Centrizonal hepatocyte dropout has been described in diverse liver pathologies, including viral hepatitis, venous outflow obstruction, and allograft cellular rejection. However, its clinical significance remains uncertain.

We designed a clinicopathologic study of 206 allograft liver biopsies with centrizonal hepatocyte dropout. Centrizonal hepatocyte dropout was associated most frequently cellular rejection (n=62), asymptomatic/protocol biopsies (n=56), immediate post-transplantation biopsies (n=21), biliary obstruction (n=14), and viral hepatitis (n=13). The differential diagnosis is informed by timing post-transplantation, biliary imaging, and laboratory test results. “Cholestatic” and “hepatocytic” laboratory patterns were associated with biliary obstruction and cellular rejection, respectively. A mixed pattern peaking after biopsy was observed in viral hepatitis. In the context of cellular rejection, dropout was not associated with time interval to normalization of serum ALT but was associated with shorter transplant-free survival (hazard ratio 4, p = 0.01) compared to histologic severity-matched controls. In time zero allograft biopsies, time to ALT normalization was prolonged (median 15 versus 11 days, p=0.002) in allografts with centrizonal dropout, with no effect on re-transplant free survival.

Centrizonal hepatocyte dropout has low clinicopathologic diagnostic specificity. However, it correlates with adverse clinical outcomes in allograft cellular rejection and time zero biopsies.