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In Type 1 Diabetes, Cardiac Measures Improved After Pancreas Transplant
BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.
After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.
She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.
Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.
At last follow-up, fasting plasma glucose level had normalized, hemoglobin A1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.
There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.
Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m2 to 73 mg/m2; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.
Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.
In this group, there were no significant changes in HbA1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.
Dr. Occhipinti said she had no relevant financial disclosures.
BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.
After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.
She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.
Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.
At last follow-up, fasting plasma glucose level had normalized, hemoglobin A1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.
There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.
Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m2 to 73 mg/m2; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.
Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.
In this group, there were no significant changes in HbA1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.
Dr. Occhipinti said she had no relevant financial disclosures.
BERLIN -- A pancreas-only transplant improved cardiac function and morphology in a group of patients with type 1 diabetes.
After 5 years, the patients showed significantly improved posterior wall and interventricular septal thickness, as well as a significantly increased left ventricular ejection fraction, Dr. Margherita Occhipinti said at the annual meeting of the European Societies for the Study of Diabetes.
She reported 5-year follow-up data on 35 patients with type 1 diabetes who underwent the procedure. The patients were a mean of 38 years old and had a mean disease duration of 25 years. Their mean insulin requirement was 43 U/day.
Most of the transplants (74%) were performed with a portal-enteric drain technique; the remainder had systemic-enteric drainage, said Dr. Occhipinti of the University of Pisa (Italy). The majority (77%) had induction therapy with basiliximab; the rest had antithymocyte globulin (rabbit) induction. The maintenance immunosuppressant regimen was a combination of mycophenolate mofetil, tacrolimus, and steroids.
At last follow-up, fasting plasma glucose level had normalized, hemoglobin A1c level had fallen from 9% to just under 6%, and C-peptide level had increased from under 1 ng/mL to almost 3 ng/mL.
There were no significant changes in either systolic or diastolic blood pressure. However, the number of patients taking ACE inhibitors or angiotensin receptor blockers decreased from 59% to 43%. Total and LDL cholesterol levels decreased significantly, although there were no significant changes in HDL cholesterol or triglycerides.
Cardiac morphology changed significantly, Dr. Occhipinti said, including a significant decrease in posterior wall thickness during diastole, from 8.1 mm to 7.0 mm, and interventricular septum thickness during diastole, from 9.3 mm to 8.7 mm. The left ventricular mass index decreased significantly, from 82 mg/m2 to 73 mg/m2; and the left ventricular ejection fraction increased significantly, from 55.3% to 57.9%.
Dr. Occhipinti compared these changes to 2-year findings in a group of 11 control patients who were on a transplant waiting list or who had a failed pancreatic transplant.
In this group, there were no significant changes in HbA1c, left ventricular ejection fraction, or any of the measures of cardiac morphology.
Dr. Occhipinti said she had no relevant financial disclosures.
AT THE ANNUAL MEETING OF THE EUROPEAN SOCIETIES FOR THE STUDY OF DIABETES
Major Finding: Cardiac morphology and function improved significantly after pancreas-only transplant: Posterior wall thickness and interventricular septum thickness decreased during diastole, from 8.1 mm to 7.0 mm and from 9.3 mm to 8.7 mm, respectively; left ventricular mass index decreased from 82 mg/m2 to 73 mg/m2; and left ventricular ejection fraction increased, from 55.3% to 57.9%.
Data Source: Data are from 35 patients with longstanding type 1 diabetes.
Disclosures: Dr. Occhipinti said she had no relevant financial disclosures.
Triple Therapy Boosts HCV Response After Transplant
BOSTON – Liver transplant recipients with hepatitis C virus infection who underwent triple-drug therapy achieved a high extended rapid virologic response rate but often contended with treatment complications in a retrospective multicenter cohort study.
The extended rapid virologic response (eRVR) rate seen in 57% of patients was "encouraging, given a very difficult-to-cure population," Dr. James R. Burton, Jr., said at the annual meeting of the American Association for the Study of Liver Diseases. He noted, however, that it’s not clear if the encouraging eRVR rate will predict sustained virologic response (SVR) as it does in non-liver transplant patients.
The use of peginteferon plus ribavirin in liver transplant recipients with hepatitis C virus infection has an SVR of only 30%. While triple therapy with peginterferon, ribavirin, and a protease inhibitor (boceprevir or telaprevir) has significantly improved rates of SVR in patients infected with genotype 1 hepatitis C virus, its safety and efficacy in liver transplant recipients is unknown, said Dr. Burton, medical director of liver transplantation at the University of Colorado Hospital, Aurora.
With 101 patients, the five-center study is the largest involving triple therapy in liver transplant recipients with hepatitis C virus infection.
Telaprevir was the protease inhibitor used most often in patients (90% vs. 10% with boceprevir). Nearly all patients (96%) had a lead-in treatment phase with peginterferon plus ribavirin. A minority of patients (14%) had an extended lead-in phase of at least 90 days (median of 189 days) and were excluded from efficacy, but not safety, analyses. The other patients had a lead-in lasting a median of 29 days. The patients with a long lead-in phase had a median of 398 total treatment days, compared with a median of 154 days for those with a shorter lead-in time.
The efficacy study population involved genotype 1–infected patients (54% genotype 1a, 39% 1b, and 7% mixed) from five medical centers. Most patients were men (76%); they had a median age of 58 years and a median duration of 54 months from their liver transplant to starting a protease inhibitor. An unfavorable IL28B genotype was found in 69% of 45 patients tested. In the 60% of patients who had undergone previous antiviral therapy, 29% had a partial response. On liver biopsy, another 47% of patients had either bridging fibrosis or cirrhosis.
The immunosuppressive agents used by the patients included cyclosporine (66%) and tacrolimus (23%). A small percentage did not receive a calcineurin inhibitor or rapamycin. Another 27% were taking corticosteroids, and 72% were taking mycophenolate mofetil or mycophenolic acid.
On treatment, the percentage of patients who had an HCV RNA level less than the limit of detection increased from 55% at 4 weeks to 63% at 8 weeks. At 12 weeks the percentage was 71%. An eRVR, defined as negative HCV RNA tests at 4 and 12 weeks, occurred in 57%. An eRVR occurred significantly more often among patients who had at least a 1 log drop in HCV RNA levels during the lead-in phase than did those with less than a 1 log drop (76% vs. 35%).
Overall, 12% of patients experienced virologic breakthrough, and treatment was stopped. This occurred more often among those with a long lead-in vs. those with a short lead-in (21% vs. 10%, respectively). Another 14% discontinued treatment early because of an adverse event; discontinuations occurred more often among patients with a long lead-in (40% vs. 11%).
Protease inhibitors are known to inhibit the metabolism of calcineurin inhibitors, which was reflected in the study by the need to reduce the median daily doses of cyclosporine (from 200 mg to 50 mg) and tacrolimus (from 1.0 mg to 0.06 mg) after protease inhibitor therapy began.
Many patients (49%) required blood transfusions during triple therapy. During the first 16 weeks of therapy, these patients used a median of 2.5 units. The majority of patients (86%) used growth factors, including granulocyte-colony stimulating factor in 44% and erythropoietin in 79%. Medication dose reductions were most frequent for ribavirin (in 78%). A total of 7% were hospitalized for anemia, Dr. Burton said.
Renal insufficiency, defined as an increase in creatinine of greater than 0.5 mg/dL from baseline, developed in 32%. Of two rejection episodes in the study, one involved a patient coming off a protease inhibitor.
Dr. Burton suggested that future studies should focus on identifying predictors for nonresponse to avoid unnecessary treatment and associated toxicities such as complications of anemia and adverse events related to significant protease inhibitor–calcineurin inhibitor interactions, such as worsening renal function and graft rejection when transitioning off a protease inhibitor.
Dr. Burton disclosed that he is an investigator in a clinical trial sponsored by Vertex Pharmaceuticals, which makes telaprevir.☐
BOSTON – Liver transplant recipients with hepatitis C virus infection who underwent triple-drug therapy achieved a high extended rapid virologic response rate but often contended with treatment complications in a retrospective multicenter cohort study.
The extended rapid virologic response (eRVR) rate seen in 57% of patients was "encouraging, given a very difficult-to-cure population," Dr. James R. Burton, Jr., said at the annual meeting of the American Association for the Study of Liver Diseases. He noted, however, that it’s not clear if the encouraging eRVR rate will predict sustained virologic response (SVR) as it does in non-liver transplant patients.
The use of peginteferon plus ribavirin in liver transplant recipients with hepatitis C virus infection has an SVR of only 30%. While triple therapy with peginterferon, ribavirin, and a protease inhibitor (boceprevir or telaprevir) has significantly improved rates of SVR in patients infected with genotype 1 hepatitis C virus, its safety and efficacy in liver transplant recipients is unknown, said Dr. Burton, medical director of liver transplantation at the University of Colorado Hospital, Aurora.
With 101 patients, the five-center study is the largest involving triple therapy in liver transplant recipients with hepatitis C virus infection.
Telaprevir was the protease inhibitor used most often in patients (90% vs. 10% with boceprevir). Nearly all patients (96%) had a lead-in treatment phase with peginterferon plus ribavirin. A minority of patients (14%) had an extended lead-in phase of at least 90 days (median of 189 days) and were excluded from efficacy, but not safety, analyses. The other patients had a lead-in lasting a median of 29 days. The patients with a long lead-in phase had a median of 398 total treatment days, compared with a median of 154 days for those with a shorter lead-in time.
The efficacy study population involved genotype 1–infected patients (54% genotype 1a, 39% 1b, and 7% mixed) from five medical centers. Most patients were men (76%); they had a median age of 58 years and a median duration of 54 months from their liver transplant to starting a protease inhibitor. An unfavorable IL28B genotype was found in 69% of 45 patients tested. In the 60% of patients who had undergone previous antiviral therapy, 29% had a partial response. On liver biopsy, another 47% of patients had either bridging fibrosis or cirrhosis.
The immunosuppressive agents used by the patients included cyclosporine (66%) and tacrolimus (23%). A small percentage did not receive a calcineurin inhibitor or rapamycin. Another 27% were taking corticosteroids, and 72% were taking mycophenolate mofetil or mycophenolic acid.
On treatment, the percentage of patients who had an HCV RNA level less than the limit of detection increased from 55% at 4 weeks to 63% at 8 weeks. At 12 weeks the percentage was 71%. An eRVR, defined as negative HCV RNA tests at 4 and 12 weeks, occurred in 57%. An eRVR occurred significantly more often among patients who had at least a 1 log drop in HCV RNA levels during the lead-in phase than did those with less than a 1 log drop (76% vs. 35%).
Overall, 12% of patients experienced virologic breakthrough, and treatment was stopped. This occurred more often among those with a long lead-in vs. those with a short lead-in (21% vs. 10%, respectively). Another 14% discontinued treatment early because of an adverse event; discontinuations occurred more often among patients with a long lead-in (40% vs. 11%).
Protease inhibitors are known to inhibit the metabolism of calcineurin inhibitors, which was reflected in the study by the need to reduce the median daily doses of cyclosporine (from 200 mg to 50 mg) and tacrolimus (from 1.0 mg to 0.06 mg) after protease inhibitor therapy began.
Many patients (49%) required blood transfusions during triple therapy. During the first 16 weeks of therapy, these patients used a median of 2.5 units. The majority of patients (86%) used growth factors, including granulocyte-colony stimulating factor in 44% and erythropoietin in 79%. Medication dose reductions were most frequent for ribavirin (in 78%). A total of 7% were hospitalized for anemia, Dr. Burton said.
Renal insufficiency, defined as an increase in creatinine of greater than 0.5 mg/dL from baseline, developed in 32%. Of two rejection episodes in the study, one involved a patient coming off a protease inhibitor.
Dr. Burton suggested that future studies should focus on identifying predictors for nonresponse to avoid unnecessary treatment and associated toxicities such as complications of anemia and adverse events related to significant protease inhibitor–calcineurin inhibitor interactions, such as worsening renal function and graft rejection when transitioning off a protease inhibitor.
Dr. Burton disclosed that he is an investigator in a clinical trial sponsored by Vertex Pharmaceuticals, which makes telaprevir.☐
BOSTON – Liver transplant recipients with hepatitis C virus infection who underwent triple-drug therapy achieved a high extended rapid virologic response rate but often contended with treatment complications in a retrospective multicenter cohort study.
The extended rapid virologic response (eRVR) rate seen in 57% of patients was "encouraging, given a very difficult-to-cure population," Dr. James R. Burton, Jr., said at the annual meeting of the American Association for the Study of Liver Diseases. He noted, however, that it’s not clear if the encouraging eRVR rate will predict sustained virologic response (SVR) as it does in non-liver transplant patients.
The use of peginteferon plus ribavirin in liver transplant recipients with hepatitis C virus infection has an SVR of only 30%. While triple therapy with peginterferon, ribavirin, and a protease inhibitor (boceprevir or telaprevir) has significantly improved rates of SVR in patients infected with genotype 1 hepatitis C virus, its safety and efficacy in liver transplant recipients is unknown, said Dr. Burton, medical director of liver transplantation at the University of Colorado Hospital, Aurora.
With 101 patients, the five-center study is the largest involving triple therapy in liver transplant recipients with hepatitis C virus infection.
Telaprevir was the protease inhibitor used most often in patients (90% vs. 10% with boceprevir). Nearly all patients (96%) had a lead-in treatment phase with peginterferon plus ribavirin. A minority of patients (14%) had an extended lead-in phase of at least 90 days (median of 189 days) and were excluded from efficacy, but not safety, analyses. The other patients had a lead-in lasting a median of 29 days. The patients with a long lead-in phase had a median of 398 total treatment days, compared with a median of 154 days for those with a shorter lead-in time.
The efficacy study population involved genotype 1–infected patients (54% genotype 1a, 39% 1b, and 7% mixed) from five medical centers. Most patients were men (76%); they had a median age of 58 years and a median duration of 54 months from their liver transplant to starting a protease inhibitor. An unfavorable IL28B genotype was found in 69% of 45 patients tested. In the 60% of patients who had undergone previous antiviral therapy, 29% had a partial response. On liver biopsy, another 47% of patients had either bridging fibrosis or cirrhosis.
The immunosuppressive agents used by the patients included cyclosporine (66%) and tacrolimus (23%). A small percentage did not receive a calcineurin inhibitor or rapamycin. Another 27% were taking corticosteroids, and 72% were taking mycophenolate mofetil or mycophenolic acid.
On treatment, the percentage of patients who had an HCV RNA level less than the limit of detection increased from 55% at 4 weeks to 63% at 8 weeks. At 12 weeks the percentage was 71%. An eRVR, defined as negative HCV RNA tests at 4 and 12 weeks, occurred in 57%. An eRVR occurred significantly more often among patients who had at least a 1 log drop in HCV RNA levels during the lead-in phase than did those with less than a 1 log drop (76% vs. 35%).
Overall, 12% of patients experienced virologic breakthrough, and treatment was stopped. This occurred more often among those with a long lead-in vs. those with a short lead-in (21% vs. 10%, respectively). Another 14% discontinued treatment early because of an adverse event; discontinuations occurred more often among patients with a long lead-in (40% vs. 11%).
Protease inhibitors are known to inhibit the metabolism of calcineurin inhibitors, which was reflected in the study by the need to reduce the median daily doses of cyclosporine (from 200 mg to 50 mg) and tacrolimus (from 1.0 mg to 0.06 mg) after protease inhibitor therapy began.
Many patients (49%) required blood transfusions during triple therapy. During the first 16 weeks of therapy, these patients used a median of 2.5 units. The majority of patients (86%) used growth factors, including granulocyte-colony stimulating factor in 44% and erythropoietin in 79%. Medication dose reductions were most frequent for ribavirin (in 78%). A total of 7% were hospitalized for anemia, Dr. Burton said.
Renal insufficiency, defined as an increase in creatinine of greater than 0.5 mg/dL from baseline, developed in 32%. Of two rejection episodes in the study, one involved a patient coming off a protease inhibitor.
Dr. Burton suggested that future studies should focus on identifying predictors for nonresponse to avoid unnecessary treatment and associated toxicities such as complications of anemia and adverse events related to significant protease inhibitor–calcineurin inhibitor interactions, such as worsening renal function and graft rejection when transitioning off a protease inhibitor.
Dr. Burton disclosed that he is an investigator in a clinical trial sponsored by Vertex Pharmaceuticals, which makes telaprevir.☐
AT THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES
Major Finding: An extended rapid virologic response occurred significantly more often among patients who had at least a 1 log drop in HCV RNA levels during the lead-in phase than did those with less than a 1 log drop (76% vs. 35%)
Data Source: This was a multicenter retrospective cohort study of triple therapy for hepatitis C virus infection in 101 patients with post liver transplant.
Disclosures: Dr. Burton disclosed that he is an investigator in a clinical trial sponsored by Vertex Pharmaceuticals, which makes telaprevir.
Kidneys Benefited From Everolimus After Liver Transplant
BOSTON – Everolimus given with a reduced dose of tacrolimus to liver transplant patients yielded similar rates of acute rejection, graft loss, and death, but better kidney function than standard-dose tacrolimus alone at 2 years in a randomized, open-label, multicenter, controlled trial.
These 2-year results confirm and build on the recently published results of the trial at 1 year (Am. J. Transpl. 2012;12:3008-20), lead investigator Dr. Faouzi Saliba of Paul Brousse Hospital, Villejuif, France, reported at the annual meeting of the American Association for the Study of Liver Diseases.
Since the first study was published 9 years ago documenting a cumulative incidence of chronic renal failure of 28% after 10 years of tacrolimus treatment after liver transplant (N. Engl. J. Med. 2003;349:931-40), another study has reported estimated glomerular filtration rates (eGFRs) of less than 60 mL/min per 1.73 m2 (stage 3 chronic kidney failure) for 58% of liver transplant recipients after 5 years of treatment with tacrolimus (Liver Transpl. 2009:15:1083-91).
On the basis of the effectiveness of everolimus in reducing the dose of calcineurin inhibitor needed for immunosuppression without reducing efficacy in patients with de novo kidney transplantation (Am. J. Transpl. 2010;10:1401-13), Dr. Saliba and his coinvestigators conducted the current trial.
Following a 30-day run-in period in which liver transplant recipients received tacrolimus with or without mycophenolate mofetil and prednisone, the investigators randomized 719 patients to three arms: two arms with everolimus 3-8 ng/mL, tacrolimus reduced to 3-5 ng/mL, and prednisone, and a control arm with tacrolimus dosed to a standard 8-12 ng/mL plus prednisone. After 4 months, in one of the reduced-dose arms, tacrolimus was withdrawn and the everolimus dose was increased to 8-10 ng/mL (231 patients), whereas the dose of everolimus was kept constant in the other reduced-dose arm (245 patients) and the dose of tacrolimus was kept the same in the control arm (243 patients). Prednisone could be eliminated at 4 months in any arm. However, enrollment into the tacrolimus withdrawal arm was stopped at the time of conversion to everolimus alone because of a high rate of rejection episodes, and the trial’s protocol was amended to compare efficacy between only the reduced-dose and control arms.
By 2 years, the number of patients who completed the study was similar in both the reduced-dose and control arms (82% vs. 84%, respectively), and similar percentages in each group remained on the study medications at 2 years (58% vs. 68%, respectively).
In each group, recipients were mostly men (74%) and white (80%-86%), with a mean age of 54 years and mean donor age of 49 years. They had a Model for End-Stage Liver Disease score of 19, and eGFRs of about 80 mL/min per 1.73 m2.
Mean levels of tacrolimus dropped from 10.5 ng/mL at randomization to 4 ng/mL at 2 years in the dose-reduction arm, compared with 10 ng/mL to 7 ng/mL in the control arm.
At 2 years in the intent-to-treat population, the groups had similar rates of the composite primary end point of treated biopsy-proven acute rejection, graft failure, and death (10.5% in the dose-reduction arm and 12.5% in the control arm). Biopsy-proven acute rejection occurred at a significantly lower rate among dose-reduced patients (6%) than among control patients (13%). All of the episodes of acute rejection in the tacrolimus dose-reduced patients were borderline or mild based on the Banff rejection activity index. However, liver biopsies at 1 and 2 years were only part of the trial’s protocol for hepatitis C virus (HCV)-infected patients. The decision to biopsy was otherwise left up to the physicians of each center.
At 1 year, there appeared to be less fibrosis in patients who received everolimus, Dr. Saliba said in response to a question from the audience. In about half of the 75 HCV-infected patients in the dose-reduction arm, liver biopsies showed less fibrosis of at least stage 1 than in patients with HCV infection in the other group. The investigators are now analyzing 2-year data, he said.
The dose-reduced group maintained significantly better eGFR than the control group, through the duration of the trial, finishing with levels of 66 vs. 78 mL/min per 1.73 m2.
Several types of adverse events with an incidence of at least 10% occurred more often in the dose-reduction arm than in the control arm, including leucopenia (13% vs. 5%), peripheral edema (20% vs. 13%), and hypercholesterolemia (11% vs. 4%).
Proteinuria of less than 0.5 g/24 hours occurred in 92%-93% of the patients; none of the patients had severe proteinuria of 3 g/24 hours or more.
One audience member noted that the most important patients to study in this clinical population are those on the borderline of renal failure with low eGFR and elevated creatinine, who would benefit most from improved renal function. Dr. Saliba said that at the time of randomization, the investigators looked at levels of eGFR in each group and over the course of the 2 years, more patients in the standard-dose tacrolimus arm had worsened renal function, whereas many in the dose-reduction arm had improved or at least stable renal function, and few had worsened function.
The study was sponsored by Novartis, which manufactures everolimus. Dr. Saliba reported financial ties to Novartis and Astellas Pharma (manufacturer of tacrolimus), as well as other companies that manufacture drugs used by liver transplant patients. Several other investigators reported financial ties to companies that manufacture antirejection drugs used in liver transplant patients, including Novartis. Three study investigators are employees of Novartis.
BOSTON – Everolimus given with a reduced dose of tacrolimus to liver transplant patients yielded similar rates of acute rejection, graft loss, and death, but better kidney function than standard-dose tacrolimus alone at 2 years in a randomized, open-label, multicenter, controlled trial.
These 2-year results confirm and build on the recently published results of the trial at 1 year (Am. J. Transpl. 2012;12:3008-20), lead investigator Dr. Faouzi Saliba of Paul Brousse Hospital, Villejuif, France, reported at the annual meeting of the American Association for the Study of Liver Diseases.
Since the first study was published 9 years ago documenting a cumulative incidence of chronic renal failure of 28% after 10 years of tacrolimus treatment after liver transplant (N. Engl. J. Med. 2003;349:931-40), another study has reported estimated glomerular filtration rates (eGFRs) of less than 60 mL/min per 1.73 m2 (stage 3 chronic kidney failure) for 58% of liver transplant recipients after 5 years of treatment with tacrolimus (Liver Transpl. 2009:15:1083-91).
On the basis of the effectiveness of everolimus in reducing the dose of calcineurin inhibitor needed for immunosuppression without reducing efficacy in patients with de novo kidney transplantation (Am. J. Transpl. 2010;10:1401-13), Dr. Saliba and his coinvestigators conducted the current trial.
Following a 30-day run-in period in which liver transplant recipients received tacrolimus with or without mycophenolate mofetil and prednisone, the investigators randomized 719 patients to three arms: two arms with everolimus 3-8 ng/mL, tacrolimus reduced to 3-5 ng/mL, and prednisone, and a control arm with tacrolimus dosed to a standard 8-12 ng/mL plus prednisone. After 4 months, in one of the reduced-dose arms, tacrolimus was withdrawn and the everolimus dose was increased to 8-10 ng/mL (231 patients), whereas the dose of everolimus was kept constant in the other reduced-dose arm (245 patients) and the dose of tacrolimus was kept the same in the control arm (243 patients). Prednisone could be eliminated at 4 months in any arm. However, enrollment into the tacrolimus withdrawal arm was stopped at the time of conversion to everolimus alone because of a high rate of rejection episodes, and the trial’s protocol was amended to compare efficacy between only the reduced-dose and control arms.
By 2 years, the number of patients who completed the study was similar in both the reduced-dose and control arms (82% vs. 84%, respectively), and similar percentages in each group remained on the study medications at 2 years (58% vs. 68%, respectively).
In each group, recipients were mostly men (74%) and white (80%-86%), with a mean age of 54 years and mean donor age of 49 years. They had a Model for End-Stage Liver Disease score of 19, and eGFRs of about 80 mL/min per 1.73 m2.
Mean levels of tacrolimus dropped from 10.5 ng/mL at randomization to 4 ng/mL at 2 years in the dose-reduction arm, compared with 10 ng/mL to 7 ng/mL in the control arm.
At 2 years in the intent-to-treat population, the groups had similar rates of the composite primary end point of treated biopsy-proven acute rejection, graft failure, and death (10.5% in the dose-reduction arm and 12.5% in the control arm). Biopsy-proven acute rejection occurred at a significantly lower rate among dose-reduced patients (6%) than among control patients (13%). All of the episodes of acute rejection in the tacrolimus dose-reduced patients were borderline or mild based on the Banff rejection activity index. However, liver biopsies at 1 and 2 years were only part of the trial’s protocol for hepatitis C virus (HCV)-infected patients. The decision to biopsy was otherwise left up to the physicians of each center.
At 1 year, there appeared to be less fibrosis in patients who received everolimus, Dr. Saliba said in response to a question from the audience. In about half of the 75 HCV-infected patients in the dose-reduction arm, liver biopsies showed less fibrosis of at least stage 1 than in patients with HCV infection in the other group. The investigators are now analyzing 2-year data, he said.
The dose-reduced group maintained significantly better eGFR than the control group, through the duration of the trial, finishing with levels of 66 vs. 78 mL/min per 1.73 m2.
Several types of adverse events with an incidence of at least 10% occurred more often in the dose-reduction arm than in the control arm, including leucopenia (13% vs. 5%), peripheral edema (20% vs. 13%), and hypercholesterolemia (11% vs. 4%).
Proteinuria of less than 0.5 g/24 hours occurred in 92%-93% of the patients; none of the patients had severe proteinuria of 3 g/24 hours or more.
One audience member noted that the most important patients to study in this clinical population are those on the borderline of renal failure with low eGFR and elevated creatinine, who would benefit most from improved renal function. Dr. Saliba said that at the time of randomization, the investigators looked at levels of eGFR in each group and over the course of the 2 years, more patients in the standard-dose tacrolimus arm had worsened renal function, whereas many in the dose-reduction arm had improved or at least stable renal function, and few had worsened function.
The study was sponsored by Novartis, which manufactures everolimus. Dr. Saliba reported financial ties to Novartis and Astellas Pharma (manufacturer of tacrolimus), as well as other companies that manufacture drugs used by liver transplant patients. Several other investigators reported financial ties to companies that manufacture antirejection drugs used in liver transplant patients, including Novartis. Three study investigators are employees of Novartis.
BOSTON – Everolimus given with a reduced dose of tacrolimus to liver transplant patients yielded similar rates of acute rejection, graft loss, and death, but better kidney function than standard-dose tacrolimus alone at 2 years in a randomized, open-label, multicenter, controlled trial.
These 2-year results confirm and build on the recently published results of the trial at 1 year (Am. J. Transpl. 2012;12:3008-20), lead investigator Dr. Faouzi Saliba of Paul Brousse Hospital, Villejuif, France, reported at the annual meeting of the American Association for the Study of Liver Diseases.
Since the first study was published 9 years ago documenting a cumulative incidence of chronic renal failure of 28% after 10 years of tacrolimus treatment after liver transplant (N. Engl. J. Med. 2003;349:931-40), another study has reported estimated glomerular filtration rates (eGFRs) of less than 60 mL/min per 1.73 m2 (stage 3 chronic kidney failure) for 58% of liver transplant recipients after 5 years of treatment with tacrolimus (Liver Transpl. 2009:15:1083-91).
On the basis of the effectiveness of everolimus in reducing the dose of calcineurin inhibitor needed for immunosuppression without reducing efficacy in patients with de novo kidney transplantation (Am. J. Transpl. 2010;10:1401-13), Dr. Saliba and his coinvestigators conducted the current trial.
Following a 30-day run-in period in which liver transplant recipients received tacrolimus with or without mycophenolate mofetil and prednisone, the investigators randomized 719 patients to three arms: two arms with everolimus 3-8 ng/mL, tacrolimus reduced to 3-5 ng/mL, and prednisone, and a control arm with tacrolimus dosed to a standard 8-12 ng/mL plus prednisone. After 4 months, in one of the reduced-dose arms, tacrolimus was withdrawn and the everolimus dose was increased to 8-10 ng/mL (231 patients), whereas the dose of everolimus was kept constant in the other reduced-dose arm (245 patients) and the dose of tacrolimus was kept the same in the control arm (243 patients). Prednisone could be eliminated at 4 months in any arm. However, enrollment into the tacrolimus withdrawal arm was stopped at the time of conversion to everolimus alone because of a high rate of rejection episodes, and the trial’s protocol was amended to compare efficacy between only the reduced-dose and control arms.
By 2 years, the number of patients who completed the study was similar in both the reduced-dose and control arms (82% vs. 84%, respectively), and similar percentages in each group remained on the study medications at 2 years (58% vs. 68%, respectively).
In each group, recipients were mostly men (74%) and white (80%-86%), with a mean age of 54 years and mean donor age of 49 years. They had a Model for End-Stage Liver Disease score of 19, and eGFRs of about 80 mL/min per 1.73 m2.
Mean levels of tacrolimus dropped from 10.5 ng/mL at randomization to 4 ng/mL at 2 years in the dose-reduction arm, compared with 10 ng/mL to 7 ng/mL in the control arm.
At 2 years in the intent-to-treat population, the groups had similar rates of the composite primary end point of treated biopsy-proven acute rejection, graft failure, and death (10.5% in the dose-reduction arm and 12.5% in the control arm). Biopsy-proven acute rejection occurred at a significantly lower rate among dose-reduced patients (6%) than among control patients (13%). All of the episodes of acute rejection in the tacrolimus dose-reduced patients were borderline or mild based on the Banff rejection activity index. However, liver biopsies at 1 and 2 years were only part of the trial’s protocol for hepatitis C virus (HCV)-infected patients. The decision to biopsy was otherwise left up to the physicians of each center.
At 1 year, there appeared to be less fibrosis in patients who received everolimus, Dr. Saliba said in response to a question from the audience. In about half of the 75 HCV-infected patients in the dose-reduction arm, liver biopsies showed less fibrosis of at least stage 1 than in patients with HCV infection in the other group. The investigators are now analyzing 2-year data, he said.
The dose-reduced group maintained significantly better eGFR than the control group, through the duration of the trial, finishing with levels of 66 vs. 78 mL/min per 1.73 m2.
Several types of adverse events with an incidence of at least 10% occurred more often in the dose-reduction arm than in the control arm, including leucopenia (13% vs. 5%), peripheral edema (20% vs. 13%), and hypercholesterolemia (11% vs. 4%).
Proteinuria of less than 0.5 g/24 hours occurred in 92%-93% of the patients; none of the patients had severe proteinuria of 3 g/24 hours or more.
One audience member noted that the most important patients to study in this clinical population are those on the borderline of renal failure with low eGFR and elevated creatinine, who would benefit most from improved renal function. Dr. Saliba said that at the time of randomization, the investigators looked at levels of eGFR in each group and over the course of the 2 years, more patients in the standard-dose tacrolimus arm had worsened renal function, whereas many in the dose-reduction arm had improved or at least stable renal function, and few had worsened function.
The study was sponsored by Novartis, which manufactures everolimus. Dr. Saliba reported financial ties to Novartis and Astellas Pharma (manufacturer of tacrolimus), as well as other companies that manufacture drugs used by liver transplant patients. Several other investigators reported financial ties to companies that manufacture antirejection drugs used in liver transplant patients, including Novartis. Three study investigators are employees of Novartis.
AT THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES
Major Finding: At 2 years in the intent-to-treat population, the groups had similar rates of the composite primary end point of treated biopsy-proven acute rejection, graft failure, and death (10.5% in the dose-reduction arm and 12.5% in the control arm).
Data Source: This was a randomized, open-label, multicenter, controlled trial of 719 liver transplant recipients testing the addition of everolimus with or without the withdrawal of tacrolimus (4 months after transplant) or tacrolimus alone.
Disclosures: The study was sponsored by Novartis, which manufactures everolimus. Dr. Saliba reported financial ties to Novartis and Astellas Pharma (manufacturer of tacrolimus), as well as other companies that manufacture drugs used by liver transplant patients. Several other investigators reported financial ties to companies that manufacture antirejection drugs used in liver transplant patients, including Novartis. Three study investigators are employees of Novartis.
Benefit of Young Liver Donors Scrutinized in Study
BOSTON – Younger age of deceased liver donors appeared to improve patient and graft survival when donors and recipients were both of younger age, but not when younger donor livers went to older recipients, according to a secondary analysis of the Organ Procurement and Transplantation Network national database from 2002 to 2011.
"Matching younger recipients with younger donors appears to be the best strategy in order to maximize life years after liver transplantation. However, before this can be considered for allocation policy, much more work needs to be done," including analyses specific to United Network for Organ Sharing regions, Model for End-Stage Liver Disease groups, and modeling of the potential life-years saved with a change in allocation policy, said lead investigator Dr. Neehar D. Parikh of the Comprehensive Transplant Center at Northwestern University, Chicago.
The risk of recipient death is known to increase with advancing donor age, beginning at ages older than 40 years and especially with donors older than 60 years. Also, advancing recipient age has been shown, with some controversy, to affect outcomes negatively, Dr. Parikh said at the annual meeting of the American Association for the Study of Liver Diseases.
Dr. Parikh and his colleagues’ study of the Organ Procurement and Transplantation Network database analyzed 26,849 cases of liver transplantation in which the donor was younger than the recipient, 782 cases in which they were the same age, and 12,107 cases in which the donor was older than the recipient. They also looked at outcomes of patients aged 18-40 years and those 60 years or older, based on the donor age.
As would be expected, recipients had progressively younger mean ages as the donor age increased: 56 years for recipients with younger donors, 52 years for same-age donors, and 48 years for older donors. Hepatitis C virus seropositivity was lowest in recipients who had an older donor (41%), followed by same-age recipient-donor pairs (51%), and recipients who had a younger donor (50%).
In Kaplan-Meier analyses, patient survival at 1 year was significantly worse for those who received a liver from a donor with an older age (86%) or the same age (86%) than from a younger donor (87.4%). Similar results were seen at 3 years between recipients of livers from older (74.5%), same age (73.5%), and younger donors (77.9%).
Older donor age increased the risk for patient death by 14% and graft failure by 13%, in comparison with younger donor age in an adjusted analysis.
For every 10-year increase in patient age for younger donors, the risk of patient mortality increased by 24% and graft failure by 17%. For every 10 years the donor was younger than the recipient, however, there was a 27% decline in the risk of patient mortality and 30% decrease in the risk of graft failure. A small but significance beneficial interaction was found between young donor age and young recipient age on both outcomes.
In contrast, for every 10 years the donor was older than the recipient, the risk of patient mortality increased 9% and the risk of graft failure increased by 22%, and there was no significant interaction between recipient and donor age.
When compared against donor and recipient pairs who were both aged 18-40 years, the risk of patient mortality and graft failure increased significantly for all other combinations of donor and recipient pairs: recipients aged 18-40 years and donors aged 60 years or older (hazard ratios of 1.76 and 1.49, respectively), recipients aged 60 years older and donors aged 18-40 years (HRs of 1.67 and 1.83), and recipients and donors both aged 60 years or older (HRs of 2.12 and 1.87). These results were consistent at both 1 and 3 years.
The overall results "suggest that there is something intrinsic about being older or having an older graft that cannot be remediated by graft or patient age factors," Dr. Parikh said.
The results might be explained in livers from older donors by impaired liver regeneration and increased susceptibility to ischemic reperfusion injury, while older recipients might have decreased circulating stem cells and more competing risks that are not adequately risk adjusted in the available data in older recipients, he said.
One audience member noted that there is still a "huge survival advantage" in all patient populations that receive younger donor livers and that allocating organs based on age is a slippery slope.
Dr. Parikh and his colleagues had no relevant financial disclosures.
BOSTON – Younger age of deceased liver donors appeared to improve patient and graft survival when donors and recipients were both of younger age, but not when younger donor livers went to older recipients, according to a secondary analysis of the Organ Procurement and Transplantation Network national database from 2002 to 2011.
"Matching younger recipients with younger donors appears to be the best strategy in order to maximize life years after liver transplantation. However, before this can be considered for allocation policy, much more work needs to be done," including analyses specific to United Network for Organ Sharing regions, Model for End-Stage Liver Disease groups, and modeling of the potential life-years saved with a change in allocation policy, said lead investigator Dr. Neehar D. Parikh of the Comprehensive Transplant Center at Northwestern University, Chicago.
The risk of recipient death is known to increase with advancing donor age, beginning at ages older than 40 years and especially with donors older than 60 years. Also, advancing recipient age has been shown, with some controversy, to affect outcomes negatively, Dr. Parikh said at the annual meeting of the American Association for the Study of Liver Diseases.
Dr. Parikh and his colleagues’ study of the Organ Procurement and Transplantation Network database analyzed 26,849 cases of liver transplantation in which the donor was younger than the recipient, 782 cases in which they were the same age, and 12,107 cases in which the donor was older than the recipient. They also looked at outcomes of patients aged 18-40 years and those 60 years or older, based on the donor age.
As would be expected, recipients had progressively younger mean ages as the donor age increased: 56 years for recipients with younger donors, 52 years for same-age donors, and 48 years for older donors. Hepatitis C virus seropositivity was lowest in recipients who had an older donor (41%), followed by same-age recipient-donor pairs (51%), and recipients who had a younger donor (50%).
In Kaplan-Meier analyses, patient survival at 1 year was significantly worse for those who received a liver from a donor with an older age (86%) or the same age (86%) than from a younger donor (87.4%). Similar results were seen at 3 years between recipients of livers from older (74.5%), same age (73.5%), and younger donors (77.9%).
Older donor age increased the risk for patient death by 14% and graft failure by 13%, in comparison with younger donor age in an adjusted analysis.
For every 10-year increase in patient age for younger donors, the risk of patient mortality increased by 24% and graft failure by 17%. For every 10 years the donor was younger than the recipient, however, there was a 27% decline in the risk of patient mortality and 30% decrease in the risk of graft failure. A small but significance beneficial interaction was found between young donor age and young recipient age on both outcomes.
In contrast, for every 10 years the donor was older than the recipient, the risk of patient mortality increased 9% and the risk of graft failure increased by 22%, and there was no significant interaction between recipient and donor age.
When compared against donor and recipient pairs who were both aged 18-40 years, the risk of patient mortality and graft failure increased significantly for all other combinations of donor and recipient pairs: recipients aged 18-40 years and donors aged 60 years or older (hazard ratios of 1.76 and 1.49, respectively), recipients aged 60 years older and donors aged 18-40 years (HRs of 1.67 and 1.83), and recipients and donors both aged 60 years or older (HRs of 2.12 and 1.87). These results were consistent at both 1 and 3 years.
The overall results "suggest that there is something intrinsic about being older or having an older graft that cannot be remediated by graft or patient age factors," Dr. Parikh said.
The results might be explained in livers from older donors by impaired liver regeneration and increased susceptibility to ischemic reperfusion injury, while older recipients might have decreased circulating stem cells and more competing risks that are not adequately risk adjusted in the available data in older recipients, he said.
One audience member noted that there is still a "huge survival advantage" in all patient populations that receive younger donor livers and that allocating organs based on age is a slippery slope.
Dr. Parikh and his colleagues had no relevant financial disclosures.
BOSTON – Younger age of deceased liver donors appeared to improve patient and graft survival when donors and recipients were both of younger age, but not when younger donor livers went to older recipients, according to a secondary analysis of the Organ Procurement and Transplantation Network national database from 2002 to 2011.
"Matching younger recipients with younger donors appears to be the best strategy in order to maximize life years after liver transplantation. However, before this can be considered for allocation policy, much more work needs to be done," including analyses specific to United Network for Organ Sharing regions, Model for End-Stage Liver Disease groups, and modeling of the potential life-years saved with a change in allocation policy, said lead investigator Dr. Neehar D. Parikh of the Comprehensive Transplant Center at Northwestern University, Chicago.
The risk of recipient death is known to increase with advancing donor age, beginning at ages older than 40 years and especially with donors older than 60 years. Also, advancing recipient age has been shown, with some controversy, to affect outcomes negatively, Dr. Parikh said at the annual meeting of the American Association for the Study of Liver Diseases.
Dr. Parikh and his colleagues’ study of the Organ Procurement and Transplantation Network database analyzed 26,849 cases of liver transplantation in which the donor was younger than the recipient, 782 cases in which they were the same age, and 12,107 cases in which the donor was older than the recipient. They also looked at outcomes of patients aged 18-40 years and those 60 years or older, based on the donor age.
As would be expected, recipients had progressively younger mean ages as the donor age increased: 56 years for recipients with younger donors, 52 years for same-age donors, and 48 years for older donors. Hepatitis C virus seropositivity was lowest in recipients who had an older donor (41%), followed by same-age recipient-donor pairs (51%), and recipients who had a younger donor (50%).
In Kaplan-Meier analyses, patient survival at 1 year was significantly worse for those who received a liver from a donor with an older age (86%) or the same age (86%) than from a younger donor (87.4%). Similar results were seen at 3 years between recipients of livers from older (74.5%), same age (73.5%), and younger donors (77.9%).
Older donor age increased the risk for patient death by 14% and graft failure by 13%, in comparison with younger donor age in an adjusted analysis.
For every 10-year increase in patient age for younger donors, the risk of patient mortality increased by 24% and graft failure by 17%. For every 10 years the donor was younger than the recipient, however, there was a 27% decline in the risk of patient mortality and 30% decrease in the risk of graft failure. A small but significance beneficial interaction was found between young donor age and young recipient age on both outcomes.
In contrast, for every 10 years the donor was older than the recipient, the risk of patient mortality increased 9% and the risk of graft failure increased by 22%, and there was no significant interaction between recipient and donor age.
When compared against donor and recipient pairs who were both aged 18-40 years, the risk of patient mortality and graft failure increased significantly for all other combinations of donor and recipient pairs: recipients aged 18-40 years and donors aged 60 years or older (hazard ratios of 1.76 and 1.49, respectively), recipients aged 60 years older and donors aged 18-40 years (HRs of 1.67 and 1.83), and recipients and donors both aged 60 years or older (HRs of 2.12 and 1.87). These results were consistent at both 1 and 3 years.
The overall results "suggest that there is something intrinsic about being older or having an older graft that cannot be remediated by graft or patient age factors," Dr. Parikh said.
The results might be explained in livers from older donors by impaired liver regeneration and increased susceptibility to ischemic reperfusion injury, while older recipients might have decreased circulating stem cells and more competing risks that are not adequately risk adjusted in the available data in older recipients, he said.
One audience member noted that there is still a "huge survival advantage" in all patient populations that receive younger donor livers and that allocating organs based on age is a slippery slope.
Dr. Parikh and his colleagues had no relevant financial disclosures.
AT THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES
Major Finding: For every 10-year increase in patient age for younger donors, the risk of patient mortality increased by 24% and graft failure by 17%; for every 10 years the donor was younger than the recipient, there was a 27% decline in the risk of patient mortality and a 30% decrease in the risk of graft failure.
Data Source: This was a secondary analysis of the Organ Procurement and Transplantation Network national database from 2002 to 2011 for adult cadaveric liver transplantation.
Disclosures: Dr. Parikh and his colleagues had no relevant financial disclosures.
Acetaminophen Liver Failure Least Likely to Get Transplant
BOSTON – Acetaminophen toxicity is the most frequent cause of acute liver failure in the United States and its usually milder presentation, along with comorbid psychosocial issues, explain why fewer patients with the etiology undergo liver transplantation, compared with other causes, according to a 10-year retrospective study of the National Institute of Diabetes and Digestive and Kidney Diseases Acute Liver Failure database.
Dr. K. Rajender Reddy and his colleagues in the National Institutes of Health Acute Liver Failure Study Group set out to determine factors that could help clinicians to improve their selection of acute liver failure patients for liver transplantation listing and their decision to proceed with transplantation.
At the annual meeting of the American Association for the Study of Liver Diseases, Dr. Reddy reported that of 1,144 patients who had at least 1 year of follow-up in the database, 491 (43%) had an acetaminophen etiology for acute liver failure, but only 26% of all patients listed for transplantation had an acetaminophen etiology and just 14% of all transplants occurred in patients with acetaminophen toxicity as the underlying cause.
In comparison, patients with other etiologies had higher listing and transplantation rates, with the highest being for autoimmune hepatitis (62% of all patients listed and 50% of all transplanted).
Overall during 2000-2010, 697 patients were not listed and not transplanted (group A), 177 were listed and not transplanted (group B), and 270 were listed and transplanted (group C). After 2 years of follow-up, patient survival was highest in group C (82%), followed by group A (47%) and group B (41%). Survival at 21 days followed the same pattern (C, 89%; A, 58%; B, 45%). Patients in groups A and B with acetaminophen etiology had greater 21-day survival than did those without an acetaminophen etiology.
Patients in group A had significantly higher rates of positive toxicology screens than did groups B and C (43% vs. 35% and 19%, respectively) and history of illicit drug use (10% vs. 4% and 2%).
Comparisons between patients who died in group B and all patients in group C could not find significant risk factors to explain the higher mortality in group B, including longer wait list times and variations in survival and transplant rates by geographic location, although greater coma severity may have contributed to the higher mortality, said Dr. Reddy, professor of medicine in the division of gastroenterology at the Hospital of the University of Pennsylvania, Philadelphia.
Dr. Reddy said that he had no relevant financial disclosures. The study was funded by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases to the National Institutes of Health Acute Liver Failure Study Group.
BOSTON – Acetaminophen toxicity is the most frequent cause of acute liver failure in the United States and its usually milder presentation, along with comorbid psychosocial issues, explain why fewer patients with the etiology undergo liver transplantation, compared with other causes, according to a 10-year retrospective study of the National Institute of Diabetes and Digestive and Kidney Diseases Acute Liver Failure database.
Dr. K. Rajender Reddy and his colleagues in the National Institutes of Health Acute Liver Failure Study Group set out to determine factors that could help clinicians to improve their selection of acute liver failure patients for liver transplantation listing and their decision to proceed with transplantation.
At the annual meeting of the American Association for the Study of Liver Diseases, Dr. Reddy reported that of 1,144 patients who had at least 1 year of follow-up in the database, 491 (43%) had an acetaminophen etiology for acute liver failure, but only 26% of all patients listed for transplantation had an acetaminophen etiology and just 14% of all transplants occurred in patients with acetaminophen toxicity as the underlying cause.
In comparison, patients with other etiologies had higher listing and transplantation rates, with the highest being for autoimmune hepatitis (62% of all patients listed and 50% of all transplanted).
Overall during 2000-2010, 697 patients were not listed and not transplanted (group A), 177 were listed and not transplanted (group B), and 270 were listed and transplanted (group C). After 2 years of follow-up, patient survival was highest in group C (82%), followed by group A (47%) and group B (41%). Survival at 21 days followed the same pattern (C, 89%; A, 58%; B, 45%). Patients in groups A and B with acetaminophen etiology had greater 21-day survival than did those without an acetaminophen etiology.
Patients in group A had significantly higher rates of positive toxicology screens than did groups B and C (43% vs. 35% and 19%, respectively) and history of illicit drug use (10% vs. 4% and 2%).
Comparisons between patients who died in group B and all patients in group C could not find significant risk factors to explain the higher mortality in group B, including longer wait list times and variations in survival and transplant rates by geographic location, although greater coma severity may have contributed to the higher mortality, said Dr. Reddy, professor of medicine in the division of gastroenterology at the Hospital of the University of Pennsylvania, Philadelphia.
Dr. Reddy said that he had no relevant financial disclosures. The study was funded by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases to the National Institutes of Health Acute Liver Failure Study Group.
BOSTON – Acetaminophen toxicity is the most frequent cause of acute liver failure in the United States and its usually milder presentation, along with comorbid psychosocial issues, explain why fewer patients with the etiology undergo liver transplantation, compared with other causes, according to a 10-year retrospective study of the National Institute of Diabetes and Digestive and Kidney Diseases Acute Liver Failure database.
Dr. K. Rajender Reddy and his colleagues in the National Institutes of Health Acute Liver Failure Study Group set out to determine factors that could help clinicians to improve their selection of acute liver failure patients for liver transplantation listing and their decision to proceed with transplantation.
At the annual meeting of the American Association for the Study of Liver Diseases, Dr. Reddy reported that of 1,144 patients who had at least 1 year of follow-up in the database, 491 (43%) had an acetaminophen etiology for acute liver failure, but only 26% of all patients listed for transplantation had an acetaminophen etiology and just 14% of all transplants occurred in patients with acetaminophen toxicity as the underlying cause.
In comparison, patients with other etiologies had higher listing and transplantation rates, with the highest being for autoimmune hepatitis (62% of all patients listed and 50% of all transplanted).
Overall during 2000-2010, 697 patients were not listed and not transplanted (group A), 177 were listed and not transplanted (group B), and 270 were listed and transplanted (group C). After 2 years of follow-up, patient survival was highest in group C (82%), followed by group A (47%) and group B (41%). Survival at 21 days followed the same pattern (C, 89%; A, 58%; B, 45%). Patients in groups A and B with acetaminophen etiology had greater 21-day survival than did those without an acetaminophen etiology.
Patients in group A had significantly higher rates of positive toxicology screens than did groups B and C (43% vs. 35% and 19%, respectively) and history of illicit drug use (10% vs. 4% and 2%).
Comparisons between patients who died in group B and all patients in group C could not find significant risk factors to explain the higher mortality in group B, including longer wait list times and variations in survival and transplant rates by geographic location, although greater coma severity may have contributed to the higher mortality, said Dr. Reddy, professor of medicine in the division of gastroenterology at the Hospital of the University of Pennsylvania, Philadelphia.
Dr. Reddy said that he had no relevant financial disclosures. The study was funded by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases to the National Institutes of Health Acute Liver Failure Study Group.
AT THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES
Major Finding: A total of 43% in the study had an acetaminophen etiology for acute liver failure, but only 26% of all patients listed for transplantation had an acetaminophen etiology and just 14% of all transplants occurred in patients with acetaminophen toxicity as the underlying cause.
Data Source: This was a 10-year retrospective study of the National Institute of Diabetes and Digestive and Kidney Diseases Acute Liver Failure database.
Disclosures: Dr. Reddy said he had no relevant financial disclosures. The study was funded by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases to the National Institutes of Health Acute Liver Failure Study Group.
IGRA Tests Top Skin Pricks for TB Screening of Transplant Candidates
SAN FRANCISCO – Interferon-gamma release assay tests appear to be better than tuberculin skin tests for picking up latent TB in solid organ transplant candidates, according to Dr. Shimon Kusne.
It’s not just because of IGRA’s well-known benefits—as a blood test, results are known after one visit so patients don’t need to return for skin spots to be read, and there are no false positives in patients vaccinated against TB or exposed to environmental strains of mycobacterium.
Instead, IGRA tests simply seem to be better at picking up latent TB, Dr. Kusne, professor of medicine in the division of infectious diseases at the Mayo Clinic Hospital in Phoenix, said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
He and his colleagues gave 179 kidney, liver, or heart transplant candidates TB skin prick tests and two IGRA tests, the QuantiFERON-TB Gold In-Tube test (QFT-GIT) and the T-Spot test.
QFT-GIT was 2.74 times more likely to be positive than tuberculin purified protein derivative skin tests and T-Spots were 3.10 times more likely to be positive. The findings were statistically significant.
"It may be that IGRA is better in these immune-suppressed hosts. Time will tell," said Dr. Kusne, because these tests are relatively new.
IGRA tests appear to be a fine-toothed comb; positive tests might turn negative the second time around in a small minority of patients. What that means, exactly, still needs to be worked out (Chest 2012;142:55-62). For now, the Centers for Disease Control and Prevention is okay with hospitals checking for latent TB with either IGRA or skin tests in most cases, he said.
Even so, the Mayo Clinic has moved away from skin tests in transplant candidates. "I think mainly it’s because CDC has said it’s okay to use either and because many [patients] come to get their [skin test] and then disappear," Dr. Kusne said.
"But cost is always a consideration, too. It’s very cheap" to do a skin test, he said at the meeting, which was sponsored by the American Society for Microbiology.
Dr. Kusne said he had no relevant financial disclosures.
SAN FRANCISCO – Interferon-gamma release assay tests appear to be better than tuberculin skin tests for picking up latent TB in solid organ transplant candidates, according to Dr. Shimon Kusne.
It’s not just because of IGRA’s well-known benefits—as a blood test, results are known after one visit so patients don’t need to return for skin spots to be read, and there are no false positives in patients vaccinated against TB or exposed to environmental strains of mycobacterium.
Instead, IGRA tests simply seem to be better at picking up latent TB, Dr. Kusne, professor of medicine in the division of infectious diseases at the Mayo Clinic Hospital in Phoenix, said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
He and his colleagues gave 179 kidney, liver, or heart transplant candidates TB skin prick tests and two IGRA tests, the QuantiFERON-TB Gold In-Tube test (QFT-GIT) and the T-Spot test.
QFT-GIT was 2.74 times more likely to be positive than tuberculin purified protein derivative skin tests and T-Spots were 3.10 times more likely to be positive. The findings were statistically significant.
"It may be that IGRA is better in these immune-suppressed hosts. Time will tell," said Dr. Kusne, because these tests are relatively new.
IGRA tests appear to be a fine-toothed comb; positive tests might turn negative the second time around in a small minority of patients. What that means, exactly, still needs to be worked out (Chest 2012;142:55-62). For now, the Centers for Disease Control and Prevention is okay with hospitals checking for latent TB with either IGRA or skin tests in most cases, he said.
Even so, the Mayo Clinic has moved away from skin tests in transplant candidates. "I think mainly it’s because CDC has said it’s okay to use either and because many [patients] come to get their [skin test] and then disappear," Dr. Kusne said.
"But cost is always a consideration, too. It’s very cheap" to do a skin test, he said at the meeting, which was sponsored by the American Society for Microbiology.
Dr. Kusne said he had no relevant financial disclosures.
SAN FRANCISCO – Interferon-gamma release assay tests appear to be better than tuberculin skin tests for picking up latent TB in solid organ transplant candidates, according to Dr. Shimon Kusne.
It’s not just because of IGRA’s well-known benefits—as a blood test, results are known after one visit so patients don’t need to return for skin spots to be read, and there are no false positives in patients vaccinated against TB or exposed to environmental strains of mycobacterium.
Instead, IGRA tests simply seem to be better at picking up latent TB, Dr. Kusne, professor of medicine in the division of infectious diseases at the Mayo Clinic Hospital in Phoenix, said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
He and his colleagues gave 179 kidney, liver, or heart transplant candidates TB skin prick tests and two IGRA tests, the QuantiFERON-TB Gold In-Tube test (QFT-GIT) and the T-Spot test.
QFT-GIT was 2.74 times more likely to be positive than tuberculin purified protein derivative skin tests and T-Spots were 3.10 times more likely to be positive. The findings were statistically significant.
"It may be that IGRA is better in these immune-suppressed hosts. Time will tell," said Dr. Kusne, because these tests are relatively new.
IGRA tests appear to be a fine-toothed comb; positive tests might turn negative the second time around in a small minority of patients. What that means, exactly, still needs to be worked out (Chest 2012;142:55-62). For now, the Centers for Disease Control and Prevention is okay with hospitals checking for latent TB with either IGRA or skin tests in most cases, he said.
Even so, the Mayo Clinic has moved away from skin tests in transplant candidates. "I think mainly it’s because CDC has said it’s okay to use either and because many [patients] come to get their [skin test] and then disappear," Dr. Kusne said.
"But cost is always a consideration, too. It’s very cheap" to do a skin test, he said at the meeting, which was sponsored by the American Society for Microbiology.
Dr. Kusne said he had no relevant financial disclosures.
AT THE ANNUAL INTERSCIENCE CONFERENCE ON ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Major Finding: Interferon-gamma release assay tests were about three times more likely than skin prick tests to be positive for latent TB.
Data Source: Data are from a prospective study of 179 kidney, liver, or heart transplant candidates.
Disclosures: The lead investigator said he had no relevant financial disclosures.
Liver Candidates Decline Many Organ Offers
Eighty-four percent of candidates on the wait-list for liver transplant who either died or were removed from the list before they were able to undergo transplantation declined at least one offer of a donor liver, Dr. Jennifer Cindy Lai of the University of California, San Francisco, and her colleagues reported in the November issue of Gastroenterology.
Even more surprising, most of these candidates declined "not just one or two but a median of six liver offers during their time on the wait-list."
The "declined" donor organs were then successfully transplanted into lower-priority recipients.
These findings suggest that mortality among wait-listed patients "is not simply a result of not having the opportunity for transplantation, as many of us assume. Rather, wait-list mortality appears to result from opportunities for transplantation that were declined," Dr. Lai and her associates wrote.
The reasons that so many viable donor livers were initially declined are not yet clear. General, somewhat vague reasons were listed but not fully explained in the records the researchers analyzed for this study, which they obtained from the United Network for Organ Sharing/Organ Procurement Transplantation Network database.
The investigators assessed organ offers to 33,389 liver transplant candidates aged 18 years and older who were wait-listed across the United States between 2005 and 2010.
The reasons that proffered organs were declined, as listed in the medical records, fit into six broad categories: unfavorable donor age or quality of organ; unfavorable donor organ size/weight; other unfavorable donor factors, such as ABO blood transfusion incompatibility, "social history," "positive serologic tests," or "organ anatomical damage or defect"; unreadiness of the recipient, usually because he or she was ill, unavailable, refused the organ, or required multiple organ transplants at the same time; problems with the transplant program itself, such as a "heavy workload" or unavailability of a surgeon or operating room at the recipient’s medical center, failure to respond to the offer in a timely way, or excessive distance to ship the organ.
A total of 20% of the study population (6,737 patients) died or were removed from the wait-list because they became too sick before they could undergo transplantation. A total of 5,680 (84%) of those patients had been offered one or more donor livers before they died or were taken off the list.
Offers of donor livers were declined most often (68%) because of "unfavorable donor age or quality of organ," whereas 9% were declined because of unfavorable organ size, 15% because of "other donor factors," 4% because the recipient wasn’t ready, and 4% because of transplant program or miscellaneous other factors.
However, the dominant use of the "donor quality or age" refusal code in the database almost certainly "does not accurately or fully capture the true refusal reason," Dr. Lai and her associates said.
Even livers judged to be of high quality according to standard criteria were declined because of supposed "unfavorable donor age or quality of organ." But the investigators found no difference in the risk of graft failure between such high-quality livers that were declined and other high-quality livers that were accepted on the first offer.
Other reasons must be playing an important role in this high rate refusal, but "the nuances of these refusals cannot be determined" without more individualized data, they said.
Dr. Lai and her colleagues suggested that to cut down on refusals of apparently viable organs, the transplant community should "reduce the stigma associated with non–ideal livers, and set realistic expectations for wait-listed candidates" so that they’re less likely to pass up a suitable donation while assuming that a better offer will come along.
Patients also should be educated about the unpredictability of death or of sudden worsening of liver disease while on the wait-list. They should be advised that there is a survival benefit associated with the transplantation of any graft, compared with continuing on the wait-list.
In addition, the current regulatory environment focuses on transplant centers’ outcomes, which may influence some centers to discourage the acceptance of less than optimal donor organs. "This may be especially relevant for low-volume transplant centers, for whom even a small number of poor outcomes ... may make a relatively large difference in the centers’ perceived performance," the researchers wrote.
Finally, wait-list candidates should be encouraged to complete their transplant work-ups as expeditiously as possible to avoid having to refuse a donor offer simply because they have not yet undergone the necessary cardiac testing or cancer screening.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of California, San Francisco. No financial conflicts of interest were reported.
Eighty-four percent of candidates on the wait-list for liver transplant who either died or were removed from the list before they were able to undergo transplantation declined at least one offer of a donor liver, Dr. Jennifer Cindy Lai of the University of California, San Francisco, and her colleagues reported in the November issue of Gastroenterology.
Even more surprising, most of these candidates declined "not just one or two but a median of six liver offers during their time on the wait-list."
The "declined" donor organs were then successfully transplanted into lower-priority recipients.
These findings suggest that mortality among wait-listed patients "is not simply a result of not having the opportunity for transplantation, as many of us assume. Rather, wait-list mortality appears to result from opportunities for transplantation that were declined," Dr. Lai and her associates wrote.
The reasons that so many viable donor livers were initially declined are not yet clear. General, somewhat vague reasons were listed but not fully explained in the records the researchers analyzed for this study, which they obtained from the United Network for Organ Sharing/Organ Procurement Transplantation Network database.
The investigators assessed organ offers to 33,389 liver transplant candidates aged 18 years and older who were wait-listed across the United States between 2005 and 2010.
The reasons that proffered organs were declined, as listed in the medical records, fit into six broad categories: unfavorable donor age or quality of organ; unfavorable donor organ size/weight; other unfavorable donor factors, such as ABO blood transfusion incompatibility, "social history," "positive serologic tests," or "organ anatomical damage or defect"; unreadiness of the recipient, usually because he or she was ill, unavailable, refused the organ, or required multiple organ transplants at the same time; problems with the transplant program itself, such as a "heavy workload" or unavailability of a surgeon or operating room at the recipient’s medical center, failure to respond to the offer in a timely way, or excessive distance to ship the organ.
A total of 20% of the study population (6,737 patients) died or were removed from the wait-list because they became too sick before they could undergo transplantation. A total of 5,680 (84%) of those patients had been offered one or more donor livers before they died or were taken off the list.
Offers of donor livers were declined most often (68%) because of "unfavorable donor age or quality of organ," whereas 9% were declined because of unfavorable organ size, 15% because of "other donor factors," 4% because the recipient wasn’t ready, and 4% because of transplant program or miscellaneous other factors.
However, the dominant use of the "donor quality or age" refusal code in the database almost certainly "does not accurately or fully capture the true refusal reason," Dr. Lai and her associates said.
Even livers judged to be of high quality according to standard criteria were declined because of supposed "unfavorable donor age or quality of organ." But the investigators found no difference in the risk of graft failure between such high-quality livers that were declined and other high-quality livers that were accepted on the first offer.
Other reasons must be playing an important role in this high rate refusal, but "the nuances of these refusals cannot be determined" without more individualized data, they said.
Dr. Lai and her colleagues suggested that to cut down on refusals of apparently viable organs, the transplant community should "reduce the stigma associated with non–ideal livers, and set realistic expectations for wait-listed candidates" so that they’re less likely to pass up a suitable donation while assuming that a better offer will come along.
Patients also should be educated about the unpredictability of death or of sudden worsening of liver disease while on the wait-list. They should be advised that there is a survival benefit associated with the transplantation of any graft, compared with continuing on the wait-list.
In addition, the current regulatory environment focuses on transplant centers’ outcomes, which may influence some centers to discourage the acceptance of less than optimal donor organs. "This may be especially relevant for low-volume transplant centers, for whom even a small number of poor outcomes ... may make a relatively large difference in the centers’ perceived performance," the researchers wrote.
Finally, wait-list candidates should be encouraged to complete their transplant work-ups as expeditiously as possible to avoid having to refuse a donor offer simply because they have not yet undergone the necessary cardiac testing or cancer screening.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of California, San Francisco. No financial conflicts of interest were reported.
Eighty-four percent of candidates on the wait-list for liver transplant who either died or were removed from the list before they were able to undergo transplantation declined at least one offer of a donor liver, Dr. Jennifer Cindy Lai of the University of California, San Francisco, and her colleagues reported in the November issue of Gastroenterology.
Even more surprising, most of these candidates declined "not just one or two but a median of six liver offers during their time on the wait-list."
The "declined" donor organs were then successfully transplanted into lower-priority recipients.
These findings suggest that mortality among wait-listed patients "is not simply a result of not having the opportunity for transplantation, as many of us assume. Rather, wait-list mortality appears to result from opportunities for transplantation that were declined," Dr. Lai and her associates wrote.
The reasons that so many viable donor livers were initially declined are not yet clear. General, somewhat vague reasons were listed but not fully explained in the records the researchers analyzed for this study, which they obtained from the United Network for Organ Sharing/Organ Procurement Transplantation Network database.
The investigators assessed organ offers to 33,389 liver transplant candidates aged 18 years and older who were wait-listed across the United States between 2005 and 2010.
The reasons that proffered organs were declined, as listed in the medical records, fit into six broad categories: unfavorable donor age or quality of organ; unfavorable donor organ size/weight; other unfavorable donor factors, such as ABO blood transfusion incompatibility, "social history," "positive serologic tests," or "organ anatomical damage or defect"; unreadiness of the recipient, usually because he or she was ill, unavailable, refused the organ, or required multiple organ transplants at the same time; problems with the transplant program itself, such as a "heavy workload" or unavailability of a surgeon or operating room at the recipient’s medical center, failure to respond to the offer in a timely way, or excessive distance to ship the organ.
A total of 20% of the study population (6,737 patients) died or were removed from the wait-list because they became too sick before they could undergo transplantation. A total of 5,680 (84%) of those patients had been offered one or more donor livers before they died or were taken off the list.
Offers of donor livers were declined most often (68%) because of "unfavorable donor age or quality of organ," whereas 9% were declined because of unfavorable organ size, 15% because of "other donor factors," 4% because the recipient wasn’t ready, and 4% because of transplant program or miscellaneous other factors.
However, the dominant use of the "donor quality or age" refusal code in the database almost certainly "does not accurately or fully capture the true refusal reason," Dr. Lai and her associates said.
Even livers judged to be of high quality according to standard criteria were declined because of supposed "unfavorable donor age or quality of organ." But the investigators found no difference in the risk of graft failure between such high-quality livers that were declined and other high-quality livers that were accepted on the first offer.
Other reasons must be playing an important role in this high rate refusal, but "the nuances of these refusals cannot be determined" without more individualized data, they said.
Dr. Lai and her colleagues suggested that to cut down on refusals of apparently viable organs, the transplant community should "reduce the stigma associated with non–ideal livers, and set realistic expectations for wait-listed candidates" so that they’re less likely to pass up a suitable donation while assuming that a better offer will come along.
Patients also should be educated about the unpredictability of death or of sudden worsening of liver disease while on the wait-list. They should be advised that there is a survival benefit associated with the transplantation of any graft, compared with continuing on the wait-list.
In addition, the current regulatory environment focuses on transplant centers’ outcomes, which may influence some centers to discourage the acceptance of less than optimal donor organs. "This may be especially relevant for low-volume transplant centers, for whom even a small number of poor outcomes ... may make a relatively large difference in the centers’ perceived performance," the researchers wrote.
Finally, wait-list candidates should be encouraged to complete their transplant work-ups as expeditiously as possible to avoid having to refuse a donor offer simply because they have not yet undergone the necessary cardiac testing or cancer screening.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of California, San Francisco. No financial conflicts of interest were reported.
FROM GASTROENTEROLOGY
Soliciting Organ Donors on Facebook Pushes Ethical Envelope
NATIONAL HARBOR, MD. – Facebook is being used to directly solicit living kidney donors, and some aspects of that use raise privacy and ethical issues, according to Dr. Alex Chang.
The social networking site has been widely praised since its May 1 launch of a program allowing users to add organ donor status to their timelines and facilitating users’ linking to their state or national organ donor registries. However, its use for directly soliciting living donors raises issues of concern that organ transplant programs need to recognize and respond to, said Dr. Chang, a nephrology fellow at Loyola University Medical Center, Maywood, Ill.
"What I like about what Facebook has done is that it increases organ donation awareness and makes it personal. ... Facebook, I think, will dramatically increase organ registries if this is implemented well. However, careful consideration of the risks and benefits should be taken prior to being a living kidney donor," Dr. Chang said in an interview at a meeting sponsored by the National Kidney Foundation.
In their poster presentation at the meeting, Dr. Chang and his colleagues analyzed 144 English-language pages on Facebook devoted to soliciting a living kidney donor for a specific person in need. Potential organ recipients ranged in age from 2 to 69 years, and included all racial and ethnic groups and blood types. Of the pages for which the relationships between the page creator and the patient could be determined, 37% were created by the patients themselves, 31% by their children, and 32% by other family or friends.
People posted a range of information from one-sentence requests to explicit medical histories, as well as photographs of family and of the patient receiving hemodialysis.
"Much more careful consideration of the ethical implications of using social media is needed. The privacy issue is huge. ... Many people do not realize the vast amount of information that can be garnered from their Facebook pages, and when you add medical information to that, the risk is increased more," he said.
Although the contribution of Facebook in soliciting donors couldn’t be determined, 30% of the pages reported that donors had been tested, and 12% that a kidney transplant had been received. Individuals for whom donors were tested were significantly more likely to be white and to have more than 50 posts by others on their sites.
The risks of kidney donation were mentioned by 5% of the pages; only 11% mentioned associated costs. "I thought that was pretty astonishing since you are asking a very serious favor of your friends and family and/or strangers, and there is little mention of the actual risks and costs. Oftentimes, donors are caught unaware of certain financial costs such as missing 2 weeks of work and [the fact that] the long-term consequences of living kidney donation are still not totally certain. I believe this deserves fair mention if this method of media is being used for this purpose," Dr. Chang said.
Also of concern: Offers to sell kidneys were posted on 3% of pages.
"In my view I think it is premature to promote using Facebook to solicit living kidney donors. However it is happening and will continue to happen. I think that transplant programs have to recognize this and come up with plans on how to deal with social media–mediated living kidney transplant."
Dr. Chang said he had no relevant financial disclosures.
NATIONAL HARBOR, MD. – Facebook is being used to directly solicit living kidney donors, and some aspects of that use raise privacy and ethical issues, according to Dr. Alex Chang.
The social networking site has been widely praised since its May 1 launch of a program allowing users to add organ donor status to their timelines and facilitating users’ linking to their state or national organ donor registries. However, its use for directly soliciting living donors raises issues of concern that organ transplant programs need to recognize and respond to, said Dr. Chang, a nephrology fellow at Loyola University Medical Center, Maywood, Ill.
"What I like about what Facebook has done is that it increases organ donation awareness and makes it personal. ... Facebook, I think, will dramatically increase organ registries if this is implemented well. However, careful consideration of the risks and benefits should be taken prior to being a living kidney donor," Dr. Chang said in an interview at a meeting sponsored by the National Kidney Foundation.
In their poster presentation at the meeting, Dr. Chang and his colleagues analyzed 144 English-language pages on Facebook devoted to soliciting a living kidney donor for a specific person in need. Potential organ recipients ranged in age from 2 to 69 years, and included all racial and ethnic groups and blood types. Of the pages for which the relationships between the page creator and the patient could be determined, 37% were created by the patients themselves, 31% by their children, and 32% by other family or friends.
People posted a range of information from one-sentence requests to explicit medical histories, as well as photographs of family and of the patient receiving hemodialysis.
"Much more careful consideration of the ethical implications of using social media is needed. The privacy issue is huge. ... Many people do not realize the vast amount of information that can be garnered from their Facebook pages, and when you add medical information to that, the risk is increased more," he said.
Although the contribution of Facebook in soliciting donors couldn’t be determined, 30% of the pages reported that donors had been tested, and 12% that a kidney transplant had been received. Individuals for whom donors were tested were significantly more likely to be white and to have more than 50 posts by others on their sites.
The risks of kidney donation were mentioned by 5% of the pages; only 11% mentioned associated costs. "I thought that was pretty astonishing since you are asking a very serious favor of your friends and family and/or strangers, and there is little mention of the actual risks and costs. Oftentimes, donors are caught unaware of certain financial costs such as missing 2 weeks of work and [the fact that] the long-term consequences of living kidney donation are still not totally certain. I believe this deserves fair mention if this method of media is being used for this purpose," Dr. Chang said.
Also of concern: Offers to sell kidneys were posted on 3% of pages.
"In my view I think it is premature to promote using Facebook to solicit living kidney donors. However it is happening and will continue to happen. I think that transplant programs have to recognize this and come up with plans on how to deal with social media–mediated living kidney transplant."
Dr. Chang said he had no relevant financial disclosures.
NATIONAL HARBOR, MD. – Facebook is being used to directly solicit living kidney donors, and some aspects of that use raise privacy and ethical issues, according to Dr. Alex Chang.
The social networking site has been widely praised since its May 1 launch of a program allowing users to add organ donor status to their timelines and facilitating users’ linking to their state or national organ donor registries. However, its use for directly soliciting living donors raises issues of concern that organ transplant programs need to recognize and respond to, said Dr. Chang, a nephrology fellow at Loyola University Medical Center, Maywood, Ill.
"What I like about what Facebook has done is that it increases organ donation awareness and makes it personal. ... Facebook, I think, will dramatically increase organ registries if this is implemented well. However, careful consideration of the risks and benefits should be taken prior to being a living kidney donor," Dr. Chang said in an interview at a meeting sponsored by the National Kidney Foundation.
In their poster presentation at the meeting, Dr. Chang and his colleagues analyzed 144 English-language pages on Facebook devoted to soliciting a living kidney donor for a specific person in need. Potential organ recipients ranged in age from 2 to 69 years, and included all racial and ethnic groups and blood types. Of the pages for which the relationships between the page creator and the patient could be determined, 37% were created by the patients themselves, 31% by their children, and 32% by other family or friends.
People posted a range of information from one-sentence requests to explicit medical histories, as well as photographs of family and of the patient receiving hemodialysis.
"Much more careful consideration of the ethical implications of using social media is needed. The privacy issue is huge. ... Many people do not realize the vast amount of information that can be garnered from their Facebook pages, and when you add medical information to that, the risk is increased more," he said.
Although the contribution of Facebook in soliciting donors couldn’t be determined, 30% of the pages reported that donors had been tested, and 12% that a kidney transplant had been received. Individuals for whom donors were tested were significantly more likely to be white and to have more than 50 posts by others on their sites.
The risks of kidney donation were mentioned by 5% of the pages; only 11% mentioned associated costs. "I thought that was pretty astonishing since you are asking a very serious favor of your friends and family and/or strangers, and there is little mention of the actual risks and costs. Oftentimes, donors are caught unaware of certain financial costs such as missing 2 weeks of work and [the fact that] the long-term consequences of living kidney donation are still not totally certain. I believe this deserves fair mention if this method of media is being used for this purpose," Dr. Chang said.
Also of concern: Offers to sell kidneys were posted on 3% of pages.
"In my view I think it is premature to promote using Facebook to solicit living kidney donors. However it is happening and will continue to happen. I think that transplant programs have to recognize this and come up with plans on how to deal with social media–mediated living kidney transplant."
Dr. Chang said he had no relevant financial disclosures.
FROM A MEETING SPONSORED BY THE NATIONAL KIDNEY FOUNDATION
Major Finding: Almost a third of the Facebook pages set up for soliciting living kidney donors were associated with the testing of a potential donor, and 12% have resulted in an actual kidney transplant, according to people who happened to report such outcomes. The risks of kidney donation were mentioned by 5% of the pages, and only 11% mentioned associated costs.
Data Source: The findings are based on an analysis of 144 Facebook pages created for the sole purpose of soliciting a living kidney donor for a particular individual.
Disclosures: Dr. Chang said he had no relevant financial disclosures.
Sleeve Gastrectomy Feasible in Obese Transplant Candidates
SAN DIEGO – Laparoscopic sleeve gastrectomy is safe and effective in obese candidates for organ transplantation, results from a novel pilot study demonstrated.
Nationwide, 15%-20% of patients on the transplant waiting list are morbidly obese, with a body mass index of greater than 35 kg/m2, "but many cannot be transplanted unless they lose weight," said Dr. Matthew Y. Lin of the surgery department at the University of California, San Francisco (UCSF). "Morbid obesity can contribute to end-stage kidney or liver failure. For example, obesity-related nonalcoholic steatohepatitis is now the third most common indication for liver transplant in the United States and will likely become first in the future."
In what Dr. Lin said is the only reported case series of bariatric surgery in obese transplant candidates, he and his associates conducted a pilot study of 26 morbidly obese patients with liver or kidney failure who underwent laparoscopic sleeve gastrectomy at UCSF from 2006 to 2012. They chose sleeve gastrectomy over gastric banding "to avoid foreign body implantation, in anticipation of post-transplant immunosuppression," Dr. Lin explained at the annual meeting of the American Society for Metabolic and Bariatric Surgery.
"We chose sleeve gastrectomy over gastric bypass to maintain endoscopic access to the biliary system, to reduce surgical complexity, and to avoid unpredictable immunosuppression absorption," he said.
Morbid obesity is a relative contraindication for solid organ transplantation at most centers because of poor post-transplant outcomes, according to Dr. Lin. "At UCSF, the selection criteria are a BMI of less than 40 for liver transplant, less than 38 for kidney transplant, and less than 34 for kidney transplant in patients with diabetes." The researchers hypothesized that laparoscopic sleeve gastrectomy could be safely performed in high-risk patients with liver or kidney failure and achieve enough weight loss to allow for transplantation.
The 26 patients had a mean age of 57 years, 17 were women, 20 were white, and their average preoperative BMI was 48. Twenty patients had liver insufficiency with a mean Model for End-Stage Liver Disease (MELD) score of 11, and 6 had kidney insufficiency with a mean glomerular filtration rate of 10 mL/min. Five of these patients were on hemodialysis.
All 26 patients had laparoscopic sleeve gastrectomy performed by the same surgeon. The mean operative time was 151 minutes, and the mean length of stay was 4.2 days. Complications that occurred within 30 days were two cases of superficial wound infection and one case each of worsened hepatic encephalopathy, acute renal insufficiency, need for blood transfusion, and staple line leak. There was no mortality within 30 days, but after that period two patients died awaiting transplant and one patient died from complications of the staple line leak and progressive liver failure 4 years after surgery.
After 2 years, the average BMI of study participants dropped from a mean of 48 to a mean of 29. "Between the 6- and 12-month marks, most patients were able to achieve a BMI that would make them acceptable for transplant," Dr. Lin said.
At 1, 3, 12, and 24 months, the percent of excess body weight lost was 17%, 26%, 50%, and 66%, respectively. "The weight-loss profile is similar to [those of] the general bariatric sleeve gastrectomy population," he noted.
Of the 13 patients who had diabetes preoperatively, 7 had complete resolution after the procedure and 1 had partial resolution. Mean postoperative albumin levels for all 26 patients after sleeve gastrectomy were 3.1 g/dL at 6 months and 3.3 g/dL at 12 months.
Eight patients went on to receive their organ transplant, Dr. Lin said. Their mean age was 56 years, and six were women. They waited a mean of 17 months for their procedures, which included six liver transplants, one liver and kidney transplant, and one kidney transplant. Their mean BMI before sleeve gastrectomy was 46, and their mean BMI prior to transplantation was 31. Immediately before transplant, their mean albumin level was 3.2 g/dL, and the most current measurement remained the same. "No increased acute rejection or difficulty maintaining immunosuppression was observed," he said.
Dr. Lin acknowledged certain limitations of the study, including its single-center design, lack of a control population, and the fact that "there is very little statistical power to estimate the true complication rate in this high-risk surgical group. Furthermore, we only have short-term follow-up."
Dr. Lin said that he had no relevant financial conflicts to disclose.
SAN DIEGO – Laparoscopic sleeve gastrectomy is safe and effective in obese candidates for organ transplantation, results from a novel pilot study demonstrated.
Nationwide, 15%-20% of patients on the transplant waiting list are morbidly obese, with a body mass index of greater than 35 kg/m2, "but many cannot be transplanted unless they lose weight," said Dr. Matthew Y. Lin of the surgery department at the University of California, San Francisco (UCSF). "Morbid obesity can contribute to end-stage kidney or liver failure. For example, obesity-related nonalcoholic steatohepatitis is now the third most common indication for liver transplant in the United States and will likely become first in the future."
In what Dr. Lin said is the only reported case series of bariatric surgery in obese transplant candidates, he and his associates conducted a pilot study of 26 morbidly obese patients with liver or kidney failure who underwent laparoscopic sleeve gastrectomy at UCSF from 2006 to 2012. They chose sleeve gastrectomy over gastric banding "to avoid foreign body implantation, in anticipation of post-transplant immunosuppression," Dr. Lin explained at the annual meeting of the American Society for Metabolic and Bariatric Surgery.
"We chose sleeve gastrectomy over gastric bypass to maintain endoscopic access to the biliary system, to reduce surgical complexity, and to avoid unpredictable immunosuppression absorption," he said.
Morbid obesity is a relative contraindication for solid organ transplantation at most centers because of poor post-transplant outcomes, according to Dr. Lin. "At UCSF, the selection criteria are a BMI of less than 40 for liver transplant, less than 38 for kidney transplant, and less than 34 for kidney transplant in patients with diabetes." The researchers hypothesized that laparoscopic sleeve gastrectomy could be safely performed in high-risk patients with liver or kidney failure and achieve enough weight loss to allow for transplantation.
The 26 patients had a mean age of 57 years, 17 were women, 20 were white, and their average preoperative BMI was 48. Twenty patients had liver insufficiency with a mean Model for End-Stage Liver Disease (MELD) score of 11, and 6 had kidney insufficiency with a mean glomerular filtration rate of 10 mL/min. Five of these patients were on hemodialysis.
All 26 patients had laparoscopic sleeve gastrectomy performed by the same surgeon. The mean operative time was 151 minutes, and the mean length of stay was 4.2 days. Complications that occurred within 30 days were two cases of superficial wound infection and one case each of worsened hepatic encephalopathy, acute renal insufficiency, need for blood transfusion, and staple line leak. There was no mortality within 30 days, but after that period two patients died awaiting transplant and one patient died from complications of the staple line leak and progressive liver failure 4 years after surgery.
After 2 years, the average BMI of study participants dropped from a mean of 48 to a mean of 29. "Between the 6- and 12-month marks, most patients were able to achieve a BMI that would make them acceptable for transplant," Dr. Lin said.
At 1, 3, 12, and 24 months, the percent of excess body weight lost was 17%, 26%, 50%, and 66%, respectively. "The weight-loss profile is similar to [those of] the general bariatric sleeve gastrectomy population," he noted.
Of the 13 patients who had diabetes preoperatively, 7 had complete resolution after the procedure and 1 had partial resolution. Mean postoperative albumin levels for all 26 patients after sleeve gastrectomy were 3.1 g/dL at 6 months and 3.3 g/dL at 12 months.
Eight patients went on to receive their organ transplant, Dr. Lin said. Their mean age was 56 years, and six were women. They waited a mean of 17 months for their procedures, which included six liver transplants, one liver and kidney transplant, and one kidney transplant. Their mean BMI before sleeve gastrectomy was 46, and their mean BMI prior to transplantation was 31. Immediately before transplant, their mean albumin level was 3.2 g/dL, and the most current measurement remained the same. "No increased acute rejection or difficulty maintaining immunosuppression was observed," he said.
Dr. Lin acknowledged certain limitations of the study, including its single-center design, lack of a control population, and the fact that "there is very little statistical power to estimate the true complication rate in this high-risk surgical group. Furthermore, we only have short-term follow-up."
Dr. Lin said that he had no relevant financial conflicts to disclose.
SAN DIEGO – Laparoscopic sleeve gastrectomy is safe and effective in obese candidates for organ transplantation, results from a novel pilot study demonstrated.
Nationwide, 15%-20% of patients on the transplant waiting list are morbidly obese, with a body mass index of greater than 35 kg/m2, "but many cannot be transplanted unless they lose weight," said Dr. Matthew Y. Lin of the surgery department at the University of California, San Francisco (UCSF). "Morbid obesity can contribute to end-stage kidney or liver failure. For example, obesity-related nonalcoholic steatohepatitis is now the third most common indication for liver transplant in the United States and will likely become first in the future."
In what Dr. Lin said is the only reported case series of bariatric surgery in obese transplant candidates, he and his associates conducted a pilot study of 26 morbidly obese patients with liver or kidney failure who underwent laparoscopic sleeve gastrectomy at UCSF from 2006 to 2012. They chose sleeve gastrectomy over gastric banding "to avoid foreign body implantation, in anticipation of post-transplant immunosuppression," Dr. Lin explained at the annual meeting of the American Society for Metabolic and Bariatric Surgery.
"We chose sleeve gastrectomy over gastric bypass to maintain endoscopic access to the biliary system, to reduce surgical complexity, and to avoid unpredictable immunosuppression absorption," he said.
Morbid obesity is a relative contraindication for solid organ transplantation at most centers because of poor post-transplant outcomes, according to Dr. Lin. "At UCSF, the selection criteria are a BMI of less than 40 for liver transplant, less than 38 for kidney transplant, and less than 34 for kidney transplant in patients with diabetes." The researchers hypothesized that laparoscopic sleeve gastrectomy could be safely performed in high-risk patients with liver or kidney failure and achieve enough weight loss to allow for transplantation.
The 26 patients had a mean age of 57 years, 17 were women, 20 were white, and their average preoperative BMI was 48. Twenty patients had liver insufficiency with a mean Model for End-Stage Liver Disease (MELD) score of 11, and 6 had kidney insufficiency with a mean glomerular filtration rate of 10 mL/min. Five of these patients were on hemodialysis.
All 26 patients had laparoscopic sleeve gastrectomy performed by the same surgeon. The mean operative time was 151 minutes, and the mean length of stay was 4.2 days. Complications that occurred within 30 days were two cases of superficial wound infection and one case each of worsened hepatic encephalopathy, acute renal insufficiency, need for blood transfusion, and staple line leak. There was no mortality within 30 days, but after that period two patients died awaiting transplant and one patient died from complications of the staple line leak and progressive liver failure 4 years after surgery.
After 2 years, the average BMI of study participants dropped from a mean of 48 to a mean of 29. "Between the 6- and 12-month marks, most patients were able to achieve a BMI that would make them acceptable for transplant," Dr. Lin said.
At 1, 3, 12, and 24 months, the percent of excess body weight lost was 17%, 26%, 50%, and 66%, respectively. "The weight-loss profile is similar to [those of] the general bariatric sleeve gastrectomy population," he noted.
Of the 13 patients who had diabetes preoperatively, 7 had complete resolution after the procedure and 1 had partial resolution. Mean postoperative albumin levels for all 26 patients after sleeve gastrectomy were 3.1 g/dL at 6 months and 3.3 g/dL at 12 months.
Eight patients went on to receive their organ transplant, Dr. Lin said. Their mean age was 56 years, and six were women. They waited a mean of 17 months for their procedures, which included six liver transplants, one liver and kidney transplant, and one kidney transplant. Their mean BMI before sleeve gastrectomy was 46, and their mean BMI prior to transplantation was 31. Immediately before transplant, their mean albumin level was 3.2 g/dL, and the most current measurement remained the same. "No increased acute rejection or difficulty maintaining immunosuppression was observed," he said.
Dr. Lin acknowledged certain limitations of the study, including its single-center design, lack of a control population, and the fact that "there is very little statistical power to estimate the true complication rate in this high-risk surgical group. Furthermore, we only have short-term follow-up."
Dr. Lin said that he had no relevant financial conflicts to disclose.
AT THE ANNUAL MEETING OF THE AMERICAN SOCIETY FOR METABOLIC AND BARIATRIC SURGERY
Perihilar Cholangiocarcinoma: Neoadjuvant Therapy and Liver Transplant Effective
Neoadjuvant chemoradiation followed by liver transplantation is an effective and appropriate strategy for treating unresectable perihilar cholangiocarcinoma, according to a multicenter, retrospective study reported by Dr. Sarwa Darwish Murad and her colleagues in the July issue of Gastroenterology.
Historically, treatment options for the highly aggressive malignancy have been limited because many patients present with unresectable disease, and even among those in whom resection is possible, 5-year survival rates have been low. Further, the efficacy of orthotopic liver transplantation in these patients has been compromised by a high rate of tumor recurrence, and thus the disease has been considered a contraindication to the procedure, the authors wrote (Gastroenterology 2012 July [doi: 10.1053/j.gastro.2012.04.008]).
In 2006, based on reports of excellent single-center outcomes of the chemoradiation/transplantation protocol, the United Network of Organ Sharing (UNOS) developed a standardized Model of End-stage Liver Disease (MELD) exception for perihilar cholangiocarcinoma (Liver Transpl. 2006;12:S95-7).
In the current study, Dr. Murad of the Mayo Clinic in Rochester, Minn., and her coinvestigators analyzed data from 12 large-volume transplant centers in the United States that had treated three or more perihilar cholangiocarcinoma patients with neoadjuvant therapy and liver transplantation during 1993-2010.
A total of 287 patients met the study criteria. External radiation, brachytherapy, radiosensitizing therapy, and maintenance chemotherapy were completed by 99%, 75%, 98%, and 65%, respectively. Prior to liver transplantation, 71 patients (24.7%) dropped out after a median of 4.6 months. In the first 3.5 months of therapy, 11.5% dropped out, demonstrating the appropriateness of the MELD exception.
The median follow-up from the time of listing for transplantation was 2.5 years. During this period, 122 patients died after a median of 1.2 years from presentation. Of these deaths, 60 (49%) occurred prior to transplant, and resulted from tumor progression (52), liver failure (3), cardiovascular causes (2), multiorgan failure (2), and sepsis (1). Post transplant, 43 (20%) patients developed recurrence and 62 (22%) patients died, including those whose death was attributed to recurrence (40), sepsis (8), multiorgan failure (3), liver failure (3), post-transplant lymphoproliferative disease (2), and other causes (6).
Post transplant, the 2-, 5-, and 10-year recurrence-free survival rates were 78%, 65%, and 59%, respectively, "demonstrating this therapy to be highly effective," the authors said. No significant differences in recurrence-free survival were observed between patients who underwent deceased vs. living donor transplantation, or in patients with underlying primary sclerosing cholangitis compared with those without.
But survival times were significantly shorter for patients who did not meet the UNOS criteria, including those with a tumor greater than 3 cm, transperitoneal tumor biopsy, or metastatic disease. Specifically, the hazard ratio for patients transplanted outside of the current MELD exception criteria was 2.98 relative to those within the criteria. "Mass size caused the greatest disparity, with 5-year recurrence-free survival of 32% for those larger than 3 cm compared to 69% for smaller tumors," they wrote.
No significant differences were observed between patients who underwent operative staging and those who did not, nor was the timing of staging significantly associated with survival, the authors wrote. Similarly, recurrence-free survival for patients who had received brachytherapy did not differ from that of those who did not.
In an analysis of possible center effects, the investigators determined that there were no significant differences in recurrence-free survival despite the fact that one center contributed the largest number of patients (193). In a multivariate Cox regression model, "selection remained the only significant determinant of recurrence-free survival," according to the authors. In fact, they added, not only is selection the only variable that acts as an independent predictor of outcome and is modifiable at the same time, but "by adjusting selection alone, 5-year recurrence-free survival can be maximized to 72%."
The unadjusted 5-year disease-free survival rate of 65% "is not only similar to results from earlier single-center series but also similar to outcomes of liver transplantation for other malignant and nonmalignant indications," the authors wrote. In addition, the average 3-month dropout rate of 11.5% approximates the expected 10% (as per the standardized MELD exception score equivalent), and as such justifies "using scarce liver allografts for this otherwise lethal disease," they said.
The study is limited by its retrospective design and the fact that a large number of patients (193) came from one center, the authors acknowledged. Also, "due to heterogeneity in duration, type, and dose of maintenance chemotherapy administered at different centers, we were unable to determine the independent impact of maintenance chemotherapy," they wrote.
Although the findings confirm the excellent outcomes of neoadjuvant chemoradiation followed by liver transplantation in patients with perihilar cholangiocarcinoma, an important challenge for the future will be to "gain a greater understanding of the tumor biology in order to reduce wait-list dropout and post-transplant recurrence, either by further refinements in patient selection or, ideally, by more effective chemoradiotherapy," the authors concluded.
The authors had no financial conflicts of interest to disclose.
Neoadjuvant chemoradiation followed by liver transplantation is an effective and appropriate strategy for treating unresectable perihilar cholangiocarcinoma, according to a multicenter, retrospective study reported by Dr. Sarwa Darwish Murad and her colleagues in the July issue of Gastroenterology.
Historically, treatment options for the highly aggressive malignancy have been limited because many patients present with unresectable disease, and even among those in whom resection is possible, 5-year survival rates have been low. Further, the efficacy of orthotopic liver transplantation in these patients has been compromised by a high rate of tumor recurrence, and thus the disease has been considered a contraindication to the procedure, the authors wrote (Gastroenterology 2012 July [doi: 10.1053/j.gastro.2012.04.008]).
In 2006, based on reports of excellent single-center outcomes of the chemoradiation/transplantation protocol, the United Network of Organ Sharing (UNOS) developed a standardized Model of End-stage Liver Disease (MELD) exception for perihilar cholangiocarcinoma (Liver Transpl. 2006;12:S95-7).
In the current study, Dr. Murad of the Mayo Clinic in Rochester, Minn., and her coinvestigators analyzed data from 12 large-volume transplant centers in the United States that had treated three or more perihilar cholangiocarcinoma patients with neoadjuvant therapy and liver transplantation during 1993-2010.
A total of 287 patients met the study criteria. External radiation, brachytherapy, radiosensitizing therapy, and maintenance chemotherapy were completed by 99%, 75%, 98%, and 65%, respectively. Prior to liver transplantation, 71 patients (24.7%) dropped out after a median of 4.6 months. In the first 3.5 months of therapy, 11.5% dropped out, demonstrating the appropriateness of the MELD exception.
The median follow-up from the time of listing for transplantation was 2.5 years. During this period, 122 patients died after a median of 1.2 years from presentation. Of these deaths, 60 (49%) occurred prior to transplant, and resulted from tumor progression (52), liver failure (3), cardiovascular causes (2), multiorgan failure (2), and sepsis (1). Post transplant, 43 (20%) patients developed recurrence and 62 (22%) patients died, including those whose death was attributed to recurrence (40), sepsis (8), multiorgan failure (3), liver failure (3), post-transplant lymphoproliferative disease (2), and other causes (6).
Post transplant, the 2-, 5-, and 10-year recurrence-free survival rates were 78%, 65%, and 59%, respectively, "demonstrating this therapy to be highly effective," the authors said. No significant differences in recurrence-free survival were observed between patients who underwent deceased vs. living donor transplantation, or in patients with underlying primary sclerosing cholangitis compared with those without.
But survival times were significantly shorter for patients who did not meet the UNOS criteria, including those with a tumor greater than 3 cm, transperitoneal tumor biopsy, or metastatic disease. Specifically, the hazard ratio for patients transplanted outside of the current MELD exception criteria was 2.98 relative to those within the criteria. "Mass size caused the greatest disparity, with 5-year recurrence-free survival of 32% for those larger than 3 cm compared to 69% for smaller tumors," they wrote.
No significant differences were observed between patients who underwent operative staging and those who did not, nor was the timing of staging significantly associated with survival, the authors wrote. Similarly, recurrence-free survival for patients who had received brachytherapy did not differ from that of those who did not.
In an analysis of possible center effects, the investigators determined that there were no significant differences in recurrence-free survival despite the fact that one center contributed the largest number of patients (193). In a multivariate Cox regression model, "selection remained the only significant determinant of recurrence-free survival," according to the authors. In fact, they added, not only is selection the only variable that acts as an independent predictor of outcome and is modifiable at the same time, but "by adjusting selection alone, 5-year recurrence-free survival can be maximized to 72%."
The unadjusted 5-year disease-free survival rate of 65% "is not only similar to results from earlier single-center series but also similar to outcomes of liver transplantation for other malignant and nonmalignant indications," the authors wrote. In addition, the average 3-month dropout rate of 11.5% approximates the expected 10% (as per the standardized MELD exception score equivalent), and as such justifies "using scarce liver allografts for this otherwise lethal disease," they said.
The study is limited by its retrospective design and the fact that a large number of patients (193) came from one center, the authors acknowledged. Also, "due to heterogeneity in duration, type, and dose of maintenance chemotherapy administered at different centers, we were unable to determine the independent impact of maintenance chemotherapy," they wrote.
Although the findings confirm the excellent outcomes of neoadjuvant chemoradiation followed by liver transplantation in patients with perihilar cholangiocarcinoma, an important challenge for the future will be to "gain a greater understanding of the tumor biology in order to reduce wait-list dropout and post-transplant recurrence, either by further refinements in patient selection or, ideally, by more effective chemoradiotherapy," the authors concluded.
The authors had no financial conflicts of interest to disclose.
Neoadjuvant chemoradiation followed by liver transplantation is an effective and appropriate strategy for treating unresectable perihilar cholangiocarcinoma, according to a multicenter, retrospective study reported by Dr. Sarwa Darwish Murad and her colleagues in the July issue of Gastroenterology.
Historically, treatment options for the highly aggressive malignancy have been limited because many patients present with unresectable disease, and even among those in whom resection is possible, 5-year survival rates have been low. Further, the efficacy of orthotopic liver transplantation in these patients has been compromised by a high rate of tumor recurrence, and thus the disease has been considered a contraindication to the procedure, the authors wrote (Gastroenterology 2012 July [doi: 10.1053/j.gastro.2012.04.008]).
In 2006, based on reports of excellent single-center outcomes of the chemoradiation/transplantation protocol, the United Network of Organ Sharing (UNOS) developed a standardized Model of End-stage Liver Disease (MELD) exception for perihilar cholangiocarcinoma (Liver Transpl. 2006;12:S95-7).
In the current study, Dr. Murad of the Mayo Clinic in Rochester, Minn., and her coinvestigators analyzed data from 12 large-volume transplant centers in the United States that had treated three or more perihilar cholangiocarcinoma patients with neoadjuvant therapy and liver transplantation during 1993-2010.
A total of 287 patients met the study criteria. External radiation, brachytherapy, radiosensitizing therapy, and maintenance chemotherapy were completed by 99%, 75%, 98%, and 65%, respectively. Prior to liver transplantation, 71 patients (24.7%) dropped out after a median of 4.6 months. In the first 3.5 months of therapy, 11.5% dropped out, demonstrating the appropriateness of the MELD exception.
The median follow-up from the time of listing for transplantation was 2.5 years. During this period, 122 patients died after a median of 1.2 years from presentation. Of these deaths, 60 (49%) occurred prior to transplant, and resulted from tumor progression (52), liver failure (3), cardiovascular causes (2), multiorgan failure (2), and sepsis (1). Post transplant, 43 (20%) patients developed recurrence and 62 (22%) patients died, including those whose death was attributed to recurrence (40), sepsis (8), multiorgan failure (3), liver failure (3), post-transplant lymphoproliferative disease (2), and other causes (6).
Post transplant, the 2-, 5-, and 10-year recurrence-free survival rates were 78%, 65%, and 59%, respectively, "demonstrating this therapy to be highly effective," the authors said. No significant differences in recurrence-free survival were observed between patients who underwent deceased vs. living donor transplantation, or in patients with underlying primary sclerosing cholangitis compared with those without.
But survival times were significantly shorter for patients who did not meet the UNOS criteria, including those with a tumor greater than 3 cm, transperitoneal tumor biopsy, or metastatic disease. Specifically, the hazard ratio for patients transplanted outside of the current MELD exception criteria was 2.98 relative to those within the criteria. "Mass size caused the greatest disparity, with 5-year recurrence-free survival of 32% for those larger than 3 cm compared to 69% for smaller tumors," they wrote.
No significant differences were observed between patients who underwent operative staging and those who did not, nor was the timing of staging significantly associated with survival, the authors wrote. Similarly, recurrence-free survival for patients who had received brachytherapy did not differ from that of those who did not.
In an analysis of possible center effects, the investigators determined that there were no significant differences in recurrence-free survival despite the fact that one center contributed the largest number of patients (193). In a multivariate Cox regression model, "selection remained the only significant determinant of recurrence-free survival," according to the authors. In fact, they added, not only is selection the only variable that acts as an independent predictor of outcome and is modifiable at the same time, but "by adjusting selection alone, 5-year recurrence-free survival can be maximized to 72%."
The unadjusted 5-year disease-free survival rate of 65% "is not only similar to results from earlier single-center series but also similar to outcomes of liver transplantation for other malignant and nonmalignant indications," the authors wrote. In addition, the average 3-month dropout rate of 11.5% approximates the expected 10% (as per the standardized MELD exception score equivalent), and as such justifies "using scarce liver allografts for this otherwise lethal disease," they said.
The study is limited by its retrospective design and the fact that a large number of patients (193) came from one center, the authors acknowledged. Also, "due to heterogeneity in duration, type, and dose of maintenance chemotherapy administered at different centers, we were unable to determine the independent impact of maintenance chemotherapy," they wrote.
Although the findings confirm the excellent outcomes of neoadjuvant chemoradiation followed by liver transplantation in patients with perihilar cholangiocarcinoma, an important challenge for the future will be to "gain a greater understanding of the tumor biology in order to reduce wait-list dropout and post-transplant recurrence, either by further refinements in patient selection or, ideally, by more effective chemoradiotherapy," the authors concluded.
The authors had no financial conflicts of interest to disclose.
FROM GASTROENTEROLOGY