Aims-To use laboratory data and liver biopsies, prospectively obtained from
hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-H
Be) positive patients, for the assessment of: (1) the relation between biop
sy length/number of portal tracts and sampling error; (2) the relation betw
een the severity of piecemeal necrosis and the new grading terminology (min
imal, mild, moderate, and severe chronic hepatitis); and (3) liver patholog
y, which has not been studied in patients with this specific serological pr
ofile.
Methods-The study group (n = 174) included 104 patients with normal aminotr
ansferase concentrations and no cases with clinically apparent cirrhosis. T
he specimen length and number of portal tracts were measured art light micr
oscopy examination. Sampling error analysis was related to the discrepancie
s between aminotransferase concentrations versus histological grade. Detail
ed histological scorings were undertaken by the reference pathologist and c
ompared with laboratory and hepatitis B virus (HBV) DNA precore sequence da
ta.
Results-Sampling error seemed to be a constant feature, even for biopsies g
reater than or equal to 20 mm, but increased dramatically in biopsies < 5 m
m long and/or containing less than four portal tracts. Between 25% and 30%
of biopsies, graded as "mild" or "moderate" activity showed features of mod
erate and severe piecemeal necrosis, respectively. Ten per cent of the pati
ents with normal aminotransferase values had stage III-IV hepatic fibrosis,
and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antige
n expression was a strong predictor of high hepatitis B viraemia. There was
no association between precore stop codon mutations, grade/stage of liver
disease, and hepatitis B core antigen (HBcAg) expression.
Conclusions-The specimen available for light microscopical examination shou
ld be > 5 mm long and should contain more than four portal tracts. In addit
ion, the new grading terminology might give the clinician an inappropriatel
y mild impression of the severity of piecemeal necrosis. Furthermore, even
in the presence of normal aminotransferase concentrations, considerable liv
er pathology can be found in 10-20% of HBsAg and anti-HBe positive individu
als; such pathology is not associated with the occurrence of precore stop c
odon mutations.