Publications by authors named "Shin Hwang"

472 Publications

Impact of diabetes, obesity, and dyslipidemia on the risk of HCC in patients with chronic liver diseases.

Clin Mol Hepatol 2022 Aug 8. Epub 2022 Aug 8.

Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, Republic of Korea.

Despite the increasing prevalence of metabolic disorders, the potential effects of metabolic factors on hepatocellular carcinoma (HCC) development in individuals with chronic liver diseases (CLDs) are not well understood. For a metabolic factor to be identified as a risk factor for HCC in patients with CLDs, such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, there should be a strong synergistic interaction between the carcinogenic mechanisms of the metabolic factor and the CLD itself. This review aims to comprehensively summarize the published data on the relationship between metabolic factors such as diabetes mellitus (DM), obesity, and blood lipids and the risk of HCC in patients with CLDs. DM consistently increases the risk of HCC in patients with CLD. When associated with DM, the risk of HCC seems to be highest in HCV and non-alcoholic fatty liver disease (NAFLD), followed by alcoholic liver disease (ALD) and HBV. However, HCV and NAFLD increase the incidence of DM, and comorbid DM can be a marker of CLD severity. Therefore, at least part of the effects of DM reflects reverse causality. Obesity may increase the risk of HCC; however, the magnitude of effects seems to be modest in patients with CLDs compared to that in the general population. Among CLDs, the evidence is relatively consistent and clear for ALD, while clear evidence is limited in other CLDs including HBV, HCV, and NAFLD. Total cholesterol, potentially low-density lipoprotein cholesterol and triglyceride, seems to have strong inverse associations with HCC in individuals with CLDs. Since the attained low levels after statin use are not associated with a higher risk of HCC, low cholesterol levels are more of a strong predictor than a risk factor for HCC. Despite evidence from observational studies, statins had no effect in preventing HCC in randomized controlled trials. Whether statins have a preventive effect against HCC is unclear. A better understanding and management of metabolic factors may be beneficial to reduce the risk of HCC in patients with CLDs.
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http://dx.doi.org/10.3350/cmh.2021.0383DOI Listing
August 2022

Pediatric living donor liver transplantation for biliary embryonal rhabdomyosarcoma: a case report of a case showing disease-free survival over 2 years.

Korean J Transplant 2022 Jun 31;36(2):148-153. Epub 2021 Aug 31.

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

Biliary rhabdomyosarcoma is a rare tumor, but it is still the most common tumor of the biliary tract in children. We report a case of a 6-year-old boy with biliary embryonal rhabdomyosarcoma and liver metastasis, which were treated with neoadjuvant and adjuvant chemotherapy combined with living donor liver transplantation (LDLT). Initial imaging studies showed a low-attenuation intraductal mass from the left hepatic duct to the intrapancreatic common bile duct with diffuse upstream dilatation of the intrahepatic duct and liver metastasis. Endoscopic biopsy revealed embryonal rhabdomyosarcoma. After tumor size reduction through neoadjuvant chemotherapy, LDLT was planned to remove the tumor completely. A left lateral section graft weighing 330 g was harvested from his 38-year-old mother and the graft-to-recipient weight ratio was 1.94%. Routine pediatric LDLT operation was performed with deep excavation of intrapancreatic distal bile duct. The explant liver showed minimal residual embryonal rhabdomyosarcoma with no lymph node metastasis. The patient recovered uneventfully from LDLT operation. Scheduled adjuvant chemotherapy was performed for 6 months. The patient is doing well without any evidence of tumor recurrence for 26 months after LDLT. In conclusion, liver transplantation could be an effective treatment for unresectable biliary rhabdomyosarcoma in children according to the location of tumor.
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http://dx.doi.org/10.4285/kjt.21.0008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296975PMC
June 2022

Non-Renal Risk Factors for Chronic Kidney Disease in Liver Recipients with Functionally Intact Kidneys at 1 Month.

J Clin Med 2022 Jul 20;11(14). Epub 2022 Jul 20.

Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea.

Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD (<60 mL/min/1.73 m), examining liver recipients with functionally intact kidneys one month after grafting using nationwide cohort data. Baseline risk factors were analyzed with multivariable Cox regression analyses and post-transplant risk factors were investigated with the time-dependent Cox model and matched analyses of time-conditional propensity scores. Of the 2274 recipients with a one-month eGFR ≥ 60 mL/min/1.73 m, 494 (22.3%) developed CKD during a mean follow-up of 36.6 ± 14.4 months. Age, female sex, lower body mass index, pre-transplant diabetes mellitus, and lower performance status emerged as baseline risk factors for CKD. Time-dependent Cox analyses revealed that recurrent hepatocellular carcinoma (HR = 1.93, 95% CI 1.06-3.53) and infection (HR = 1.44, 95% CI 1.12-1.60) were significant post-transplant risk factors for CKD. Patients who experienced one of those factors showed a significantly higher risk of subsequent CKD compared with the matched controls who lacked these features ( = 0.013 for recurrent hepatocellular carcinoma, and = 0.003 for infection, respectively). This study clarifies pre- and post-transplant non-renal risk factors, which lead to renal impairment after LT independently from patients' renal functional reserve.
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http://dx.doi.org/10.3390/jcm11144203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315935PMC
July 2022

Diagnostic and prognostic impact of fluorodeoxyglucose-positron emission tomography in diagnosing intraductal papillary neoplasms of the bile duct of the liver.

Ann Surg Treat Res 2022 Jun 7;102(6):335-341. Epub 2022 Jun 7.

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

Purpose: Malignant intraductal papillary neoplasm of the bile duct of the liver (IPNB-L) cannot readily be diagnosed through preoperative CT or MRI, but fluorodeoxyglucose (FDG)-PET is a viable alternative. This study evaluated the diagnostic and prognostic impacts of FDG-PET in patients with IPNB-L.

Methods: This was a retrospective single-center study of 101 IPNB-L patients who underwent hepatectomy between 2010 and 2019.

Results: Mean age was 64.4 ± 8.3 years and 76 (75.2%) were male. Anatomical hepatic resection was performed in 99 (98.0%). Concurrent bile duct resection and pancreaticoduodenectomy were performed in 41 (40.6%) and 1 (1.0%), respectively. R0 and R1 resections were performed in 88 (87.1%) and 13 (12.9%), respectively. Low-grade intraepithelial neoplasia and high-grade neoplasia/invasive carcinoma were diagnosed in 19 (18.8%) and 82 (81.2%), respectively. Median FDG-PET maximal standardized uptake values (SUVmax) in low-grade neoplasia and high-grade neoplasia/carcinoma were 3.6 (range, 1.7-7.6) and 5.2 (range, 1.5-18.7) (P = 0.019), respectively. Receiver operating characteristic curve analysis of SUVmax showed area under the curve of 0.674, with sensitivity of 84.2% and specificity of 47.4% at SUVmax cutoff of 3.0. This cutoff had no significant influence on tumor recurrence (P = 0.832) or patient survival (P = 0.996) in patients with IPNB-L of high-grade neoplasia or invasive carcinoma.

Conclusion: IPNB-L is a rare type of biliary neoplasm and encompasses a histological spectrum ranging from benign disease to invasive carcinoma. An FDG-PET SUVmax cutoff of 3.0 appears to effectively discern high-grade neoplasia/carcinoma from low-grade neoplasia, which will assist with the surgical strategy for these cases.
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http://dx.doi.org/10.4174/astr.2022.102.6.335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204025PMC
June 2022

Salvage aorto-hepatic jump graft for hepatic artery thrombosis following living donor liver transplantation: a case report with 10-year follow-up.

Korean J Transplant 2021 Dec;35(4):268-274

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

Hepatic artery thrombosis (HAT) following living donor liver transplantation (LDLT) is a lethal complication. We present the case of a patient who underwent salvage redo hepatic artery reconstruction using an aorto-hepatic jump graft because of HAT following LDLT. A 64-year-old female patient diagnosed with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma underwent salvage LDLT using a modified right liver graft. Partial graft infarct was identified at posttransplant day 4, and by day 9, it had spread. Celiac arteriography showed complete occlusion of the graft hepatic artery. We performed redo hepatic artery reconstruction using a fresh iliofemoral artery homograft 10 days after the LDLT operation because such a vessel homograft was available at our institutional tissue bank. The infrarenal aorta was dissected and an iliofemoral artery graft was anastomosed. Soon after hepatic artery revascularization, liver function progressively improved, and the infarct area at the liver graft was reduced. The patient has been doing well for 10 years without any vascular complications. In conclusion, our experience with this case suggests that salvage redo hepatic artery reconstruction using an aorto-hepatic jump graft is a feasible option to treat HAT following LDLT, as in deceased donor liver transplantation.
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http://dx.doi.org/10.4285/kjt.21.0009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235459PMC
December 2021

An analysis of the number of liver and kidney transplantations during COVID-19 pandemic in Korea.

Korean J Transplant 2021 Dec;35(4):247-252

Organ Transplantation Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: The severity of the coronavirus disease 2019 (COVID-19) pandemic has discouraged organ donation. However, the prevalence of COVID-19 in Korea was much lower in comparison to Western countries. With this, the authors decided to determine the real-world impact of COVID-19 on organ donation and transplantation in Korea.

Methods: The number of kidney transplantations (KTs) and liver transplantations (LTs) performed in 2020 were compared with those in 2019 using the Korean Network for Organ Sharing database and Asan Medical Center (AMC) database.

Results: The annual number of deceased donors (DDs) was 450 in 2019 compared to 478 in 2020. Monthly DD number was 37.5±5.9 in 2019 and 39.8±4.4 in 2020 (P=0.284). Annual number of DD kidney transplant (DDKT) was 794 in 2019 and 848 in 2020, and monthly number was 66.1±10.4 in 2019 and 70.7±9.8 in 2020 (P=0.285). The annual number of DDLT was 391 in 2019 and 395 in 2020, and the monthly number was 32.6±5.7, 2019 and 32.9±4.7 in 2020 (P=0.877). The annual number of living donor (LD) KT was 2,293 in 2019 and 1,432 in 2020, and the monthly number was 191.1±19.5 in 2019 and 119.3±11.7 in 2020 (P<0.001). Annual number of living donor LDLT was 1,577 in 2019 and 1,146 in 2020, and monthly number was 131.4±18.1 in 2019 and 95.5±8.0 in 2020 (P<0.001). In the AMC, not all types of KT and LT changed significantly.

Conclusions: The results of this study indicate that the number of DD organ transplantations remained stable in Korea in 2020, but the number of LD organ transplantations was significantly reduced. However, the number of organ transplantations did not change in the AMC.
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http://dx.doi.org/10.4285/kjt.21.0030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235458PMC
December 2021

Recipient liver splitting to facilitate piggyback hepatectomy in adult living donor liver transplantation.

Korean J Transplant 2021 Jun 10;35(2):124-129. Epub 2021 May 10.

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

Recipient hepatectomy for an enlarged stony-hard liver is a demanding procedure, thus it is often accompanied by massive blood loss. Recipient liver splitting under prolonged hepatic inflow occlusion would facilitate the piggyback recipient hepatectomy. We herein present a case of recipient liver splitting, which was used for living donor liver transplantation (LDLT). A 48-year-old male patient diagnosed with acute-on-chronic liver failure underwent LDLT. During the recipient operation, the native liver was stony-hard and heavily adherent to the retrohepatic inferior vena cava (IVC). During liver mobilization, diffuse oozing occurred due to disseminated intravascular coagulation. As a change in the concept, we decided to perform liver splitting of the recipient liver to facilitate dissection of the retrohepatic IVC. Under hepatic inflow occlusion, right-left liver splitting was performed along the usual plane of extended left hepatectomy. The procedures time for recipient liver splitting and removal was 60 minutes. A modified right liver graft recovered from his daughter was implanted according to the standard procedures of LDLT. We think that recipient liver splitting is a feasible technical option for coping with difficult recipient hepatectomy, especially in patients with an enlarged stony-hard liver and heavy adhesion around the IVC.
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http://dx.doi.org/10.4285/kjt.20.0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235329PMC
June 2021

Salvage living donor liver transplantation for post-resection recurrence of combined hepatocellular carcinoma-cholangiocarcinoma.

Korean J Transplant 2021 Jun 11;35(2):116-123. Epub 2021 Jan 11.

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

Salvage liver transplantation (LT) is a definite treatment for recurrent hepatocellular carcinoma (HCC) after hepatectomy. Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is not eligibly indicated for LT because of high post-transplant recurrence. We present a case of salvage living donor liver transplantation (LDLT) in a patient with tumor recurrence after surgical resection of cHCC-CC. A 61-year-old male patient diagnosed with chronic hepatitis B underwent right posterior sectionectomy for HCC. The pathological diagnosis revealed presence of a 3.2-cm-sized cHCC-CC with stem cell features and intermediate cell-subtype. Intrahepatic tumor recurrence occurred 9 months later and transarterial chemoembolization was performed. Due to the progress of recurrent tumors, ABO-incompatible LDLT was performed. The explant liver pathology revealed four small masses of cHCC-CC with stem cell features. Pulmonary metastasectomy and chest wall resection were performed for metastatic lesions at 10 months after LT. Multiple tumor recurrence was detected at 21 months after LT with progression despite sorafenib administration. Currently, the patient is alive for past 26 months after LT. In conclusion, the clinical sequences of this case suggest that the role of salvage LT for cHCC-CC is much more limited than that for HCC because the tumor biology of cHCC-CC is more aggressive compared with HCC.
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http://dx.doi.org/10.4285/kjt.20.0037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235333PMC
June 2021

Recipient hepatectomy under total hepatic vascular exclusion to prevent hepatocellular carcinoma spread in living donor liver transplantation.

Korean J Transplant 2021 Jun 7;35(2):130-136. Epub 2021 Jun 7.

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

We present a case of recipient hepatectomy under total hepatic vascular exclusion (THVE) and venovenous bypass for living donor liver transplantation (LDLT) in a patient with multiple hepatocellular carcinomas (HCCs) closely located to the retrohepatic inferior vena cava (IVC). A 19-year-old male patient diagnosed with multiple HCCs underwent left lateral sectionectomy 14 months before and received four sessions of transarterial chemoembolization due to post-hepatectomy tumor recurrence. These pretransplant sequences implicated high risk of posttransplant HCC recurrence. However, LDLT was performed with expectation of prolonged survival. During recipient operation, the portal vein was transected and active venovenous bypass was performed. Supra- and infra-hepatic portions of the retrohepatic IVC were then clamped. Under THVE and portal vein bypass, recipient hepatectomy was meticulously performed. A modified right liver graft recovered from his brother was implanted according to standard procedures of LDLT. The patient recovered uneventfully from LDLT operation. However, multiple pulmonary metastasis occurred. The patient has been doing well for 12 months after LDLT, with administration of chemotherapeutic agents. Although early pulmonary metastasis occurred in this patient, we suggest that recipient hepatectomy under THVE and venovenous bypass can be a feasible technical option to cope with risk of iatrogenic tumor cell spread during LDLT operation.
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http://dx.doi.org/10.4285/kjt.20.0056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235345PMC
June 2021

Outcomes of deceased donor liver transplantation from elderly donors.

Korean J Transplant 2021 Jun 7;35(2):100-107. Epub 2021 Apr 7.

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

Background: Favorable outcomes achieved after deceased donor liver transplantation (DDLT) suggest that use of elderly donors may be an effective way to expand donor pool.

Methods: This was a retrospective analysis of adult DDLT using elderly donors. It was a double-arm study that compared posttransplant outcomes to ascertain whether use of elderly donors (aged ≥76 years) has adverse effects on outcome of DDLT. Elderly donor study group included 14 donors aged ≥76 years and elderly donor control group comprised 39 donors aged 66-75 years.

Results: Mean donor age of the study and control groups was 78.2±3.1 years and 68.9±2.7 years, respectively (P<0.001). Other clinical parameters were comparable between these two donor groups. The 1-, 3-, and 5-year graft survival rates in the elderly study group were 83.6%, 59.7%, and 59.7%, respectively, and those in the elderly control group were 79.4%, 68.1%, and 59.6%, respectively (P=0.97). The overall 1-, 3-, and 5-year survival rates after donation from elderly study group were 83.6%, 59.7%, and 59.7%, respectively, and those after donation from control group were 79.3%, 72.1%, and 64.1%, respectively (P=0.74). Regarding overall patient survival, univariate analysis identified pretransplant requirement for ventilator support (P=0.021) and pretransplant renal replacement therapy (P=0.025) as statistically significant risk factors; however, neither was significant on multivariate analysis.

Conclusions: The results of this study suggest that using an elderly donor graft might not worsen the posttransplant outcomes significantly; thus, advanced age per se may not be an exclusion criterion for organ donation.
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http://dx.doi.org/10.4285/kjt.20.0051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235342PMC
June 2021

Institutional standard framework and experience of living donor liver transplantation for overseas non-Korean patients at Asan Medical Center.

Korean J Transplant 2021 Jun 7;35(2):93-99. Epub 2021 Apr 7.

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

Background: Liver transplantation (LT) for foreign patients is a sensitive issue because of possibility of transplant tourism and difficulty in posttransplant follow-up. This study describes the institutional standard framework and experience of living donor LT (LDLT) for overseas non-Korean patients in a Korean high-volume LDLT center.

Methods: The framework and experience of LDLT for 105 non-Korean patients from 2010 to 2019 were retrospectively investigated.

Results: Only 3.1% of patients who underwent LDLT were overseas non-Koreans; of these, 83.8% were from the United Arab Emirates and Mongolia. Selection criteria for recipients and donors were the same as for Korean citizens. Of the 105 recipients, 95 (90.5%) were adults. The most common reasons for transplantation were hepatitis B or C virus-associated liver cirrhosis. Of the 95 adults, 78 (82.1%) received right liver grafts, and 16 (16.8%) received dual grafts. The most frequent donors for adult recipients were sons and daughters, whereas the most frequent donors for pediatric recipients were parents. Of the 10 pediatric patients, eight were from the United Arab Emirates; their common primary diseases were biliary atresia, acute liver failure, hepatoblastoma, and genetic metabolic diseases. The 1-, 3-, and 5-year posttransplant overall patient survival rates in all patients were 96.2%, 92.4%, and 92.4%, respectively. The 5-year overall patient survival rates were 91.8% in adult recipients and 100% in pediatric recipients (P=0.47).

Conclusions: LDLT at Korean high-volume LT centers including our institution is safe and effective for non-Korean patients with end-stage liver disease seeking alternatives not available in their own countries.
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http://dx.doi.org/10.4285/kjt.20.0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235324PMC
June 2021

Living donor liver transplantation in an infant patient with progressive familial intrahepatic cholestasis along with hepatocellular carcinoma: a case report.

Korean J Transplant 2022 Mar;36(1):73-78

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

Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease requiring liver transplantation (LT). Hepatocellular carcinoma (HCC) is very rare in infants. We present a case of living donor LT using a left lateral section graft performed in a 7-month-old female infant diagnosed with PFIC type II and HCC. No mutation on gene was identified. Because of progressive deterioration of liver function, living donor LT with her mother's left lateral section graft was performed. Pretransplant serum alpha-fetoprotein (AFP) level was increased to 2,740 ng/mL, but HCC was not taken into account because of its rarity. The explant liver showed micronodular liver cirrhosis, multiple infantile hemangiomas and two HCCs of 0.7 cm and 0.3 cm in size. The patient recovered uneventfully from the LT operation. This patient has been regularly followed up with abdomen ultrasonography and AFP measurement every 6 months. The patient has been continually doing well for 8 years after the LT. In conclusion, LT is currently the only effective treatment for PFIC-associated end-stage liver diseases. HCC can develop at the cirrhotic liver of any cause, thus elevation of HCC tumor markers in pediatric patients is an important clue to perform further investigation before LT.
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http://dx.doi.org/10.4285/kjt.21.0007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235533PMC
March 2022

Twenty-year longitudinal follow-up after liver transplantation: a single-center experience with 251 consecutive patients.

Korean J Transplant 2022 Mar;36(1):45-53

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

Background: The outcomes of liver transplantation (LT) have improved, but actual 20-year survival data have rarely been presented.

Methods: Longitudinal follow-up data of 20-year LT survivors were retrospectively analyzed. The LT database of our institution was searched to identify patients who underwent primary LT from January 2000 to December 2001. The study cohort of 251 patients was divided into three groups 207 adults who underwent living donor LT (LDLT), 22 adults who underwent deceased donor LT (DDLT), and 22 pediatric patients who underwent LT.

Results: Hepatitis B virus-associated liver cirrhosis and biliary atresia were the most common indications for adult and pediatric LT, respectively. Seven patients required retransplantation, including six who underwent DDLT and one who underwent LDLT. Twenty-two patients died within 3 months after LT and 69 died at later intervals. The overall survival rates at 1, 3, 5, 10, and 20 years were 86.4%, 79.6%, 77.7%, 72.8%, and 62.6%, respectively, in the adult LDLT group; 86.4%, 72.7%, 72.7%, 72.7%, and 68.2%, respectively, in the adult DDLT group; and 86.4%, 86.4%, 81.8%, 81.8%, and 77.3%, respectively, in the pediatric LT group (P=0.545). Common immunosuppressive regimens at 20 years included tacrolimus monotherapy, tacrolimus-mycophenolate dual therapy, cyclosporine monotherapy, and mycophenolate monotherapy.

Conclusions: The present study is the first report of actual 20-year survival data from a Korean high-volume LT center. The graft and patient survival outcomes reflected the early experiences of LT in our institution, with long-term outcomes being similar regardless of graft type and patient age.
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http://dx.doi.org/10.4285/kjt.21.0031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235526PMC
March 2022

Indications and outcomes of liver transplantation for post-Kasai biliary atresia in young adults.

Korean J Transplant 2021 Sep;35(3):177-182

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

Background: Some young adults have a long survival period with native liver after Kasai portoenterostomy (KPE) for biliary atresia (BA). However, a considerable proportion of these patients require liver transplantation (LT). This study aimed to analyze the indications and outcomes of LT in young adults after a long survival period with native liver after KPE.

Methods: We selected seven patients who were 18 years or older at the time of LT out of 116 BA patients who underwent primary LT from 2008 to 2019 at Asan Medical Center.

Results: The mean ages at KPE and LT were 2.1±0.9 months and 22.0±5.1 years, respectively. Mean serum total bilirubin level and model for end-stage liver disease score at LT were 7.91±7.22 mg/dL and 15.3±6.0, respectively. The main reasons for LT were liver cirrhosis with portal hypertension-associated complications in five patients and intractable cholangitis in two patients. There were five cases of living donor LT and two cases of deceased donor LT. All the seven patients are currently alive during the mean follow-up period of 74.7±40.9 months. One patient suffered from outflow graft vein obstruction requiring endovascular stenting. Another patient showed core antibody-positivity-induced de novo hepatitis B virus infection, which was well managed with antiviral therapy.

Conclusions: Young adult patients with BA are a unique group of patients requiring specialist care regarding transition from pediatric to adult services. The outcomes of LT in young adult BA patients were excellent. Therefore, LT should be considered in patients showing serious BA-associated complications.
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http://dx.doi.org/10.4285/kjt.21.0018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235452PMC
September 2021

Clinical sequence of an adult recipient undergone split liver transplantation using a right liver graft with erroneous deprivation of the middle hepatic vein trunk: a case report.

Korean J Transplant 2021 Sep 14;35(3):189-194. Epub 2021 Jul 14.

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

The anatomy of middle hepatic vein (MHV) varies widely, and some individuals have aberrant MHV anatomy, thus there is risk of iatrogenic damage to graft MHV during liver splitting. We present the clinical sequences of an adult recipient who received a split right liver graft with erroneous deprivation of the MHV trunk. This is the case was a 58-year-old male patient with hepatitis B virus-associated liver cirrhosis who suffered from hepatic encephalopathy. The split right liver graft had a graft-to-recipient weight ratio of 2.1%. Soon after graft reperfusion, large-sized hepatic venous congestion (HVC) appeared at the graft liver surface, indicating lack of MHV drainage. The amount of HVC was approximately 20% of the right liver graft mass at day 1, which had gradually reduced on follow-up computed tomography (CT) scans. Although liver function recovered progressively, the patient remained bed-ridden because of pre-existing hypoxic brain damage. The patient passed away 4 years after transplantation because of pneumonia and multi-organ failure. The present case implies that there is some possibility of unrecognized damage to the graft MHV during liver splitting, suggesting the necessity of preoperative donor abdomen CT scan and preparation of intraoperative ultrasonography for easy evaluation of graft liver MHV anatomy.
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http://dx.doi.org/10.4285/kjt.21.0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235449PMC
September 2021

Use of minor donors for living donor liver transplantation and associated ethical issues.

Korean J Transplant 2021 Sep;35(3):161-167

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

Background: Living liver donation by minors is regarded as justifiable only if minors possess the capacity to consent to donation and the procedure is in their best interests. This study analyzed the incidence of and reasons for living donor liver transplantation (LDLT) by minor donors in Korea, and discussed ethical issues regarding liver donation by minors.

Methods: The databases of the Korean Network for Organ Sharing (KONOS) and Asan Medical Center (AMC) from 2010 to 2019 were retrospectively reviewed to determine the incidence of LDLT by minor donors.

Results: From 2010 to 2019, 590 (4.1%) of 14,243 liver donors in the KONOS database and 276 (7.5%) of 3,401 liver donors in the AMC database were minors. The proportions of minor donors in the KONOS and AMC databases were highest in 2012, at 4.1% and 12.6%, respectively, and lowest in 2019, at 1.1% and 3.0%, respectively. Because most LDLT recipients had relatively low model for end-stage liver disease scores and hepatocellular carcinoma, they were unlikely candidates for deceased-donor liver transplantation and were highly likely to drop out of LDLT if they waited for 1-2 years. The donor-recipient relationship of minor donors in the AMC database was first-degree in 256 (92.8%) and second- or third-degree in 20 (7.2%).

Conclusions: Liver donation by minors is limitedly acceptable only when the minor proves informed, well-considered, and autonomous consent to the procedure and the procedure is in the minor's best interests. We suggest that minors be allowed to donate only to first-degree family members.
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http://dx.doi.org/10.4285/kjt.21.0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235445PMC
September 2021

Hepatic artery reconstruction using interposition of autologous saphenous vein conduit for living donor liver transplantation: a case report.

Korean J Transplant 2021 Sep 14;35(3):183-188. Epub 2021 May 14.

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

We have preferentially used the right gastroepiploic artery (RGEA) as an alternative for the recipient hepatic artery (HA) inflow during living donor liver transplantation (LDLT), but it was not always available. We herein present a case of adult LDLT with HA reconstruction using a greater saphenous vein (GSV) conduit because of the absence of the RGEA due to prior subtotal gastrectomy. A 55-year-old male patient diagnosed with hepatitis B virus-associated liver cirrhosis and secondary biliary cirrhosis underwent LDLT using a modified right liver graft. The upper abdominal cavity was heavily adhered due to prior abdominal surgeries, thus we had to sacrifice the common bile duct and the right HA completely. A 6-cm-long GSV segment was harvested from the left ankle and interposed between the recipient gastroduodenal artery and the graft HA. The patient recovered from LDLT and HA complications did not occur. However, 8 years after LDLT, chronic rejection occurred, thus repeated deceased donor liver transplantation was performed. This patient has been doing well for 2 years after retransplantation. In conclusion, we suggest that interposition of an autologous GSV conduit can be an alternative for establishing HA inflow in LDLT when other inflow source is not available.
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http://dx.doi.org/10.4285/kjt.20.0059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235453PMC
September 2021

Whole genome sequencing of matched tumor and adjacent normal tissues of HBV-induced hepatocellular carcinoma.

Asian J Surg 2022 Jun 9. Epub 2022 Jun 9.

Department of Surgery, School of Medicine, Kyung Hee University, Seoul, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.05.125DOI Listing
June 2022

Morbidity analysis of left hepatic trisectionectomy for hepatobiliary disease and live donor.

Hepatobiliary Pancreat Dis Int 2022 Aug 24;21(4):362-369. Epub 2022 May 24.

Department of Surgery, Gold Coast University Hospital, Southport, QLD 4215, Australia.

Background: Despite remarkable advances in surgical techniques and perioperative management, left hepatic trisectionectomy (LHT) remains a challenging procedure with a somewhat high postoperative morbidity rate compared with less-extensive resections. This study aimed to analyze the short- and long-term outcomes of LHT and identify factors associated with the postoperative morbidity of this technically demanding surgical procedure.

Methods: The medical records of 53 patients who underwent LHT between June 2005 and October 2019 at a single institution were retrospectively reviewed. The independent prognostic factor of postoperative morbidity was analyzed using the logistic regression model.

Results: Hepatocellular carcinoma was the most common indication for surgery (n = 21), followed by hilar cholangiocarcinoma (n = 14), intrahepatic cholangiocarcinoma (n = 10), and other pathologies (including colorectal liver metastasis, hepatolithiasis, gallbladder cancer, living donor, hemangioma, and multilocular biliary cyst; n = 8). The rates of postoperative morbidities of Clavien-Dindo grade 3 or higher and 90-day mortality were 39.6% and 1.9%, respectively. The 1-, 3-, and 5-year overall survival rates were 81.1%, 61.4%, and 44.6%, respectively. Multivariate analysis revealed that preoperative jaundice [hazard ratio (HR) = 6.15, 95% confidence interval (CI): 1.57-24.17, P = 0.009] and operative time > 420 min (HR = 4.66, 95% CI: 1.27-17.17, P = 0.021) were independent predictors of postoperative morbidity.

Conclusions: The in-hospital mortality of LHT surgery can be minimalized by a reliable preoperative evaluation of liver function and selection of the dominant anatomic features of right posterior sector, active and appropriate preoperative management for obstructive cholangitis and compensatory hypertrophy of the future remnant posterior sector, and the experience of the surgeon.
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http://dx.doi.org/10.1016/j.hbpd.2022.05.010DOI Listing
August 2022

Safety of Tacrolimus Monotherapy within 12 Months after Liver Transplantation in the Era of Reduced Tacrolimus and Mycophenolate Mofetil: National Registry Study.

J Clin Med 2022 May 17;11(10). Epub 2022 May 17.

Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea.

Tacrolimus monotherapy is accepted as a feasible option during early post-liver transplantation as per current international consensus guidelines. However, its effects in the recent era of reduced tacrolimus (TAC) and mycophenolate mofetil (MMF) remain unclear. Liver recipients who either received TAC monotherapy from the treatment onset or switched from TAC/MMF to TAC-mono within 12 months (TAC-mono group; n = 991) were chronologically matched to patients who continued to receive TAC/MMF (TAC/MMF group; n = 991) at the corresponding time points on time-conditional propensity scores. Outcomes within 12 months after matched time points were compared. Biopsy-proven rejection (TAC/MMF: 3.5% vs. TAC-mono: 2.6%; = 0.381) and graft failure (0.2% vs. 0.7%; = 0.082) were similar in both groups. However, the decline in eGFR was 3.1 mL/min/1.73 m (95% CI: 0.8-5.3) greater at six months ( = 0.008) and 2.4 mL/min/1.73 m (95% CI: -0.05-4.9) greater at 12 months ( = 0.048) after the matched time points in TAC-mono group than that in TAC/MMF group. TAC trough levels were also higher in the TAC-mono group throughout the study period. TAC-mono within 12 months after liver transplantation is immunologically safe. However, it can increase the required TAC dose and the decline in renal function than that in TAC/MMF combination therapy.
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http://dx.doi.org/10.3390/jcm11102806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145025PMC
May 2022

Analysis of outcomes and renal recovery after adult living-donor liver transplantation among recipients with hepatorenal syndrome.

Am J Transplant 2022 May 26. Epub 2022 May 26.

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

When timely access to deceased-donor livers is not feasible, living-donor liver transplantation (LDLT) is an attractive option for patients with hepatorenal syndrome (HRS). This study's primary objective was to describe outcomes after LDLT among HRS recipients, and the secondary objective was to determine predictors of poor renal recovery after LDLT. This single-center, retrospective study included 2185 LDLT recipients divided into HRS (n = 126, 5.8%) and non-HRS (n = 2059, 94.2%) groups. The study outcomes were survival and post-LT renal recovery. The HRS group had a higher death rate than the non-HRS group (17.5% vs. 8.6%, p < 0.001). In the HRS group, post-LT renal recovery occurred in 69.0%, and the death rate was significantly lower in association with HRS recovery compared with non-recovery (5.7% vs. 43.6%, p < 0.001). Multivariable analysis indicated that post-LT sepsis (p < 0.001) and non-recovery of HRS (p < 0.001) were independent negative prognostic factors for survival. Diabetes mellitus (p = 0.01), pre-LT peak serum creatinine ≥3.2 mg/dl (p = 0.002), time interval from HRS diagnosis to LDLT ≥38 days (p = 0.01), and post-LT sepsis (p = 0.03) were important negative prognostic factors for renal recovery after LDLT. In conclusion, post-LT renal recovery was important for survival, and the interval from HRS to LDLT was significantly associated with post-LT renal recovery.
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http://dx.doi.org/10.1111/ajt.17105DOI Listing
May 2022

Pure laparoscopic versus open left lateral sectionectomy for hepatocellular carcinoma: A propensity score matching analysis.

Ann Hepatobiliary Pancreat Surg 2022 May;26(2):133-137

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

Backgrounds/aims: Anatomical resection has superior oncologic outcomes over non-anatomical resection in hepatocellular carcinoma, and left lateral sectionectomy is the simplest and easiest perform anatomical resection procedure among liver resections. The purpose of this study was to find out the safety and feasibility of pure laparoscopic left lateral sectionectomy (PLLLS) for hepatocellular carcinoma.

Methods: Patients who underwent left lateral sectionectomy at a tertiary referral hospital, from August 2007 to April 2019 were enrolled in this retrospective study. After matching the 1 : 3 propensity score, 17 open and 51 pure laparoscopic cases were selected out of 102 cases of total left lateral resection for hepatocellular carcinoma. The group was analyzed in terms of patient demographics, preoperative data, and postoperative outcomes.

Results: During the study period, there was no open conversion case. The mean operative time and complication were not statistically significant different between the two groups. There was no statistically significant difference in disease-free survival and overall survival had no statistical between the two groups. There were no mortality cases, and postoperative hospital stay was significantly shorter in the PLLLS group than in the open left lateral sectionectomy (OLLS) group.

Conclusions: The oncologic outcomes and complication rate were the same in the PLLLS and OLLS groups. However, the hospital stay was shorter in the PLLLS group than in the OLLS group. The present study findings demonstrate that the PLLLS is a safe and feasible procedure for hepatocellular carcinoma.
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http://dx.doi.org/10.14701/ahbps.21-161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136418PMC
May 2022

Optimizing pre-donation physiologic evaluation for enhanced recovery after living liver donation - Systematic review and multidisciplinary expert panel recommendations.

Clin Transplant 2022 May 3:e14680. Epub 2022 May 3.

Department of Surgery & Interventional Science, University College London, UK.

Background: While pre-operative physiologic evaluation of live liver donors is routinely performed to ensure donor safety and minimize complications, the optimal approach to this evaluation is unknown.

Objectives: We aim to identify pre-donation physiologic evaluation strategies to improve post-operative short-term outcomes, enhance donor's recovery, and reduce length of stay. We also aim to provide multidisciplinary expert panel recommendations.

Data Sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.

Methods: The systematic review followed PRISMA guidelines, and the recommendations were formulated using GRADE approach and expert's opinion. The search included retrospective or prospective studies, describing outcomes of physiologic evaluation pre-donation. The outcomes of interest were length of stay, post-operative complications (POC), recovery after donation, and mortality. PROSERO protocol ID CRD42021260662.

Results: Of 1386 articles screened, only three retrospective cohort studies met eligibility criteria. Two studies demonstrated no impact of age (<70 years) on POC. Increased body mass index's (BMI) association with POC was present in one study (23.8 vs 21.7 kg/m , OR 1.67 (1.14-2.48), p = 0.01) and absent in another (<30 vs 30-35 kg/m , p = 0.61). One study demonstrated decreased risk for post-donation subclinical hepatic dysfunction in donors with higher normal platelet count (PLT). None of the studies noted donor death. Given the scarce data on pre-donation physiologic testing, the expert panel recommended a battery of tests to guide clinical practice and future investigations.

Conclusion: Advancing age (60-69 years) is not a contraindication for liver donation. There is insufficient evidence for a specific pre-donation BMI cut-off. Abbreviated pre-donation physiologic testing is recommended in all candidates. Comprehensive testing is recommended in high-risk candidates while considering the pretest probability in various populations (Quality of evidence; Low to Very Low | Grade of Recommendation; Strong). This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/ctr.14680DOI Listing
May 2022

Renal safety of tenofovir disoproxil fumarate and entecavir in liver transplant patients: a nationwide Korean registry study.

Hepatol Int 2022 Jun 23;16(3):537-544. Epub 2022 Apr 23.

Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background And Aims: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have been recommended after liver transplantation to prevent recurrence of hepatitis B virus infection. Despite its proven efficacy, the renal safety of TDF has not been established in liver transplant recipients. We aimed to compare the effects of TDF and ETV on renal function in liver transplant recipients and to evaluate risk factors for renal dysfunction after liver transplantation.

Methods: This is a retrospective, observational multicenter study of data from the Korean Organ Transplantation Registry. We included adults who underwent liver transplantation for hepatitis B virus-related complications from April 2014 to December 2017 and received TDF or ETV post-transplantation. Renal dysfunction was defined as an estimated glomerular filtration rate decline by at least 20% from baseline (1 month post-transplantation). Median duration of follow-up was 29 months (interquartile range 19-42).

Results: A total of 804 liver transplant patients were included. The cumulative probability of renal dysfunction was significantly higher in the TDF group than in the ETV group. Multivariable analysis confirmed that TDF was independently associated with an increased risk of renal dysfunction (hazard ratio = 1.47, 95% confidence interval 1.12-1.92; p = 0.005). Independent risk factors for renal dysfunction included older age, worse baseline renal function, and low body mass index. Overall survival rate was significantly lower in patients with renal dysfunction than in those without.

Conclusions: In this nationwide study, the use of TDF was associated with an increased risk of renal dysfunction, when compared with ETV.
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http://dx.doi.org/10.1007/s12072-022-10320-zDOI Listing
June 2022

Assessment of pathogens and risk factors associated with bloodstream infection in the year after pediatric liver transplantation.

World J Gastroenterol 2022 Mar;28(11):1159-1171

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul 05505, South Korea.

Background: Bloodstream infection (BSI) is one of the most significantly adverse events that can occur after liver transplantation (LT) in children.

Aim: To analyze the profile of BSI according to the postoperative periods and assess the risk factors after pediatric LT.

Methods: Clinical data, collected from medical charts of children ( = 378) who underwent primary LT, were retrospectively reviewed. The primary outcome considered was BSI in the first year after LT. Univariate and multivariate analyses were performed to identify risk factors for BSI and respective odds ratios (ORs).

Results: Of the examined patients, 106 (28%) experienced 162 episodes of pathogen-confirmed BSI during the first year after LT. There were 1.53 ± 0.95 episodes children (mean ± SD) among BSI-complicated patients with a median onset of 0.4 mo post-LT. The most common pathogenic organisms identified were , followed by and About half (53%) of the BSIs were of unknown origin. Multivariate analysis demonstrated that young age (≤ 1.3 year; OR = 2.1, = 0.011), growth failure (OR = 2.1, = 0.045), liver support system (OR = 4.2, = 0.008), and hospital stay of > 44 d (OR = 2.3, = 0.002) were independently associated with BSI in the year after LT.

Conclusion: BSI was frequently observed in patients after pediatric LT, affecting survival outcomes. The profile of BSI may inform clinical treatment and management in high-risk children after LT.
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http://dx.doi.org/10.3748/wjg.v28.i11.1159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985487PMC
March 2022

Operative and long-term oncologic outcomes of laparoscopic versus open major liver resection in patients with a high body mass index (> 25 kg/m): a propensity score matching analysis.

Surg Endosc 2022 Aug 17;36(8):5772-5783. Epub 2022 Mar 17.

Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul, 138-736, Korea.

Background: With the recent rapid increase in the prevalence of obesity, the number of obese patients requiring liver resection, including laparoscopy, has increased. Accordingly, evaluating the outcome of laparoscopic liver resection in obese patients is increasingly important. This study aimed to compare the safety and feasibility of laparoscopic major liver resection (LMR) and open major liver resection (OMR) in patients with a high body mass index (BMI > 25.0 kg/m).

Methods: We reviewed 521 patients with high BMI (> 25.0 kg/m) who underwent major liver resection for various indications between January 2009 and November 2018 at Asan Medical Center. We performed 1:1 propensity score matching of the LMR and OMR groups, with 120 patients subsequently included in each group.

Results: LMR was associated with lower blood loss and shorter postoperative hospital stays (p < 0.001). Although there was no significant difference in overall complications (p = 0.080), non-liver-specific complications were observed less frequently after LMR (p = 0.025). American Society of Anesthesiologists class > II, BMI > 30 kg/m, and malignancy were independent predictors of morbidity. In a subgroup analysis of patients with hepatocellular carcinoma, there was no significant difference between the two groups in overall survival (hazard ratio 0.225; 95% confidence interval 0.049-1.047; p = 0.057) and recurrence-free survival (hazard ratio 0.761; 95% confidence interval 0.394-1.417; p = 0.417).

Conclusions: Obesity should not be considered a contraindication for major liver resection using a laparoscopic approach; however, when applying this approach for resecting malignancies in patients with a BMI > 30 kg/m and comorbid diseases, special attention should be paid to the possibility of complications.
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http://dx.doi.org/10.1007/s00464-022-09114-zDOI Listing
August 2022

Impact of overweight and obesity on the risk of hepatocellular carcinoma: a prospective cohort study in 14.3 million Koreans.

Br J Cancer 2022 07 5;127(1):109-115. Epub 2022 Mar 5.

Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, 25601, Republic of Korea.

Background: Whether obesity and being overweight, defined by body mass index (BMI), increase hepatocellular carcinoma (HCC) has been less apparent in Asian populations.

Methods: Overall, 14,265,822 Korean adults who underwent routine health examinations during 2003-2006 were followed up for HCC. Multivariable-adjusted hazard ratios (HRs) associated with BMI were calculated.

Results: During 13.7 years (mean) of follow-up, 47,308 individuals developed HCC. HRs of HCC associated with BMIs of 25.0-26.4, 26.5-27.9, 28.0-29.4, 29.5-30.9 and ≥31 kg/m² compared to those for 23.5-24.9 kg/m² were 1.05, 1.20, 1.39, 1.59 and 2.13, respectively. For BMI < 25 kg/m², linear associations were not apparent. For BMI ≥ 25 kg/m, the HR per 5 kg/m increase in BMI was 1.60 (total), 1.60 (men), and 1.59 (women). The corresponding HRs were 1.56, 1.61 and 1.60 for individuals aged <45, 45-64 and ≥65 years, respectively. Further adjustment for alanine transaminase (ALT) levels substantially reduced the HRs for high BMI, especially in men and younger adults.

Conclusions: Overweight and obesity clearly increase HCC risk in Koreans. ALT levels are a mediator of the impact of obesity, but it may not accurately predict high BMI-induced liver damage that can potentially progress to HCC, especially in women and older adults.
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http://dx.doi.org/10.1038/s41416-022-01771-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276765PMC
July 2022

Gα overexpression in hepatocytes by ER stress exacerbates acute liver injury via ROCK1-mediated miR-15a and ALOX12 dysregulation.

Theranostics 2022 9;12(4):1570-1588. Epub 2022 Jan 9.

College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang-si, Kyeonggi-do 10326, Republic of Korea.

Liver injury must be further characterized to identify novel therapeutic approaches. Endoplasmic reticulum (ER) stress may cause hepatocyte death. Gα affects cell viability and its expression varies depending on physiological conditions. This study investigated whether hepatocyte-specific Gα overexpression affects acute liver injury, and if so, what the underlying mechanisms and treatment strategies are. All experiments were performed using human liver, hepatocytes, and toxicant injury models with KO and/or hepatocyte-specific Gα overexpression. RNA-sequencing, immunoblotting, immunohistochemistry, reporter assays, and mutation assays were conducted. Hepatic Gα was overexpressed in mice challenged with acetaminophen or other ER stress inducers or in patients with acute liver injury or fibrosis/cirrhosis. Several Gα and ER-associated pathways were identified using transcriptomic analysis. Acetaminophen intoxication was characterized by lipid peroxide-induced ferroptosis and was less severe in Gα-deficient animals and cells. Conversely, Gα overexpression in wild-type or KO hepatocytes increased hepatotoxicity, promoting lipid peroxidation, inflammation, and ferroptosis. IRE1α-dependent Xbp1 transactivated . Moreover, Gα overexpression enhanced the ability of acetaminophen to induce ALOX12, while downregulating GPX4. The level of miR-15a, herein identified as an ALOX12 inhibitor, was decreased. siRNA knockdown or pharmacological inhibition of ROCK1 prevented dysregulation of ALOX12 and GPX4, rescuing animals from toxicant-induced ferroptosis. These changes or correlations among the targets were confirmed in human liver specimens and datasets of livers exposed to other injurious medications. Gα overexpression by ER stress facilitates hepatocyte ferroptosis through ROCK1-mediated dysregulation of ALOX12, and miR-15a, supporting the concept that inhibition of Gα overexpression and/or ROCK1 axis may constitute a promising strategy for acute liver injury.
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http://dx.doi.org/10.7150/thno.67722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825599PMC
April 2022

Clinicopathological Features and Long-Term Outcomes of Intraductal Papillary Neoplasms of the Bile Duct of the Liver: Single-Institution Experience with 146 Patients.

J Gastrointest Surg 2022 Jul 9;26(7):1394-1405. Epub 2022 Feb 9.

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

Background: Intraductal papillary neoplasm of the bile duct (IPNB) has a wide range of histopathology and intra- and extrahepatic tumor locations.

Methods: This retrospective single-center study evaluated the clinicopathological features and long-term outcomes of 146 patients with IPNB of the liver (IPNB-L) who underwent hepatic resection between January 2002 and June 2019.

Results: The 146 patients included 97 (66.4%) men and 49 (33.6%) women, of mean age 64.3 ± 8.0 years. Seventy-two (49.3%) patients were incidentally diagnosed, with no specific symptoms, and 18 (12.3%) were found to have hepatolithiasis. Sixty-one (41.8%) and two (1.4%) patients underwent concurrent bile duct resection and pancreaticoduodenectomy, respectively, and 130 (89.0%) underwent R0 resection. Low-grade and high-grade intraepithelial neoplasia, and invasive carcinoma were identified in 26 (17.8%), 50 (34.2%), and 70 (47.9%) patients, respectively. Five-year tumor recurrence and patient survival rates were 8.4% and 93.9%, respectively, in patients with high-grade neoplasia; and 41.5% and 72.3%, respectively, in patients with invasive carcinoma. CA19-9 > 37 U/mL and R1 resection were independent risk factors for tumor recurrence and reduced survival in patients with carcinoma. The combination of hypermetabolic fluorodeoxy-glucose-positron emission tomography (FDG-PET) or elevated CA19-9 showed a sensitivity of 91.8% and a specificity of 61.9% for the prediction of IPNB-L with high-grade neoplasia and carcinoma.

Conclusions: IPNB-L is a rare type of intrahepatic biliary neoplasm that can range histologically from benign disease to invasive carcinoma. Surgical curability is the most important prognostic factor, thus aggressive resection is highly recommended to achieve R0 resection.
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http://dx.doi.org/10.1007/s11605-022-05268-2DOI Listing
July 2022
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