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Medline ® Abstracts for References 1-6

of 'Liver transplantation: Diagnosis of acute cellular rejection'

1
TI
Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure.
AU
Wiesner RH, Ludwig J, van Hoek B, Krom RA
SO
Hepatology. 1991;14(4 Pt 1):721.
 
Hepatic allograft rejection is presently classified into acute and chronic rejection based on histological features, timing and reversibility. However, because features of both types of rejection can occur at any time, and in many combinations, the terms "acute" and "chronic" seem inappropriate in some instances. Thus the term "cellular rejection" better defines the histological features of portal hepatitis, nonsuppurative destructive cholangitis and endotheliitis, which are independent of time and response to therapy. Similarly, because progressive bile duct destruction leading to a decrease in the number of interlobular and septal bile ducts is the major histological feature of "chronic rejection," the term "ductopenic rejection," defined as the loss of bile ducts in 50% or more of portal tracts independent of time and reversibility, seems more appropriate. The pathogenesis of cell-mediated rejection has not been completely explained; however, direct immunocytic attack on small bile ducts and small arteries appear to be the major feature. The process may lead to bile duct loss ("ductopenia"). The pathogenetic role of foam-cell arteritis resulting in ischemic bile duct injury and the role of humoral mechanisms in causing ductopenic rejection awaits further clarification. In the past, irreversible ductopenic rejection occurred in approximately 10% of all patients who underwent their first liver transplantation; this figure, however, appears to be decreasing. The clinical features of irreversible rejection include persistent and progressive cholestasis; rising serum levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase; and a decrease in hepatic synthetic function. Ductopenic rejection can occur early (2 to 5 wk after liver transplantation) but most often develops between 6 wk and 6 mo after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
AD
Division of Hepatology and Gastroenterology, Mayo Clinic, Rochester, Minnesota 55905.
PMID
2
TI
Rejection in liver transplantation.
AU
Klintmalm GB, Nery JR, Husberg BS, Gonwa TA, Tillery GW
SO
Hepatology. 1989;10(6):978.
 
One hundred four liver transplant recipients were retrospectively reviewed for the incidence of liver allograft rejection, the response to antirejection therapy and the impact of rejection on graft and patient survival. Liver biopsies were performed weekly during episodes of graft dysfunction and to follow response to treatment. Baseline immunosuppression consisted of cyclosporine and low-dose prednisolone. Rejection was treated with steroids and with OKT3 as rescue. Azathioprine was given to patients with preoperative or perioperative renal insufficiency and was added to patients' treatment after the first sign of rejection. Seven complications were observed in approximately 1,100 liver biopsies, only one necessitating surgery. We found that 39.4% of the patients never experienced acute rejection, and 60.6% had at least one episode of acute rejection. Overall, 42.3% of the patients had only one episode of acute rejection, 13.5% had two, 3.8% had three and 1% had five episodes of acute rejection. Sixty of 63 first acute rejection episodes occurred within 21 days of transplant. Primary disease, sex or patient age had no significant influence on the incidence of rejection. There was a lower incidence of rejection (p less than 0.005) in patients transplanted after October, 1986, despite lower mean cyclosporine levels. Mean cyclosporine level during the first postoperative month was 679 ng per ml vs. a mean level of 910 ng per ml prior to October, 1986, when the immunosuppressive protocol was altered. Antirejection therapy was very effective in that only two of the 63 patients had graft failure due to acute rejection. Both of these patients were subsequently retransplanted.(ABSTRACT TRUNCATED AT 250 WORDS)
AD
Department of Surgery, Baylor University Medical Center, Dallas, Texas 75246.
PMID
3
TI
Rejection in liver allograft recipients: Clinical characterization and management
AU
Emond JC, Thistlethwaite JR, Baker AL
SO
Clin Transpl. 1987; 1:143.
 
AD
4
TI
Infection and rejection of primary hepatic transplant in 93 consecutive patients treated with triple immunosuppressive therapy.
AU
Ascher NL, Stock PG, Bumgardner GL, Payne WD, Najarian JS
SO
Surg Gynecol Obstet. 1988;167(6):474.
 
Ninety-three consecutive patients who underwent primary orthotopic hepatic transplantation were treated, after transplantation, with prophylactic immunosuppressive therapy consisting of cyclosporine, prednisone and azathioprine. Weekly percutaneous biopsies were performed to diagnose rejection rapidly. Rejection was treated using a sequential multidrug therapeutic approach based on histologic findings. Mild rejection was initially treated with steroids; moderate to severe rejection was initially treated with steroids; moderate to severe rejection was treated with Minnesota antilymphoblast globulin (mALG) or OKT3 monoclonal antibody (Orthoclone, Ortho Pharmaceutical Corp.), or both. The one year actuarial survival rate for adults was 80 per cent and for children, 70 per cent. The incidence of biopsy-proved rejection was 75 per cent in adults and 80 per cent in children; however, the rejection was relatively easily reversed in both groups using biopsy-guided multimodal therapy. In 21 of 22 patients treated with steroids alone, rejection was reversed. Forty-one patients with moderate to severe rejection required treatment with mALG or OKT3, or both; in 38, rejection was resolved, and in three, chronic rejection required retransplantation. The incidence of bacterial, fungal and viral infections was high after transplantation and was further exacerbated by antirejection therapy requiring mALG Or OKT3, or both. Although the rate of infections was high, most were easily treated with antimicrobial agents. Thus, triple drug immunoprophylaxis followed by biopsy-guided antirejection therapy provided effected treatment of rejection without promoting fatal infections.
AD
Department of Surgery, University of Minnesota, Minneapolis.
PMID
5
TI
A histometric analysis of chronically rejected human liver allografts: insights into the mechanisms of bile duct loss: direct immunologic and ischemic factors.
AU
Oguma S, Belle S, Starzl TE, Demetris AJ
SO
Hepatology. 1989;9(2):204.
 
Conspicuous pathologic features of chronic liver allograft rejection include bile duct loss and chronic obliterative arteriopathy. A quantitative histometric analysis was performed to document the extent of bile duct loss, the size of the "vanished" ducts and the extent of chronic obliterative arteriopathy and to determine whether there was any relationship between chronic obliterative arteriopathy and bile duct loss. All failed liver allograft specimens with chronic rejection were reviewed and categorized according to the degree of chronic obliterative arteriopathy, assessed by the degree of luminal narrowing of hilar hepatic artery branches. Histometric analysis of the grafts revealed: (i) there was a loss of small portal arterioles (less than 35 microns); (ii) bile ducts which should accompany arteries less than 35, 35 to 54 or 55 to 74 microns in diameter were missing, with the greatest decrease occurring among the smallest ducts; (iii) bile duct loss was seen in the absence of significant large vessel chronic obliterative arteriopathy, and (iv) the severity of arteriole and bile duct loss, as well as the size of the vanished ducts, was directly proportional to the degree of chronic obliterative arteriopathy. Furthermore, the size of the "vanished" bile ducts in liver allografts appeared to differ from the size of ducts destroyed in primary biliarycirrhosis. These studies offer indirect, but suggestive proof that two mechanisms are operative in the bile duct loss seen in chronic rejection: direct lymphocytotoxicity and ischemic damage.
AD
Department of Pathology, Presbyterian University Hospital, Pittsburgh, Pennsylvania 15213.
PMID
6
TI
The first 100 liver transplantations at the Mayo Clinic.
AU
Krom RA, Wiesner RH, Rettke SR, Ludwig J, Southorn PA, Hermans PE, Taswell HF
SO
Mayo Clin Proc. 1989;64(1):84.
 
Between March 1985 and June 1987, the first 100 liver transplantations at the Mayo Clinic were performed in 83 patients (primarily adults). The most frequent diagnoses were chronic active hepatitis (in 24 patients), primary sclerosing cholangitis (in 22), and primary biliary cirrhosis (in 20). The median operating time was 406 minutes, and the median usage of erythrocytes was 13.2 units. A venovenous bypass was used in all patients older than 10 years of age. Hepatic artery thrombosis occurred in 10% of the 100 transplants. A choledochocholedochostomy was done in 58 patients and a choledochojejunostomy in 25 patients. Revision of the biliary anastomosis was necessary in 9 of the 83 patients (11%). Rejection, diagnosed by clinical and histologic criteria, occurred in 50 patients (60%) and was treated with a corticosteroid bolus, followed by OKT3 (monoclonal antibody) treatment if necessary. Selective bowel decontamination helped prevent infections; only 16 bacteremias occurred, 1 of which was caused by a gram-negative organism. Fungal infections were rare. Cytomegalovirus infection occurred in 47 patients (57%). Of the 83 patients, 16 required retransplantation, in 11 of whom graft rejection had occurred. One- and 2-year patient survival was 83% and 70%, respectively. Although problems still remain, liver transplantation is a reasonable option for patients with end-stage liver disease.
AD
Section of Transplantation Surgery, Mayo Clinic.
PMID