活体肝移植治疗HBV相关性急性亚急性肝功能衰竭

目的 探讨活体肝移植(living donor liver transplantation,LDLT)HBV感染导致的急性肝功能衰竭(acute liver failure,ALF)和亚急性肝功能衰竭(subacute liver failure,SALF)患者的可行性,并评价其疗效.方法 回顾性分析2000年11月至2007年10月完成的10例LDLT治疗ALF、SALF患者的临床资料.10例LDLT的供、受者均为成人,切取右半肝为移植物,8例含肝中静脉(middle hepatic vein,MHV).10例供者的评估均在确定实施LDLT的24 h内完成,供、受者手术均在确定供者后的12 h内完成.移植物质量与受者体质量比为(1.03±0.17)%(0.86%～1.22%),移植物体积与受者标准肝体积比为(52.2±11.8)%(47.6%～70.1%).结果 10例受者中,2例分别于术后7、28 d时因肺部感染、十二指肠球部溃疡穿孔腹腔感染死亡.1例胆管吻合口胆漏,经十二指肠镜下置入鼻胆管引流治愈.2例术后1周出现轻度急性排斥反应,增强免疫抑制强度后肝功能恢复正常.8例中位随访期9.6个月(2～84个月),生存质量优良.10例供者中,1例出现急性门静脉高压症导致脾脏破裂,行脾脏切除术,其后出现胆管断端胆漏,经鼻胆管引流结合经皮穿刺腹腔引流治愈.其余9例无并发症发生.结论 LDLT适宜治疗HBV感染导致的ALF、SALF,而且能获得较好的中、远期疗效.     

Living related donor liver transplantation in children

Objective

The objective of this study was to report our experience with pediatric orthotopic liver transplantation (OLT) with living related donors.

Methods

We performed a retrospective chart analysis of 121 living related donor liver transplantations (LRDLT) from June 1998 to June 2010.

Results

Indications were biliary atresia (BA; n = 81), primary sclerosing cholangitis (n = 5), α-1 antitrypsin deficiency (n = 4); cholestasis (n = 9), fulminant hepatic failure (n = 8), autoimmune hepatitis (n = 2), Alagille syndrome (n = 4), hepatoblastoma (n = 3), tyrosinemia (n = 2), and congenital hepatic fibrosis (n = 3). The age of the recipients ranged from 7-174 months (median, 22) and the weights ranged from 6-58 kg (median, 10). Forty-nine children (40.5%) weighed ≤10 kg. The grafts included the left lateral segment (n = 108), the left lobe (n = 12), and the right lobe (n = 1). The donors included 71 mothers, 45 fathers, 2 uncles, 1 grandmother, 1 grandfather, and 1 sister with a median age of 29 years (range, 16-53 ys) and a median weight of 68 kg (range, 47-106). Sixteen patients (12.9%) required retransplantation, most commonly due to hepatic artery thrombosis (HAT; n = 13; 10.7%). The other complications were biliary stenosis (n = 25; 20.6%), portal vein thrombosis (PVT; n = 11; 9.1%), portal vein stenosis (n = 5; 4.1%), hepatic vein stenosis (n = 6; 4.9%), and lymphoproliferative disorders (n = 8; 6.6%). The ultimate survival rate of recipients was 90.3% after 1 year and 75.8% after 3 years. Causes of early death within 1 month were HAT (n = 6), PVT (n = 2), severe graft dysfunction (n = 1), sepsis (n = 1), and intraoperative death in children with acute liver failure (n = 2). Causes of late deaths included lymphoproliferative disease (n = 3), chronic rejection (n = 2), biliary complications (n = 3), and recurrent disease (n = 3; hepatoblastoma and primary sclerosing cholangitis).

Conclusions

Despite the heightened possibility of complications (mainly vascular), LRDLT represented a good alternative to transplantation from cadaveric donors in pediatric populations. It was associated with a high survival ratio.     

Living related liver transplantation in adults.

OBJECTIVE: To evaluate the outcome of living related liver transplantation (LRLT) in adult patients and to assess graft size disparity and graft regeneration. SUMMARY BACKGROUND DATA: Although LRLT has been accepted as an optional life-saving procedure for pediatric patients with end-stage liver disease, the feasibility of LRLT for adult patients has not been reported with reference to a clinical series. METHODS: Adult-to-adult LRLT was performed using whole left lobar grafts in 13 patients (5 with primary biliary cirrhosis, 6 with familial amyloid polyneuropathy, 1 with biliary atresia, and 1 with citrullinemia). The 13 donors comprised 5 husbands, 3 sons, 2 sisters, 2 fathers, and 1 mother. The ratio of the graft volume to standard liver volume (GV/SV ratio) was calculated for use as a parameter of graft size disparity. RESULTS: Although the liver graft was markedly small for size (GV/SV ratio 32%-59% at the time of LRLT), none of the 13 patients developed postoperative liver failure. Eleven of the patients are still alive and well with satisfactory graft function 2 to 35 months after LRLT. Graft liver volume increased rapidly after LRLT and approximated the standard liver volume with time. CONCLUSIONS: Our LRLT program for adult patients has produced good results. LRLT in adults can be indicated for selected donor-recipient combinations.     

Living related liver transplantation

Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.This report is the gist of a paper read at the 91st Annual Meeting of the Japanese Surgical Society, Kyoto, Japan, 1991     

Orthotopic liver transplantation for acute hepatic failure in children

Abstract Thirty children received 35 liver transplants for fulminant or late-onset liver failure between March 1988 and May 1993. Aetiology included non-A non-B hepatitis in 12, Wilson's disease in 8, drug-induced hepatic failure in 6, hepatitis B in 1, hepatitis A in 1, tyrosinaemia in 1 and congenital haemochromatosis in 1. Three patients were retransplanted, one each for hepatic artery thrombosis, non-A non-B graft reinfection, and chronic rejection. Two of these three patients received a third transplant for chronic rejection and hepatic artery thrombosis. One patient in the retransplant group survived. Overall, graft and patient survival at a mean follow-up of 17 months were 49% and 57%, respectively. Mortality was related to vascular complications in three patients (hepatic venous obstruction, portal vein thrombosis and hepatic artery thrombosis). Two patients died of primary sepsis (cerebral aspergillosis and cytomegalovirus (CMV) pneumonitis in association with graft-versus-host disease). Systemic sepsis and multiorgan failure was documented as a cause of death in four children and sepsis in association with chronic rejection in a further three patients. One child died of respiratory failure 4 weeks after transplantation. Mortality in eight children less than 2 years was 75% and this was significantly greater than for older children ( P < 0.003, Mantel Cox). Earlier referral, even in the absence of a definitive diagnosis and particularly in children under 2 years is advisable and may improve survival.     

Living related liver transplantation in children with hypoxemia related to intrapulmonary shunting

Abstract  Living related liver transplantation (LRLT) was performed in seven children with hypoxemia related to intrapulmonary shunting. Based on the degree of the shunt ratio calculated by technetium ⁹⁹m macroaggregated albumin (MAA) scintigraphy, the seven patients were classified in the moderate (shunt ratio under 40 %, n = 4) or severe group (shunt ratio over 40 %, n = 3). While Pa was maintained over 60 mmHg in the moderate group, that in the severe group continued at a low level of under 40 mmHg in the early postoperative period. However, 48 h after surgery the arterial ketone body ratio recovered to a safe level of 1.0 in both groups. Values of aspartate aminotransferase and serum total bilirubin decreased at a constant rate in both groups. Six patients survived, but one died of portal vein thrombosis on the 53 rd postoperative day. Five of six surviving patients recovered from hypoxemia. We concluded that the transplanted liver can tolerate the stress of severe hypoxemia after LRLT.     

Living related liver transplantation for polycystic liver disease

Polycystic liver disease (PCLD) is a rare inherited disorder, often associated with polycystic disease of the kidney. Although liver failure is unusual, some patients suffer from hepatic enlargement associated with severe complications such as abdominal distention, cachexia and dyspnea. Until recently, many surgical attempts had been made to reduce hepatic size, however, results have been unsatisfactory [3, 9, 10]. Today, liver transplantation is recommended as a therapeutic option, and excellent outcome has been demonstrated [1, 2, 4, 5, 6, 8, 11]. In this paper, we present the first case study of total hepatectomy and partial liver transplantation for PCLD, from a living, related donor. The patient is a 38-year-old man with PCLD who underwent living related liver transplantation (LRLT). He is alive and well 21 months after the operation, with complete resolution of the symptoms. He has returned to his previous job, with a marked improvement in his quality of life. Our experience demonstrates that LRLT can be an option for treatment of PCLD.     

Temporary liver transplantation in acute liver failure.

The ability of a heterotopic graft to prolong life in animals dying in hepatic coma due to liver necrosis has never been definitely established. Acute hepatic failure was produced in 15 dogs by an hour of total interruption of the hepatic blood supply. Nine dogs received an intrathoracic hepatic homograft concurrently. Nontransplanted dogs died within 21 hours in hepatic coma, while transplanted dogs survived significantly longer (P less than .001). In all transplanted dogs, biological signs of hepatic failure were corrected in 24 hours. In four animals, the graft was removed on the fifth postoperative day. Two of those survived for 10 and 15 days respectively with normal hepatic function. These results demonstrate that a temporary heterotopic liver transplant is able to support life during the acute, normally lethal phase in dogs with massive liver necrosis.     

Hepatocellular transplantation in acute liver failure.

Acute liver failure carries a high rate of mortality, but if metabolic support can be maintained for a critical period, liver healing and recovery are possible. Current techniques of temporary hepatic support are cumbersome and inconsistently effective. We studied the ability of dispersed hepatocytes to provide metabolic support when transplanted to rats with liver failure induced by dimethylnitrosamine (DMNA), a rapidly metabolized agent that is selectively toxic to liver cells. DMNA (20 mg/kg) was administered intravenously to 92 Lewis rats. Animals were divided into four groups receiving the following treatments 24 hours after DMNA administration: group I-intraperitoneal transplantation of hepatocytes prepared from 2.0 gm of normal isologous rat liver; group II-infusion into the portal vein of hepatocytes prepared from 1.5 gm of liver; group III-infusion of saline into the portal vein; group IV-no further treatment. The percentages surviving in each group 3 weeks after DMNA administration were 63%, 71%, 17%, and 6%, respectively. Mean serum glutamic oxaloacetic transaminase (SGOT) levels 3 days after DMNA administration were similar in the four groups, indicating that the degree of liver damage was equivalent. A significantly higher proportion of hepatocyte treated rats survived. Liver histology after DMNA administration showed hemorrhagic central lobular necrosis. A return to near-normal architecture occurred by 3 weeks in surviving animals. In group II hepatocytes were seen in portal venules, sinusoids, and central veins. We conclude that dispersed hepatocytes, transplanted either intraperitoneally or via the portal vein, can provide sufficient metabolic support to allow for recovery from drug-induced hepatic necrosis.     

Pediatric liver transplantation for acute liver failure

The only proven therapy for patients unlikely to recover from acute liver failure (ALF) is liver transplantation. Correct diagnosis of these individuals and rapid referral to a transplant center are crucial. We evaluated 12 pediatric patients with ALF who underwent liver transplantation (LT) at our institution during a 3-year period. The reasons for transplantation were hepatitis A (3 patients); non-A, non-E hepatitis (3); autoimmune hepatitis (1); fulminant Wilson's disease (3); Amanita phalloides (mushroom) poisoning (1); and hepatitis B and toxic hepatitis with leflunomide treatment (1). Seven of the participants were female and five were male (mean age, 9.1 +/- 4.2 years). Three received right liver-lobe grafts, one received a whole liver graft, and the remainder received left or left-lateral liver lobe grafts. All patients recovered from hepatic coma the second postoperative day. Two patients died at postoperative days 57 and 71 due to adult respiratory distress syndrome and sepsis with multiorgan failure, respectively. One patient required retransplantation because of chronic rejection 7 months after the initial transplantation. That patient died 10 days after retransplantation because of sepsis. Nine patients were healthy at follow-up (range, 2-46 months). LT is the only treatment option for ALF in patients in countries with low organ-donation rates. In this scenario, donor preparation in a limited time frame is difficult. We have been able to decrease the duration of donor preparation to approximately 4 hours (including biopsy of the donated liver tissue).     

Living donor liver transplantation for fulminant hepatic failure

BACKGROUND: Living donor liver transplantation (LDLT) was originally indicated only for elective cases of pediatric patients with end-stage liver disease. In Japan, however, where liver transplantation from brain-dead donor is performed very rarely, this indication has been expanded to emergency cases such as fulminant hepatic failure (FHF). METHODS: Thirty-eight patients with FHF were treated between May 1992 and April 1999. Causes of acute liver failure were non-A, non-B hepatitis in 27 patients, hepatitis B virus in seven, and hepatitis A virus, Epstein-Barr virus, herpes simplex virus, and chrome poisoning in one each. RESULTS: Four patients did not undergo LDLT because of severe brain damage or combined multiple organ failure. The remaining 34 patients underwent a total of 36 LDLTs, including two retransplantations; 16 children received transplants of 17 lateral segments, three children and eight adults transplants of 11 left lobes, and seven adults transplants of eight right lobes. A total of 15 recipients died, four of primary graft dysfunction, three of refractory acute rejection, two of pneumonia, and one each of ductopenic rejection, sepsis, aplastic anemis, recurrence of Epstein-Barr virus hepatitis, multiple organ failure by chrome poisoning, and unknown hepatic failure. Primary graft dysfunction developed in adult recipients with small-for-size graft transplants, whereas refractory acute rejection and ductopenic rejection occurred in six grafts each of children with non-A, non-B FHF. CONCLUSIONS: LDLT can be safely expanded to cases of FHF in adult patients. Primary graft dysfunction in adult recipients with small-for-size left lobe grafts can be overcome by using right lobes. However, refractory acute rejection and ductopenic rejection in children remain a major problem.     

Living related liver transplantation for hepatocellular carcinoma in Egypt

BACKGROUND: Living related liver transplantation (LRLT) for hepatocellular carcinoma (HCC) in cirrhotic patients has emerged as a rewarding therapy for a cure. Extensions of the Milan criteria have been proposed with encouraging results. PATIENTS AND METHODS: From October 2001 to June 2004, 47 adult patients with end-stage liver disease (ESLD) have been treated using LRLT, including 11 (9 males and 2 females) with HCC superimposed on hepatitis C virus (HCV)-related (n = 10) or hepatitis B virus-related (n = 1) cirrhosis. Their mean age was 50 years (range, 40-61). HCC was confirmed preoperatively in 9 subjects whereas it was an incidental finding in 2 cases. Alpha fetoprotein (AFP) levels were elevated in 5 of them. Radiologically, tumor number and sizes ranged from 1 to 2 nodules and from 1.5 to 7 cm, respectively. Five of the 11 subjects underwent pretransplantation tumor control therapy. RESULTS: Nine patients are alive, all of them being disease free during follow-up periods ranging from 6 to 30 months. Two subjects died: one of HCC recurrence at 1 year posttransplantation, and another of a pulmonary embolism on day 7. AFP levels decreased to normal values in 4 cases. Excluding the 2 incidental tumors, pathological examination of the explants revealed a higher number and larger size of the nodules in 3 and 5 cases, respectively. Microvascular invasion was documented in 3 explants, 1 of which experienced HCC recurrence and the other 2 received 6 cycles of Doxorubicin following normalization of their liver profile. Postoperative complications included the following: recurrent HCC (n = 1), recurrent HCV (n = 2), acute cellular rejection (n = 3), anastomotic biliary stricture (n = 1), and subphrenic collection (n = 1). CONCLUSION: Our current data confirm the efficacy of LRLT for treatment of HCC superimposed on liver cirrhosis.     

Living related liver transplantation. Progress or regress?

The impetus for the devolopment of living related liver programmes lies with donor shortage, which relates inversely to the success of generating cadaveric donors. A shrinking or non-existent cadaveric donor pool leads to an increased death rate among potential recipients awaiting transplantation. The living related liver programmes have by and large been successful, though it is accepted that there is potentially a significant risk to the donors. The technique of live donor liver transplantation is clearly here to stay, but the selection of suitable donors is between the family and the unit. Consequently, because of the lack of international guidelines, the programmes are open to abuse. Steps should be taken to establish either mechanisms of control or a worldwide register to combat this potential.     

Living donor liver transplantation for acute liver failure: a 10-year experience in a single center

BACKGROUND: Living donor liver transplantation has become an accepted treatment for various terminal liver diseases. STUDY DESIGN: Forty-two living donor liver transplantations performed for acute liver failure during a 10-year period at Kyushu University Hospital were reviewed. RESULTS: Causes of liver failure included hepatitis B (n=12), hepatitis C (n=1), autoimmune hepatitis (n=2), Wilson's disease (n=3), and unknown causes (n=24). The graft types were: left lobe (n=33), right lobe (n=8), and lateral segment (n=1). The mean graft volume to standard liver volume ratios were 42.2+/-9.2% in left lobe grafts and 50.5+/-3.9% in right lobe grafts (p < 0.05). Extubation was significantly delayed in grade IV encephalopathy patients (73.7 +/-18.2 hours) compared with patients with other grades (p < 0.01 to grades I and II, p < 0.05 to grade III). All other patients, except one with a subarachnoid hemorrhage, had complete neurologic recovery after transplantation. The 1- and 10-year survival rates were 77.6% and 65.5%, respectively, for grafts, and 80.0% and 68.2%, respectively, for patients. CONCLUSIONS: Outcomes of living donor liver transplantation for acute liver failure are fairly acceptable despite severe general conditions and emergent transplant settings. Living donor liver transplantation is now among the currently accepted life-saving treatments of choice for acute liver failure, although innovative medical treatments for this disease entity are still anticipated.