Relationship between immunosuppression and osteoporosis in an outpatient liver transplant clinic.

BACKGROUND: The aim of this study is to determine the relationship between immunosuppression, disease state, and osteoporosis in an outpatient liver transplant clinic. METHODS: All liver transplant recipients visiting an outpatient transplant clinic received bone density scanning with a dual-energy X-ray absorptiometry (DEXA) device of the calcaneal bone after completing a questionnaire assessing risk and medications currently being used. RESULTS: Of the 137 liver transplant (OLT) recipients completing questionnaires and receiving DEXA screening, patients with low bone density (n = 50) were older (56.6 +/- 12.7 years vs 50.2 +/- 10.1 years; P = .02) compared with normal density patients (n = 87) and were predominately female (64.0% vs 35.6%; P = .01). Based on disease state, patients with cholestatic liver failure had lower bone calcaneal area (17.3 +/- 1.3 cm2 vs 18.9 +/- 1.57 cm2; P < .01). Patients taking tacrolimus (n = 112), as compared with cyclosporine (n = 25), had a tendency toward fewer findings of low bone density (37.5% [42 of 112] vs 56.0% [14 of 25]; P = .08) but had more risk factors (3.1 +/- 1.2 vs 2.1 +/- 0.8; P = .001) and a higher prednisone dose (4.4 +/- 5.9 mg/d vs 2.1 +/- 3.8 mg/d; P = .026). For patients weaned from prednisone, the tacrolimus patients were less likely to have low bone density (36.2% vs 68.8%; P = .02). Mycophenolate mofetil did not influence bone density or area measured. CONCLUSIONS: After liver transplantation, patients taking cyclosporine were more likely to have low bone density compared with those taking tacrolimus.

Duct-to-duct biliary anastomosis for patients with sclerosing cholangitis undergoing liver transplantation.

BACKGROUND: Due to the association of strictures within the biliary ductal system, Roux-en-Y choledochojejunostomy has been the preferred method of anastomosis for liver transplant recipients with primary sclerosing cholangitis (PSC). The aim of this study was to evaluate duct-to-duct anastomosis in patients with PSC who undergo liver transplantation. METHODS: Data were collected and evaluated based on demographics, type of anastomosis preformed, malignancies, outcomes comparisons, and survival. RESULTS: Of the 60 patients transplanted for PSC, 58 were diagnosed PSC prior to transplantation and 2 were diagnosed on explant. The Roux-en-Y group (n = 38) were similar in age, gender, and race when compared to the duct-to-duct (d-d) group (n = 22). There were similar rates of anastomotic revisions when comparing d-d anastomosis with Roux-en-Y (2 [9.1%] versus 2 [5.3%], P = NS) owing to bile leaks. Based on radiologic interventions of the bile ducts, seven (18.4%) in the Roux-en-Y group had interventions compared to two (9.1%) in the duct-to-duct group (P = NS). There was also no difference in recurrence of PSC: three (7.9%) in the Roux-en-Y group compared to two (5.3%) in the duct-to-duct group (P = NS). Survival at 4 years were similar between each group (76.5% [+/- 0.07] Roux-en-Y versus 84.9% [+/- 0.08] duct-to-duct, P = NS). CONCLUSION: Duct-to-duct anastomosis at the time of liver transplantation is both safe and efficacious when used in patients with PSC. Outcomes as described by surgical interventions, radiologic interventions, retransplantation, and survival were similar between groups.

Adult and pediatric liver transplantation for autoimmune hepatitis.

BACKGROUND: Due to the early age that pediatric patients with autoimmune hepatitis (AIH) are transplanted, it is theorized that older AIH patients may have different outcomes than pediatric patients following liver transplantation. METHODS: This is a retrospective review of both the adult and pediatric liver transplant programs consisting of 56 patients. Rejection and recurrence of AIH were determined by biopsy. RESULTS: The autoimmune patient having rejection episodes had a 1.76-fold increase in relative risk to develop autoimmune recurrence when compared to patients without rejection [RR = 1.76; 95% CIRR (1.08, 2.86)]. The pediatric group had a 6.62-fold increase in relative risk to develop colitis following liver transplantation [RR = 6.62; 95% C.I.R.R. (1.36, 32.13); P =.02]. Mean days to recurrence of AIH were similar in both groups (1364 +/- 1074 vs 936; P = NS). There were more hospitalized days in the pediatric group compared to the adults (20.5 +/- 13.3 days vs 51.7 +/- 22.2 days, P =.039). OKT-3 was rarely used (n = 5) in either group (9.3% vs 7.7%, P = NS) and was not correlated with which patients would be weaned from steroids or recurrence. CONCLUSIONS: Based on this review, pediatric patients were more likely to develop ulcerative colitis following liver transplantation and they incurred longer hospital stays than adults. The adult group was more likely to be weaned from steroids, with AIH recurrence unrelated to weaning.

Hepatic artery thrombosis in pediatric liver transplantation.

PURPOSE: Children have been reported to be at greater risk for hepatic artery thrombosis when compared to adults due to small arterial size, nonuse of intraoperative microscope, and postoperative hypercoagulable state. METHODS: We evaluated arterial anastomosis type, intraoperative field magnification, and hepatic artery complications and how they were managed. All patients underwent ultrasound, anticoagulation consisted of 41 mg aspirin once a day, and 35 patients received alprostadil (PGE) for the first 7 days after transplantation. No patients were administered intravenous heparin following liver transplantation. RESULTS: Of the 74 livers transplanted, 36 grafts (48.6%) were whole organ transplants and 38 grafts (51.4%) were partial livers. We observed HAT in 1 of 74 (1.35%) transplants in our pediatric liver transplant population. The only patient with HAT was a young girl with a history of biliary atresia. The occurrence of a hepatic artery thrombosis on day 7 was caused by the migration of an intimal plaque dissection within the artery graft. She was emergently taken back into the operating room for graft revision. This individual currently has a survival time of 426 days following her last transplant. CONCLUSIONS: Hepatic artery thrombosis may be minimized in pediatric liver transplantation without the use of microsurgery. Anticoagulation utilizing ASA and alprostadil is sufficient to avoid HAT. Accurate use of ultrasound is crucial to avoid this complication. Graft and patient salvage is possible with expedient surgical treatment; microsurgery, anticoagulant therapy, site of arterial inflow, and recipient size and weight.

Biliary complications after pediatric liver transplantation revisited.

BACKGROUND: Biliary complications in pediatric liver transplantation (PLT) are associated with increased morbidity and mortality. METHODS: Prospectively, data was collected on 89 consecutive liver transplants performed in 82 children. Eighty-nine consecutive PLTs were tracked for transplant type (partial versus whole), recipient age/weight, duct anastomosis type, surgical technique, and biliary complications. Treatments of biliary complications (surgical versus interventional radiology) were also evaluated. RESULTS: Forty-six children (51.7%) received partial transplants and 43 (48.3%) children received whole organs. The average age for whole liver transplanted children was 8.95 +/- 6.62 years and average weight was 36.2 +/- 28.7 kg; for those receiving partial livers, 3.19 +/- 3.52 years and 14.1 +/- 13.0 kg. Duct-to-duct anastomosis was performed for 26 grafts and Roux-en-Y choledochojejunostomy for 63 grafts. Biliary complications occurred in 10 of 89 (11.2%) grafts. Complications included anastomotic strictures in four (40%), bile leak in five (50%), intraparenchymal biloma in one (10%). The complication rate for whole organs was 1/43 (2.3%) and 9/46 (19.6%) for partial organ (P =. 015). No difference in complication rates were seen in type of ductal anastomosis (7.7% vs 12.7%, P = NS). Reoperation for biliary complication was necessary in only 2/10 (20%) of grafts. CONCLUSIONS: Technical advances have reduced the incidence of biliary complications in PLT. Partial liver grafts have a statistically higher risk of biliary complication than whole grafts. Most biliary complications can be managed with radiological intervention without surgical exploration. Pediatric biliary complications are not associated with graft loss.

Nonresponders of interferon/ribavirin treatment for recurrent hepatitis C following liver transplantation.

BACKGROUND: Treatment of recurrent hepatitis C (HCV) following liver transplant currently includes alpha-interferon with ribavirin. OBJECTIVE: The aim of this study is to evaluate nonresponder protocols for patients failing current treatment for recurrent hepatitis C following liver transplantation. METHODS: From February 1998 through November 2002, 67 patients, all serum RNA-positive for hepatitis C with histological evidence of recurrent hepatitis C, underwent treatment with alpha-interferon and ribavirin. For patients who failed initial treatment, patients were begun on either amantadine along with interferon/ribavirin or peginterferon with ribavirin. RESULTS: Of the initial 67 patients, there was a complete viral clearance in only 14.9% (10/67). Of the 57 remaining patients not clearing the virus, 30 (52.6%) were taken off treatment due to adverse events associated with bone marrow or hemoglobin suppression. In the amantadine group (n = 12), three (25%) had to discontinue due to CNS side effects of slurred speech, dizziness, and increased depression. In the amantadine group, no patients cleared the virus but there was a one log drop in viral load (1.6 x 10(6) vs 0.9 x 10(6); P =.4). In the peginterferon group, there were three (20%) patients with complete viral clearance during treatment with similar drops to amantadine. There was also seen a biochemical response by month 3 with peginterferon, which was not seen with amantadine. CONCLUSIONS: Peginterferon with ribavirin appears to be superior to amantadine with interferon/ribavirin when used in nonresponders for hepatitis C viral clearance.

Interferon-alpha and ribavirin for the treatment of recurrent hepatitis C after liver transplantation.

BACKGROUND: Initial studies utilizing interferon-alpha and ribavirin for the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation showed promising results. Here we report our single-center experience using this combination therapy. METHODS: Liver transplant recipients with recurrent HCV (elevated serum aminotransferases, positive serum HCV RNA, and biopsy-proven hepatitis without rejection) received interferon-alpha (1.5-3 million units subcutaneously three times a week) and ribavirin (400-1000 mg p.o. daily) for 12 months or more. Serum aminotransferases, HCV RNA, and severity of hepatitis were followed. RESULTS: Thirty-two patients have been treated for at least 3 months, including 13 who have been on 12 or more months of therapy. Three died from allograft failure due to recurrent HCV. Dose reductions of interferon-alpha and/or ribavirin occurred in 22 patients. Thirteen had their medications permanently discontinued for severe adverse effects. Twenty-six patients (81%) had a biochemical response (BR; normalization of serum aminotransferases) after 3 months. End-of-treatment and sustained BR were 77% and 71%, respectively. Mean viral loads decreased 68-77%; however, only three patients became serum HCV RNA negative. After 12 months of therapy, no histological improvement was observed in 11 patients who were biopsied. Patients who received mycophenolate mofetil or daclizumab had a less likelihood of achieving a BR. CONCLUSIONS: A significant number of patients did not tolerate interferon-alpha or ribavirin. Although BR was excellent and mean viral loads decreased significantly, virological clearance was poor and no histological improvement was noted. A more efficacious treatment with less adverse effects for recurrent HCV after liver transplantation is needed.

Steroid withdrawal in liver transplant recipients.

Because of troublesome side effects associated with steroid use, many transplant centers have tried to withdraw steroids from stable, solid organ transplant recipients. The objective of this study was to evaluate the ability to wean liver transplant recipients off steroids, depending on both their primary immunosuppressive regimen and their primary disease state. This was a retrospective, single-center review of steroid weaning in adult orthotopic liver transplant recipients. Based on primary immunosuppression, patients could be weaned off steroids similarly if they were taking cyclosporine or tacrolimus (53.9% vs 61.4%). When triple immunosuppressive regimens were compared with dual regimens, a difference was found in ability to wean patients off steroids (52.4% vs 74.5%, P = .001). When steroid weaning was stratified for primary immunosuppression and primary disease state, patients with autoimmune-mediated diseases (autoimmune hepatitis, sclerosing cholangitis, and primary biliary cirrhosis) were less likely to be weaned if they were receiving cyclosporine-based immunosuppressants (36.8% vs 62.2%, P = .03). In conclusion, it appears that a large number of liver transplant recipients can safely be tapered off steroids.