A study published in Hepatobiliary & Pancreatic Diseases International (DOI:10.1016/j.hbpd.2026.04.008) reveals that a new composite scoring system, the Seven Up score, could spare one in three liver transplant recipients from unnecessary steroid treatment for early rejection. 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 Seven Up score combines routine day 7 biopsy findings with simple blood test trends to identify which patients actually require treatment for T cell-mediated rejection (TCMR). While more than one third of patients (37.3%) showed histological signs of moderate to severe TCMR (Banff scores 6-9), only 4.5% actually required treatment when the Seven Up score was applied. This approach spared 138 patients (32.8%) from early steroid boluses without compromising long-term graft and patient survival.
The 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) capturing 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 with Banff scores of 6-9 would have received steroid treatment. However, when the Seven Up score was applied—requiring both Banff ≥6 and Bio-score ≥2—only 19 patients qualified for treatment during the first 15 days.
The findings address a long-standing challenge in liver transplantation: the fear of graft loss has driven high-dose immunosuppression protocols, yet clinical experience has 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 Seven Up score offers a more refined approach to distinguish patients who truly require therapy from those who can be safely observed.
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). Notably, long-term graft and patient survival were comparable between treated and untreated groups, suggesting that treating based on biopsy alone may expose patients to avoidable steroid-related harm without improving outcomes.
"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."
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 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.
