Milan criteria with liver function preserved who underwent resection, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) between 2009 and 2013 were analyzed. Propensity-score (PS) matching was conducted.

Results: Five-year overall survival (OS) and recurrence-free survival (RFS) were better in the resection group than that in the RFA or TACE group. Patients who underwent resection had more preserved liver function and different tumor characteristics compared to those received RFA or TACE. With similar baseline characteristics generated in the PS model, there was no difference in 5-year OS among 3 groups (79.5% vs. 72.3% or 62.0%, P = 0.232), but the 5-year RFS was better for patients who received resection than those who received RFA or TACE (51.9% vs. 22.0% or 0.0%, P < 0.001). Although the major complication rate was slightly higher than RFA or TACE, there was no significant difference between the 3 groups before and after PS matching.

Conclusion: Resection was associated with better RFS than RFA or TACE and showed comparable OS in multiple HCC patients within the Milan criteria, but at a cost of slightly increased risk of complication. Resection can be considered as a first-line option if selected appropriately.
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http://dx.doi.org/10.4174/astr.2020.99.4.238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520230PMC
October 2020

Novel Model to Predict HCC Recurrence after Liver Transplantation Obtained Using Deep Learning: A Multicenter Study.

Cancers (Basel) 2020 Sep 29;12(10). Epub 2020 Sep 29.

Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea.

Several models have been developed using conventional regression approaches to extend the criteria for liver transplantation (LT) in hepatocellular carcinoma (HCC) beyond the Milan criteria. We aimed to develop a novel model to predict tumor recurrence after LT by adopting artificial intelligence (MoRAL-AI). This study included 563 patients who underwent LT for HCC at three large LT centers in Korea. Derivation ( = 349) and validation ( = 214) cohorts were independently established. The primary outcome was time-to-recurrence after LT. A MoRAL-AI was derived from the derivation cohort with a residual block-based deep neural network. The median follow-up duration was 74.7 months (interquartile-range, 18.5-107.4); 204 patients (36.2%) had HCC beyond the Milan criteria. The optimal model consisted of seven layers including two residual blocks. In the validation cohort, the MoRAL-AI showed significantly better discrimination function (c-index = 0.75) than the Milan (c-index = 0.64), MoRAL (c-index = 0.69), University of California San Francisco (c-index = 0.62), up-to-seven (c-index = 0.50), and Kyoto (c-index = 0.50) criteria (all 0.001). The largest weighted parameter in the MoRAL-AI was tumor diameter, followed by alpha-fetoprotein, age, and protein induced by vitamin K absence-II. The MoRAL-AI had better predictability of tumor recurrence after LT than conventional models. The MoRAL-AI can also evolve with further data.
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http://dx.doi.org/10.3390/cancers12102791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650768PMC
September 2020

Effect of on the Once-Daily Tacrolimus Conversion in Stable Liver Transplant Patients.

J Clin Med 2020 Sep 8;9(9). Epub 2020 Sep 8.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 13557, Korea.

Cytochrome P450 () polymorphism influences tacrolimus metabolism, but its effect on the drug pharmacokinetics in liver transplant recipients switched to once-daily extended-release formulation remains unknown. The aim of this study is to analyze the effect of polymorphism on liver function after once-daily tacrolimus conversion in liver transplant patients. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for polymorphism. The study was registered at ClinicalTrials.gov (NCT02882113). Twenty-eight patients were enrolled in the expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus ( = 0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (-42.9% vs. -26.1%) and dose/kg-adjusted trough level of tacrolimus (-40.0% vs. -23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. A pharmacokinetic analysis was performed in 10 patients and tacrolimus absorption in the non-expressor group was slower than in the expressor group. In line with this observation, the area under the curve for once-daily tacrolimus correlated with trough level (Cmin) in the non-expressors and peak concentration (Cmax) in the expressors. genotyping in liver transplant recipients leads to prediction of pharmacokinetics after switching from a twice-daily regimen to a once-daily dosage form, which makes it possible to establish an appropriate dose of tacrolimus.
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http://dx.doi.org/10.3390/jcm9092897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563461PMC
September 2020

Tenofovir does not induce renal dysfunction compared to entecavir in post-liver-transplant hepatitis B virus patients.

Ann Surg Treat Res 2020 Sep 27;99(3):180-187. Epub 2020 Aug 27.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Tenofovir disoproxil fumarate is accepted as an effective and tolerable drug for treatment of HBV, similar to entecavir. However, there are some concerns about the nephrotoxicity of tenofovir. The aim of this study is to compare the renal-function change of liver recipients who received tenofovir or entecavir for HBV.

Methods: Among 468 patients with HBV who underwent liver transplantation at Samsung Medical Center between January 2008 and December 2015, the patients treated with tenofovir (n = 39) or entecavir (n = 429) were reviewed retrospectively. Baseline characteristics and renal-function change after 1 month, 1 year, and 2 years were compared. Propensity-score matching was performed for 37 patients using tenofovir and 132 patients using entecavir. We also analyzed risk factors of renal dysfunction.

Results: Age, preoperative creatinine, estimated glomerular filtration rate (e-GFR), and hepatic encephalopathy score showed statistical difference between the tenofovir and entecavir groups. The proportion of patients with 'decreased renal function (e-GFR < 60 mL/min/1.73 m)' was higher in the tenofovir group than in the entecavir group (33.3% 12.4% at postoperative one year, P < 0.005). After propensity-score matching, there was no statistical difference in preoperative characteristics. Postoperative 1-, 2-, and 3-year e-GFR and creatinine showed no statistical difference in either group. On multivariate analysis, only preoperative high e-GFR showed a protective effect on renal-function change (odds ratio, 0.97; P < 0.001), and there was no aggravating factor.

Conclusion: Tenofovir disoproxil fumarate does not induce renal dysfunction in liver-transplanted patients with HBV more than does entecavir.
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http://dx.doi.org/10.4174/astr.2020.99.3.180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463039PMC
September 2020
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