Auxiliary Liver Transplantation Research Articles

P.374: Domino cross auxiliary liver transplantation with whole graft for familial hypercholesterolemia in children.

P.374: Domino cross auxiliary liver transplantation with whole graft for familial hypercholesterolemia in children.

In-depth Clinical, Hemodynamic, and Volumetric Assessment of the Resection and Partial Liver Transplantation With Delayed Total Hepatectomy-Type Auxiliary Liver Transplantation in Noncirrhotic Setting: Are We Simply Dealing With a Transplant Model of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy?

The Resection And Partial Liver Transplantation with Delayed total hepatectomy (RAPID) procedure involves left hepatectomy with orthotopic implantation of a left lobe and right portal vein ligation. This technique induces volumetric graft increase, allowing for a right completion hepatectomy within 15 days. Notably, there is a lack of data on the hemodynamics of small-for-size grafts exposed to portal overflow without triggering small-for-size syndrome. A prospective single-center protocol included 8 living donors and 8 RAPID noncirrhotic recipients. Comprehensive clinical and biological data were collected, accompanied by intraoperative arterial and portal flow and pressure measurements. Early kinetic growth rate (eKGR%) and graft function were assessed using computed tomography and 99Tc-mebrofenin scintigraphy on postoperative days 7 and 14. Findings were compared with retrospective data from 13 left living donor liver transplantation (LDLT) recipients. The median Graft-body weight ratio was 0.41% (interquartile range: 0.34-0.49), markedly lower than in LDLT. However, there was no significant difference in eKGR between RAPID and LDLT grafts. Sequential analysis revealed variable eKGR per day: 10.6% (7.8-13.2) in the first week and 7.6% (6-9.1) in the second week posttransplantation. Indexed portal flow (indexed portal vein flow) was significantly higher in RAPID compared with left LDLT ( P = 0.01). No hemodynamic parameters were found to correlate with regeneration speed. We modulated portal flow in 2 out of 8 cases. This study presents the first report of hemodynamic and volumetric data for the RAPID technique. Despite initial graft volumes falling below conventional LDLT recommendations, the study highlights acceptable clinical outcomes.

Auxiliary Partial Orthotopic Liver Transplantation Is a Safe and Effective Option for Yellow Phosphorus Toxin-induced Acute Liver Failure.

Ingestion of yellow phosphorus-containing rodenticides (YPR) or firecrackers is an important cause of acute liver failure (ALF) in young adults and children, particularly in South and South-East Asia and South America. Emergency liver transplantation is indicated in cases refractory to intensive supportive therapy, including low-volume plasma exchange. There are no published reports on the feasibility of auxiliary partial orthotopic liver transplantation (APOLT) for YPR-induced ALF. Clinical details of patients undergoing APOLT for YPR-induced ALF in 1 unit are reported. Details of postoperative follow-up, native remnant regeneration, and immunosuppression withdrawal are also reported. Between January 2021 and December 2023, 3 patients (4 y, 1.5 y, and 26 y) underwent emergency living donor liver transplantation for YPR-induced ALF. All patients were refractory to supportive therapies, including therapeutic plasma exchange, and demonstrated progression of liver injury in the form of severe encephalopathy needing intubation, ventilation, and organ support. APOLT was considered because of their young age and minimal intraoperative inotropic requirement. All explants showed confluent parenchymal necrosis with microvesicular and macrovesicular steatosis. Patients were initially maintained on standard immunosuppression. Good remnant regeneration was noted on follow-up imaging in all cases, enabling gradual withdrawal of immunosuppression. Currently, 1 child has been off immunosuppression for 15 mo and 2 others are on reduced doses of immunosuppression. All patients demonstrated good liver function. APOLT procedure can be an appropriate transplant option in YPR-related ALF for children and young adults without severe hemodynamic instability.

Comment on "Refining Auxiliary Orthotopic Liver Transplantation (AOLT) Improves Outcomes in Adult Patients With Acute Liver Failure".

Comment on "Refining Auxiliary Orthotopic Liver Transplantation (AOLT) Improves Outcomes in Adult Patients With Acute Liver Failure".

Auxiliary partial orthotopic liver transplantation (APOLT) for Crigler-Najjar syndrome: a retrospective analysis

Auxiliary partial orthotopic liver transplantation (APOLT) for Crigler-Najjar syndrome: a retrospective analysis

Developments and challenges of liver transplantation in China

With the vigorous promotion of organ donation after citizen death in China, increased utilization of marginal livers, and continuous expansion of hepatocellular carcinoma indications for liver transplantation, innovations in techniques such as auxiliary liver transplantation, pediatric liver transplantation laparoscopic liver transplantation, magnetic liver transplantation,and non-ischemic liver transplantation have significantly improved the number of liver transplantation surgery performed, patient survival rates, and graft survival rates in China, while complication rates have gradually decreased. As such,liver transplantation in China has now reached leading or advanced levels internationally. In the new development context,Chinese liver transplantation faces new opportunities and challenges for development. Evolutions in basic diseases of transplant recipients and tumor classifications of will further broaden the population eligible for transplantation and introduce new demands for liver transplantation procedures. Emerging technologies including artificial organs, xenotransplantation,and artificial intelligence are bringing prospects for advancing liver transplantation. Looking ahead, the progression of liver transplantation will go beyond prioritizing patient survival rates and graft survival rates alone, instead emphasizing improved quality of life for transplant recipients post-surgery to an even greater extent.

Xiao-Ping Chen: the “Master of the Scalpel” who saves lives by entering the forbidden territory of hepatopancreatobiliary surgery

In his 50 years of practice, he has performed more than 20,000 hepatopancreatobiliary surgeries, being the first one to propose the concept of the “auxiliary partial orthotopic liver transplantation” internationally. Furthermore, he developed the “Chen's inserting biliary-enteric anastomosis and pancreato-enteric anastomosis,” “Chen's hepatic vascular occlusion,” “Chen's liver double-hanging maneuver,” and “Chen's hepatic vascular occlusion without liver portal dissection.” He also popularized these theories and techniques both in China and worldwide. His name is Xiao-Ping Chen, an academician of the Chinese Academy of Sciences and honorary president of the Tongji Medical College of Huazhong University of Science and Technology.

Auxiliary partial orthotopic liver transplantation (APOLT) for Crigler-Najjar syndrome: A retrospective analysis

BackgroundCrigler-Najjar syndrome is an ultra-rare hereditary disorder characterized by severe jaundice and risk of neurological complications. Current treatments, such as phototherapy, have limitations, and liver transplantation is often necessary. Auxiliary partial orthotopic liver transplantation (APOLT) is a potential treatment option. Still, its safety and efficacy in Pakistani patients with Crigler-Najjar syndrome Type I (CNS-I) have not been well established. MethodsThis retrospective study reviewed the outcomes of five pediatric patients with CNS-I who underwent APOLT at a tertiary care center in Pakistan. Patient demographics, surgical details, postoperative course, complications, and follow-up data were analyzed. The primary endpoint was the feasibility and safety of APOLT, while secondary endpoints included improvement in serum bilirubin levels, neurological symptoms, and survival rates. ResultsAmong five patients diagnosed with CNS-I, APOLT was performed without intraoperative complications. During the median follow-up period of 6 months, there were no cases of relaparotomy, graft rejection, biliary complications, or portal venous thrombosis. One patient developed a portal venous stricture, but his symptoms were controlled with conservative measures. Postoperative liver function tests showed a significant improvement, with an average reduction of 90% in serum bilirubin levels. There was some improvement in neurological symptoms, and the overall patient and graft survival rate was 100%. ConclusionThis study suggests that APOLT is a feasible and safe treatment option in patients with CNS-I. It improves liver function, bilirubin levels, and neurological symptoms. Further research with larger sample sizes is warranted to confirm these findings and evaluate the long-term outcomes of APOLT in this patient population.

Refining Auxiliary Orthotopic Liver Transplantation (AOLT) Improves Outcomes in Adult Patients With Acute Liver Failure.

To investigate whether and how experience accumulation and technical refinements simultaneously implemented in auxiliary orthotopic liver transplantation (AOLT) may impact on outcomes. AOLT for acute liver failure (ALF) provides the unique chance of complete immunosuppression withdrawal after adequate native liver remnant regeneration but is a technically demanding procedure. Our department is a reference center for ALF and an early adopter of AOLT. This is a single-center retrospective before/after study of a prospectively maintained cohort of 48 patients with ALF who underwent AOLT between 1993 and 2019. In 2012, technical refinements were implemented to improve outcomes: (i) favoring the volume of the graft rather than that of the native liver, (ii) direct anastomosis of graft hepatic artery with recipient right hepatic artery instead of the use of large size vessels, (iii) end-to-side hepaticocholedocostomy instead of bilioenteric anastomosis. Early experience (1993-2011) group (n=26) and recent experience (2012-2019) group (n=22) were compared. Primary endpoint was 90-day severe morbidity rate (Clavien-Dindo≥IIIa) and secondary endpoints were overall patient survival and complete immunosuppression withdrawal rates. Compared with the earlier experience group, the recent experience group was associated with a lower severe complication rate (27% vs 65%, P <0.001), as well as less biliary (18% vs 54%, P =0.017) and arterial (0% vs 15%, P =0.115) complications. The 1-, 3-, and 5-year patient survival was significantly improved (91%, 91%, 91% vs 76%, 61%, 60%, P =0.045). The rate of complete immunosuppression withdrawal increased to 94% vs 70%, ( P =0.091) with no need of long-term graft explant. These technical refinements favoring the liver graft and reducing morbidity may promote AOLT implementation among LT centers.

CT Volumetry Can Be Used for Monitoring Liver Function Recovery in Auxiliary Partial Orthotopic Liver Transplantation.

Scintigraphy with a 99m TC-trimethyl-Br-IDA tracer (TBIDA) is used to monitor liver function regeneration after auxiliary partial orthotopic liver transplantation (APOLT) for acute liver failure (ALF). As computed tomography (CT) is also regularly performed during patient follow-up, CT volumetry could be used as an alternative to monitor native liver recovery after APOLT for ALF. This was a retrospective cohort study of all patients who underwent APOLT (October 2006-July 2019). Collected data included liver graft and native liver CT volumetry measurements (expressed as fractions), TBIDA scintigraphy results, and biological and clinical data including immunosuppression therapy after APOLT. Four follow-up time points were defined (baseline, discontinuation of mycophenolate mofetil, beginning of tacrolimus reduction, and tacrolimus discontinuation) for analysis. Twenty-four patients (7 men; median age 28.5 y old) were included. The main etiologies of ALF were acetaminophen intoxication (n = 12), hepatitis B virus (n = 5), and amanita phalloides intoxication (n = 3). The median native liver function fractions on scintigraphy at baseline, at discontinuation of mycophenolate mofetil, at tacrolimus reduction, and at tacrolimus discontinuation were 22.0% (interquartile range 14.0-30.8), 30.5% (21.5-49.0), 32.0% (28.0-62.0), and 93.0% (77.0-100.0), respectively. The corresponding median native liver volume fractions on CT were 12.8% (10.4-17.3), 20.5% (14.2-27.3), 24.7% (21.3-48.4), and 77.9% (62.5-96.9), respectively. Volume and function were strongly correlated (r = 0.918; 95% confidence interval, 0.878-0.945; P < 0.01). Median time-to-immunosuppression discontinuation was 25.0 (17.0-35.0) mo. Estimated time-to-immunosuppression discontinuation was shorter in patients with acetaminophen-induced ALF (22 versus 35 mo; P = 0.035). In patients who receive APOLT for ALF, CT-based liver volumetry closely parallels native liver function recovery evaluated on TBIDA scintigraphy.

Fk506 Inhibit Liver Regeneration in HOC Model Rat

Studies have shown that lymphocytes support hepatic oval cell (HOC)-dependent liver regeneration and FK506（Tacrolimus） is known as an immunosuppressor. Therefore, we studied the role of FK506 in HOC activation and/or proliferation to guide the clinical use of FK506. Thirty male Lewis rats were randomly divided into 4 groups: (A) intervene in activation (n=8), (B) intervene in proliferation (n=8), (C) control HOC model (n=8), and (D) pure partial hepatectomy (PH) (n=6). The HOC model was established by 2AAF(2-acetylaminofluorene)/PH in groups A to C. FK506 (at a dose of 1 mg/kg/d) was given subcutaneously in group A except on operation day, and not until day 8 post-operation (PO) in group B. Half of the animals were euthanized on days 10 and 14 PO, respectively. The remnant liver was weighed and stained by hematoxylin and eosin and immunohistochemical staining of proliferating cell nuclear antigen and epithelial cell adhesion molecule enabled HOC proliferation analysis. FK506 intervention exacerbated liver damage and hindered the recovery of the HOC model rat. Weight gain was severely retarded or even negative. Liver weight and the liver body weight ratio were lower than control group. HE and immunohistochemistry showed pooer proliferation of hepatocytes and fewer HOC numbers in group A. FK506 inhibited HOC activation by affecting T and NK cells, ultimately blocking liver regeneration. Poor liver regeneration after auxiliary liver transplantation might be associated with the inhibition of HOC activation and proliferation caused by FK506 treatment.

Utilizing ultra-small volume graft in auxiliary liver transplantation for portal hypertension

Objective: To examine the clinical effect of auxiliary liver transplantation with ultra-small volume graft in the treatment of portal hypertension. Methods: Twelve cases of portal hypertension treated by auxiliary liver transplantation with small volume graft at Liver Transplantation Center,Beijing Friendship Hospital, Capital Medical University between December 2014 and March 2022 were studied retrospectively. There were 8 males and 4 females,aged 14 to 66 years. Model for end-stage liver disease scores were 1 to 15 points and Child scores were 6 to 11 points. The grafts was derived from living donors in 9 cases,from split cadaveric donors in 2 cases,from whole cadaveric liver of child in 1 case. The graft recipient body weight ratios of 3 cadaveric donor livers were 0.79% to 0.90%, and of 9 living donor livers were 0.31% to 0.55%.In these cases, ultra-small volume grafts were implanted. The survivals of patient and graft, complications, portal vein blood flow of residual liver and graft, abdominal drainage and biochemical indexes of liver function were observed. Results: All the grafts and patients survived. Complications included outflow tract torsion in 2 cases, acute rejection in 1 case, bile leakage in 1 case, and thyroid cancer at the later stage of follow-up in 1 case, all of which were cured. The torsion of outflow tract was attributed to the change of anastomotic angle after the growth of donor liver. After the improvement of anastomotic method, the complication did not recur in the later stage. There was no complication of portal hypertension. The measurement of ultrasonic portal vein blood flow velocity showed that the blood flow of residual liver decreased significantly in the early stage after operation, and maintained a very low blood flow velocity or occlusion in the long term after operation, and the blood flow of transplanted liver was stable. Conclusions: Auxiliary liver transplantation can implant ultra-small donor liver through compensation of residual liver. This method may promote the development of living donor left lobe donation and split liver transplantation. However, the auxiliary liver transplantation is complex, and it is difficult to control the complications. Therefore, this method is currently limited to centers that are skilled in living related liver transplantation and that have complete ability to monitor and deal with complications.

Successful combined auxiliary partial liver and intestinal transplantation in two highly sensitized, cross-match positive patients.

Sensitization to human leukocyte antigen (HLA) creates an immunological barrier to intestinal transplantation (ITx). Current desensitization therapies are limited and ineffective in the most highly sensitized patients. A co-transplanted whole liver transplant can protect a kidney, heart, or intestinal allograft from antibody-mediated injury. Whether an auxiliary partial liver allograft provides effective protection for highly sensitized intestinal transplant recipients is unknown. Two patients with strong HLA donor-specific antibody at high titer against their deceased donors underwent combined auxiliary partial liver and ITx across a positive cross-match. The left lateral lobes from the combined-graft recipients and the right liver lobes from the deceased donors were transplanted as a domino procedure to other four patients. Two combined-graft recipients have had an uneventful postoperative course without major complications at a 12- and 24-month follow-up, respectively. Intestinal graft function has been excellent with no evidence of humoral or cellular rejection. While a positive cross-match turned negative, titers of donor-specific HLA antibodies gradually declined over time after transplant. The left liver lobes procured from the combined-graft recipients were successfully transplanted into two pediatric patients (age 1.9, 2.4years) and the right lobes from two deceased donors were successfully transplanted into two adult patients. All transplant procedures went well, without post-operative complications related to the splitting technique. Our results indicate that an auxiliary liver transplant can effectively protect a co-transplanted intestinal allograft against rejection and suggest that this combined procedure may serve as a useful therapeutic adjunct for a highly sensitized intestinal transplant candidate.

Native/Graft Volume and Function Assessment Using 99m Tc-Mebrofenin Scintigraphy with SPECT-CT Scan Following Auxiliary Liver Transplantation

Native/Graft Volume and Function Assessment Using 99m Tc-Mebrofenin Scintigraphy with SPECT-CT Scan Following Auxiliary Liver Transplantation

Refining Auxiliary Partial Orthotopic Liver Transplantation (APOLT) for Acute Liver Failure in 48 Adult Patients

Refining Auxiliary Partial Orthotopic Liver Transplantation (APOLT) for Acute Liver Failure in 48 Adult Patients

In-depth Clinical, Haemodynamic and Volumetric Assessment of the RAPID-type Auxiliary Liver Transplantation; Are We Simply Dealing with a Transplant Model of ALPPS?

In-depth Clinical, Haemodynamic and Volumetric Assessment of the RAPID-type Auxiliary Liver Transplantation; Are We Simply Dealing with a Transplant Model of ALPPS?

Managing recurrent portal steal in auxiliary liver transplantation for non‐cirrhotic metabolic liver disease

APOLT has been proposed as a treatment modality for certain types of NCMLD. While the short-term outcomes of this operation have been comparable with orthotopic LT, its long-term outcomes have sparsely been reported. We present one such case of Citrullinemia type I who underwent APOLT and developed recurrent PS. A 2-year-old male child with a diagnosis of Citrullinemia type I underwent APOLT with a left lateral segment from a split deceased donor liver, and his postoperative period was unremarkable. Ammonia-lowering agents were stopped 1 week following the operation and the child was discharged home on a normal diet. Four years following APOLT, the child presented with altered sensorium and seizures. A diagnosis of PS was made. Subsequent to an embolization of the native liver's right anterior portal vein his sensorium improved and he remained clinically stable on a normal diet. Six years following the APOLT, the child again presented with features of acute encephalopathy. Imaging was suggestive of PS. A portal vein embolization of the native portal vein was performed and the child's clinical condition improved. At 6 months' follow-up, the child remains well on a normal diet. While the early impediments in this technique may have been overcome, in the absence of any realistic clinical application gene therapy, the debate of long-term phenotypic metabolic correction for NCMLD by APOLT needs to be revisited.

A modified kidney-sparing portal vein arterialization model of heterotopic auxiliary liver transplantation increases liver IL-6, TNF-α, and HGF levels and enhances liver regeneration: an animal model

Background and AimThe success of partial donor liver transplantation is affected by the implantation site of the donor liver and the vascular reconstruction approach. We investigated the effects of different donor liver implantation sites and vascular reconstruction approaches on liver regeneration using a rat kidney-sparing heterotopic auxiliary liver transplantation model, with portal vein arterialization (PVA).MethodsSixty male Sprague–Dawley rats underwent end-to-end anastomosis of the donor liver portal vein and the right renal artery stent (control group), or end-to-side anastomosis of the donor liver portal vein and the left common iliac artery (experimental group).ResultsThe experimental group had significantly lower plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and cholinesterase than the control group (all, P < 0.05). The levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and hepatocyte growth factor (HGF) in the liver were significantly higher in the experimental group than that in the control group (all, P < 0.05). Hematoxylin and eosin (HE) staining of the liver tissue specimens indicated that the experimental group had greater hepatocyte regeneration compared to the control group.ConclusionsThe modified kidney-sparing PVA model of heterotopic auxiliary liver transplantation is more conducive to liver regeneration with quicker return of liver function.

A systematic review of auxiliary liver transplantation of small-for-size grafts in patients with chronic liver disease

Background & AimsThe shortage of liver grafts continues to worsen. Because the expanded use of small-for-size grafts (SFSGs) would substantially alleviate this shortage, we aimed to analyse the available knowledge on auxiliary liver transplantation (ALT) with SFSGs in patients with chronic liver disease (CLD) to identify opportunities to develop ALT with SFSGs in patients with CLD.MethodsThis is a systematic review on ALT using SFSGs in patients with CLD. The review was completed by updates obtained from the authors of the retained reports.ResultsHeterotopic ALT was performed in 26 cases between 1980 and 2017, none for SFGS stricto sensu, and auxiliary partial orthotopic liver transplantation (APOLT) in 27 cases (from 1999 to 2021), all for SFSG. In APOLT cases, partial native liver resection was performed in most of cases, whereas the second-stage remnant native liver hepatectomy was performed in 9 cases only. The median graft-to-body weight ratio was 0.55, requiring perioperative or intraoperative portal modulation in 16 cases. At least 1 complication occurred in 24 patients following the transplant procedure (morbidity rate, 89%). Four patients (4/27, 15%) died after the APOLT procedure. At the long term, 19 (70%) patients were alive and well at 13 months to 24 years (median, 4.5 years) including 18 with the APOLT graft in place and 1 following retransplantation.ConclusionsDespite high postoperative morbidity, and highly reported technical variability, the APOLT technique is a promising technique to use SFSGs in patients with CLD, achieving satisfactory long-term results. The results need to be confirmed on a larger scale, and a standardised technique could lead to even better results.Lay summaryAt the cost of a high postoperative morbidity, the long-term results of APOLT for small-for-size grafts are good. Standardisation of the procedure and of portal modulation remain needed.

Auxiliary Liver Transplantation for Cirrhosis: From APOLT to RAPID: A Scoping Review.

To survey the available literature regarding the use of auxiliary liver transplantation (ALT) in the setting of cirrhosis. ALT is a type of liver transplantation (LT) procedure in which part of the cirrhotic liver is resected and part of the liver graft is transplanted. The cirrhotic liver left in situ acts as an auxiliary liver until the graft has reached sufficient volume. Recently, a 2-stage concept named RAPID (Resection and Partial Liver segment 2/3 transplantation with Delayed total hepatectomy) was developed, which combines hypertrophy of the small graft followed by delayed removal of the native liver. A scoping review of the literature on ALT for cirrhosis was performed, focusing on the historical background of RAPID and the status of RAPID for this indication. The new comprehensive nomenclature for hepatectomy ("New World" terminology) was used in this review. A total of 72 cirrhotic patients underwent ALT [heterotopic (n = 34), orthotopic (Auxiliary partial orthotopic liver transplantation, n = 34 including 5 followed by resection of the native liver at the second stage) and RAPID (n = 4)]. Among the 9 2-stage LTs (APOLT, n = 5; RAPID, n = 4), portal blood flow modulation was performed in 6 patients by deportalization of the native liver (n = 4), portosystemic shunt creation (n = 1), splenic artery ligation (n = 3) or splenectomy (n = 1). The delay between the first and second stages ranged from 18 to 90 days. This procedure led to an increase in the graft-to-recipient weight ratio between 33% and 156%. Eight patients were alive at the last follow-up. Two-stage LT and, more recently, the RAPID procedure are viable options for increasing the number of transplantations for cirrhotic patients by using small grafts.