Living donor liver transplantation and hepatitis C

Preliminary results indicate that living donor liver transplantation patients infected with hepatitis C virus (HCV) develop earlier and more severe recurrence than their cadaveric counterparts. The mechanisms underlying this observation are unknown, but could include hepatic regeneration, differences in living donor liver transplantation recipient demographics, immune homology between donor and recipients, or other factors not previously considered. The optimum clinical approach is to only consider living donor liver transplantation in HCV-infected recipients as a life-saving procedure and to attempt to eradicate HCV before transplantation to prevent recurrent infection.     

Living donor liver transplantation to patients with hepatitis C virus cirrhosis

Living donor liver transplantation (LDLT) is an alternative therapeutic option for patients with end-stage hepatitis C virus (HCV) cirrhosis because of the cadaveric organ shortage. HCV infection is now a leading indication for LDLT among adults worldwide, and there is a worse prognosis with HCV recurrence. The antivirus strategy after transplantation, however, is currently under debate. Recent updates on the clinical and therapeutic aspects of living donor liver transplantation for HCV are discussed in the present review.     

Living donor liver transplantation for hepatitis B cirrhosis

BACKGROUND AND AIM: Living donor liver transplantation (LDLT) has particular advantages for Turkey where hepatitis B virus (HBV) infection is the most common cause of cirrhosis, both because LDLT circumvents the difficulties encountered in the emerging world in providing deceased donor organs, and because it allows preemptive antiviral therapy. The aim of this study was to review one institution's experience with LDLT in patients with chronic HBV infection. METHODS: A total of 109 patients with chronic HBV infection underwent LDLT between September 1999 and June 2005, of whom 40 were coinfected with hepatitis D virus and 23 had hepatocellular carcinoma. Antiviral prophylaxis was attempted in all, beginning prior to transplantation with lamivudine or adefovir, and continuing after transplantation with low dose intramuscular hyperimmune B immunoglobulin (HBIg) plus lamivudine or adefovir. RESULTS: In a median follow up of 20 months (range 1-66 months), there was no donor mortality. One-year recipient survival was 90%, and in total 16 recipients died. None of the deaths was related to HBV. Recurrence of HBV infection was detected by reappearance of serum hepatitis B surface antigen in six patients (5.5%) at 5, 8, 12, 17, 34 and 46 months after transplantation, respectively. There was no influence of donor hepatitis B core antibody status on the likelihood of recurrence of HBV in the allograft. CONCLUSION: The results indicate that LDLT with antiviral treatment and low dose HBIg provides excellent results for donors and recipients.     

Living donor liver transplantation

The introduction of living donor liver transplantation (LDLT) has been one of the most remarkable steps in the field of liver transplantation (LT). First introduced for children in 1989, its adoption for adults has followed only 10 years later. As the demand for LT continues to increase, LDLT provides life-saving therapy for many patients who would otherwise die awaiting a cadaveric organ. In recent years, LDLT has been shown to be a clinically safe addition to deceased donor liver transplantation (DDLT) and has been able to significantly extend the scarce donor pool. As long as the donor shortage continues to increase, LDLT will play an important role in the future of LT.     

Living donor liver transplantation.

Initially living donor liver transplantation (LDLT) was almost exclusively performed in infants and children. Adult LDLT programmes were initiated several years later. In the west this programme was introduced in view of a critical shortage of deceased donors and a constant increase in waiting list mortality. At present, this procedure is accepted as a therapeutic option for patients with end-stage liver disease to make up for the shortage of donor organs from dead patients. In Asia, however, LDLT has become the predominant means of liver transplantation as donor organs from the diseased cannot be used for religious and ethical reasons. Although there have been significant improvements in surgical techniques and consequently in recipient outcome over recent years, the LDLT procedure is still associated with donor morbidity and even mortality. The overall reported donor mortality was 0.2% and donor morbidity ranged between 0% and 100%. Biliary complications and infections were the most commonly reported donor complications. Therefore, a thorough medical as well as psychological evaluation of the donor and recipient are necessary prior to this procedure. To date, LDLT comprises less than 5% of adult liver transplantations in Europe and in the United States. Recipient and graft survival are almost identical to those seen with liver transplantations from deceased donors (DD). Biliary and vascular complications are more often seen in the LDLT setting. So far, no studies have focussed on the impact of LDLT on waiting list mortality. There is international consensus that this procedure should be restricted to centres with large experience in deceased donor liver transplantations as well as in hepatobiliary surgery. Ethical issues, optimal utility and application of adult LDLT and optimal recipient and donor characteristics have yet to be defined.     

Living donor liver transplantation for hepatitis C related hepatocellular carcinoma in a haemophilia A patient

We report the first case of unrelated living liver transplantation for hepatitis C related hepatocellular carcinoma (HCC) in a Chinese patient with haemophilia A. The development of cirrhosis and HCC was insidious in this patient, who has previously failed interferon treatment despite low viral load and genotype 6a. With factor VIII and novoseven support, there were no operative complications and there was no need for blood transfusion. Postoperative pegulated interferon treatment resulted in viral clearance with no increased cellular rejection. The use of living donors represent a potential life saving therapeutic options for hepatitis C virus related complications in haemophiliac, especially in countries of organ shortage. Careful patient and donor choice, meticulous surgical expertise and proper counselling, however, are prudent requirements.     

Living donor liver transplantation in adults

Adult-to-adult living donor liver transplantation (LDLT) using right hemi-liver has become a promising treatment modality for patients with end-stage liver disease. The rapid adoption of the procedure has been triggered mainly by the significant gap between available cadaver grafts and the number of patients on the waiting list for liver transplant. Since the arguments against LDLT focus only on the safety of the donor, the demonstration that the donor operation can be performed with minimal morbidity will make it more ethically acceptable. The advantages of LDLT are the possibility of performing an elective operation, access to a graft in best condition, and the possibility of lowering the likelihood of death while waiting for a suitable organ. As well as the standard indications for liver transplantation, LDLT opens up the possibility of treatment of patients with borderline indications. Further improvement of surgical and medical technology, careful long-term follow-up of donors and recipients, and profound analysis of socioeconomic aspects are essential issues for the transplantation community.     

Living donor liver transplantation in India.

The world over, liver transplantation has emerged a panacea for thousands of patients suffering from end-stage liver disease. The strides made in living donor liver transplantation (LDLT) by Asian centres particularly in Japan, Korea, Hong Kong and Taiwan made many Indian centres realise that in order to sustain liver transplant activity in the country, a similar solution had to be found. Even though LDLT is very resource intensive and requires skilled multidisciplinary manpower, 22 centres in India have performed liver transplants, of which 14 have performed at least one LDLT procedure. 140 LDLT procedures have been performed at our centre, of which 13 have been done in emergency circumstances. LDLT has certain advantages over DDLT. It allows for adequate preparation of the patient for elective transplant and recipients are not in competition with others over the same donor organ. Major concerns with LDLT are of donor safety and biliary complications. In conclusion, establishing a high volume LDLT centre with excellent success rates is feasible in the Indian setting.     

Living donor liver transplantation: Eastern experiences

BACKGROUND: The techniques of living donor liver transplantation (LDLT) developed rapidly in the 1990s to compensate for a severe deficiency in the availability of liver grafts from cadaveric donors for the treatment of patients with end-stage liver disease. This tendency was particularly prominent in East Asia, as brain-death donors have remained largely unavailable for a variety of reasons. Thanks to refinements in surgical technique and postoperative management for LDLT, the cumulative total of LDLTs in East Asian countries has exceeded 2000 and, importantly, donor mortality has yet to be encountered. Moreover, indications for LDLT have been successfully expanded from paediatric to adult cases, following the introduction of right lobe graft. The significance of LDLT under conditions of limited opportunities for cadaveric liver transplantation, as experienced in these countries, differs significantly from that seen with the numerous opportunities for cadaveric donors in Europe and the USA. This review describes not only the experiences of East Asia, but also the specific differences from Western countries, such as indications, graft size issues and ABO blood type combinations, to shed light on the future of liver transplantation.     

Cholestatic hepatitis due to hepatitis C virus after a living donor liver transplantation

Recurrence of hepatitis C virus after liver transplantation is common and cholestatic hepatitis occurs in approximately 10% of the patients and leads to accelerated graft failure and death. A 47-year-old man underwent living donor liver transplantation for hepatitis C-related liver cirrhosis. Preemptive antiviral therapy was started using interferon-alpha2b (6 MU x 3 per week) and ribavirin (600 mg per day) two months after living donor liver transplantation. The response to the combined therapy was not satisfactory. He developed liver failure and expired 11 months after the transplantation. The present results indicate that a rapid development of graft failure can occur in spite of preemptive antiviral therapy after living donor liver transplantation.     

Living donor liver transplantation for pediatric and adult recipients

Living donor liver transplantation (LDLT) was initially developed to provide suitable liver grafts for pediatric patients with end-stage liver disease. This innovation was remarkable for the prospective nature of its development and the public discussions that resolved the ethical dilemma of removing a portion of a liver from a healthy donor for the benefit of another person. Since its inception, this procedure has been uniformly adopted by most pediatric transplant centers, with excellent results. Unfortunately, liver grafts obtained from this procedure did not provide sufficient hepatocyte mass for use in adult recipients. An adult donor procedure was, therefore, developed to provide larger liver grafts, which were derived from the right lobe of the liver. Much of the driving force for adult-to-adult LDLT has been in countries that lack the health-care infrastructure for obtaining deceased donors or have cultural objections to deceased donor transplantation. In developed countries, the initial growth of adult-to-adult LDLT has been tempered by notable donor complications, including death, but it continues to have an important role in providing life-saving liver grafts for recipients who are unable to compete for deceased donor grafts in the current organ-allocation system.     

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.     

Living donor liver transplantation: issues regarding left liver grafts

BackgroundThe necessity of widening the indications for living donor liver transplantation (LDLT) has been emphasised. Clarification of the advantages and limitations of using a left liver graft for LDLT in adults is essential for donor safety.MethodsBetween June 1990 and November 2002, 185 patients underwent LDLT at Shinshu University Hospital, Japan. In 97 of these, the graft comprised the left liver with or without the left portion of the caudate lobe. The peri-hepatectomy profiles of the donors, significance of left liver grafts, postoperative courses of the donors and recipients, and survival of the recipients were investigated.ResultsAll the donors recovered well and returned to a normal lifestyle. None required banked-blood transfusion or repeat surgery, and postoperative liver function tests had satisfactory results. The cold ischaemic time for the graft was 127±54 minutes. The graft volumes (GVs) ranged from 230 to 625 ml, and GV/standard liver volume (SV) ratios varied from 22% to 65%, at the time of transplantation. Although 85% of the liver grafts had GV/SV ratios <50%, no patient developed immediate postoperative liver failure. Patient survival rates were 89%, 84% and 84% at 1, 3 and 5 years, respectively.DiscussionAlthough LDLT using a left liver graft imposes potential postoperative complications (a small liver is more vulnerable to injury, and recipients of small grafts are at higher risk of complications during recovery), such grafts have yielded acceptable results in adult LDLT, with minimal burden to the donors.     

Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C

BACKGROUND: Chronic hepatitis C virus (HCV) infection is frequently associated with elevated markers of iron stores. Recessively inherited mutations in the HFE gene are responsible for iron accumulation in most cases of hereditary haemochromatosis and may have a role in HCV infection. They may also be associated with progressive liver fibrosis although this remains controversial. AIMS: To assess the prevalence of HFE mutations in Scottish HCV infected patients and to explore the effect of the carrier state on serum and liver iron stores, and the severity of liver disease. PATIENTS: A total of 164 patients with antibodies to HCV who underwent liver biopsy were assessed prospectively. METHODS: Each patient was screened for HFE mutations (Cys282Tyr and His63Asp). Iron markers were assessed in serum (ferritin, transferrin saturation) and on liver biopsy (stainable iron, liver iron concentration (LIC) and hepatic iron index). RESULTS: There were 67 (41%, 26 Cys282Tyr, 33 His63Asp, eight compound) heterozygotes. Forty four (28%) patients had elevated serum iron markers, 24 (15%) had stainable liver iron, and five (3%) had elevated LICs. Carriage of HFE mutations was not associated with any clinical, biochemical, virological, or pathological features, including accumulation of liver iron. Elevated serum iron markers were associated with male sex, increased alcohol consumption, and increased liver inflammation and fibrosis. Patients with elevated LICs were older, acquired HCV infection earlier, and had more liver inflammation. CONCLUSIONS: Patients with chronic HCV infection frequently have elevated serum iron markers although elevated LICs are uncommon. Elevated serum iron studies and LICs occur in patients with more severe liver disease. Carriage of HFE mutations, although frequently observed in these HCV infected patients, does not have a role in the accumulation of iron or the progression of liver disease in HCV infection.