Portal Hemodynamics in Liver Resection and Transplantation.

The hepatic blood supply and its several homeostatic and pathologic processes has always been a matter of great interest. Many views commonly held today are derived from an earlier era, but major reorientations have occurred recently in almost all aspects of knowledge of the role and regulation of hepatic blood flow. Moreover, with the advent of liver transplantation (LT), especially living donor LT (LDLT) there has been a resurgence of interest in attempting to comprehend this deceptively simple topic. It is nonetheless important to concede that even though our knowledge on the practical modulation of hepatic hemodynamics has expanded enormously, there still remain the need to explore the depths of our remaining ignorance to further improve outcomes in LDLT. This review focuses on the current view, controversies and gaps in knowledge of the hepatic vascular bed, with an emphasis on the importance of portal hemodynamics in liver disease and its impact on liver regeneration and LT.

Deceased Donor Liver Transplantation in India: First Report of 5-Y Outcomes.

BACKGROUND: Paucity of deceased donor livers has resulted in a 10-fold rise in living donor liver transplantations (LDLTs) performed in India over the past decade. Nonetheless, number of deceased donor liver transplantation (DDLT) performed has improved with the establishment of simplified legal framework for certification of brain death and organ donation. In this study, we present our outcomes of DDLT performed at various centers, comparing their outcomes and provide a snapshot of the increasing number of DDLT across the state over the years. METHODS: All consecutive patients who underwent liver transplants from January 2010 till December 2019 by our transplant team in the state of Tamil Nadu, India, were included in the study. The program was established initially at the primary hospital in the year 2010 and with the evolution of the initial experience, transplant programs were expanded to the others hospital from the year 2015. Preoperative clinical data, intraoperative characteristics, and posttransplant outcomes of DDLT were analyzed from our prospective database. RESULTS: A total of 362 DDLTs (331 adults, 31 children) were performed at 11 centers. Median (range) model for end-stage liver disease score was 16 (6-39). Forty-eight split, 11 combined liver kidney, and 4 auxiliary DDLTs were performed. One-, 3-, and 5-y survival was 87.2%, 80.4%, and 76.6% in adults and 80.6%, 80.6%, and 80.6% in children, respectively. CONCLUSIONS: In a country where over 80% of the LTs are performed as LDLT, we provide the first report of a heartening trend of increasing number of DDLT programs being established with excellent 5-y outcomes.

Aggressive Variant of Hepatic Epstein-Barr Virus-Associated Inflammatory Pseudotumor-like Follicular Dendritic Cell Sarcoma with PD-L1 and SSTR2a Expression.

An aggressive Epstein-Barr virus (EBV)-associated inflammatory pseudotumor-like follicular dendritic cell (IPT-like FDC) sarcoma is reported in an adult female. The patient developed multifocal recurrence and passed away 13 months after the initial surgical resection. A bright field microscopic examination of the tumor demonstrated a classical growth pattern and the diffuse expression of Programmed death ligand 1 (PD-L1) and somatostatin receptor 2a (SSTR2a).

Preventing Small-for-size Syndrome in Living Donor Liver Transplantation: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients.

Experience With Establishing a Robotic Donor Hepatectomy Program for Pediatric Liver Transplantation.

BACKGROUND: The benefits of minimal invasive donor hepatectomy, especially for left lateral sectionectomy (LLS) have been unequivocally demonstrated. Moreover, donors in pediatric liver transplantation (LT) are usually parents who need to recover quickly to take care of the child. There are inherent limitations to conventional laparoscopic surgery including surgeon's experience with advanced laparoscopic surgery and steep learning curve which limits the wide application of minimal invasive donor hepatectomy. We share our experience of establishing a program of robotic donor hepatectomy (RDH) and achieving proficiency in performing RDH for pediatric LT. METHODS: Data were prospectively collected of consecutive LLS RDH based on a structured learning algorithm. Donor and recipient outcomes were analyzed. RESULTS: Seventy-five consecutive cases of LLS RDH were performed. The median primary warm ischemia time was 6 min (interquartile range [IQR]: 5-7 min). No major complications (grade ≥IIIb Clavien-Dindo) were noted in the cohort. There were no emergency conversion to open surgery and neither were there postoperative explorations through a laparotomy. Seven grafts were hyper-reduced and 5 required venoplasty. Two recipients died because of severe sepsis and multiorgan failure. Major complications occurred in 15 children (20%), none of which were attributable to RDH. Median hospital stay of the donors and recipients was 5 d (IQR: 5-6) and 12 d (IQR: 10-18) respectively. CONCLUSIONS: We share our experience of starting a RDH program for pediatric LT. We highlight the challenges and our learning algorithm to spur teams on the cusp of starting robotic transplant programs.

Frequent expression of PD-L1 in lymphocyte-rich hepatocellular carcinoma: A report of 4 cases.

BACKGROUND: Programmed death ligand 1 (PD-L1) is an immune checkpoint inhibitor. PD-L1 binds to its receptor programmed death receptor (PD-1) expressed by immune cells and plays a key role in regulating immune responses. Engagement of PD-L1 on cancer cells and PD-1 on immune cells avoid destruction of tumour cells by immune cells. Immunostaining with PD-L1 has been suggested as a biomarker predictive of antiPD-L1 immunotherapy. Lymphocyte-rich hepatocellular carcinoma (LrHCC) is a rare histological HCC subtype which is characterised by neoplastic epithelial cells intermixed with numerous immune cells. METHODS: Here in we investigated immunohistochemical PD-L1 expression in 4 cases of LrHCC. Tumour proportion score (TPS) and immune cell score was recorded. Immunophenotypic characterization of the tumour and inflammatory cells was also done. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) assay as performed in all four tumours. RESULTS: Expression of PD-L1 was demonstrated in tumour epithelial cells and immune cells in all four cases. Incomplete to membranous staining was demonstrated in the tumour cells. Tumour proportion score (TPS) was 1.2-20 %. Immune cells demonstrated membranous and cytoplasmic immunostaining. Immune cell score was ≥1 % to >10 %. CONCLUSION: PD-L1 expression in both tumour and immune cells suggests distinct immunogenic feature and potential role of antiPD-L1 therapies in cases with inoperable disease.

Living Donor Liver transplantation in an alloimmunised patient: Immunological challenges and Management in Indian Settings.

Liver transplantation (LT) is often associated with hematological abnormalities with immune or non-immune etiologies and require timely diagnosis and interventions. We report a case of a patient suffering from non-alcoholic steato-hepatitis (NASH) related end stage liver disease (ESLD) with multiple red cell antibodies who underwent LT surgery. In postoperative phase, she developed immune hemolysis as well as acute antibody mediated rejection (AMR) which was managed with therapeutic plasma exchange and IVIG. The case highlights the need to develop an algorithm for red cell and HLA antibody screening in high-risk patients for timely detection and management.

Anatomical variations of left hepatic vein and outflow reconstruction techniques in pediatric living donor liver transplantation.

Anatomical variations of left hepatic vein are observed in nearly a third of left lateral segment (LLS) donors in living donor liver transplantation. However, there is a paucity of studies and no structured algorithm for customized outflow reconstruction in LLS grafts with variant anatomy. Analysis of a prospectively collected database of 296 LLS pediatric living donor liver transplantation was done to identify different venous drainage patterns of segments 2 (V2) and 3 (V3). Left hepatic vein anatomy was classified into 3 types: type 1 (n = 270, 91.2%): V2 and V3 joined to form a common trunk which drains into the middle hepatic vein/inferior vena cava (IVC), subtype 1a length of trunk ≥9 mm and subtype 1b length of trunk <9 mm; type 2(n = 6, 2%): V2 and V3 drain independently into IVC; type 3 (n = 20, 6.8%): V2 and V3 drain into IVC and middle hepatic vein respectively. Analysis of postoperative outcomes between LLS grafts with single and reconstructed multiple outflows showed no difference in the occurrence of hepatic vein thrombosis/stenosis, major morbidity (P = .91), and 5-year survival (log-rank P = .562). This classification is a simple yet effective tool for preoperative donor assessment, and we propose a schema for the customized reconstruction of LLS grafts with excellent and consistently reproducible outcomes.

Newly proposed classification of celiac artery variations based on embryology and correlation with computed tomography angiography.

Purpose: We studied the prevalence of celiac trunk and its anatomical variations on diagnostic computed tomography angiography (CTA) studies and have proposed a new classification to define the celiac artery (CA) variations based on embryology. Material and methods: We retrospectively assessed the celiac trunk variations in 1113 patients who came to our department for diagnostic CTA for liver and renal donor workup. The patient data were acquired from the Picture Archiving and Communication System of our institutions. We analysed the celiac trunk's origin and branching pattern, including the superior mesenteric artery (SMA) and inferior phrenic artery (IPA). Results: We evaluated the CTA studies of 1050 patients. A normal trifurcation pattern, the most common type, was observed in 39% of cases. Variation with CA + left IPA was the most common subtype. Other variations noted in the study and their incidences are listed in the table below. We attempted to propose a new classification based on embryo-logy, which comprises 6 main types and their subtypes. We also analysed previous studies from the literature, including cadaveric, post-mortem, CTA, and digital subtraction angiography studies and compared them with the present study. Conclusions: Because variations of CA classifications reported to date do not encompass all CA branching pattern variants, we have proposed a new classification that incorporates most of the variants. We reiterate the clinical importance of anatomical variants of CA, IPA, and SMA in surgical and interventional radiology procedures.

Nonalcoholic Steatohepatitis: A Rapidly Increasing Indication for Liver Transplantation in India.

Background and aims: Recently, there has been a considerable increase in patients with nonalcoholic fatty liver disease. Availability of high-efficacy drugs for hepatitis B and hepatitis C virus (HCV) infection may have changed the disease prevalence. We aimed to study the impact of this changing epidemiology in patients undergoing liver transplantation (LT) over a 10-year period. Methods: The study population was stratified into Period 1 (2009-2014) and Period 2 (2015-2019). Demographics, indications for LT and changes in the epidemiology between two periods were analysed. Aetiology-based posttransplant survival analysis was carried out. Results: Indication for LT among 1017 adult patients (277 in Period 1 and 740 in Period 2) showed a significant increase in nonalcoholic steatohepatitis (NASH; 85 [30.7%] and 311 [42%]; P = 0.001), decrease in hepatitis C (49 [17.7%] and 75 [10.1%]; P = 0.002), and increase in hepatocellular carcinoma from Period 1 to Period 2 (13 [26.5%] to 38 [50.7%]; P = 0.009) among HCV patients. Patients transplanted for NASH had a lower 5-year survival compared with viral hepatitis (75.9% vs 87.4%; P = 0.03). There was a strong association between coronary artery disease and NASH (hazard ratio = 1.963, 95% confidence interval, 1.19-3.22). Conclusion: NASH is the leading indication for liver transplantation in India, surpassing viral hepatitis in recent years.

Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review.

Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree. There is a wide geographical variation with regards to its incidence, and risk-factor associations which may include liver fluke infection, primary sclerosing cholangitis, and hepatolithiasis amongst others. These tumours are classified into intrahepatic, perihilar and distal based on their anatomical location. Morphologically, intrahepatic cholangiocarcinomas are further sub-classified into small and large duct variants. Perihilar and distal cholangiocarcinomas are usually mucin-producing tubular adenocarcinomas. Cholangiocarcinomas develop through a multistep carcinogenesis and are preceded by dysplastic and in situ lesions. While clinical characteristics and management of these tumours have been extensively elucidated in literature, their ultra-structure and tumour biology remain relatively unknown. This review focuses on the current knowledge of pathological characteristics, molecular alterations of cholangiocarcinoma, and its precursor lesions (including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).

Total Internal Biliary Diversion for Post-Liver Transplant PFIC-1-Related Allograft Injury.

Steatohepatitis and diarrhea are well-known complications in children undergoing liver transplantation (LT) for progressive familial intrahepatic cholestasis (PFIC) type 1. Despite medical management with bile acid binders, the condition is progressive and can be associated with allograft loss. We report the case of a seven-year-old boy who underwent LT at the age of 2 years for PFIC type 1. Over the next five years, he developed refractory diarrhea, emaciation, worsening liver function, and steatohepatitis. Aiming to interrupt the enterohepatic circulation, at the age of 7 years, he underwent a total internal biliary diversion. The patient's postprocedure period was uneventful. His diarrhea settled and the transaminases normalized his follow-up liver biopsy after a year showed a complete resolution of steatohepatitis. At 18 months' follow-up, he has gained weight and remains asymptomatic. In this report, we show post-LT complications especially allograft injury related to the pathology of PFIC-1 can be safely and effectively managed by performing a total internal biliary diversion.

Robotic monosegment donor hepatectomy for pediatric liver transplantation: First report.

BACKGROUND: LT for infants less than 5 kg remains a challenge with high technical complication rates, which is further compounded by large-for-size grafts requiring hyper-reduction. The benefits of MIDH especially for standard left lateral segment (LLS) resection have been unequivocally demonstrated. However, given the fine margins of error, the highly challenging technical aspects of anatomical graft reduction test the limits of safety and may not be routinely feasible with the conventional laparoscopic approach. CASE REPORT: A 14-month-old girl weighing 4.4 kg with extrahepatic biliary atresia was referred to our unit for an LT. Her mother volunteered to donate and the calculated volume of the LLS was 342 ml, with an estimated GRWR of 7.6. Given the extremely high GRWR, a segment II monosegment graft was planned. A RMDH was performed, with a final GRWR of 4. The donor and recipient were discharged on the 5th and 12th post-operative days, respectively. CONCLUSION: We present the first-ever report of an RMDH. Our report highlights the fact that robotic surgery can safely replicate a highly precise surgical operation, thereby safely pushing the limits of MIDH.

Nonhepatic Cancer in the Pediatric Liver Transplant Population: Guidelines From the ILTS-SETH Consensus Conference.

The incidence and geographical distribution of cancers in children are dramatically different from the adult population. Consequent to improvements in postcancer survival, there is a progressive increase in the number of patients requiring liver transplantation (LT) who are in remission from pretransplant malignancy (PTM). Conventionally, however, PTM has been considered a relative contraindication to LT. Furthermore, with improving post-LT survival now extending beyond decades, the cumulative effect of immunosuppression and the increasing risk of de novo cancers need to be acknowledged. A working group was formed to evaluate, discuss, and retrieve all the evidence and provide guidelines with regards to best practices surrounding nonhepatic cancer in the pediatric LT (PLT) population. Further subsections of research included (a) extrahepatic solid tumors, leukemia, lymphoma, and other hematological disturbances before PLT and (b) malignancies following PLT (including posttransplant lymphoproliferative disorders). This guidance provides a collection of evidence-based expert opinions, consensus, and best practices on nonhepatic cancers in PLT.

Right hepatic arterial girdle around the common hepatic duct in liver donors: technical considerations for successful living donor liver transplantation.

PURPOSE: Variations in hepatic arterial anatomy can result in multiple arterial trunks in the graft liver. We describe our experience in dealing with five right lobe liver donors where in the right hepatic artery (RHA) branches were passing anterior and posterior to the common hepatic duct (CHD) forming an arterial girdle around it. METHODS: Five of 771 right lobe living donor liver transplants (January 2012 and March 2020) demonstrated the RHA girdle around the CHD. Three patients had the typical girdle resulting in two graft arteries which were reconstructed using arterial Y grafts. Arterial girdle was formed by the right anterior hepatic artery branches in one patient resulting in 3 graft arteries of which two were reconstructed using a Y graft. One donor had the arterial girdle and an accessory artery from SMA giving rise to 3 graft arteries. Two of them were ligated (brisk back bleed), and one was reconstructed. RESULTS: All donors (median follow-up 17 months, range 6-60 months) had an uneventful postoperative recovery. No vascular or biliary complications were encountered in the recipients. One recipient died due to sepsis and multiorgan failure, while the other 4 recipients recovered uneventfully and continue to have stable graft function. CONCLUSION: Adhering to safe surgical principles during RHA mobilization, ligation of minor arterial branches, and precise reconstruction of multiple major branches can ensure successful outcomes in the donor and recipient in this scenario.

Renal Implications of Left Renal Vein Ligation for Portal Flow Augmentation in Liver Transplantation.

BACKGROUND: Spontaneous lienorenal shunts (SLS) siphon blood away from the portal circulation and may compromise portal inflow in liver transplantation (LT). Performing a left renal vein ligation (LRVL) is a relatively easy and efficacious method of overcoming this portal 'steal'. However, given the delicate state of renal function in these patients, its short and long term effects remain undefined. The aim of this study was to evaluate the efficacy of LRVL in augmenting portal flow and safety with regards to renal function. METHODS: A prospectively collected database of 1638 consecutive LT recipients between January 2010 and August 2020 was reviewed. Twenty-eight patients who underwent LRVL were identified. There were six paediatric recipients, who were analysed separately. Data with regards to imaging, renal function, intraoperative portal hemodynamics, and renal morbidity were analysed. RESULTS: Of the 22 adults, 21 underwent live donor LT. 22.5% had a pre-transplant history of acute kidney injury (AKI). Pre-operative CT demonstrated portal vein thrombosis and SLS in 63.6% and 92.9% of patients respectively. LRVL resulted in a significant augmentation of portal hemodynamics in both the adult and paediatric recipients. Postoperatively, 14.3% and 35.7% of patients developed chylous drain output and AKI respectively. Of 13 patients who underwent CT at various timeframes, 5 patients had a partial re-canalisation of LRV at 6 months. CONCLUSION: From renal and portal standpoints, LRVL is a safe and effective technique of augmenting portal inflow. Further large-scale multicentre studies and consensus will help define an objective algorithmic approach to LT recipients with SLS.

Anatomical Basis for Selective Multiple Arterial Reconstructions in Living Donor Liver Transplantation.

BACKGROUND: Need for routine reconstruction of all arteries in grafts with multiple arterial inflows remains an unsettled debate. The aim of following article is to review an anatomical basis of a decision-making strategy to deal with multiple arteries in living donor liver transplantation (LDLT). METHODS: LDLT performed between August 2009-2019 were included. Grafts were classified into grafts with single artery (group 1); multiple arteries, all reconstructed (group 2); and multiple arteries, one reconstructed (group 3). Frequency of double arteries in relation to graft type, type of reconstruction, incidence of arterial and biliary complications and survival was compared. RESULTS: 1086 LDLT were analysed (adults: 750, paediatric: 336). 1007 grafts (92.2%) had single artery (group 1), and 79 (7.8%) grafts had multiple arteries. All arteries were reconstructed in 19 (24%) patients (group 2), while 60 grafts (75.9%) had only one artery reconstructed (group 3). Left lobe (18.8%) and left lateral segments (10.7%) grafts were more likely to have multiple arteries (p = 0.001). The likelihood of reconstructing multiple arteries was similar in all graft types, 27.3% in right and 25% and 21.4% in left lobe and left lateral segments, respectively (p > 0.05). There was no difference in biliary complications (p = 0.85), hepatic artery thrombosis (p = 0.82), and post-surgical hospital stay (p = 0.38) between the three groups. The presence of multiple arteries or their selective reconstruction did not affect survival (p = 0.73). CONCLUSIONS: Multiple arterial inflows are not an uncommon entity and demonstration of good hilar collateralization helps in avoiding unnecessary arterial reconstruction without adverse outcomes.

Propensity Score-Matched Analysis of Posttransplant Outcomes in Living Donor Liver Transplantation for Older Adult Recipients.

The impact of increasing recipient age on morbidity and mortality following living donor liver transplantation (LDLT) remains controversial. The study aims to analyze the impact of recipient age on outcomes following LDLT. Data on adult LDLTs performed between November 2009 and February 2020 were retrieved from a prospectively maintained database. Patients were stratified into 2 groups based on recipient age: 18 to 65 years (younger adults) and >65 years (older adults). Propensity score matching (PSM) using nearest-neighbor matching was used to match each older recipient with up to 2 younger adult recipients using multiple preoperative parameters. Outcomes evaluated were duration of ventilation, need for reintubation, tracheostomy, intensive care unit (ICU) readmission, length of ICU and hospital stays, postoperative complications, reoperation within 90 days, and patient survival. A total of 801 adult LDLT recipients were included in the study; 751 (93.7%) were younger adults, and 50 (6.3%) were older adults. Older recipients were more likely to be diabetic (60.0% versus 39.7%) and hypertensive (44.0% versus 20.4%) with preexisting cardiac disease (28.0% versus 11.2%). However, their pretransplant Model for End-Stage Liver Disease score was significantly lower (14.5 versus 17.7), and they were more likely to receive a transplant because of hepatocellular carcinoma (38.0% versus 17.7%). Older recipients had longer durations of ventilation after LT both before (3.7 versus 1.9 days) and after PSM (4.0 versus 1.5 days). After PSM, the 30-day (13.0% versus 2.4%), 90-day (15.2% and 2.4%), and overall mortality rates (21.7% versus 7.1%) were significantly higher for older recipients when compared with younger recipients. There was no difference between the younger and older recipients with respect to other postoperative outcomes. This propensity score-matched study shows that the older LDLT recipients have higher 30-day, 90-day, 1-year, and 5-year mortality rates when compared with matched younger counterparts.

Live Liver Donors: Is Right Still Right?

BACKGROUND: Conventional wisdom dictates that a larger hepatectomy is more prone to complications. Consequently, with the donor safety as paramount, the transplant community has intuitively been proponents of left lobe donation in live donor liver transplantation (LDLT), thereby satisfying the tenet of double equipoise. More recently some data suggest that this may not always be the case, especially in established centres. Our aim was to compare right and left lobe donor outcomes in LDLT from a centre with cumulative experience. METHODS: Review of a prospectively collected database of right and left lobe liver donors operated between August 2009 and July 2017 was performed. Their preoperative demographics, operative and post-operative outcomes were compared. RESULTS: Of 904 liver transplantations, 458 were right lobe donors [379 without middle hepatic vein (MHV), 79 with MHV] and 58 left lobe donors. There was a significant difference in GRWR and functional liver remnant between the right and left lobe donors (1.27 ± 0.45 vs. 1.03 ± 0.28 p = 0.004, and 63.2 ± 7.9 vs. 37.7 ± 16.3, respectively, p value). The end portal pressure (7 vs. 8 mmHg p = <0.001), peak bilirubin (1.6 ± 0.8 vs. 2.9 ± 1.5 p = <0.001) and day 5 bilirubin (0.8 ± 0.3 vs. 1.4 ± 0.9 p = <0.001) were significantly higher in right lobe donors. There was no difference in blood loss, duration of surgery or peak lactate between the groups. Complications (20.7% vs. 25.9% p = 0.48), including serious complications (Clavien-Dindo > III) (6.9% vs. 8.1% p = 0.95), duration of ICU and hospital stay, were comparable between the groups. Subgroup analysis between left lobe and right lobe with and without MHV donor was also comparable. CONCLUSION: Though biochemical differences exist between the groups, no difference in outcomes was noted. Despite larger liver mass loss in right lobe donors, a strict protocol-based approach to donor selection leads to comparable outcomes between left lobe and right lobe donations.