The history of organ transplantation is limited to the last century. To overcome the barrier of the host immune system, which results in transplant rejection, the pioneers of transplantation achieved their first success by performing a kidney transplantation between identical twins. This achievement led the transplant clinicians to perform transplantations with immunological barriers present. Strategies such as whole-body irradiation combined with steroids yielded success in kidney transplantation between non-identical twins and siblings. However, owing to the toxicity related to irradiation, the paradigm shifted to the use of immunosuppressants. Azathioprine, steroids, and anti-lymphocyte globulin became the first multiple immunosuppressive regimens. With the introduction of cyclosporine, the 1-year survival rate increased by more than 80%. Cyclosporine, azathioprine, and steroids became the new standard maintenance regimens until the introduction of tacrolimus and mycophenolate mofetil, which replaced cyclosporine and azathioprine, respectively. The most recent change in immunosuppressants was the development of monoclonal antibodies with specific binding sites, such as CD20 (rituximab) and CD25 (basiliximab). With the innovation of molecular engineering and new insights into the costimulatory pathways, new molecules are under investigation in the field of transplantation.

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.

Background: Liver transplant (LT) recipients were considered a vulnerable population during the coronavirus disease 2019 (COVID-19) pandemic. The clinical efficacy of the COVID-19 vaccine is unknown in immunocompromised patients. The purpose of this study was to provide evidence of antibody responses after COVID-19 vaccination in LT recipients. Methods: This study enrolled 46 patients who underwent LT at Samsung Medical Center (Seoul, Korea) before implementation of the one-dose vaccine in Korea. Those who completed the two-dose COVID-19 vaccine between August 2021 and September 2021 were included and followed through December 2021. Semiquantitative anti-spike serologic testing was performed using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (Roche Diagnostics, Rotkereuz, Switzerland) with a positive cutoff of at least 0.8 U/mL. Results: Among all 46 participants, 40 (87%) demonstrated an antibody response after the second dose of a COVID-19 vaccine, while six (13%) had no antibody response after the second dose. Upon univariate analysis, patients with higher antibody titer had longer years since LT (2.3 ± 2.8 vs. 9.4 ± 5.0, P < 0.001). A lower median tacrolimus (TAC) level before vaccination and after the second dose of COVID-19 vaccine indicated a significantly higher antibody response (2.3 [1.6–3.2] vs. 7.0 [3.7–7.8], P = 0.006, 2.5 [1.6–3.3] vs. 5.7 [4.2–7.2], P = 0.003). Period between 2nd vaccination and serologic testing was significantly higher in the antibody-response group compared to the no-antibody-response group (30.2 ± 24.0 vs. 65.9 ± 35.0, P = 0.012). A multivariate analysis of antibody responses revealed TAC level before vaccination as a statistically significant factor. Conclusion A higher TAC level before vaccination resulted in less effective vaccination in LT patients. Booster vaccinations are required, especially for patients in the early stage after LT who have compromised immune function.

Purpose: Liver fibrosis plays an important role in the development of hepatocellular carcinoma (HCC) and determining its prognosis. Although many staging systems and liver reserve models have been developed without the intention of predicting prognosis of HCC, some studies have investigated their prognostic values in HCC after curative liver resection (LR). The aim of this study is to evaluate prognostic value of non-invasive biomarkers after curative LR. Methods: Between 2006 and 2013, HCC patients underwent LR were included and total 962 patients were enrolled. All non-invasive biomarkers (fibrosis 4 index (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and albumin-bilirubin (ALBI) score) were measured at the time of HCC diagnosis. To binarize each biomarker, an optimal cut-off value for fibrosis stage was selected using the value of minimum distance from the left-upper corner of the receiver operating characteristic curve with a specificity >60%. We performed Cox regression analysis on 2-year recurrence-free survival (RFS) and overall survival (OS). Results: The area under curve values for FIB-4 and APRI were the largest for fibrosis stage compared to other biomarkers, 0.669 (95% confidential interval (CI), 0.610–0.719) and 0.748 (95% CI, 0.692–0.800), respectively. Between those two indices, FIB-4 is considered a statistically significant prognostic factor of RFS in HCC patients after LR. The HR for 2-year RFS and OS were 1.81 (95% CI, 1.18–2.77; P = 0.007) and 2.36 (95% CI, 0.99–5.65; P = 0.054), respectively. Conclusion FIB-4 is identified as a statistically significant predictor of HCC prognosis after curative LR even in HBV dominant populations.

Background: /Aim: Since the introduction of laparoscopy for liver resection in the 1990s, the performance of laparoscopic liver resection (LLR) has been steadily increasing. However, there is currently no data on the extent to which laparoscopy is used for liver resection. Herein, we investigated the extent to which laparoscopy is performed in liver resection and sought to determine whether surgeons prefer laparoscopy or laparotomy in the posterosuperior (PS) segment. Methods: For this retrospective observational study, we enrolled patients who had undergone liver resection at the Samsung Medical Center between January 2020 and December 2021. The proportion of LLR in liver resection was calculated, and the incidence and causes of open conversion were investigated. Results: A total of 1,095 patients were included in this study. LLR accounted for 79% of the total liver resections. The percentage of previous hepatectomy (16.2% vs. 5.9%, P<0.001) and maximum tumor size (median 4.8 vs. 2.8, P<0.001) were higher in the open liver resection (OLR) group. Subgroup analysis revealed that tumor size (median 6.3 vs. 2.9, P<0.001) and surgical extent (P<0.001) in the OLR group were larger than those in the LLR group. The most common cause of open conversion (OC) was adhesion (57%), and all OC patients had tumors in the PS. Conclusions We investigated the recent preference of practical surgeons in liver resection, and found that surgeons preferred OLR to LLR when treating a large tumor located in the PS.

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.

BACKGROUND: This study was designed to analyze the clinical usefulness of mycophenolic acid trough concentration monitoring in kidney transplantation patients who were maintained with cyclosporine. METHODS: The data of patients who underwent mycophenolic acid trough concentration monitoring after their first kidney transplant between November 2006 and August 2013 and were prescribed with cyclosporine, mycophenolate, and methylprednisolone were reviewed retrospectively. Cox analysis was used to analyze the risk factors for acute rejection within 1 year post-transplantation. RESULTS: Among 90 patients, 41 (45.6%) achieved both the target levels of cyclosporine and mycophenolic acid, while three patients (3.3%) failed to achieve the target level of either cyclosporine or mycophenolic acid. Nine patients (10.0%) only achieved the mycophenolic acid target level and 37 patients (41.1%) only achieved the cyclosporine target level. While patients who achieved only the mycophenolic acid target concentration had no statistically increased risk compared to patients who achieved both target levels (hazard ratio [HR], 1.569; 95% confidence interval [CI], 0.316 to 7.778; P=0.581), patients who only achieved the cyclosporine target concentration showed an increased risk of rejection compared to the both achievement group (HR, 4.112; 95% CI, 1.583 to 10.683; P=0.004). Patients who had no achievement in the target levels showed significantly increased rejection risk compared to the patients who achieved both target levels (HR, 17.811; 95% CI, 3.072 to 103.28; P=0.001). CONCLUSIONS: Mycophenolic acid trough concentration monitoring combined with cyclosporine trough concentration monitoring is useful for avoiding acute cellular rejection if the first 1 year post-transplantation.
Cyclosporine* ; Drug Monitoring ; Humans ; Kidney Transplantation ; Kidney* ; Methylprednisolone ; Mycophenolic Acid* ; Retrospective Studies ; Risk Factors

PURPOSE: This study was designed to analyze factors related to the success of salvage liver transplantation (SLT) in hepatocellular carcinoma (HCC). While liver resection (LR) is considered the best locoregional therapy in HCC, there is a high recurrence rate. SLT may be the best treatment option when feasible. METHODS: Patients who underwent living donor SLT for recurrent HCC after LR from November 1996 to May 2017 were included. Patient demographic data, clinical and pathologic characteristics, operative data, hospital course, and follow-up data regarding initial LR, locoregional therapy after recurrence and SLT were reviewed. Prognostic factors for recurrence were analyzed using Cox proportional hazard ratio. RESULTS: Eighty-five of 123 SLT patients were included. Patients who had five or more locoregional therapies prior to SLT (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.45–9.64, P = 0.006), hepatitis B (HR, 9.20; 95% CI, 1.13–74.89; P = 0.04), outside Milan criteria at the time of SLT (HR, 2.66, 95% CI, 1.26–5.63; P = 0.011) and an alpha-fetoprotein level above 1,000 ng/mL at the time of recurrence after initial LR (HR, 6.48; 95% CI, 1.83–22.92; P = 0.004) and at the time of transplantation (HR, 3.43; 95% CI, 1.26–5.63; P = 0.011) were related to significant risk of recurrence. CONCLUSION: Continuing five or more locoregional therapies for recurrent HCC after LR is related to poor recurrence-free survival after SLT.
alpha-Fetoproteins ; Carcinoma, Hepatocellular* ; Follow-Up Studies ; Hepatitis B ; Humans ; Liver Transplantation* ; Liver* ; Living Donors* ; Recurrence

Background: /Aim: Hepatocellular carcinoma (HCC) tumor thrombi located in the first branch of the portal vein (Vp3) or in the main portal trunk (Vp4) are associated with poor prognosis. This study aimed to investigate the clinicopathological characteristics and risk factors for HCC recurrence and mortality following liver resection (LR) in patients with Vp3 or Vp4 HCC. Methods: The study included 64 patients who underwent LR for HCC with Vp3 or Vp4 portal vein tumor thrombosis (PVTT). Results: Fifty-eight patients (90.6%) had Vp3 PVTT, whereas the remaining six patients exhibited Vp4 PVTT. The median tumor size measured 8 cm, with approximately 36% of patients presented with multiple tumors. Fifty-four patients (84.4%) underwent open LR, whereas 10 patients underwent laparoscopic LR. In the Vp4 cases, combined LR and tumor thrombectomy were performed. The 3-year cumulative disease-free survival rate was 42.8% for the Vp3 group and 22.2% for the Vp4 group. The overall survival (OS) rate at 3 years was 47.9% for the Vp3 group and 60.0% for the Vp4 group. Intrahepatic metastasis has been identified as an important contributor to HCC recurrence. High hemoglobin levels are associated with high mortality. Conclusion LR is a safe and effective treatment modality for selected patients with Vp3 or Vp4 HCC PVTT. This suggests that LR is a viable option for these patients, with favorable outcomes in terms of OS.

PURPOSE: It is believed that blood from the superior mesenteric vein and splenic vein mixes incompletely in the portal vein and maintains a streamline flow influencing its anatomic distribution. Although several experimental studies have demonstrated the existence of streamlining, clinical studies have shown conflicting results. We investigated whether streamlining of portal vein affects the lobar distribution of colorectal liver metastases and estimated its impact on survival. METHODS: Data of patients who underwent hepatectomy for colorectal liver metastases were retrospectively collected. The chi-square test was used for analyzing the distribution of metastasis. Cox analysis was used to identify risk factors of survival. Fisher exact test was used for subgroup analysis comparing hepatic recurrence. RESULTS: A total of 410 patients were included. The right-to-left ratio of liver metastases were 2.20:1 in right-sided colon cancer and 1.39:1 in left-sided cancer (P = 0.017). Cox analyses showed that margin < 5 mm (P < 0.001; 95% confidence interval [CI], 1.648–4.884; hazard ratio [HR], 2.837), age ≥ 60 years (P = 0.004; 95% CI, 1.269–3.641; HR, 2.149), N2 status (P < 0.001, 95% CI, 1.598–4.215; HR, 2.595), tumor size ≥ 45 mm (P = 0.014; 95% CI, 1.159–3.758; HR, 2.087) and other metastasis (P = 0.012; 95% CI, 1.250–5.927; HR, 2.722) were risk factors of survival. However, in 70 patients who underwent right hemihepatectomy for solitary metastasis, left-sided colorectal cancer was a risk factor (P = 0.019; 95% CI, 1.293–17.956; HR, 4.818), and was associated with higher recurrence than right-sided cancer (43.1% and 15.8%, respectively, P = 0.049). CONCLUSION: This study showed significant difference in lobar distribution of liver metastases between right colon cancer and left colorecral cancer. Furthermore, survival of left-sided colorectal cancer was poorer than that of right-sided cancer in patients who underwent right hemihepatectomy for solitary metastasis. These findings can be helpful for clinicians planning treatment strategy.
Colonic Neoplasms ; Colorectal Neoplasms ; Hepatectomy ; Humans ; Liver* ; Mesenteric Veins ; Neoplasm Metastasis* ; Portal Vein* ; Recurrence ; Retrospective Studies ; Risk Factors ; Splenic Vein