USEFULNESS OF FIBRO-Q INDEX FOR PREDICTING FIBROSIS IN ...

AAMJ, VOL10, NO4, OCT 2013 – SUPLL 1

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USEFULNESS OF FIBRO-Q INDEX FOR PREDICTING

FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C,

COMPARED WITH LIVER BIOPSY

Ehab Mahfouz¹, Ehsan H. Hassen², Faten Mahmoud1 And

Kamal El-Atrebi3.

Departments of Clinical and chemical pathology ¹; Pathology ²; Internal

Medicine and Hepatology3, National Hematology and Tropical Medicine

Research Institute (NHTMRI), Cairo, Egypt.

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ABSTRACT

Background: Egypt has the highest HCV prevalence in the world. Today,

HCV infection and its complications are among the leading public health

challenges in Egypt. The natural course of chronic hepatitis C is characterized

by progressive fibrosis in the inflamed liver leading to cirrhosis. Liver biopsy is

the gold standard for assessment of liver fibrosis before all antiviral treatment.

However, this procedure has its own limitations, risks, and costs. Hence,

noninvasive indices have been proposed to assess the severity of hepatic

fibrosis. Aim of the work : The aim of the current study was to assess the

predictive value of noninvasive indices of Fibro-Q, Alanine Aminotransferase

Ratio (AAR)& Aspartate aminotransferase to platelet ratio Index (APRI) in

patients with chronic hepatitis C, compared with liver biopsy and to determine

their cutoff values to differentiate significant fibrosis and cirrhosis in a

community hospital in an area with hyperendemic HCV infection. Patients and

Methods: A case study included 100 patients with chronic hepatitis C who had

undergone percutaneous liver biopsy before treatment. Our patients were

attending the outpatient clinic of NHTMRI in the period of April 2012 to

Ehab Mahfouz et al

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September 2013. Their ages ranged from 20 to 59 years old of both sexes.

Biochemical markers assessed were: AST, ALT, platelet count, prothrombin

time (PT), international normalized ratio (INR). Liver fibrosis was evaluated

according to the Metavir scoring system. Fibro-Q index, APRI, and AAR were

calculated. Receiver operating characteristic (ROC) curves were constructed to

compare the accuracies of these three noninvasive indices in predicting

significant fibrosis and cirrhosis in patients with chronic hepatitis C. Results:

Fibro-Q , APRI, and AAR results increased significantly as fibrosis advanced (p

< 0.05). Fibro-Q performed better than AAR, but was equal to APR, in the

prediction of significant fibrosis [ area under the ROC (AUC): 0.87 vs 0.71 (p=

0.003) and 0.87 vs 0.88 (p= 0.7), respectively]. As regard cirrhosis, Fibro-Q

performed better than AAR, but was inferior to APRI [ AUC: 0.88 vs 0.7

(p=0.2) and 0.88 vs 0.98 ( p=0.1), respectively]. Using a cutoff value of the

Fibro-Q index > 2.41, the presence of significant fibrosis could be correctly be

identified with high accuracy (100% PPV) in all of the 100 patients.

Conclusion: Fibro-Q is a simple and useful index for predicting significant

fibrosis in patients with chronic hepatitis C.

Keywords: Liver fibrosis; Noninvasive test; Fibro-Q; Aspartate

aminotransferase/ Alanine aminotransferase ratio (AAR); Aspartate

aminotransferase to platelet ratio Index (APRI)

INTRODUCTION

Hepatitis C virus (HCV) infection is a serious human liver health problem

and has infected 200 million people worldwide. ⁽25⁾ Persistent HCV infection

can lead to chronic hepatitis C, which is a significant risk of serious hepatic

diseases such as hepatic steatosis, hepatic fibrosis and hepatocellular carcinoma.

⁽²4⁾ Egypt has the highest prevalence of (HCV) in the world, estimated nationally



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at 14.7%. Today, HCV infection and its complications are among the leading

public health challenges in Egypt. ⁽9⁾

The natural course of chronic hepatitis C is characterized by progressive

fibrosis in the inflamed liver with structural and hemodynamic changes leading

to cirrhosis, which is followed by end stage complications.⁽1⁾ Accordingly, the

assessment of liver fibrosis in chronic hepatitis C has become of paramount

importance; to guide management decisions, predict outcome (prognosis), and

monitor disease activity in individual patients.⁽2⁾

Because antiviral treatment is costly and may be associated with significant

side effects, the pathological staging of hepatic fibrosis through liver biopsy, is

fundamental for clinical management of chronic hepatitis C.(20) Patients showing

Metavir fibrosis score ≥ 2 are at significant risk of developing cirrhosis within

5-10 years and have priority for antiviral therapy in all International and

National guidelines .⁽23⁾ On the other hand, many experts believe that

therapy is not mandatory in patients with no or minimal fibrosis (F0-F1),

particularly when the chance of achieving a favorable response is not high, like

in patients with contraindications or with poor motivation towards therapy,

patients with high viral load or difficult-to-treat HCV genotypes.⁽³⁾ Thus, liver

biopsy is often necessary to assess prognosis and to decide management.

Liver biopsy is the gold standard for fibrosis staging in chronic hepatitis C.

⁽5⁾ However, liver biopsy has several limitations that prevent its routine use as a

clinical tool. For example, the invasive nature of the liver biopsy with its

morbidity and mortality. Moreover, sampling errors and inter-observer

variations may lead to understaging of fibrosis .⁽4⁾

Therefore, several noninvasive tests have been proposed to attempt to

predict the degree of liver fibrosis, with the objective of replacing liver

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biopsy.⁽¹4⁾ Some of the noninvasive models are expensive, need complicated

calculations, or involved tests that are generally not a part of the routine

monitoring and investigations of patients with chronic liver disease. For these

reasons, such tests are only available in some research centers and cannot be

widely used in clinical practice.⁽8⁾

AIM OF WORK

The aim of the current study was to assess the predictive value of

noninvasive indices of Fibro-Q, AAR & APRI in patients with chronic hepatitis

C, compared with liver biopsy and to determine their cutoff values to

differentiate significant fibrosis and cirrhosis in a community hospital in an area

with hyperendemic HCV infection.

PATIENTS AND METHODS

A case study was conducted on100 interferon –naïve patients with chronic

hepatitis C attending the outpatients clinic of NHTMRI in the period of April

2012 to September 2013. Their ages ranged from 20 to 59 years old of both

sexes. The diagnosis of HCV infection was confirmed by the presence of anti-

HCV antibodies and HCV RNA by PCR. All patients were subjected to detailed

history taking, thorough clinical examination, routine laboratory investigations

including AST, ALT, alkaline phosphatase (ALP), total and direct bilirubin,

albumin, gamma glutamyl transferase (GGT), prothrombin time (PT), and

complete blood picture (CBC), abdominal ultrasonography, and liver biopsy.

According to the histopathological assessment of liver biopsies, patients

were classified into 3 distinct groups. Group (ǀ) included 51 cases with minimal



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or mild fibrosis (Metavir fibrosis score,F1, insignificant fibrosis). Group (ǁ)

included 43 cases with significant fibrosis ( F2 and F3). Group (ǀǁ) included 6

cases with liver cirrhosis (F4).

Patients with other conditions affecting liver enzymes were excluded such

as HBV infection, thyroid disease, muscle disease, primary hepatic or metastatic

lesions, passive congestion of liver, recent intramuscular injection or

medications. In addition, patients with metabolic liver disease, prior antiviral or

immunosuppressive therapy, recent anticoagulant therapy, and those whose

biopsy samples were shorter than 1 cm or containing less than 6 portal tracts

were excluded as well .⁽7⁾

Noninvasive indices Assay

Ten ml of venous blood were withdrawn under complete aspetic conditions

into vacutainer tubes from each patient at the day of liver biopsy. Samples were

divided into 2 parts: 5 ml were added to both citrate and EDTA tubes and the

remaining whole blood were incubated to clot in serum tubes at room

temperature for 20 minutes and then sera were separated by centrifugation at

2000 rpm for 15 minutes. Routine laboratory investigations were assayed.

Fibro-Q index was then calculated from a special formula: 10X (age X AST X

PTINR)/ (ALT X platelet count). In addition, APRI was calculated using the

following formula: ([ AST/ upper limit of normal, ULN] / platelet count [X

10⁹/L]) X 100. AAR was also calculated as a ratio between AST and ALT.

Histopathological study

All biopsies were obtained with 18G automatic guillotine type needle.

Liver tissues were fixed in 10% neutral formalin immediately after biopsy,

processed, and embedded in paraffin; 4- µm sections were cut with a microtome

( Microm HMSIS,Thermo Scientfic, Germeny). The slides were stained with

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hematoxylin-eosin for assessment of hepatic inflammatory activity and with

Masson´s trichrome stain for evaluation of the stage of fibrosis (13).Histological

staging (fibrosis score) were performed blindly according to the METAVIR

scoring system by one expert pathologist (E.H.).

According to the Metavir system, fibrosis was staged on a scale from F0 to

F4; F0- no fibrosis; F1- portal fibrosis without septa; F2-few septa; F3- many

septa without cirrhosisand F4- cirrhosis. The F0 and F1 were considered

insignificant (minimal or no) fibrosis ,whereas the scores F2-F4 were

considered significant fibrosis .⁽26⁾

STATISTICAL ANALYSIS

Statistical analysis was performed using SPSS software version 15.

Patients characteristics were represented as mean ± SD. One way ANOVA test

was used to assess the relationship between the clinical variables and degree of

fibrosis. r was considered weak if ˂ 0.25, mild if ≥ 0.25- ˂ 0.5, moderate if ≥

0.5- ˂ 0.75 , and strong if ≥ 0.75. P- value was considered significant if ˂ 0.05.

Receiver operating characteristic (ROC) curves were constructed for each

test.To evaluate the diagnostic accuracies of the noninvasive tests for liver

fibrosis, their sensitivities, specificities, positive predictive values (PPV),

negative predictive values (NPV), and the area under the ROC curves (AUC)

were compared according to the procedure proposed by Hanley and McNeil .⁽¹¹⁾

RESULTS

Our results were conducted at tables 1- 6 and figures 1- 2. Table (1) shows

laboratory investigations of all patients. Histopathological features of the

studied groups are summarized in Table (2). Group (ǀ) included 51 patients

whose liver biopsies showed Metavir stage F1 fibrosis (insignificant fibrosis).



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Group (ǁ ) included 43 patients whose biopsies showed either F2 (22 patients)

or F3 (21 patients) stages (significant fibrosis). Group (ǀǁ) included 6 patients

whose biopsies showed F4 stage (liver cirrhosis).

Correlations between Metavir fibrosis score and laboratory investigations

in all cases was constructed in table (3). A mild positive correlation was found

between Metavir score and AAR (p= 0.0001 & r= 0.39), whereas moderate

positive correlations were found with AST, ALT, PTINR, and Fibro-Q (p=

0.0001 & r= 0.64, 0.53, 0.68 & 0.74 respectively). A strong positive correlation

was found between Metavir score and APRI (p=0.0001 & r=0.77). On the other

hand, a mild negative correlation was found with platelet count (p=0.0001 & r=

- 0.34).

Table (4) is conducted to determine the way in which the means of the 3

noninvasive indices were affected by different Metavir fibrosis score, or in other

words, to compare means of these indices in the 3 studied patient´s groups. It

was found that the p-value of 0.0001 indicated a highly significant difference

between Fibro-Q, APRI, and AAR means of group ǀ vs both group ǁ & group ǀǁ,

and group ǁ vs group ǀǁ. In other words, the results of Fibro-Q index, APRI, and

AAR increased significantly as the fibrosis advanced.

Predicting significant fibrosis

The ROC curves evaluating the diagnostic accuracies of Fibro-Q, APRI,

and AAR were constructed and superimposed to determine which test would

have the most clinical utility to predict significant fibrosis (group ǁ) ( Figure 1).

Table (5) shows a comparison of AUCs at 95% confidence interval (CI) for

noninvasive indices (Fibro-Q, APRI, AAR) . It was found a superior diagnostic

accuracy of Fibro-Q (AUC= 0.87) over AAR (AUC= 0.71; p=0.003,

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statistically significant), but equal to APRI (AUC = 0.88; p=0.7, not statistically

significant), in the prediction of significant fibrosis (group ǁ).

The ROC analysis was done to select the most balanced cutoff values for

Fibro-Q, APRI, AAR in order to predict significant fibrosis.These values were

2.41,1.04, and 1.0, respectively. Moreover, ROC analysis was used to calculate

the sensitivity, specificity, positive predictive value (PPV), and negative

predictive value (NPV) of the simple fibrosis prediction tests using our cutoff

values.

Table (6) shows the predictive values of noninvasive indices for significant

fibrosis. Using Fibro-Q, at a cutoff ≥ 2.41, the PPV to predict significant

fibrosis was 100 % with a specificity of 100 %. At a cutoff < 2.41, the NPV of

Fibro-Q to exclude significant fibrosis was 79.7 % with a sensitivity of 69.8 %.

At a cutoff ≥ 1.04, the PPV of APRI to predict significant fibrosis was 88.6 %

with a specificity of 92.3 %. At a cutoff < 1.04, the NPV of APRI to exclude

significant fibrosis was 81.4 % with a sensitivity 74.4 %. In AAR, the cutoff

value to predict the presence (AAR ≥ 1.0) or absence (AAR < 1.0) of significant

fibrosis had a PPV of 94.7% and a NPV of 66.7%.

Therefore, our study found that Fibro-Q had better accuracy than AAR but

equal to APRI. Using a cutoff value of Fibro-Q index ≥ 2.41, the presence of

significant fibrosis could be correctly be identified with a high accuracy with

100% PPV.

Predicting cirrhosis

The ROC curves evaluating the diagnostic accuracies of Fibro-Q, APRI,

AAR were constructed and superimposed to predict cirrhosis(group ǀǁ) (Figure

2). Comparison of the AUCs ( 95% CI) for the 3 noninvasive indices, showed a

superior diagnostic accuracy of Fibro-Q (AUC= 0.88) over AAR (AUC=0.7;



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p= 0.2, not statistically significant) but inferior to APRI (AUC=0.98; p= 0.1, not

statistically significant), in the prediction of liver cirrhosis. However, APRI had

a superior diagnostic accuracy over AAR ( p= 0.02, statistically significant) in

the prediction of cirrhosis (Table 5).

Similarly we used the ROC analysis to select the most balanced cutoff

values for Fibro-Q, APRI, AAR in order to predict liver cirrhosis. These values

were 2.6, 1.82, and 0.96, respectively. Moreover, ROC analysis was used to

calculate the sensitivity, specificity, PPV, and NPV of the simple fibrosis

prediction tests using our cutoff values.

Table (7) shows predictive values of noninvasive indices for liver cirrhosis.

Using Fibro-Q, at a cutoff ≥ 2.6, the PPV to predict liver cirrhosis was 18.8 %

with a specificity of 72.3 %. At a cutoff > 2.6, the NPV of Fibro-Q to exclude

cirrhosis was 100 % with a sensitivity of 100 %. At a cutoff ≥ 1.82, the PPV of

APRI to predict liver cirrhosis was 37.5 % with a specificity of 89.4 %. At a

cutoff < 1.82, the NPV of APRI to exclude cirrhosis was 98.8 % with sensitivity

100 %. In AAR, the cutoff value to predict the presence (AAR ≥ 0.96) or

absence (AAR < 0.96) of cirrhosis had a PPV of 16.7 % and a NPV of 98.6%.

Therefore, we concluded that the three noninvasive prediction tests had

relatively low PPVs for prediction of liver cirrhosis. Conversely, they had high

NPVs for exclusion of cirrhosis. Using a cutoff value of a Fibro-Q index > 2.6,

the presence of cirrhosis was totally excluded with 100% NPV.

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Table (1): Laboratory investigations of all studied cases.

Mean± SD Laboratory investigations

61.4± 34.1 AST (U/L)

71.4± 39.2 ALT (U/L)

200± 57.4 Platelet count (x 10ᶟ/µL)

1.18± 0.15 PT INR

2.34± 1.26 Fibro- Q

1.08± 0.73 APRI

0.88± 0.23 AAR

Table (2): Histopathological features of the 3 studied groupss.

Patient number (%) Metavir fibrosis stages Patient´s groups

51% F1

Group (ǀ)

(insignificant fibrosis)

22%

21%

F2

F3

Group (ǁ)

(significant fibrosis)

6% F4 Group (ǀǁ)

(liver cirrhosis)

Table (3). Correlations of Metavir fibrosis score with laboratory

investigations of all cases.

p-value r Metavir fibrosis score

vs.

0.0001 0.64 AST (U/L)

0.0001 0.53 ALT (U/L)

0.0001 0.34- Platelet count (x 10ᶟ/µL)

0.0001 0.68 PT INR

0.0001 0.74 Fibro- Q

0.0001 0.77 APRI

0.0001 0.39 AAR



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Table (4). Correlations of Metavir fibrosis score with noninvasive indices in

the 3 studied groups.

Metavir fibrosis

score

vs.

Group ǀ Group ǁ Group ǁǀ

P- value

FibroQ

mean± SD mean± SD mean±

SD

0.0001

ǀ vs ǁ, ǁǀ

ǁ vs ǁǀ

1.53± 0.51 3.05± 1.2 4.21± 1.31

APRI

0.62± 0.32 1.4± 0.59 2.72± 0.53 0.0001

ǀ vs ǁ, ǁǀ

ǁ vs ǁǀ

AAR

0.79± 0.15 0.97± 0.26 0.98± 0.15 0.0001

ǀ vs ǁ, ǁǀ

ǁ vs ǁǀ

Table (5): Performance of simple fibrosis prediction tests for significant

fibrosis and cirrhosis.

Metavir fibrosis

score

vs.

AUC (group ǁ)

AUC (group ǀǁ)

Fibro-Q 0.87 (95 % CI: 0.8-0.9) 0.88 (95 % CI: 0.80-0.94)

APRI 0.88 (95% CI:0.8-0.9) 0.98 (95 % CI: 0.93-1.0)

AAR 0.71 (95% CI:0.6-0.8) 0.7( 95% CI: 0.6-0.8)

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Table(6). Predictive values of noninvasive indices for significant fibrosis.

. Fibro-Q AAR APRI Noninvasive test

2.41 1.0 1.04 Cut off value

69.8 41.9 74.4 Sensitivity

100 98.0 92.3 Specificity

100 94.7 88.6 PPV

79.7 66.7 81.4 NPV

86.2 72.3 84.0 Overall accuracy

Table (7): Predictive values of noninvasive indices for liver cirrhosis

.Fibro-Q AAR APRI Noninvasive test

2.6 0.96 1.82 Cut off value

100 83.3 100 Sensitivity

72.3 73.4 89.4 Specificity

18.8 16.7 37.5 PPV

100 98.6 98.8 NPV

74.0 73.0 90.0 Overall accuracy

Figure (1): ROC curves of the noninvasive indices for prediction of

significant fibrosis.



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Figure (2): ROC curves of the noninvasive indices for prediction of liver

cirrhosis.

DISCUSSION

Simple fibrosis tests are not yet widely applied in clinical practice and

recent American Association for the Study of Liver Diseases (AASLD)

guidelines on diagnosis and treatment of chronic hepatitis C do not include

recommendations for their use .⁽10⁾ This may be related to the fact that their

diagnostic accuracies have not yet been sufficiently validated by other

investigators in different study populations.

We believe that an ideal noninvasive test for assessing liver fibrosis should

be reliable, reproducible, and based on readily available tests and parameters.(17)

Since APRI and AAR, fulfilled these criteria,⁽19⁾ the aim of the current study

was to assess the predictive value of noninvasive indices of Fibro-Q, AAR &

APRI in patients with chronic hepatitis C, compared with liver biopsy and to

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determine their cutoff values to differentiate significant fibrosis and cirrhosis in

a community hospital in an area with hyperendemic HCV infection.

Furthermore, we should notice that three different staging systems were

used in the original studies for liver fibrosis tests. AAR results were based on

the Scheuer system; APRI was based on the Ishak system; and Fibro-Q was

based on the Metavir system.⁽21⁾ The different staging systems using either a 5-

stage (F0-F4) or a 7- stage (F0-F6) scale prevented us from comparing fibrosis

scores more precisely.

The current study had some advantages over previous studies. First, the

patients were all from a treatment-naïve population with HCV infection as the

only problem. Second, we compared 3 fibrosis markers that combined routine

blood tests rather than markers only available in the research laboratory. Third,

all histological assessment was performed blindly by one pathologist, thus

preventing inter-observer bias in fibrosis staging. Finally, using a 5- stage

fibrosis scoring system in this study resulted in a lower tendency to induce

interpretation error than would be the case with a 7- stage scoring system⁽6⁾.

In the current study we divided the patients in two different ways to

obviate liver biopsy. The first grouping was group (ǀ) vs group (ǁ). The rationale

for this patient grouping was that there was no need for treatment in patients

with minimal fibrosis. Patients with cirrhosis need screening for hepatocellular

carcinoma, esophageal varices, and complications of portal hypertension,

therefore, we made a second patient grouping of group (ǀ) and group (ǁ) vs

group (ǀǁ). Applying the cutoff values, we were able to discriminate patients

according to two relevant thresholds of fibrosis based on the needs for clinical

treatment decision-making.



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The clinical use of AAR in the diagnostic workup of patients with chronic

liver disease is supported by several studies.⁽22⁾ Nevertheless, the use of AAR as

a clinical decision-making aid in patients with chronic liver disease has been a

matter of debate.⁽18⁾

We also attempted to use AAR to detect either significant fibrosis or

cirrhosis and found it to have a low diagnostic accuracy in predicting significant

fibrosis ( AUC 0.71) and cirrhosis ( AUC 0.7). Consistent with our findings,

Wai et al., (2003) ⁽27⁾ also reported that the AUCs of the ROC curve in

differentiating significant fibrosis and cirrhosis were 0.6 and 0.76, respectively.

Also in accordance to our findings, Hsieh et al., (2009), found that AAR was

useful in differentiating significant fibrosis and cirrhosis , with AUCs,0.733 and

0.782, respectively. ⁽12⁾

In contrast to the results of Hsieh et al., (2009) which suggested that AAR

performed better than APRI (but, p ˃0.05, not statistically significant) in

predicting significant fibrosis and cirrhosis, the results of our present study

showed that APRI was superior to AAR ( p < 0.05, statistically significant) in

this regard. Consistent with our findings, Parise et al. (2006) reported that APRI

was superior to AAR in predicting significant fibrosis and cirrhosis. ⁽18⁾

In contrast to the other tests, APRI uses 2 different cutoff values for

exclusion or prediction of significant fibrosis ( < 0.5/ ≥ 1.5) and thus allowed

reliable diagnosis or exclusion of significant fibrosis in approximately 50% of

patients in the study by Wai et al., (2003).We could confirm a high PPV for

significant fibrosis of an APRI ≥ 1.5 in 34.8 % of our patients; however, the

NPV of an APRI < 0.5 for exclusion of significant fibrosis was found to be

slightly lower (78.5% vs. 86% in the Wai et al., 2003). In a systematic review,

Lin et al., (2011) ⁽15⁾ concluded that the AUCs of APRI for predicting significant

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fibrosis and cirrhosis were 0.76 and 0.82, respectively. At a 40% prevalence of

significant fibrosis, the cutoff values of < 0.5 had a NPV of 80%, but could

reduce the necessity of liver biopsy by only 35%. The results of our current

study showed the AUC of APRI for predicting significant fibrosis and cirrhosis

were 0.88 and 0.98, respectively, which were higher than those reported

previously. This discrepancy may be attributable to differences in the study

populations.

Liu et al., (2006) ⁽16⁾ demonstrated a low accuracy of APRI and AAR for

predicting significant fibrosis in viral hepatitis C carriers with persistently

normal ALT levels. The AUCs of the ROC curve in differentiating significant

fibrosis were only 0.673 for APRI and 0.504 for AAR in their study. In order to

optimize the usefulness of simple noninvasive tests, Hsieh et al., (2009)

formulated a novel index, named Fibro-Q. They found that the Fibro-Q

performed better than APRI (p< 0.05, statistically significant) , and had similar

results to AAR (p > 0.05, not statistically significant), in the prediction of

significant fibrosis (AUC,0.783) and cirrhosis (AUC, 0.791). Furthermore, they

reported that among patients with Fibro-Q scores of > 1.6, 92 of 99 (92.9%)

had significant fibrosis, and only seven patients without significant fibrosis were

classified incorrectly.

In contrast to Hsieh et al. (2009), the result of our current study showed a

superior diagnostic accuracy of Fibro-Q over AAR (p < 0.05, statistically

significant) but equal to APRI (p >0.05, not statistically significant), in the

prediction of significant fibrosis. Moreover, when we used the originally

described cutoff value for Fibro-Q (1.6), we found that among the 43 patients

who had significant fibrosis, only six patients had Fibro-Q scores of 1.6 or less

and among patients with Fibro-Q scores of > 1.6, 37 of 61 (60.7%) had

significant fibrosis, and 24 patients without significant fibrosis were classified



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incorrectly. Therefore , in order to optimize the usefulness of Fibro-Q for our

patients, we then selected the most balanced cutoff value for Fibro-Q (2.41)

from the ROC analysis. As a result, the accuracy of Fibro-Q increased to 86.2%

at a cutoff value of 2.41.

As regard the prediction of liver cirrhosis, our study showed that the Fibro-

Q performed better than AAR (p > 0.05, not statistically significant) but inferior

to APRI (p > 0.05, not statistically significant), however, Fibro-Q, APRI and

AAR had relatively low PPVs for prediction of cirrhosis (18.8%, 37.5%, and

16.7% at cutoff levels 2.6, 1.82, and 0.96 respectively). Consistent with our

findings, Hsieh et al., (2009) also reported low diagnostic accuracy of Fibro-Q,

APRI and AAR in predicting cirrhosis. The PPVs were 11.3%, 6.9%, and 10.2%

at cutoff levels 2.6,1.5, and 0.75 respectively. Conversely, our study showed

that the three tests had high NPVs for exclusion of cirrhosis. In this regard, our

results were similar to that of the three tests as described by Hsieh et al.,(2009) (

NPVs 100%,98.5%, and 98.9% respectively) .

In conclusion: the results of our current study demonstrated that Fibro-Q

proved to be a better biomarker than AAR, and equal to APRI, for predicting

significant fibrosis in patients with chronic viral hepatitis C.

Further prospective studies involving larger scale of patients are

warranted to validate the usefulness of Fibro-Q in clinical practice.

Ehab Mahfouz et al


66

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