R. Patrick Wood

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.

Use of Decellularized Porcine Liver for Engineering Humanized Liver Organ

BACKGROUND New bioartificial liver devices are needed to supplement the limited supply of organ donors available for patients with end-stage liver disease. Here, we report the results of a pilot study aimed at developing a humanized porcine liver by transplanting second trimester human fetal hepatocytes (Hfh) co-cultured with fetal stellate cells (Hfsc) into the decellularized matrix of a porcine liver. MATERIAL AND METHODS Ischemic livers were removed from 19 Yorkshire swine. Liver decellularization was achieved by an anionic detergent (SDS). The decellularized matrix of three separate porcine liver matrices was seeded with 3.5 × 10(8) and 1 × 10(9) of Hfsc and Hfh, respectively, and perfused for 3, 7, and 13 d. The metabolic and synthetic activities of the engrafted cells were assessed during and after perfusion. RESULTS Immunohistologic examination of the decellularized matrix showed removal of nuclear materials with intact architecture and preserved extracellular matrix (ECM) proteins. During perfusion of the recellularized matrices, measurement of metabolic parameters (i.e., oxygen concentration, glucose consumption, and lactate and urea production) indicated active metabolism. The average human albumin concentration was 29.48 ± 7.4 μg/mL. Immunohistochemical analysis revealed cell differentiation into mature hepatocytes. Moreover, 40% of the engrafted cells were actively proliferating, and less than 30% of cells were apoptotic. CONCLUSION We showed that our decellularization protocol successfully removed the cellular components of porcine livers while preserving the native architecture and most ECM protein. We also demonstrated the ability of the decellularized matrix to support and induce phenotypic maturation of engrafted Hfh in a continuously perfused system.

Diffuse biliary tract injury after orthotopic liver transplantation

An unusual type of diffuse biliary tract injury after liver transplantation that is characterized by multiple intrahepatic biliary strictures, ductal dilatations, fluid collections, or intrahepatic abscesses has been identified. Over a 5-year period, a total of 10 patients (2%) developed diffuse intrahepatic biliary injury with established vascular patency and no obvious source for their biliary tract pathology. All patients received livers preserved in University of Wisconsin solution with a mean preservation time of 16 hours. This biliary tract injury was associated with the presence of severe preservation injury and Roux limb biliary reconstruction. Of the 10 patients, 5 were treated nonoperatively with multiple stricture dilations and stent placements, 3 underwent retransplantation, 1 was treated operatively with hepaticojejunostomy, and 1 died of sepsis. This study suggests that this complication appears to be related to preservation injury and that the etiology may be ischemic in origin.

Nutritional support for the infant with extrahepatic biliary atresia

Some infants with biliary atresia obtain dramatic improvement for prolonged periods after the performance of hepatic portoenterostomy. Such infants may have life styles not substantially different from those of normal children. In others, the benefit from this operation, if any, is short lived. These infants are very vulnerable to the debilitating effects of severe, prolonged malabsorption and ultimately require orthotopic liver transplantation to sustain life. The physician caring for infants awaiting liver transplantation can do much, not only to prolong survival but to maintain satisfactory growth and development. The key consideration is to provide adequate nitrogen and nonnitrogen calories, liberally utilizing modern methods of enteral alimentation when necessary. In addition, attention must be directed toward several vitamin and mineral deficiencies, particularly those of the fat-soluble vitamins, that inevitably accompany severe malabsorption in children. Management of extrahepatic biliary atresia in infants is difficult and requires meticulous attention to details. Nevertheless, the long-term cure of this disorder provided by liver transplantation makes their care a rewarding experience.

The role of choledochoscopy in the diagnosis and management of biliary tract diseases

BACKGROUND The diagnosis and management of biliary tract disorders in certain cases may be incomplete without direct visualization of the bile ducts. METHODS We report our experience of 61 choledochoscopies (33 women, 27 men, mean age 44.6 years). Twenty patients had previously undergone orthotopic liver transplantation. All except two choledochoscopies were performed via the transpapillary route. Indications included suspected large bile duct stones in 18 patients, anastomotic strictures in 16, abnormal cholangiograms in 5, elevated liver function tests in 7, suspected cholangiocarcinoma in 4, occluded biliary metallic stent in 4, hemobilia in 4, primary sclerosing cholangitis in 2 and ischemic bile duct injury in 1 patient. RESULTS Choledochoscopy confirmed the anticipated diagnosis in 36 of 61 (59%) patients. Importantly, it provided additional unsuspected diagnostic information in 18 of the 61 (29.5%) patients. In addition, for patients in whom standard cholangiography was deemed abnormal, choledochoscopy demonstrated normal results in 7 (11.4%) patients. Fifty-two choledochoscopies were performed with therapeutic intentions, and the procedure was helpful in providing targeted treatment in 27 (44.2%) patients. CONCLUSIONS Choledochoscopy is a safe and useful endoscopic modality that can provide specific diagnoses and direct treatment in various biliary tract diseases. The additional information provided by choledochoscopy may change overall patient management and outcome.

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.

Optimal therapy for patients with biliary atresia: portoenterostomy ("Kasai" procedures) versus primary transplantation.

As the results with liver transplantation have improved, a controversy has arisen regarding the precise role of a portoenterostomy in the treatment of infants with biliary atresia. The controversy centers around three issues: (1) the short- and long-term survival rates achieved with both procedures, (2) the influence of a portoenterostomy on a subsequent transplant, and (3) the shortage of suitable liver donors for very small infants. To address these questions, we retrospectively reviewed the charts of 48 children with biliary atresia who underwent liver transplantation and compared these results with 35 children transplanted for other liver diseases. As a group, the biliary atresia patients had significantly lower mean body weights and ages and spent a significantly longer time on the waiting list. In addition, significantly more of the biliary atresia patients had undergone prior abdominal surgery when compared with the non-biliary atresia group. There was no difference in the intraoperative variables of mean anesthesia time, mean operative time, mean anesthesia preparation time, nor the mean amount of blood transfused intraoperatively between the two groups. However, when the biliary atresia patients who had undergone a portoenterostomy with a stoma were compared with either the biliary atresia patients who did not have a stoma created as part of their portoenterostomy or the non-biliary atresia patients, significant differences were noted in mean total anesthesia time, mean operative time, and the mean amount of blood transfused intraoperatively. The survival rate of the biliary atresia patients was significantly greater than the non-biliary atresia patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A selective approach to preexisting portal vein thrombosis in patients undergoing liver transplantation

Splanchnic venous inflow is considered mandatory to ensure graft survival after liver transplantation. Over a 68-month period, we performed 570 liver transplants in 495 patients. Portal vein thrombosis was present in 16 patients. At transplant, the extent of the occlusion included portal vein alone (n = 4), portal including confluence of the splenic and superior mesenteric veins (n = 8), portal, splenic, and distal superior mesenteric veins (n = 2), and the entire portal vein, splenic vein, and superior mesenteric vein (n = 2). The operative approach included thrombectomy alone (n = 5), anastomosis at the confluence of the splenic and superior mesenteric splenic veins (n = 8), and extra-anatomic venous reconstruction (n = 3). The mean operative blood loss was 22 +/- 22 units, and the mean operative time was 9.7 +/- 4.8 hours. The 1-year actuarial survival rate was 81%, with a mean follow-up of 12.5 months. In summary, with a selective approach and the use of innovative forms of splanchnic venous inflow, portal vein thrombosis is no longer a contraindication to liver transplantation.

The impact of extended preservation on clinical liver transplantation.

The introduction of UW solution into clinical transplantation has permitted extended cold storage preservation of the liver. Over a 46-month period, we have performed 308 orthotopic liver transplants (268 primary, 42 retransplants) in 266 recipients. Our experience is divided into cold-storage preservation in Eurocollins (163 transplants in 140 recipients) and UW (145 transplants in 131 recipients) solutions. Donor and recipient factors were comparable between the two groups. The use of UW solution has permitted an increase in the mean preservation time from 5.2±1.0 [EC] to 12.8±4.3 [UW] hr (P<0.001). The mean total operating time was reduced but intraoperative blood loss was unchanged with UW preservation. The number of transplants performed during the daytime hours has increased dramatically (21.5% [EC] vs. 71% [UW], P<0.001). The incidence of primary nonfunction, hepatic artery thrombosis, 1-month graft survival, and early retransplantation were similar in the 2 groups. Initial allograft function as determined by bile production, histology, and clinical assessment were likewise similar. Mean serum bilirubin, transaminase, and prothrombin levels were virtually identical by 5 days post-transplant. The enhanced margin of safety afforded by extended preservation has increased the capability for distant organ procurement and sharing, minimized organ wastage, and improved the efficiency of organ retrieval. With the relaxation of logistical constraints, our rate of liver import has nearly doubled (20.9% [EC] vs. 39.3% [UW]. P<0.001). Extended preservation has permitted the development of reduced-size liver grafting (n=12), resulting in a significant reduction in the number of deaths occurring while awaiting transplantation. Therefore, we advocate the use of UW solution with selective extension of preservation based not only on donor and recipient factors but also on manpower, resource, and logistical considerations.

Morphological features of advanced hepatocellular carcinoma as a predictor of downstaging and liver transplantation: An intention‐to‐treat analysis

In selected patients, locoregional therapy (LRT) has been successful in downstaging advanced hepatocellular carcinoma (HCC) so that the conventional criteria for liver transplantation (LT) can be met. However, the factors that predict successful treatment are largely unidentified. To determine these factors, we analyzed our experience with multimodal LRT in downstaging advanced HCC before LT in a retrospective cohort study. Thirty‐two patients with advanced HCC exceeding conventional and expanded criteria for LT underwent therapy, but only those patients whose tumors were successfully downstaged were considered for LT. Eighteen patients (56%) had their tumors successfully downstaged; 14 patients (44%) did not. No intergroup differences existed with respect to patient characteristics or the types and number of treatments. However, mean alpha‐fetoprotein levels were significantly higher in the non‐downstaged group than in the downstaged group (P < 0.048), and significantly more patients in the non‐downstaged group had infiltrative tumors (P = 0.0001). The median survival time was 42 and 7 months for the downstaged and non‐downstaged groups, respectively (P = 0.0006). Fourteen patients (43.3%) underwent LT. After a median follow‐up period of 35 months (range, 1.5–50 months) after LT, 2 patients (14.2%) developed tumor recurrence. The Kaplan‐Meier survival rates after LT were 92% at 1 year and 75% at 2 years. The noninfiltrative expanding tumor type was the sole predictor of successful downstaging and improved outcome on univariate and multivariate analyses. Our study suggests that, in patients with advanced HCC, morphological characteristics of the tumor may predict a good response to downstaging and an improved outcome after LT. Liver Transpl 16:289–299, 2010.