Concurrent Increase in Hepatic Mitosis and Apoptosis: A Marker for Hepatic Artery Thrombosis in Transplant Liver Biopsies
Ta-Chiang Liu, Thong Nguyen, Michael S Torbenson. Johns Hopkins Univ., Baltimore; Alegent Health, Omaha
Background: Liver biopsies are critical in managing patients after liver transplantation. One of the key histological patterns in transplant pathology is spotty hepatocyte necrosis without significant lobular inflammation, which is typical of recurrent hepatitis C (HCV). Over the past years, we have noticed a unique pattern of injury that mimicks recurrent HCV, but is not HCV: increased spotty hepatocyte necrosis without significant inflammation, but with increased concurrent hepatocyte mitosis. This pattern was found in individuals transplanted for HCV as well as non-HCV disease. To better understand this unique pattern of injury, we examined the clinicopathological findings, using a control group with typical recurrent HCV.
Design: Cases with this unique pattern of injury and controls of recurrent HCV were identified by computer search of the pathology files. Cases were scored for portal and lobular inflammation (Ishak score). Hepatocyte apoptosis and mitosis were quantified by counting 10 high power fields (HPF).
Results: We identified 8 biopsies with the injury pattern of lobular spotty necrosis and increased mitotic figures, but without significant lobular inflammation. The underlying native liver diseases were HCV (n=5), autoimmune (n=2), and polycystic (n=1). There was an average of 62 days between transplantation and biopsy (range, 8 - 150). Interestingly, examination of the medical records for these cases found a very strong association with acute hepatic arterial problems: 6/8 cases had acute hepatic artery thrombosis, 1/8 had acute cellular rejection with arteritis, and 1/8 had artery flow abnormalities on ultrasound suggestive of stenosis. In contrast, none in the control group of recurrent HCV had hepatic artery problems (p < 0.0001). The HCV control group did not differ from the study group in gender distribution, average age at biopsy, or average time interval between transplantation and biopsy. There was also no significant difference between the two groups in portal or lobular inflammation. In contrast, there was more hepatic apoptosis in the study cases than the controls (average of 10.25 vs. 2.77 apoptotic bodies/10HPF; p = 0.0004). Likewise, there were more mitoses in the study cases than the controls (average 6.25 vs. 0.14/10HPF; p < 0.0001).
Conclusions: The pattern of increased hepatocyte apoptosis and mitosis and in transplant liver biopsies without significant inflammation is strongly associated with hepatic arterial problems. This previously undescribed histological pattern should prompt evaluation of the hepatic artery.
Monday, March 19, 2012 2:15 PM
Platform Session: Section E, Monday Afternoon