barcelona . spain - European Association for the Study of the Liver

BARCELONA . SPAIN
64 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 65
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
No sampling variability was found for fatty liver, alcoholic hepatitis, nonspecific hepatitis, fulminant hepatitis,
leukemic infiltrate, and venous congestion. Cirrhosis was diagnosed in 80% of cases at the first biopsy
but in all cases after three biopsies. Chronic aggressive and chronic persistent hepatitis were diagnosed
correctly in two of three cases each at the first biopsy, and in all cases after three biopsies. Metastatic
carcinoma was detected in 46% of cases at the first biopsy and in 69% after three biopsies. Granulomas
were missed once on the first biopsy, but found on a subsequent biopsy. The amounts of fat and fibrosis in
the biopsy specimens often were not representative of the amounts present at autopsy.
3 Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology
2003;38:1449-57.
Surgical samples of livers from patients with chronic hepatitis C were studied. Measurement of fibrosis was
performed on the whole section by using both image analysis and METAVIR score (reference value). From
the digitized image of the whole section, virtual biopsy specimens of increasing length were produced.
Fibrosis was assessed independently on each individual virtual biopsy specimen. Results were compared
with the reference value according to the length of the biopsy specimen. By using image analysis, the
coefficient of variation of fibrosis measurement with 15-mm long biopsy specimens was 55%; and for
biopsy specimens of 25-mm length it was 45%. By using the METAVIR scoring system, 65% of biopsies
15 mm in length were categorized correctly according to the reference value. This increased to 75% for
a 25-mm liver biopsy specimen without any substantial benefit for longer biopsy specimens. Sampling
variability of fibrosis is a significant limitation in the assessment of fibrosis with liver biopsy. In conclusion,
this study suggests that a length of at least 25 mm is necessary to evaluate fibrosis accurately with a
semiquantitative score. Sampling variability becomes a major limitation when using more accurate methods
such as automated image analysis
The slides were blindly coded and randomly divided among two hepatopathologists. Inflammation and
fibrosis were scored according to the standard grading (inflammation) and staging (fibrosis) method based
on the modified Scheuer system. Following the interpretation, the slides were uncoded to compare the
results of the right and left lobes. Fifty of the samples were blindly resubmitted to each of the pathologists to
determine the intraobserver variation. RESULTS: Thirty of 124 patients (24.2%) had a difference of at least
one grade, and 41 of 124 patients (33.1%) had a difference of at least one stage between the right and left
lobes. In 18 patients (14.5%), interpretation of cirrhosis was given in one lobe, whereas stage 3 fibrosis was
given in the other. A difference of two stages or two grades was found in only three (2.4%) and two (1.6%)
patients, respectively. Of the 50 samples that were examined twice, the grading by each pathologist on the
second examination differed from the first examination in 0% and 4%, and the staging differed in 6% and
10%, respectively. All observed variations were of one grade or one stage. CONCLUSIONS: Liver biopsy
samples taken from the right and left hepatic lobes differed in histological grading and staging in a large
proportion of chronic hepatitis C virus patients; however, differences of more than one stage or grade were
uncommon. A sampling error may have led to underdiagnosis of cirrhosis in 14.5% of the patients. These
differences could not be attributed to intraobserver variation, which appeared to be low.
In addition, the accuracy of liver biopsy in assessing fibrosis is limited due to sampling error and interobserver
variability [2, 3, 4, 5, 6].
Figure 2
4Cadranel JF, Rufat P, Degos F. Practices of liver biopsy in France: results of a prospective nationwide
survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF).
Hepatology 2000;32:477-81.
5Maharaj B, Maharaj RJ, Leary WP, et al. Sampling variability and its influence on the diagnostic yield of
percutaneous needle biopsy of the liver. Lancet 1986;1:523-5.
In an investigation to determine the influence of sampling variability on the diagnostic yield of liver biopsy,
3 consecutive samples were obtained from each of 75 patients by redirecting the biopsy needle through
a single entry site. In 14.7% of patients all 3 specimens were normal, and in 36% there were similar
abnormalities in all 3 specimens. In the other patients, sampling variability between specimens was present.
In those patients with cirrhosis, hepatocellular carcinoma, metastatic carcinoma, or hepatic granulomas the
histological abnormality was present in all 3 biopsy specimens in only 50%, 54.5%, 50%, and 18.8% of
patients, respectively. No complications were recorded. These findings show that important pathology can
be overlooked if only a single biopsy specimen is taken, and that the method of obtaining 3 consecutive
specimens improves the diagnostic yield of liver biopsy without an associated increase in complications.
Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients
with chronic HCV infection. Am J Gastroenterol 2002;97:2614-8.
The aim of this study was to determine the rate and extent of sampling error in patients with chronic hepatitis
C virus infection, and to assess the intraobserver variation with the commonly used scoring system proposed
by Scheuer and modified by Batts and Ludwig. METHODS: A total of 124 patients with chronic hepatitis
C virus infection underwent simultaneous laparoscopy-guided biopsies of the right and left hepatic lobes.
Formalin-fixed paraffin-embedded sections were stained with hematoxylin and eosin and with trichrome.