A study published in Hepatobiliary & Pancreatic Diseases International (DOI:10.1016/j.hbpd.2026.04.008) introduces a new composite scoring system that could significantly reduce unnecessary steroid treatment in liver transplant recipients. The Seven Up score, which combines routine day 7 biopsy findings with simple blood test trends, revealed that while more than one third of patients showed histological signs of moderate to severe T cell mediated rejection (TCMR), only 4.5% actually required treatment. This suggests that most early rejection episodes resolve on their own, and treating based solely on biopsy results may expose patients to avoidable steroid-related complications without improving long-term outcomes.
Long-term outcomes after liver transplantation are often hampered by complications linked to intensive immunosuppression, including infections, cardiovascular events, kidney dysfunction, and metabolic disorders, which affect 10% to 40% of recipients. The fear of graft loss has historically 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. A more refined approach is needed to distinguish patients who truly require therapy from those who can be safely observed.
The research, conducted at Université catholique de Louvain in Brussels, Belgium, under the leadership of Prof. Jan P. Lerut, included 421 consecutive adult liver transplant recipients with complete follow-up through December 2024. The Seven Up score integrates two components: a histological component using the Banff score (0–9) from a protocol biopsy performed on post-operative day 7, and a biological component (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 the Seven Up score was applied—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).
“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.
