Experience with primary liver transplantation across ABO blood groups.
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ABO Blood-Group System↗
Biomedical subjects
S Iwatsuki
Publications and source records attributed to S Iwatsuki.
Clinical considerations in orthotopic liver transplantation.
Progress in immunosuppression, surgical techniques, and perioperative care has promoted orthotopic liver transplantation from an experimental procedure to an accepted clinical treatment. Orthotopic liver transplantation, in turn, has changed the treatment of terminal liver disease from care that is largely treatment of symptoms and support to cure, but at the price of major surgery and life-long immunosuppression. This article reviews the current status of liver transplantation as practiced at the University of Pittsburgh.
Graft Rejection↗
Late mortality and morbidity after liver transplantation.
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Adolescent↗
Liver transplantation in patients with patent splenorenal shunts.
Patent distal splenorenal shunts (Warren shunt) have been reported to cause decreases in the portal perfusion pressure and the total hepatic blood flow. Such hemodynamic alterations could have adverse effects on the transplanted liver. The experience with hepatic replacement in four patients with patent Warren shunts is reported. Operative findings were phlebosclerotic portal veins of small size and diminished portal blood flows. Hepatofugal collateral channels created by the construction of the Warren shunt were eliminated by division of the shunt and splenectomy in three patients and splenectomy alone in the other. All patients recovered; thus the presence of a patent Warren shunt should not be a contraindication for hepatic transplantation.
Adult↗
Functional characterization of infiltrating T lymphocytes in human hepatic allografts.
We have employed recently developed techniques in T-cell culturing to study the nature and function of infiltrating hepatic allograft T cells. Using the rationale that intragraft T cells are activated during cell mediated damage to the allograft, we were able to show that these cells would propagate and remain functionally active in the presence of the T-cell growth factor, IL-2. In several instances, phenotypic analysis of cells grown in this manner was very similar to that found within the graft. Both proliferative and cytotoxic responses could be detected from the cultured cell lines. The majority of the proliferative responses were donor-directed and immunogenetic analysis could define donor-directed HLA reactivity, to either class I or class II antigens, or both. Monoclonal anti-HLA antibodies inhibition profiles verified the apparent HLA reactivity. In a smaller percentage of cases, only IL-2 responsiveness could be detected, and no HLA reactivity could be determined. Cytotoxicity could be detected against both class I and class II antigens, however, those cells which demonstrated a greater magnitude of donor-directed cytotoxicity appeared to be directed against class I antigens. A significant correlation between donor-directed proliferation of biopsy cultured lymphocytes and cellular rejection was found. This model appears to be useful in delineating functions of the intragraft T-cell population during rejection.
Adolescent↗
Indications for liver transplantation in the cyclosporine era.
One hundred seventy orthotopic liver transplants were performed under conventional immunosuppression with azathioprine and steroids with 1- and 5-year survivals of 32.9 per cent and 20.0 per cent, respectively. Since the introduction of cyclosporine-prednisone therapy in March 1980, 313 primary orthotopic liver transplants have been performed. Actuarial survivals at 1 and 5 years have improved to 69.7 per cent and 62.8 per cent, respectively. Biliary atresia is now the most common indication for liver replacement. In adults, primary biliary cirrhosis and sclerosing cholangitis have become more common indications for transplantation, and alcoholic cirrhosis and primary liver malignancy as indications have declined. Early enthusiasm for liver transplantation in patients with hepatic cancer has been tempered by the finding that recurrence is both common and rapid. An increasing number of patients with inborn errors of metabolism originating in the liver are receiving transplants, including patients with Wilson's disease, tyrosinemia, alpha-1-antitrypsin deficiency, glycogen storage disease, familial hypercholesterolemia, and hemochromatosis. Survival in this group of patients has been excellent (74.4 per cent at 1 and 5 years). A hemophiliac who received a transplant for postnecrotic cirrhosis has survived and may have been cured of his hemophilia. About 20 per cent of patients require retransplantation for rejection, technical failure, or primary graft failure. Only four of the patients receiving retransplants under conventional immunosuppression survived beyond 6 months, and all died within 14 months of retransplantation. Sixty-eight patients have received retransplants under cyclosporine-prednisone. Thirty-one patients are surviving, all for at least 1 year. Six of the twelve patients requiring a third transplant are alive 2 to 3 years after the primary operation. An aggressive approach to retransplantation in the patient with a failed graft is justified.
Adult↗
Development and organization of a multiple organ transplantation program.
Multiple organ transplantation has come of age. Indications are that it will continue to grow, if not flourish. The complexity of modern surgical care, its multiperson dependency, and the need for the surgeon to retain knowledge and involvement with his patient's care and problems are nowhere more evident than in multiple organ transplantation. Each organ presents its own associated challenges, the prime solution of which lies with a skillful and dedicated surgeon; but with all organs there are challenges of expectantly waiting patients, housing during the wait and for postoperative observation, procurement, erratic scheduling of the operating room, nursing, social service, immunosuppression, immunopathology, interest of hospital public relations and of the news media, and perennial care. This report concerns the growth and development of the multiple organ transplant program at the University Health Center of Pittsburgh and describes some answers to the challenges presented.
Academic Medical Centers↗
Liver transplantation in the ciclosporin era.
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Age Factors↗
Progression of neurovisceral storage disease with supranuclear ophthalmoplegia following orthotopic liver transplantation.
A 7-year-old girl with progressive ataxia, spasticity, supranuclear ophthalmoplegia, and sea-blue histiocytes in her bone marrow underwent orthotopic liver transplantation for hepatocellular carcinoma. After an initial period of stabilization, she has shown progression of neurologic symptoms with recurrence of storage material in the transplanted liver.
Carcinoma, Hepatocellular↗
Treatment of fibrolamellar hepatoma with partial or total hepatectomy and transplantation of the liver.
Fourteen patients with fibrolamellar hepatoma were treated with radical excision. In eight, a subtotal hepatic resection was performed from 16 months to more than 16 years ago. None of the patients have died and recurrences have been seen in only one patient. Six other patients had total hepatectomy and hepatic replacement. Two of these six patients have died of metastases and a third is living with recurrent tumor. This experience has justified the continuing use of quite aggressive extirpative procedures for the treatment of fibrolamellar hepatoma.
Adolescent↗
Liver transplantation across ABO blood groups.
Six hundred seventy-one first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of donor-recipient mismatches or incompatibilities for the ABO blood groups on graft survival. A significant advantage for ABO donor-recipient identity was found, especially in adults and for first grafts. However, a surprisingly large number of ABO incompatible grafts were successful. We recommend that nonidentical or incompatible grafts be limited to patients such as small children for whom the supply of available donors is severely limited or for patients in urgent need of transplantation or retransplantation.
ABO Blood-Group System↗
The antibody crossmatch in liver transplantation.
Six hundred sixty-seven first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of recipient panel-reactive antibody (PRA) and donor-recipient antibody crossmatch on 2-year patient and liver allograft survival rates. Neither a high panel-reactive antibody nor a positive crossmatch for donor-specific preformed antibody was associated with decreased patient or liver allograft survival for primary grafts or retransplants. Two patients have been given kidney transplants immediately after a liver allograft from a donor with whom each patient had an initial strongly positive donor-specific antibody crossmatch. The liver apparently removed or neutralized circulating anti-donor antibody, since the renal allografts functioned promptly and did not experience hyperacute rejection.
Actuarial Analysis↗
Recurrent hepatitis B in liver allograft recipients. Differentiation between viral hepatitis B and rejection.
The histologic findings in the original liver obtained from 9 liver allograft patients with active B virus hepatitis were compared with 28 posttransplant pathology specimens. All specimens were studied with the use of light and immunohistochemical microscopy in conjunction with pertinent clinical data. Eight of the 9 patients had chronic active hepatitis B (HB) with cirrhosis, prior to transplant, one of which had coexistent hepatocellular carcinoma. The ninth patient had fulminant hepatic necrosis secondary to acute HB prior to transplantation. In all of the patients with chronic HB prior to transplantation who survived more than 2 months after transplantation recurrent infection of the graft developed despite perioperative HB immunoglobulin therapy. The patient with acute fulminant hepatitis B pretransplant has done well postoperatively and has evidence of HB virus immunity (positive anti-HBs) 15 months after transplantation. Examination of tissue specimens obtained during episodes of allograft dysfunction in these 9 patients indicate that pathologic alterations of active HB infection of the allograft are associated with a preferential lobular insult, whereas those occurring in rejection preferentially involve portal tract structures. Serologic data combined with biopsy histopathologic data are essential in distinguishing between the two quite different events.
Diagnosis, Differential↗
Cyclosporine pharmacokinetic profiles in liver, heart, and kidney transplant patients as determined by high-performance liquid chromatography.
Cs pharmacokinetic profiles using HPLC have aided in predicting necessary dosage alterations for specific groups of transplant patients. Additional information has been gained by HPLC profiles in nontransplant subjects who are healthy or have a stable disease state. The clinician now knows that liver disease not only impairs Cs elimination but may also have a pronounced effect upon drug absorption. While the cardiac failure patient may have reversible inhibition of Cs clearance, other factors may affect the distribution of the drug to lower dosage requirements. Impaired renal function is not an impediment to Cs elimination, but malabsorption similar to that observed in liver and bone marrow transplant patients may still occasionally complicate therapy. Pharmacokinetic information on Cs must be integrated into the complex care plan of a transplant patient to optimally utilize and monitor this pharmacologic agent.
Adult↗
Cyclosporine trough concentration monitoring in liver transplant patients.
Trough blood or plasma concentration measurements of CsA must be carefully interpreted in OLT patients in relation to hepatic function, sample timing, assay specificity, and concurrent drug therapy. The RIA:HPLC ratio of blood or plasma measurements will vary with the patient's liver function, the time of blood sampling in reference to the time of drug administration, the absolute CsA concentration, and concurrent use of drugs that may alter the metabolism of CsA. The RIA assay should be used in conjunction with HPLC for trough blood or plasma measurement during the first postoperative weeks, during periods of changing hepatic function, and during changing drug regimens. In the future, the specific measurement of active or toxic metabolites of CsA should improve trough CsA concentration monitoring in OLT patients.
Chromatography, High Pressure Liquid↗
Liver resection for metastatic colorectal cancer.
From 1975 to 1985, 60 patients with isolated hepatic metastases from colorectal cancer were treated by 17 right trisegmentectomies, five left trisegmentectomies, 20 right lobectomies, seven left lobectomies, eight left lateral segmentectomies, and three nonanatomic wedge resections. The 1-month operative mortality rate was 0%. One- to 5-year actuarial survival rates of the 60 patients were 95%, 72%, 53%, 45%, and 45%, respectively. The survival rate after liver resection was the same when solitary lesions were compared with multiple lesions. However, none of the seven patients with four or more lesions survived 3 years. The interval after colorectal resection did not influence the survival rate after liver resection, and survival rates did not differ statistically when synchronous metastases were compared with metachronous tumors. A significant survival advantage of patients with Dukes' B primary lesions was noted when compared with Dukes' C and D lesions. The pattern of tumor recurrence after liver resection appeared to be systemic rather than hepatic. The patients who received systemic chemotherapy before clinical evidence of tumor recurrence after liver resection survived longer than those who did not.
Actuarial Analysis↗
Primary cancers of extrahepatic biliary passages.
We analyzed the records of 22 patients with cancers of extrahepatic biliary passages (EHBP) to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From our data, it is difficult to comment on the effectiveness of chemotherapy. We have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed.
Adenocarcinoma↗
Changing concepts: liver replacement for hereditary tyrosinemia and hepatoma.
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Adult↗