Diagnosing antibody-mediated rejection in liver transplant recipients is hindered by a lack of biomarkers and co-occurrence of rejection and allograft damage.
Despite recent advances, notably the Banff 2016 Working Group Criteria, the diagnosis and treatment of antibody-mediated rejection of the liver still impose substantial challenges due to indeterminate characteristics, according to a review published in the Journal of Liver Transplantation.
“Antibody-mediated rejection (AMR) has emerged as a defining barrier to maintenance of long-term liver allograft function,” Kevin Toomer, MD, PhD, and colleagues noted. “The liver’s unique anatomy, high regenerative capacity, and tolerogenic immunological environment tend to mitigate the severest AMR manifestations. Consequently, the clinical importance of AMR in the liver has been recognized more slowly than for other solid organ allografts.”
According to the researchers, this makes signs of AMR in the liver less apparent and severe compared with other organ transplant sites. Moreover, while there has been notable progress in recent years, predominantly with the Banff 2016 criteria for liver AMR, diagnosing AMR in the liver remains challenging.
“The goal of this review is to summarize the current understanding of AMR in the context of liver transplantation, including risk factors, pathogenesis, and current diagnostic and treatment strategies,” the researchers wrote. “Potential directions of future research are also addressed.”
Need for More Biomarkers of AMR
Scientific data and evidence from clinical and laboratory studies presented in this review demonstrate that liver transplantation can protect from immune-mediated damage to other concurrently transplanted solid organs, which may offer the potential to employ the liver’s tolerogenic properties to develop novel immune-modulating therapies.
However, one barrier to the precise diagnosis of AMR in liver transplant is “the frequent co-occurrence of T-cell mediated rejection and non-immunologic allograft damage (including recurrence of primary disease),” according to Dr. Toomer and colleagues.
Other challenges with the diagnosis of AMR in liver transplantation include “an urgent need” for new clinical and histologic AMR biomarkers. Specifically, Dr. Toomer and colleagues found that current histopathologic definitions of AMR lack sensitivity and specificity. Further, “C4d staining is an imperfect biological surrogate for antibody-mediated injury” that is impacted by significant technical limitations, according to the researchers.
They noted that such biomarkers stand to improve diagnosis, risk stratification, and therapy. The reviewers also emphasized that molecular genetic approaches “will likely be crucial to these efforts.”
