The frequency and histological pattern of multiple hepatitis virus inf
ection was studied in 161 Italian patients who had consecutively under
gone liver biopsy from 1989 to 1991. The histological features were co
mpared with that of infection with a single virus. Thirty-nine per cen
t of patients had evidence of past or present multiple infection, the
commonest of which was hepatitis C virus (HCV) in patients with eviden
ce of previous infection with hepatitis B virus (HBV). In general, the
severity of the histological pattern of each viral infection was main
tained even when more than one virus was involved; there was neither e
xacerbation nor diminution of the histological changes. The delta-viru
s (HDV) was not associated with severe necro-inflammatory lesions, but
HDV-positive patients were few in this cohort. Lymphoid follicle form
ation (a putative histological marker of HCV infection) was also found
in a high proportion of HCV-negative patients but expressing much HBc
Ag or HDAg in liver tissue. Possible explanations for this finding are
that follicles are relatively non-specific for HCV infection, or that
these cases represent HCV infection with false-negative serology. The
results of this study suggest that multiple hepatitis virus infection
is common in the population investigated and that HBV and HCV co-infe
ction cannot be reliably diagnosed histologically. Whether double infe
ction with these viruses influences the cirrhotic evolution of the liv
er lesion remains unclear.