Transplant

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.

BOSTON — Long-term outcomes of hand transplant patients show that recipients can have good graft functionality and quality of life if they comply with immunosuppressive regimens, according to speakers at the 2006 World Transplant Congress.

Worldwide experience with hand transplants now includes 24 hands in 18 patients with “excellent results,” said Dr. Suzanne T. Ildstad, director of the Institute for Cellular Therapeutics at the University of Louisville (Ky.).

Patients are reluctant to undertake a hand transplant “until we modify or reduce the intensity of immunosuppression,” said Dr. Ildstad. “There are discussions right now with our group and other groups of using steroid-sparing protocols as well as attempts to induce tolerance,” she noted.

Dr. Ildstad presented the 7-year results of a 37-year-old, left-hand-dominant man (patient No. 1, currently the recipient of the longest-surviving hand transplant in the world) and the 4-year results of a 36-year-old, right-hand-dominant man (patient No. 2). Both men lost their left hands in fireworks accidents.

On measurements with the United Kingdom Medical Research Council strength scale, patient No. 1 had an excellent return of function of intrinsic muscles whereas patient No. 2 had an improved, but somewhat delayed, return of function because of a period of noncompliance with his immunosuppressive regimen.

Sensation gradually improved in patient No. 1 to the point where it has become “essentially normal” after 7 years of follow-up, Dr. Ildstad said. Patient No. 2 also experienced gradual improvement in sensation, but it was slightly delayed in comparison with patient No. 1.

In skin biopsy specimens from both patients, low-grade cellular infiltrates have been detected. The patients did not have rejections treated unless they were severe, she said.

When patient No. 2 decided to stop taking his immunosuppressive medications, he subsequently had a grade 3 rejection episode that was “relatively readily reversed” with antithymocyte globulins (Thymoglobulin), increased doses of tacrolimus (Prograf), and corticosteroid boluses, which is contrary to what Dr. Ildstad and many transplant immunologists would have predicted because of the presumed antigenicity of the skin.

In a study of two men who received bilateral hand transplants, improvement in function was accompanied by changes in brain function and good quality of life, reported Dr. Palmina Petruzzo of the department of transplantation at Hôpital Edouard Herriot, Lyon, France.

Functional MRI shows that the patients' representation of their hands in their brains progressively shifted from lateral to medial regions of the motor cortex.

By 2 years following transplantation, hand motor coordination had improved in both patients to the point where they could perform complex movements involving intersegmental coordination, which were assessed while the patients wore a CyberGlove containing 22 sensors that monitor hand movement, according to Dr. Ildstad.

A recipient of a transplant of a left hand demonstrated his manual dexterity and control by tying his shoe at his 4-year checkup. Courtesy Jewish Hospital/Kleinert, Kutz and Associates Hand Care Center/University of Louisville

BOSTON — Long-term outcomes of hand transplant patients show that recipients can have good graft functionality and quality of life if they comply with immunosuppressive regimens, according to speakers at the 2006 World Transplant Congress.

Worldwide experience with hand transplants now includes 24 hands in 18 patients with “excellent results,” said Dr. Suzanne T. Ildstad, director of the Institute for Cellular Therapeutics at the University of Louisville (Ky.).

Patients are reluctant to undertake a hand transplant “until we modify or reduce the intensity of immunosuppression,” said Dr. Ildstad. “There are discussions right now with our group and other groups of using steroid-sparing protocols as well as attempts to induce tolerance,” she noted.

Dr. Ildstad presented the 7-year results of a 37-year-old, left-hand-dominant man (patient No. 1, currently the recipient of the longest-surviving hand transplant in the world) and the 4-year results of a 36-year-old, right-hand-dominant man (patient No. 2). Both men lost their left hands in fireworks accidents.

On measurements with the United Kingdom Medical Research Council strength scale, patient No. 1 had an excellent return of function of intrinsic muscles whereas patient No. 2 had an improved, but somewhat delayed, return of function because of a period of noncompliance with his immunosuppressive regimen.

Sensation gradually improved in patient No. 1 to the point where it has become “essentially normal” after 7 years of follow-up, Dr. Ildstad said. Patient No. 2 also experienced gradual improvement in sensation, but it was slightly delayed in comparison with patient No. 1.

In skin biopsy specimens from both patients, low-grade cellular infiltrates have been detected. The patients did not have rejections treated unless they were severe, she said.

When patient No. 2 decided to stop taking his immunosuppressive medications, he subsequently had a grade 3 rejection episode that was “relatively readily reversed” with antithymocyte globulins (Thymoglobulin), increased doses of tacrolimus (Prograf), and corticosteroid boluses, which is contrary to what Dr. Ildstad and many transplant immunologists would have predicted because of the presumed antigenicity of the skin.

In a study of two men who received bilateral hand transplants, improvement in function was accompanied by changes in brain function and good quality of life, reported Dr. Palmina Petruzzo of the department of transplantation at Hôpital Edouard Herriot, Lyon, France.

Functional MRI shows that the patients' representation of their hands in their brains progressively shifted from lateral to medial regions of the motor cortex.

By 2 years following transplantation, hand motor coordination had improved in both patients to the point where they could perform complex movements involving intersegmental coordination, which were assessed while the patients wore a CyberGlove containing 22 sensors that monitor hand movement, according to Dr. Ildstad.

A recipient of a transplant of a left hand demonstrated his manual dexterity and control by tying his shoe at his 4-year checkup. Courtesy Jewish Hospital/Kleinert, Kutz and Associates Hand Care Center/University of Louisville

BOSTON — Long-term outcomes of hand transplant patients show that recipients can have good graft functionality and quality of life if they comply with immunosuppressive regimens, according to speakers at the 2006 World Transplant Congress.

Worldwide experience with hand transplants now includes 24 hands in 18 patients with “excellent results,” said Dr. Suzanne T. Ildstad, director of the Institute for Cellular Therapeutics at the University of Louisville (Ky.).

Patients are reluctant to undertake a hand transplant “until we modify or reduce the intensity of immunosuppression,” said Dr. Ildstad. “There are discussions right now with our group and other groups of using steroid-sparing protocols as well as attempts to induce tolerance,” she noted.

Dr. Ildstad presented the 7-year results of a 37-year-old, left-hand-dominant man (patient No. 1, currently the recipient of the longest-surviving hand transplant in the world) and the 4-year results of a 36-year-old, right-hand-dominant man (patient No. 2). Both men lost their left hands in fireworks accidents.

On measurements with the United Kingdom Medical Research Council strength scale, patient No. 1 had an excellent return of function of intrinsic muscles whereas patient No. 2 had an improved, but somewhat delayed, return of function because of a period of noncompliance with his immunosuppressive regimen.

Sensation gradually improved in patient No. 1 to the point where it has become “essentially normal” after 7 years of follow-up, Dr. Ildstad said. Patient No. 2 also experienced gradual improvement in sensation, but it was slightly delayed in comparison with patient No. 1.

In skin biopsy specimens from both patients, low-grade cellular infiltrates have been detected. The patients did not have rejections treated unless they were severe, she said.

When patient No. 2 decided to stop taking his immunosuppressive medications, he subsequently had a grade 3 rejection episode that was “relatively readily reversed” with antithymocyte globulins (Thymoglobulin), increased doses of tacrolimus (Prograf), and corticosteroid boluses, which is contrary to what Dr. Ildstad and many transplant immunologists would have predicted because of the presumed antigenicity of the skin.

In a study of two men who received bilateral hand transplants, improvement in function was accompanied by changes in brain function and good quality of life, reported Dr. Palmina Petruzzo of the department of transplantation at Hôpital Edouard Herriot, Lyon, France.

Functional MRI shows that the patients' representation of their hands in their brains progressively shifted from lateral to medial regions of the motor cortex.

By 2 years following transplantation, hand motor coordination had improved in both patients to the point where they could perform complex movements involving intersegmental coordination, which were assessed while the patients wore a CyberGlove containing 22 sensors that monitor hand movement, according to Dr. Ildstad.

A recipient of a transplant of a left hand demonstrated his manual dexterity and control by tying his shoe at his 4-year checkup. Courtesy Jewish Hospital/Kleinert, Kutz and Associates Hand Care Center/University of Louisville

Although nerve transplantations are rarely performed, they can provide an alternative to amputation, and some surgeons say they should be considered for seriously injured patients.

Surgeons interviewed for this article identified a total of nine neurosurgeons and plastic surgeons, including themselves, who have transplanted nerves from living donors for more than 10 years.

The surgeons believe that thousands of patients—including soldiers returning from Iraq—could benefit from transplantations and similar procedures. Soldiers who suffer blunt injuries to an isolated spot of nerve would be especially good candidates, said Dr. Andrew Elkwood in an interview.

Dr. Susan Mackinnon, a plastic surgeon at Washington University in St. Louis, performed the first nerve transplantation from a live donor in 1989 in Canada. Transplantation is used as a last resort if patients do not have enough of their own nerve tissue for a graft, she said.

Grafts of patients' own nerve tissues have been around for years, said Dr. Elkwood, a plastic surgeon who practices in New Jersey.

Both surgeons prefer live donors over cadavers for transplantations because family members usually are willing to donate nerve tissue immediately and such tissue is less likely to be rejected than cadaver tissue. It can take several months to find an appropriate cadaver, they added.

The ideal time for a transplantation is 3 months after injury, according to Dr. Elkwood.

In November, Dr. Allan Belzberg, a neurosurgeon at Johns Hopkins University, performed his first allograft transplantation of nerves from a 40-year-old mother to her 19-year-old son, to restore the use of his hand 1 year after an automobile accident left him with left leg amputation and 14-cm gaps in the median and ulnar nerves of the left arm going to the hand.

Dr. Belzberg opted against an autologous graft of expendable leg nerves because the patient had already lost one leg and the other had been broken in seven places. Nor did he want to remove nerves from the patient's one good arm.

Dr. Belzberg harvested nerves from the mother's legs and arms.

Within 3 months, Dr. Belzberg should know if the patient's nerves have regenerated. If all goes well, he will regain motion in his fingers within 8 months and, within 2 years, bend his elbow, grasp with his fingers, and feel protective sensations such as pain, cold, and heat, Dr. Belzberg said. He estimated the chances of achieving these outcomes as 50%–75%.

The patient will take the immunosuppression drug tacrolimus (FK 506) for about 2 years. One side effect of the drug is nerve growth, but Dr. Belzberg said he and a team of other doctors believe the drug is unlikely to spur tumor formation.

Dr. Mackinnon and other surgeons are now using another technique, nerve transfer, to treat patients in whom part of the brachial plexus has been torn. Nerve transfer consists of sacrificing the function of expendable portions of a patient's healthy nerves to revive function in a seriously injured, more crucial nerve.

Bundles of a healthy nerve near the motor end plate of the damaged muscle are teased apart and redirected to revive function in the recipient nerve and muscle. No grafting is necessary.

The technique changes the nerve injury from a proximal injury to a distal one, so nerves—which regenerate only about an inch a month—have less distance to grow, Dr. Mackinnon said.

For example, an injury to the ulnar nerve in the upper arm can require 2 years of recovery after grafting. But “stealing” nerve fibers from the pronator quadratus would require only a few months of recovery, Dr. Mackinnon said.

“There's a strong need for these procedures [transplantations and transfers],” Dr. Elkwood said, adding that too many physicians are unaware they are being done successfully. “We need massive education [about these procedures]. They need to become more mainstream in the lay and medical communities,” he said.

Although nerve transplantations are rarely performed, they can provide an alternative to amputation, and some surgeons say they should be considered for seriously injured patients.

Surgeons interviewed for this article identified a total of nine neurosurgeons and plastic surgeons, including themselves, who have transplanted nerves from living donors for more than 10 years.

The surgeons believe that thousands of patients—including soldiers returning from Iraq—could benefit from transplantations and similar procedures. Soldiers who suffer blunt injuries to an isolated spot of nerve would be especially good candidates, said Dr. Andrew Elkwood in an interview.

Dr. Susan Mackinnon, a plastic surgeon at Washington University in St. Louis, performed the first nerve transplantation from a live donor in 1989 in Canada. Transplantation is used as a last resort if patients do not have enough of their own nerve tissue for a graft, she said.

Grafts of patients' own nerve tissues have been around for years, said Dr. Elkwood, a plastic surgeon who practices in New Jersey.

Both surgeons prefer live donors over cadavers for transplantations because family members usually are willing to donate nerve tissue immediately and such tissue is less likely to be rejected than cadaver tissue. It can take several months to find an appropriate cadaver, they added.

The ideal time for a transplantation is 3 months after injury, according to Dr. Elkwood.

In November, Dr. Allan Belzberg, a neurosurgeon at Johns Hopkins University, performed his first allograft transplantation of nerves from a 40-year-old mother to her 19-year-old son, to restore the use of his hand 1 year after an automobile accident left him with left leg amputation and 14-cm gaps in the median and ulnar nerves of the left arm going to the hand.

Dr. Belzberg opted against an autologous graft of expendable leg nerves because the patient had already lost one leg and the other had been broken in seven places. Nor did he want to remove nerves from the patient's one good arm.

Dr. Belzberg harvested nerves from the mother's legs and arms.

Within 3 months, Dr. Belzberg should know if the patient's nerves have regenerated. If all goes well, he will regain motion in his fingers within 8 months and, within 2 years, bend his elbow, grasp with his fingers, and feel protective sensations such as pain, cold, and heat, Dr. Belzberg said. He estimated the chances of achieving these outcomes as 50%–75%.

The patient will take the immunosuppression drug tacrolimus (FK 506) for about 2 years. One side effect of the drug is nerve growth, but Dr. Belzberg said he and a team of other doctors believe the drug is unlikely to spur tumor formation.

Dr. Mackinnon and other surgeons are now using another technique, nerve transfer, to treat patients in whom part of the brachial plexus has been torn. Nerve transfer consists of sacrificing the function of expendable portions of a patient's healthy nerves to revive function in a seriously injured, more crucial nerve.

Bundles of a healthy nerve near the motor end plate of the damaged muscle are teased apart and redirected to revive function in the recipient nerve and muscle. No grafting is necessary.

The technique changes the nerve injury from a proximal injury to a distal one, so nerves—which regenerate only about an inch a month—have less distance to grow, Dr. Mackinnon said.

For example, an injury to the ulnar nerve in the upper arm can require 2 years of recovery after grafting. But “stealing” nerve fibers from the pronator quadratus would require only a few months of recovery, Dr. Mackinnon said.

“There's a strong need for these procedures [transplantations and transfers],” Dr. Elkwood said, adding that too many physicians are unaware they are being done successfully. “We need massive education [about these procedures]. They need to become more mainstream in the lay and medical communities,” he said.

Although nerve transplantations are rarely performed, they can provide an alternative to amputation, and some surgeons say they should be considered for seriously injured patients.

Surgeons interviewed for this article identified a total of nine neurosurgeons and plastic surgeons, including themselves, who have transplanted nerves from living donors for more than 10 years.

The surgeons believe that thousands of patients—including soldiers returning from Iraq—could benefit from transplantations and similar procedures. Soldiers who suffer blunt injuries to an isolated spot of nerve would be especially good candidates, said Dr. Andrew Elkwood in an interview.

Dr. Susan Mackinnon, a plastic surgeon at Washington University in St. Louis, performed the first nerve transplantation from a live donor in 1989 in Canada. Transplantation is used as a last resort if patients do not have enough of their own nerve tissue for a graft, she said.

Grafts of patients' own nerve tissues have been around for years, said Dr. Elkwood, a plastic surgeon who practices in New Jersey.

Both surgeons prefer live donors over cadavers for transplantations because family members usually are willing to donate nerve tissue immediately and such tissue is less likely to be rejected than cadaver tissue. It can take several months to find an appropriate cadaver, they added.

The ideal time for a transplantation is 3 months after injury, according to Dr. Elkwood.

In November, Dr. Allan Belzberg, a neurosurgeon at Johns Hopkins University, performed his first allograft transplantation of nerves from a 40-year-old mother to her 19-year-old son, to restore the use of his hand 1 year after an automobile accident left him with left leg amputation and 14-cm gaps in the median and ulnar nerves of the left arm going to the hand.

Dr. Belzberg opted against an autologous graft of expendable leg nerves because the patient had already lost one leg and the other had been broken in seven places. Nor did he want to remove nerves from the patient's one good arm.

Dr. Belzberg harvested nerves from the mother's legs and arms.

Within 3 months, Dr. Belzberg should know if the patient's nerves have regenerated. If all goes well, he will regain motion in his fingers within 8 months and, within 2 years, bend his elbow, grasp with his fingers, and feel protective sensations such as pain, cold, and heat, Dr. Belzberg said. He estimated the chances of achieving these outcomes as 50%–75%.

The patient will take the immunosuppression drug tacrolimus (FK 506) for about 2 years. One side effect of the drug is nerve growth, but Dr. Belzberg said he and a team of other doctors believe the drug is unlikely to spur tumor formation.

Dr. Mackinnon and other surgeons are now using another technique, nerve transfer, to treat patients in whom part of the brachial plexus has been torn. Nerve transfer consists of sacrificing the function of expendable portions of a patient's healthy nerves to revive function in a seriously injured, more crucial nerve.

Bundles of a healthy nerve near the motor end plate of the damaged muscle are teased apart and redirected to revive function in the recipient nerve and muscle. No grafting is necessary.

The technique changes the nerve injury from a proximal injury to a distal one, so nerves—which regenerate only about an inch a month—have less distance to grow, Dr. Mackinnon said.

For example, an injury to the ulnar nerve in the upper arm can require 2 years of recovery after grafting. But “stealing” nerve fibers from the pronator quadratus would require only a few months of recovery, Dr. Mackinnon said.

“There's a strong need for these procedures [transplantations and transfers],” Dr. Elkwood said, adding that too many physicians are unaware they are being done successfully. “We need massive education [about these procedures]. They need to become more mainstream in the lay and medical communities,” he said.