A new composite scoring system, dubbed the Seven-Up score, could spare one in three liver transplant recipients from unnecessary steroid treatment for early rejection, according to a study published in Hepatobiliary & Pancreatic Diseases International. The research, conducted at Université catholique de Louvain in Brussels, Belgium, under the leadership of Prof. Jan P. Lerut, analyzed 421 consecutive adult liver transplant recipients with complete follow-up through December 2024.
The study found that while more than one third of patients showed histological signs of moderate to severe T cell mediated rejection (TCMR) on day 7 biopsy, only 4.5% actually required treatment. The Seven-Up score integrates two components: the histological Banff score (0-9) from a protocol biopsy on post-operative day 7, and a biological Bio-score (0-4) that captures dynamic changes in three routine blood markers between day 5 and day 7—rising total bilirubin, rising eosinophil count (with absolute eosinophils ≥600/μL as an additional marker), and declining platelet count.
Under a biopsy-only strategy, all 157 patients (37.3%) with Banff scores of 6-9 would have received steroid treatment. However, when applying the Seven-Up score—requiring both Banff ≥6 and Bio-score ≥2 to define clinically relevant rejection—only 19 patients (4.5%) qualified for treatment during the first 15 days. This approach spared 138 patients (32.8%) from early steroid boluses. Notably, long-term graft and patient survival were comparable between treated and untreated groups, and the Bio-score demonstrated good diagnostic accuracy for very early clinically relevant TCMR (area under the curve = 0.78; 95% confidence interval: 0.68–0.89; P < 0.001).
Long-term outcomes after liver transplantation remain hampered by complications linked to intensive immunosuppression—infections, cardiovascular events, kidney dysfunction, and metabolic disorders affect 10% to 40% of recipients. For decades, the fear of graft loss has driven high-dose immunosuppression protocols, yet clinical experience has long hinted that some rejection episodes may resolve spontaneously. The Banff histology system—the current gold standard—relies on biopsy findings alone to guide treatment, but studies have shown that clinical suspicion correlates poorly with biopsy results, and interobserver variability is high.
"The key message is simple: not every rejection seen under the microscope needs to be treated," the authors said. "For decades, we've been treating the biopsy rather than the patient. Our data show that the liver allograft is remarkably resilient—most early histological rejection resolves without intervention. The Seven-Up score gives clinicians a practical, objective way to distinguish the rare cases that truly need therapy from the many that can be safely observed. In an era when we're increasingly aware of the long-term harms of over-immunosuppression, this is a step toward more personalized, safer care."
The Seven-Up score offers an immediately implementable framework for early post-transplant decision-making. For centers using immunosuppression-minimization strategies, the score can help avoid unnecessary steroid pulses—reducing the risk of infections, diabetes, and other steroid-related complications without compromising graft survival. The biological component may also serve as a non-invasive surrogate for liver biopsy, particularly relevant in partial liver transplantation (split and living donor) where early biopsies carry higher procedural risks. Beyond clinical practice, the score provides a more meaningful endpoint for future immunosuppression trials—moving beyond histological rejection to clinically relevant rejection that actually requires treatment.
The study is published with DOI: 10.1016/j.hbpd.2026.04.008 and the original source can be accessed at https://doi.org/10.1016/j.hbpd.2026.04.008.
