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Ubiquitin: an immunohistochemical marker of Mallory bodies and alcoholic liver disease.

One hundred forty eight liver needle biopsies, comprising 88 consecutive biopsies from patients with clinically diagnosed or suspected alcoholic liver disease and 60 selected biopsies from non-alcoholics, were immunostained for the cell stress protein ubiquitin (Ub). Ub + cells were detected in all of 33 biopsies with alcoholic hepatitis (AH). Practically all Mallory bodies (MBs) showed intense Ub-staining. In addition, many cells revealed Ub + granules lying aggregated (pre-MBs) or dispersed in the cytoplasm of ballooned cells. The mean number of Ub + cells in 10 biopsies with AH was more than 30 times the number of MBs and more than 6 times the number of MBs + pre-MBs found in adjacent Haematoxylin-Eosin (HE) stained sections. Among 55 biopsies from alcoholic patients without AH (i.e. without MBs or pre-MBs in HE stained sections), Ub + cells occurred in eight (14.5%). Among the 60 selected biopsies from non-alcoholic patients with liver diseases in which hepatocyte ballooning and occasionally MBs are seen, a few Ub + cells were revealed in two out of ten with primary biliary cirrhosis (one of which also showed MBs) but none in biopsies with primary sclerosing cholangitis, long-standing large duct obstruction, or various hepatitides. Thus Ub-immunostaining appears to be a highly sensitive and specific method in the detection of MBs and MB precursor stages, making it a valuable tool in the study of alcoholic liver disease, and particularly a more objective method (compared to conventional staining methods) of diagnosing alcoholic hepatitis.