Isolated donor specific alloantibody-mediated rejection after ABO compatible liver transplantation.

Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.

Hepatitis B and C and renal failure.

Hepatitis C is the most common cause of liver disease in the dialysis patient. The prevalence of chronic hepatitis C determined by anti-HCV testing in this population ranges from 6% to 38%. Using second generation EIA assays, the prevalence of anti-HCV among patients participating in the 1997 National Surveillance of Dialysis Associated Diseases in the United States was 9.3%. Polymerase chain reaction testing for HCV RNA has shown that the prevalence of HCV infection can be as high as 20% to 30% of dialysis patients. The causes and source of infection in patients with chronic renal failure on hemodialysis are multiple. Before the introduction of routine screening of blood donors for anti-HCV, blood transfusions were an important risk factor for acquisition of hepatitis C. Other potential sources of infection include exposure to contaminated equipment and nosocomial routes such as patient-to-patient exposure. The risk of infection appears to correlate with the duration of hemodialysis and the number of transfusions. Interestingly, dialysate and buffers have been shown to be virus free even when used in hepatitis C infected patients. The natural history of chronic hepatitis C infection in patients with renal failure is not well characterized. Although persistent elevations in ALT levels occur in 12% to 50% of dialysis patients, the frequency of persistently normal ALT levels in HCV-infected dialysis patients appears to be higher than in HCV-infected patients without renal failure. Overt liver disease and liver failure rarely occur. The degree of inflammation in liver biopsies of renal failure patients is usually mild. Thus, progressive liver disease may be less common in patients with advanced renal disease but further studies are required to assess the true impact of hepatitis C infection in this high risk population. The impact of hepatitis C infection on morbidity and mortality of patients with end-stage renal disease remains poorly defined. Initial studies have failed to show a significant increase in mortality among HCV-infected hemodialysis or renal transplant patients within the first 5 years following transplantation. In contrast, recent studies with extended follow-up of renal transplant recipients suggest that hepatitis C infection may affect patient and graft survival during the second decade. Further studies are required to identify the mechanisms of infection of patients with end-stage renal disease and to define better treatment strategies for these patients before and after kidney transplantation.

Use of transjugular intrahepatic portosystemic shunt as a bridge to liver transplantation in a patient with severe hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is defined by the presence of the triad of liver disease, arterial hypoxemia, and intrapulmonary vascular dilatation. The clinical implication of this disorder is impairment of gas exchange. Numerous reports in the literature show that this condition is reversible with orthotopic liver transplantation (OLT). However, patients with HPS often present with PaO(2) levels that are quite low. OLT with a preoperative PaO(2) less than 50 mm Hg is associated with unacceptably high mortality and morbidity. We report a case of severe HPS in which a transjugular intrahepatic portosystemic shunt was successfully used to improve oxygenation, thus allowing a successful elective OLT.

Internal biliary stenting in orthotopic liver transplantation.

Biliary complications account for significant morbidity in orthotopic liver transplantation (OLT), with a reported incidence ranging from 6% to 47%, and many centers are reassessing the need and options available for stenting the biliary anastomosis. We report on our experience using a 6F Silastic, double-J, ureteral stent as an internal biliary stent in OLT. From October 15, 1995, to September 30, 1998, a total of 99 patients at our institution underwent 108 OLTs. Of these, 77 patients received an end-to-end choledochocholedochostomy over an internal stent. Three patients died within 1 week post-OLT, leaving 74 patients for evaluation (follow-up, 2 to 38 months). Stents were placed transanastomotic and transsphincteric at the time of OLT and secured with a dissolvable suture. At 4 to 6 weeks post-OLT, stents visible within the biliary tree on kidney, ureters, and bladder radiograph were removed endoscopically. Graft and patient survival rates were 92% and 96%, respectively. There were 12 biliary complications (18%): anastomotic leak in 6 patients (9%), anastomotic stricture in 5 patients (7.6%), and stent migration in 1 patient (1.5%). Thirty-two patients (43%) passed the biliary stent without intervention, whereas 42 patients (57%) underwent esophagogastro duodenoscopy (EGD) stent removal at 4 to 6 weeks without incident. Treatment of the complications included percutaneous drainage, endoscopic dilatation with stenting, and/or conversion to Roux-en-Y choledochojejunostomy. The use of the 6 F Silastic, double-J, ureteral stent provides a safe and effective means of stenting the biliary anastomosis in OLT. Major advantages to this method are that it: (1) is completely internal, (2) is biliary decompressive, (3) is radiopaque, (4) can be spontaneously passed, and (5) is easily accessible for EGD extraction.

Cost-effectiveness analysis of transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic therapy for the prevention of recurrent esophageal variceal bleeding.

For the prevention of recurrent esophageal variceal bleeding, studies show that patients treated with transjugular intrahepatic portosystemic shunt (TIPS) have lower rebleeding rates compared with endoscopic therapy. However, TIPS is associated with higher rates of portosystemic encephalopathy and possibly higher costs. The aim of this study was to conduct a cost-effectiveness analysis comparing TIPS with endoscopic sclerotherapy and endoscopic ligation for the prevention of recurrent esophageal variceal bleeding. Data for rates of rebleeding, death, complications, and crossover from endoscopy to TIPS were obtained from the literature. Costs for procedures and hospitalizations were obtained from two medical centers. Sensitivity analyses were performed varying probabilities of key variables. The patient population consisted of a hypothetical cohort of cirrhotic patients successfully treated for esophageal variceal bleeding with endoscopic sclerotherapy who received prophylactic sclerotherapy, ligation, or TIPS over 1 year. Endoscopic patients would receive propranolol. Mortality was similar for the three groups. The number of bleeds per patient for sclerotherapy, ligation, and TIPS would be 0.39, 0.32, and 0.07, respectively. The total annual costs per patient for sclerotherapy, ligation, and TIPS were $23,459, $23,111, and $26,275, respectively. The incremental cost per bleed prevented for TIPS compared with sclerotherapy and ligation was $8,803 and $12, 660, respectively. The incremental cost per bleed prevented for TIPS compared with sclerotherapy or ligation was sensitive to the cost of TIPS and the TIPS stenosis rate. Ligation had lower costs and lower recurrent bleeding rates than sclerotherapy. Compared with endoscopic therapy, TIPS leads to lower recurrent variceal bleeding rates and it is more cost effective in the short term for the prevention of recurrent esophageal variceal bleeding.

Decision-analysis of transjugular intrahepatic portosystemic shunt versus distal splenorenal shunt for portal hypertension.

Transjugular intrahepatic portosystemic shunt (TIPS) and surgical distal splenorenal shunt (DSRS) are treatments for complications of portal hypertension. TIPS is widely used because it is relatively easy to place. Because TIPS may malfunction over time, it is unclear whether TIPS is superior to DSRS in patients with Child's class A cirrhosis who enjoy a longer survival. This study compared the cost-effectiveness of TIPS to DSRS for portal hypertension in Child's class A cirrhosis. A decision analysis model was used to evaluate the number of procedures, life expectancy, and costs over the first 2 years in patients with Child's class A cirrhosis who underwent a TIPS or DSRS. Patients who received TIPS survived 1.96 years, required 1.7 procedures, and incurred $41,685 in costs. Patients who underwent a DSRS survived 1.86 years, required 1.0 procedure, and incurred $26,951 in costs. The cost-effectiveness of TIPS compared with DSRS was $147,340 per life-year saved. Adjusting the rate of TIPS dysfunction, 1-year survival, or the number of ultrasounds to detect TIPS dysfunction did not change the results. In patients with Child's class A cirrhosis, DSRS is a more cost-effective treatment than TIPS. Until the results of a randomized controlled trial comparing TIPS with DSRS are available, TIPS should be regarded as experimental and prohibitively expensive in Child's class A cirrhosis.