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 After 4 months, in one of the reduced-dose arms, tacrolimus was withdrawn and the everolimus dose was increased to 8-10 ng/mL (231 patients), whereas the dose of everolimus was kept constant in the other reduced-dose arm (245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.

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.

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.

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.

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.

SAN FRANCISCO – Both donor and recipient interleukin 28B genotype affect the risk of recurrence of hepatitis C after liver transplantation, but they do so in opposite directions.

Investigators led by Dr. Andres Duarte-Rojo of the Mayo Clinic in Rochester, Minn., studied a cohort of more than 200 patients with hepatitis C who underwent liver transplantation, finding that 32% had a histologic recurrence 1 year later.

The risk of such recurrence was reduced by more than half when the recipient had the interleukin 28B (IL28B) CC genotype, as compared with the CT or TT genotype, according to results reported at the annual meeting of the American Association for the Study of Liver Diseases. In sharp contrast, the risk was almost tripled if the donor had the CC genotype for IL28B instead of one of the others.

"Variations in the phenotypic expression of IL28B genotype occur in relation to its source, either the recipient or the donor. This paradoxical effect suggests variation in the activation of the adaptive immune system according to hepatic and nonhepatic IL28B genotype," Dr. Duarte-Rojo commented.

Other research by his group suggests that donor and recipient CC genotype have a synergistic effect in promoting sustained virologic response after transplantation. "However, according to current results, allocation of a CC allograft to hepatitis C patients may predispose to a more severe disease in those untreated or not achieving a sustained virologic response," he said.

IL28 is a cytokine playing a role in antiviral defenses. The genotype for the B isoform "affects hepatitis C virus eradication, whether spontaneous or therapy driven," Dr. Duarte-Rojo noted. "It is important to study the associations of IL28B in the posttransplant setting to unravel mechanisms driving viral-host interactions and help the understanding of this polymorphism in hepatitis C pathobiology."

The investigators studied 241 consecutive patients with hepatitis C virus infection who underwent liver transplantation between 1995 and 2010. Average age was 52 years and the mean Model for End-Stage Liver Disease (MELD) score was 15.

IL28B genotype of recipient and donor was assessed from liver biopsies done at the time of transplantation, and serial biopsies of the liver graft were done after transplantation to assess virologic and histologic measures of recurrence.

Only 31% of the recipients had the IL28B CC genotype, compared with 52% of the donors, Dr. Duarte-Rojo reported.

The time to virologic recurrence after transplantation was longer when the recipient had the CC genotype vs. a non-CC genotype (4.6 vs. 4.1 months), whereas it was nonsignificantly shorter when the donor had the CC vs. a non-CC genotype.

Similarly, the proportion of patients that developed histologic recurrence as defined by stage 2 or greater fibrosis 1 year post transplantation was lower when the recipient had the CC vs. a non-CC genotype (19% vs. 38%). In contrast, recurrence rate was higher when the donor had the CC vs. a non-CC genotype (43% vs. 23%).

And there was also an interaction, whereby the proportion with recurrence ranged from a low of 17% with a CC recipient and non-CC donor, to a high of 52% with a non-CC recipient and a CC donor.

In a multivariate analysis that included factors such as alanine aminotransferase level, MELD score, viral genotype, surgical and biliary complications, cytomegalovirus infection, and diabetes, the risk of recurrence was still markedly decreased when the recipient had the CC genotype (odds ratio, 0.40) and markedly increased when the donor had the CC genotype (OR, 2.71).

The results were essentially the same after exclusion of patients who received antiviral therapy, according to Dr. Duarte-Rojo.

He noted that the recipient and donor IL28B genotypes also had opposite effects on alanine aminotransferase levels, viral loads, and rates of acute cellular rejection during follow-up.

Dr. Duarte-Rojo reported that he had no relevant conflicts of interest.

SAN FRANCISCO – Both donor and recipient interleukin 28B genotype affect the risk of recurrence of hepatitis C after liver transplantation, but they do so in opposite directions.

Investigators led by Dr. Andres Duarte-Rojo of the Mayo Clinic in Rochester, Minn., studied a cohort of more than 200 patients with hepatitis C who underwent liver transplantation, finding that 32% had a histologic recurrence 1 year later.

The risk of such recurrence was reduced by more than half when the recipient had the interleukin 28B (IL28B) CC genotype, as compared with the CT or TT genotype, according to results reported at the annual meeting of the American Association for the Study of Liver Diseases. In sharp contrast, the risk was almost tripled if the donor had the CC genotype for IL28B instead of one of the others.

"Variations in the phenotypic expression of IL28B genotype occur in relation to its source, either the recipient or the donor. This paradoxical effect suggests variation in the activation of the adaptive immune system according to hepatic and nonhepatic IL28B genotype," Dr. Duarte-Rojo commented.

Other research by his group suggests that donor and recipient CC genotype have a synergistic effect in promoting sustained virologic response after transplantation. "However, according to current results, allocation of a CC allograft to hepatitis C patients may predispose to a more severe disease in those untreated or not achieving a sustained virologic response," he said.

IL28 is a cytokine playing a role in antiviral defenses. The genotype for the B isoform "affects hepatitis C virus eradication, whether spontaneous or therapy driven," Dr. Duarte-Rojo noted. "It is important to study the associations of IL28B in the posttransplant setting to unravel mechanisms driving viral-host interactions and help the understanding of this polymorphism in hepatitis C pathobiology."

The investigators studied 241 consecutive patients with hepatitis C virus infection who underwent liver transplantation between 1995 and 2010. Average age was 52 years and the mean Model for End-Stage Liver Disease (MELD) score was 15.

IL28B genotype of recipient and donor was assessed from liver biopsies done at the time of transplantation, and serial biopsies of the liver graft were done after transplantation to assess virologic and histologic measures of recurrence.

Only 31% of the recipients had the IL28B CC genotype, compared with 52% of the donors, Dr. Duarte-Rojo reported.

The time to virologic recurrence after transplantation was longer when the recipient had the CC genotype vs. a non-CC genotype (4.6 vs. 4.1 months), whereas it was nonsignificantly shorter when the donor had the CC vs. a non-CC genotype.

Similarly, the proportion of patients that developed histologic recurrence as defined by stage 2 or greater fibrosis 1 year post transplantation was lower when the recipient had the CC vs. a non-CC genotype (19% vs. 38%). In contrast, recurrence rate was higher when the donor had the CC vs. a non-CC genotype (43% vs. 23%).

And there was also an interaction, whereby the proportion with recurrence ranged from a low of 17% with a CC recipient and non-CC donor, to a high of 52% with a non-CC recipient and a CC donor.

In a multivariate analysis that included factors such as alanine aminotransferase level, MELD score, viral genotype, surgical and biliary complications, cytomegalovirus infection, and diabetes, the risk of recurrence was still markedly decreased when the recipient had the CC genotype (odds ratio, 0.40) and markedly increased when the donor had the CC genotype (OR, 2.71).

The results were essentially the same after exclusion of patients who received antiviral therapy, according to Dr. Duarte-Rojo.

He noted that the recipient and donor IL28B genotypes also had opposite effects on alanine aminotransferase levels, viral loads, and rates of acute cellular rejection during follow-up.

Dr. Duarte-Rojo reported that he had no relevant conflicts of interest.

SAN FRANCISCO – Both donor and recipient interleukin 28B genotype affect the risk of recurrence of hepatitis C after liver transplantation, but they do so in opposite directions.

Investigators led by Dr. Andres Duarte-Rojo of the Mayo Clinic in Rochester, Minn., studied a cohort of more than 200 patients with hepatitis C who underwent liver transplantation, finding that 32% had a histologic recurrence 1 year later.

The risk of such recurrence was reduced by more than half when the recipient had the interleukin 28B (IL28B) CC genotype, as compared with the CT or TT genotype, according to results reported at the annual meeting of the American Association for the Study of Liver Diseases. In sharp contrast, the risk was almost tripled if the donor had the CC genotype for IL28B instead of one of the others.

"Variations in the phenotypic expression of IL28B genotype occur in relation to its source, either the recipient or the donor. This paradoxical effect suggests variation in the activation of the adaptive immune system according to hepatic and nonhepatic IL28B genotype," Dr. Duarte-Rojo commented.

Other research by his group suggests that donor and recipient CC genotype have a synergistic effect in promoting sustained virologic response after transplantation. "However, according to current results, allocation of a CC allograft to hepatitis C patients may predispose to a more severe disease in those untreated or not achieving a sustained virologic response," he said.

IL28 is a cytokine playing a role in antiviral defenses. The genotype for the B isoform "affects hepatitis C virus eradication, whether spontaneous or therapy driven," Dr. Duarte-Rojo noted. "It is important to study the associations of IL28B in the posttransplant setting to unravel mechanisms driving viral-host interactions and help the understanding of this polymorphism in hepatitis C pathobiology."

The investigators studied 241 consecutive patients with hepatitis C virus infection who underwent liver transplantation between 1995 and 2010. Average age was 52 years and the mean Model for End-Stage Liver Disease (MELD) score was 15.

IL28B genotype of recipient and donor was assessed from liver biopsies done at the time of transplantation, and serial biopsies of the liver graft were done after transplantation to assess virologic and histologic measures of recurrence.

Only 31% of the recipients had the IL28B CC genotype, compared with 52% of the donors, Dr. Duarte-Rojo reported.

The time to virologic recurrence after transplantation was longer when the recipient had the CC genotype vs. a non-CC genotype (4.6 vs. 4.1 months), whereas it was nonsignificantly shorter when the donor had the CC vs. a non-CC genotype.

Similarly, the proportion of patients that developed histologic recurrence as defined by stage 2 or greater fibrosis 1 year post transplantation was lower when the recipient had the CC vs. a non-CC genotype (19% vs. 38%). In contrast, recurrence rate was higher when the donor had the CC vs. a non-CC genotype (43% vs. 23%).

And there was also an interaction, whereby the proportion with recurrence ranged from a low of 17% with a CC recipient and non-CC donor, to a high of 52% with a non-CC recipient and a CC donor.

In a multivariate analysis that included factors such as alanine aminotransferase level, MELD score, viral genotype, surgical and biliary complications, cytomegalovirus infection, and diabetes, the risk of recurrence was still markedly decreased when the recipient had the CC genotype (odds ratio, 0.40) and markedly increased when the donor had the CC genotype (OR, 2.71).

The results were essentially the same after exclusion of patients who received antiviral therapy, according to Dr. Duarte-Rojo.

He noted that the recipient and donor IL28B genotypes also had opposite effects on alanine aminotransferase levels, viral loads, and rates of acute cellular rejection during follow-up.

Dr. Duarte-Rojo reported that he had no relevant conflicts of interest.

Performing liver transplantation early in patients with severe alcoholic hepatitis unresponsive to medical therapy, rather than requiring that they demonstrate 6 months of sobriety before transplantation, improves their survival, according to a Nov. 10 report in the New England Journal of Medicine.

Six-month survival was 77% in a study of such patients who underwent early transplantation, compared with only 23% among matched control subjects who did not, said Dr. Philippe Mathurin of Hôpital Claude Huriez and Université Lille Nord de France, and his associates.

There were no alcoholic relapses during that 6 months. However, 3 of the 26 transplant patients resumed alcohol use during an extended 2-year follow-up; none of them developed graft dysfunction.

"Our findings challenge both the notion of a prescribed abstinence period as the only alcoholism-related criterion for transplant eligibility and the opinion of experts that alcoholic hepatitis is a contraindication for transplantation," the investigators noted.

Liver transplantation for alcoholic hepatitis usually has a favorable outcome but is controversial. Among those who oppose it, clinicians tend to think that the patient will resume drinking and eventually destroy the graft, and the public tends to prefer alloting scarce donor livers to nonalcoholic patients whom they perceive as more deserving.

The requirement that patients with severe alcoholic hepatitis demonstrate 6 months of sobriety is recognized as an arbitrary constraint, since the duration of abstinence is known to be a poor predictor of relapse of alcoholism. And 70%-80% of such patients die during that mandated interval.

Dr. Mathurin and his colleagues performed a comparative study to determine whether earlier transplantation would improve 6-month survival in patients whose severe alcoholic hepatitis was nonresponsive to medical management. They recruited patients at seven transplant centers in France.

A total of 26 patients were selected using very strict criteria to undergo early transplant. They were eligible only if the hepatitis was their first liver-decompensating event, if they had a good support network of family and friends, if they had no concomitant psychiatric disorders, and if they agreed to lifelong total alcohol abstinence.

"The stringency of our selection process resulted in our selecting a very small number of patients with alcoholic hepatitis for early transplantation" from a large pool of potential transplant recipients, the researchers noted.

The transplant patients were matched for age, sex, Maddrey’s discriminant function (a measure of liver disease severity), and Lille score (a predictor of likeliness to respond to medical therapy) to 26 control subjects.

Six-month survival was significantly higher among the transplant patients (77%) than among the controls (23%).

Eighteen of the 20 deaths among the control subjects (90%) occurred within 2 months of discovery that they were not responding to medical management – that is, well before the 6-month abstinence period had elapsed, the investigators said (N. Engl. J. Med. 2011;365:1790-1800).

When follow-up was extended to 2 years, early transplantation remained associated with significantly improved survival (72%), compared with control subjects (23%).

Investigators had also sought to measure the rate of posttransplantation alcohol relapse in patients selected free of the 6-month rule. None of the transplant recipients resumed drinking during the 6-month follow-up, but three did so later, at 720 days, 740 days, and 1,140 days. None of these three grafts has yet demonstrated dysfunction.

"Previous studies of patients with alcoholism who underwent transplantation suggest that the rate of relapse over the long term may be approximately 25%-35%," Dr. Mathurin and his associates noted.

In weighing the burden of early transplantation on the overall transplantation activity of participating centers, investigators said that only 2.9% of the grafts used during the study period were for early liver transplantation. While some observers contend that the public may be less willing to donate if guidelines are modified regarding alcoholic patients, the authors said that has not happened where transplantation is offered to intravenous drug users or patients who have voluntarily overdosed on acetaminophen.

The findings show that "early liver transplantation may be an appropriate rescue option for selected patients whose first episode of severe alcoholic hepatitis is not responsive to medical therapy, after careful assessment of their addiction profile," the investigators said.

This study was supported by the Société Nationale Française de Gastroentérologie. Dr. Mathurin and his associates reported numerous ties to industry sources.

Performing liver transplantation early in patients with severe alcoholic hepatitis unresponsive to medical therapy, rather than requiring that they demonstrate 6 months of sobriety before transplantation, improves their survival, according to a Nov. 10 report in the New England Journal of Medicine.

Six-month survival was 77% in a study of such patients who underwent early transplantation, compared with only 23% among matched control subjects who did not, said Dr. Philippe Mathurin of Hôpital Claude Huriez and Université Lille Nord de France, and his associates.

There were no alcoholic relapses during that 6 months. However, 3 of the 26 transplant patients resumed alcohol use during an extended 2-year follow-up; none of them developed graft dysfunction.

"Our findings challenge both the notion of a prescribed abstinence period as the only alcoholism-related criterion for transplant eligibility and the opinion of experts that alcoholic hepatitis is a contraindication for transplantation," the investigators noted.

Liver transplantation for alcoholic hepatitis usually has a favorable outcome but is controversial. Among those who oppose it, clinicians tend to think that the patient will resume drinking and eventually destroy the graft, and the public tends to prefer alloting scarce donor livers to nonalcoholic patients whom they perceive as more deserving.

The requirement that patients with severe alcoholic hepatitis demonstrate 6 months of sobriety is recognized as an arbitrary constraint, since the duration of abstinence is known to be a poor predictor of relapse of alcoholism. And 70%-80% of such patients die during that mandated interval.

Dr. Mathurin and his colleagues performed a comparative study to determine whether earlier transplantation would improve 6-month survival in patients whose severe alcoholic hepatitis was nonresponsive to medical management. They recruited patients at seven transplant centers in France.

A total of 26 patients were selected using very strict criteria to undergo early transplant. They were eligible only if the hepatitis was their first liver-decompensating event, if they had a good support network of family and friends, if they had no concomitant psychiatric disorders, and if they agreed to lifelong total alcohol abstinence.

"The stringency of our selection process resulted in our selecting a very small number of patients with alcoholic hepatitis for early transplantation" from a large pool of potential transplant recipients, the researchers noted.

The transplant patients were matched for age, sex, Maddrey’s discriminant function (a measure of liver disease severity), and Lille score (a predictor of likeliness to respond to medical therapy) to 26 control subjects.

Six-month survival was significantly higher among the transplant patients (77%) than among the controls (23%).

Eighteen of the 20 deaths among the control subjects (90%) occurred within 2 months of discovery that they were not responding to medical management – that is, well before the 6-month abstinence period had elapsed, the investigators said (N. Engl. J. Med. 2011;365:1790-1800).

When follow-up was extended to 2 years, early transplantation remained associated with significantly improved survival (72%), compared with control subjects (23%).

Investigators had also sought to measure the rate of posttransplantation alcohol relapse in patients selected free of the 6-month rule. None of the transplant recipients resumed drinking during the 6-month follow-up, but three did so later, at 720 days, 740 days, and 1,140 days. None of these three grafts has yet demonstrated dysfunction.

"Previous studies of patients with alcoholism who underwent transplantation suggest that the rate of relapse over the long term may be approximately 25%-35%," Dr. Mathurin and his associates noted.

In weighing the burden of early transplantation on the overall transplantation activity of participating centers, investigators said that only 2.9% of the grafts used during the study period were for early liver transplantation. While some observers contend that the public may be less willing to donate if guidelines are modified regarding alcoholic patients, the authors said that has not happened where transplantation is offered to intravenous drug users or patients who have voluntarily overdosed on acetaminophen.

The findings show that "early liver transplantation may be an appropriate rescue option for selected patients whose first episode of severe alcoholic hepatitis is not responsive to medical therapy, after careful assessment of their addiction profile," the investigators said.

This study was supported by the Société Nationale Française de Gastroentérologie. Dr. Mathurin and his associates reported numerous ties to industry sources.

Performing liver transplantation early in patients with severe alcoholic hepatitis unresponsive to medical therapy, rather than requiring that they demonstrate 6 months of sobriety before transplantation, improves their survival, according to a Nov. 10 report in the New England Journal of Medicine.

Six-month survival was 77% in a study of such patients who underwent early transplantation, compared with only 23% among matched control subjects who did not, said Dr. Philippe Mathurin of Hôpital Claude Huriez and Université Lille Nord de France, and his associates.

There were no alcoholic relapses during that 6 months. However, 3 of the 26 transplant patients resumed alcohol use during an extended 2-year follow-up; none of them developed graft dysfunction.

"Our findings challenge both the notion of a prescribed abstinence period as the only alcoholism-related criterion for transplant eligibility and the opinion of experts that alcoholic hepatitis is a contraindication for transplantation," the investigators noted.

Liver transplantation for alcoholic hepatitis usually has a favorable outcome but is controversial. Among those who oppose it, clinicians tend to think that the patient will resume drinking and eventually destroy the graft, and the public tends to prefer alloting scarce donor livers to nonalcoholic patients whom they perceive as more deserving.

The requirement that patients with severe alcoholic hepatitis demonstrate 6 months of sobriety is recognized as an arbitrary constraint, since the duration of abstinence is known to be a poor predictor of relapse of alcoholism. And 70%-80% of such patients die during that mandated interval.

Dr. Mathurin and his colleagues performed a comparative study to determine whether earlier transplantation would improve 6-month survival in patients whose severe alcoholic hepatitis was nonresponsive to medical management. They recruited patients at seven transplant centers in France.

A total of 26 patients were selected using very strict criteria to undergo early transplant. They were eligible only if the hepatitis was their first liver-decompensating event, if they had a good support network of family and friends, if they had no concomitant psychiatric disorders, and if they agreed to lifelong total alcohol abstinence.

"The stringency of our selection process resulted in our selecting a very small number of patients with alcoholic hepatitis for early transplantation" from a large pool of potential transplant recipients, the researchers noted.

The transplant patients were matched for age, sex, Maddrey’s discriminant function (a measure of liver disease severity), and Lille score (a predictor of likeliness to respond to medical therapy) to 26 control subjects.

Six-month survival was significantly higher among the transplant patients (77%) than among the controls (23%).

Eighteen of the 20 deaths among the control subjects (90%) occurred within 2 months of discovery that they were not responding to medical management – that is, well before the 6-month abstinence period had elapsed, the investigators said (N. Engl. J. Med. 2011;365:1790-1800).

When follow-up was extended to 2 years, early transplantation remained associated with significantly improved survival (72%), compared with control subjects (23%).

Investigators had also sought to measure the rate of posttransplantation alcohol relapse in patients selected free of the 6-month rule. None of the transplant recipients resumed drinking during the 6-month follow-up, but three did so later, at 720 days, 740 days, and 1,140 days. None of these three grafts has yet demonstrated dysfunction.

"Previous studies of patients with alcoholism who underwent transplantation suggest that the rate of relapse over the long term may be approximately 25%-35%," Dr. Mathurin and his associates noted.

In weighing the burden of early transplantation on the overall transplantation activity of participating centers, investigators said that only 2.9% of the grafts used during the study period were for early liver transplantation. While some observers contend that the public may be less willing to donate if guidelines are modified regarding alcoholic patients, the authors said that has not happened where transplantation is offered to intravenous drug users or patients who have voluntarily overdosed on acetaminophen.

The findings show that "early liver transplantation may be an appropriate rescue option for selected patients whose first episode of severe alcoholic hepatitis is not responsive to medical therapy, after careful assessment of their addiction profile," the investigators said.

This study was supported by the Société Nationale Française de Gastroentérologie. Dr. Mathurin and his associates reported numerous ties to industry sources.