Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation

Familial amyloid polyneuropathy (FAP) associated with transthyretin (TTR) mutations is the commonest type of hereditary amyloidosis. Plasma TTR is produced almost exclusively in the liver and orthotopic liver transplantation is the only available treatment, although the clinical outcome varies. Serum amyloid P component (SAP) scintigraphy is a method for identifying and quantitatively monitoring amyloid deposits in vivo, but it has not previously been used to study the outcome of visceral amyloid deposits in FAP following liver transplantation. Whole body scintigraphy following injection of iodine-123 labelled SAP was performed in 17 patients with FAP associated with TTR Met30 and in five asymptomatic gene carriers. Follow-up studies were performed in ten patients, eight of whom had undergone orthotopic liver transplantation 1-5 years beforehand. There was abnormal uptake of 123I-SAP in all FAP patients, including the kidneys in each case, the spleen in five cases and the adrenal glands in three cases. Renal amyloid deposits were also present in three of the asymptomatic carriers. Follow-up studies 1-5 years after liver transplantation showed that there had been substantial regression of the visceral amyloid deposits in two patients and modest improvement in three cases. The amyloid deposits were unchanged in two patients. In conclusion, 123I-SAP scintigraphy identified unsuspected visceral amyloid in each patient with FAP due to TTR Met30. The universal presence of renal amyloid probably underlies the high frequency of renal failure that occurs in FAP following liver transplantation. The variable capacity of patients to mobilise amyloid deposits following liver transplantation may contribute to their long-term clinical outcome.     

Renal replacement therapy in multiple myeloma and systemic amyloidosis

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.     

Renal insufficiency after heart transplantation: a case-control study

BACKGROUND: In Rotterdam 304 heart transplants have been performed since 1984. End-stage renal failure, necessitating renal replacement therapy, has developed in 24 patients (8%) after an interval of 25-121 months (median 79 months). After starting renal replacement therapy one-year survival was only 60%. Overall survival after heart transplantation, however, was favourable: 5 and 10 year survival rates of 79% and 50% respectively. METHODS: A case-control study was performed to identify possible risk factors in cases who went on to develop end-stage renal failure compared to controls. RESULTS: We found that renal failure was not limited to elderly patients with ischaemic heart disease, but also occurred in young patients having dilated cardiomyopathy. A significant rise in the serum creatinine was found in cases compared to controls as early as 3 months after transplantation. Cyclosporin dose and trough levels were not different between cases and controls. Neither were there differences in the use of calcium-antagonists or other antihypertensive drugs, allopurinol or diuretics. Rejection incidence was also similar between the two groups. CONCLUSIONS: Renal failure after heart transplantation is a long term complication of cyclosporin use that is not limited to elderly patients with ischaemic heart disease. Cyclosporin dose and trough levels in the cases were not different from patients maintaining stable good renal function, indicating that cyclosporin nephrotoxicity is the result of an individually determined susceptibility to cyclosporin. Suggestions for future strategies to prevent renal failure are given.     

Inherited diseases of the glomerular basement membrane

The inherited diseases of the glomerular basement membrane include Alport's syndrome (AS), nail-patella syndrome, and thin basement membrane nephropathy. Classical AS is inherited in an X-linked manner and accounts for approximately 85% of the cases. Its manifestations include hematuria, sensorineural hearing loss, ocular defects, and a progression to renal failure. A defect(s) in the alpha 5 (IV) chain of type IV collagen is believed to be the etiology of classic AS, and alterations in its encoding gene localized to the X-chromosome have been elucidated. Although isolated cases of anti-glomerular basement membrane glomerulonephritis have been reported following renal transplantation in patients with AS, it is considered an effective form of renal replacement therapy. Less is known regarding the genetic basis of the autosomal-dominant form of AS, which apparently accounts for the remaining 15% of the cases. Nail-patella syndrome is characterized by nail dysplasia, patellar hypoplasia or aplasia, and nephropathy. It is inherited in an autosomal-dominant fashion with the gene locus assigned to the long arm of chromosome 9. Possible linkage between the COL5A1 gene and the gene for nail-patella syndrome has been suggested. Approximately 30% of the patients progress to end-stage renal failure. Renal transplantation has been successful in treating patients who progress to end-stage renal failure. Thin basement membrane nephropathy is an autosomal dominant trait that accounts for approximately 30% of the cases presenting as persistent, asymptomatic hematuria. The cause of thin basement membrane nephropathy is unknown at present. No decline in renal function is associated with thin basement membrane nephropathy.     

Effects of different types of light guides on shear bond strength

Several patients with end-stage renal disease went to Bombay for renal transplantation from nonrelated living donors and then returned to Turkey for posttransplantation follow-up. The aims of this study are to evaluate the long-term results of renal transplantation from nonrelated living donors in Turkish patients with end-stage renal disease and to discuss the ethical and social aspects of nonrelated kidney donation. One hundred and twenty-seven patients (89 males, 38 females; mean age 38.1, range 17-63 years) were investigated retrospectively. None of the patients went to Bombay on our advice. All transplantations were performed between 1991 and 1995. The mean follow-up period after transplantation was 34.2 (range 1-68) months. Graft survival rates were 85, 83, and 57% after 3 months and 1 and 5 years, respectively. Patient survival rates were 94, 93, and 92% after 3 months and 1 and 5 years, respectively. Seven patients died within the first 3 months after the transplantation. Surgical problems, infections, acute rejection, ciclosporin nephrotoxicity, and hepatic problems were common complications. We conclude that medical and surgical complications occur frequently in paid kidney transplantation, but most of these complications can be prevented by adequate preoperative management, and precautionary measures should be taken to prevent commercialization of renal transplantation before the spread of emotionally related living kidney donation.     

Non-real-time computed tomography-guided percutaneous ethanol injection therapy for hepatocellular carcinoma undetectable by ultrasonography

Fibrosing cholestatic hepatitis (FCH) has recently been described after solid organ transplantation in patients with hepatitis C virus (HCV) infection. Typically, FCH is characterized by an ominous clinical course leading to progressive hepatic failure and death if liver transplantation is not performed. Two HCV-infected patients underwent cadaveric renal transplantation for end-stage renal disease resulting from membranous nephropathy and diabetic nephropathy. The time intervals between transplantation and the biopsy diagnosis of FCH for the two patients were 7 months and 10 years. Both patients presented with jaundice, hyperbilirubinemia, and mild-to-moderate elevations in serum aspartate aminotransferase. One patient was also found to have type II mixed cryoglobulinemia. Interferon-alpha therapy was begun after a diagnosis of FCH was established by liver biopsy. Liver test abnormalities normalized rapidly. When cholestatic hepatic deterioration develops in an HCV-infected organ allograft recipient, the diagnosis of FCH should be considered and a liver biopsy performed. Our observations indicate that FCH can respond to antiviral therapy.     

Vascular complications of kidney transplantation

584 kidney transplantations (208 from cadaveric donors, 376 from living relative donors) were performed in Medical Faculties of the Istambul University in 1986-1997. Thrombosis of the renal artery was observed in 2 patients (0.35%). One of them had diffused arterial atherosclerosis 4 months after the kidney transplantation. In spite of two successful thrombectomies, the patient died 3 months after the last surgical procedure from cerebral thrombosis. The other patient underwent nephrectomy. Hypertension was observed in 63 patients. In 5 of them about 50% stenosis of the anastomotic area was detected by doppler duplex scan and selective angiogram. Transluminal angioplasty was performed in one patient, open surgical correction in one case. Renal vein thrombosis took place in 1 (0.2%) patient. In 2 cases (0.35%) 5 and 12 years after the transplantation aortic aneurysmal dissection was observed.     

Diabetic nephropathy

Diabetic nephropathy is one of the microvascular complications of diabetes. Its incidence is decreasing in insulin dependent patients, but extremely increasing in non-insulin dependent patients in developed countries. The development of nephropathy in an individual patient cannot be predicted in spite of new information about genetics and pathophysiology of the disease. Clinical course progresses from microalbuminuria to overt proteinuria and than to renal failure. The disease cannot be cured, but can be prevented or limited in progression. The most important measures are maintaining of normoglycaemia and blood pressure in low-normal values (best using ACE inhibitors), treatment of hypercholesterolaemia and protein restriction. Renal replacement therapy is available for all diabetic patients in our country without restriction, the best method is kidney transplantation if not contraindicated.     

Superior outcomes in pediatric renal transplantation

BACKGROUND: Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults. OBJECTIVE: To determine factors important for success in renal transplantation in children. DESIGN: Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry. RESULTS: One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery. CONCLUSIONS: Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.     

Temporomandibular joint derangement after air bag deployment: report of two cases

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.     

Renal transplantation in a patient with methylmalonic acidaemia

Renal insufficiency is frequently reported in mutase-deficient methylmalonic acidaemia. We present a case report of a patient with mut- methylmalonic acidaemia who developed chronic tubulointerstitial nephropathy during adolescence. At 24 years of age, she developed end-stage renal failure and underwent renal transplantation. Both plasma and urine methylmalonic acid levels decreased significantly with improved renal function following transplantation. Complications included cyclosporin toxicity and development of diabetes. Renal, metabolic, and clinical status remained improved at 3 years after the kidney transplant.     

GTR treatment of degree III furcation defects following application of enamel matrix proteins. An experimental study in dogs

Ankylosing spondylitis (AS) can be accompanied by extraarticular manifestations in the cardiovascular, pulmonary, neurologic and renal organs. Secondary renal amyloidosis is the most common cause of renal involvement in AS (62%) followed by IgA nephropathy (30%), mesangioproliferative glomerulonephritis (5%) as well as rarely membranous nephropathy (1%), focal segmental glomerulosclerosis (1%) and focal proliferative glomeruleonephritis (1%). Treatment associated nephrotoxicity may result from non-steroidal anti-inflammatory drugs or disease modifying agents. The purpose of this paper was to alert for the possibility of renal damage in AS and to analyse the frequencies of different etiologies of renal involvement. Two typical case reports of renal involvement in AS are presented to illustrate the clinical course of such patients. Renal side effects and possible pre-existing renal diseases should be taken into account while choosing the appropriate medication for patients with AS.     

Autosomal dominant polycystic kidney disease: urologic complications and results of kidney transplantation: 217 patients

The authors report a retrospective series of 217 cases of autosomal dominant renal polycystic disease collected over a period of 30 years in the urology and nephrology departments of Nantes university hospital. They study the incidence of urological complications, observed in 87 patients (40%), consisting of calculi (15%), infection (22%, with 4 deaths), intracystic haemorrhages (3.5%) and urinary tract compression (2%). The diagnostic and therapeutic methods are presented and discussed. The results of renal transplantation are also analysed: 39 patients were transplanted, 72% retained a functioning kidney with a mean follow-up of 44.9 months (range: 12-108 months) and three patients died as a result of infectious complications. The 1-year and 3-year actuarial transplant survival rate of 92% was similar to that of renal transplantations performed for another form of renal disease. Preparation for renal transplantation remains an essential problem: the two major indications for pre-transplantation nephrectomy were the size of the kidneys and the presence of infection.     

Objectives to direct the training of emergency medicine residents on off-service rotations: surgery, Part 3

Immunoglobulin A nephropathy (IgAN) frequently recurs in patients after renal transplantation (RT) on a conventional regimen of immunosuppressive therapy, but little is known about the influence of cyclosporine (Cs) on such a recurrence. We studied 84 patients retrospectively who underwent RT for renal failure attributable to IgAN (n = 71) or Henoch-Sch?nlein purpura nephropathy (HSPN) (n = 13) in two transplantation units, between January 1985 and June 1991 and were treated with Cs. Four patients died 3 months to 8 years after RT. Graft survival was 88% at 1 year, 75.2% at 5 years, and 63% at 8 years. Fifty patients underwent at least one graft biopsy, but studies with immunofluorescence were performed on only 28 (23 IgAN and 5 HSPN). After a mean follow-up of 68.1 +/- 37.2 months, mesangial IgA deposits recurred in 13 of the 28 patients (12 IgAN and 1 HSP) (prevalence, 46.4%). Among the 13 patients with recurrence of IgA deposits, all but 4 had urinary abnormalities. Light microscopy showed mesangial deposits and focal and segmental glomerular changes in 9 cases. Four patients lost their graft function 69 to 119 months after RT, and 2 had severe graft dysfunction. The rates of graft failure and mean serum creatinine at 1, 5, and 8 years were similar in the 13 patients with recurrence and the 15 patients without proven recurrence. In conclusion, Cs did not reduce the incidence or severity of IgAN recurrence. The latter was the cause of graft loss or dysfunction in 46.1 % of the patients with recurrent IgA deposits. Recurrent glomerulonephritis did not influence the 8-year graft survival in patients with IgAN or HSPN, but it may be an important cause of graft loss as evidenced by more extended follow-up.     

Renal transplantation in patients with renal cell carcinoma and von Hippel-Lindau disease

This study reviewed the management and outcome of patients with von Hippel-Lindau disease (VHLD) who underwent renal transplantation after being rendered anephric to treat multifocal bilateral renal cell carcinoma (RCC). Five patients with bilateral RCC and VHLD underwent renal transplantation at our hospital. Initial treatment of RCC consisted of bilateral nephrectomy in 2 patients and unilateral nephron-sparing surgery with contralateral nephrectomy in 3 patients. All of the latter 3 patients experienced isolated tumor recurrence in the renal remnant at 48, 64, and 66 months postoperatively; this was managed by complete excision of the renal remnant. Renal transplantation was performed 11 to 24 months after initiation of dialysis. Postoperatively, all of the allografts functioned well with no further requirement for dialysis. Currently, 4 patients are alive at a mean post-transplant follow-up interval of 26 months (range, 7 to 66 months) with excellent graft function and no evidence of malignancy. One patient died 17 months following transplantation due to metastatic disease. Renal transplantation can provide satisfactory replacement therapy for patients with end-stage renal disease with VHLD and treated RCC.     

The great success of Asian kidney transplant recipients

BACKGROUND: Little has been written about allograft survival in non-African-American minority groups. We examine the success of kidney transplantation in 1900 Asian recipients. METHODS: Data from 42,252 cadaveric and 16,115 live donor kidney transplant recipients were monitored from the United Network for Organ Sharing Scientific Renal Transplant Registry from 1991 through 1996. RESULTS: Asian recipients exhibited the highest cadaveric allograft survival rates (89% 1-year and 83% 3-year survival) and the longest mean allograft half-life (18 years). Asian women had the highest mean graft half-life (23 years). Asians were less likely to be broadly sensitized and had a high incidence of IgA nephropathy causing end-stage renal disease. Although it has been suggested that their low body weights may help explain the excellent allograft outcome, Asians exhibited superior graft survival rates even when compared with low body weight recipients of other races. CONCLUSION: Asian renal allograft recipients, particularly Asian females, have the highest allograft survival rates of all racial groups.     

Treatment of end-stage renal failure after heart transplantation

BACKGROUND: Five to 10% of heart-transplant recipients develop end-stage renal failure (ESRF). Little is known about the outcome of these patients under renal replacement therapy. METHODS: We conducted a retrospective study in 16 men (mean age 52.8+/-7.4 years at heart transplantation) who developed ESRF 5.3+/-2.1 years later. Results. Haemodialysis (HD) was the first-line treatment (mean Kt/V 1.35+/-0.4). Vascular access was unsuccessful in six patients (37.5%) due to peripheral arteriopathy and they were treated with tunnelled catheters for an average 15 months without bacterial infection. Mean weight was 68.4+/-10 kg at onset of HD and 61.7+/-9 kg one month later. Despite this reduction in extracellular overload, one antihypertensive drug was required in 75% of patients and two drugs in 12.5%. One patient tolerated automated peritoneal dialysis (PD) for 16 months (weekly Kt/V 2.1) despite persistent anuria. Renal transplantation (RT) was contraindicated in eight patients because of aortoiliac arteriopathy (n=5), poor general status (n=2), or ischaemic heart disease (n=1). RT was performed in eight patients with no acute episode of heart or renal graft rejection. There were no serious infectious complications. Three months after RT, mean serum creatinine was 115 micromol/l. One patient developed post-transplant lymphoproliferative disorder 3.5 months after RT and was successfully treated with transplant nephrectomy. Sudden death occurred in two patients 18 and 33 months after RT. Overall patient survival was 100, 78, and 59%, 1, 2 and 3 years after HD onset respectively. Using a time-dependent variable, the Cox model analysis demonstrated that heart-transplant recipients with ESRF have a relative risk of death 3.2 times higher than those without ESRF (95% CI = 1.3-7.8). CONCLUSIONS: HD, PD, and RT can be useful for the treatment of ESRF after heart transplantation. After initiating HD, patient survival is nearly the same as that reported in patients in Europe undergoing HD for other causes. But ESRF seems to reduce life expectancy in heart-transplant recipients.     

Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure

Thin glomerular basement membrane (GBM) nephropathy, also called familial benign hematuria, is characterized by chronic hematuria and uniform thinning of the lamina densa of the glomerular basement membrane. It generally holds an excellent renal prognosis. Alport syndrome in early stages can also show attenuation of the GBM; conversely, renal insufficiency has been reported in familial benign hematuria. To discern early Alport syndrome from thin GBM nephropathy, we carried out a prospective epidemiological study in which 19 normotensive and non-azotemic adult patients with chronic microscopic (18 of 19) and macroscopic (1 of 19) hematuria and biopsy-proven thin GBM nephropathy were followed for a median of 12 years (range 9 to 15 years). Renal biopsies of thin GBM patients at entry showed an increased incidence of focal global glomerulosclerosis when compared to disease controls as IgA nephropathy (P = 0.047) and normal renal tissue (P = 0.0075). All renal biopsies showed the presence of the Goodpasture antigen when tested immunohistochemically. Presence of Alport syndrome was excluded clinically as none of the patients had complaints of hearing loss or abnormalities by audiography and ophthalmology. At the end of follow-up, the incidence of hypertension in thin GBM nephropathy (35%) exceeded that of healthy clinical controls (P = 0.048), and one hypertensive patient developed mild renal failure. In the normotensive patients, the glomerular filtration rate at follow-up as measured by inulin clearance was reduced in three out of seven; these were over 50 years of age. Although no family members were known to have renal disease at inclusion, within four families six elderly first degree relatives had developed unexplained renal insufficiency at the end of follow-up. Thus, thin GBM nephropathy predisposes to premature glomerular obsolescence, leading in time to increased incidences of hypertension and late onset renal insufficiency.     

Glomerular nephropathy with IgA mesangium deposits and Crohn disease

BACKGROUND: Renal disease is an unfrequent extraintestinal manifestation of chronic inflammatory bowel disease. CASE REPORT: A 12-year-old girl suffered from recurrent abdominal pain, diarrhea and growth impairment due to Crohn's disease of ileocaecal region. After six months of nutritional rehabilitation, an ileo-caecal resection was performed because of intestinal stenosis. The surgical procedure was followed by parietal abcess and cutaneous fistula. One year later, a purulent secretion came out of the fistula associated with fever, hematuria and acute renal failure. Renal biopsy confirmed IgA nephropathy. The course was favorable under parenteral nutrition and after surgical closure of the sigmoido-cutaneous fistula. The microscopic hematuria only persisted but the nephropathy did not relapse even during a further digestive exacerbation. CONCLUSION: IgA nephropathy has been reported in association with chronic inflammatory bowel disease. Its mechanism remains unclear: increased mucosal IgA production in inflammatory bowel, increased serum IgA and/or immune complex deposition in the renal mesangium appear the most relevant hypotheses.     

Liver transplantation in acute liver failure

Acute hepatic failure is characterized by jaundice and hepatic encephalopathy within eight weeks after the onset of disease. Although acute hepatic failure is a rare occurrence, its rapid progression and high mortality (50 to 90%, depending on the etiology of disease) necessitate immediate intervention. In the absence of causal therapy, orthotopic liver transplantation is currently the only definitive and effective means of treating acute hepatic failure in Europe, acute hepatic failure accounts for 11% of all liver transplantations. At the University department of transplantation surgery in Vienna a total of 27 patients with acute hepatic failure underwent 31 liver transplantations in the last 10 years (1.1.1987 to 31.12.1996). Twenty (74%) of the 27 patients survived the acute event and were discharged from hospital in good general condition after a median postoperative stay of 25 days (range 14-81 days). Seven patients (26%) died between the first and 34th postoperative day (median 26 days) in the intensive care unit, although all potential modern options of intensive care and surgery were used. The causes of death were irreversible cerebral edema (n = 3), multiple organ failure due to bacterial sepsis (n = 3) and uncontrollable haemolysis (n = 1). With a 3-year graft survival rate of 70% the 3-year patient survival rate was 74%. A retrospective analysis of our patients revealed that the postoperative graft function and the incidence of re-transplantation were significant prognostic factors (p < 0.05) for survival following orthotopic liver transplantation for acute hepatic failure. In the absence of further prognostically relevant preoperative indices and in consideration of the potentially fulminant progression of disease, we strongly recommend that any patient, in whom acute hepatic failure is suspected, is immediately transferred to a specialized center with experience both in the conservative treatment of acute hepatic failure and emergency liver transplantation.