Orthotopic Liver Transplantation: A Pathological Study of 63 Serial Liver Biopsies from 17 Patients with Special Reference to the Diagnostic Features and Natural History of Rejection (original) (raw)
Related papers
Transplantation Proceedings, 2006
Introduction. Acute hepatic allograft rejection remains an important problem following liver transplantation. Liver biopsy specimens show a combination of characteristic changes, first observed by Snover as a diagnostic triad: portal inflammation, bile duct damage, and central or portal vein endothelial inflammation (endothelitis or endothelialitis). The aim of this study was to describe our histopathological assessment of liver transplants. Materials and methods. In the period between September 2000 and June 2004, we evaluated 150 liver biopsy specimens from 105 liver recipients. Results. Acute rejection was diagnosed in 26.6% of liver biopsies taken from 31.4% patients who demonstrated clinical symptoms of liver damage. In 90% of cases the rejection was described as minimal or mild, and in 10% as moderate. There was no episode of severe acute rejection. Only four biopsies (10%) showed nothing but Snover triad changes. In 9 (22.5%) cases only acute rejection was diagnosed; the remaining showed in addition to acute rejection the possibility of other concomitant pathologies: viral infection in 15 cases (37.5%), biliary flow obstruction in 11 cases (28.5%), functional cholestasis in two cases (5%), and ischemic complications in three cases (7.5%). Conclusions. Histologically confirmed acute rejection episodes were diagnosed in 14.9% liver recipients. Liver biopsy specimens, aside from Snover triad features, often showed other unspecific morphological changes. Differentiation of acute rejection from other accompanying diseases is sometimes difficult, requiring precise clinical data and pathologist experience.
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).
Clinical and pathologic observations after orthotopic transplantation of the human liver
Surgery, gynecology & obstetrics, 1969
ALTHOUGH all of the first attempts at orthotopic liver transplantation in man resulted in the early death of the recipient, after 23 days or less, the experience gained since the summer of 1967 has established the fact that this procedure can prolong life in patients dying of hepatic disease (10,12,13). Nevertheless, the operation has proved to be an exceptionally hazardous one, not only because of technical difficulties in its performance but also because of a number of complications which have been seen later. In this article, attention will be directed to these unsatisfactory aspects of orthotopic liver transplantation, to a consideration of how improvements might be made, and to a description of the histologic features of hepatic homografts, studied from a few hours to more than a year postoperatively. CLINICAL OBSERVATIONS Survival Statistics Since 23 July 1967, 14 patients have undergone orthotopic liver transplantation. Five of the recipients are still alive after eight and one-half, seven, six, five, and three months. The other recipients died one-half, one, four, 35, 60, 105, 133, 186, and 400 days postoperatively. Recurrent Carcinoma The four patients in whom the indication for transplantation was hepatoma all survived operation and had at least a brief period of untroubled convalescence. The tumor was thought, in advance, to be confined to the liver in each instance. One of the recipients, a 24 year old woman, died 35 days postoperatively of pneumonitis caused by Pseudomonas aeruginosa. At autopsy, metastases were not detectable.
Adult liver transplantation: An analysis of the early causes of death in 40 consecutive cases
Hepatology, 1986
One hundred twenty-nine adult patients who received an orthotopic liver transplantation and survived at least 24 hr after surgery were evaluated. During the period of follow-up, 48 of the 129 patients (37%) died. Only 40 of these 48 patients died at our institution and were included in this study. Seventeen of the 40 deaths (42.5%) occurred during the first month after orthotopic liver transplantation and 30 of the 40 deaths (75%) occurred during the first 60 days post-orthotopic liver transplantation. Death was related to infection in 21 cases (52.5%), to multiorgan failure in 8 (20%) and to uncontrollable rejection in 3 (7.6%). The remaining eight deaths (20%) were attributed to a variety of other causes. Eleven of the 21 deaths related to infection (52%) occurred during the first month after orthotopic liver transplantation. Bacterial sepsis was the leading cause of death and accounted for 17 of the 21 deaths (81 %) in which infection was present at the time of death. The most frequently isolated bacteria were Pseudomonas and other enteric Gram-negative bacilli. Three patients had complete occlusion of the hepatic artery of the grafted liver. Six patients developed massive infarction of the liver despite patent vascular anastomoses. Histological signs of rejection were seen in 9 of the 31 patients autopsied (29 %), but in only 3 of these (9.6%) was rejection the principal cause of death. The biliary anastomoses were patent in all 31 cases examined at autopsy.
Histopathology of Post-Transplant Liver Biopsies, the First Report From Iran
Hepatitis Monthly, 2013
Background: Evaluation of a transplanted liver by Imaging techniques and enzyme changes is sensitive to hepatocellular or biliary problems, but in most instances liver allograft biopsies are performed in order to find out the final reason for these changes. Objectives: It's been about 17 years (with more than 1326 cases) since the first liver transplantation in the Namazi Hospital of Shiraz University of Medical Sciences while during the last five years the number of post liver transplant biopsies have increased. Until now there has been no report of the pathological results of post liver transplant needle biopsies from Iran. Materials and Methods: During the last 5 years, there have been 382 post liver transplant biopsies. We studied the clinical charts and pathological results of all needle biopsies. Results: A total of 382 needle biopsies were performed on 287 patients aged between 1 and 64 years old. The earliest specimen was obtained within the first few hours following transplantation, and the last was gathered 3209 days (261 ± 523) post-transplantation. Acute rejection was the most common diagnosis, which occurred in 180 (47%) of specimens. Among other complications were vascular problems (8.6%), preservation/reperfusion (I/R) injury (7%), chronic rejection (5.2%), biliary injury/obstruction (3.4%), recurrence of primary disease (2.6%), druginduced hepatic injury (1.8%), cirrhosis (1.6%), sepsis (1.4%), cytomegalovirus hepatitis (1.4%), post-transplantation lymphoproliferative disease (1%) and Venous outflow obstruction (0.5%). Conclusions: The most common pathological diagnosis of post-transplant liver needle biopsies has been acute rejection, followed by ischemia due to hepatic artery thrombosis, preservation/reperfusion injury, and chronic rejection.
Transplantation Proceedings, 2008
Background and Aim. Histopathologic differential diagnosis of acute cellular rejection (ACR) and cholangitis continue to pose important problems following liver transplantation. The purpose of the present study was to evaluate the histopathologic features of ACR versus cholangitis. Methods. The following variables were evaluated among 36 hepatic allograft biopsy specimens, consisting of 21 with ACR (group 1) and 15 with cholangitis (group 2) for ductal neutrophilic infiltration, presence/density of portal eosinophilia, centrilobular necrosis, central/portal vein endothelialitis, pericentral inflammation, hepatocyte ballooning, hepatocanalicular/ductular cholestasis, hepatocyte apoptosis, lobular inflammation, ductular proliferation, periductal fibrosis/edema, ductular epithelial damage, and portal inflammation. Only the first biopsy samples of the ACR group were included in this study.
Orthotopic liver transplantation in ninety-three patients
PubMed, 1976
During the 11 1/2 year period ending 13 months ago, 93 consecutive patients were treated with orthotopic liver transplantation. Fifty-six of the recipients were 18 years old or younger, and the other 37 were adults. The most common indications for operation were biliary atresia, primary hepatic malignant tumor, chronic aggressive hepatitis and alcoholic cirrhosis. There has been a gradual improvement in results throughout the period of study, although to a satisfactory level. Twenty-seven of the 93 patients survived for at least one year after liver replacement with a maximum of six years, and 16 are still alive after 13 to 71 months. The 11 late deaths after one to six years were caused by chronic rejection, biliary obstruction, recurrence of hepatoma, systemic infection or hepatitis of the homograft. Rejection of the liver as judged by classical histopathologic criteria played a surprisingly small role in the heavy over-all mortality, accounting for less than 10 per cent of the deaths. Technical or mechanical problems, especially those of biliary duct reconstruction, were a far greater cause of failure, as were systemic infections. Six of the 37 adult recipients had lethal cerebrovascular accidents during, or just after, operation. When abnormalities of liver function developed in the postoperative period, the nearly automatic diagnosis of homograft rejection, in retrospect, proved to have been wrong in most instances. Further development of liver transplantation depends upon two kinds of progress. There must be reduction of operative and early postoperative accidents and complications by more discriminating patient selection, purely technical improvement and better standardization of biliary duct reconstruction. The second area will be in sharpening the criteria for the differnetial diagnosis of postoperative hepatic malfunction, including the liberal use of transhepatic cholangiography and needle biopsy. Only then can better decisions be made about changes in medication or about the need for secondary corrective surgical procedures.
Annals of Surgery, 1988
The purpose of this study was to identify which of the biochemical, immunological, or functional parameters derived before surgery as part of a systemic evaluation were helpful in predicting the frequency of rejection episodes, the chance of survival, and the cause risk of death (should death occur) of patients after orthotopic liver transplantation (OLTx). Ninetyeight adult patients who had an extensive preoperative protocol evaluation were studied before OLTx. The biochemical parameters assessed were albumin, prothrombin time, bilirubin, and ICG clearance. The immunologic parameters assessed included total lymphocytes, T3 cells, T4 cells, T8 cells, and the T4/18 ratio. The degree of histocompatibility antigen