Achieving 400 Living Donor Liver Transplantations Annually During the COVID-19 Pandemic: A Single-Center Experience.

BACKGROUND: The COVID-19 pandemic has had a major impact on liver transplantation (LT) and living donor programs globally. PURPOSE: In this study, we aimed to present the principles and strategies of our LT program during the pandemic period and describe its achievements. BASIC PROCEDURES: We retrospectively reviewed the outcomes of 1417 LTs performed at Asan Medical Center, Seoul, Korea, from 2020 to 2022. Of these, 216 recipients who received transplants from deceased donors were excluded, and 1201 recipients who received transplants from 1268 live donors were included in the study, including 38 children <18 years old. MAIN FINDINGS: Among the 1201 living donor LT (LDLT) recipients, the most common indication for LT was unresectable hepatocellular carcinoma (315/1163, 27.1%) in adults and biliary atresia (29/38, 76.3%) in pediatric recipients. Emergency LDLT was performed in 40 patients (3.3%). The median model of end-stage liver disease and pediatric end-stage liver disease scores were 13.9 ± 7.2 and 13.8 ± 7.1, respectively. In-hospital mortality of recipients was higher than usual at 2.2%, but the cause of death was not related to COVID-19 infection. Of the 1268 live donors who underwent hepatectomy for liver donation, 660 (52.1%) underwent hepatectomy using a minimally invasive approach. Although 17 (1.3%) live donors experienced major complications, there were no serious life-threatening complications and no mortality. CONCLUSION: Even in a pandemic era, a team with well-established infection control protocols, patient-tailored surgical strategies, and thorough perioperative care can maintain LDLT at a similar quantitative and qualitative level as in a non-pandemic era.

Safety and outcome of treatment of latent tuberculosis infection in liver transplant recipients.

PURPOSE: Liver transplant (LT) recipients have an increased risk of tuberculosis (TB), which is associated with higher mortality rates. This retrospective cohort study assessed the outcome and tolerability of screening and treatment of latent tuberculosis infection (LTBI) in LT recipients. METHODS: Between March 2020 and February 2022, all adult LT candidates at our institution were screened for LTBI. The candidates who tested positive for interferon-γ-releasing assay or met epidemiological or clinical-radiological criteria for LTBI were treated and monitored. RESULTS: Among the 857 LT recipients, 199 (23.2%) were diagnosed with LTBI, of which 171 (85.9%) initiated LTBI treatment. The median duration of follow-up was 677 days. Adequate LTBI treatment occurred in 141/171 (82.5%) patients and was discontinued prematurely in 30/171 (17.5%) patients. The most common reason for discontinuation was liver enzyme elevation (11/30, 36.7%), although only five discontinued treatment due to suspicion of isoniazid-associated hepatotoxicity. None of the LTBI-treated patients developed active TB during the follow-up period, while 3.6% (1/28) of untreated LTBI patients and 0.6% (4/658) of patients without LTBI developed TB. CONCLUSION: These findings demonstrate that LTBI screening and treatment is a safe and effective strategy to prevent TB in LT recipients. However, monitoring for adverse events and liver enzyme elevation is recommended.

Mini-incision Right Hepatectomy for Living Donor Hepatectomy.

BACKGROUND: The application of a minimally invasive technique to graft procurement in living donor liver transplantation has minimized skin incisions and led to early recovery in donor hepatectomy while ensuring donor safety. This study aimed to evaluate the safety and feasibility of mini-incision living donor right hepatectomy compared with conventional open surgery. METHODS: The study population consisted of 448 consecutive living donors who underwent living donor right hepatectomy performed by a single surgeon between January 2015 and December 2019. According to the incision type, the donors were divided into 2 groups: a right subcostal mini-incision group (M group: n = 187) and a conventional J-shaped incision group (C group: n = 261). A propensity score matching analysis was conducted to overcome bias. RESULTS: The estimated graft volume and measured graft weight were significantly lower in the M group ( P = 0.000). The total of 17 (3.8%) postoperative complications were identified. The readmission rate and overall postoperative complication rate of donors was not significantly different between the groups. The biliary complication rates in the recipients were 12.6% and 8.6% in the C group and M group, respectively ( P = 0.219). Hepatic artery thrombosis requiring revision developed in 2 patients (0.8%) in the C group and 7 patients (3.7%) in the M group ( P = 0.038). After propensity score matching, these complications were not significantly different between the groups. CONCLUSIONS: Mini-incision living donor right hepatectomy shows comparable biliary complications to open surgery and is considered a safe and feasible operative technique.

Efficacy and safety of adhesion barrier in living-donor liver transplantation with right liver graft to prevent delayed gastric emptying.

Delayed gastric emptying (DGE) is a common complication of liver transplantation. This study aimed to clarify the efficacy and safety of the application of an adhesion barrier for preventing DGE in living-donor liver transplantation. This retrospective study included 453 patients who underwent living-donor liver transplantation using a right lobe graft between January 2018 and August 2019, and the incidence of postoperative DGE and complications was compared between patients in whom adhesion barrier was used (n=179 patients) and those in whom adhesion barrier was not used (n=274 patients). We performed 1:1 propensity score matching between the 2 groups, and 179 patients were included in each group. DGE was defined according to the International Study Group for Pancreatic Surgery classification. The use of adhesion barrier was significantly associated with a lower overall incidence of postoperative DGE in liver transplantation (30.7 vs. 17.9%; p =0.002), including grades A (16.8 vs. 9.5%; p =0.03), B (7.3 vs. 3.4%; p =0.08), and C (6.6 vs. 5.5%; p =0.50). After propensity score matching, similar results were observed for the overall incidence of DGE (29.6 vs. 17.9%; p =0.009), including grades A (16.8 vs. 9.5%; p =0.04), B (6.7 vs. 3.4%; p =0.15), and C (6.1 vs. 5.0%; p =0.65). Univariate and multivariate analyses showed a significant correlation between the use of adhesion barrier and a low incidence of DGE. There were no statistically significant differences in postoperative complications between the 2 groups. The application of an adhesion barrier could be a safe and feasible method to reduce the incidence of postoperative DGE in living-donor liver transplantation.

Role of extracorporeal membrane oxygenation as a salvage therapy for liver transplantation recipients in a high-volume transplant center.

Extracorporeal membrane oxygenation (ECMO) has been used sporadically in adult orthotopic liver transplantation (OLT) recipients for the treatment of acute cardiopulmonary failure. This retrospective study aimed to identify OLT patients who would benefit from ECMO support. We reviewed 109 OLT patients who received ECMO support for more than 24 h from January 2007 to December 2020. Among the enrolled patients, 15 (13.8%) experienced 18 ECMO-related complications and 12 (11.0%) experienced ECMO reapplication after weaning during the same hospitalization period. The successful weaning rates were 50.98% in patients who received ECMO support during the peritransplantation period (0-30 days from transplantation) and 51.72% in patients who received ECMO support in the post-OLT period (more than 30 days after OLT); 24 (47.1%) and 23 (39.7%) patients survived until hospital discharge, respectively. The 109 enrolled OLT recipients who received ECMO support during the perioperative period had a 1-year survival rate of 42.6%. Multivariate analyses identified the following as significant and independent risk factors for in-hospital mortality: ECMO treatment prior to 2011 ( p = 0.04), septic shock as the indication for ECMO treatment ( p = 0.001), and a total bilirubin level of ≥5.0 mg/dl ( p = 0.02). The outcomes of adult OLT recipients with ECMO treatment were acceptable in terms of weaning success and survival until hospital discharge. This study confirmed that ECMO treatment for OLT recipients with septic shock and elevated bilirubin levels might be associated with a higher in-hospital mortality and demonstrated the importance of a multidisciplinary ECMO team approach.

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

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

Vertically and Horizontally Drawing Formation of Graphite Pencil Electrodes on Paper by Frictional Sliding for a Disposable and Foldable Electronic Device.

The objective of this study is to fabricate an electrode by frictional sliding caused by a rough paper surface. The pressure exerted during drawing induces adsorption of the graphite particles by the rough paper and simultaneously reduces the surface roughness of the paper electrode. Repetitive drawing in one-way direction reduced the roughness of the paper surface, decreasing the grain boundaries of graphite. This increases the electron pathway at the electrode, thus reducing the resistance to less than 50 Ω. At the same time, repetitive drawing could confirm that unstable errors caused by the hand could help converge within a certain margin of error. We quantified the relationship between pressure and resistance when drawing on the electrode using a pencil hardness tester. In addition, the electrodes formed by repeated drawing generated a new surface grain and boundary, parallel to the drawing direction, and changed the electrode characteristics with respect to the drawing direction. The grain boundary difference based on the drawing direction was measured via a heating test of the foldable device, a sound pressure level, and laser scattering vibrometer measurements of a linear speaker. The fabricated graphite electrodes can be used in disposable foldable paper electronics because they are prepared using inexpensive materials.

Thermal conductivity enhancement in electrospun poly(vinyl alcohol) and poly(vinyl alcohol)/cellulose nanocrystal composite nanofibers.

The thermal conductivity enhancement of neat poly(vinyl alcohol) and poly(vinyl alcohol) (PVA)/cellulose nanocrystal (CNC) composite was attempted via electrospinning. The suspended microdevice technique was applied to measure the thermal conductivity of electrospun nanofibers (NFs). Neat PVA NFs and PVA/CNC NFs with a diameter of approximately 200 nm showed thermal conductivities of 1.23 and 0.74 W/m-K, respectively, at room temperature, which are higher than that of bulk PVA by factors of 6 and 3.5, respectively. Material characterization by Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis confirmed that the thermal conductivity of the PVA/CNC NFs was enhanced by the reinforcement of their backbone rigidity, while that of the neat PVA NFs was attributed to the increase in their crystallinity that occurred during the electrospinning.

Splenic devascularization can replace splenectomy during adult living donor liver transplantation - a historical cohort study.

Simultaneous splenectomy (SSPX) in adult living donor liver transplantation (ALDLT) has definitely beneficial roles such as portal flow modulation in small-for-size graft and correction of hypersplenism-related pancytopenia, and so on, but disastrous complications after SSPX often occur. For the first time, we devised unique and innovative splenic devascularization (SDV) procedure to alleviated untoward effects of SSPX but to maintain its benefits for the indicated patients. From April 2013 to December 2014, 520 recipients underwent ALDLT, and the SSPX and SDV were simultaneously performed in 62 (11.9%) and 61 (11.7%) patients, respectively. The most common indication was hypersplenism-related pancytopenia (n = 101), small-for-size graft (n = 14), hepatitis C virus (HCV) (n = 7), and splenic artery aneurysm (n = 1). Postoperative small-for-size graft syndrome (SFSS) was absent in both SSPX and SDV, and preoperative pancytopenia was improved in both groups since postoperative 1 week, although SSPX was more substantial than SDV. Preoperative splenic volume (706.2 ± 282.9 ml) after SDV significantly decreased to 425.5 ± 204.4 ml on 1 month, respectively. In contrast to SDV, SSPX resulted in longer operation time and higher incidence of postoperative complications including mortality. In conclusion, SDV can replace SSPX during ALDLT without hampering its beneficial roles seriously, but get rid of splenectomy-related lethal complication.

Validation of the OncoHepa test, a multigene expression profile test, and the tumor marker-volume score to predict postresection outcome in small solitary hepatocellular carcinomas.

PURPOSE: OncoHepa test is a multigene expression profile test developed for assessment of hepatocellular carcinoma (HCC) prognosis. Multiplication of α-FP, des-γ-carboxy prothrombin (DCP) and tumor volume (TV) gives the α-FP-DCP-volume (ADV) score, which is also developed for assessment of HCC prognosis. METHODS: The predictive powers of OncoHepa test and ADV score were validated in 35 patients who underwent curative hepatic resection for naïve solitary HCCs ≤5 cm. RESULTS: Median tumor diameter was 3.0 cm. Tumor recurrence and patient survival rates were 28.6% and 100% at 1 year, 48.6% and 82.9% at 3 years, and 54.3% and 71.4% at 5 years, respectively. The site of first tumor recurrence was the remnant liver in 18, lung in 1, and the peritoneum in 1. All patients with HCC recurrence received locoregional treatment. OncoHepa test showed marginal prognostic significance for tumor recurrence and patient survival. ADV score at 4log also showed marginal prognostic difference with respect to tumor recurrence and patient survival. Combination of these 2 tests resulted in greater prognostic significance for both tumor recurrence (P = 0.046) and patient survival (P = 0.048). CONCLUSION: Both OncoHepa test and ADV score have considerably strong prognostic power, thus individual and combined findings of OncoHepa test and ADV score will be helpful to guide postresection surveillance in patients with solitary HCCs ≤5 cm.

Results of Adult Living Donor Liver Transplantation with Sixth-Decade Donors: A Propensity Score Matching Study in a High-Volume Institution.

BACKGROUND We assessed the prognostic impact of donor age on the outcome of adult living donor liver transplantation (LDLT). MATERIAL AND METHODS The study population comprised adult donor and recipients of right lobe grafts for LDLT performed from January 2005 to December 2016. There were 35 living donors aged ≥50 years (old-age donor group). As a control group, donors in their 20s (young-age donor group) were selected after one-to-one propensity score matching based on sex, model for end-stage liver disease (MELD) score, and primary diagnosis. RESULTS Donor age was 52.5±1.5 years versus 25.4±3.1 years in the old- and young-age donor groups, respectively. Remnant volumes of the 2 groups were 38.9±3.0% versus 38.1±2.9%, respectively (p=0.98). One-month regeneration rate of the remnant liver was 101.1±10.6% versus 104.5±11.8%, respectively (p=0.08), and there was no significant difference in the incidences of donor complications. Mean MELD score was 15 versus 14, respectively (p=0.82). Graft-to-recipient weight ratio was 1.02±0.43 versus 0.91±0.63, respectively (p=0.28). In the recipients, biliary complication occurred in 11.4% versus 8.6%, respectively (p=0.12), and there was no difference in 5-year survival rates of both groups (p=0.15). The 1-week and 1-month regeneration rates of the remnant left liver were 71.6±9.9% and 100.1±10.6% in the old-age group, respectively, whereas those were 80.2±12.1% and 104.5±11.8% in the young-age group, respectively (p=0.08). CONCLUSIONS Right lobe grafts from donors aged ≥50 years showed the usual recovery of graft function but rather delayed liver regeneration. Thus, old-aged donors should be selected prudently after consideration of hepatic resection rate, graft size, and hepatic steatosis.

Clinical Features and Surveillance of Very Late Hepatocellular Carcinoma Recurrence After Liver Transplantation.

BACKGROUND This study aimed to assess patterns of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and to establish long-term surveillance protocols for late HCC recurrence. MATERIAL AND METHODS The 232 LT recipients experiencing subsequent HCC recurrence were categorized as Group 1, early recurrence (within 1 year of LT; n=117); Group 2, late recurrence (occurring in years 2-5; n=93); and Group 3, very late recurrence (after year 5; n=22). RESULTS Recurrence was detected by only elevated tumor marker levels in 11.1%, 30.1%, and 45.5% of patients in Groups 1, 2, and 3, respectively (p<0.001). The proportion of intrahepatic and extrahepatic metastases was similar in all 3 groups. Common sites of extrahepatic metastasis were the lung and bone; these were also similar across the 3 groups. Overall post-recurrence patient survival rates were 60.2% at 1 year, 28.2% at 3 years, 20.5% at 5 years, and 7.0% at 10 years. Median post-recurrence survival periods were 10.2, 23.8, and 37.0 months in Groups 1, 2, and 3, respectively. CONCLUSIONS While the pattern of HCC recurrence was similar regardless of time of recurrence, post-recurrence survival was significantly longer in patients with later recurrence. Long-term surveillance for HCC recurrence beyond 5 years after LT is recommended.

Management of very late peritoneal metastasis of hepatocellular carcinoma 10 years after liver transplantation: Lessons from two cases.

Recurrence of hepatocellular carcinoma (HCC) 10 years after liver transplantation (LT) is very rare. Here, we present two cases of peritoneal metastasis of HCC that occurred 10 and 12 years after LT. A 77-year-old male who had undergone deceased-donor LT 10 years earlier showed slow progressive elevation of tumor marker levels over 6 months. Close observation with frequent imaging studies and monthly tumor marker analyses revealed a solitary peritoneal seeding mass. Imaging studies revealed that the mass was highly likely to be metastatic HCC. After excision of the mass, all tumor markers returned to the normal range. Over past 10 months, the patient has received everolimus monotherapy and half-dose sorafenib, and has shown no evidence of HCC recurrence. In the second case, marginally elevated tumor marker levels were detected in a 65-year-old male who had undergone living-donor LT 12 years earlier. After observation for 3 months, follow-up studies revealed a peritoneal seeding mass. Thorough imaging studies revealed that the mass was highly likely to be metastatic HCC. Two mass lesions were excised, and the patient was administered low-dose calcineruin inhibitor, sirolimus, and full-dose sorafenib. Subsequently, the tumor marker levels increased again and growth of new peritoneal seeding nodules was observed; therefore, sorafenib was stopped after 2 years of administration. During 6 years since HCC recurrence diagnosis, the patient has experienced slowly growing tumors, but has been doing well. For very late peritoneal metastasis of HCC, the therapeutic modalities include surgical resection if possible, everolimus monotherapy, and long-term use of sorafenib.

ALPPS in a patient with periductal infiltrating intrahepatic cholangiocarcinoma.

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a novel method to prevent post-hepatectomy hepatic failure. We present a case of periductal infiltrating intrahepatic cholangiocarcinoma undergone ALPPS, that was conducted as intraoperative choice instead of conducting preoperative portal vein embolization (PVE). A 65-year-old male patient was to undergo extended right posterior sectionectomy, but the operation plan was changed to conduct right hepatectomy with/without bile duct resection due to invasion of the right hepatic duct. After deciding to conduct ALPPS, we stopped further perihilar dissection and liver was transected. The right portal vein was ligated and Surgicel was densely packed between the transected hemilivers. There was rapid regeneration of the left liver on computed tomography follow-up, thus the second-stage right hepatectomy was conducted 10 days after the first-stage operation. Bile duct resection (BDR) was not performed due to heavy perihilar adhesion and inflammation, but fortunately tumor-negative bile duct resection margin was achieved after meticulous dissection. This patient recovered uneventfully and discharged nine days after the second-stage right hepatectomy. Thereafter he underwent concurrent chemoradiation therapy. He is doing well so far without evidence of tumor recurrence for 20 months after operation. In conclusion, this case suggests that ALPPS may be applied to an unexpected situation requiring PVE, but ALPPS is not recommend for treatment of perihilar malignancy requiring BDR.

Preoperative prognostic values of α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients with hepatocellular carcinoma for living donor liver transplantation.

BACKGROUND: Adult living donor liver transplantation (LDLT) is one of the best treatments for hepatocellular carcinoma (HCC). However, when recurrence of HCC after LDLT occurs, the prognosis is poor because of rapid progression. Preoperative level of α-fetoprotein (AFP) and protein induced by vitamin K antagonist-II (PIVKA-II) reportedly correlate with recurrence of HCC after LDLT. METHODS: We examined AFP and PIVKA-II preoperatively as predictors of HCC recurrence in 461 patients who underwent LDLT using right liver graft for HCC from May 2007 to December 2013. RESULTS: Among these, 77 patients (16.7%) who experienced recurrence were retrospectively reviewed. Multivariate analysis revealed tumor size >5 cm, AFP >150 nag/mol and PIVKA-II >100 maul/mol as significant independent risk factors for recurrence. The median time to recurrence was 10 months. The median survival time after recurrence was 26 months, and the 1-, 3- and 5-year survival rates after recurrence were 80.5%, 58%, and 28.3% respectively. CONCLUSIONS: Preoperatively, not only morphology of the tumor but also AFP and PIVKA-II levels can offers important information for the recurrence after LDLT for HCC. Thus, combination of tumor markers might be used for expansion of pre-existing strict selection criteria of liver transplantation for HCC.

Paradoxical uptake of Gd-EOB-DTPA on the hepatobiliary phase in the evaluation of hepatic metastasis from breast cancer: is the "target sign" a common finding?

PURPOSE: The purpose was to describe magnetic resonance imaging (MRI) findings of breast cancer liver metastasis using gadoxetic acid (Gd-EOB-DTPA) with an emphasis on the added value of the hepatobiliary phase (HBP). MATERIAL AND METHODS: Nine patients with 13 liver metastases were included in the study after the medical records of 29 breast cancer patients who underwent Gd-EOB-DTPA-enhanced MRI between February 2008 and June 2010 were reviewed. The diagnoses of liver metastasis were established by percutaneous liver biopsy or surgery and on the basis of image findings. Two radiologists retrospectively evaluated signal intensity (SI) and sizes of metastases and patterns of enhancement in an HBP. The SI ratio was calculated as the SI of the central hyperintense portion in "target" lesions divided by the SI of nearby normal liver parenchyma on the HBP. We also measured apparent diffusion coefficient (ADC) values from Diffusion Weighted Image (DWI). RESULTS: Liver metastases were all hypointense [n=13/13 (100%)] on T1-weighted imaging (WI), and many lesions had a "target" appearance with a central high SI and a peripheral low SI rim (47%) on T2WI. Dynamic study showed rim enhancement on the arterial phase (85%) and a "target" appearance, consisting of a central enhancing portion with peripheral washout or hypointense rim, on the HBP (62%). The mean SI ratio was 0.7. The mean ADC value of "target" appearing metastases was 1.25 (×10(-3) mm(2)/s; range 1.3-1.6) compared with a mean value of 0.8 (×10(-3) mm(2)/s; range 0.8-1.4) in homogeneous defect on the HBP. There was statistically significant difference (P<.05). CONCLUSION: Breast cancer liver metastases commonly demonstrated as a peripheral ring enhancement on arterial dominant phase and a target sign with a central round enhancing portion and a peripheral hypointense rim on the HBP.