Auxiliary Liver Transplantation Research Articles

Auxiliary partial orthotopic liver transplantation for adult onset type II citrullinemia

Adult-onset type II citrullinemia (CTLN2) is a disorder caused by an inborn error of metabolism affecting the liver. CTLN2 is an autosomal recessive disorder characterized by recurrent encephalopathy with hyperammonemia due to highly elevated plasma levels of citrulline and ammonia, caused by a deficiency of argininosuccinate synthetase in the liver. A small number of patients have undergone liver transplantation with favorable results. In Korea, the limitations of the deceased donor pool have made living donor liver transplantation a common alternative treatment option. We report the case of a patient with type II citrullinemia who was treated successfully with auxiliary partial orthotopic liver transplantation (APOLT) from a living donor. This is the first description of an APOLT for a patient with adult onset type II citrullinemia in Korea.

Hepatofugal portal flow associated with acute rejection in living-donor auxiliary partial orthotopic liver transplantation: A report of one case and literature review

We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study. On postoperative day 6, continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein. Based on histological findings, acute rejection was the suspected cause. The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies. The patient was discharged on the 30th postoperative day. It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection, and can be successfully treated by anti-rejection therapy.

Auxiliary partial orthotopic living donor liver transplantation with a small-for-size graft for congenital absence of the portal vein

Congenital absence of the portal vein (CAPV) with an extrahepatic portosystemic shunt is a rare malformation; the completely absent type, Abernethy malformation type I, is especially rare. Liver transplantation for CAPV type I has been recently recognized as the only curative operation, but few reports have been published so far; meanwhile, auxiliary partial orthotopic liver transplantation (APOLT) has been proposed to be a very effective option, especially for pediatric patients. Here we present an 18-year-old adult patient with CAPV, asplenia, and an iliac shunt vessel who was managed successfully with APOLT using a small-for-size graft. To the best of our knowledge, this is the first adult patient who has experienced success with APOLT for CAPV. This is a feasible procedure: it not only fulfills the metabolic demands of the liver for adult patients but also potentially cures CAPV.

Barriers to the successful treatment of liver disease by hepatocyte transplantation

Management of patients with hepatic failure and liver-based metabolic disorders is complex and expensive. Hepatic failure results in impaired coagulation, altered consciousness and cerebral function, a heightened risk of multiple organ system failure, and sepsis [1]. Such manifold problems are only treatable today and for the foreseeable future by transplantation. In fact, whole or auxiliary partial liver transplantation is often the only available treatment option for severe, even if transient, hepatic failure.

Portal Vein Arterialization for Hepatic Artery Thrombosis in Liver Transplantation: A Case Report, Doppler-Ultrasound Aspects, and Review of the Literature

Portal vein arterialization (PVA) is a salvage procedure for insufficient hepatic arterial or portal vascularization. It plays a role in auxiliary and orthotopic liver transplantation (OLT). In OLT, current indications for PVA include hepatic artery thrombosis (HAT), pre-OLT or post-OLT extended splanchnic vein thrombosis, intraoperative low portal flow, and anatomic variations like the absence of portal and mesenteric veins. Out of the transplantation domain, PVA is used both in extensive surgery for malignancies of the liver, biliary tract, and pancreas and in the treatment of fulminant hepatic failure (FHF) due to intoxications. We describe a case of acute post-OLT HAT successfully treated with PVA as a short bridge to retransplantation. By Doppler ultrasound of clinical PVA we detected an increased intrahepatic portal flow velocity, with disappearance of the arterial spikes, a finding that needs further investigation. PVA represents a rare surgical procedure. In fact, it has been used most of all in urgent conditions or in case of abrupt vascular complications during surgery. According to the literature, PVA emerges as a salvage procedure for poor arterial or portal hepatic flow, both in OLT and in general abdominal surgery. The outcome of this procedure is unpredictable. The aim of the shunt is to gain time, awaiting the onset of collateral arterial vessels or the performance of definitive surgery. Its early thrombosis may be a catastrophic event, due to acute liver ischemia. In contrast, a late occlusion is often well tolerated. Strict surveillance is always useful because sometimes it is mandatory to embolize the arterioportal fistula to treat or to prevent the onset of portal hypertension.

Auxiliary Partial Orthotopic Living Donor Liver Transplantation for Fulminant Hepatic Failure With Flat Electroencephalogram: A Case Report

A 54-year-old woman with hepatic encephalopathy grade IV (coma) and flat electroencephalogram (EEG) due to fulminant liver failure (FHF) due to hepatitis B virus infection was admitted to our hospital on May 24, 2002. We performed a living donor auxiliary partial orthotopic liver transplantation (APOLT) emergently on the day of admission. The donor was the patient's son, whose ABO blood group was identical. The immunosuppressant regimen consisted of tacrolimus and low-dose steroids. The left lobe (260 g) of the recipient, which was removed using a Pringle maneuver, was reconstructed with a left lobe (417 g) graft from the donor, which was orthotopically positioned as an auxiliary support. The patient remained in a coma for the first 5 days but on day 6 her eyes opened and followed objects. Finally, she recovered an almost normal appearance. Abdominal compartment syndrome, bile leak, and a mild rejection episode occurred during the postoperative course; all were treated successfully. The patient was discharged on the postoperative day 142. Computed tomography (CT) scan and biopsy were used to follow the changes in the graft and the native liver. On postoperative day 520, a CT scan showed a remarkable improvement in native liver size (493 cm3). Immunosuppression was tapered off and stopped on the postoperative day 635 to surrender the grafted liver. The graft liver biopsy specimen showed severe chronic rejection. The present status of the patient, who is now more than 7 years after transplantation, is an absence of neurological findings with normal liver function.

Auxiliary Liver Transplantation for Acute Liver Failure in Children

The aim of this study is to present the largest experience of auxiliary liver transplantation for acute liver failure (ALF) in children over the past 19 years. Between 1990 and 2009, a total of 128 liver transplants were performed on children with ALF. Of these, 20 received auxiliary liver transplants (19 were cadaveric and 1 living graft). The recipient median age was 12 years (range: 1 -16). Indications for auxiliary partial orthotopic liver transplantation were seronegative non-A non-B hepatitis in 16 children, drug induced in 2, and 1 autoimmune hepatitis and 1 mushroom poisoning. The median waiting time for transplantation was 2 days (range: 1-9). After native liver partial hepatectomy, 20 grafts were implanted orthotopically and included 8 right lobes, 8 left lateral segments, 3 left lobes, and 1 whole liver. Regeneration of the native liver was assessed by radiologic, nuclear medicine imaging, and histology. Follow-up imaging and biopsies were performed at intervals of 3 to 6 months and yearly. Patient survival was 85% at 1, 5, and 10 years. There were 3 deaths at a median of 9 days (range: 8-52) post-transplantation. There was 1 retransplant for chronic rejection 15 months post-transplantation. There were no biliary or vascular complications. Of 17 survivors, 14 (82%) have successfully regenerated their native liver and so far 11 children (65% of the survivors) have been withdrawn from immunosuppression at a median time of 23 months (range: 4-106) after transplantation. Auxiliary partial orthotopic liver transplantation should be considered in children presenting with ALF who fulfill criteria for liver transplantation.

First Example of Hepatocyte Transplantation to Alleviate Ornithine Transcarbamylase Deficiency, Monitored by NMR-Based Metabonomics

We demonstrate the effective use of NMR spectroscopic profiles of urine and plasma from the first successful use of hepatocyte transplantation as a bridge to auxiliary partial orthotopic liver transplantation in a child antenatally diagnosed with severe ornithine transcarbamylase deficiency. In this single-patient study, NMR profiles indicated that the disrupted urea cycle could be normalized by hepatocyte cell infusion and this was confirmed using orthogonal partial least-squares-based chemometrics. However, despite dietary manipulations and adminstration of ammonia scavengers, the desired reduction in plasma ammonia was not consistently achieved between sessions of hepatocyte transplantation due to episodes of sepsis. A subsequent liver transplant corrected the metabolic abnormalities. The use of metabolic profiling has been shown to be a promising method for evaluating the efficacy of cell infusions and has demonstrated the capability for the early detection of response to therapy in real time, an approach that may be of use in wider clinical settings.

Prognosis of adult patients transplanted with liver grafts < 35% of their standard liver volume

We have previously reported that a graft volume (GV) > 30% of the recipient's standard liver volume (SLV) can meet the recipient's metabolic demands. Here we report our experience with adult-to-adult living donor liver transplantation using left side grafts < 35% of the recipient's SLV. Of 143 adult living donor liver transplants, 13 auxiliary partial orthotopic liver transplants, 8 right side grafts, and 2 retransplantation cases were excluded. The resulting 120 cases were divided into 2 groups: group S consisted of 33 patients who received liver grafts < 35% of their SLV, and group L consisted of 87 patients who received liver grafts > or = 35% of their SLV. Patient characteristics, postoperative liver function, duration of hospital stay, and recipient survival rates were compared between the 2 groups. There were no significant differences between groups in recipient or donor background characteristics. The mean GV/SLV ratio of group S was 31.8%, whereas that of group L was 42.5%. There were no significant differences in the postoperative serum total bilirubin levels, prothrombin time international normalized ratio, daily ascites volume, or duration of postoperative hospital stay between the groups. The 1- and 5-year survival rates in group S were 80.7% and 64.2%, respectively, whereas those of group L were 90.8% and 84.9%, respectively, with no significant difference between groups. In conclusion, graft size was not considered to be the only cause of so-called small-for-size graft syndrome, and left side grafting appears to be the procedure of choice for adult-to-adult living donor liver transplantation because of the lower risk to donors in comparison with right lobe grafting.

Is Indoleamine 2,3-Dioxygenase Important for Graft Acceptance in Highly Sensitized Patients After Combined Auxiliary Liver-Kidney Transplantation?

In the clinical setting, transplanted liver seems to protect other grafts from the same donor from rejection. Our previous findings suggest that an auxiliary liver transplantation a few hours before a renal transplantation not only inhibits hyperacute antibody-mediated rejection but also improves long-term kidney graft survival in sensitized recipients. Here, we investigated indoleamine 2,3-dioxygenase (IDO) activity, as one potential mechanism for liver-induced long-term acceptance of kidney grafts. Tryptophan degradation was measured to estimate IDO activity in patient sera and cell culture supernatants with high performance liquid chromatography. Gene expression in the grafted organs and cell lysates was studied using real time polymerase chain reaction analysis. Tryptophan degradation increased in peripheral blood from patients undergoing combined auxiliary liver-kidney transplantation, whereas it decreased in patients after regular renal transplantation. A 100-fold increase in IDO mRNA, preceded by upregulation of the IDO-inducing cytokines tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, was observed in the transplanted organs after graft reperfusion in patients undergoing combined graft transplantation. Subsequent studies in vitro revealed that immature dendritic cells, but not hepatocytes, strongly activated IDO on maturation with tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma. Finally, serum from liver-transplanted patients elicited an even stronger IDO-activity in such cytokine-stimulated dendritic cells. Taken together these findings suggest that the liver-induced long-term acceptance seen in human combined auxiliary liver and kidney transplantation is at least partly mediated by IDO activity.

A case of adult onset type II citrullinemia with portal-systemic shunt

A 48-year-old woman who had conscious disturbance and abnormal behaviors had been misdiagnosed as having hepatic encephalopathy due to hyperammonemia and portal-systemic shunt, and retrograde transvenous obliteration of the shunt did not improve her symptoms. Thereafter, analyses of plasma amino acids and citrin gene revealed a diagnosis of adult onset type II citrullinemia (CTLN2). She underwent auxiliary partial orthotopic liver transplantation (APOLT) using a left lobe graft from her brother, and her symptoms as well as hyperammonemia improved. Our case demonstrates the importance of CTLN2 as a differential diagnosis in patients with hyperammonemia and consciousness disturbance, even if they present with a portal-systemic shunt.

Evolving Surgical Approaches in Liver Transplantation

The growing discrepancy between the need and the availability of donor livers has resulted in evolving surgical approaches in liver transplantation during the last two decades to expand the donor pool. One approach is to transplant partial grafts, obtained either from a living donor or splitting a cadaveric donor liver. For both surgical methods, it is important to obtain a minimal viable graft volume to prevent small-for-size syndrome and graft failure. This minimal volume, expressed as graft-to-whole body ratio, must be between 0.8 and 1%. Living donor liver transplantation (LDLT) became the primary transplant option in many Asian countries and is increasingly performed as an adjunct transplant option in countries with low donation rates. Split liver transplantation (SLT) is a surgical method that creates two allografts from one deceased donor. The most widely used splitting technique is the division of the liver into a left lateral sectoral graft (segments 2 and 3) for a pediatric patient and a right trisegmental graft (segments 1 and 4 to 8) for an adult patient. Both LDLT and SLT are also important and established methods for the treatment of pediatric patients. Another evolving surgical approach is auxiliary liver transplantation, which describes the transplanting a whole or partial graft with preservation of the partial native liver. This bridging technique is applied in patients with fulminate liver failure and should allow the regeneration of the injured liver with the potential to discontinue immunosuppression. Other methods such as xenotransplantation, as well as hepatocyte and stem cell transplantation, are promising approaches that are still in experimental phases.

Auxiliary liver transplantation: Location, location, location...

Auxiliary liver transplantation: Location, location, location...

Feasibility of Auxiliary Partial Living Donor Liver Transplantation for Fulminant Hepatic Failure as an Aid for Small-for-Size Graft: Single Center Experience

Auxiliary partial orthotopic liver transplantation (APOLT) or heterotopic auxiliary partial liver transplantation (HAPLT) was initially indicated for potentially reversible fulminant hepatic failure (FHF). We started auxiliary partial living donor liver transplantation (LDLT) for FHF in February 2002. Since then, 5 FHF patients (3 females and 2 males) underwent auxiliary partial LDLT: 3 cases of APOLT and 2 cases of HAPLT. All of them received a small-for-size graft: graft-to-recipient weight ratio (GRWR) ≤ 1.0%. The etiologies of FHF were hepatitis B virus (HBV) in 1, Wilson's disease in 1, and unknown origin in 3 cases. Three were the acute type and 2 the subacute type of FHF. Median age was 45 years (range, 14–54 years). Blood type was identical in all cases. A left lobe graft was used in 4 instances and a right lobe graft in 1 case. Median GRWR was 0.74 (range, 0.42–0.85). Median follow-up was 42 months (range, 3 days to 70 months). Three of 5 patients (60%) were alive (at 42, 67, and 70 months) and 1 was free of immunosuppression after sufficient recovery of the native liver. Two cases succumbed: 1 at postoperative day 3 because of cytomegalovirus pneumonia and 1 at 10 months after APOLT because of sepsis. Complications were seen in all 5 patients: Relaparotomy for hemostasis in 3, decompression surgery of the abdominal cavity in 1, rehepaticojejunostomy in 1, and biliary strictures in 2 cases. Auxiliary partial LDLT may be a choice as an aid for a small-for-size graft in FHF.

Auxiliary Partial Orthotopic Living Donor Liver Transplantation in a Patient With Wilson's Disease: A Case Report

A patient with end-stage liver cirrhosis and neurological disorder due to Wilson's disease (WD) underwent auxiliary partial orthotopic liver transplantation (APOLT) using a living donor. He first visited our institute complaining of hand tremor, which was diagnosed as WD. Despite medical therapy, hepatic impairment progressed toward portal hypertensive complications. He was considered a suitable candidate for living donor-related liver transplantation. However, because of the impossibility of mobilization of the lateral section due to severe splenomegaly at the time of the recipient operation, we performed an APOLT using a right lobe graft. After transplantation, he suffered hepatic vein stenosis and biliary stenosis, receiving interventional therapy. The remnant native liver volume decreased, and the volume of the graft increased serially after transplantation. At the time of reporting, the patient had a normal working life with normal serum ceruloplasmin level and without neurologic problems at 26 months posttransplantation. APOLT may be a therapeutic option for patients with WD.

Current concept of small-for-size grafts in living donor liver transplantation

The extended application of living donor liver transplantation (LDLT) has revealed the problem of graft size mismatching called "small-for-size (SFS) graft syndrome." The initial trials to resolve this problem involved increasing the procured graft size, from left to right, and even extension to include a right lobe graft. Clinical cases of living right lobe donations have been reported since then, drawing attention to the risks of increasing the liver volume procured from a living donor. However, not only other modes of increasing graft volume such as auxiliary or dual liver transplantation, but also control of the increased portal pressure caused by an SFS graft, such as a portosystemic shunt or splenectomy, have been trialed with some positive results. To establish an effective strategy for transplanting SFS grafts and preventing SFS graft syndrome, it is essential to have precise knowledge and tactics to evaluate graft quality and graft volume, when performing these LDLTs with portal pressure control. We reviewed the updated literature on the pathogenesis of and strategies for using SFS grafts.

Long‐term survival in a patient after heterotopic segmental auxiliary liver transplantation

Auxiliary liver transplantation has been used mostly for patients with acute liver failure, but between 1980 and 2000, it has gained wider application for patients with both acute and chronic liver diseases. It is particularly applicable in patients in whom there is specific indication for removing the native liver. However, to date, very few patients have survived auxiliary liver transplantation in the long term. In this report, we describe a patient with normal liver function following heterotopic segmental auxiliary liver transplantation whom we followed for nine yr.

Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration

Auxiliary liver transplantation (ALT) permits the serial assessment of regeneration in livers of patients with acute liver failure (ALF). Forty-nine ALF patients [32 adults (median age, 23 years; range, 16-40 years) and 17 children (median age, 12 years; range, 1-15 years)] underwent ALT between 1994 and 2004 at King's College Hospital. Twenty-four patients had seronegative liver failure, 15 had acetaminophen toxicity, 4 had hepatitis B virus (HBV) infection, 3 had drug-induced liver failure, 2 had autoimmune hepatitis, and 1 had mushroom poisoning. Nine patients without post-ALT native liver histology were excluded from review. All acetaminophen-induced, HBV, and drug-related patients had diffuse injury. Twelve seronegative patients and the autoimmune hepatitis patient had a map-like injury. On follow-up, 9 acetaminophen-induced patients, 9 seronegative patients, 2 drug-induced ALF patients, 3 HBV patients, and the autoimmune patient recovered to a near-normal native liver with inconsequential scarring. The hepatocyte proliferative rate in diffuse necrosis was 27.4% (range, 3.1%-69.4%) at hepatectomy and sharply decreased after 8 days post-ALT, being minimal months and years after ALT. In conclusion, in patients undergoing ALT for ALF with a diffuse pattern of liver injury-mainly acetaminophen toxicity-hepatocyte proliferation occurs in the native liver within a few days of transplantation. If the injury is map-like (most cases of seronegative ALF), regeneration seems to involve variable hepatocellular proliferation and potential ductular hepatopoiesis, but sequential assessment is difficult because of sampling variation. The likelihood of histological recovery appears to be minimal in livers with total hepatocyte loss at the time of ALT.

Cryopreservation of Whole Murine and Porcine Livers

Preservation of vascularized organs, such as the liver, is limited to 24 h before destructive processes disqualify them for transplantation. This narrow window of opportunity prevents the performance of optimal pathogen screening and matching tests and possibly results in the need for retransplantation. Numerous problems are associated with freezing and thawing a whole liver while preserving its viability upon thawing, including complicated geometry, poor heat transfer, release of latent heat, and the difficulty of generating a uniform cooling rate. On the basis of our past success with sheep ovaries, we have now applied our novel freezing technique to a larger solid organ, the liver. Whole rat and pig livers were frozen and thawed using directional solidification apparatus, and viability of these livers was tested by means of integrity and functionality in vitro and in auxiliary liver transplantation. The thawed rat and porcine livers were intact and demonstrated >80% viability. Histology revealed normal architecture. Bile production and blood flow following auxiliary transplantation were normal as well. Our encouraging results in applying this novel cryopreservation technique in rat and pig livers suggest that this method may enable better human organ donor-recipient matching in the future.

Competition Between Native Liver and Graft in Auxiliary Liver Transplantation in a Rat Model

The competition between the native and the grafted liver in heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was investigated in a rat model. The experimental groups were: HALT with flow-regulated PVA and 70% resection of a native liver and graft (n = 32; group I) versus 70% liver resection (n = 32; group II). After HALT, the weight of the native liver increased until the sixth postoperative week (431% ± 55% of the intraoperative weight), whereas, the graft weight was only 76% ± 31% of the intraoperative weight at this time. In group II, liver weight increased continuously to 529% ± 30% of the intraoperative weight after 6 weeks. On postoperative day 2, there was significantly increased proliferative hepatocellular activity in all groups. This was highest in the resected livers of group II, followed by the native livers of group I, and the grafts of group I (301 ± 126 vs 262 ± 97 vs 216 ± 31 Ki-67-positive hepatocytes/10 visual fields). However, the differences between the groups were not significant. With regard to hepatocellular apoptosis, the livers were similar among all groups and at all time points, M30-positive hepatocyte counts were ≤1/10 visual fields, which was equivalent to normal values. After HALT with flow-regulated PVA, the native liver regenerated and the graft showed atrophy, most likely caused by the lack of hepatotrophic factors in the arterialized graft portal vein blood. Regeneration of the 70% resected native liver in the presence of an arterialized heterotopic auxiliary liver graft was less pronounced than the regeneration of a 70% resected liver without HALT. Native liver regeneration seemed negatively influenced by a graft, suggesting a competition between the 2 livers.