Relationship between in vivo FK506 clearance and in vitro 13-demethylation activity in living-related liver transplantation.

BACKGROUND: Although it is important to maintain an appropriate blood concentration of FK506 after liver transplantation, significant interindividual variability in the actual FK506 dosage has been observed, presumably due to the wide variability of cytochrome P450 3A4 activity in liver microsomes. METHODS: A study was conducted in patients undergoing living-related liver transplantation and their donors to investigate the relationship between the in vitro FK506 demethylation activity in graft liver microsomes and the in vivo blood clearance of FK506. Liver biopsy tissue was obtained from 17 living donors to measure the in vitro formation rate of 13-demethyl derivative (M-I: the major metabolite of FK506). Erythromycin N-demethylation activity in vitro was also assessed in 11 cases. The FK506 blood clearance (CLss) was calculated from its constant infusion rate and steady-state blood concentration on day 4 after transplantation in 17 recipients. RESULTS: The FK506 infusion rate varied 4.6-fold from 8.3 to 38.4 ng/min/kg. The mean CLss of FK506 was 22.1+/-10.8 ml/min (10.1-45.2 ml/min). The M-I formation rate showed a wide variability, ranging from 0.098 to 0.571 nmol/min/mg protein. A significant correlation was observed between the in vitro estimated total metabolic ability of the graft for FK506 (M-I formation rate x graft weight) and the in vivo CLss of FK506 (r=0.770, P<0.001). Erythromycin N-demethylation (0.066-0.443 nmol/min/mg protein) showed a strong correlation with the M-I formation rate (r=0.891, P<0.01). CONCLUSIONS: The in vivo FK506 clearance can mainly reflect in vitro FK506 demethylation activity.

Efficacy of quantitative analysis of Epstein-Barr virus-infected peripheral blood lymphocytes by in situ hybridization of EBER1 after living-related liver transplantation: a case report.

BACKGROUND: We describe a 1-year-old female who underwent living-related liver transplantation for biliary atresia and developed Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder. This disorder was resolved after withdrawal of immunosuppression therapy and administration of a high dose of acyclovir. METHODS: To quantify the extent of EBV activation and EBV load in peripheral blood, we measured the levels of EBV-infected peripheral lymphocytes by in situ hybridization (ISH) of EBV-encoded small mRNA 1 (EBER1). RESULTS: The decline in the number of EBER1-positive lymphocytes (from 362/50,000 mononuclear cells to 0/50,000) after treatment was in accord with the patient's clinical improvement. CONCLUSIONS: This finding showed that quantitative analysis of EBV-infected peripheral lymphocytes by ISH of EBER1 is very useful for monitoring the EBV load and response to treatment of patients with EBV-related disorders. Furthermore, ISH may become an important tool for the early diagnosis and prevention of life-threatening posttransplant lymphoproliferative disorder in posttransplant patients.

Urgent living-related liver transplantation using a graft with multiple intrahepatic arterioportal fistulae.

BACKGROUND: We describe the case of a man with intrahepatic arterioportal fistulae located in the left lobe, whose left lateral segment was transplanted into his son who was suffering from severe acute hepatitis B. METHODS: A male infant with severe acute hepatitis B was considered to be a candidate for liver transplantation. The father was willing to be the donor. Preoperative evaluation of the donor revealed intrahepatic arterioportal fistulae, however, duplex ultrasonography showed normograde portal blood flow. A living-related liver transplantation was performed. RESULTS: The postoperative course for both the donor and recipient was uneventful. The recipient is free of recurrent hepatitis B and has normograde portal blood flow. CONCLUSIONS: The present case suggests that there may be a symptomless population with intrahepatic arterioportal fistulae, which cause various degrees of disruption of the portal blood flow. Duplex ultrasonography might be helpful in the evaluation of candidates for liver donation.

Fatal hemophagocytic syndrome after living-related liver transplantation: a report of two cases.

BACKGROUND: Hemophagocytic syndrome (HPS) is a serious hematological disorder caused by activated T lymphocytes in immunologically compromised patients. There is no report of HPS in liver transplant recipients. METHODS: Among 135 patients who underwent living-related liver transplantation between June 1990 and October 2000, HPS developed in two pediatric patients (1.5%) on the 15th and 134th postoperative day, respectively. The courses of these patients were evaluated. RESULTS: The cause of HPS was unknown in patient 1 and suspected to be Epstein-Barr virus infection in patient 2. The course of patient 2 was also complicated by posttransplant lymphoproliferative disorder. Both patients had high fever, pancytopenia, coagulopathy, and marked elevation of serum-soluble interleukin 2 receptor, serum ferritin, and urine beta2-microglobulin levels. The diagnosis was established based on clinical findings, laboratory data, and bone marrow biopsy. Both patients died in an acute course despite intensive care. CONCLUSIONS: HPS should be recognized as a severe hematological complication in liver transplant patients. Prompt institution of adequate treatment is necessary to prevent fatality.

Long-term results of living-related donor liver graft transplantation: a single-center analysis of 110 transplants.

BACKGROUND: Difficulties of cadaveric donation and serious donor shortage have led to the development and popularization of living-related donor liver graft transplantation (LRLT). Because the history of this procedure is rather short, important aspects specific to this procedure have not been sufficiently documented. The objective of this study was to analyze a single center's 10-year experience with 110 LRLT in pediatric and adult patients with end-stage liver diseases. METHODS: The medical records of 110 consecutive patients who underwent LRLT were reviewed. The recipients were comprised of 72 children and 38 adults. The graft volume corresponded to 26-192% of the recipient's standard liver volume. The relationship between pretransplant covariates and patient and graft survival was analyzed. Actuarial patient/graft survival rates were determined at 1, 3, and 5 years. The type and incidence of posttransplant complications were analyzed, as was long-term graft function. RESULTS: The 1-, 3-, and 5-year actuarial patient and graft survival rates were 88%, 85%, and 85%, respectively. Log-rank test demonstrated that ABO-compatibility predicted patient survival rate, whereas patient age, underlying disease, patient's clinical status, donor-recipient relation, donor age, and graft volume/standard liver volume ratio did not. Long-term liver function remains excellent. All the donors have returned to normal daily lives with an uneventful course. CONCLUSIONS: LRLT is an efficacious procedure that provides excellent short-term and long-term survival. The indication criteria for both recipient and donor were legitimate in this series, except for transplant across ABO-incompatibility. Cautious expansion of this procedure may be justified under the situation of serious shortage of cadaveric donor.

Systemic reactive amyloidosis associated with Castleman's disease: serial changes of the concentrations of acute phase serum amyloid A and interleukin 6 in serum.

A case is reported of a 21 year old woman who suffered from Castleman's disease and systemic reactive amyloidosis. The serum concentrations of serum amyloid A (SAA) and interleukin 6 (IL-6) were extremely high and amyloid protein was immunohistochemically identified as AA. After surgical excision of a large retroperitoneal lymph node with the pathological findings of plasma cell type of Castleman's disease, both serum SAA and IL-6 declined, showing a similar pattern of reduction curves. All clinical symptoms and laboratory abnormalities greatly improved. The biochemical feature of Castleman's disease is abnormal production of IL-6 and this cytokine continuously may stimulate the synthesis of an amyloid precursor, SAA, causing systemic reactive (AA) amyloidosis. This pathogenetic theory is strongly supported by the present study.

Esophageal intramural pseudodiverticulosis associated with esophageal perforation.

We report a rare case of esophageal intramural pseudodiverticulosis with lower esophageal stricture which perforated into the peritoneal cavity after the patient vomited. A 61-year-old man was admitted with severe chest and epigastric pain after dysphagia and vomiting. Under a diagnosis of upper gastrointestinal perforation, laparotomy was performed. The anterior wall of the abdominal esophagus was found to have ruptured, and proximal gastrectomy with abdominal esophagectomy was performed. Histological examination revealed esophageal intramural pseudodiverticulosis with esophageal stricture distal to the site of rupture, and postoperative endoscopy showed diffuse pseudodiverticulosis in the remaining esophagus. The patient is free of symptoms 5 years after the surgery. This case suggests that careful treatment may be indicated in patients with esophageal intramural pseudodiverticulosis with stricture and elevated intraluminal pressure, to minimize the possibility of severe complications such as esophageal perforation.

Resection of a large liver cell adenoma originating in the caudate lobe.

A rare case is reported of a large liver cell adenoma originating in the caudate lobe of the liver in a 38-year-old women with no history of liver cirrhosis or use of oral contraceptives: Caudate lobectomy of the liver is described. Passing tapes around the inferior vena cava was useful for controlling the bleeding from a torn short hepatic vein. This resection of a large hepatocellular adenoma originating in the caudate lobe is to our knowledge only the second case to be reported in the English literature.

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.

Preoperative measurement of segmental liver volume of donors for living related liver transplantation.

Segmental liver volume determination by computed tomographic scan was carried out preoperatively in nine donors for living related liver transplantation. The calculated volume was compared with the graft size actually obtained by three types of donor hepatectomy. The volume of the left lateral segment (175 to 241 ml) and the left lobe (310 to 490 ml) varied markedly among the donors. The ratio of the left lobar to total liver volume also showed a wide range of values (23.2% to 35.9%). The value of the left lobar volume did not correlate positively with the donor's body weight, suggesting that graft size cannot be predicted only on the basis of the donor's body size. Segmental graft liver volume was estimated by use of computed tomographic scan, with acceptable accuracy on comparison with the graft volume actually obtained. In living related liver transplantation, the type of donor hepatectomy should be selected on the basis of the segmental liver volume of the donor in addition to the recipient's body size so that liver failure can be prevented in recipients and the donor's safety can be assured as far as possible.

Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure.

The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF.