Top Highlights in Hepatology: The Liver Meeting 2014
Top Highlights in Hepatology: The Liver Meeting 2014
Author's Note: Significant advances in the diagnosis and management of patients with liver disease were presented at The Liver Meeting® 2014, which is the annual meeting of the American Association for the Study of Liver Diseases (AASLD). Investigators highlighted progress in the understanding of common issues, including the availability of novel diagnostic and therapeutic options, as well as valid screening methodology to ensure optimal outcomes for patients. Some of the concepts that emerged from the many outstanding presentations in liver transplantation, primary sclerosing cholangitis, primary biliary cirrhosis, biliary atresia, and pediatric liver disease are highlighted here.
Key presentations addressed questions about donor shortages and the challenges facing patients who have undergone transplantation—specifically, recurrence of disease and complications of immune suppression. Can we reduce renal and infectious complications through immunosuppressive withdrawal?
Venkat and colleagues described the clinical response to protocolized immunosuppression withdrawal in an ongoing multicenter study of 74 children who were more than 4 years post-transplantation, had normal alanine aminotransferase (ALT) and gamma-glutamyltransferase levels, and were receiving calcineurin inhibitor monotherapy. Supervised withdrawal of immunosuppression was highly structured over eight steps (75% tapering to 0% of the immunosuppression dose over 36-48 weeks).
At the interim analysis point, immunosuppression had been withdrawn in 42% of the patients, and 31% were still in the process. The remainder (27%) had elevated liver enzyme levels and were documented to have biopsy-proven acute rejection; these rejection episodes occurred when the tapering dose reached < 33% of prewithdrawal maintenance tacrolimus doses. Rejection was histologically mild or moderate and was readily reversed with steroids and restoration of tacrolimus therapy.
The data suggest that immunosuppression withdrawal may be possible for selected children after liver transplantation. Ongoing clinical and histologic follow-up will need to confirm whether withdrawal of immunosuppression is safe in the long term.
Living donor liver transplantation (LDLT), which can help to bridge the current organ supply/demand mismatch, accounts for only 3%-4% of adult liver transplants in the United States. Although early national data demonstrated inferior outcomes in LDLT recipients, recent data reveal excellent outcomes when the procedure is performed at an experienced center. The improved outcomes have been attributed to a greater appreciation of the technical aspects, advanced perioperative management, and optimal qualities of the donor/recipient dyad. Nevertheless, LDLT is viewed as controversial.
Goldberg and colleagues examined national Organ Procurement and Transplantation Network/United Network for Organ Sharing data from 2002 to 2012 to determine whether LDLT (n = 2103) conferred a long-term survival benefit relative to deceased donor liver transplantation (DDLT) (n = 46,674). Overall unadjusted graft and patient post-transplant survival was significantly higher for LDLT recipients, although the benefit was restricted to centers that had performed more than 15 LDLT procedures.
The investigators also developed a risk score to predict post-LDLT graft outcomes; this will help to identify optimal donor/recipient matches and counsel wait-listed patients considering LDLT to optimize outcomes and provide objective criteria for donor selection.
The outcomes of patients who undergo liver transplantation are also dependent on the prevention of recurrent or de novo disease, especially autoimmune disease and viral hepatitis.
Primary sclerosing cholangitis (PSC)recurs in 15%-25% of patients. Factors associated with an increased risk for PSC recurrence include a high Model for End-Stage Liver Disease score, first-degree relative donors, post-transplant cytomegalovirus infection, and early biliary anastomotic complications.
Gordon and colleagues compared the risk for PSC recurrence in LDLT (n = 241) vs DDLT (n = 65) recipients. The overall long-term PSC recurrence probabilities were 9% and 25% at 5 and 10 years after transplant, respectively. There was no significant difference in the probability of recurrent PSC in DDLT vs LDLT recipients, regardless of the degree of relatedness.
Strategies for the prevention of recurrent hepatitis C infection post-transplantation are discussed in a separate article.
Author's Note: Significant advances in the diagnosis and management of patients with liver disease were presented at The Liver Meeting® 2014, which is the annual meeting of the American Association for the Study of Liver Diseases (AASLD). Investigators highlighted progress in the understanding of common issues, including the availability of novel diagnostic and therapeutic options, as well as valid screening methodology to ensure optimal outcomes for patients. Some of the concepts that emerged from the many outstanding presentations in liver transplantation, primary sclerosing cholangitis, primary biliary cirrhosis, biliary atresia, and pediatric liver disease are highlighted here.
Liver Transplantation: Can We Improve Outcomes?
Key presentations addressed questions about donor shortages and the challenges facing patients who have undergone transplantation—specifically, recurrence of disease and complications of immune suppression. Can we reduce renal and infectious complications through immunosuppressive withdrawal?
Venkat and colleagues described the clinical response to protocolized immunosuppression withdrawal in an ongoing multicenter study of 74 children who were more than 4 years post-transplantation, had normal alanine aminotransferase (ALT) and gamma-glutamyltransferase levels, and were receiving calcineurin inhibitor monotherapy. Supervised withdrawal of immunosuppression was highly structured over eight steps (75% tapering to 0% of the immunosuppression dose over 36-48 weeks).
At the interim analysis point, immunosuppression had been withdrawn in 42% of the patients, and 31% were still in the process. The remainder (27%) had elevated liver enzyme levels and were documented to have biopsy-proven acute rejection; these rejection episodes occurred when the tapering dose reached < 33% of prewithdrawal maintenance tacrolimus doses. Rejection was histologically mild or moderate and was readily reversed with steroids and restoration of tacrolimus therapy.
The data suggest that immunosuppression withdrawal may be possible for selected children after liver transplantation. Ongoing clinical and histologic follow-up will need to confirm whether withdrawal of immunosuppression is safe in the long term.
Is Survival Similar Using Living Donors?
Living donor liver transplantation (LDLT), which can help to bridge the current organ supply/demand mismatch, accounts for only 3%-4% of adult liver transplants in the United States. Although early national data demonstrated inferior outcomes in LDLT recipients, recent data reveal excellent outcomes when the procedure is performed at an experienced center. The improved outcomes have been attributed to a greater appreciation of the technical aspects, advanced perioperative management, and optimal qualities of the donor/recipient dyad. Nevertheless, LDLT is viewed as controversial.
Goldberg and colleagues examined national Organ Procurement and Transplantation Network/United Network for Organ Sharing data from 2002 to 2012 to determine whether LDLT (n = 2103) conferred a long-term survival benefit relative to deceased donor liver transplantation (DDLT) (n = 46,674). Overall unadjusted graft and patient post-transplant survival was significantly higher for LDLT recipients, although the benefit was restricted to centers that had performed more than 15 LDLT procedures.
The investigators also developed a risk score to predict post-LDLT graft outcomes; this will help to identify optimal donor/recipient matches and counsel wait-listed patients considering LDLT to optimize outcomes and provide objective criteria for donor selection.
Does Donor Type Influence Recurrence of Liver Disease?
The outcomes of patients who undergo liver transplantation are also dependent on the prevention of recurrent or de novo disease, especially autoimmune disease and viral hepatitis.
Primary sclerosing cholangitis (PSC)recurs in 15%-25% of patients. Factors associated with an increased risk for PSC recurrence include a high Model for End-Stage Liver Disease score, first-degree relative donors, post-transplant cytomegalovirus infection, and early biliary anastomotic complications.
Gordon and colleagues compared the risk for PSC recurrence in LDLT (n = 241) vs DDLT (n = 65) recipients. The overall long-term PSC recurrence probabilities were 9% and 25% at 5 and 10 years after transplant, respectively. There was no significant difference in the probability of recurrent PSC in DDLT vs LDLT recipients, regardless of the degree of relatedness.
Strategies for the prevention of recurrent hepatitis C infection post-transplantation are discussed in a separate article.
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