Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis: A comparative study

[Guest guest]

http://www.wjgnet.com/1007-9327/16/4832.asp

ISSN 1007-9327 CN 14-1219/R World J Gastroenterol 2010 October 14; 16(38):

4832-4837

BRIEF ARTICLE

Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis: A

comparative study

Ioan Sporea, Roxana Åžirli, andra Deleanu, Tudora, Alina Popescu,

a Curescu, Simona Bota

--------------------------------------------------------------------------------

Ioan Sporea, Roxana Åžirli, andra Deleanu, Tudora, Alina Popescu,

Simona Bota, Department of Gastroenterology and Hepatology, University of

Medicine and Pharmacy, 300736 TimiÅŸoara, Romania

a Curescu, Department of Infectious Diseases, University of Medicine and

Pharmacy, 300736 TimiÅŸoara, Romania

Author contributions: Sporea I wrote the paper, and designed and supervised the

study; Åžirli R, Deleanu A, Tudora A, Curescu M, Popescu A and Bota S performed

the research; Åžirli R and Deleanu A analyzed the data; Åžirli R revised the

manuscript.

Correspondence to: Dr. Ioan Sporea, Professor, Department of Gastroenterology

and Hepatology, University of Medicine and Pharmacy, 300736 TimiÅŸoara, Romania.

isporea@...

Telephone: +40-256-309455 Fax: +40-256-488003

Received: March 26, 2010 Revised: May 26, 2010

Accepted: June 2, 2010

Published online: October 14, 2010

Abstract

AIM: To assess the values of liver stiffness (LS) in patients with hepatitis B

virus (HBV) chronic hepatitis and to compare them with those in patients with

hepatitis C virus (HCV) chronic hepatitis.

METHODS: The study included 140 patients with HBV chronic hepatitis, and 317

patients with HCV chronic hepatitis, in which LS was measured

(FibroScan®-Echosens®) and liver biopsy was performed in the same session

(assessed according to the Metavir score).

RESULTS: According to the Metavir score of the 140 HBV patients: one had F0, 32

had F1, 67 had F2, 33 had F3 and 7 had F4. Of the 317 HCV patients: 5 had F0, 34

had F1, 146 had F2, 93 had F3 and 39 had F4. For the same severity of fibrosis,

the mean values of LS in HBV patients were similar to those in HCV patients: F1,

6.5 ± 1.9 kPa vs 5.8 ± 2.1 kPa (P = 0.0889); F2, 7.1 ± 2 kPa vs 6.9 ± 2.5

kPa (P = 0.3369); F3, 9.1 ± 3.6 kPa vs 9.9 ± 5 kPa (P = 0.7038); F4, 19.8 ±

8.6 kPa vs 17.3 ± 6.1 kPa (P = 0.6574). A significant direct correlation

between LS measurements and fibrosis was found in HCV patients (Spearman’s r =

0.578, P < 0.0001), as well as in HBV patients (r = 0.408, P < 0.0001). The

correlation was more significant in HCV than in HBV patients (Fisher’s Z-test,

Z = 2.210, P = 0.0271).

CONCLUSION: In our group, the mean values of LS in patients with chronic B

hepatitis were similar to those in patients with chronic HCV hepatitis, for the

same stage of fibrosis. Also, LS was correlated with the severity of fibrosis

both in HBV and HCV chronic hepatitis patients.

© 2010 Baishideng. All rights reserved.

Key words: Chronic B hepatitis; Chronic C hepatitis; Fibrosis; Transient

elastography; Liver biopsy

Peer reviewers: Ming-Lung Yu, MD, PhD, Professor, Division of Hepatology,

Department of Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Rd,

Kaohsiung 807, Taiwan, China; Ilker Tasci, MD, Associate Professor, Gulhane

School of Medicine, Department of Internal Medicine, Etlik, Ankara, 06018,

Turkey

Sporea I, Åžirli R, Deleanu A, Tudora A, Popescu A, Curescu M, Bota S. Liver

stiffness measurements in patients with HBV vs HCV chronic hepatitis: A

comparative study. World J Gastroenterol 2010; 16(38): 4832-4837 Available

from: URL: http://www.wjgnet.com/1007-9327/full/v16/i38/4832.htm DOI:

http://dx.doi.org/10.3748/wjg.v16.i38.4832

INTRODUCTION

The non-invasive assessment of fibrosis in chronic hepatitis, especially of

viral etiology, is accepted more and more, partially replacing liver biopsy (LB)

in some countries[1]. Guidelines from France[1] recommend that the first-line

test for untreated patients with hepatitis C virus (HCV) chronic hepatitis, with

no comorbities, should be a non-invasive procedure (either FibroTest® or

FibroScan®).

The non-invasive methods used for the evaluation of chronic hepatitis are: serum

markers (the best known is FibroTest-ActiTest - a biochemical test which uses 6

serum biomarkers, correlated with the age and gender of the patient in a

mathematical formula)[2-5]; transient elastography (TE) (FibroScan®)[6,7];

SonoElastography (Real-Time Tissue Elastography)[8-11] and magnetic resonance

imaging elastography[12,13].

Recent meta-analyses[7,8] have tried to assess the practical value of TE for the

evaluation of patients with chronic hepatitis. Many studies were published

regarding the value of TE for evaluation of patients with HCV chronic hepatitis,

but only a few studies in patients with chronic hepatitis B virus (HBV)

infection. On the other hand, published data showed discordant results regarding

liver stiffness (LS) in patients with HBV and HCV chronic hepatitis[14,15].

The aim of our study was to determine whether the values of LS evaluated by

means of TE (FibroScan®) were similar for the same degree of fibrosis

(evaluated by means of LB), in patients with chronic HBV and HCV hepatitis.

MATERIALS AND METHODS

Patients

Our study included a total of 457 successive patients, 140 with HBV chronic

hepatitis and 317 with HCV chronic hepatitis. All the patients were referred to

our department during a 2-year period (January 2008 to December 2009) for

hepatitis assessment (according to the guidelines valid in Romania in that

period, LB was mandatory for fibrosis staging). LS was evaluated in all patients

by means of FibroScan, and LB was performed in the same session during the

standard of care evaluation of patients with chronic hepatitis. The inclusion

criteria were: (1) HCV chronic hepatitis: patients with positive anti-HCV

antibodies for at least 6 mo, with or without cytolysis; detectable viral load

by polymerase chain reaction (PCR); pathological lesions of chronic hepatitis

demonstrated by LB; no signs of decompensated liver disease (actual or history

of jaundice, ascites); and (2) HBV chronic hepatitis: patients with positive

HBsAg for at least 6 mo, with or without cytolysis; positive or negative HBeAg;

HBV DNA > 2000 IU/mL (> 10 000 copies/mL) by PCR; pathological lesions of

chronic hepatitis demonstrated by LB; no signs of decompensated liver disease

(actual or history of jaundice, ascites).

TE

TE was performed in all 457 patients with the FibroScan® (Echosens®, Paris,

France) by 3 experienced physicians (each having performed more than 1000 TE

examinations). In each patient, 10 valid measurements were performed, after

which a median value of LS was obtained, measured in kilopascals (kPa). Only

patients in which LS measurements had a success rate of at least 60%, with an

interquartile range (IQR) < 30%, were included in our study. The success rate

was calculated as the ratio of the number of successful acquisitions over the

total number of acquisitions. IQR is the difference between the 75th percentile

and the 25th percentile, essentially the range of the middle 50% of the data.

LB

Echo-assisted LB was performed in all 457 patients, using Menghini type modified

needles, 1.4 and 1.6 mm in diameter. Only LB fragments of at least 2 cm,

including at least 8 portal tracts, were considered adequate for the

pathological interpretation. All the LBs were assessed according to the Metavir

score, by a senior pathologist. Fibrosis was staged on a 0-4 scale: F0, no

fibrosis; F1, portal fibrosis without septa; F2, portal fibrosis and few septa

extending into lobules; F3, numerous septa extending to adjacent portal tracts

or terminal hepatic venules and F4, cirrhosis.

Statistical analysis

For a statistical analysis of quantitative variables, the mean and standard

deviation were calculated. Two-way ANOVA test and t-tests were performed, to

compare mean values of LS in various fibrosis subgroups in HBV vs HCV patients.

To compare correlations, Fisher’s Z test was used (hypotheses about the value

of the population correlation coefficient Ï between variables X and Y can be

tested using the Fisher transformation applied to the sample correlation

coefficient r)[16]. The diagnostic performance of LS measurements was assessed

using receiver operating characteristics (ROC) curves. ROC curves were used for

the detection of significant fibrosis (F ≥ 2 Metavir) and severe fibrosis (F

≥ 3 Metavir). Optimal cut-off values for LS measurements were chosen to

maximize the sum of sensitivity and specificity. The statistical analysis was

performed using Microsoft Excel 2007, GraphPad Prism 5 and MedCalc programs.

RESULTS

Patients

The subgroup of HBV patients consisted of 140 subjects (31 women, 109 men; mean

age 39.2 ± 12.8 years). According to the Metavir scoring system, one had F0, 32

had F1, 67 had F2, 33 had F3 and 7 had F4.

The subgroup of HCV patients consisted of 317 subjects (213 women, 104 men; mean

age 49.7 ± 10.2 years). According to the Metavir scoring system, 5 had F0, 34

had F1, 146 had F2, 93 had F3 and 39 had F4.

LS measurements by TE

The mean values of LS in HBV patients were not statistically significantly

different from those of HCV patients for the same degree of fibrosis (Table 1).

A significant direct correlation of LS measurements with fibrosis was found to

exist in HCV patients (Spearman’s correlation coefficient r = 0.578, P <

0.0001), as well as in HBV patients (r = 0.408, P < 0.0001). The correlation was

more significant in HCV than in HBV patients (Fisher’s Z-test, Z = 2.210, P =

0.0271).

The predictive values of LS measurements for the presence of significant

fibrosis (F2), severe fibrosis (F3) and cirrhosis (F4) are presented in Table 2.

DISCUSSION

After a number of articles were published in France regarding the value of

transient elastographic LS measurement in the evaluation of fibrosis in chronic

hepatitis[17-22], numerous papers have been published in other

countries[15,23-29] making this method a recognized test worldwide[30]. A

meta-analysis published in 2008[30] proved that TE had an excellent diagnostic

accuracy for the diagnosis of cirrhosis [mean area under the ROC (AUROC), 0.94

(95% CI: 0.93-0.95)]. However, a high variation of the AUROC was found regarding

the diagnosis of significant fibrosis, dependent on the underlying liver disease

[AUROC for significant fibrosis, 0.84 (95% CI: 0.82-0.86)].

The vast majority of studies assessing TE as compared to LB, were performed in

patients with HCV chronic hepatitis[22,24,28,31,32]. At the same time, many

studies were performed to evaluate this method in other chronic hepatopathies,

such as nonalcoholic steatohepatitis, hemochromatosis and primary biliary

cirrhosis[6,20,23,25].

Published studies regarding the value of LS measurement by means of TE in

patients with HBV chronic hepatitis have shown conflicting results.

A Korean study performed by Seo et al[14] included 64 patients with chronic HBV

hepatitis and 27 patients with chronic HCV hepatitis who underwent LB and TE in

the same session (about two-thirds male; mean age 40 years, range 14-68 years).

In that study, LS measurements were better correlated with the fibrosis score in

patients with chronic HCV hepatitis than in those with chronic HBV hepatitis

(0.773 vs 0.557, P < 0.001). The AUROC was larger in the group of patients with

chronic HCV hepatitis (0.944, 0.982, and 0.958 for F ≥ 2, F ≥ 3, and F4,

respectively) than in those with chronic HBV hepatitis (0.881, 0.863, and 0.850,

respectively). The optimal cut-off values for F ≥ 2 and F ≥ 3 were similar

for patients with chronic HCV hepatitis (7.05 and 11.4 kPa, respectively) and

chronic HBV hepatitis (7.15 and 10.75 kPa, respectively). However, sensitivity

and specificity were superior in patients with chronic HCV hepatitis. The

conclusion of the study was that the efficacy of LS measurement for the

assessment of liver fibrosis was superior in patients with chronic HCV hepatitis

than in patients with chronic HBV hepatitis.

In a study performed by Ogawa et al[15] in 68 patients with chronic HBV

hepatitis and 161 patients with chronic HCV hepatitis, the mean values of LS

measurements were 3.5 kPa for F0, 6.4 kPa for F1, 9.5 kPa for F2, 11.4 kPa for

F3, and 15.4 kPa for F4 in patients with chronic HBV infection, and 6.3 kPa for

F0, 6.7 kPa for F1, 9.1 kPa for F2, 13.7 kPa for F3, and 26.4 kPa for F4 in

those with chronic HCV infection. The values were significantly correlated with

fibrosis stage for both groups of patients (HBV, r = 0.559, P = 0.0093, and HCV,

r = 0.686, P < 0.0001). This study concluded that TE was an efficient and simple

method for the evaluation of liver fibrosis in patients with chronic viral

infection, both in HBV and HCV hepatitis.

Our study, performed on a large cohort of patients (457 subjects) aimed to find

out if there were significant differences in LS in patients with HBV vs HCV

chronic hepatitis for the same degree of fibrosis, as compared to the LB. LS

measurement has a well established value for staging fibrosis in HCV chronic

hepatitis, proved by 2 meta-analyses[7,30]. In patients with HBV chronic

infection, data regarding LS measurement for fibrosis staging are conflicting.

Why? One explanation could be that the necroinflammatory activity in HBV

infection can vary with time, as well as the fact that fluctuations in

aminotransferases can occur. Different studies have proposed various cut-off

values for different stages of fibrosis, as seen in Table 3.

In our cohort of 140 chronic HBV infected patients, the mean values for F1, F2,

F3 and F4 were: 6.5, 7.1, 9.1 and 19.8 kPa, respectively, similar to those

obtained in the study performed by Marcellin. Also, we must bear in mind that

only the Marcellin study was performed in a Caucasian population (such as ours),

the others being performed in Asian populations. In our study, the sensitivity

of TE for cirrhosis prediction was better in HBV than in HCV patients, but this

finding needs further confirmation since the number of F4 patients in the HBV

group was small (only 7) vs 39 in the HCV group.

Regarding the correlation between fibrosis and LS, a significant direct

correlation of TE measurements with fibrosis was found to exist in HCV patients

(Spearman’s correlation coefficient r = 0.578, P < 0.0001), more significant

than in HBV patients (r = 0.408, P < 0.0001) (Z = 2.210, P = 0.0271). Thus it is

likely that the correlation between LS and fibrosis in HBV patients can be of

use in clinical practice.

As mentioned earlier, high levels of aminotransferases can influence the LS

values obtained by means of TE, so that LS measurements have to be interpreted

in a biochemical context, otherwise there is a risk of overestimating the

severity of fibrosis. Also this is why LS measurements are not performed in

acute hepatitis or during alanine aminotransferase (ALT) flares in HBV chronic

hepatitis[29,36]. In order to minimize the risk of overestimating fibrosis

during ALT flares, Chan et al[34] calculated LS cut-off values for various

stages of fibrosis considering also the aminotransferase levels. In this study,

the LS cut-off value for F3 was 9 kPa in patients with normal ALT and 12 kPa in

patients with ALT higher than 5 times the upper limit of normal. The cut-offs

for cirrhosis were 12 kPa in patients with normal ALT and 13.4 kPa in those with

high ALT.

In conclusion, in our study, LS measured by TE was correlated with the degree of

fibrosis both in HBV and HCV patients, the correlation being more significant in

HCV patients. Our data showed that there were no statistically significant

differences between the mean values of LS in HBV and in HCV patients for the

same degree of fibrosis.

COMMENTS

Background

Non-invasive methods for fibrosis assessment in chronic hepatitis, such as

transient elastography (TE), are being accepted more and more, replacing the

invasive methods, especially in hepatitis C virus (HCV) chronic hepatitis.

Research frontiers

Many studies have been published regarding the value of TE evaluation of

patients with HCV chronic hepatitis, but only a few studies in chronic hepatitis

B virus (HBV) infection, showing discordant results.

Innovations and breakthroughs

This research article determined if the authors can also use liver stiffness

(LS) measurement by TE for the evaluation of patients with HBV chronic

hepatitis, and concluded that LS is correlated with fibrosis in both HBV and HCV

patients, and that there are no statistically significant differences between

the mean LS values in HBV vs HCV patients, for the same degree of fibrosis.

These findings are concordant with previous studies by Wang et al, Marcellin et

al, and Ogawa et al, indicating that the diagnostic accuracy of LS is comparable

in HBV and HCV infection related fibrosis.

Applications

This study showed that LS evaluated by means of TE was correlated with degree of

fibrosis in both HBV and HCV patients and that there were no statistically

significant differences between the mean values of LS in HBV vs HCV patients for

the same degree of fibrosis, so the authors can also use this method for the

evaluation of patients with HBV chronic hepatitis in daily practice.

Terminology

TE (FibroScan) is an ultrasound-based method that uses the transmission of low

frequency vibrations to create an elastic shear wave that propagates into the

liver, followed by the detection of wave propagation velocity, which is

proportional to the tissue stiffness, with faster wave progression occurring

through stiffer tissue.

Peer review

The authors present the data from their research on whether the accuracy of LS

measurement in estimating liver fibrosis differs in people with chronic HCV or

HBV infection. Although many reports on small or large populations exist on the

same issue, the readers of the journal may find reading the data interesting.

REFERENCES<CUT>