Partial Orthotopic Liver Transplantation Research Articles

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

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.

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.

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

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.

Auxiliary Liver Graft Can Be Protected From HBV Infection in HBsAg Positive Blood Circulation.

Auxiliary grafts have a high risk of Hepatitis B virus (HBV) infection in patients with chronic HBV-related diseases. Hepatitis B virus-related auxiliary partial orthotopic liver transplantation (APOLT) cases were reviewed to show the results of current methods to block native-to-graft HBV transmission. Three patients received APOLT for HBV-related liver cirrhosis and a recurrent upper gastrointestinal hemorrhage between April 2015 and January 2017 by the liver transplant team of Beijing Friendship Hospital affiliated with Capital Medical University. All three patients were positive for HBV surface antigen (HBsAg) and had a negative HBV DNA test result before transplantation. After auxiliary transplantations, HBsAg was found to be positive in two patients and negative in one patient. To avoid graft infection of HBV, entecavir-based therapy was employed and the remnant native livers of the recipients were removed 51–878 days after liver transplantation. Then, serum conversions of HBsAg were found in all three cases. For the first time, this case series shows the possibility of blocking the transmission of HBV from a native liver to a graft in auxiliary transplantation by entecavir-based therapy. Among the cases, a left lobe graft was successfully implanted as a replacement of the right lobe of the recipient, which is also discussed.

Auxiliary partial orthotopic liver transplantation series in single center

Auxiliary partial orthotopic liver transplantation (APOLT) is a technically challenging procedure in which a segmental liver graft is implanted orthotopically following a native liver partial hepatectomy. Despite being considered an innovative technique, it is gradually gaining acceptance as a bridge therapy in acute liver failure with the possibility of immunosuppression free survival. We had four patients who underwent APOLT. The first patient was diagnosed as factor H deficiency. He underwent APOLT from his father who was a 33-year-old. He died post-transplant lymphoproliferative (PTLD) disorder after 9 month of APOLT. The second patient was diagnosed as fulminant liver cirrhosis due to alcoholic liver cirrhosis. He underwent APOLT from his son who was a 24-year-old donor. After 14 years, we found native liver hepatocellular carcinoma (HCC). He got Transcatheter arterial chemoembolization and radiofrequency ablation for HCC. The third patien was diagnosed as HELLP syndrome. She developed hepatic encephalopathy and eventually required ventilator and renal replacement therapy. After emergent C-section, she referred to acute to our center for management of fulminant liver failure (UNOS status 1). She underwent APOLT from a 35-year-old deceased donor. Cold ischemic time was 723 minutes and warm ischemic time was 33 minutes. Initially she took triple therapy of immunosuppressants. Finally she stop immnosuppressnats. The last patient was diagnosed as Wilson's disease. Cold ischemic time was 121 minutes and warm ischemic time was 33 minutes. APOLT is a technically challenging procedure, but there is chance of immunosuppression free survival.

Pediatric metabolic liver diseases: Evolving role of liver transplantation.

Metabolic liver diseases (MLD) are the second most common indication for liver transplantation (LT) in children. This is based on the fact that the majority of enzymes involved in various metabolic pathways are present within the liver and LT can cure or at least control the disease manifestation. LT is also performed in metabolic disorders for end-stage liver disease, its sequelae including hepatocellular cancer. It is also performed for preventing metabolic crisis’, arresting progression of neurological dysfunction with a potential to reverse symptoms in some cases and for preventing damage to end organs like kidneys as in the case of primary hyperoxalosis and methyl malonic acidemia. Pathological findings in explant liver with patients with metabolic disease include unremarkable liver to steatosis, cholestasis, inflammation, variable amount of fibrosis, and cirrhosis. The outcome of LT in metabolic disorders is excellent except for patients with mitochondrial disorders where significant extrahepatic involvement leads to poor outcomes and hence considered a contraindication for LT. A major advantage of LT is that in the post-operative period most patients can discontinue the special formula which they were having prior to the transplant and this increases their well-being and improves growth parameters. Auxiliary partial orthotopic LT has been described for patients with noncirrhotic MLD where a segmental graft is implanted in an orthotopic position after partial resection of the native liver. The retained native liver can be the potential target for future gene therapy when it becomes a clinical reality.

Auxiliary Partial Orthotopic Liver Transplantation for Acute Liver Failure: Not Supportive Enough?

Auxiliary Partial Orthotopic Liver Transplantation for Acute Liver Failure: Not Supportive Enough?

Liver Transplantation for Metabolic Liver Disease Patients: A Single-Center Experience

Introduction: Metabolic liver disease (MLD) is life threatening. The efficacy of liver transplantation (LT) for MLD patients are well reported. There are some options of surgical procedures, but a few reports of collecting data was reported from a single-center. Here we present our experiences of LT procedures including deceased donor (DD) LT, living donor (LD) LT and auxiliary partial orthotopic liver transplantation (APOLT), and outcome in those patients. Methods: Medical records of 61 MLD adult (≧18 years old) recipients underwent LT in our institute were reviewed retrospectively. Perioperative factors were investigated. The patient survival rate was calculated. Results: The causes of LT were familial amyloid polyneuropathy in 42, adult-onset type 2 citrullinemia in 17, glycogen storage disease in 1 and Wilson's disease in 1. The median age at LT was 37.1 (range 18.8 to 58.4) years old. All DDLT recipients received whole liver graft (n=7). In all LDLT cases (n=54), the left liver grafts were used. The median volume of graft was 392g that was correspond to 38.0% of the recipient standard liver volume (range 230 (22.1) to 580g (58.8%)). In 18 cases of those, APOLT was selected because of extremely small size of graft or expectation of future gene therapy. The 10-year survival rate of MLD recipients was 86.8%. Conclusions: Even though a graft is relatively small, LT for MLD patients could be successfully achieved with APOLT. The 10-year survival rate of MLD recipient in our institute was thought to be satisfactory.

Auxiliary partial orthotopic liver transplantation in pre-eclampsia

Auxiliary partial orthotopic liver transplantation in pre-eclampsia

Successful living donor liver transplantation plus domino-auxiliary partial orthotopic liver transplantation for pediatric patients with metabolic disorders.

To investigate the efficacy of living donor liver transplantation (LDLT) plus domino-auxiliary partial orthotopic liver transplantation (D-APOLT) in pediatric patients with metabolic disorders. From May 2017 to October 2018, two patients with ornithine aminotransferase deficiency (OTCD) and one patient with type I Crigler-Najjar syndrome (CNS1) received LDLT, their livers were prepared as donors for D-APOLT. Two patients with CNS1 received domino liver grafts from OTCD patients; one OTCD patient received a domino liver graft from a CNS1 patient. The mean follow-up was 26.6months. The liver function and ammonia remained in the normal range at the end of the follow-up in all recipients. One D-APOLT patient experienced portal vein thrombosis 2days after transplantation and required reoperation, this patient presented an imbalance of portal blood perfusion between the native and the domino liver at 8months after liver transplant. The imbalance was improved by interventional radiology treatment. Two LDLT patients experienced early mild acute rejection. The non-cirrhotic livers from pediatric patients with metabolic liver disease can be used as domino donor grafts for selected pediatric patients with different metabolic liver disease. D-APOLT achieves ideal recipient outcomes and provides a strategy to expand donor source for children.

Prognosis and treatment options in cases of acute liver failure caused by mushroom poisoning due to Amanita phalloides

Poisoning due to mushroom ingestion is a relatively rare but deadly cause of acute liver failure (ALF). Consumption of the poisonous mushroom Amanita phalloides, also known as ‘death cap’, is one of the most common causes of mushroom poisoning worldwide, being involved in the majority of human fatalities caused due to mushroom ingestion. A major portion of the liver damage due to Amanita phalloides is related to powerful toxins known as amanitins, which cause impairment in protein synthesis and subsequent cell necrosis by the inhibition of RNA polymerase II. Initially the presentation is that of an asymptomatic lag phase, followed by gastrointestinal symptoms and hepato-renal involvement. Amatoxin poisoning may progress into fulminant hepatic failure and eventually death if liver transplantation is not performed. It is based on a careful assessment of history of type and duration of mushroom ingestion, as well as the clinical manifestations. Diagnosis can be confirmed by laboratory tests measuring urinary amatoxin levels and identification of the mushroom. Although N-Acetyl Cysteine and Penicillin-G have proven to be effective therapeutic agents, Orthotopic Liver Transplantation (OLT) or Auxiliary Partial Orthotopic Liver Transplantation (APOLT) is the only treatment option for most of the cases carrying a poor prognosis.

Partial orthotopic liver transplantation in combination with two-stage hepatectomy: A proof-of-concept explained by mathematical modeling

BackgroundResection And Partial Liver Segment 2/3 Transplantation with Delayed total hepatectomy (RAPID) includes total hepatectomy in 2 steps with small graft transplantation at first stage. To avoid graft portal hyperperfusion, portal vein pressure monitoring is required after revascularization and right portal vein clamping. To date, portal flow modulation has not been reported but simulating hemodynamics in RAPID patients would be useful to anticipate these procedures.Our team developed hemodynamic 0D modeling; we aimed to assess if this mathematical model could be accurately used in the RAPID setting. MethodsThe modified 0D model was retrospectively tested on 3 patients. We compared our estimated portal vein pressures and portocaval gradients to those intraoperatively measured, as indication to modulate portal flow relies on these measures. FindingsPortal pressures measured after right portal vein clamping (end of RAPID procedure) in patients 1, 2 and 3 were respectively of 14, 16 and 12 mmHg while the simulated pressures were of 13.1, 14.8 and 11.5 mmHg (p = 0.25).Portocaval gradients measured after right portal vein clamping in the 3 patients were respectively of 10, 11 and 7 mmHg while the simulated gradients were of 9.9, 11.6 and 8.3 mmHg (p = 0.5). InterpretationWe succeeded to predict portal vein pressures and portocaval gradients after RAPID. This promising report demonstrates that 0D simulation could be a useful tool for human decision-making. Moreover, such a patient-specific model could be of importance if we transpose RAPID experience to hepatocellular carcinoma bearing cirrhotics, a population with high probability of portal hypertension after RAPID.

Auxiliary living donor liver transplantation combined with two-stage hepatectomy for unresectable colorectal liver metastases.

To review the role of liver transplantation for unresectable colorectal liver metastases (u-CRLM) and to describe the intial experience with auxiliary living donor liver transplantation combined with two-stage hepatectomy for u-CRLM (i.e. living donor RAPID). Patients affected with u-CRLM have a poor prognosis with 5 years overall survival (OS) rate less than 10% under standard modern chemotherapy.There is an actual international consensus that liver transplantation for u-CRLM represents a viable option in highly selected patients with OS rate at 5 years up to 80% notwithstanding high recurrence rates. Due to the scarcity of whole liver graft from deceased donors, the RAPID procedure (i.e. resection and partial liver segment 2-3 transplantation from deceased donors with delayed total hepatectomy) has been introduced as possible alternative. The RAPID procedure represents the most actual and modern fusion of the two most challenging procedures of modern hepatobiliary and liver transplant surgery: that is auxiliary partial orthotopic liver transplantation and associating liver partition and portal vein ligation for staged hepatectomy. Although the deceased donor-RAPID procedure may show promising results, the basic problem of scarcity of organs from deceased donors and mainly the lack of splittable organs still remains. The living donor RAPID, based on transplantation of left lateral segments from living donor, may represent the way out to this problem. It is feasible and safe (for both donor and recipient), but characterized by a very challenging high-end transplantological procedure.

6. Auxiliary Partial Orthotopic Liver Transplantation for Selected Non Cirrhotic Metabolic Liver Disease

Background and Aims: Auxiliary Partial Orthotopic Liver Transplantation (APOLT) in selected non-cirrhotic metabolic liver diseases (NCMLD) is a viable alternative to orthotopic liver transplantation as it supplements the function of the native liver with the missing functional protein. APOLT for NCMLD is not universally accepted due to concerns of increased technical complications and long-term graft atrophy. Methods: Review of a prospectively collected database of all paediatric patients (age ≤16 years) who underwent liver transplant for non-cirrhotic MLD (NCMLD), from August 2009 up to June 2017 was performed. Patients were divided into two groups; Group 1 underwent APOLT and group 2 orthotopic liver transplant (OLT). Results: Eighteen OLT and 12 APOLT were performed for NCMLD during the study period. There was no significant difference in the age and weight of the recipients in both groups. All APOLT patients needed intra-operative portal flow modulation. Intraoperative peak and end of surgery lactate were significantly higher in the OLT group, and Cold ischemia time (CIT) was longer in the APOLT group. There were no differences in postoperative liver function tests apart from higher peak INR in the OLT group. The incidence of postoperative complications, duration of hospital stay and 1 & 5 year survivals were similar in both groups. Conclusions: We present the largest series of APOLT for NCMLD. APOLT is a safe and effective alternative to OLT, and may even be better than OLT due to lesser physiological stress, and smoother postoperative period for selected patients with NCMLD. The authors have none to declare.

Application of 3-Dimensional Printing in Pediatric Living Donor Liver Transplantation: A Single-Center Experience.

Three-dimensional (3D) printing has been used to support organ transplantations. However, whether it helps remains unclear. This study aimed to present and assess the application of 3D-printed liver models in pediatric living donor liver transplantation (LDLT). The 3D images were printed to touchable liver models with transparent liver parenchyma, specifically colored hepatic vessels, and biliary structures. A total of 30 consecutive recipients were enrolled in the study: 10 were operated on with the support of 3D printing (3D-printing group) and 20 (control group) were operated on without it. Detailed photographs and data of the cases in the 3D-printing group were presented. One patient underwent auxiliary partial orthotopic liver transplantation using the left lobe graft, in which the abdominal cavity model was also printed to test whether the planned graft fit the recipient's abdominal cavity. The 3D-printed models facilitated surgical planning and procedures, particularly in the management of hepatic veins and in the prevention of large-for-size syndrome. The operative time of donors in the 3D-printing group was significantly shorter compared with the control group (2.3±0.4 versus 3.0±0.4 hours; P<0.001). Inpatient costs for donors in the 3D-printing group were 17.1% lower than those in the control group (34.6±6.6 versus 41.7±10.4 thousand ¥; P=0.03). In conclusion, in small infants and complicated pediatric LDLT patients, 3D-printed models can help minimize the risk of large-for-size syndrome and graft reduction. The 3D-printed models may be conducive to liver graft procurement and intraoperative assistance in pediatric LDLT.

Auxiliary partial orthotopic liver transplantation for acute liver failure in mice

Auxiliary partial orthotopic liver transplantation for acute liver failure in mice