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.     

Auxiliary partial orthotopic living donor liver transplantation in a patient with alcoholic liver cirrhosis to overcome donor steatosis

The efficacy of auxiliary partial orthotopic liver transplantation (APOLT) to overcome the problems associated with a markedly steatotic graft in a living donor has not been fully explored. We have recently performed APOLT in a patient with alcoholic liver disease, where the only potential candidate donor was affected by 50% macrovesicular steatosis and 30% microvesicular steatosis. The recipient's left liver was resected and the donor's left liver, corresponding to a 0.46% graft-to-recipient weight ratio, was orthotopically transplanted. The postoperative course of this patient was uneventful, except for a transient large amount of ascites. Native liver volume in the recipient serially decreased, and the volume of the graft serially increased after transplantation. Four months after transplantation, the donor and recipient are doing well with a normal liver function. In conclusion, APOLT may be a feasible solution for a markedly steatotic living donor graft in patients with alcoholic liver disease.     

Auxiliary partial orthotopic living donor liver transplantation for a child with congenital absence of the portal vein.

Congenital absence of the portal vein (CAPV) is a rare malformation of the mesenteric vasculature in which visceral venous blood bypasses the liver, completely draining into the systemic circulation through a congenital porto-systemic shunt. Liver transplantation has rarely been indicated for patients with this disease. We present a child with CAPV who was managed successfully by living donor auxiliary partial orthotopic liver transplantation (APOLT), while preserving the right lobe of the native liver. In conclusion, APOLT for patients with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is not necessary.     

大鼠原位辅助性部分肝移植

本研究旨在建立大鼠原位辅助性部分肝移（ａｕｘｉｌｉａｒｙｐａｒｔｉａｌｏｒｔｈｏｔｏｐｉｃｌｉｖｅｒｔｒａｓｐｌａｎｔａｔｉｏｎ,ＡＰＯＬＴ）模型,进一步推动肝移植的实验和临床研究。在半肝血流阻断下切除受体肝脏的７５％。然后将３０％的供肝移植于原位。作者成功地施行大鼠原位辅助性部分肝移植４０次。受体５天生存率为８７．５％。移植肝５天存活率为７５％。术后第５天移植肝重量增加一倍,肝细胞增生活跃,ＤＮＡ呈二倍体,ＤＮＡ合成期肝细胞占２２．６％±２．７５％明显高于正常肝细胞的１２．２２％±１．４８％（Ｐ＜０．００１）。作者认为,大鼠ＡＰＯＬＴ是一个较理想的动物模型。     

Impact of donor gender on male rat recipients of small-for-size liver grafts.

The aim of this study was to assess the impact of donor gender on small-for-size (SFS) liver transplantation in male recipients using a rat model. Adult female or male Lewis rats were used as donors and male Lewis rats as recipients. Size-matched (SM) and SFS liver grafts from either male or female donors were transplanted into male recipients. Animals receiving SFS grafts were sacrificed at postoperative week 1, week 4, and week 12, respectively (n = 6-8 per group), those receiving SM grafts after 3 months. The cumulative survival rate (SVR) in the female-to-male (F-M) SFS group was significantly lower (62%; 13 of 21) compared with the male-to-male (M-M) group (90%; 18 of 20) (P < 0.05). Spontaneous death occurred in the F-M SFS combination either in the early postoperative period (<3 weeks) in animals with confluent hepatic necrosis or in the late postoperative period (>8 weeks) in animals with biliary obstruction. In contrast, no death was observed in the early posttransplantation period after M-M liver transplantation. The relative graft size in the SM F-M group was significantly higher (graft-to-recipient weight ratio [GRWR] 2.40% +/- 0.8%) than in the SFS M-M group (GRWR 1.35% +/- 0.2%; P < 0.001). Regardless of graft size, the outcome was worse in terms of SVR as well as regarding the incidence and severity of biliary complications in F-M compared with M-M liver transplantation. In conclusion, male recipients of female livers had a less favorable outcome irrespective of graft size. Confluent hepatic necrosis as well as biliary obstruction were perceived as consequence of a severe perfusion problem in F-M liver transplantation, which was possibly related to an enhancement of ischemia-reperfusion (I/R) injury by the lack of estrogen in male recipients of female grafts.     

End-to-side portocaval shunting for a small-for-size graft in living donor liver transplantation.

In the development of adult-to-adult living donor liver transplantation (LDLT), the small-for-size graft has been associated with poor clinical outcome. Persistent portal hypertension or portal venous overperfusion are considered to be causative factors, and partial diversion of portal flow to systemic circulation may be effective for avoiding injuries that occur in the small-for-size (SFS) graft. Recently, we constructed an end-to-side portocaval shunting using 1 of the portal branches and anastomosed the other branch with the portal vein of the graft in 2 cases of LDLT recipients transplanted with a SFS graft. With the suppression of portal hypertension, as well as sufficient portal flow to the graft, the recipients recovered successfully with favorable graft function. This new and simple technique may be able to be used as a feasible and effective method to attenuate the SFS syndrome.     

小体积肝移植和辅助性原位小体积肝移植治疗猪急性肝功能衰竭的近期疗效观察

目的观察小体积肝移植和辅助性原位小体积肝移植治疗猪急性肝功能衰竭的近期疗效。方法急性肝功能衰竭猪随机分为3组接受肝移植治疗:A组行全肝移植(n=5);B组行小体积肝移植(n=5);C组行辅助性原位小体积肝移植(n=5)。各组动物开腹后即刻、切脾后即刻和再灌注后30 min分别监测门静脉压力,并观察术后生化指标变化、病理改变和1周生存率。结果A、B和C三组的移植肝重量与受体体重之比分别为(2．44±0．30)％、(0．76±0．02)％和(0．75±0．03)％。再灌注后30 min,B组移植肝门静脉压力显著高于其它两组(A:B:C=13．3:17．5:12．2 cmH2O, P<0．01),C组原肝门静脉压力显著高于移植肝门静脉压力(14．3:12．2 cmH2O,P<0．05)。A组和C组术后第2天起血清天冬氨酸转氨酶、总胆红素、凝血酶原时间、乳酸和血氨水平明显下降,术后第7天基本恢复至正常水平。B组术后上述生化指标一直维持在较高的水平,术后第2～4天明显高于其它两组(P<0．01)。A组、B组和C组1周生存率分别为100％、20％和80％,B组明显低于其它两组(P<0．05)。结论辅助性原位小体积肝移植治疗急性肝功能衰竭近期疗效优于小体积肝移植,术中不必干预原肝门静脉。     

Auxiliary partial orthotopic liver transplantation for Crigler-Najjar syndrome type I

OBJECTIVE: To determine if auxiliary partial orthotopic liver transplantation (APOLT) has the long-term potential to correct the underlying abnormality in Crigler-Najjar syndrome type 1 (CNS1) without the need for total liver replacement. BACKGROUND: Orthotopic liver transplantation has been used successfully to replace the defective enzyme in CNS1. Experimental studies have shown that only 1% to 2% of the normal hepatocyte mass is needed for bilirubin conjugation. If APOLT corrects the underlying metabolic abnormality, it has the advantage of preserving the native liver, which would serve as a "safety net" should the graft fail, and there is the potential for gene therapy in the future with possible withdrawal of immunosuppression. METHODS: Seven APOLT procedures were performed in six recipients with CNS1. Median age at transplantation was 10.5 years. Six transplants were performed as a left auxiliary liver transplant, and one was performed as a right auxiliary liver transplant. Median serum bilirubin level at transplantation was 320 micromol/L. All patients required 12 to 16 hours of phototherapy daily before the transplant to maintain serum bilirubin levels between 250 and 350 micromol/L. RESULTS: Median serum bilirubin level was 50 micromol/L at day 5 after the transplant and 23 micromol/L at a median follow-up of 32 months. In four children, early severe acute rejection developed, requiring conversion to tacrolimus; one underwent a second transplant for chronic rejection and graft atrophy but died from lymphoproliferative disease 6 months after the second transplant. CONCLUSIONS: This report shows that APOLT is technically feasible and provides adequate hepatocyte mass to correct the underlying metabolic abnormality in CNS1.     

Auxiliary partial orthotopic liver transplantation for fulminant hepatitis. The Paul Brousse experience.

OBJECTIVE: The authors objective is to report their experience with auxiliary partial orthotopic liver transplantation in fulminant hepatitis (FH) and to discuss the principles that may help in its safe application. SUMMARY BACKGROUND DATA: Auxiliary partial orthotopic liver transplantation is an attractive therapeutic method in FH because it provides hepatic function, whereas the remaining native liver is given the possibility to recover. Despite early encouraging reports, its place in the treatment of FH remains to be defined. METHODS: Evaluation of 5 cases of FH treated with auxiliary partial orthotopic liver transplantation from a collective of 22 transplantations for 35 cases of FH referred to the authors' center from January 1994 to November 1995. The grafts were one left lobe, two left livers, and two right livers. RESULTS: The native liver regenerated in three patients: one with Reye's syndrome who died of irreversible neurologic damage, one with FH caused by the hepatitis B virus who is alive 20 months after ABO incompatible graft removal, and one with FH caused by the hepatitis A virus who had her graft removed at 4 months. In two patients, regeneration did not occur: one with drug-induced FH who died of sepsis 3 months after surgery and one with FH of unknown origin who was retransplanted with a standard liver transplantation at 4 months for uncontrollable biliary rejection of an ABO incompatible graft (alive at 10 months). Two of the three patients who survived suffered severe neurologic complications. CONCLUSIONS: Auxiliary partial orthotopic liver transplantation is an attractive treatment for FH, especially in the presence of good prognostic factors for native liver regeneration: a young patient, rapid onset of the disease, and viral hepatitis. It should be considered cautiously in patients with advanced encephalopathy. By providing a smaller mass of liver tissue than with standard orthotopic liver transplantation, and as a more complex operative procedure, auxiliary partial orthotopic liver transplantation may not be as effective in arresting the progression of neurologic damage.     

Functional portal flow competition after auxiliary partial orthotopic living donor liver transplantation in noncirrhotic metabolic liver disease

Auxilliary partial orthotopic liver transplantation (APOLT) was introduced initially as a tentative or permanent support for patients with potentially reversible fulminant hepatic failure and has extended its indication to congenital metabolic disorder of the liver that has otherwise normal functional integrity. Postoperative management of APOLT is complicated because of functional portal flow competition between the native and graft liver. The native portal vein diversion to the graft is sometimes indicated to prevent functional competition; however, it is still an open question whether this technique can be theoretically indicated for APOLT patients. The authors report a on patient with ornithine transcarbamylase deficiency who received APOLT from a living donor without native portal vein diversion. Because of functional portal vein competition between the native and graft liver, the patient had to have portal vein diversion, portal vein embolization, and finally native hepatectomy to induce the graft regeneration after APOLT. After the experience of the current case, primary portal vein diversion for APOLT with noncirrhotic metabolic liver disease patients to prevent functional portal flow competition is recommended.     

预防活体肝移植后肝小体积综合征的综合措施

目的 通过术前选择合适的供肝、术中建立充分的流出道及术后调整门静脉压等综合措施预防活体肝移植术后肝小体积综合征.方法 总结2007年12月至2009年11月的113例活体肝移植的临床资料,术前通过影像系统评估供肝体积,测算供肝体积与受者体重比(GRWR),根据供肝解剖及GRWR确定采用的供体类型(含肝中静脉右半肝,不含肝中静脉右半肝,含肝中静脉左半肝等),术中通过建立充分的流出道,根据GRWR、术前脾功能亢进情况、肝动脉开放后门静脉血流量及门静脉压力,确定是否采用脾动脉结扎等方法将门静脉压力控制在＜20 mm Hg(2.67 kPa),门静脉血流量控制在＜250 ml·min-1·100 g-1,观察采取上述措施后肝小体积综合征的发生情况.结果 75例受者接受含肝中静脉的右半肝,37例接受不含肝中静脉的右半肝,1例接受含肝中静脉左半肝.随访6个月,所有受者均未出现持续黄疸、败血症等严重的肝小体积综合征表现,1例受者于术后42 d死于脑卒中及呼吸衰竭,受者术后6个月存活率为99.1％(112/113).结论 术前根据供肝血管解剖及GRWR选择适当的供肝类型,术中建立充分的流出道,通过脾动脉结扎等方式调整门静脉血流及压力的综合方法可有效预防肝小体积综合征.     

影像学检查在成人活体肝移植术后小肝综合征中的应用

小肝综合征（SFSS）是成人活体肝移植术后一种发病率和死亡率都很高的临床并发症。目前如何有效防治SFSS已成为研究热点。除改进外科技术外,影像学检查在成人活体肝移植术后SFSS的预防、检测及治疗方面也发挥着越来越重要的作用。本文对影像学检查在成人活体肝移植术后小肝综合征中的应用作一综述。     

Histologic eosinophilia as an aid to diagnose acute cellular rejection after living donor liver transplantation

The significance of histologic eosinophilia in the diagnosis of acute cellular rejection (ACR) after living donor liver transplantation was evaluated. A retrospective analysis was performed on 185 liver biopsy specimens to determine the presence of eosinophil infiltration around the portal tracts. Data were collected and analyzed to determine whether there was a correlation between ACR and the maximum eosinophil counts per portal triad (Em) and the rate of portal triads that included at least one eosinophil (Er). A receiver operating characteristic curve revealed the best cut-off value of Em and Er as 2% and 8% respectively. The sensitivity and specificity of an Em of two to predict ACR were 54% and 84% respectively. The sensitivity and specificity of Er were 72% and 65% respectively. One-way analysis of variance revealed that both Em and Er correlated with ACR severity. Histologic eosinophilia can be a useful parameter for confirming the occurrence of ACR and for evaluating ACR severity.     

Adult-to-adult living donor liver transplantation using extended right lobe grafts.

OBJECTIVE: The authors report their experience with living donor liver transplantation (LDLT) using extended right lobe grafts for adult patients under high-urgency situations. SUMMARY BACKGROUND DATA: The efficacy of LDLT in the treatment of children has been established. The major limitation of adult-to-adult LDLT is the adequacy of the graft size. A left lobe graft from a relatively small volunteer donor will not meet the metabolic demand of a larger recipient. METHODS: From May 1996 to November 1996, seven LDLTs, using extended right lobe grafts, were performed under high-urgency situations. All recipients were in intensive care units before transplantation with five having acute renal failure, three on mechanical ventilation, and all with hepatic encephalopathy. The median body weight for the donors and recipients was 58 kg (range, 41-84 kg) and 65 kg (range, 53-90 kg), respectively. The body weights of four donors were less than those of the corresponding recipients, and the lowest donor-to-recipient body weight ratio was 0.62:1. The extended right lobe graft was chosen because the left lobe volume was <40% of the ideal liver mass of the recipient. RESULTS: Median blood loss for the donors was 900 mL (range, 700-1600 mL) and hospital stay was 19 days (range, 8-22 days). Homologous blood transfusion was not required. Two donors had complications (one incisional hernia and one bile duct stricture) requiring reoperation after discharge. All were well with normal liver function 5 to 10 months after surgery. The graft weight ranged from 490 g to 1140 g. All grafts showed immediate function with normalization of prothrombin time and recovery of conscious state of the recipients. There was no vascular complication, but six recipients required reoperation. One recipient died of systemic candidiasis 16 days after transplantation and 6 (86%) were alive with the original graft at a median follow-up of 6.5 months (range, 5-10 months). CONCLUSIONS: When performed by a team with experience in hepatectomy and transplantation, LDLT, using an extended right lobe graft, can achieve superior results. The technique extends the success of LDLT from pediatric recipients to adult recipients and opens a new donor pool for adults to receive a timely graft of adequate function.