Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation.

Numerous case reports describe patients with previously documented immunity developing active hepatitis B virus (HBV) infection after transplantation. However, the risk of reactivation of HBV under long-term immunosuppression in hepatitis B core antibody (HBcAb)-positive, hepatitis B surface antigen (HBsAg)-negative transplant recipients has not been clearly described. Herein, we present a long-term follow-up for 49 HBcAb-positive, HBsAg-negative recipients (27 liver, 18 kidney, 4 pancreas) transplanted between June 1996 and April 2001. Among these, 37 recipients (76%) were HBsAb positive at transplantation. Immunosuppression consisted of various antibody induction regimens in 20 (41%) of the recipients with either tacrolimus (33 [67%])- or cyclosporine (16 [33%])-based maintenance immunosuppression. The incidence and duration of HBV prophylaxis was not significant. No patient received hepatitis B immunoglobulin (HBIG) before or after transplantation. Additionally, only two patients received lamivudine, which was started post transplant without clinical indication. The mean length of follow-up was 3.1+/-1.4 years. At the last follow-up, overall patient and graft survival were 98% and 96%, respectively. Patient survival was 96% in liver, 100% in kidney, and 100% in pancreas transplant recipients. The graft survival for each organ type was 93% in liver, 100% in kidney, and 75% in pancreas transplant recipients at the end of follow-up. There was no incidence of HBV reactivation defined as recurrence of HBsAg and/or HBV DNA positivity. These data suggest that the risk of reactivation of HBV in HBcAb-positive, HBsAg-negative transplant recipients under immunosuppression is negligible, regardless of immunosuppressive regimen, lamivudine prophylaxis, or HBsAb status. These patients should have access to transplantation as they enjoy excellent patient and graft survival rates.

Polyomavirus in kidney and kidney-pancreas transplant recipients.

PURPOSE: To report the incidence and clinical characteristics of polyomavirus (PV) nephritis in kidney (KTX) and kidney-pancreas transplant (KPTX) recipients. METHODS: Single center retrospective analysis of all cases of PV nephritis in KTX and KPTX patients transplanted between 1994 and 1999. RESULTS: Thirteen (5 KTX and 8 KPTX) patients (2.1%) had PV nephritis diagnosed on multiple biopsies (n = 22) among 504 KTX and 106 KPTX recipients. The incidence of PV nephritis was higher in cadaver donor transplants (2.6% cadaver vs. 0.7% living donors), after KPTX (1% KTX vs. 7.5% KPTX), in males (3.3% male vs. 0.7% female), and in diabetic patients (4.4% diabetic vs. 0.8% nondiabetic). The mean time to diagnosis of PV nephritis was 18 (range 6-48) months after KTX and 17 (range 9-31) months after KPTX. Three KTX patients and 5 KPTX patients had calcineurin inhibitor toxicity on biopsy prior to developing PV nephritis. Reduction in immunosuppression occurred in 100% of KTX and 63% of KPTX patients. Three patients (23%) developed rejection within 3 months of diagnosis of PV, 1 after a reduction in immunosuppression. Despite multiple antiviral treatment regimens, renal allograft failure requiring dialysis occurred in 60% of KTX and 50% of KPTX patients. All KPTX patients remain insulin independent and 2 were successfully retransplanted with living donor kidneys. 2 patients (15%) died but there was no mortality directly related to the virus. CONCLUSIONS: Polyomavirus nephritis may be increasing in incidence and appears to be unresponsive to either conventional antiviral agents or a reduction in immunosuppression. Most of our cases occurred in male diabetic patients undergoing cadaveric donor transplantation and were preceded by biopsy-proven nephrotoxicity. Further studies are needed to better define the pathogenesis of PV and effective antiviral treatment.

Long-term experience with simultaneous kidney-pancreas transplantation with portal-enteric drainage and tacrolimus/mycophenolate mofetil-based immunosuppression.

UNLABELLED: Refinements in surgical techniques and advances in clinical immunosuppression have led to steadily improving results in pancreas transplantation (PTX). Although there is renewed interest in enteric exocrine drainage, most PTXs are performed with systemic venous delivery of insulin. To improve the physiology of PTX, we developed a novel technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric [P-E]). The purpose of the study was to analyse outcomes in patients undergoing PTX with P-E drainage and contemporary immunosuppression. MATERIALS AND METHODS: From January 1997 through September 2002, we performed 67 primary simultaneous kidney-PTXs (SKPT) with P-E drainage. Maintenance immunosuppression consisted of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids. No antibody induction therapy occurred in 33 patients (49%) with the remainder receiving daclizumab (n = 15), basiliximab (n = 2), or thymoglobulin (n = 14) induction therapy. The patient group included 38 males and 29 females with a mean age of 39.7 year (range 23-58) and a mean duration of pretransplant diabetes of 24.5 year (9-46). Fourteen patients (21%) were African-American. RESULTS: The mean waiting time for SKPT was 3.3 months (range 0.1-10). Mean kidney and pancreas cold ischaemia times were 15.1 and 15.4 h, respectively. Patient, kidney and pancreas graft survival rates were 97%, 92.5% and 82%, respectively, with a mean follow-up of 20 months (range 1-56). Two deaths (one sepsis, one cardiac event) occurred at 1 month after SKPT; both patients died with functioning grafts (DWFG). Three patients (4.5%) had delayed renal allograft function and received temporary dialysis after SKPT. Five kidney graft losses occurred (two DWFG, one thrombosis, two chronic rejection). All but four patients (6%) had immediate PTX function. A total of 12 pancreas graft losses occurred (two DWFG, five thrombosis, five chronic rejection). The incidence of acute rejection was 28%, but no grafts were lost due to isolated acute rejection. The incidence of major infection was 51%, but only five patients (7.5%) developed cytomegalovirus infection. A total of 19 patients (28%) underwent early relaparotomy within 3 months of SKPT. The composite endpoint of no rejection, graft loss, or mortality was attained by 63% of patients. At present, 58 patients (87%) are both dialysis and insulin-independent (including four retransplants). CONCLUSION: These findings suggest that SKPT with P-E drainage and contemporary immunosuppression may result in excellent intermediate-term outcomes.

Evolving experience of hepatitis B virus prophylaxis in liver transplantation.

Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is important to prevent recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) for chronic HBV cirrhosis. With availability of lamivudine (3TC), the use of combination prophylaxis with long-term HBIG/3TC has been shown to prevent short-term HBV recurrence. This report compares HBV recurrence rates between groups receiving no/short-term HBIG, long-term HBIG alone, or HBIG/3TC prophylaxis, and describes HBIG requirements during the first 6 and 12 months in the latter two groups. This study involved patients undergoing OLT at the University of Tennessee-Memphis between May 1990 and July 2001. During this period, 388 liver transplants were performed at our center. All hepatitis B surface antigen (HBsAg)-positive recipients (n = 27) were included in this retrospective analysis. The groups were similar with regard to pre-transplant demographic characteristics such as age, gender, weight, and pre-transplant diagnosis. Owing to the retrospective study design, median follow-up was longer for the no-prophylaxis (5.6 years) and the HBIG-alone (6.0 years) groups compared to the HBIG/3TC group (4.2 years). Patient survival was 50% in the no-prophylaxis and 71% in the HBIG-alone groups compared to 100% in the HBIG/3TC group (P = 0.09). When censored for death with a functioning graft, graft survival was 50% in the no-prophylaxis and 86% in the HBIG-alone group compared to 100% in the HBIG/3TC group (P = 0.07). The overall incidence of HBV recurrence in the no-prophylaxis era was 100% and 21% in the HBIG-alone era compared to 0% in the HBIG/3TC era (P < 0.001), despite similar mean and median HBIG trough titers in the HBIG-alone and HBIG/3TC groups. The incidence of HBV recurrence in HBV DNA-positive recipients was 100% in the no-prophylaxis era, 30% in the HBIG-alone era, and 0% in the HBIG/3TC era (P < 0.001). Recipients in the HBIG-alone group had a nearly two-fold increase in HBIG requirement at 6 and 12 months in order to maintain similar HBIG trough titers post-transplant compared to recipients in the HBIG/3TC group despite similar pre-transplant HBV serology. This increased HBIG requirement in the HBIG-alone group resulted in a marked increase in the mean overall cost of HBV prophylaxis in this group ($47,367 US dollars at 6 months; $84,280 US dollars at 12 months) compared to the HBIG/3TC group ($25,931 US dollars at 6 months; $49,599 US dollars at 12 months). These data demonstrate an improvement in patient and graft survival rates in the group receiving combination HBIG/3TC prophylaxis compared to the HBIG-alone and no-prophylaxis groups. There was a significant reduction in HBV recurrence in the group receiving combination HBIG/3TC when compared to the groups receiving HBIG alone or no prophylaxis. Furthermore, we demonstrated that the addition of 3TC to the long-term HBIG regimen led to elimination of the disparity previously described in HBV recurrence rates between HBV DNA-positive and HBV DNA-negative recipients. Importantly, our data demonstrates a complete lack of HBV recurrence in the HBIG/3TC group at a median follow-up of 4.2 years. Additionally, the data show that the addition of 3TC to the post-operative prophylaxis regimen resulted in a reduction in the requirement of HBIG at 6 and 12 months, which markedly reduced the overall cost of post-transplant HBV prophylaxis.

Rhodococcus equi pulmonary infection in a pancreas-alone transplant recipient: consequence of intense immunosuppression.

We report the case of a pancreas-alone transplant recipient who developed Rhodococcus equi pneumonia after receiving multiple courses of antilymphocyte therapy for the treatment of recurrent acute pancreas allograft rejection. We also review and discuss the diagnosis, clinical course, and treatment of 18 cases of R. equi infection reported in solid organ transplant recipients. The lung is the most common primary site of infection, but R. equi infection is difficult to diagnose because of the pleomorphic, gram-positive, and partially acid-fast nature of the organism. Treatment usually involves a combination of antibiotics including rifampin, macrolides, vancomycin, and ciprofloxacin. The optimal duration of therapy is unknown, but relapse is common if the duration of treatment is less than 14 days. The duration of therapy should be guided by clinical recovery, culture results, and radiographic findings. Monitoring levels of immunosuppressive agents-such as tacrolimus and cyclosporine-is needed in order to avoid clinically significant drug interactions with rifampin or the macrolides when these agents are used in order to treat R. equi infection in the transplant population.

Renal allograft outcomes in African American versus Caucasian transplant recipients in the tacrolimus era.

METHODS: Between January 1995 and December 1999, 185 kidney transplants were performed with tacrolimus (TAC)-based immunosuppression including 120 African American (AA, 65%) and 65 Caucasian recipients (C, 35%). Mean follow-up was 34 months. The AA group was characterized by a higher incidence of renal disease due to hypertension (72% AA vs 37% C, P <.001), pretransplant dialysis (95% AA vs 82% C, P =.003), waiting time (1.9 years AA vs 1.1 years C, P =.02), cadaveric donation (88% AA vs 68% C, P =.01), HLA mismatching (mean 3.5 AA vs 2.4 C, P <.001), and delayed graft function (DGF; 50% AA vs 22% C, P =.001). RESULTS: The 5-year actuarial patient and graft survival rates were 96% AA versus 83% C (P = NS) and 83% AA versus 75% C, (P = NS), respectively. The incidence of acute rejection (21% AA vs 12% C, P = NS) and mean time to acute rejection (12 months AA vs 11 months C) were similar. Although the incidence of chronic allograft nephropathy (CAN) was comparable (7% AA vs 5% C), the mean time to CAN was shorter in AA recipients (18 months AA vs 37 months C, P =.03). CONCLUSIONS: These results suggest marked improvement in post-transplant outcomes in the TAC era in patients with multiple immunologic risk factors including AA ethnicity, cadaveric donor source, DGF, and HLA mismatching.

A 9-year experience with 126 pancreas transplants with portal enteric drainage.

HYPOTHESIS: A novel technique of pancreas transplantation (PTX) with portal venous delivery of insulin and enteric exocrine drainage (portal enteric) was developed at our center to improve the PTX procedure. DESIGN: Case series. SETTING: Single-center experience at a university hospital. PATIENTS AND INTERVENTION: From October 1990 through December 1999, we performed 126 PTXs with portal enteric drainage, including 90 simultaneous kidney PTXs (SKPT) and 36 solitary PTXs (18 sequential PTXs after kidney transplantation and 18 PTXs alone). MAIN OUTCOME MEASURES: Patient and graft survival rates; medical and surgical morbidity. Three groups, representing 3 eras of immunosuppression, were compared. Thirty patients underwent SKPT with muromonab-CD3 induction and cyclosporine-based therapy in era 1 (October 1990 through June 1995); 42 SKPTs received tacrolimus and mycophenolate mofetil-based immunosuppression without antibody induction in era 2 (July 1995 through May 1998); and 18 SKPTs were performed in era 3 (June 1998 through December 1999) with either basiliximab or daclizumab induction. RESULTS: One-year patient survival rates after SKPT were 77% in era 1, 93% in era 2, and 100% in era 3 (P =.03). The 1-year kidney graft survival rates were 77% in era 1, 93% in era 2, and 94% in era 3 (P =.08). The 1-year pancreas graft survival rates after SKPT were 60% in era 1, 83% in era 2, and 83% in era 3 (P =.06). The incidences of rejection (63% vs. 33% vs. 39%; P<.001) and thrombosis (20% vs. 7% vs. 6%; P<.001) were decreased in eras 2 and 3. CONCLUSION: Simultaneous kidney PTXs with portal enteric drainage can be performed with improved outcomes.

Long-term outcomes in simultaneous kidney-pancreas transplant recipients with portal-enteric versus systemic-bladder drainage.

We retrospectively reviewed long-term outcomes in simultaneous kidney-pancreas transplant (SKPT) recipients with portal-enteric (P-E) versus systemic-bladder (S-B) drainage. Forty-five patients were alive with functioning grafts 1 year after SKPT and were followed up for a minimum of 3 years (mean, 5.9 years), including 26 patients with P-E drainage and 19 patients with S-B drainage. Recipient demographic and transplant characteristics were similar between the two groups. In both groups, hospital admissions decreased significantly with increasing time after SKPT, although significantly fewer readmissions occurred in the first year in the P-E than the S-B group. The most common reason for readmission in both groups was infection, followed by miscellaneous, surgical, and immunologic morbidity. The incidence of readmission for dehydration was significantly less in the P-E group (P < 0.01). Mean systolic and diastolic blood pressures were similar between groups, although the number of antihypertensive medications was significantly less in the S-B group. Although fasting C-peptide levels were significantly greater in the S-B group, the two groups were similar with regard to carbohydrate (fasting serum glucose, hemoglobin A(1c)) and lipid (total cholesterol) metabolism. Renal and pancreas allograft functions were similar between the two groups. At 1 year post-SKPT, stabilization in most diabetic complications was reported. Four quality-of-life surveys that provided 29 scores were completed 6 to 24 months (mean, 18.5 months) after SKPT. Improved quality of life was reported in all but one of the scales, with many dimensions showing significant improvements. At 3 years after SKPT, no activity limitation was reported in 76% of patients with P-E drainage versus 53% with S-B drainage (P = 0.11). Five-year actual patient, kidney, and pancreas graft survival rates after P-E versus S-B drainage are 92% and 84%, 81% and 79%, and 88% and 74%, respectively (P = not significant). SKPT with P-E drainage is a safe and effective method to treat advanced diabetic nephropathy and is associated with decreasing morbidity, improving rehabilitation and quality of life, and stablizing metabolic function over time. The long-term prognosis after the first year is excellent and at least similar to the results achieved with S-B drainage.

Patterns of cytomegalovirus infection in simultaneous kidney-pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and prednisone with ganciclovir prophylaxis.

BACKGROUND: The impact of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroid immunosuppression on cytomegalovirus (CMV) infection in combination with ganciclovir prophylaxis in simultaneous kidney-pancreas transplantation (SKPT) has not been well studied. METHODS: A retrospective analysis was made of 75 SKPTs performed between 1 January 1996 and 7 January 1999. All patients received ganciclovir for 3 months, but CMV donor (D)+ / recipient (R)- patients received ganciclovir for 6 months. RESULTS: 16/74 (22%) were CMV D+/R-, 25 (33%) D+/R+, 16 (22%) D-/R+, and 17 (23%) D-/R- (1 patient with unknown donor serology was excluded). The mean time to CMV infection was 198 days post-transplant. The incidence of either CMV infection or tissue invasive CMV disease was 16/74 (22%), including 9 (12%) with CMV infection and 7 (10%) CMV disease. The one-year patient, kidney, and pancreas graft survival rates were 91%, 89%, and 83%, respectively. The mean follow-up was 29 months (minimum of 12 months). CMV infection was not associated with an increased incidence of graft failure or mortality. The D+/R- group had the highest incidence of CMV infection (44%) compared with the other serologic groups (17%, P=0.02). Concurrent CMV and rejection occurred more frequently in the D+/R- than the other serologic groups (25% vs. 7%, P=0.03). The D-/R- group had the best outcomes, with no CMV infection, improved kidney graft survival at the end of follow-up (82% vs. 72%, P=0.04) and the highest event-free survival (no CMV infection, rejection, or graft loss) when compared to the other groups (76% vs. 33%, P<0.01). CONCLUSIONS: Compared to previous studies, ganciclovir prophylaxis delayed the onset and reduced the severity of CMV infection in patients receiving TAC, MMF, and steroids. Despite ganciclovir prophylaxis, CMV seronegative patients receiving CMV D+ organs had worse outcomes than seronegative recipients receiving CMV D- organs.

Human granulocytic ehrlichiosis in pancreas transplant recipients.

Human ehrlichioses are tick-borne infections caused by bacteria in the genus Ehrlichia of the family Rickettsiaceae. To date there have been three cases of ehrlichiosis reported in the transplant population, a human monocytic ehrlichiosis (HME) infection in a liver transplant recipient and two cases of human granulocytic ehrlichiosis (HGE) in kidney transplant recipients. We report three pancreas transplant patients who developed HGE in the last two years at a single southeastern center in the United States. All three patients had clinical, laboratory, and pathophysiologic findings on bone marrow biopsy and peripheral blood smears consistent with HGE, and responded to doxycycline therapy. In the setting of potent immunosuppression, ehrlichiosis should be considered in the differential diagnosis of transplant patients presenting with persistent fever, pancytopenia, and abnormal liver function. Patients with ehrlichiosis infection may be at risk for developing other opportunistic infections or lymphoproliferative disease.

A prospective comparison of simultaneous kidney-pancreas transplantation with systemic-enteric versus portal-enteric drainage.

OBJECTIVE: To compare pancreas transplantation with systemic-enteric (SE) versus portal-enteric (PE) drainage in a prospective fashion. SUMMARY BACKGROUND DATA: To improve the physiology of pancreas transplantation, the authors developed a new technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions. METHODS: During a 26-month period, the authors prospectively alternated 54 consecutive simultaneous kidney and pancreas transplants to either SE (n = 27) or PE (n = 27) drainage. The two groups were well matched for numerous characteristics. Maintenance immunosuppression in both groups consisted of tacrolimus, mycophenolate mofetil, and steroids. RESULTS: Patient survival rates were 93% SE versus 96% PE; kidney graft survival rates were 93% in both groups. Pancreas transplantation survival (complete insulin independence) was 74% after SE versus 85% after PE drainage with a mean follow-up of 17 months. The mean length of initial hospital stay was 12.4 days in the SE group and 12.8 days in the PE group. The SE group was characterized by a slight increase in the number of readmissions. The incidences of acute rejection (33%) and major infection (52%) were similar in both groups. The incidence of intraabdominal infection was slightly higher in the SE group. However, the early relaparotomy rate was similar between groups. The composite endpoint of no rejection, graft loss, or death was attained in 56% of SE versus 59% of PE patients. CONCLUSIONS: These results suggest that simultaneous kidney and pancreas transplantation with SE or PE drainage can be performed with comparable short-term outcomes.

Surgical technique for right lobe adult living donor liver transplantation without venovenous bypass or portocaval shunting and with duct-to-duct biliary reconstruction.

OBJECTIVE: To report the authors' experience with adult living donor liver transplantation (ALDLT) without venovenous bypass and to describe modifications that will allow for a direct duct-to-duct biliary reconstruction. SUMMARY BACKGROUND DATA: Adult living donor liver transplantation is being evaluated as a method to alleviate the organ shortage. Descriptions of the procedure have emphasized the use of venovenous bypass, portocaval decompression, and the mandatory use of a Roux-en-Y biliary enteric anastomosis. The authors describe a technique for ALDLT without venovenous bypass, portocaval decompression, or caval clamping in 11 recipients and describe the modifications to the procedure that may allow a duct-to-duct biliary reconstruction in certain cases. METHODS: Between March 1999 and March 2000, 11 ALDLTs were performed at the authors' institution. All procedures were performed without venovenous bypass, portocaval decompression, or caval clamping. After a modification to the procedure, five of the last six recipients underwent biliary reconstruction with a direct duct-to-duct anastomosis. Data regarding donor, recipient, and graft survival, complications, and graft function were collected. RESULTS: Recipients comprised five women and six men, mean age 48 years. Donors comprised five women and six men, mean age 36.5 years. Donor to recipient relationships included sibling, spouse, son, and daughter. Indications for transplantation were hepatitis C, hepatitis C with hepatocellular carcinoma, primary biliary cirrhosis, primary sclerosing cholangitis, ethanol, and cryptogenic. No case required venovenous bypass or portocaval shunting. The right hepatic vein of the donor graft was anastomosed to the confluence of the left and middle hepatic veins in all cases. All donors are alive and well, with no adverse complications reported. Recipient and graft survival rates were 91% and 82%, respectively, for ALDLT versus 92% and 92% for recipients of cadaveric organs during the same time period. One recipient died of multiple organ failure and sepsis. Biliary reconstruction was performed by Roux-en-Y hepaticojejunostomy in the six cases. In five of the last six recipients, direct duct-to-duct biliary reconstruction with a T tube was used. No anastomotic leaks or strictures occurred in the patients undergoing duct-to-duct reconstruction. CONCLUSIONS: Adult living donor liver transplantation can be performed safely and may help alleviate the organ shortage. Neither venovenous bypass nor portocaval shunting is necessary to perform the procedure, and modifications to both the donor and recipient hepatectomy procedures may allow biliary reconstruction to be performed by a direct duct-to-duct anastomosis in selected cases.