Orthotopic Hepatic Transplantation Research Articles

Cold Ischemia Time as a Factor in Post-transplantation Complications for Orthotopic Hepatic Transplantation

ObjectiveThis study aims to compare a shorter cold ischemia time with the present one in relation to the complications developed in liver transplantations. DesignThis is a retrospective, observational study of orthotopic liver transplantations performed with grafts from brain-dead donors during 12 months at a University Hospital (Seville). We compare incidence rates of complications (reperfusion syndrome, arterial and biliary complications, and prostaglandin requirements) between two groups according to cold ischemia times (group A < 6 hours; group B > 6 hours). ResultsSixty cases were included. There were more males in both groups as donors (55.5%) and recipients (75%). The median age was higher in group B in two cases. The Model for End-stage Liver Disease score was higher in patients with a shorter cold ischemia time, with a median of 20 hours (range, 16 to 26.5 hours). We observed that reperfusion syndrome (3.4% vs. 13.3%; P = .353), vascular complications (6.9% vs. 24.1%; P = .144), biliary tract complications (13.8% vs. 20.7%; P = .730), and prostaglandin requirements (3.4% vs. 20.7%; P = .102) were more common in group B, although without reaching statistical significance. After uni- and multivariate analyses, cold ischemia time longer than 6 hours was the only risk factor to develop complications (odds ratio: 3.578; 95% confidence interval: 1.125 to 11.374, P = .031). ConclusionAccording to the results of our analysis, cold ischemia times longer than 6 hours, as tends to be the usual procedure in most centers, imply higher rates of complications after liver transplantation.

Multifocal Osteonecrosis Glucocorticoid Induced

The present study describes a 29 years old patient diagnosed with aseptic osteonecrosis with multiple localization occurred after a corticoid treatment for chronic toxic hepatitis. The clinical and para-clinical examinations determined the diagnosis of Wilson disease and avascular necrosis with multiple localizations. The evolution of the disease was favourable following the surgical treatment consisting of bilateral total hip arthroplasty with cementless prosthesis, hemi-arthroplasty of the left shoulder with cementless prosthesis, orthotopic hepatic transplantation with an entire liver from donor in cerebral death and immunosuppressive, anticoagulant, antiretroviral and gastro-protective treatment. There is an increase of the number of patients undergoing a glucocorticoids treatment for several months, years or lifelong periods. This type of treatment increases the risk of osteonecrosis depending on the dosage and the duration of the treatment.

Melatonin Rhythms in Patients With Cirrhosis

Montagnese, Sara MD, PhD1,3; Middleton, Benita PhD2; Mani, Ali R MD, PhD1; Skene, Debra J PhD2; Morgan, Marsha Y MD1 Author Information

Transfusion of Blood Components during Orthotopic Hepatic Transplantation

Objective: to define preoperative factors determining a need for intraoperative packed red cell transfusion and its impact of the frequency and pattern of postoperative complications during orthotopic hepatic transplantation (OHT). Subjects and methods. The study included 31 recipients undergoing cadaveric liver transplantation. Group 1 comprised patients who were given allogenic blood red cells in the intraoperative period; Group 2 consisted of 11 (36%) recipients in whom OHT was made without allogenic red blood transfusion. Results. The baseline levels of hemoglobin (Hb) and hematocrit (Ht) were significantly higher in Group 2 (95±18 g/l (28±5%) versus 111±16 g/l (33±4%) in Groups 1 and 2, respectively). Conclusion. It is shown that cadaveric liver transplantation may be performed, without using donor packed red cells and that the preoperative levels of Hb and Ht are the indicators of blood transfusion.

Pyruvate carboxylase deficiency—insights from liver transplantation

Pyruvate carboxylase deficiency, complex form, presents in early infancy with lethal metabolic acidosis, resulting from ketoacidosis and lactic acidemia. Renal tubular acidosis, hyperammonemia, and citrullinemia complete the picture. In an infant with this disease, large amounts of glucose ameliorated the ketoacidosis, but worsened the lactic acidosis. Orthotopic hepatic transplantation completely reversed the ketoacidosis and the renal tubular abnormality and ameliorated the lactic acidemia. Concentrations of glutamine in cerebrospinal fluid were low and did not improve with liver transplantation.

Liver and intestinal lactate metabolism in patients with acute hepatic failure undergoing liver transplantation.

To determine the relative contribution of the gastrointestinal tract and the liver in lactate metabolism in patients with acute liver failure (ALF) and the effect of liver transplantation on this. We hypothesized that the liver and gut are net producers of lactate in ALF and that this is reversed after liver transplantation. A university-affiliated specialist liver transplant operating theater. Eleven patients with ALF undergoing liver transplantation. After ethical approval, 11 patients with ALF listed for orthotopic hepatic transplantation were studied. Whole blood was analyzed for lactate concentration from radial artery (RA) catheter, portal vein (PV), and hepatic vein (HV) during the dissection phase and was repeated postreperfusion of the liver graft. Gradients across the gut and the liver were calculated to see if there was net production or consumption. HV lactate was significantly higher than arterial (p =.028) in patients with ALF before liver transplantation, suggesting splanchnic production of lactate. Total splanchnic lactate gradient (HV-RA) is positive in ALF. Both the gut (PV-RA) and the liver (HV-PV) were net producers of lactate. After liver transplantation, hepatic venous lactate falls below arterial levels but not significantly. The gradient across the gut (PV-RA) remained positive, but the transhepatic gradient (HV-PV) became significantly negative, showing consumption by the graft (p =.021). The magnitude of lactate consumption after transplantation correlated positively with portal venous lactate concentration (p =.029) and inversely with graft cold ischemic time (p =.007). The liver is a net producer of lactate in patients with ALF and an elevated whole blood lactate. After liver transplantation, the graft becomes a consumer of lactate as shown by the negative lactate gradient. The degree of consumption is dependent on portal venous lactate concentration and cold ischemic time.

A Serine Protease Inhibitor, N-α-Tosyl-[formula omitted]-lysine Chloromethyl Ketone, Prolongs Rat Hepatic Allograft Survival

Background. Serine protease inhibitors have profound suppressive effects on cellular and humoral immune responses. We investigated the effect of a serine protease inhibitor, N-α-tosyl-l-lysine chloromethyl ketone (TLCK), on hepatic allograft survival in rats.Methods. Orthotopic hepatic transplantation was performed in an ACI (RT1a)-to-LEW (RT11) rat combination. TLCK was administered continuously at a dose of 4.4 mg/kg/day using an osmotic subcutaneous infusion minipump.Results. TLCK prolonged hepatic allograft survival. Histologic staging of acute rejection based on Banff criteria in TLCK-treated hepatic allografts was significantly lower than in untreated allografts. TLCK significantly reduced serum concentrations of interferon (IFN)-γ and tumor necrosis factor (TNF) α in allograft recipients. TNF-α mRNA levels in TLCK-treated allografts were significantly lower than in untreated allografts. TLCK also decreased perforin mRNA levels in hepatic allografts. Hepatic infiltrates eluted from TLCK-treated allografts showed significantly lower cell-mediated lympholytic activity against donor Con A blast cervical lymph node cells than those from untreated allografts. In vitro, TLCK suppressed interleukin-2 production and [3H]thymidine incorporation into an allogeneic mixed lymphocyte reaction.Conclusion. TLCK suppressed acute allograft rejection, suggesting a novel immunosuppressive strategy for therapy of acute organ rejection.

Primary sclerosing cholangitis: MR imaging findings with pathologic correlation.

The purpose of this study was to evaluate MR imaging findings of primary sclerosing cholangitis, to compare them with histopathologic findings, and to determine if these findings help differentiate primary sclerosing cholangitis from other disorders that result in end-stage liver disease. MR imaging was performed in 40 patients (27 men, 13 women; age range, 13-72 years; mean, 47 years) with primary sclerosing cholangitis over a 9-year period. In 16 patients who underwent orthotopic hepatic transplantation and in seven patients who underwent needle biopsy, correlation was made between MR imaging and pathologic findings. Focal signal changes in the liver parenchyma were seen on T2-weighted images as peripheral wedge-shaped zones of increased signal intensity in 29 patients (72%), as a reticular pattern in 15 patients (38%), and as periportal edema in 16 patients (40%). Lobar atrophy involved the right lobe in three patients (8%) and the left lobe in 11 patients (28%); hypertrophy of the caudate lobe was seen in nine patients (23%). Features of portal hypertension were seen in 14 patients (35%). Histologic assessment showed zones of segmental atrophy and scarring on the periphery of the liver. Peripheral wedge-shaped areas of high T2 signal intensity and dilatation of bile ducts are characteristic MR features of primary sclerosing cholangitis. Pathologic correlation suggests that these features may be related to underlying perfusion changes and bile duct inflammation in patients with primary sclerosing cholangitis.

Technique for orthotopic reduced-size hepatic transplantation combined with ex vivo liver cut down in the rat.

A technique is described for orthotopic reduced-size hepatic transplantation combined with ex vivo liver cut down in the rat. Following perfusion of the donor liver with cold heparinized saline, the portal veins, bile ducts, and hepatic arteries to the median and left lobes together were dissected in situ, encircled, and divided. After harvesting the donor liver, a hepatectomy was performed by ex vivo liver cut down of the median and left lobes. The remnant amounted to 32% of the whole liver. As a result, the suprahepatic vena cava could be well visualized with adequate exposure for vascular anastomosis. Orthotopic reduced-size hepatic transplantation was performed using the right and caudate lobes of the liver. The suprahepatic vena cava was anastomosed with a 7-0 silk running suture. A simplified cuff without processes was made with an obliquely cut polyethylene tube and used for the portal and infrahepatic caval anastomoses. A Teflon tube stent was used for the biliary anastomosis. The newly devised angled clamp and flexible arm were used for the cuff attachment and operative procedure. Transplant survival following ex vivo liver cut down was as good as that with whole liver transplantation. Reestablishment of the hepatic artery restores liver function following transplantation. The maximum hepatocyte labeling index (LI) occurs 24 hr after a 68% hepatectomy, and at 36 hr following a reduced-size hepatic transplantation with or without hepatic arterialization. Possible explanations for the slight delay in achieving the maximal LI may include damage that is induced by the operation itself, pregraft preservation, and reperfusion injuries. In conclusion, the anatomical features of the hepatic lobes in rats are well suited to successful completion of ex vivo liver cut down.

The treatment of alcoholic hepatitis.

Alcoholic hepatitis is a precirrhotic lesion; it develops in only a minority of chronic alcohol abusers even after decades of abuse. The clinical spectrum of disease varies from asymptomatic hepatomegaly to florid hepatocellular failure with gastrointestinal bleeding and hepatic encephalopathy. Corresponding variation is observed both in morbidity and mortality. The majority of individuals with mild to moderate alcoholic hepatitis improve significantly following abstinence from alcohol and the provision of a diet sufficient to meet their nutritional requirements; their long-term outcome is determined largely by their ability to maintain abstinence from alcohol. Individuals with severe alcoholic hepatitis require intensive nutritional support and vigorous management of the complications of their liver injury; their outcome is generally poor. A small, carefully selected subgroup of these very sick patients may benefit, at least in the short-term, from treatment with corticosteroids; the place of orthotopic hepatic transplantation, in this patient group, is still the subject of debate. No other treatment modalities have been shown to confer benefit consistently. A number of new therapeutic approaches have been proposed and need to be explored.

Liver Transplantation After Severe Poisoning Due to Amatoxin-ContainingLepiota-Report of Three Cases

Four cases of severe Lepiota poisoning, including three which developed toxic fulminant hepatitis treated by orthotopic hepatic transplantation, are reported here. The toxicity of the Lepiota is discussed as well as the indications for hepatic transplantation in poisonings due to amatoxin-containing mushrooms.

INDUCTION OF UNRESPONSIVENESS IN RATS AFTER EITHER INTRAPORTAL INJECTION OF DONOR ANTIGEN OR INTRAVENOUS INJECTION COMBINED WITH SPLENECTOMY1

Recently, we reported that hepatic allografts are permanently accepted when transplanted after intraportal injection (IP) of donor spleen cells (SPCs). The mechanism of this effect was investigated using various protocols for antigen injection. ACI (RT1a) and Buffalo (RT1b) rats were used as donors and recipients, respectively. Experimental groups were divided into the following groups depending on treatment: IP, intravenous injection (IV), splenectomy (Spx), and intravenous injection after splenectomy (IV+Spx). Accumulation of donor antigen in the various organs was examined by injecting 51Cr-labeled SPCs. Cellular and humoral responses after SPC injection was assessed by delayed-type hypersensitivity response and complement-dependent cytotoxicity (CDC) assay. Heterotopic cardiac transplantation and orthotopic hepatic transplantation were performed 10 days after each treatment. The accumulation ratio in the liver was significantly higher in the IP and IV+Spx groups than in the IV group. Delayed-type hypersensitivity responses were lower in the IP and IV+Spx groups than in the IV or Spx groups. The CDC titer 7 days after inoculation was significantly lower in the IP and IV+Spx groups than in the IV group. In order to examine whether the treatment actively suppressed the immune response, the animals were rechallenged with SPCs given intravenously 10 days after the initial injection. Elevation of CDC titer was suppressed in the IP and IV+Spx groups, but not in the IV and Spx groups. Significant prolongation of cardiac allograft survival was not observed in the IV and Spx groups. Prolongation was observed in the IP and IV+Spx groups. The survival of hepatic allografts in the IV group was decreased. No significant prolongation of graft survival was observed in the Spx group. In contrast, all hepatic allotransplants in the IP and IV+Spx groups survived over 45 days. These findings suggest that the accumulation of donor SPCs in the liver may play an important role in inducing unresponsiveness after intraportal injection of donor SPCs.

Orthotopic reduced-size hepatic transplantation in rats

Orthotopic reduced-size hepatic transplantation in rats

Effect of cyclosporine on liver regeneration after orthotopic reduced-size hepatic transplantation in the rat

These experiments were undertaken to study the effects of cyclosporine A (CsA) on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation (RSHT) in rats. Male Wistar rats were treated with or without a daily injection of CsA beginning 24 hr before surgery and were subjected to a 68% partial hepatectomy. A isogeneic orthotopic reduced-size hepatic transplantation was performed in recipient rats pretreated with or without CsA. A daily injection of CsA was continued until the recipient rats were sacrificed. Animals were sacrificed at various time points (12, 24, 36, 48, and 72 hr) postoperatively. The incorporation of bromodeoxyuridine (BrdU) into the DNA of the remnant hepatocytes was evaluated by immunohistochemical staining with a monoclonal antibody against BrdU. CsA (10 mg/kg/day) significantly augmented BrdU incorporation into hepatocytes after hepatectomy. The maximum labeling index (LI) was observed at 24 hr after hepatectomy. In contrast, the maximum LI in the recipient rats not receiving CsA was seen at 36 hr after RSHT, and 10 mg/kg/day of CsA decreased the LI at 36 hr after RSHT. A lower dose of CsA (3 mg/kg/day), however, significantly increased the LI in the recipient rats (P < 0.01), and it reached a peak at 24 hr after RSHT when compared to the transplant recipients not receiving CsA. The time course of the increase in the LI in the transplant recipient rats receiving 3 mg/kg/day of CsA was similar to that observed in the rats after hepatectomy. This dosage improved the delay in the reduced-size hepatic transplant LI reaching its peak.(ABSTRACT TRUNCATED AT 250 WORDS)

Orthotopic hepatic transplantation in the dog.

Orthotopic hepatic transplantation has become a well-established treatment modality for end-stage liver disease, and research in this field is constantly evolving. Of the 34 canine liver transplants performed in this study, 17 (50%) survived more than 3 days (mean survival time 15 days). Causes of perioperative death included hemorrhage (4), anesthetic complications (3), systemic anaphylaxis (3), portal vein thrombosis (3), hepatic venous outflow block (2), and hepatic artery thrombosis (2). Gentle handling with minimal dissection of the donor liver in situ resulted in a decreased incidence of hepatic venous outflow block. The incidence of biliary leak was similar irrespective of the method of biliary reconstruction, although the incidence of acute cholangitis was 56% in the cholecystoduodenostomy group compared with 0% in the choledochocholedochostomy cohort. Using celiac to common hepatic end-to-side arterial anastomosis with preservation of the gastroduodenal artery, thrombosis of the hepatic artery was encountered in four instances, an incidence similar to previously reported studies where end-to-end hepaticohepatic arterial anastomosis or donor aortic conduit was utilized. The incidence of postoperative intestinal intussusception was reduced from 40 to 0% in those who underwent transmesenteric intestinal plication following implantation of the liver. Among short-term survivors, sepsis was the most frequent noted complication (10), followed by intestinal intussusception (6), rejection (6), and gastrointestinal bleeding (1). Among recipient dogs that survived more than 3 days, rejection was the most common cause of graft loss (5), followed by biliary leak (4) and hepatic artery thrombosis (2).

Quality of Life Before and After Orthotopic Hepatic Transplantation

Fifty-three nonalcoholic patients were evaluated prior to liver transplantation and again approximately 3 years after surgery using the Sickness Impact Profile and Social Behavior Adjustment Schedule. Test-retest scores reflected significant improvement across all health and psychosocial scales of the Sickness Impact Profile. On the Social Behavior Adjustment Schedule, significant improvement was observed on scales measuring disturbed behavior, social role performance, and burden. Comparisons between groups indicated that the liver transplant patients were still impaired on eight of the Sickness Impact Profile scales after transplant; however, the severity of disturbance was not considered to be clinically significant. No between-group differences were noted on the Social Behavior Adjustment Schedule. These results indicate that liver transplantation is associated with substantial improvement in life quality, although as a group, the patients undergoing this surgery do not recover to the level of functioning demonstrated by normal individuals.

Quality of life before and after orthotopic hepatic transplantation

Quality of life before and after orthotopic hepatic transplantation

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.

Transplantation hépatique orthotopique pour un syndrome carcinoïde métastasé

We report a case of bronchial carcinoïde tumor with hepatic metastasis in a 42 years-old man, for which successfully orthotopic hepatic transplantation was performed after somatostatin trial, pulmonary lobectomy and systemic chemotherapy with steptozotocin and 5-Fluoro-uracil.

Segmental orthotopic hepatic transplantation as a means to improve patient survival and diminish waiting-list mortality

Pediatric liver transplantation continues to be limited by the availability of suitable liver donors, a factor that restricts programmatic development and ultimately contributes to death on the recipient waiting list. We report the application of segmental liver transplantation as a technique to address both these problems as well as improving the outcome of the child undergoing the transplant procedure. Since 1986, 37 children have undergone orthotopic liver transplantation. Twenty-three children have received whole-organ grafts; 81% survived. Of those receiving whole-organ grafts, 15% had arterial thrombotic complications and 23% required retransplantation. More importantly, 29% of those children listed for transplantation died while waiting for a donor organ to become available, with a mean interval of 1.7 months (range, 2 days to 4.5 months). Since July 1988, segmental liver transplantation has been a component of our therapeutic armamentarium, and of the past 20 liver recipients, 16 have received a left lobe segmental graft. The results of the segmental transplant series have shown striking improvements. First, no child has died while awaiting donor organ availability. Second, segmental liver recipient survival is equivalent to that of whole-organ graft recipients (81%). Third, hepatic arterial thrombosis, especially a problem in high-risk infant transplants, was reduced by this technique (5%). Retransplantation due to graft complications has not increased (21%). These data suggest a vital role for segmental liver transplantation not only as a remedial salvage procedure for the critically ill child, but also as a primary transplant option.