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Centrizonal hepatocyte dropout in allograft liver biopsies: a clinicopathological study
Dustin E Bosch1,2, Paul E Swanson1,3, Matthew M Yeh1,3
1Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Insights
Centrizonal hepatocyte dropout in liver allografts has low diagnostic specificity but indicates poor outcomes in cellular rejection and early post-transplant periods. This finding impacts transplant patient survival and recovery timelines.
Area of Science:
- Hepatology
- Transplant Pathology
- Clinical Diagnostics
Background:
- Centrizonal hepatocyte dropout is observed in various liver conditions, including viral hepatitis, venous outflow obstruction, and allograft cellular rejection.
- The precise clinical significance and diagnostic utility of centrizonal hepatocyte dropout remain uncertain in liver transplantation.
Purpose of the Study:
- To investigate the clinicopathological significance of centrizonal hepatocyte dropout in liver allograft biopsies.
- To determine the association of centrizonal hepatocyte dropout with specific liver pathologies and patient outcomes.
Main Methods:
- A clinicopathological study analyzed 206 liver allograft biopsies exhibiting centrizonal hepatocyte dropout.
- Correlations were assessed between dropout, specific diagnoses (cellular rejection, biliary obstruction, viral hepatitis), and clinical outcomes, including transplant-free survival and alanine aminotransferase (ALT) normalization time.
Main Results:
- Centrizonal hepatocyte dropout was most frequently associated with cellular rejection, asymptomatic/protocol biopsies, and immediate post-transplantation biopsies.
- In cellular rejection cases, dropout correlated with shorter transplant-free survival.
- In time-zero biopsies, centrizonal hepatocyte dropout prolonged the time to ALT normalization.
Conclusions:
- Centrizonal hepatocyte dropout demonstrates low clinicopathological diagnostic specificity.
- Despite low specificity, centrizonal hepatocyte dropout is linked to adverse clinical outcomes in allograft cellular rejection and time-zero biopsies, highlighting its prognostic value.
Aims:
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.
Methods And Results:
We designed a clinicopathological study of 206 allograft liver biopsies with centrizonal hepatocyte dropout. Centrizonal hepatocyte dropout was associated most frequently with 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 cases. In the context of cellular rejection, dropout was not associated with the time interval to normalisation of serum alanine aminotransferase (ALT), but was associated with shorter transplant-free survival (hazard ratio 4, P = 0.01) than that of histological severity-matched controls. In time zero allograft biopsies, time to ALT normalisation was prolonged (median, 15 versus 11 days, P = 0.002) in allografts with centrizonal dropout, with no effect on retransplant-free survival.
Conclusions:
Centrizonal hepatocyte dropout has low clinicopathological diagnostic specificity. However, it correlates with adverse clinical outcomes in allograft cellular rejection and time zero biopsies.
