Auxiliary Liver Transplantation Research Articles

Postoperative imaging findings in children with auxiliary partial orthotopic liver transplant (APOLT).

Auxiliary partial orthotopic liver transplant (APOLT) is a treatment technique for people who have acute hepatic failure secondary to fulminant hepatic failure and might ultimately recover normal liver function. This surgical procedure is complicated, involving the placement of a liver graft while maintaining viability of the remaining native portion of the liver. This method allows the native liver to recover hepatic function, therefore eliminating the need for long-term immunosuppression, as is typically needed in post-transplant settings. Postoperative imaging in these cases can be challenging given the complex anatomy, specifically the vascular anastomosis. Therefore it is important for radiologists and clinicians to be aware of the anatomy as well as the variable imaging appearances of the liver. We review the imaging findings in children who have undergone auxiliary partial orthotopic liver transplant (APOLT).

Liver transplantation in acute liver failure: A challenging scenario

Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation.

Surgical Model of Auxiliary Partial Liver Transplantation in the Rat

Surgical Model of Auxiliary Partial Liver Transplantation in the Rat

Early Application of Auxiliary Partial Orthotopic Liver Transplantation in Murine Model of Wilson Disease.

Liver transplantation (LT) is the only option of treatment for Wilson disease (WD) when chelation therapy fails, but it is limited due to the shortage of donor. Auxiliary partial orthotopic LT (APOLT) has been performed successfully in end-stage WD patients, which expands the donor pool. Atp7bmice were used as experimental model of WD. Eight- and 20-week-old mice were used as different timepoints to perform APOLT. Serum copper, tissue copper, serum ceruloplasmin (CP), and liver histological examination were observed after operation. Hepatic and serum copper levels in Atp7b mice decreased after APOLT, and copper metabolism disorder of WD mice was relieved at both early and late stages. The progression of pathology in the native liver was delayed only when transplantation was performed at an early stage. Auxiliary partial orthotopic LT can significantly improve copper metabolism disorder in the Atp7b mice, and early transplantation may prevent the disease progression.

Updates of heterotopic auxiliary liver transplantation with portal vein arterialization

In recent years, liver transplantation donor shortage as one of world medical problems is paid more attention by domestic and overseas scholars. In view of that, heterotopic auxiliary liver transplantation emerges which transplants the whole or some parts of a donor liver outside the original liver position on the condition that some parts or the whole of the original liver were retained. As for the liver transplantation with poor conditions on portal vein, reconstruction of portal vein has become an aporia. Based on this, some scholars put forward the theory–arterialization of portal vein(PVA), namely a method to increase arterial blood supply or replace portal vein blood perfusion of liver by establishing some pathes among artery and portal vein or its branches. The research background and current situation of heterotopic auxiliary liver transplantation with portal vein arterialization, the transplanting position of donor liver, vessel reconstruction, dynamics mechanism after reconstruction and liver regene-ration are summarized in this review. Key words: End stage liver disease; Portal vein arteria-lizations; Revascularization; Heterotopic auxiliary liver transplantation

Simplified technique for auxiliary orthotopic liver transplantation using a whole graft.

BackgroundAcute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival.AimTo describe an alternative technique to auxiliary liver transplant on acute liver failure.MethodWas performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness.ResultsThe procedure improved liver function and decreased intracranial hypertension in the postoperative period.ConclusionThis technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil.

Combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation in a highly sensitized recipient

Objective To report the clinical effectiveness and safety of combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation for highly sensitized recipients with uremia. Methods In March 2014, combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation from the same donor was performed in a highly sensitized recipient with positive panel reactive antibodies (PRA) (31% class Ⅰ, 63% class Ⅱ). Compendious technical scheme: the partial liver from the same donor was transplanted in splenic recess of the recipient before the renal transplantation operation. Hyperacute rejection and the function of kidney after the transplantation were observed. Serum samples were also collected before and after reperfusion of the liver and each time points after the transplant surgery to detect the antibody level. Results The operation took 8 hours and 25 minutes with bleeding of 700 ml. The renal transplant functioned well without hyperacute rejection after transplantation. All the human leukocyte antigen antibodies turned to negative at 3 hour post-transplantation. The concentration of serum creatinine was 141 μmol/L and the level of PRA was 80% at 6 day post-transplantation. At 7 day post-transplantation, the creatinine level increased and acute rejection of transplant kidney occurred, which was controlled by plasmapheresis, anti-thymocyte globulin and intravenous immunoglobulin. The recipient was followed up for 12 months, serum creatinine value was 131 μmol/L. Conclusions A simultaneous transplantation of a partial auxiliary liver graft from the same donor in splenic fossa, with the sole purpose of protecting the kidney from harmful lymphocytotoxic antibodies, may solve the problem of kidney transplantation in highly sensitized recipients. Key words: Highly sensitization; Kidney transplantation; Combined transplantation; Splenic fossa auxiliary heterotopic liver transplantation; Hyperacute rejection

Portal flow modulation in auxiliary partial orthotopic liver transplantation.

APOLT is a suitable technique of liver transplantation in patients with ALF and some types of MLD. Portal venous steal is a problem with this procedure that leads to graft dysfunction and failure. Modulation of the portal flow to the graft and native liver can help in preventing this problem. We discuss the pathophysiology of this complication, review available literature regarding its management, and describe our results using the technique of graded hemiportal banding to achieve adequate perfusion for the graft and native liver.

Auxiliary Partial Orthotopic Liver Transplantation as a Treatment for Hemophilia A: A Case Report

A 37-year-old man with moderately severe hemophilia A (factor VIII of 1.2%), who had a normal liver without liver cirrhosis or hepatocellular carcinoma, was referred to our liver transplantation (LT) team. LT was planned for sufficient coagulation factor level maintenance and prophylaxis against future hemorrhagic complications. The donor was the patient's 35-year-old wife, who was nonhemophilic. We performed an auxiliary partial orthotopic liver transplantation (APOLT) with the approval of the Institutional Ethics Committee. A left partial liver graft taken from the donor was orthotopically transplanted to the recipient after resection of the native left hemiliver while preserving the native right lobe. After surgery, the patient tolerated the procedure, and tacrolimus was used to maintained immunosuppression. In this recipient, factor VIII activity significantly increased soon after the APOLT, and has been maintained at >20% without any further bleeding episodes for the past 74 months since the procedure. This finding suggests that APOLT may be an effective alternative treatment for patients with hemophilia A.

Recent advances in management of acute liver failure.

Acute liver failure (ALF) is a life-threatening illness, where a previously normal liver fails within days to weeks. Sudden loss of synthetic and detoxification function of liver results in jaundice, encephalopathy, coagulopathy, and multiorgan failure. The etiology of ALF varies demographically. The mortality of ALF is as high as 40–50%. The initial care of patients with ALF depends on prompt recognition of the condition and early detection of etiology. Management includes intensive care support, treatment of specific etiology if present and early detection of candidates for liver transplantation. Liver transplantation remains the only therapeutic intervention with proven survival benefit in patients with irreversible ALF. Living related liver transplantation, auxiliary liver transplantation, and ABO-incompatible liver transplantation are coming up in a big way. Liver assist devices and hepatocyte transplant remain experimental and further advances are required. Public health measures to control hepatitis A, B, E, and drug-induced liver injury will reduce the incidence and mortality of ALF.

Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

Background: The activation of tissue factor (TF) is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI) is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. Methods: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility. Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI were tested for their ability to inhibit clotting in vitro. Results: TF from recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs) transfected with human TFPI showed a prolonged recalcification time in vitro and in a rodent model. Conclusion: Recipient TF is relevant to dysregulated coagulation after xenotransplantation. Kunitz domain 1 plays the most important role in species incompatibility between pig TFPI and human TF, and clotting can be inhibited by human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the incompatibility of pig TFPI.

Pre-transplant Predictors for 3-Month Mortality after Living Donor Liver Transplantation

Background: High model for end-stage liver disease (MELD) scores (≥35) is closely associated with poor posttransplantation out- comes in patients who undergo living donor liver transplantation (LDLT). There is little information regarding factors that negatively impact the survival of patients with high MELD scores. The aim of this study was to identify factors associated with 3-month mortal- ity of patients after LDLT. Methods: We retrospectively analyzed 774 patients who underwent adult LDLT with right lobe grafts between 1996 and 2012. Exclusion criteria were re-transplantation, left graft, auxiliary partial orthotopic liver transplantation, and inadequate medical recording. Preoperative variables were analyzed retrospectively. Results: The overall 3-month survival rate was 92%. In univariate analysis, acute progression of disease, severity of hepatic ence- phalopathy, Child-Pugh class C, hepatorenal syndrome, use of continuous renal replacement therapy, use of ventilator, intensive care unit (ICU) care before transplantation, and MELD scores ≥35 were identified as potential risk factors. However, only ICU care before transplantation and MELD scores ≥35 were independent risk factors for 3-month mortality after LDLT. Three-month and 1-year patient survival rates for those with no risk factors were 95.5% and 88.6%, respectively. In contrast, patients with at least one risk factor had 3-month and 1-year patient survival rates of 88.4% and 81.1%, respectively, while patients with two risk factors had 3-month and 1-year patient survival rates of 55.6% and 55.6%, respectively. Conclusions: Patients with both risk factors (ICU care before LDLT and MELD scores ≥35) should be cautiously considered for treatment with LDLT.

A new rat model of auxiliary partial heterotopic liver transplantation with liver dual arterial blood supply.

Auxiliary partial heterotopic liver transplantation (APHLT) with portal vein arterialization is a valuable procedure to be considered in the treatment of patients with acute liver failure and metabolic liver diseases. The aim of this study was to develop a new rat model of APHLT with liver dual arterial blood supply (LDABS). A total of 20 rats were used. The donor liver was resected, and the celiac trunk was reserved. Left and medial hepatic lobes accounting for 70% of the liver mass were removed en bloc and the suprahepatic caval vein was ligated simultaneously. Thus, 30% of the donor liver was obtained as the graft. Sleeve anastomosis of the graft portal vein and splenic artery were performed after narrowing the portal vein lumen through suturing. The right kidney of the recipient was removed, and sleeve anastomosis was performed between the celiac trunk of the graft and the right renal artery of the recipient. In addition, end-to-end anastomosis was performed between the infrahepatic caval vein of the graft and the right renal vein of the recipient. Following the reperfusion of the graft, the blood flow of the arterialized portal vein was controlled within the physiological range through suturing and narrowing under monitoring with an ultrasonic flowmeter. The bile duct of the graft was implanted into the duodenum of the recipient through an internal stent catheter. A 70% section of the native liver (left and medial hepatic lobes) was resected using bloodless hepatectomy. The mean operative duration was 154.5±16.4 min, and the warm and cold ischemia times of the graft were 8.1±1.1 min and 64.5±6.6 min, respectively. The blood flow of the arterialized portal vein to the graft was 1.8±0.3 ml/min/g liver weight. The success rate of model establishment (waking with post-surgical survival of >24 h) was 70% (7/10). Following successful model establishment, all rats survived 7 days post-surgery (100%; 7/7). The graft was found to be soft in texture and bright red in color following exploratory laparotomy. In conclusion, a new rat model of APHLT with LDABS without stent for vascular reconstruction was developed. This is a feasible and reliable rat model for liver transplantation study.

Effects of dual arterial blood supply on liver regeneration in the graft and the host following heterotopic auxiliary liver transplantation.

This study aimed to investigate the effect of the dual arterial blood supply method used in auxiliary liver transplantation on the regeneration of grafted and host liver. A total of 72 male Sprague-Dawley rats were randomly assigned to three experimental groups, namely the 68% hepatectomy group (group A), the 68% hepatectomy with dual arterial blood supply group (group B) and the auxiliary liver transplantation with dual arterial blood supply group (group C). Group C was further divided into the host liver subgroup (group Ca) and the transplanted liver subgroup (group Cb). Six animals from each group were sacrificed at 1, 2 and 7 days after surgery. The calculation of the liver regeneration rate (LRR) was based on measuring liver weight. Liver function was assessed by measuring serum alanine aminotransferase (ALT) levels. Immunohistochemistry was employed to detect the expression of proliferating cell nuclear antigen (PCNA). Apoptotic changes in the grafts and host livers were evaluated using TUNEL staining. The LRR in each group exhibited a tendency to increase over time. At each time point, the LRR of transplanted livers in group C exhibited no significant difference from that of host livers in group C (P>0.05). The ALT levels for each group exhibited a time-dependent decreasing tendency. The ALT level in group C was significantly higher compared to that in groups A and B at each time point (P<0.05). The expression of PCNA in transplanted and host livers in group C was significantly lower compared to that in groups A and B at the same time point (P<0.001). Although the number of apoptotic cells in each group varied at different time points, there was no statistically significant difference (P>0.05). In auxiliary liver transplantation with the dual arterial blood supply method, the capacity of the liver regeneration in the grafts was similar to that of the host livers. Therefore, this technique may reduce the potential risk of graft liver atrophy caused by functional competition.

Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney. The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure until the native liver regenerates.

Heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure.

In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.(1-3) The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.(4) In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.(5-6) We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney. The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor's portal vein was carried out via the recipient's right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient's aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. (7) In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft's weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure until the native liver regenerates.

Long Term Outcomes of Auxiliary Partial Orthotopic Liver Transplantation in Pre-Teenage Children With Fulminant Hepatic Failure.

Objectives: To evaluate long-term outcomes of auxiliary partial orthotopic liver transplantation (APOLT) in pre-teenage children with fulminant hepatic failure (FHF). Methods: A retrospective chart review of thirteen pre-teenage children who underwent APOLT for FHF. Results: One case was done in 1997 and the remaining 12 since 2005. Recipients' left lobes were removed and either the left lateral segment or left lobe of the donor liver was transplanted. Etiology was unknown in the majority of cases (10/13, 69%) and was otherwise hepatitis A (n=1), autoimmune (n=1), and drug toxicity (n=1). All native livers showed submassive to massive necrosis at the time of transplantation. All children (100%) are currently alive with a median follow-up of 5.0 years (range 0.6-16.3 years). All children except one (92.3%) showed native liver regeneration. The first nine recipients (61.5%) are currently off immunosuppression (ISP) with fully regenerated native livers, and two additional patients are currently weaning off ISP. After the ISP withdrawal, the graft liver became completely atrophic in 6 patients and was removed in 2. Incidence of acute rejection prior to ISP withdrawal was 30.8% (4/13). Other postoperative complications included hepatic artery thrombosis requiring a second APOLT graft (n=1), bile leak (n=1), biliary stricture (n=1), bowel obstruction (n=1), anastomotic bleed (n=1), fungal peritonitis (n=1), abscess (n=3), CMV viremia (n=1), and de novo development of autoimmune hepatitis (n=2). Median post-transplant length of stay was 15 days. Conclusions: APOLT was successfully performed in pre-teenage children with FHF. This is the largest such case series reported to date, although previous smaller case series have shown similar good results. Recipients displayed native liver regeneration, and nearly all have been successfully withdrawn or are weaning from immunosuppression.

Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen-associated acute liver failure

BackgroundAn acetominophen overdose (AOD) is the leading cause of acute liver failure (ALF) in the UK and USA. For patients who meet the King's College Hospital criteria, (mortality risk > 85%), an emergency orthotopic liver transplantation (OLT) is conventionally performed with subsequent life-long immunosuppression. A new technique was developed in 1998 for AOD-induced ALF where a subtotal hepatectomy (right hepatic trisectionectomy) and whole graft auxiliary liver transplant (WGALT) was performed with complete withdrawal of immunosupression during the first year post-operatively. ResultsDuring 1998–2010, 68 patients were listed for an emergency transplantation for AOD ALF at our institution: 28 died waiting, 16 underwent OLT and 24 a subtotal hepatectomy with WGALT. Eight OLT (50%) and 16 WGALT remain alive (67%); actuarial survival at 5 years OLT 50%, WGALT 63%, P = 0.37. All patients who had successful WGALT are off immunosuppression. Poor prognostic factors in the WGALT group included higher donor age (40.4 versus 53.9, P = 0.043), requirements for a blood transfusion (4.3 versus 7.6, P = 0.0043) and recipient weight (63.1 versus 54kg, P = 0.036). ConclusionAlthough OLT remains standard practice for AOD-induced ALF, life-long immunosuppression is required. A favourable survival rate using a subtotal hepatectomy and WGALT has been demonstrated, and importantly, all successful patients have undergone complete immunosuppression withdrawal. This technique is advocated for patients who have acetominophen hepatotoxicity requiring liver transplantation.

Auxiliary Liver Transplant Is an Ineffective Treatment of Primary Hyperoxaluria

Auxiliary Liver Transplant Is an Ineffective Treatment of Primary Hyperoxaluria

Auxiliary Liver Transplant is an Effective and Safe Treatment of Primary Hyperoxaluria

Auxiliary Liver Transplant is an Effective and Safe Treatment of Primary Hyperoxaluria