1) 2) 2)

3) 4) 4)

1)

2)

3)

4)

With regard to the long-term prognosis of hepatitis C, there have been reports of the relationship between the risk of
hepatocellular carcinoma and the stage of hepatic fibrosis. Histological diagnosis by liver biopsy is important for assessing
the stage of liver fibrosis, but assessment is sometimes difficult due to the invasive nature of the procedure. Recently devel-
oped Elastography uses the combined autocorrelation method to rapidly calculate the relative hardness of tissue from the
degree of tissue distortion, and display this information as real-time, color images. We examined the usefulness of Elasto-
graphy for the evaluation of hepatic fibrosis in patients with chronic hepatitis C.
The results indicated that non-invasive assessment was possible with Elastography, with the obtained liver elasticity
score becoming significantly higher as the staging increased, satisfactorily reflecting the degree of fibrosis. The view is that
Elastography would be useful for determining high-risk cancer groups.

Key Words: Elastography, Liver Elasticity Score, Chronic Hepatitis, Tissue Characterization

More than one million people worldwide die annually of acknowledged 3)-5). However, due to its invasive nature,
hepatocellular carcinoma, the third highest cause of death liver biopsy is limited when constant monitoring of the
due to malignant neoplasm. Hepatocellular carcinoma time course of changes in hepatic fibrosis is required, and
often develops from viral hepatitis. It has been reported non-invasive tests should be performed as well. Measure-
that the risk of hepatocellular carcinoma is related to the ment of platelet count6) and the determination of hepatic
stage of hepatic fibrosis, making it a particularly important fibrosis markers are useful as non-invasive tests for evalu-
factor in the long-term prognosis of chronic hepatitis C. ation of the liver fibrosis stage but the basic procedure for
The incidence of hepatocellular carcinoma increases along assessment of staging is the combined use of these tests
with progression of the stage 1). It is therefore vital to with imaging diagnostic methods such as ultrasonography.
devise a treatment plan for preventing lesion progression, Abdominal ultrasonography is the most useful imaging
such as interferon therapy, after diagnosis of hepatic fibro- diagnostic technique for the assessment of chronic hepati-
sis. It has been shown that interferon therapy improves tis. The indexes for assessment of staging include the pres-
hepatic fibrosis and dramatically reduces the incidence of ence or absence of change on the liver surface, deteriora-
hepatocellular carcinoma , so it is considered important to
2)
tion of liver periphery, a decrease in the volume of the
evaluate the stage of hepatic fibrosis over time even after right hepatic lobe and increase in the volume of the left
completion of treatment. lobe, a coarse internal echo, and narrowing of the hepatic
The importance of histological diagnosis by liver biopsy vein. However, for the assessment of staging in borderline
for the assessment of the stage of hepatic fibrosis is widely cases, ordinary ultrasonography is limited because images

24 MEDIX Suppl. 2007

can change very slightly due to differences in the resolving ject briefly held his or her breath. This equipment displays
power and/or image settings of the equipment used. Inter- real-time tissue elasticity images showing the ROI as a
pretation of the images is also greatly dependent on the semitransparent, colored area, juxtaposed with B-mode
experience and subjectivity of the person making the images. The colors in the ROI range from blue to red to
assessment. The general idea of ultrasonic tissue diagnosis show the relative hardness and softness of areas inside the
is to offset these problems through the quantitative evalu- ROI (Fig. 1). The same area in the liver was set as the ROI
ation of tissues obtained from ultrasonographic images. in all subjects, with the liver surface as the top. The Elasto-
For histological diagnosis of the liver, measurement of the graphy findings were rated as the liver elasticity scores
raw signal intensity, the extent of scattering 7)8)
and the (Fig. 2).
speed of transmission of an audible vibration generated by Six blind reviewers experienced in ultrasonography
a probe in the liver have been reported as techniques for assessed the scores, the mean score was obtained for each
the assessment of tissue elasticity 9). subject, and the stagings of each of the liver biopsy sam-
ples were compared. Statistical analysis was performed to
determine the correlation between the mean liver elastici-
ty score and ALT, total bilirubin, albumin, choline
Recently developed Elastography uses the combined esterase, total cholesterol, prothrombin time, platelet
autocorrelation method to rapidly calculate the relative count and Type IV Collagen 7S.
hardness of tissue from the degree of tissue distortion, and
display this information as real-time, color images 10)11). Clin-
ical application of Elastography has so far been reported
for the breast, thyroid, prostate and pancreas. We investi-
gated the usefulness of Elastography for the evaluation of
hepatic fibrosis in patients with diffuse liver disease.

The subjects in this study were a total of 43 patients

with chronic hepatitis C or cirrhosis diagnosed by tissue
biopsy. The indicated stages of fibrosis were F1 in 7 sub-
Fig. 1 : ROI Setting for Elastography
jects, F2 in 12 subjects, F3 in 15 subjects, and F4 in 9 sub-
jects (Table 1). HITACHI EUB-8500 and HI VISION 900
were used for ultrasonography and the probes used were
score 1
an EUP-L54M Linear probe (13-6MHz) and an EUP-L53
Linear probe (10-5MHz) respectively. After examination in
B-mode, the mode was switched to Elastography, and the
score 2
probe scanned vertically from the epigastrium to observe a
sagittal section of the left hepatic lobe or the right hepatic
lobe from the right intercostal space. An identical area was
set as the ROI for all subjects, with the liver surface as the score 3
top. Because heartbeat distorts the liver, observation was
made using a freehand technique, keeping the probe in
position by applying slight manual pressure while the sub-
score 4

Table 1 : Subject Characteristics

Patients with Fibrosis Stage (F) (n=43) Fig. 2 : Liver Elasticity Score
F1 F2 F3 F4
(n=7) (n=12) (n=15) (n=9)
p value Score 1 : The entire colored area of the ROI is distorted
age (yr) 65.0 6.2 57.7 5.9 61.0 8.4 70.0 11.8 p 0.05
(the entire colored area is shown as relatively
gender (n: M/F) 2/5 7/5 10/5 7/2 n.s. uniform light green).
ALT (IU/l) 23.25 6.19 45.67 26.10 65.00 38.79 53.50 40.74 p 0.05
Total Bilirubin (mg/dl) 0.45 0.10 1.15 0.46 0.77 0.22 1.17 0.15 p 0.05, vs F4 Score 2 : Partially mottled blue regions are shown in the
Albumin (g/dl) 4.30 0.14 4.20 0.42 4.10 0.33 3.52 0.66 p 0.05, vs F4
Choline Esterase (IU/l) 293.0 56.5 334.3 50.2 225.5 55.6 149.8 80.8 p 0.05, vs F4 light green colored area.
Total Cholesterol (mg/dl) 187.8 35.3 151.8 33.9 162.8 28.7 131.8 36.8 p 0.05
Prothrombin Time (%) 95.98 9.73 80.73 39.15 91.25 7.75 74.70 8.82 n.s.
Score 3 : Light green and blue are mixed in the colored
Platelet count ( 104/ l) 18.56 5.38 15.97 3.50 16.43 5.62 10.10 4.67 p 0.05, vs F4 area (almost a fifty-fifty mix).
TypeIV Collagen 7S (ng/ml) 4.51 0.20 4.71 0.66 6.33 1.75 10.11 1.09 p 0.05
Score 4 : Most of the colored area is shown as blue.

MEDIX Suppl. 2007 25

 that showed as blue. Statistical analysis for comparison of
stages revealed that the mean liver elasticity score became
significantly higher with progression of stage (Fig. 7).
Of the hematological data derived from the patient
characteristics reviewed in this study, a significant differ-
ence was observed only in Type IV Collagen 7S at all
stages. A significant difference between F4 and other The correlation between the mean liver elasticity score
stages was observed for total bilirubin, albumin, and and ALT, total bilirubin, albumin, choline esterase, total
choline esterase (Table 1). cholesterol, prothrombin time, platelet count and Type IV
Collagen 7S was examined. Only Type IV Collagen 7S
showed a significant correlation with the mean liver elas-
ticity score (Fig. 8).
It was easy to utilize distortion due to heartbeat for
Elastography observation of the liver. a b
Slight distortion of the liver by heartbeat itself was
observed when a subject held his or her breath for a few
seconds, and the aforementioned signals were shown with-
in the Elastography ROI in all subjects.
Fig. 3 to 6 show histopathological images of liver biopsy 4
tissue and Elastography images of each stage. The results
of observation showed that as the stage progressed, there Fig. 5 : Case 3 : 66-year-old male
tended to be more signals inside the Elastography ROI a : Histopathological image of liver biopsy sample, stage F3.
b : The Elastography ROI shows green and blue signal to
almost the same degree.
The liver elasticity score was judged to be 3.
a
c

a b

b
4

Fig. 6 : Case 4 : 65-year-old male

10 a : Histopathological image of liver biopsy sample, stage F4.
b : The Elastography ROI shows mostly blue signals, with
Fig. 3 : Case 1 : 52-year-old male fewer green than blue signals.
a, b : Histopathological images of liver biopsy samples, The liver elasticity score was judged to be 4.
stage F1. (There is signal dropout where distortion in a deep area
c : The Elastography ROI is almost entirely uniform green prevents calculation (arrow)).
with some red areas.
The liver elasticity score was judged to be 1.
p 0.001
(points)
a b p 0.05
4 (Fisher’s PLSD)
Elastography Score

3.5

2.5 Median
2
4
1.5
Fig. 4 : Case 2 : 54-year-old female 1
a : Histopathological image of liver biopsy sample, stage F2. 1 2 3 4
staging (F)
b : The Elastography ROI is uniform green with some mot-
tled blue areas. Fig. 7 : Comparison of Histopathological Stage and Elasto-
The liver elasticity score was judged to be 2. graphy Score

26 MEDIX Suppl. 2007

 graphy could be used for screening chronic hepatic disease
(points)
during medical examinations or for visually explaining the
4
risk of cancer when obtaining informed consent from a
patient considered suitable for interferon therapy. It is also
Elastography Score

3
anticipated that it will be used to determine the stage of
patients who refuse biopsy, for the evaluation of stages
2
r = 0.720 during and after IFN treatment (for the evaluation of
p 0.0001 improvement of fibrosis), for understanding the stages in
1
patients not treated with IFN, and for evaluating patients
3 4 5 6 7 8 9 10 11 12 (ng/ml) with diseases other than viral hepatitis (NASH etc.).
IV Collagen 7S In conclusion, Elastography liver elasticity scores
became significantly higher with progression of staging,
Fig. 8 : Correlation between Type IV Collagen 7S and
Elastography Score accurately reflecting fibrosis. The view is that it would be
particularly useful for determining high-risk cancer groups.

Evaluation of histopathological tissue obtained by liver

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