We have discovered that non-A, non-B, non-C, non-D, non-E (so-called t
ype F) acute and chronic hepatitis is caused by a hepatitis B virus (H
BV) variant with mutations in the X open reading frame. This silent HB
V mutant does not induce immunoserological markers. In the present inv
estigation we attempted to elucidate the putative mechanism of hepatoc
ellular necrosis and expression patterns of hepatitis B surface antige
n (HBsAg) and core antigen (HBcAg) in biopsied liver tissue. The subje
cts consisted of 14 patients with acute hepatitis, 11 with chronic hep
atitis and eight with liver cirrhosis, all of whom had been previously
diagnosed as having so-called hepatitis F. Nine of the 14, 10 of the
11 and all eight, respectively, of the above patients exhibited signif
icant positive immunostaining for HBsAg within their hepatocellular cy
toplasm, diffusely or focally. HBcAg stained in a few hepatocellular n
uclei in 24.2% of the patients. Histological features were characteriz
ed by necroinflammation, indicating immune-mediated hepatocellular nec
rosis. Despite the serological-marker negativity, the results of immun
ostaining for HBsAg and HBcAg support replication and expression of HB
V DNA, though weak.