Living donor liver transplantation for fulminant hepatic failure

Aim: The aim of this study was to investigate the safety of living donor liver transplantation (LDLT) for fulminant hepatic failure (FHF) patients. Methods: We reviewed the clinical indications, operative procedures and prognosis of LDLT performed on patients with FHF at the University of Tokyo. From January 1996 to August 2007, 96 patients were referred to our department due to severe acute hepatitis or FHF. Of these, 36 underwent LDLT and were the subjects of this study. Of the 36 patients who underwent LDLT, 32 were over 18 years old. The etiologies of FHF included non‐A, non‐B hepatitis in 23, hepatitis B virus in 11, Wilson's disease in one, and auto‐immune hepatitis in one. Graft type included right liver in 18, left liver in 16 and right paramedian sector in two. Results: Patient and graft survival rates at 5 years were 87% and 82%, respectively. Twenty‐three patients had postoperative complications: acute cellular rejection in 12, biliary stricture in eight, bile leakage in six, peritoneal hemorrhage in six and hepatic arterial thrombosis in four. Conclusion: The LDLT procedure provided satisfactory survival rates for FHF patients.     

Animal models of fulminant hepatic failure

The six requirements for a satisfactory animal model of fulminant hepatic failure are reversibility, reproducibility, death from liver failure, a therapeutic window, a large animal model, and minimal hazard to personnel. Different models may be required to evaluate the various types of liver failure seen in man. The available models include surgical anhepatic and devascularization procedures, as well as hepatotoxic drug administration using agents such as carbon tetrachloride, acetaminophen, or galactosamine. Currently combined surgical and drug models appear to provide the best model but the search for the ideal models continues.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.     

Microsurgical reconstruction of hepatic artery in living donor liver transplantation:experiences and lessons

BACKGROUND:Hepatic artery(HA) reconstruction is one of the key steps for living donor liver transplantation(LDLT).The incidence of HA thrombosis has been reduced by the introduction of microsurgical techniques under a high resolution microscope or loupe.METHODS:We report our experience in 101 cases of HA reconstruction in LDLTs using the graft-artery-unclamp and posterior-wall-first technique.The reconstructions were completed by either a plastic surgeon or a transplant surgeon.RESULTS:The rate of HA thromb...     

Living donor liver transplantation as a means of rescuing post-embolization hepatic failure in a patient with idiopathic intrahepatic arteriovenous malformation in the liver

Interventional radiology used to be a first-line treatment for cardiac failure caused by idiopathic hepatic arteriovenous malformation (AVM). Here, we report a 64-year-old male patient treated by living donor liver transplantation (LDLT) following failed hepatic artery embolization for idiopathic hepatic AVM. Hepatic artery reconstruction in LDLT was very difficult in this case due to the adverse effects of the pre-transplant intervention. In the treatment of widespread AVM in the liver, arterial embolization should be avoided and primary liver transplantation should be considered.     

Anatomical keys and pitfalls in living donor liver transplantation

The surgery of living donor liver transplantation is more technically challenging than cadaveric whole liver transplantation and liver resection for the treatment of various pathological conditions. It requires a thorough understanding of the intra- and extra-hepatic anatomical relationships between the portal vein, hepatic artery, biliary tract, and hepatic vein, and also their respective contributions to liver physiology. Although a precise understanding of general anatomical principles is the key to correctly performing living donor liver transplantation procedures, anatomic anomalies are often present, and the means of detecting them and the surgical methods of coping with them represent technical challenges. In this monograph, we describe the anatomical keys and pitfalls of living donor liver transplantation surgery based on our own experience with more than 1800 hepatectomies, and 150 living donor liver transplantations. We also elaborate on techniques of selective intermittent vascular occlusion and their teleological and practical background.     

Hepatic stimulator substance administration ameliorates liver regeneration in an animal model of fulminant hepatic failure and encephalopathy

Abstract: Aims/Background: Hepatic stimulator substance (HSS) is a liver‐specific growth factor implicated in hepatocellular proliferation and hepatoprotection in models of acute liver injury. In the present study, we examined the effect of exogenous HSS administration on liver proliferating capacity and survival outcome in an experimental animal model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA) in rats. Methods: Fulminant hepatic failure was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA (400 mg/kg of body weight), at 24 h time intervals. The animals received intraperitoneally either a saline solution or HSS (50 mg protein/kg of body weight), 2 h after the second and third TAA injections. The animals were killed at 6, 12 and 18 h post the last injection of TAA. Results: Levels of liver enzymes and urea in serum, blood ammonia values, liver histology, stage of hepatic encephalopathy and survival were statistically significantly improved in TAA‐intoxicated and HSS‐treated rats compared to TAA‐intoxicated and saline‐treated ones. Furthermore, HSS ameliorated liver regenerative indices – DNA biosynthesis, thymidine kinase activity and hepatocyte mitotic activity – in a statistically significant manner. Conclusions: Our data suggest the beneficial effect of HSS administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of HSS as supportive therapy, by increasing hepatocellular proliferation, in management of FHF.     

Animal models of fulminant hepatic failure: need to test liver support devices

Fulminant hepatic failure is one of the most dramatic entities in clinical medicine, but experimental studies of its pathogenesis, evolution and treatment have, so far been limited by the lack of satisfactory animal models for testing new supportive treatment options. The variable aetiology, complex pathogenetic mechanisms and inconstant clinical evolution of human fulminant hepatic failure make it particularly difficult to establish an "ideal fulminant hepatic failure animal model" suitable for all studies: it is no longer mandatory to develop one single model serving all possible scientific needs, but the use of a specific model for a specific issue is more advisable. The currently available animal models of fulminant hepatic failure are the hepatotoxic, surgical and combined hepatotoxic and surgical models. From a general point of view, surgical models may be particularly appropriate for studying the consequences of hepatic necrosis on cerebral oedema. The anhepatic model is very useful for validating new supportive measures to bridge the period between the onset of fulminant hepatic failure and the time at which a suitable organ becomes available and, despite the many difficulties involved in their development, hepatotoxic models may still be useful for mimicking an acetaminophen overdose. The efficacy and reproducibility of a liver support system can be demonstrated by means of preclinical experimental models that mimic the specific application required in humans as closely as possible.     

Efficacy of middle hepatic vein reconstruction in adult right-lobe living donor liver transplantation

BACKGROUND:Congestion of the right anterior segment may lead to graft dysfunction in right-lobe living donor liver transplantation(LDLT)without a middle hepatic vein(MHV) trunk.Selective reconstruction of MHV tributaries with the interposition of vascular grafts has been introduced to overcome this problem.However,there is still no consensus on the definite criteria of MHV reconstruction. METHODS:LDLT patients were reviewed to evaluate the effects of MHV reconstruction.From March 2005 to September 2008 in o...     

Problems in adult living donor liver transplantation using the right hepatic lobe

BACKGROUND: Adult living donor liver transplantation (LDLT) is now widely applied to patients, children or adults, and the graft extends from the left hepatic lobe to the right hepatic lobe. Harvesting the right hepatic lobe would mean putting the donor at high risk. The congestion of a graft may cause small-for-size syndrome. The safety of the donor and its evaluation, which are related to the outcome for the recipient,play an important role in LDLT. How to decrease the congestion of the graft is another challenge to transplant experts. DATA SOURCES: A literature search from MEDLINE about adult LDLT in recent years was made to analyze the safety of the living donor and the innovation of surgical techniques for preventing small-for-size syndrome. RESULTS: The top priority for adult LDLT is donor safety. Preoperative donor evaluation consists of three stages: phase 1 for general evaluation, phase 2 for laboratory tests, and phase 3 for radiological evaluation of graft volume and vessel anatomy. The potential pathogenic mechanisms of small-for-size syndrome seem to be related to persistent portal hypertension and portal overperfusion. Improved surgical techniques for decreasing portal hypertension and preventing congestion of a graft may reduce the incidence of small-for-size syndrome. The improved techniques include reconstruction of the tributaries of the middle hepatic vein, end-to-side portocaval shunting, ligation of the splenic artery, dual-graft transplantation, and modified reconstruction of hepatic veins. CONCLUSION: With the careful preoperative assessment and the safety of the living donor, as well as improved surgical techniques, adult LDLT using the right lobe is safe.     

HBV-related fulminant hepatic failure: successful intensive medical therapy in a candidate for liver transplantation

Received: April 3, 2000 / Accepted: July 14, 2000     

Adult-to-adult living donor liver transplantation for acute liver failure in China

AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation(AALDLT) for acute liver failure(ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio(INR) ≥ 1.5] and degree of mental alteration without pre-ex-isting cirrhosis and with an illness of 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic(ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B(n = 18),drug-induced(n = 1) and indeterminate(n = 1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe(n = 17) and dual graft(n = 3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-torecipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65%(13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients.Multivariate analysis showed that waiting duration was independently correlated with increased mortality(P = 0.014).Furthermore,ROC curve revealed the cut-off value of waiting time was 5 d(P = 0.011,area under the curve = 0.791) for determining the mortality.The short-term creatinine level with different recipient's waiting duration was described.The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration 5 d(66.7% vs 9.1%,P = 0.017).In addition,all donors had no residual morbidity.Furthermore,univariate analysis did not show that short assessment time induced the high morbidity(P = 0.573).CONCLUSION:Timely AALDLT for patients with ALF greatly improves the recipient survival.However,further systemic review is needed to investigate the optimal treatment strategy for ALF.     

Activated sub-populations of lymphocytes and natural killer cells in normal liver and liver grafts before transplantation

ABSTRACT— Aims/Background: The anatomic structure of the liver suggests that it is a place of intense trafficking between intra-hepatic and peripheral blood compartment leukocytes. Furthermore, the liver contains a large number of passenger leukocytes that may play a role in the appearance of donor-type microchimerism after transplantation. In this study, we aimed to define the principal lymphocyte sub-populations contained in donor peripheral blood and liver grafts and in normal liver removed during minimally invasive surgery. Methods: Liver biopsies were taken at the time of vascular clampage during liver extraction from donors in a brain dead state (GI: n=14). Normal liver biopsies were removed during minimaly invasive surgery (GII: n=10). Results: We observed evidence of the presence of lymphocytic activation associated with the two major CD8+ lymphocyte and natural killer (NK) cell populations in the two groups, with a significant increase in TCR γδ-bearing lymphocyte receptors between normal liver and the liver graft. Conclusions: The presence of activated leukocytes in the graft could have a fundamental role in induction of peripheral tolerance. This activation could be the result of a basic immunological response linked to the interaction of T cells and NK cells, and of secondary activation due to stress and the conditions necessary for organ removal from donors in a brain dead state.     

Reconstruction of the middle hepatic vein tributary in adult right lobe living donor liver transplantation

BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 ℃ University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From June 2007 to January 2008, 11 adult LDLT patients recei...     

All-in-one sleeve patch graft venoplasty for multiple hepatic vein reconstruction in living donor liver transplantation

Objectives

This paper presents an innovative technique to address complex multiple hepatic vein (HV) reconstruction in right lobe graft living donor liver transplantation (RL-LDLT).

Methods

A patient with hepatitis C virus-related cirrhosis underwent RL-LDLT. The graft had seven HVs, including: the right HV (17 mm); one segment VII HV (11 mm); two segment VI HVs (6 mm and 16 mm), and three segment V HVs. The graft weighed 663 g (53% of standard liver volume; ratio of graft weight to recipient body weight: 0.96). Each HV had significant drainage territory requiring reconstruction. A cryopreserved iliac vein graft was used to create a sleeve patch to incorporate the HV openings. The holes were anastomosed to their corresponding HV tributaries using continuous 6–0 polydioxanone (PDS) sutures. Two of the three segment V HVs were combined using a smaller iliac vein patch, which was anastomosed in an end-to-side fashion to a previously harvested recipient umbilical vein interposition graft. The other end of the umbilical vein graft was anastomosed to the larger iliac vein sleeve patch.

Results

Overall, six HV openings were incorporated in one sleeve patch to allow a single wide anastomosis with the recipient inferior vena cava. Doppler ultrasound after reconstruction showed adequate flow patterns in all the HVs.

Conclusions

All-in-one sleeve patch graft venoplasty simplifies the reconstruction of multiple HVs and reduces warm ischaemia time in RL-LDLT with excellent outcomes.     

Treatment of hepatic failure secondary to isoniazid hepatitis with liver transplantation

Summary Two patients with liver failure secondary to isoniazid hepatotoxicity were successfully treated with orthotopic liver transplantation. A 49-year-old man received isoniazid prophylaxis for a positive tuberculin test, and a 60-year-old woman was treated for active pulmonary tuberculosis with isoniazid, rifampin, and pyrazinamide. Both patients developed hepatic failure 4 and 1.5 months after initiation of antituberculous drug therapy, respectively. Liver transplantation was performed for progressive hepatic failure and was successful in both patients. The patient with active pulmonary tuberculosis was successfully treated with a modified antituberculous drug regimen while taking standard doses of immunosuppressive drugs after transplantation. In conclusion, liver transplantation is feasible and effective therapy for patients with isoniazid-induced hepatic failure, and active pulmonary tuberculosis may represent a relative rather than absolute contraindication to transplantation.     

Effect of extracorporeal bioartificial liver support system on fulminant hepatic failure rabbits

AIM To evaluate the possibility of using cultured human hepatocytes as a bridge between bioartificial liver and liver transplantation. METHODS In this experiment, the efficacy of extracorporeal bioartificial liver support system (EBLSS) consisting of spheriodal human liver cells and cultured hepatocytes supernatant was assessed in vivo using galactosamine induced rabbit model of fulminant hepatic failure. RiESULTS There was no difference of survival between the two groups of rabbits, but in the supported rabbits serum alanine aminotransferase, total bilirubin and creatinine were significantly lower and hepatocyte necrosis was markedly milder than those in control animals. In addition, a good viability of human liver cells was noted after the experiment. CONCLUSION EBLSS plays a biologic role in maintaining and compensating the function of the liver.     

Increased serum and hepatic tissue levels of interleukin-18 in patients with fulminant hepatic failure

BACKGROUND: Fulminant hepatic failure is a serious clinical condition associated with a high mortality rate. Interleukin (IL)-18 is a pro-inflammatory cytokine that is associated with several inflammatory diseases. The purpose of the present paper was therefore to investigate whether IL-18 is elevated in patients with fulminant hepatic failure. METHODS: Serum levels of IL-18 were measured in patients with fulminant hepatic failure before and after liver transplantation. Native liver tissue samples were collected and the tissue levels of IL-18 were determined. Liver tissues were stained immunohistochemically with antihuman IL-18 antibody. The serum levels of IL-1beta, IL-6, IL-8, IL-12, interferon-gamma, and tumor necrosis factor-alpha were also determined in patients with fulminant hepatic failure before and after liver transplantation. RESULTS: Elevated levels of IL-18 in serum and hepatic tissue were observed in patients with fulminant hepatic failure. Native liver tissue samples were immunohistochemically positive for IL-18. Interleukin-18 levels were markedly reduced after liver replacement. No other inflammatory cytokines were substantially elevated in patients with fulminant hepatic failure. CONCLUSION: The serum levels of IL-18 levels are elevated much more than those of other cytokines in patients with fulminant hepatic failure.