Diagnostic accuracy of biochemical markers of fibrosis in black African patients with chronic hepatitis B

doi:10.4236/health.2010.212210

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Vol.2, No.12, 1413-1420 (2010) Health

doi:10.4236/health.2010.212210

Diagnostic accuracy of biochemical markers of fibrosis

in black African patient s wit h c hron ic hepatitis B

Alassan Kouamé Mahassadi1*, Alain Koffi Attia1, Fulgence M. Yao Bathaix1,

Narcisse Baudouin Agbé1, Stanislas Doffou1, Henriette Ya Kissi1,

Isidore Mouhenou Diomandé2, Paul Cales3, Thérese Ndri-Yoman1

1Service d’hépato-gastroentérologie, CHU de Yopougon, Abidjan, Côte d’Ivoire; *Corresponding Author: mahassadi@yahoo.com;

2Laboratoire d’anatomie pathologique, Faculté de médecine de Cocody, Abidjan, Côte d’Ivoire;

3Service d’hépato-gastroentérologie, CHU d’Angers, France.

Received 15 August 2010; revised 6 October 2010; accepted 11 October 2010

ABSTRACT

Contradictory results of the accuracy of bio-

chemical markers to p redict th e st age of fibrosis

in black Afri can p atients with chronic hepatitis B

(CHB) were previously published. We con-

ducted a prospective cohort study to determine

the diagnostic accuracy of aspartate aminotr ans-

ferase to platelet ratio (APRI), aspartate ami-

notransferase to alanine aminotransferase ratio

(AAR), platelet count, age-platelet (AP) index,

and FIB-4 index for the prediction of significant

fibrosis or cirrhosis in 117 black African p atient s

(median age: 38 years, males: 73%) with CHB

not previously treated. Among them, 45 had

significant fibrosis and 18 had cirrhosis using

the METAVIR score system. Factors associated

either with significant fibrosis or cirrhosis were

determined in logistic multivariate analysis.

Areas under receiver operating curve were as-

sessed and compared for APRI, AAR, AP index,

FIB-4 index and platelet count. Sensitivity,

specificity, positive and negative predictive

values were determined for each biochemical

markers. Multivariate analysis showed that as-

partate aminotransferase (p < 0.0001) and

platelets (p = 0.03) were the independent factors

associated with significant fibrosis and only

platelets (p = 0.01) were associated with cirrho-

sis. APRI (cut-off > 1.1) and FIB-4 index

(cut-off > 2.1) ruled out significant fibrosis with

high specificity of 84.7% and 86.1% respectively

and negative predictive values of 78.2% and

72.9% respectively. More accurately, APRI

(cut-off > 0.63) or FIB-4 index (cut-off > 1.26)

ruled out cirrhosis with high sensitivity of 94.4%

and 88.9% and high negative predictive values

of 98.1% and 96.3% respectively. In conclusion,

APRI and FIB-4 index are simple readily avail-

able markers to exclude significant fibrosis or

more accurately cirrhosis in black African pa-

tient s with CHB.

Keywords: Non Invasive Models; Fibrosis;

Cirrhosis; Hepatitis B; Su b-Saharan Africa

1. INTRODUCTION

Chronic hepatitis B (CHB) is the major cause of

chronic liver disease that affects approximately 350 mil-

lions individuals worldwide leading to cirrhosis and

hepatocellular carcinoma. Africa and Asia have the high-

est prevalence of hepatitis B virus infection worldwide

[1,2]. It is obvious that treatment of CHB is a challenge

for clinicians in Africa. The assessment of liver disease in

patients with CHB by the mean of liver biopsy is not a

mandatory but needed at baseline to exclude others

causes of liver disease or to evaluate the histologic dam-

age in the liver before the initiation of treatment after

long term follow up [2-4]. However, liver biopsy is an

invasive, costly and not completely safe mean that can

lead to severe complications with a potential risk of mor-

tality. In addition, it is limited by sampling error and poor

concordance between two observers [5,6].

Viral hepatitis C is the more prevalent chronic liver

disease in western countries [7]. Non invasive means are

constructed to determine the stage of fibrosis in patients

with chronic hepatitis C with acceptable accuracies and

therefore the need of liver biopsy can be obviated [8-14].

Several studies attempt to use some of these means in

patients with CHB and yield unsatisfactorily results

[15-17]. WAI et al. show that aspartate aminotransferase

(AST) to platelet ratio (APRI), aspartate aminotrans-

ferase to alanine aminotransferase (ALT) ratio (AAR)

and platelet count were not accurate in predicting either

significant fibrosis or cirrhosis among patients with

CHB. These findings are confirmed by Kim et al. for the

A. K. Mahassadi et al. / Health 2 (2010) 1413-1420

1414

prediction of cirrhosis in patients with CHB. All these

tests are validated in Asian patients [16,17].

The diagnostic accuracy of biochemical markers for

the prediction of the stage of fibrosis or cirrhosis in

black African patients was not evaluated enough. One

study suggested that FIB-4 index was accurate to ex-

clude significant fibrosis in black African patients with

CHB [18]. Recently discordant results were published by

Bonnard et al. that demonstrated low accuracy of FIB-4

index and APRI for the prediction of significant fibrosis

or cirrhosis in this ethnic group of population [19].

The aim of this study was to evaluate the AAR, APRI,

platelet count, age-platelet (AP) index, and FIB-4 index

for the prediction of significant fibrosis and cirrhosis in

black African patients with CHB attending the hepatol-

ogy unit of the Teaching hospital of Yopougon in Abid-

jan, Ivory Coast, West Africa.

2. MATERIALS AND METHODS

2.1. Patients

All consecutive patients with positive serum hepatitis

B surface antigen (HBsAg) and HIV-negative referred to

the hepatology unit at Yopougon teaching hospital were

eligible for the study. CHB infection was considered if

HBsAg persists 6 months after the date of the onset of

acute hepatitis B infection. For those with unknown date

of the onset of acute hepatitis B infection, CHB was con-

sidered if HBsAg is present in a secondary blood test

performed 6 months after the date of the previous posi-

tive blood test [1,2]. The exclusion criteria were con-

comitant liver disease such hepatitis D superinfection,

hepatitis C coinfection, autoimmune hepatitis, decom-

pensated cirrhosis, hepatic schistosomiasis, if blood test

were positive for antibodies against schistosomiasis or

the presence in liver biopsy, granulomatous and fibrotic

reaction related to hepatic schistosomiasis [20] concomi-

tant treatment against HBV, and alcohol consumption

over 50 g/l. All patients gave the consent for liver biopsy

and data were used according to Helsinki declaration.

2.2. Methods

2.2.1. Clinical Dat a

Following clinical data collected: age, sex, occupation,

ethnicity, source of contamination, presumably date of

contamination, past history of vaccination, alcohol con-

sumption.

2.2.2. Biological Dat a

Before liver biopsy, blood test were performed in the

laboratory of the Yopougon teaching hospital and pro-

vided following variables, haemoglobin, hematocrit,

mean corpuscular volume, platelet count (Coulter T-540

Coulter Corporation Hialeah, Florida USA), prothrom-

bin index (Coagulometer Option 4 plus Biomerieux

Germany), AST, ALT (Automate Analyzer, Hitachi Ldt,

Tokyo, Japan). The upper limit of normal of AST and

ALT were different according to sex and regarding the

normal values assigned by the laboratory AST: 31 and

36 IU/L, ALT: 34 and 43 IU/L, for respectively male and

female.

2.2.3. Virological Assay

HBsAg, hepatitis B e antigen (HBeAg), and antibody,

antibody to hepatitis B core antigen (Anti-HBc) were

performed using commercial assays (Cobas, Roche Di-

agnostics, Mannheim) if treatment was needed according

to the result of liver histology, ALT level or viral load

[3,4]. All virological assays were assessed at the Centre

Intégré de Recherche Bioclinique d’Abidjan (CIRBA)

laboratory of Abidjan.

2.2.4. Histological Assessment

Liver biopsies if not contraindicated were performed

after liver ultrasonography within 7 days after blood

testing. Needles of 1.6 mm diameter (Hepafix, Braun,

Melsungen) were used for all patients and liver biopsy

was performed according the Menghini technique [5].

Liver biopsy specimens were formalin-fixed, paraffin-

embedded and stained with hematoxilin-eosin-safran and

perls coloration for iron load. Necroinfammatory activity

and fibrosis stage were assessed by one senior patholo-

gist (DMI), who was blinded to the clinical examination

and blood tests and according to the METAVIR semi

quantitative system [21]. The fibrosis stage was as fol-

low: F0: no fibrosis, F1: portal fibrosis, F2: fibrosis with

few septa, F3: fibrosis with numerous septa, F4: cirrho-

sis. The grade of activity was as follow: A0: no histo-

logical activity, A1: mild activity, A2: moderate activity,

A3: severe activity. The length of biopsy specimen was

not recorded for all patients.

2.2.5. Diagnostic Target

Two diagnostic targets (significant fibrosis and cirrho-

sis) assessed by the histologic findings after liver biopsy

were used to identify four groups of patients. Patients

with significant fibrosis (F2, F3, and F4) were compared

to those without significant fibrosis (F0 and F1) and pa-

tients with cirrhosis (F4) were compared with those

without cirrhosis (F0, F1, F2, and F3).

2.2.6. Statisti cal Analysis

Continuous variables were expressed as median and

interquartile range and qualitative variables were ex-

pressed as percentage. Mann-Withney U test and χ2 or

Fischer test (if appropriated) were used to compare

A. K. Mahassadi et al. / Health 2 (2010) 1413-1420

1415

quantitative and qualitative variables. The correlations

between AST, ALT and platelet count with the stage of

fibrosis were assessed by the non parametric Spearman’s

rho test (rho). The AAR, APRI, AP index and FIB-4 in-

dex were determined by formula previously published

and resumed in Table 1 [8,11,13,14]. Variables signifi-

cantly associated with significant fibrosis or cirrhosis in

univariate analysis were tested using a multivariate lo-

gistic regression. The diagnostic accuracy with the best

cut-off point that maximizes the sensitivity and the

specificity and express as sensitivity, specificity, predic-

tive positive and negative values were determined by the

receiver operating characteristic curve (ROC) for platelet

count, AAR, APRI, AP index and FIB-4 index. The areas

under ROC of platelet count, AAR, APRI, AP index and

FIB-4 index of each group were compared according to

the Henley and Mac Neil test [22]. Value of area under

ROC of 1.0 indicated an ideal test whereas value of 0.5

indicated that the test was not significant. All tests were

two-tailed and performed by SPSS for Windows version

11.0 (SPSS Inc., Chicago, IL). P value under 0.05 was

considered as significant.

3. RESULTS

3.1. Study Sample

Between January 2002 and December 2005, a total of

136 patients were recruited. Twenty four patients were

excluded (7 patients with chronic hepatitis C, 12 patients

with both CHB and C, 3 patients with hepatic steatosis

and 2 patients with sclerosing cholangitis). The remain-

ing 117 patients were included (73.3% were male). All

of them were Ivoirians and black Africans with a median

age (interquartile range) of 38 years (30-46). The base-

line characteristics are summarised in Tab le 2. Signifi-

cant fibrosis and cirrhosis were found respectively in 45

(42.2%) and 18 (40%) patients.

3.2. Factors Associated with Significant

Fibrosis or Cirrhosis

Patients with significant fibrosis or cirrhosis had

Table 1. Formulas of biochemical markers for the prediction of

necroinflammatory activity and fibrosis stage.

Tests Formulas

AAR AST/ALT

APRI (AST [ULN]/platelet count [103/mL]) × 100

AP index

Age (years): <30 = 0; 30-39 = 1; 40-49 = 2;

50-59 = 3; 60-69 = 4; ≥ 70 = 5

Platelet count (× 103/mL): ≥ 225 = 0; 200-224 = 1;

175-199 = 2; 150-174 = 3; 125-149 = 4; < 125 = 5

FIB-index Age[years] × AST [IU/L]/(platelet count [103/mL] ×

(ALT1/2 [IU/L])

AAR: aspartate aminotransférase to alanine aminotransferase ratio,

APRI: Aspartate aminotransferase to platelet count ratio, AP index:

age-platelet index.

Table 2. Baseline characteristic of 117 patients included.

all patients

(n = 117)

Age (years ) [median (IQR)] 38 (30-46)

Black Africans [n (%)] 117 (100)

Sex (male) [n (%)] 86 (73.5)

Blood parameters

ALT (IU/L) [median (IQR)] 45 (29-105)

ALT (ULN) [median (IQR)] 1.1 (0.7-2.6)

AST (IU/L) [median (IQR)] 44 (27-86)

AST (ULN) [median (IQR)] 1.3 (0.8-2.5)

Platelet count (× 103/mL) [median (IQR)] 196 (140.5-250)

Prothrombin time (%) [median (IQR)] 90 (80-100)

Metavir fibrosis stage

No fibrosis (F0) [n (%)] 52 (44.4)

Portal fibrosis (F1) [n (%)] 20 (17.1)

Few septa (F2) [n (%)] 16 (13.7)

Numerous septa (F3) [n (%)] 11 (9.4 )

Cirrhosis (F4) [n (%)] 18 (15.4)

Metavir histologic activity

No activity (A0) [n (%)] 45 (38.5)

Mild activity (A1) [n (%)] 30 (25.6)

Moderate activity (A2) [n (%)] 21 (17.9)

Severe activity (A3) [n (%)] 21 (17.9)

AST: aspartate aminotransferase, ALT: alanine aminotransferase,

ULN: upper limit of normal, IQR: interquartile range.

higher level of ALT (ULN) or AST (ULN) and lower

platelet count than those without significant fibrosis or

cirrhosis in univariate analysis (Table 3). AST (ULN)

and ALT (ULN) levels correlated positively (both corre-

lation coefficients rho = 0.4, p < 0.0001) whereas plate-

let count correlated negatively (rho = –0.28, p = 0.002)

with the stage of fibrosis. Overall comparison demon-

strated significant difference between AST or Platelets

count and the stage of fibrosis (Figure 1). In logistic

multivariate analysis, AST (p < 0.0001) and platelet

count (p = 0.03) were independent predictors of signifi-

cant fibrosis whereas platelet count was the only inde-

pendent factor associated with cirrhosis (p = 0.01). The

median values (with interquartile range) of biochemical

markers are summarised in Table 4. Besides AAR for

significant fibrosis, biochemical markers showed sig-

nificant but modest area under ROC either for the pre-

diction of significant fibrosis (fibrosis stage ≥ F2) or

cirrhosis (F4) in our study (Table 5).

3.3. Comp ari son of Biochemical Pa rameters

for the Prediction of Significant

Fibrosis

As illustrated in Figure 2(a), APRI, platelet count,

FIB-4 index and AP index had similar diagnostic accu-

A. K. Mahassadi et al. / Health 2 (2010) 1413-1420

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Table 3. Univariate analysis of parameters between patients with and without significant fibrosis, and between patients with and

without cirrhosis.

Fibrosis stage

F0-1 (n = 72) F2-4 ( n = 45) p-value F0-3 ( n = 99) Cirrhosis (F4)

(n = 18) p-value

Age (years) [median (IQR)] 39 (30-46) 35.5 (29-45.3) 0.9 38 (30-45) 41 (29-53) 0.5

Sex (male)[ n (%)] 52 (44.4) 34 (29.1) 0.7 72 (61.5) 14 (12) 0.8

ALT (UI/L) [median (IQR)] 39 (25.3-53.5) 85 (40.3-167.5) < 0.0001 41 (28-77) 114 (73.8-188.8)< 0.0001

ALT (ULN) [median (IQR)] 1.0 (0.7-1.3) 2.4 (1-4) < 0.0001 1.0 (0.7-1.8) 2.7 (1.9-4.4) < 0.0001

AST (UI/L) [median (IQR)] 38.5 (24.3-51.5) 70 (38-148) < 0.0001 41 (25-72) 85.5 (45.8-155) 0.002

AST (ULN) [median (IQR)] 1.6 (0.7-1.5) 2.3 (1.1-4.7) < 0.0001 1.2 (0.8-2.1) 2.5 (1.3-4.9) 0.002

Platelets count (103/mL) [median (IQR)] 215 (166.3-271) 153.5 (127.8-213.8) < 0.0001 208 (150-263) 139 (120.8-197)0.001

Prothrombin time [median (IQR)] 90 (80-75) 87.5 (79.8-100) 0.4 90 (80-100) 80.5 (78.8-96.3)0.1

ALT: alanine aminotransferase, AST: aspartate aminotransferase, F0-1: non significant fibrosis, F2-4: significant fibrosis, F0-3: no cirrhosis, F4: cirrhosis, ULN:

upper limit of normal, IQR: interquartile range.

Table 4. Distribution of biochemical markers values.

AAR: Aspartate aminotransferase to alanine aminotransferase ratio, APRI: Aspartate aminotransferase to platelet count ratio, AP index: age-platelet index, IQR:

interquartile range.

Table 5. Diagnostic accuracy of biochemical markers for the prediction of significant fibrosis and cirrhosis.

Cut-off

Area under

the ROC

(95% CI)

Sensitivity

(95% CI)

(%)

Specificity

(95% CI)

(%)

PPV

(95% CI)

(%)

NPV

(95% CI)

Diagnostic of significant

fibrosis

Platelet count (× 103/ mL) < 163 0.7 (0.61-0.78) 60 (44.3-74.3) 77.8 (66.4-86.7) 62.8 (46.7-77) 75.7 (64.3-84.9)

AAR - 0.54 (0.45-0.63) - - - -

APRI > 1.1 0.76 (0.67-0.84) 62.2 (46.5-76.2) 84.7 (74.3-92.1) 71.8 (55.1-85) 78.2 (67.4-86.7)

AP index > 3 0.67 (0.58-0.75) 66.7 (51.0-80.0) 65.3 (53.1- 76.1) 54.5 (40.6-68) 75.8 (63.3-85.8)

FIB-4 index < 2.1 0.70 (0.6-0.78) 48.89 (33.7-64.2) 86.1 (75.9-93.1) 68.7 (50-83.9) 72.9 (62.2-82)

Diagnostic of cirrhosis

Platelet count (× 103/ mL) ≤ 139 0.74 (0.65-0.82) 55.6 ( 30.8-78.5) 86.9 (78.6-92.8) 43.5 (23.2-65.5) 91.5 (83.9-96.3)

AAR ≤ 0.69 0.64 (0.54-0.72) 50.0 (26.1-74) 78.8 (69.4-86.4) 30.0 (14.7-49.4) 89.7 (81.3-95.2)

APRI > 0.63 0.76 (0.68-0.84) 94.4 (72.6-99.1) 53.5 (43.2-63.6) 27.0 (16.6-39.7) 98.1 (90.1-100)

AP index > 3 0.69 (0.60-0.78) 77.8 (52.4-93.6) 58.6 (48.2-68.4) 25.5 (14.7-39) 93.5 (84.3-98)

FIB-4 index > 1.26 0.68 (0.59-0.76 ) 88.9 (65.3-98.6) 52.5 (42.2-62.7) 25.9 (15.3-37.9) 96.3 (87.3-99,5)

AAR: Aspartate aminotransferase to alanine aminotransferase ratio, APRI: Aspartate aminotransferase to platelet count ratio, AP index: age-platelet index.

racy for the prediction of significant fibrosis. However-

better performances were observed with APRI and FIB-4

index (Tab le 5 ). With a cut-off > 1.1 of APRI, signifi-

cant fibrosis could be correctly excluded in 61 (52%) of

117 patients with 78.2% of NPV. Similar results were

obtained with FIB-4 index (cut-off > 2.1) that identified

correctly 62 (53%) of 117 as patients with no significant

fibrosis. However the number of false negative patients

was lower with FIB-4 index than APRI (8.5% and

14.5 % respectively).

3.4. Comparison of Biochemical Parameters

for the Prediction of Cirrhosis

All biochemical markers had better performances to

exclude cirrhosis (Figure 2(b)) with high negative pre-

dictive values > 80%. APRI and FIB-4 index had maxi-

mal sensitivity respectively 94.4% and 88.9% (Table 5).

All patients (n = 117 )

Significant fibrosis

Fibrosis stage F2-4

(n = 45)

cirrhosis

Fibrosis stage F4

(n = 18)

Platelet count (103/mL) [median (IQR)] 205.51 (140.5-205) 152 (127.5-210) 139 (120.8-197)

AAR [median (IQR)] 1.0 (0.69-1.32) 0.9 (0.58-1.58) 0.78 (0.49-1.14)

APRI [median (IQR)] 0.72 (0.4-1.85) 1.75 (0.68-3.62) 1.65 (0.87-4.10)

AP index [median (IQR)] 3.0 (2-5) 4 (3-6) 4.0 (3.5-6.3)

FIB-4 index [median (IQR)] 1.35 (0.78-2.20) 1.89 (1.24-4.30) 1.74 (1.46-2.77)

A. K. Mahassadi et al. / Health 2 (2010) 1413-1420

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Figure 1. Box plots of AST (a) or platelet count (b) according to the stage of fibrosis defined by META-

VIR score system. The box represents the interquartile range; the top and the bottom of the box are re-

spectively the 25 th and 75 th percentile. The line across the box is the median. The lower and upper values

are indicated by the whiskers. The circles represent the outliers.

Figure 2. Receiver operating characteristic curve of the five biochemical markers for the prediction of sig-

nificant fibrosis (a) or cirrhosis (b) according to the METAVIR stage of fibrosis in black African patients

with chronic hepatitis B. APRI: aspartate aminotransferase to platelet count ratio, AAR: aspartate ami-

notransferase to alanine aminotransferase ratio, AP: age-platelet index and FIB-4 index.

With a cut-off > 0.63 of APRI, cirrhosis was correctly

excluded in 52 (52.5%) patients among 117 with a NPV

of 98.1%. Among 18 patients with histological proven

cirrhosis, 17 (94.4%) were correctly classified and 1

(1.9 %) patient was false negative. Applying a cut-off >

1.26 of FIB-4 index, we found similar results, 51 (51.5%)

patients of 117 correctly classified as patients with no

cirrhosis. Thus 16 (88.9%) patients of 18 with cirrhosis

were diagnosed and 2 (3.8%) were false negative.

4. DISCUSSION

We demonstrated in this study that biochemical mark-

ers previously assessed in chronic hepatitis C such as

APRI, AAR, FIB-4 index, platelet count and AP index

had low accuracy regarding their respective areas under

ROC, to predict the presence of significant fibrosis or

cirrhosis among black Africans with CHB. However

some of them could be used to exclude more accurately

cirrhosis in low medicalized countries of Africa.

Indeed we found that in patient with cirrhosis, APRI

and FIB-4 index enabled to eliminate cirrhosis with high

degree of certainty better than that published by Bonnard

et al., in Burkina Faso [19]. This is probably related to

the size of our sample twice larger. Indeed our patients

(a) (b)

A. K. Mahassadi et al. / Health 2 (2010) 1413-1420

1418

were slightly older than those from Mayotte and some of

them had platelet count in normal range despite moder-

ate to severe fibrosis (Figure 1(b)) leading to misclassi-

fication of FIB-4 index. The length of liver biopsy frag-

ment was probably not large enough in our study to en-

hance the accuracy of FIB-4 index as previously demon-

strated [18]. In other hand the interaction of parasitosis

or other blood transmitted diseases as malaria and CHB

both prevalent in sub-Saharan African countries could

reduce the global performance of these biochemical

markers in African patients [24]. Nevertheless APRI and

FIB-4 index could be used to monitor patient with CHB

when liver biopsy is difficult to perform. Both were ac-

curate to exclude cirrhosis among black Africans with

high degree of NPV. This probably means that APRI and

FIB-4 index are more reliable when cirrhosis occurs in

sub Saharan African patients with CHB than westerners

or other black people. Recent studies conducted in Asia

demonstrated discordant results of APRI and FIB-4 in-

dex for the prediction of stage of fibrosis. Wu et al.,

founded low accuracy of APRI and FIB-4 index to pre-

dict significant fibrosis comparable to our findings [25].

However these two biochemical markers showed better

performances to predict severe fibrosis. Kim et al. dem-

onstrated that FIB-4 allowed detecting cirrhosis with

high degree of certainty than APRI, and AAR [26].

These recent findings emphasized the difficulty to pro-

vide definite and invariable performance of biochemical

markers in patients with CHB whatever the geographical

area. This study was conducted in West Africa where the

endemicity of HBV is high and enrolled only black Af-

ricans. Most of them acquired HBV infection perinataly

or during childhood which is the most common route of

transmission of HBV in this area [1]. Liver damage (fi-

brosis and cirrhosis) occurs mainly in adulthood with a

high risk of onset of hepatocellular carcinoma. This ex-

plained that 45% of patients in our study had significant

fibrosis or cirrhosis and were eligible for treatment [1,2].

We were not able to seek the date of the onset of acute

hepatitis B infection, to determine viral load or HBeAg

and antibody for most of patients because of the high

cost of their determination and high number of missing

values. These parameters were not included in the analy-

sis. Despite these limitations, this study pointed out

some specificities in a population of black African pa-

tients. Firstly, AST and platelet count were independent

predictors of significant fibrosis and only platelet count

were associated with cirrhosis in multivariate analysis.

Secondly, biochemical markers assessed in this study

with significant values of area under ROC had high abil-

ity to exclude patients with cirrhosis. Each of them

showed high NPV > 85%. Regarding the area under

ROC, our study confirmed the findings made by Wai et

al. and Kim et al. in Asian patients [16,17]. Furthermore

our study is consistent with that of Hongo et al., in

which the areas under the ROC of APRI and AP index

were also modest respectively 0.76 and 0.74 [23]. In

contrast to the study of Wai et al. in which only platelet

count were an independent factor associated either with

significant fibrosis or cirrhosis in multivariate analysis in

a cohort of Asian patients [16], our study suggest that

black African patients experience more flares of hepatitis

B with intermittent elevation of transaminases because

of immune pressure and high prevalence of HBeAg

negative CHB that lead to severe liver damage [2,27,28].

Indeed, cirrhosis and hepatocellular carcinoma occurred

more rapidly in patients with HBeAg negative CHB and

hepatocellular carcinoma related to HBV is more preva-

lent among blacks Africans [29,30]. Similar to others

studies, in patients with CHB even in those with chronic

hepatitis C, we found an association between platelet

count and cirrhosis as demonstrated by others [31,32].

Chronic hepatitis B is a public health concern in West

Africa where the vaccination against hepatitis B infec-

tion is not widely implemented in most sub-Saharan Af-

rican countries. Antiviral treatments are expensive for

most patients with severe liver damage. Pathologists

with a high experience in liver histologic examination

are not widely available. There is a need for accurate,

readily available and routinely feasible blood markers

for the prediction of significant fibrosis or cirrhosis in

Africa. Previous reports showed that combination of

biochemical markers that included hyaluronidase, alpha2

macroglobulin or serum globulin are accurate to predict

significant fibrosis or cirrhosis in patients with CHB but

most of then have low values of area under the ROC or

are not routinely incorporated in the panel of blood tests

in most hospital laboratories even in Europe than in Af-

rica [15,33,34]. Hui et al. demonstrate that a score in-

cluding body mass index, platelet count, serum albumin

and total bilirubin was accurate in predicting the absence

of significant fibrosis but needs complicated calculation

[35]. Mohamadnejad et al., published a score to assess

significant fibrosis only in patient with HBe Ag negative

CHB [36]. Hongbo et al. also demonstrated that combi-

nation of biochemical markers may enhance diagnosis

accuracy for either the prediction (AP index with AST in

parallel interpretation) or the exclusion (AP index with

gammaglutamyltransferase in serial interpretation) of

significant fibrosis in patient with CHB [23]. However,

we think that the procedure of calculation and interpreta-

tion is not easy to fulfil in clinical practice. Bonnard et al.

found that Elastometry were more reliable than APRI

and FIB-4 index to predict significant fibrosis in black

A. K. Mahassadi et al. / Health 2 (2010) 1413-1420

1419

African patients but the device for it determination is

expensive and not available in most hospitals of sub Sa-

haran African countries [19]. Liver biopsy remains in

this area the only means to quantify liver fibrosis in pa-

tients with CHB. Guidelines and consensus conferences

recommend to monitor patients with cirrhosis by routine

alpha-fetoprotein determination and liver ultrasonogra-

phy every 6 months [2,3]. Close surveillance is recom-

mended to detect the onset of oesophageal varices if

absent at the time of the diagnosis of cirrhosis by routine

endoscopy [37,38]. Lamivudine, a nucleoside analogue

is widely used in Africa as part of highly antiretroviral

therapy in HIV infected patients. It is a cost effective

drug affordable to most Africans for the treatment of

CHB.

However, patients with cirrhosis treated by lami-

vudine need close surveillance because of the risk of

hepatitis flares and liver decompensation during treat-

ment [2,39].

Most of these recommendations are difficult to fulfil

in developing countries of Africa. Biochemical markers

such as APRI, and FIB-4 index easy to determine and

cost effective could be used to identify African patients

with CHB who do not have cirrhosis, and in whom close

surveillance could be delayed during treatment by lami-

vudine.

5. CONCLUSION

This study demonstrated that biochemical markers

currently used in chronic hepatitis C, had low accuracy

regarding their areas under ROC. However APRI and

FIB-4 index could be used to exclude cirrhosis in black

African patients with CHB with high certainty. Further

studies enrolling a large sample of black African patients

with CHB are needed to establish the clinical relevance

of the accuracy of biochemical markers in African pa-

tient.

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