Minimizing Incision in Living Donor Liver Transplantation: Initial Experience and Comparative Analysis of Upper Midline Incision in 115 Recipients.

Living donor liver transplantation (LDLT) needs "Mercedes Benz" or "J-shaped" incision, causing short and long-term complications. An upper midline incision (UMI) is less invasive alternative but technically challenging. Reporting UMI for recipients in LDLT vs. conventional J-shaped incision. Retrospective analysis, July 2021 to December 2022. Peri-operative details and post-transplant outcomes of 115 consecutive adult LDLT recipients transplanted with UMI compared with 140 recipients with J-shaped incision. Cohorts had similar preoperative and intraoperative variables. The UMI group had significant shorter time to ambulation (3 ± 1.6 vs. 3.6 ± 1.3 days, p = 0.001), ICU stay (3.8 ± 1.3 vs. 4.4 ± 1.5 days, p = 0.001), but a similar hospital stay (15.6±7.6 vs. 16.1±10.9 days, p = 0.677), lower incidence of pleural effusion (11.3% vs. 27.1% p = 0.002), and post-operative ileus (1.7% vs. 9.3% p = 0.011). The rates of graft dysfunction (4.3% vs. 8.5% p = 0.412), biliary complications (6.1% vs. 12.1% p = 0.099), 90-day mortality (7.8% vs. 12.1% p = 0.598) were similar. UMI-LDLT afforded benefits such as reduced pleuropulmonary complications, better early post-operative recovery and reduction in scar-related complaints in the medium-term. This is a safe, non-inferior and reproducible technique for LDLT.

Are patients with hepatocellular carcinoma and portal vein tumour thrombosis candidates for liver transplantation?

In this debate, the authors consider whether patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis are candidates for liver transplantation (LT). The argument for LT in this context is based on the premise that, following successful downstaging treatment, LT confers a much greater clinical benefit in terms of survival outcomes than the available alternative (palliative systemic therapy). A major argument against relates to limitations in the quality of evidence for LT in this setting - in relation to study design, as well as heterogeneity in patient characteristics and downstaging protocols. While acknowledging the superior outcomes offered by LT for patients with portal vein tumour thrombosis, the counterargument is that expected survival in such patients is still below accepted thresholds for LT and, indeed, the levels achieved for other patients who receive transplants beyond the Milan criteria. Based on the available evidence, it seems too early for consensus guidelines to recommend such an approach, however, it is hoped that with higher quality evidence and standardised downstaging protocols, LT may soon be more widely indicated, including for this population with high unmet clinical need.

Which recipient pretransplant factors, such as MELD, renal function, sarcopenia, and recent sepsis influence suitability for and outcome after living donor liver transplantation? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Varied access to deceased donors across the globe has resulted in differential living donor liver transplant (LDLT) practices and lack of consensus over the influence of models for end stage liver disease (MELD), renal function, sarcopenia, or recent infection on short-term outcomes. OBJECTIVES: Consider these risk factors in relation to patient selection and provide recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central. METHODS: PRIMSA systematic review and GRADE. PROSPERO ID: RD42021260809 RESULTS: MELD >25-30 alone is not a contraindication to LDLT, and multiple studies found no increase in short term mortality in high MELD patients. Contributing factors such as muscle mass, acute physiologic assessment and chronic health evaluation score, donor age, graft weight/recipient weight ratio, and inclusion of the middle hepatic vein in a right lobe graft influence morbidity and mortality in high MELD patients. Higher mortality is observed with pretransplant renal dysfunction, but short-term mortality is rare. Sarcopenia and recent infection are not contraindications to LDLT. Morbidity and prolonged LOS are common, and more frequent in patients with renal dysfunction, nutritional deficiency or recent infection. CONCLUSIONS: When individual risk factors are studied mortality is low and graft loss is infrequent, but morbidity is common. MELD, especially with concomitant risk factors, had the greatest influence on short term outcome, and recent infection had the least. A multidisciplinary team of experts should carefully assess patients with multiple risk factors, and an optimal graft is recommended.

An international multicenter study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise.

BACKGROUND & AIMS: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a "sickest-first" approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - recipient outcome, donor/graft safety, waiting list mortality and healthcare resources - for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. LAY SUMMARY: There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.

Pediatric liver transplantation in severe hepatopulmonary syndrome and use of inhaled nitric oxide for post-transplant hypoxemia-a single center experience.

Data on pediatric patients with HPS undergoing LT are limited. Our aim was to study the spectrum and outcomes of pediatric patients with HPS undergoing LDLT. The role ofiNO for post-LDLT refractory hypoxemia was also assessed. Patients (aged < 18 years) undergoing LT were retrospectively studied. HPS was diagnosed based on European Respiratory Society Taskforce 2004 criteria. HPS was graded based on oxygenation criteria and contrast-enhanced echocardiogram. Post-operative course was studied. Refractory post-operative hypoxemia was treated with iNO by institutionally developed protocol. 23/150 pediatric patients undergoing LDLT had HPS. BA was the most common underlying cause (52.2%). By oxygenation criteria, 6 (26.1%) had VS-HPS. VS-HPS was associated with longer LOS (p = .031) and prolonged oxygen requirement (p = .001) compared with other HPS patients. 4/6 patients with VS-HPS had pO2 < 45 mm Hg. Among these, 2 developed ICH post-operatively and 1 died. 3 developed refractory post-operative hypoxemia, successfully treated with iNO. Mean duration of iNO was 26.3 days. In the group of patients with HPS, the incidence of HAT and portal vein thrombosis was 17.3% and 4.3%, respectively. One year post-LDLT survival of patients with HPS was similar to non-HPS patients (86.9% vs 94.4%; p = .88). We concluded that, pediatric patients with VS-HPS, especially those with pre-operative pO2 < 45 mm Hg, have long and difficult post-LT course. Refractory postoperative hypoxemia can be successfully overcome with strategic use of iNO. Vigilant monitoring and good intensive care support are essential.

Safety assessment of RhD-positive red cell transfusion in RhD-negative liver-transplant recipients: Single-centre report from India.

BACKGROUND & OBJECTIVES: The number of blood components required during a liver-transplant surgery is significant. It is challenging for blood transfusion services to provide the required RhD-negative red blood cells (RBCs) for recipients during the peri-operative period. This retrospective study presents safety data of transfusing RhD-positive RBCs in RhD-negative living donor liver-transplant (LDLT) recipients during the peri-operative period with six-month follow up for risk of developing alloantibodies. METHODS: All RhD-negative patients who underwent LDLT and were transfused ABO-compatible but RhD-positive RBC units between January 2012 and May 2018 were included in the study. Twenty one RhD-negative patients who received a total of 167 RhD-positive RBCs peri-operatively were chosen for alloantibody screening. All the patients were started on triple immunosuppression drugs as per the standard hospital protocol. Blood grouping, cross-match and antibody screening were done by column agglutination technique. RESULTS: Post-transplant antibody screen (weekly for 12 wk) was negative, and none of the patients developed anti-D alloantibodies till their last follow up (mean 21 months). INTERPRETATION & CONCLUSIONS: Our observations suggest that it may be safe to use RhD-positive RBCs peri-operatively in RhD-negative LDLT recipients with low risk of alloimmunization.

Is Portal Inflow Modulation Always Necessary for Successful Utilization of Small Volume Living Donor Liver Grafts?

Although the well-accepted lower limit of the graft-to-recipient weight ratio (GRWR) for successful living donor liver transplantation (LDLT) remains 0.80%, many believe grafts with lower GRWR may suffice with portal inflow modulation (PIM), resulting in equally good recipient outcomes. This study was done to evaluate the outcomes of LDLT with small-for-size grafts (GRWR <0.80%). Of 1321 consecutive adult LDLTs from January 2012 to December 2017, 287 (21.7%) had GRWR <0.80%. PIM was performed (hemiportocaval shunt [HPCS], n = 109; splenic artery ligation [SAL], n = 14) in 42.9% patients. No PIM was done if portal pressure (PP) in the dissection phase was <16 mm Hg. Mean age of the cohort was 49.3 ± 9.1 years. Median Model for End-Stage Liver Disease score was 14, and the lowest GRWR was 0.54%. A total of 72 recipients had a GRWR <0.70%, of whom 58 underwent HPCS (1 of whom underwent HPCS + SAL) and 14 underwent no PIM, whereas 215 had GRWR between 0.70% and 0.79%, of whom 51 and 14 underwent HPCS and SAL, respectively. During the same period, 1034 had GRWR ≥0.80% and did not undergo PIM. Small-for-size syndrome developed in 2.8% patients. Three patients needed shunt closure at 1 and 4 weeks and 60 months. The 1-year patient survival rates were comparable. In conclusion, with PIM protocol that optimizes postperfusion PP, low-GRWR grafts can be used for appropriately selected LDLT recipients with acceptable outcomes.

Living Donor Liver Transplantation for Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of previously diagnosed or undiagnosed liver disease with organ failure(s) with high short-term mortality. This study was conducted to report the outcomes of living donor liver transplantation (LDLT) in ACLF and assess the survival benefit of liver transplantation (LT) in these patients. It was a retrospective study of 218 ACLF patients on the basis of European Association for the Study of the Liver (EASL)-chronic liver failure criteria from January 2014 through November 2017. Patients were considered for LDLT if there was no improvement on standard medical therapy for 5-10 days. Prior to LDLT, active sepsis was excluded/treated, and renal, circulatory, and respiratory failures were improved to the greatest extent possible. The mean age was 42.9 years, and 181 patients were male. Sepsis was the most common acute precipitating event followed by alcohol. Of the patients, 35 (16.1%), 66 (30.3%), and 117 (53.7%) were classified into ACLF grades 1, 2, and 3, respectively. Although 80% of the ACLF 1 group and 72.7% of the ACLF 2 group underwent LDLT, only 35% of the ACLF 3 group could undergo LDLT. The circulatory and respiratory failures at admission were significantly higher in the nontransplant group with poor subsequent response to standard medical therapy, exclusion from LDLT, and poor outcomes. None of the patients on high support for circulatory and respiratory failure underwent LDLT. Posttransplant survival at 1 year was comparable among different grades of ACLF (92.9%, 85.4%, and 75.6%; P = 0.15). Among patients in the ACLF 3 group, survival at 90 days was extremely poor in those who could not undergo LDLT (5.9% versus 78%; P < 0.001). In conclusion, LDLT results in good survival with acceptable post-LT morbidity in patients with ACLF.

Laparoscopic donor hepatectomy: First experience from Indian sub-continent.

Liver transplantation is a ray of hope for thousands of patients with end-stage liver disease but is currently challenged by the scarcity of donor organs worldwide. Unlike kidney transplantation where minimally invasive donor organ procurement has almost become a norm, laparoscopic procurement of hemi-liver from a living donor is still in the infancy of development, at least in the Indian sub-continent. Minimally invasive surgery has made its way into different procedures of hepatobiliary and pancreatic surgery, but only a few centres in the world are performing pure laparoscopic donor hepatectomy. We report two cases of total laparoscopic donor hepatectomy, and to the best of our knowledge, this is the first report from Indian sub-continent.

Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study.

In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P < .001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P < .001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 vs. -12.1 mL/min/1.73 m2 , P = .108), and in patients continuing randomized treatment (-8.0 vs. -13.3 mL/min/1.73 m2 , P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432.

Readdressing the Middle Hepatic Vein in Right Lobe Liver Donation: Triangle of Safety.

For equipoising donor safety and optimal recipient outcomes, we adopted an algorithmic "triangle of safety" approach to retrieve 3 types of right lobe liver grafts (RLGs), namely, the modified extended right lobe graft (MERLG), the partial right lobe graft (PRLG), and the modified right lobe graft (MRLG). Reconstruction to achieve a single wide anterior sector outflow was ensured in all patients. We present donor and recipient outcomes based on our approach in 665 right lobe (RL) living donor liver transplantations (LDLTs) performed from January 2013 to August 2015. There were 347 patients who received a MERLG, 117 who received a PRLG, and 201 who received a MRLG. A right lobe graft (RLG) with a middle hepatic vein was retrieved only in 3 out of 18 donors with steatosis >10%. Cold ischemia time was significantly more and remnant volume was less in the MRLG group. Of the donors, 29.3% had complications (26% Clavien-Dindo grade I, II) with no statistically significant difference among the groups. The Model for End-Stage Liver Disease score was higher in the MERLG group. There were 34 out of 39 with a graft-to-recipient weight ratio (GRWR) of <0.7% who received a MERLG with inflow modulation. Out of 4 patients who developed small-for-size syndrome in this group, 2 died. The 90-day patient survival rate was similar among different GRWRs and types of RLG. In conclusion, a selective and tailored approach for RL donor hepatectomy based on optimal functional volume and metabolic demands not only addresses the key issue of double equipoise in LDLT but also creates a safe path for extending the limits.

A retrospective comparative study of venous vs nonringed expanded polytetrafluoroethylene extension grafts for anterior sector outflow reconstruction in right lobe living donor liver transplantation.

BACKGROUND: Prosthetic vessel grafts are increasingly being used for anterior sector (AS) outflow reconstruction in right lobe living donor liver transplantation (RL-LDLT) in view of easy availability and proper fit. The aim of the study was to analyze technique and outcomes of AS reconstruction using nonringed expanded polytetrafluoroethylene (ePTFE) grafts and compare outcomes with venous extension grafts. METHODS: This is a retrospective study of 437 consecutive RL-LDLTs from January 2014 to August 2015. Vein (V) and ePTFE (alone or composite) were used alternatively or best fit for particular right lobe graft. RESULT: V graft was used in 200 recipients and ePTFE in 237 recipients with comparable preoperative donor and recipient characteristics. Cold ischemia time was significantly high in the ePTFE group. Postoperative recipient outcomes were comparable between the groups. The graft patency rate was comparable between the groups at different time intervals of follow-up. However, 12-month patency was low in those with multiple venous tributaries than with single outflow reconstruction ([V 90%, ePTFE 86.7%] vs [V 97.4%, ePTFE 95.2%]). No patient was re-explored for graft blockage. There was no significant difference in 30-day (V 92%, ePTFE 94.5%, P = 0.34), 90-day (V 90%, ePTFE 90.7%, P = 0.87) and one-year (V 87.5%, ePTFE 89%, P = 0.66) patient survival between the groups. CONCLUSION: Expanded polytetrafluoroethylene gives equivalent patency and recipient outcomes with the added advantage of proper size match fit, allowing more complex AS reconstruction with ease without increased infection rate or associated complications.

Revisiting chronic rejection following living donor liver transplantation in the tacrolimus era: A single center experience.

BACKGROUND AND AIMS: Chronic rejection (CR) is an uncommon but important cause of graft dysfunction, leading to graft loss and often requires retransplantation. This study evaluates the incidence and outcome of the patients with CR at a large living donor liver transplant (LDLT) center. METHODS: Data of patients with CR were retrospectively analyzed in 1232 adult (age >18 years) LDLT on tacrolimus (mainly)-based immunosuppression. Sirolimus/everolimus (mammalian target of rapamycin [mTOR] inhibitors) was added to baseline immunosuppression as rescue therapy in patients with CR. Data are shown as median (interquartile range [IQR]). RESULTS: Twenty-three patients (22 males), aged 42 (IQR 45-56) years, had biopsy-proven chronic rejection at 21 (8-44) months after liver transplantation. The incidence of chronic rejection was 1.9% in this cohort. The patients with CR (n = 23) had a significantly higher incidence of cytomegalovirus (CMV) viremia, acute cellular rejection, and history of anastomotic biliary strictures as compared to patients without CR. Five patients were noncompliant with immunosuppression before the diagnosis of CR. Twelve patients (52%) responded to addition of mTOR inhibitors, whereas 11 did not respond and had poor outcome. CONCLUSION: The incidence of chronic rejection is low in LDLT. Treatment with mTOR inhibitors can reverse graft dysfunction in approximately half of the patients.

Right lobe donor hepatectomy: is it safe? A retrospective study.

Donor safety is utmost important in Living donor liver transplantation (LDLT). Small for size syndrome in some recipients with left lobe donors led to the evolution of right lobe LDLT. The aim of the study was to analyze the safety of large series of right lobe (RL) donor hepatectomies and compare outcomes with left lobe (LL) and left lateral segment (LLS) donations. A consecutive cohort of 726 donors from January 2011 to January 2014 were studied; RL (n = 641, 88.3%), LL (n = 36, 4.9%) or LLS (n = 49, 6.8%) depending on the type of donation. The mean age was 34.6 ± 10 years. The overall complication rate was 22.3%. Most were Clavien grade I and II. Clavien grade IIIa, IIIb, IV and V were noted in 4.2% donors. The incidence of these major complications were comparable among RL (n = 28, 4.2%), LL (n = 1, 2.7%) and LLS (n = 2, 4.08%) (P = 0.89). Bile leak was seen in 20 donors (2.7%) and 13 were managed conservatively with prolonged or additional intra-abdominal drainage. Seven underwent re-exploration for bile leak. In centres experienced in right lobe LDLT, morbidity after RL donation is similar to that of LL donation; and with adequate GRWR, same 1-year recipient outcomes.

Expert Panel Statement on Laparoscopic Living Donor Hepatectomy.

BACKGROUND: With improvements in living donor liver transplantation (LDLT) techniques and the increased experience of surgeons in laparoscopic major liver resection, laparoscopic donor hepatectomy is performed increasingly. Therefore, expert opinion on this procedure is required. OBJECTIVE: The study aimed to report the current status and summarize the expert opinion on laparoscopic donor hepatectomy. METHODS: An expert consensus meeting was held on September 8, 2016, in Seoul, Korea. RESULTS: Laparoscopic donor left lateral sectionectomy could be considered the standard practice in pediatric LDLT. In adult LDLT, laparoscopy-assisted donor hepatectomy or left hepatectomy is potentially the next need, requiring more evidence for becoming standard practice. Laparoscopic donor right hepatectomy is still in the developmental stage, and more supporting evidence is required. Waving the cost consideration, the robotic approach could be a valid alternative for the suitable approaches of laparoscopy. CONCLUSIONS: Laparoscopic donor hepatectomy is increasing its role in both pediatric and adult LDLT. However, for major donor hepatectomy, more evidence is needed.

Survey Results of the Expert Meeting on Laparoscopic Living Donor Hepatectomy and Literature Review.

BACKGROUND: Because laparoscopic donor surgery has been successful in pediatric living donor liver transplantation, its application is expanding to right hepatectomy. However, there is no consensus on the indications for laparoscopic donor hepatectomy or on the details of the surgical technique. OBJECTIVE: To evaluate the current status of laparoscopic donor hepatectomy and to summarize the expert opinion on it. METHODS: Before the expert meeting on September 8, 2016, in Seoul, Korea, a survey was undertaken from expert liver surgeons from around the world. RESULTS: Fifteen of 17 (88.2%) surgeons responded to the survey. The selection criteria for laparoscopic donor surgery are stricter than for open surgery in terms of the anatomy, remnant liver volume, and recipient's condition. There is no consensus on the instruments or equipment used. A literature review of laparoscopic donor hepatectomy showed that the use of this method is increasing and the short-term outcomes are similar to those of open surgery. CONCLUSIONS: This survey and literature review show that laparoscopic donor hepatectomy is performed by experienced surgeons in selected cases, and that its incidence is increasing worldwide.

Epidemiological Analysis of Extended-Spectrum Beta-Lactamase-Producing Bacterial Infections in Adult Live Donor Liver Transplant Patients.

INTRODUCTION: Bacterial infections are a leading cause of morbidity and mortality in patients receiving solid-organ transplants. Extended-spectrum beta-lactamases (ESBL) pathogens are the most important pathogenic bacteria infecting these patients. AIM: This study aims to evaluate for the incidence and characteristics of ESBL-positive organism, to look for the clinical outcomes in ESBL-positive infected cases, and to evaluate and draft the antibiotic policy in posttransplant patients during the first 28 days posttransplant. MATERIALS AND METHODS: This is a retrospective data analysis of liver transplant recipients infected with ESBL culture-positive infections. All the culture sites such as blood, urine, and endotracheal tube aspirates were screened for the first ESBL infection they had and noted. This data were collected till day 28 posttransplant. The antibiotic susceptibility pattern and the most common organism were also noted. RESULTS: A total of 484 patients was screened and 116 patients had ESBL-positive cultures. Out of these, 54 patients had infections and 62 patients were ESBL colonizers. The primary infection site was abdominal fluid (40.7%), with Klebsiella accounting for most of the ESBL infections. Colistin was the most sensitive antibiotic followed by tigecycline. The overall mortality was 11.4% and 31 out of 54 ESBL-infected patients died. CONCLUSIONS: Infections with ESBL-producing organism in liver transplant recipients has a high mortality and very limited therapeutic options.