Relationship Between the Diagnosis, Preoperative Evaluation, and Prognosis After Orthotopic Liver Transplantation (original) (raw)
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Hepatology, 1986
Twenty-seven clinical and laboratory data and the subsequent clinical course of 93 consecutive adult patients who underwent orthotopic liver transplantation for various chronic advanced liver diseases were analyzed retrospectively to assess the risk factors of early major bacterial infection and death after the procedure. Forty-one patients (44%) had early major bacterial infection during hospitalization for orthotopic liver transplantation. The mortality rate was 70.7% in patients with early major bacterial infection and was 7.7% in patients without early major bacterial infection (p < 0.001). Total serum bilirubin, total white blood cell count and polymorphonuclear cell count, IgG (all p < 0.05) and plasma creatinine level (p < 0.001) were higher in patients that developed early major bacterial infection than in those who did not. By step-wise discriminant analysis, the strongest risk factor for early major bacterial infection was the serum creatinine level, which achieved an accuracy of 69% for a creatinine level greater than 1.58 mg per dl.
Grading of cellular rejection after orthotopic liver transplantation
Hepatology, 1995
All 684 post-orthotopic liver transplantation (OLT) liver biopsies performed at the Royal Free Hospital (RFH) between 1988 and 1993, from 120 patients, were reviewed in order to try to define the relative importance of the histological features of immunosuppressionresponsive cellular rejection. Twenty histological features considered to be possible contributors to the diagnosis of cellular rejection were documented in a binary (present/absent) fashion. These features in 106 biopsy specimens obtained 1 to 8 days after OLT were analyzed using stepwise logistic discriminant analysis. All clinical and treatment records were reviewed, and each biopsy specimen was assigned to a diagnostic category depending on these records and follow-up information. Important determinants of the histological diagnosis of cellular rejection (which occurred in 84 of the 106 cases) were moderate/severe mixed portal inflammation, eosinophils, endotheliitis, and bile duct damage. When these all occurred together, the odds of rejection increased 3.6-fold. The original histological diagnosis was recorded, and each biopsy specimen showing cellular rejection was regraded according to the specific criteria of Snover et al., Demetris et al., and a novel RFH scoring system. The latter consists of evaluating portal inflammation, endotheliitis, eosinophils, and bile duct damage, each on a 0 to 3 scale (none, mild, moderate, or severe, respectively) and summation. The resulting cellular rejection score thus can range from 0 to 12. The agreement between the different scoring systems was analyzed using K statistics, and there was good concordance (K, 0.64 to 0.78), despite different histological criteria being used to derive each score. Each system showed a similar degree of sensitivity (87% to 96%). The specificity ranged from 59% to 77%. We conclude that the histological diagnosis of cellular rejection relies mainly on the previously described features of mixed portal inflammation, endotheliitis, eosinophils, and duct damage. There is scope for unification and simplification of the existing grading systems, which depend on differing criteria, and we suggest one such scheme. (Hepatology 1995;21:46–57).
…, 1997
ALT values are not useful in the assessment of PI. Eighty liver allografts were studied to determine the (HEPATOLOGY 1997;25:184-189.) predictive value of intraoperative biopsies and postoperative liver function tests for the development of preservation injury (PI). Peak transaminase (aspartate transaminase [AST] and alanine transaminase [ALT]) Graft viability is of the utmost importance for successful and prothrombin time (PT) values achieved by each paorthotopic liver transplantation. Virtually all liver allografts tient during postoperative days (POD) 1 through 7 were are injured during transplantation, either as a result of determined. PI in day 0 preperfusion biopsies (0Pre) (obevents leading to donor death, donor life support, or during tained immediately before implantation) and postperfuthe process of allograft extraction, cold preservation, implansion biopsies (0Post) (obtained immediately after revastation, hypoxic rewarming, and reperfusion. Allograft injury cularization) was categorized by histological criteria as resulting from the transplantation process is commonly represent or absent. PI in biopsies taken during POD 2 ferred to as preservation injury (PI). Preservation injury is through 14 was histologically graded as either moderatea major contributor to primary allograft dysfunction, a term to-severe, mild, or absent. Of the 80 allografts, 8 were encompassing both primary nonfunction, defined as complete omitted because of primary nonfunction or postoperaallograft failure in the absence of apparent technical or imtive complications. 0Pre and 0Post biopsies were availmunologic complications, and initial poor function (IPF), deable on 25 of 72 (35%) and 69 of 72 (96%) allografts, respecfined as borderline graft function immediately after transtively. Only 2 (8%) of the 0Pre biopsies showed plantation. histological PI compared with 48 (70%) of the 0Post biop-Several studies have attempted to identify donor, intraopsies. Fifty-nine patients were biopsied between POD 2 erative, and recipient factors predictive of primary allograft through 14. Of these, 15, 28, and 16 patients developed dysfunction. Primary dysfunction has been consistently assomoderate-to-severe, mild, or no evidence of PI, respecciated with prolonged cold and warm ischemia, severe macrotively. The presence of PI in the 0Post biopsy strongly vesicular steatosis, ABO blood group incompatibility, and docorrelated with the development of PI during POD 2 nor age over 50 years. 1-12 Additional risk factors include through 14 (P õ .0005). Peak AST and ALT values in retransplantation, markedly elevated donor transaminase patients with moderate-to-severe PI on POD 2 through levels, the use of pressors in the donor, and the use of re-14 were significantly elevated compared with those paduced-size liver grafts. 1-12 Despite efforts to avoid using donor tients with either mild (P Å .01 and .03) or no PI (P Å .02 organs with these and other potentially adverse variables, and .006). Because of extensive overlap in AST and ALT primary allograft dysfunction continues to occur. 9-11 It would values between the three groups, however, transamibe clinically useful to determine prospectively which patients nase values were not useful in predicting the presence were at increased risk for the development of PI. or absence of PI in the individual case. The development To date, no single test has proven clinically effective for the of PI during POD 2 through 14 correlated with advanced prediction of primary dysfunction. Histological assessment of donor age (P Å .06) but was unassociated with 0Pre biintraoperative allograft biopsy specimens should accurately opsy findings, cold ischemia time, or peak PT values. We predict the presence of preexisting disease or PI in the organ conclude that the 0Post biopsy is a valuable tool for the itself, yet few studies have carefully examined this variable. prediction of subsequent PI in the early postoperative Kakizoe et al. reported that the presence of zonal or severe period. In contrast, 0Pre biopsy findings and peak AST focal necrosis and severe neutrophilic inflammation in biopsy specimens taken after reperfusion was predictive of postoperative IPF. 8 These and other studies, however, defined IPF on Abbreviations: PI, preservation injury; IPF, initial poor function; ALT, alanine transamithe basis of elevated liver function tests alone. 1,6,8,10,11 Benase; AST, aspartate transaminase; PT, prothrombin time; POD, postoperative day; 0Post, cause elevated liver function tests following transplantation liver allograft biopsy obtained after revascularization and reperfusion of the allograft; 0Pre, may result from complications other than PI (e.g., infection, liver allograft biopsy obtained on day 0 after cold preservation but before reperfusion. From the Departments of 1 Pathology, 2 Internal Medicine, and 3 Transplantation Surgery, early acute cellular rejection, and hepatic artery thrombosis),
UCLA Liver Transplantation: Analysis of Immunological Factors Affecting Outcome
Artificial Organs, 2008
From 1988 to 1993, UCLA completed 938 first and 1,146 total orthotopic liver transplants (OLT). Race analysis demonstrated a I-year patient survival of 89% in Blacks ( n = 45) versus 80% in Whites (n = 492, p < 0.02), with no significant difference shown between Hispanics (n = 278) and Whites. The I-year patient survival in Asians was 50% (n = 58, p < 0.02 vs. Whites) even when hepatitis B was excluded (59%, n = 43). The I-year patient survival of hepatitis B surface antigen positive Asians (n = 15) was only 21% (p < 0.02 vs. all others). OLT patients whose panel reactive antibody (PRA) was
Hepatology, 1984
The histopathological features of orthotopic liver transplants were evaluated in 63 serial biopsy specimens from 17 patients. Biopsies were taken at the time of insertion of the liver (six biopsies), at the time of development of liver function abnormalities (11 biopsies) and as follow-up to previously abnormal biopsies (46 biopsies). The biopsies taken at the time of insertion all showed diffuse hepatocellular ballooning with confluent areas of necrosis in one case. Biopsies taken at the time of onset of rejection (nine cases) all showed a mixed portal inflammatory infiltrate, bile duct damage and central or portal vein endothelialitis (i.e., attachment of lymphocytes to the vein endothelium). Follow-up biopsies showed several patterns including: (i) resolution of changes of acute rejection with subsequent development of recurrent acute or chronic rejection (four cases); (ii) prolonged acute rejection simulating extrahepatic biliary obstruction (four cases); (iii) prolonged acute rejection with predominance of eosinophils simulating a drug reaction (one case); and (iv) rapidly progressive acute rejection leading to death (one case). Biopsy of the transplanted liver at the time of transplantation is useful to provide a baseline for comparison with later biopsies. Biopsy at the time of onset of changes in liver function is essential to confirm the presence of rejection prior to alteration of immunosuppression.
Experimental and Clinical Transplantation, 2022
Orthotopic liver transplantation is the treatment of choice for several otherwise irreversible forms of acute and chronic liver diseases. Early implemented immunosuppressant regimens have had disappointing results with high rejection rates. However, new drugs have reduced the daily immunosuppression requirements, thereby improving graft and patient survival as well as kidney function. Liver rejection is a T-cell-driven immune response and is the active target of immunosuppressive agents. Immunosuppressants can be divided into pharmacological or biological drugs: the gold standard is the calcineurin inhibitors, steroids, mycophenolate mofetil, and mechanistic target of rapamycin inhibitors. Compliance with these agents is essential, although they can increase the risk of infections and neoplastic diseases. In some patients, graft tolerance can be achieved. Graft tolerance is defined as the absence of acute and chronic rejection in a graft, with normal function and histology in an immunosuppression-free, fully immunocompetent host, usually as the final result of a successful attempt at immunosuppression withdrawal. The occurrence of immunosuppressive-related complications has led to new protocols aimed at protecting renal function and preventing de novo cancer and dysmetabolic syndrome. The backbone of immunosuppression remains calcineurin inhibitors in association with other drugs, mainly over the short-term period. To avoid rejection and the side effects on renal dysfunction, de novo cancer, and cardiovascular syndrome, optimal long-term immunosuppressive therapy should be tailored in liver transplant recipients.
Medical Aspects of Liver Transplantation
Hepatology, 1984
The methods used to screen prospective candidates for orthotopic liver transplantation are described. Both the indication and the contraindications for the procedure are discussed. The timing of the procedure during the course of an individual candidate's liver disease is also discussed. Additionally, the institutional requirements of a liver transplant center are identified. Finally, the problems experienced by a liver transplant patient and his physician during the postoperative period are identified and discussed.