Concurrent increase in mitosis and apoptosis: a histological pattern of hepatic arterial flow abnormalities in post-transplant liver biopsies.

Liver biopsies are critical in managing patients after liver transplantation. One key histological pattern in transplant liver pathology is spotty hepatocyte necrosis without significant lobular inflammation, which is typical of recurrent hepatitis C. Over the past years, we have observed several liver biopsies with a pattern of injury that mimicked the histological findings of early recurrent hepatitis C. This pattern consisted of increased lobular hepatocyte spotty necrosis without significant inflammation, but with the additional finding of numerous concurrent mitotic figures. To better understand this unique pattern of injury, we studied a group of 8 liver biopsies with this pattern and a control group of 22 biopsies with typical recurrent hepatitis C. Hepatocyte apoptosis and mitosis were quantified by counting 10 high-power fields (HPFs). The mean interval between transplantation and biopsy was 62 days in both groups. There was no significant difference between the study and the control groups in portal and lobular inflammation. In contrast, there was more hepatic apoptosis (acidophil bodies) in the study cases than the controls (average of 10.3 vs 2.8 apoptotic bodies/10HPF; P=0.0004). Likewise, there were more mitoses in the study cases than the controls (average 6.3 vs 0.1 /10HPF; P<0.0001). Interestingly, examination of the medical records for the cases with increased apoptosis and mitoses found a very strong association with hepatic arterial problems including thrombosis (N=3), stenosis (1), flow abnormalities consistent with stenosis (3), and arteritis associated with acute rejection (1). In summary, our findings indicate that the histological pattern of concurrent increases in both hepatocyte mitosis and apoptosis in a post-transplant liver biopsy without significant lobular inflammation is strongly associated with hepatic arterial insufficiency and should prompt evaluation of the hepatic artery.