Hepatic Allograft Research Articles

Quantitative Doppler flowmetry of the portal vein in hepatic allografts: initial results in animal and human subjects

Early detection of hepatic allograft injury is essential to ensure graft viability and to minimize patient morbidity. The hepatic microvasculature is adversely affected in ischemic preservation injury and rejection, resulting in diminished sinusoidal blood flow. We investigated whether portal vein volume flow as determined by Doppler ultrasound could provide an index of graft function. In an animal model for ischemic preservation injury we found significantly reduced portal flow in animals with allograft injury. No significant difference in flow volume was demonstrated between normally functioning allografts and non-operated controls. We have evaluated 42 human patients with hepatic allografts. In patients with normally functioning livers (n = 17), mean portal vein flow (Q) was 1659 ± 524 ml/min. Patients with chronic rejection (n = 3) demonstrated markedly reduced flow (Q = 788 ± 109 ml/min; p < 0.001), similar to that seen in cirrhotic patients undergoing preoperative evaluation for liver transplantation (Q = 668 ± 256 ml/min). Patients with acute rejection demonstrated a wide variance in flow rates. Portal flow volumes < 1050 ml/min were associated with greater long term morbidity than those with greater flow volume. Quantitative doppler flowmetry of the portal vein is a promising new non-invasive technique which may provide a unique physiologic indicator of allograft perfusion.

Lack of association between cytomegalovirus infection, HLA matching and the vanishing bile duct syndrome after liver transplantation.

In this study we evaluated the association between cytomegalovirus infection alone or in relation to human leukocyte antigen matching and the development of vanishing bile duct syndrome, a form of chronic hepatic allograft rejection. A total of 81 consecutive liver transplant recipients were studied. Cytomegalovirus infection developed in 46 recipients (57%), and vanishing bile duct syndrome occurred in 9 recipients (11%). Cytomegalovirus infection developed in only five of the nine patients with vanishing bile duct syndrome. Univariate analysis of pretransplant recipient/donor cytomegalovirus serological tests and human leukocyte antigen typing showed they were not significant risk factors for the development of vanishing bile duct syndrome. Time-dependent analysis of cytomegalovirus infection after transplantation as a risk factor for vanishing bile duct syndrome, in a multivariate analysis with human leukocyte antigen match, showed no statistical significance. In our study, no association was found between cytomegalovirus infection alone or in relation to class I or II human leukocyte antigen match and the subsequent development of vanishing bile duct syndrome.

Altered zonal expression of the CD26 antigen (dipeptidyl peptidase IV) in human cirrhotic liver.

Dipeptidyl peptidase IV is a cell surface ectopeptidase with widespread tissue distribution. Recently it was shown to display extracellular matrix-binding properties; therefore its role in cirrhosis is of interest. The aim of this study was to use monoclonal antibodies directed against the human CD26 antigen (which has been shown to be dipeptidyl peptidase IV) to study the distribution of this molecule in normal human and cirrhotic liver. Identical staining was obtained with the three monoclonal antibodies (TaI, 1F7 and TS145) and enzyme histochemistry. In normal liver (n = 11) intense staining of hepatic acinar zones 2 and 3 was present, but little staining was seen in zone I. Hepatocyte staining was confined to the bile canalicular domain. In cirrhotic livers (n = 23) obtained at transplantation, staining of regenerating nodules without a zonal pattern was present. In addition, we saw staining of the lymphoid cell infiltrate and proliferating bile ductules. In a minority of cirrhotic biopsy specimens (four) staining of the basolateral hepatocyte domain in regenerating nodules was seen. Biopsy specimens from hepatic allografts (n = 28) were used as disease controls. These samples all showed preferential staining of zones 2 and 3, similar to that in normal biopsy specimens. Eleven of these samples showed staining of the basolateral and bile canalicular domains. In conclusion, the normal acinar distribution of dipeptidyl peptidase IV (zones 2 and 3) is lost in cirrhotic nodules. Furthermore, the altered membrane distribution of this molecule in cirrhosis and allograft rejection may allow increased hepatocyte extracellular matrix interactions during organ remodeling.

Cytomegalovirus infection and disease after liver transplantation. An overview.

Cytomegalovirus is the single most important pathogen in clinical transplantation. Although much progress has been made in our understanding of the molecular biology and epidemiology of CMV infection and in our ability to diagnosis and treat CMV disease, it remains a major cause of morbidity but is no longer a major cause of mortality after liver transplantation. Risk factors for CMV disease after liver transplantation include donor and recipient serologic status, the use of antilymphocyte therapy, and retransplantation. CMV disease occurs early after transplantation, and the most frequent site of disease is the hepatic allograft. We have treated 79 patients with intravenous ganciclovir, with ultimate control of disease achieved in 69 patients (87.3%). Preliminary results using intravenous immunoglobulin and oral acyclovir for CMV prophylaxis in high-risk patients have been encouraging. In addition to producing clinical syndromes. CMV may have direct immunologic effects and is a marker of the net state of immunosuppression.

Immunologic mechanisms of hepatic allograft rejection.

Immunologic mechanisms of hepatic allograft rejection.

Terminology of hepatic allograft rejection (glossary).

Terminology of hepatic allograft rejection (glossary).

Complications of liver biopsy in liver transplant patients: Increased sepsis associated with choledochojejunostomy

We investigated the incidence and types of liver biopsy complications in our first 160 consecutive liver transplantations. A significant complication was identified by the need for therapeutic intervention (for example, hospitalization, transfusion, intravenous fluids, chest tube, surgery or antibiotic therapy). A total of 950 percutaneous hepatic allograft biopsies were performed in 136 patients (mean = 6.9 biopsies/graft; range = 1 to 29). A significant complication was reported after 17 (1.8%) liver biopsies in 13 (9.6%) patients. Bleeding complications occurred in 11 patients and serious infection developed in 6 patients, but all patients recovered with appropriate therapy. Of special interest was that five of six patients with infectious complications had undergone Roux-en-Y choledochojejunostomy as part of the transplantation operation. The incidence of infectious complications related to a series of biopsies was significantly greater in patients who underwent choledochojejunostomy (12.5%) than in patients who underwent duct-to-duct biliary anastomosis (1%) (p less than 0.01). Furthermore, all septic events in patients who underwent choledochojejunostomy were related to enteric organisms. This investigation reaffirms the safety and low incidence of complications related to percutaneous liver biopsy even in this unique patient population. However, we did identify a subgroup of patients with biliary-enteric anastomoses who appear to be at increased risk of septic complications after liver biopsy. Antibiotic prophylaxis at the time of liver biopsy may be appropriate in this high-risk subgroup to decrease the frequency of infectious complications.

Procoagulant activity and tumor necrosis factor in rat hepatic allograft rejection.

We used a model of rat hepatic allograft rejection to evaluate levels of procoagulant activity and tumor necrosis factor during acute cellular rejection. ACI livers were transplanted into Lewis rats, and Lewis-to-Lewis isografts and unoperated animals served as controls. Animals were killed on days 1, 2, 3, 4, 5, 6, 7 and 9. Splenic mononuclear cells were obtained by Ficoll-Hypaque gradients. Collagenase perfusion, metrizamide gradients and centrifugal elutriation were used to isolate Kupffer cells. Procoagulant activity assay of the splenic and Kupffer cells was done using a one-step clotting assay. Tumor necrosis factor was assayed using an L929 cytotoxicity assay. Histological evidence of acute rejection began on the 4th postoperative day, and rats died by the 9th or 10th postoperative day. Splenic procoagulant activity was significantly elevated in rejecting rats on day 4 and remained elevated until death. In contrast, Kupffer-cell procoagulant activity was elevated over controls by day 3 and remained significantly elevated until death. The tumor necrosis factor levels were elevated from day 1 and remained so until death. The data indicate that procoagulant activity is synthesized both by peripheral monocytes and locally by Kupffer cells and that procoagulant activity and tumor necrosis factor levels rise during hepatic allograft rejection. Because procoagulant activity and tumor necrosis factor mediate immune functions that are postulated to be important in acute rejection (immune cell adherence, vascular thrombosis and delayed-type hypersensitivity), these elevations may contribute to the pathogenesis of acute rejection.

Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure

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)

Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure

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)

Epstein-Barr virus and persistent graft dysfunction after liver transplantation

Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection.

A comparison of Collins and UW solutions for cold ischemic preservation of the rat liver

A new solution which can extend successful preservation times for hepatic allografts was recently developed at the University of Wisconsin (UW). To examine the mechanism of improved viability using this solution, we developed a model of orthotopic hepatic transplantation in the rat. As a baseline study, we compared parameters of viability of allografts preserved in Collins solution to those preserved in UW, including survival, bile output, peak AST, and allograft weight change during storage. Seventy-four rats were transplanted following storage in Collins solution and 70 rats were transplanted after storage in UW. Cold-storage time varied between 2 and 24 hr. The survival with preservation in UW was significantly better than that with Collins when storage time was greater than 2 hr. The preservation time for a viable organ using UW was greater than double that using Collins. The peak AST using UW was lower than that with Collins for cold ischemic times (CIT) up to 10 hr, with significance demonstrated at 5–6 and 7–8 hr when compared with Collins. Prolonged CIT resulted in an increase in liver weight with Collins-preserved livers and a decrease in weight with UW-preserved livers. Using a model of orthotopic liver transplantation in the rat, we demonstrated a doubling of preservation time when UW solution was substituted for Collins. Similar improvements in recipient survival and biochemical parameters of injury have been demonstrated in the canine model and in human clinical trials.

PGE 1 reduces injury in hepatic allografts following preservation

Prostaglandins of the E series have been shown to decrease renal and hepatic ischemic injury as well as improve hepatic function in patients with primary non-function following transplantation. We wished to determine the effect of prostaglandin E 1 (PGE 1) on hepatic allograft reperfusion injury in the isolated perfused rat liver (IPRL) model. Livers were harvested from adult male Sprague-Dawley rats and the bile duct, portal vein, and suprahepatic vena cava were cannulated. Control livers were placed immediately on the IPRL apparatus and perfused for 2 hr with a blood-Kreb's solution. Group A and B allografts were stored for 8 hr in heparinized lactated Ringer's solution at 4°C. Group A livers were then perfused with a PGE 1 infusion at 0.1 μg/kg/min while B livers received a placebo infusion of NS at the same rate. Temperature, pH, and inflow pressures were kept constant. Oxygen consumption, portal flow, and resistance were calculated for each group and found not to be statistically different. LDH, SGOT, superoxide anion (SOA), and bile flow were measured at 30-min intervals. At the end of the 2-hr perfusion, the placebo Group B ( N = 5) had LDH, SGOT, and SOA higher than those of either Group A ( N = 5) or control ( N = 4) livers. The difference between Group A and Group B was significant for SGOT and SOA ( P < 0.05). Bile flow was highest in the control group (24.2 ± 1.8 μl/g/30 min). Group A livers produced bile at a similar rate (19.1 ± 2.5 μl/g/30 min), while Group B bile rate was markedly reduced (11.2 ± 2.5 μl/g/30 min). The difference between Groups A and B was not significant ( P = 0.06). Histologically, allografts in Group B demonstrated cellular edema and pale staining while those in Group A showed normal hepatic architecture with no evidence of injury, comparable to those of control livers. In conclusion, PGE 1 infusion reduces hepatic injury following extended cold storage and reperfusion as determined by decreased SGOT, SOA, and preservation of hepatic architecture.

Eosinophil cationic protein's role in human hepatic allograft rejection

Although it is known that eosinophils consistently infiltrate rejecting human liver allografts, their function is unknown. Infiltrating eosinophils can release a cytotoxic substance, eosinophil cationic protein. Furthermore, eosinophil cationic protein may be identified in biopsy specimens using immunoperoxidase staining of an eosinophil cationic protein-specific monoclonal antibody. To study a possible effector role of eosinophils in rejecting liver allografts, 38 serial allograft biopsy specimens from 12 patients with acute rejection, 54 biopsy specimens from 11 patients with allograft dysfunction caused by other causes and 22 biopsy specimens from 8 patients without allograft dysfunction were stained for extracellular eosinophil cationic protein. In addition, the absolute blood eosinophil counts and the portal tract eosinophil percent of the total number of portal tract inflammatory cells were tabulated in these patients until 30 days after transplantation. The blood absolute eosinophil count, portal tract eosinophil percent and incidence of positive extracellular eosinophil cationic protein staining were significantly increased in patients with rejection compared with patients with dysfunction from other causes (p less than 0.05 to 0.005, t test). Furthermore, each of these parameters predicted rejection with excellent sensitivity (75% to 92%) and specificity (91% to 100%). Of patients with rejection, 59% had significant elevation of all three parameters before or during rejection, and 92% had at least two parameters elevated. Conversely, of the patients with dysfunction from other causes, 0% had elevations of any parameter. The recognized cytotoxic properties of eosinophil cationic protein and its almost exclusive presence, along with eosinophils in the blood and allograft biopsy specimens of patients during acute rejection, support the role of the eosinophil as an effector cell in tissue injury during acute liver allograft rejection.

Eosinophil cationic protein's role in human hepatic allograft rejection

Although it is known that eosinophils consistently infiltrate rejecting human liver allografts, their function is unknown. Infiltrating eosinophils can release a cytotoxic substance, eosinophil cationic protein. Furthermore, eosinophil cationic protein may be identified in biopsy specimens using immunoperoxidase staining of an eosinophil cationic protein-specific monoclonal antibody. To study a possible effector role of eosinophils in rejecting liver allografts, 38 serial allograft biopsy specimens from 12 patients with acute rejection, 54 biopsy specimens from 11 patients with allograft dysfunction caused by other causes and 22 biopsy specimens from 8 patients without allograft dysfunction were stained for extracellular eosinophil cationic protein. In addition, the absolute blood eosinophil counts and the portal tract eosinophil percent of the total number of portal tract inflammatory cells were tabulated in these patients until 30 days after transplantation. The blood absolute eosinophil count, portal tract eosinophil percent and incidence of positive extracellular eosinophil cationic protein staining were significantly increased in patients with rejection compared with patients with dysfunction from other causes (p < 0.05 to 0.005, t test). Furthermore, each of these parameters predicted rejection with excellent sensitivity (75% to 92%) and specificity (91% to 100%). Of patients with rejection, 59% had significant elevation of all three parameters before or during rejection, and 92% had at least two parameters elevated. Conversely, of the patients with dysfunction from other causes, 0% had elevations of any parameter. The recognized cytotoxic properties of eosinophil cationic protein and its almost exclusive presence, along with eosinophils in the blood and allograft biopsy specimens of patients during acute rejection, support the role of the eosinophil as an effector cell in tissue injury during acute liver allograft rejection. (HEPATOLOGY 1991;13:1117–1125.)

OKT3 THERAPY FOR HEPATIC ALLOGRAFT REJECTION

The clinical courses following OKT3 therapy for hepatic allograft rejection (HAR) in adults and children have not been individually defined. We have reviewed our experience with OKT3 therapy for HAR in adults and children to compare: (1) the initial response to OKT3 therapy, (2) the clinical course following OKT3 therapy, and (3) the antimurine antibody response and immunologic monitoring results. Children required OKT3 therapy more frequently than adults: fourteen courses of OKT3 therapy were required in 130 orthotopic liver transplants (OLT) in 108 adult patients, whereas nineteen courses of OKT3 therapy were required in 94 OLT in 78 children (P less than 0.02). Repeat OKT3 therapy was not required in adults--however, four of nineteen courses of OKT3 therapy in children were repeat OKT3 therapy for rejection. No differences existed between adult and pediatric treatment groups with respect to number of prior OLT procedures, previous graft loss to rejection, percentage of ABO-incompatible grafts, frequency of positive donor-recipient lymphocyte crossmatches, or time to first rejection. The initial response to OKT3 therapy (rapid reversal, delayed reversal, and failure) was remarkably similar in adults and children. However, nine of 13 (70%) children with clear evidence of response to OKT3 treatment experienced breakthrough rejection or early recurrent rejection, whereas none of 12 adults suffered breakthrough rejection or early recurrent rejection (P less than 0.01). Early recurrent rejection did not correlate with delayed reversal of rejection, early return of CD3+ cells by peripheral blood monitoring, or development of anti-OKT3 antibodies. All 4 courses of OKT3 retreatment in children were successful in reversing rejection, and breakthrough rejection and early recurrent rejection did not occur. Overall graft and patient survival in pediatric patients requiring OKT3 therapy (67% and 73%) was not different from that in adults (71% and 79%). Results obtained in one patient provide the first evidence that successful OKT3 retreatment of HAR can be achieved in the presence of preexisting idiotypic anti-OKT3 antibody. In conclusion, OKT3 therapy for HAR was required more frequently in children than in adults. The clinical outcome following OKT3 therapy for HAR also differs markedly, with early recurrent rejection and breakthrough rejection occurring more frequently in children.

Liver transplant biopsies with a biopsy gun.

The authors evaluated the safety and efficacy of a biopsy gun for performance of image-guided percutaneous biopsy of hepatic allografts in liver transplant recipients. Two hundred fifty-two liver biopsies were performed in 58 transplant recipients over a 27-month period by using this instrument with an 18-gauge needle. Major complications occurred in two of the 252 biopsies (0.8%): One hemopneumothorax necessitated drainage with a chest tube, and one hemorrhage necessitated transfusion. No patient required surgical exploration because of a complication of the biopsy. Specimens were adequate for accurate histopathologic diagnosis in 248 of 252 procedures (98.4%). The authors conclude that image-guided percutaneous biopsy of hepatic allografts with use of the biopsy gun is a safe and accurate method of obtaining hepatic tissue from liver transplant recipients for histopathologic analysis.

Epstein-Barr Virus Lymphoproliferative Disease Associated with Acquired Immunodeficiency

Epstein-Barr virus (EBV) lymphoproliferative disease is seen in patients with both congenital and acquired immunodeficiencies. Lymphoproliferative disease has been reported in 1 to 3% of renal transplant recipients. Most patients presented with solid tumor masses, rather than an infectious mononucleosis-like syndrome. About one third of cases had involvement of the renal allograft with tumor; the small intestine or central nervous system was also frequently affected. About half of the patients survived. The most frequent therapy used for survivors was decreasing the dose of immunosuppressive therapy and surgical resection of lymphoproliferative lesions. Compared with fatal cases, survivors more often had evidence of active EBV infection (primary or reactivated), received cyclosporine as the major immunosuppressive agent, had polyclonal lesions, and had B-cell hyperplasia rather than lymphoma. Lymphoproliferative disease has been described in 5 to 13% of heart transplant recipients. In our review, the cardiac allograft was not involved by disease in any patient; however, the lungs were involved in more than half of the cases. The soft tissues were frequent sites of lymphoproliferative disease. All patients had lymphoma or immunoblastic sarcoma on pathology and all had monoclonal lesions. While only 8% of patients survived, about half died from causes unrelated to lymphoproliferative disease. EBV lymphoproliferative disease has been reported in 9% of heart-lung transplant recipients. Most of the patients presented with pulmonary symptoms and the pulmonary allograft was involved in 80% of cases. The large and small intestine were frequently affected. About 60% of patients survived; survivors were treated with acyclovir and decreases in the dose of immunosuppressive drugs. Lymphoproliferative disease has been described in 2% of liver transplant recipients. In our review, the hepatic allograft was involved in one third of cases; the tonsils, kidneys, and small intestine were frequently affected. Half of the patients survived; survivors were most often treated with reduction in immunosuppressive therapy and surgical resection of lesions. Compared with fatal cases, survivors had fewer organs involved and fewer monoclonal lesions. Lymphoproliferative disease has been reported in 1 to 2% of bone marrow transplant recipients. Use of T-cell depleted bone marrow and infusion of anti-T-cell antibodies to prevent graft-versus-host disease increased the risk of EBV lymphoproliferative disease. In our review, the bone marrow was involved by lymphoproliferative disease in one third of cases; the liver, spleen, kidney, and lungs were frequently affected. About 16% of patients survived; 2 survivors were treated with infusions of monoclonal anti-B-cell antibodies and 1 received interferon alpha.(ABSTRACT TRUNCATED AT 400 WORDS)

Vascular complications after orthotopic liver transplantation

Over a 57-month period, we performed 430 orthotopic liver transplants in 372 patients. A total of 38 vascular complications were identified including hepatic artery thrombosis (n = 24), portal vein thrombosis (n = 6), combined hepatic artery thrombosis/portal vein thrombosis (n = 3), and hepatic artery rupture (n = 5). A number of potential risk factors for the development of vascular thrombosis were evaluated with only children, weight less than 10 kg, and cold ischemia time found to be significant. The clinical presentation included fulminant hepatic failure, allograft dysfunction, biliary sepsis, and screening ultrasound. Duplex ultrasonography was diagnostic in nearly all cases. Therapeutic modalities included revascularization, revascularization followed by retransplantation, retransplantation alone, and observation. Five cases of hepatic artery rupture occurred in four patients. Infectious arteritis was present in four patients. The 6-month actuarial survival in patients with vascular complications was 70%. Early diagnosis is critical for graft salvage, with surgical intervention the mainstay of therapy.

HEPATIC ALLOGRAFT RESCUE FOLLOWING ARTERIAL THROMBOSIS: ROLE OF URGENT REVASCULARIZATION

Hepatic artery thrombosis is a continuing source of morbidity and mortality following orthotopic liver transplantation. The cornerstone of therapy has been urgent retransplantation that is limited by organ availability. For this reason we developed a policy of urgent revascularization for allograft rescue. Hepatic artery thrombosis developed following 15 transplants of which 11 underwent urgent rearterialization. The diagnosis was made a mean of 4.8 days (range 1-10) following transplantation. Duplex ultrasonography was diagnostic in all patients and confirmed by angiography in 4 (36%). Three patients with hepatic artery thrombosis were identified following screening ultrasonography and were clinically unsuspected. Upon reexploration, a specific technical reason for hepatic artery was found in 4 patients (36%). Twelve arterial revascularization procedures were performed in 11 patients including: thrombectomy alone (n = 4); revision of anastomosis with thrombectomy (n = 5); and thrombectomy with placement of vascular conduit (n = 3). Following revascularization, 8 patients maintained hepatic artery patency. Three patients eventually required retransplantation secondary to biliary sepsis. Biliary tract complications developed in 6 patients, at a mean of 23 days following revascularization and included: breakdown of the biliary anastomosis (n = 4); stricture (n = 1); and sludge formation (n = 1). The overall graft and patient survival are 74% and 82% respectively, with a mean follow-up of 6.8 months. Hepatic allograft rescue with the use of urgent revascularization following hepatic artery thrombosis appears to be an effective means of either avoiding retransplantation or providing a bridge until a suitable donor becomes available.