Cytokeratin inclusions in alcoholic liver disease and their relation to the amount of alcohol intake


Department of Forensic Medicine, University of Helsinki, PO. Box 40 (Kytösuontie 11), SF-00014 Helsinki, Finland


ABSTRACT: In the present study, the frequency and the distribution pattern of immunoreactive hepatocytic cytokeratin (CK) inclusions was investigated using the monoclonal antibody (MAb) CAM 5.2 detecting CKs 8, 18 and 19. The CK antigenicity of the inclusions was confirmed on frozen sections with MAbs for the CKs 7, 8, 17, 18 and 19. The frequency of hepatocytic CK aggregates was compared to the presence of non-alcoholic and alcoholic liver disease (ALD) as well as to the average all-year daily ethanol intake of 195 consecutive males subjected to medicolegal autopsy. Hepatocytic CK inclusions were infrequent in patients with normal liver histology, portal fibrosis and/or portal inflammation. In ALD, however, inclusions were observed in 35.6% of patients with fatty liver, in 63.2% of patients with alcoholic hepatitis, in 30.8% of patients with bridging fibrosis and in 60.0% of patients with liver cirrhosis. In all specimens studied, the inclusions were reactive only for CKs 8 and 18, CKs 7, 17, and 19 being unreactive. The frequency of inclusion bodies increased, paralleling increasing average all-year daily alcohol consumption. Compared to non-drinkers, a daily intake of between 40 and 80 g of absolute alcohol was associated with a statistically significantly (relative risk, RR=6.6) increased risk of formation of aggregates. Similarly, daily consumption exceeding 80 g was related to increased (RR=6.0) frequency of CK aggregates. The frequency of full-blown “classical” Mallory bodies (MBs) was, however, increased (RR=8.9) only in patients with a daily intake exceeding 160 g. These results indicate that CK inclusions are unequivocally related to the presence of ALD in longitudinal autopsy series. Their frequency in autopsy series was, however, significantly lower than their frequency in previous studies comprising hospitalised patients diagnosed as having alcoholic liver disease. Furthermore, our results suggest that a daily ethanol intake between 40 and 80 g can increase the risk of appearance of smaller CK inclusions, although the risk of occurrence of “classical” full-blown MBs was associated only with heavy drinking exceeding 160 g of absolute alcohol daily.