Reuters Health Information (2012-08-06): Hep C liver transplant patients do well with living or deceased donors
Hep C liver transplant patients do well with living or deceased donors
Last Updated: 2012-08-06 19:30:25 -0400 (Reuters Health)
NEW YORK (Reuters Health) - A meta-analysis from China shows long term outcomes of liver transplantation for hepatitis C to be equally good whether grafts come from living or deceased donors.
The study was undertaken because of conflicting reports in the literature. Theoretically, liver transplants from living donors might have an increased risk of more aggressively recurrent hepatitis C, as lead authors Dr. Anbin Hu and Dr. Xiaoshun He of Sun Yat Sen University explained in an email to Reuters Health.
"Intense regeneration of hepatocytes in the graft after living donor liver transplantation (LDLT) may promote the translation and viral replication of residual hepatitis C virus," they said. "In addition, through upregulating the low-density lipoprotein receptor, hepatocyte proliferation could enhance the entry of the virus into hepatocytes. Increased HLA matching of the recipient with the donor could lead to increased intra-hepatocyte virus proliferation."
Searching the literature, the researchers identified 14 studies involving 2,024 liver recipients that met their criteria. None was randomized. They performed the meta-analysis using methods and software developed by the Cochrane Collaboration.
The LDLT and deceased donor liver transplant (DDLT) groups were demographically similar, but in many of the studies, living donors were much younger than deceased donors.
In each of the five years of follow-up, patient survival was equivalent. Graft survival data were not as consistent, with LDLT recipients having significantly worse results at one year (OR, 0.61, p=0.03) and three years (OR 0.66, p=0.03), although differences between the groups in graft survival at years two, four and five were not statistically significant.
Rates of acute rejection and recurrent hepatitis C were similar.
Donor age did play a role: when the analysis was done using only papers with donors in both groups of similar ages, the DDLT group had significantly better short-term patient survival at one year and better graft survival at years two, three and four.
Morbidity and mortality rates of living donors were not addressed in the meta-analysis but the authors cited a large study which found that 16.1% of donors experienced complications and 0.2% died.
Dr. Patricia Sheiner, director of transplantation at Hartford Hospital in Connecticut, was not involved in the study but commented on it for Reuters Health.
"I think the important part of the study is that hepatitis C recurrence was not significantly different," she said.
But, she added, "What makes this more complicated is that most of the studies are reported from 1998-2003, during which time our allocation system changed and also during a time when LDLT was just starting. I suspect the early survival differences may reflect a learning curve, not only in techniques but in patient selection."
Drs. Hu and He say there are no specific criteria for directing patients to undergo LDLT vs DDLT, nor are there established contraindications for LDLT in hepatitis C patients. Based on their results, they feel LDLT is appropriate when a deceased donor liver is not available. They say they hope their paper helps to expand the donor pool and enable more hepatitis C patients to receive curative treatment.
Dr. Sheiner, however, says candidates for LDLT need to have complications of their liver disease, yet cannot be too sick, as earlier experience has shown that they do not do as well. They may do worse with a partial graft from a living donor vs a whole graft from a deceased donor, given the risks for portal hypertension and small-for-size syndrome, and they're not as likely to tolerate complications.
Tumor cases that fall outside of the Milan criteria can still be considered candidates if the patients can be expected to do well and don't have extensive or infiltrating disease or vascular invasion, Dr. Sheiner said. Patients within Milan criteria who face extended waits for DDLT may also be candidates.
She said, "I think the major flaw of the analysis is that the causes of graft failure are missing."
Drs. Hu and He consider their study to be definitive. They write, "Our study provides the most comprehensive evidence to date. We also performed an additional cumulative meta-analysis to study the variation trend of the pooled results. The trend was considered to be consistent and stable for the comparisons regarding patient survival and graft survival. This evidence indicates that the addition of similar future studies would unlikely change the current results."
While a randomized prospective trial to settle this issue would be ideal, they feel that such a trial would be difficult if not impossible.
The study was published online ahead of print in the Journal of Hepatology.
J Hepatol 2012.