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Keywords:

  • HBV infection;
  • liver fibrosis;
  • noninvasive markers

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT). Liver biopsy (LB) is the current gold standard for assessing hepatic inflammation and fibrosis in patients with chronic HBV. However, associated risks have led to the development of noninvasive models. Their utility in patients with normal ALT is unknown. FIB-4 and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) were calculated for patients with chronic HBV infection undergoing biopsy. The performance of each model and AUROC for predicting significant fibrosis (Scheuer's score ≥ S2) were determined for the entire cohort and stratified by elevated (≥50 U/L) and normal ALT. Two-hundred and thirty-one liver biopsies were included. The number of patient with normal ALT was 140, and 22.1% had significant fibrosis. The AUROC curve for patients with normal ALT was 0.81 for FIB-4 and 0.80 for APRI, compared with 0.71 for FIB-4 and 0.72 for APRI for those with mildly elevated ALT level. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FIB-4 were 0.63, 0.88, 0.61 and 0.93, for patients with normal ALT; the values for APRI were 0.40, 0.88, 0.33 and 0.93. Both FIB-4 and APRI are useful for identification of those without significant fibrosis. However, because they have poor PPV, LB will continue to be used for assessment of HBV-infected patients with normal ALT and mildly elevated ALT.


Abbreviations
ALT

alanine aminotransferase

APRI

AST-to-platelet ratio index

AST

aspartate aminotransferase

CHB

Chronic hepatitis B virus

LB

liver biopsy

NPV

negative predictive value

PLT

platelet

PPV

positive predictive value

ROC

Receiver operating characteristic

ULN

upper limit of normal

Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

Chronic hepatitis B virus (CHB) infection can cause a spectrum of diseases ranging from the clinically asymptomatic state to the development of cirrhosis-related complications and hepatocellular carcinoma [1, 2]. The guidelines of the American Association For the Study of Liver Diseases (AASLD) and the Asian Pacific Association For the Study of Liver (APALSL) primarily rely on alanine aminotransferase (ALT) level to guide treatment decisions [3-5]. The AASLD and APASL guidelines recommend treatment for patients with an ALT level higher than two times the upper limit of normal (ULN) range and liver biopsy (LB) to guide treatment decisions for patients with an ALT level 1–2 times the ULN, particularly if they are above the age of 40 years [5]. Recently, several studies have shown that moderate inflammation and/or advanced fibrosis can be found in 28–37% of patients with CHB infection who had persistently normal ALT [6-8]. Use of ALT and HBV-DNA levels without resorting to LB to define ‘inactive carrier state’ may miss histologically significant disease in a proportion of patients [9].

Liver biopsy has long been the gold standard in assessing histological disease in chronic hepatitis B (CHB). However, liver biopsies are invasive, expensive and carry some risk of complications and concerns of sampling error, as well as interobserver and intra-observer variation in interpretation [10, 11]. Furthermore, not surprisingly, patients report a considerable dislike for undergoing the procedure. Noninvasive techniques for hepatic fibrosis such as elastography [12] requires specialized centres, so are less readily available. Consequently, there has been much interest in the use of noninvasive markers to accurately assess the extent of hepatic injury. Several unique markers have been evaluated, either alone or in combination, in noninvasive models, to predict hepatic fibrosis [13-15]. These tests, however, are not widely available and can be costly. Other noninvasive tests such as the FIB-4 index [16] and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) [17] have been developed. Previous analyses have shown FIB-4 index and APRI to be a strong predictor of liver fibrosis [16-18]. FIB-4 and APRI are calculated from standard biochemical laboratory values [platelets (PLT), ALT and aminotransferase and patient age] to give a simple and inexpensive measure of fibrosis, which may be performed without specialized equipment. Unfortunately, most studies of the FIB-4 index and APRI model have included only those with chronic hepatitis C virus infection (CHC) or with increased liver enzymes in CHB [19, 20]. Significant differences exist between CHB and CHC, not only in the aetiology but also in natural history, laboratory parameters, liver histology and associated medical conditions [21, 22]. The applicability of these models in CHB patients with normal ALT is unknown. To address this gap in knowledge, the objectives of this study were to compare the performance of two models of routine tests, the FIB-4 and APRI, in patients with HBV infection stratified by normal and mildly elevated ALT.

Patients and Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

Patients

A total of 239 patients were recruited into the trials from the liver centre of The Zhejiang provincial people's hospital between December 1, 2010 to December 1, 2011. Patients were enroled based on the following criteria: (i) chronic hepatitis B defined by HBsAg positivity for more than 6 months; detectable HBV-DNA with a level >103 copies/mL, ALT values within the normal range (our laboratory reference value was 50 U/L) or <2 × ULN; (ii) age ≧18, no previous or concomitant anti-HBV therapy; (iii) absence of liver comorbidity including hepatitis delta superinfection, HCV co-infection, chronic ethanol consumption (<30 g of pure alcohol per day), Wilson's disease, HIV co-infection or auto-immune hepatitis; (iv) no present or past evidence of any symptoms related to liver disease; patients were categorized as persistently normal ALT if they had at least 3 ALT values in the year prior to LB. Mildly elevated ALT was defined as an ALT level <2 times ULN. (v) absence of immune suppression. Eight patients were excluded from the current study due to either inadequate specimen for histological diagnosis or failure to retrieve the slides. The number of patients whose value of ALT was within the normal range was 140.

The study was approved by the ethics committee of zhejiang provincial people's hospital. Written informed consent to participate in the study was obtained from each patient.

Liver biopsy

All patients received a percutaneous LB directed by ultrasonography. LB was performed using an 18G biopsy needles. The specimens were fixed, paraffin-embedded and stained with haematoxylin and eosin (HE). A minimum of 1.5 cm of liver tissue with at least six portal tracts was required for diagnosis. Histological grading of necro-inflammation (G0–G4) and staging of the liver fibrosis (S0–S4) were carried out according to Scheuer's classification [23] by a single pathologist blinded for the clinical data. Liver fibrosis was considered significant when it spread beyond the portal tract (S2–4).

Serum markers

Blood samples of the cohort were obtained on the day before LB. Biochemical tests for glucose, total cholesterol, triglycerides, ALT, AST, alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), bilirubin, albumin and complete blood count were performed by commercial assays in our hospital laboratory. HBsAg, anti-HBs HBeAg, anti-HBe, anti-HBc and anti-HCV were measured with CLIA systems. The serum HBV-DNA level was detected with a Real-Time polymerase chain reaction (PCR) System (ABI7300; Applied Biosystems, Foster city, CA, USA). Normal laboratory values are as follows: ALT ≦ 50U/L and AST ≦ 52 U/L in both men and women.

Statistical analysis

Data were expressed as mean ± SD for continuous variables and proportions for categorical variables unless otherwise noted. Univariate analysis (Student t-test, nonparametric test or adjusted chi-square test) was carried out to identify variables that were significantly different between patients with and without significant fibrosis. The equations for the two noninvasive markers analysed were as follows:

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Both model results were compared with the fibrosis scores. Receiver operating characteristic (ROC) curves for both FIB-4 and APRI were then developed for the entire group and subsequently those with and without normal ALT. Using the previously published cut-offs for FIB-4 and APRI, patients were placed in two classes (FIB-4 ≦ 1.45, FIB-4 > 1.45 and APRI ≦ 0.5, APRI > 0.5). The performance of each model was evaluated. Sensitivity (Se), specificity (Spe), positive predictive values (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) were also calculated using cut-off value previously described.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

Patient characteristics

The characteristics of patients enrolled in the study are shown in Tables 1 and 2. Two-hundred and thirty-six biopsies were obtained from patients. 60.6% of the patients had ALT values ≦50 U/L, 17% of the men had ALT < 30 U/L and 5% of the women <19 U/L. Regarding the distribution of fibrosis scores, 22.1% (31/140) of the patients whose value of ALT was normal had significant fibrosis (S2–4). In comparison, 40.7% (37/91) of the patients with mildly elevated ALT had significant fibrosis. Those with elevated ALT was more likely to have significant fibrosis than those with normal ALT (40.7% vs 22.1%. P = 0.002) (Tables 1, 2).

Table 1. Patient characteristics
 Normal ALTElevated ALTStatisticsP value
  1. BMI, body mass index; AKP, alkaline phosphatase; GGT γ-glutamyltransferase; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CR, creatinine; GLB, globulin; WBC, white blood cell count; PLT, platelet.

  2. Continuous values are expressed as mean ± SE. Categorical variables are expressed as n (%).

N 14091  
Age (years)34.1 ± 9.834.2 ± 9.70.450.65
Male (n, %)817513.750.00
BMI21.1 ± 2.2822.3 ± 2.380.570.57
HBeAg + (n, %)96600.920.76
ALT (IU/L)28.88 ± 9.3768.20 ± 13.6624.10.00
AST (IU/L)27.30 ± 8.9547.47 ± 13.9512.250.00
BUN (mmol/L)4.74 ± 1.174.79 ± 1.160.290.77
Cr (μmol/L)71.93 ± 16.7875.37 ± 17.141.380.17
HBV DNA (log10 copies/mL)5.94 ± 1.656.12 ± 1.530.850.39
GGT (IU/L)28.96 ± 19.0944.52 ± 36.913.650.77
AKP (IU/L)76.25 ± 23.7679.65 ± 25.320.930.35
ALB (g/L)45.40 ± 2.9845.08 ± 3.32-0.860.39
GLB (g/L)26.85 ± 4.0927.03 ± 3.830.210.84
PLT (109/L)178.54 ± 54.49161.83 ± 49.132.420.02
WBC (109/L)4.48 ± 0.714.65 ± 0.83-1.680.09
Hb (g/L)13.65 ± 1.1213.84 ± 1.15-1.270.21
Table 2. Patient's histological characteristics
VariableNormal ALTElevated ALTStatisticsP value
  1. ALT, alanine aminotransferase.

Grading of inflammation
 G0410.190.66
 G11034316.470.00
 G2294318.110.00
 G3440.060.80
Stage of liver fibrosis
 S02566.060.01
 S184480.910.34
 S215226.440.01
 S3960.0020.97
 S4792.020.16

Comparison of the FIB-4 index and APRI in chronic HBV infection

On the whole sample, FIB-4 values ranged from 0.36 to 6.68. Mean values increased as a function of fibrosis score from 0.73 ± 0.24 in S0 cases to 2.98 ± 2.46 in S4. The FIB-4 values were placed in two classes (FIB-4 ≤ 1.45, FIB-4 > 1.45) and Scheuer's fibrosis scores were grouped into two categories (S0–S1–S2, S3–S4). The results are presented in Table 3. For comparison, APRI values ranged from 0.11 to 2.45, mean values increased from 0.31 ± 0.13 in S0 cases to 1.07 ± 0.51 in S4. To compare FIB-4 and APRI, three separate ROC curves were calculated to predict significant fibrosis (≧S2). The area under the ROC curve was 0.77 for both FIB-4 (95% confidence interval:0.70–0.84) and APRI (95% confidence interval: 0.71–0.84) for the entire cohort. To predict severe fibrosis (≧S3), the area under the ROC curve was increased to 0.81 for FIB-4 (95% confidence interval 0.73–0.89) for the entire cohort, slightly higher than that for APRI 0.77 (95% confidence interval 0.68–0.84). Then, data were separated by normal and elevated ALT. When the ROC curve was calculated for patients with normal ALT values, to predict significant fibrosis (≧S2), the AUC was 0.81 (95% confidence interval 0.74–0.92) for FIB-4 and 0.80 for (95% confidence interval 0.72–0.90) APRI. Furthermore, to predict severe fibrosis, the AUC was 0.83 (95% confidence interval 0.71–0.95) for FIB-4 and 0.81 for (95% confidence interval 0.71–0.92) APRI. Then, when the ROC curve was calculated only using patients with mildly elevated ALT, the AUC was decreased to 0.71 (95% confidence interval 0.60–0.82), 0.73 (95% confidence interval 0.60–0.87) for FIB-4, 0.72 and 0.76 for APRI with 95% confidence intervals of 0.61–0.83 and 0.63–0.89, respectively to predict significant fibrosis and severe fibrosis (Figs 1, 2).

image

Figure 1. (a) Receiver operating characteristic (ROC) plot for FIB-4 and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) in differentiating severe fibrosis (≧S3) in the total cohort (n = 231). FIB-4 had an AUROC of 0.81 and an AUROC of 0.77 for the APRI (b) ROC plot for FIB-4 and APRI in differentiating severe fibrosis (≧S3) in patients with normal alanine aminotransferase (ALT) (N = 140). FIB-4 had an AUROC of 0.83 and an AUROC of 0.81 for the APRI. (c) ROC plot for FIB-4 and APRI in differentiating severe fibrosis (≧S3) in patients with elevated ALT levels (n = 91). FIB-4 had an AUROC of 0.73 and an AUROC of 0.76 for the APRI.

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image

Figure 2. (a) Receiver operating characteristic (ROC) plot for FIB-4 and aspartate aminotransferase-to-platelet ratio index (APRI) in differentiating significant fibrosis (≧S2) in the total cohort (n = 231). FIB-4 had an AUROC of 0.77 and an AUROC of 0.77 for the APRI. (b) ROC plot for FIB-4 and APRI in differentiating significant fibrosis (≧S2) in patients with normal alanine aminotransferase (ALT) (N = 140). FIB-4 had an AUROC of 0.81 and an AUROC of 0.80 for the APRI. (c) ROC plot for FIB-4 and APRI in differentiating significant fibrosis (≧S2) in patients with elevated ALT levels (n = 91). FIB-4 had an AUROC of 0.71 and an AUROC of 0.72 for the APRI.

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Table 3. comparison of FIB-4 index, aspartate aminotransferase-to-platelet ratio index (APRI) and liver biopsy results
 Fibrosis scoreTotal
S0-S2S3-S4
FIB-4 ≤ 1.4516613179
FIB4 > 1.45341852
Total20031231
APRI ≤ 0.514613179
APRI > 0.5551752
Total20130231

Performance of the models

We next compared the performance of these two models. As shown in Table 3, approximately 26% of our patients had determinant values for both FIB-4 and APRI (FIB-4 > 1.45 and APRI > 0.5), in each instance. Approximately 67.2% of these patients had normal ALT values. When evaluating all patients with determinant values to predict severe fibrosis, FIB-4 had a sensitivity of 0.67, specificity of 0.80, a PPV of 0.37 and an NPV of 0.97. When patients were stratified by ALT values, the sensitivity and specificity increased to 0.73 and 0.82 for patients with normal ALT with accuracy of 81%. For comparison, the APRI sensitivity and specificity were 0.63 and 0.72 for all patients with determinant values, the sensitivity of the test decreased to 0.40 for patients with normal ALT and specificity increased to 0.88 with accuracy of 84%. The sensitivity, specificity and accuracy of the models are presented in Table 4.

Table 4. Performance of FIB-4 and aspartate aminotransferase-to-platelet ratio index (APRI) to predict severe fibrosis in those with determinant value
 SensitivitySpecificityPPVNPVAccuracy
  1. NPV, negative predictive value; PPV, positive predictive value.

FIB-40.670.800.370.970.74
APRI0.630.720.280.940.78
Nomal ALT
 FIB-40.760.820.380.960.82
 APRI0.400.880.330.930.84
Elevated ALT
 FIB-40.600.740.250.900.70
 APRI0.870.450.260.960.59

To predict significant fibrosis if we evaluated all patients with determinant values, FIB-4 had a sensitivity of 0.56, specificity of 0.75, a PPV of 0.59 and an NPV of 0.86 with accuracy of 78.4%. For APRI, the sensitivity was 59% with specificity of 0.78, a PPV of 0.59, an NPV of 0.70 and accuracy of 75.8%. When patients were stratified by ALT values, the sensitivity and specificity increased to 0.63 and 0.88 for patients with normal ALT with accuracy of 81% for FIB-4. Table 5 shows the sensitivity, specificity and accuracy of these two models for patients stratified by ALT value.

Table 5. Performance of FIB-4 and aspartate aminotransferase-to-platelet ratio index (APRI) to predict significant fibrosis with determinant value
 SensitivitySpecificityPPVNPVAccuracy
  1. ALT, alanine aminotransferase; NPV, negative predictive value; PPV, positive predictive value.

FIB-40.540.850.590.860.78
APRI0.590.790.590.700.76
Nomal ALT
 FIB-40.630.880.610.930.86
 APRI0.380.980.650.840.80
Elevated ALT
 FIB-40.500.780.560.720.67
 APRI0.790.510.560.850.68

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

The latest EASL practice guidelines on CHB recommend that patients with HBV-DNA >105copies/mL and persistent or intermittent elevation in aminotransferase levels should be evaluated further with LB [23]. In the presence of moderate or significant necroinflammation on histology, treatment is still warranted regardless of the transaminase and HBV-DNA level. Several studies have observed a high prevalence of histologically significant liver disease in HBV carriers with normal ALT levels or mildly elevated ALT levels. For example, Kumar et al. reported that 21% of hepatitis B e antigen-negative patients with persistently normal ALT levels and HBV-DNA levels below 5 log10 copies/mL had histologically active liver disease. In another study, 18% of patients who had normal ALT had significant fibrosis (Metavir score ≥ F2) [6, 7]. Given that a normal ALT does not exclude the absence of significant liver damage, it is important to identify such patients who might benefit from antiviral therapy. With advances in the treatment of CHB and now the well-accepted fact that liver fibrosis is reversible, monitoring disease progression is highly important. LB, a gold reference standard for assessing liver fibrosis, however, is associated with a finite, risk of complications of ~0.4%, patient discomfort [24], and expense. It is therefore not suitable for regular monitoring of disease progression. Noninvasive methods have been proposed to overcome the limits of LB to assess liver fibrosis.

Both FIB-4 and APRI use routine laboratory tests to predict liver fibrosis, and have been validated in patients with HBV infection and elevated ALT. Mallet et al. [18] demonstrated that FIB-4 allowed the correct identification of patients with nil-moderate fibrosis with an AUCROC of 0.81, NPV of 86% and a sensitivity of 71.1%. In a meta-analysis, Jin et al. [25] have systematically reviewed the diagnostic accuracy of the APRI for the prediction of significant fibrosis in hepatitis B-related fibrosis, and found that the AUCROC was O.79 with a sensitivity of 80% and specificity of 41% for APRI > 0.5, and the estimated PPV and NPV were 80% and 57%, respectively. In a third study, Sebastiani et al. [26] had investigated the performance of APRI and FIB-4 in 2411 patients with chronic liver disease (CLD). The results showed that APRI had an AUCROC of 0.68 with NPV of 72%, and a sensitivity of 67.9% in CHB, slighty higher than that of FIB-4, which was 0.66%, 60.1% and 65%. These findings indicated that both APRI and FIB-4 can predict significant fibrosis in CHB patients with elevated ALT levels.

In this study, we attempted to compare the performance of the two noninvasive models to predict significant or advanced fibrosis in a consecutive series of treatment-naive CHB patients with persistently normal and mildly elevated ALT levels. In our cohort, 22.1% (31/140) of patients whose value of ALT was normal had significant fibrosis (Scheuer's fibrosis scores S2–S4), and 38.5% (35/91) of patients with mildly elevated ALT had significant fibrosis. If there was significant necroinflammation (G2–G3) also 63.7% (58/91) of patients with mildly elevated ALT and 37.8% of (53/140) patients whose ALT level was normal had significant liver disease. The prevalence of severe fibrosis, defined as bridging fibrosis, was 11% in those with normal ALT and 16% in those with mildly elevated ALT. This high prevalence is supported by other studies [6, 7]. We showed that the FIB-4 index and APRI can easily exclude advanced fibrosis in CHB patients whose ALT levels were normal or mildly elevated. At first, we compared the results of the FIB-4 index and APRI with those of the LB. We found an AUROC curve of 0.81 to exclude severe fibrosis (S3-S4). The negative predictive value to exclude severe fibrosis was excellent for FIB-4 (97%) values of ≦1.45. As shown in our study, the FIB-4 index can also exclude significant fibrosis (S2–S4) in patients with normal ALT levels, the negative predictive value being 93%. Use of this index would correctly classify 71% of patients with FIB-4 values outside the 1.45–3.25 range whose ALT level was normal or mildly elevated and avoid biopsy. Of note, the FIB-4 index can be interpreted with caution in patients with a low PLT count, thus underestimating significant fibrosis.

To assess the efficiency of the FIB-4 index and APRI, we used the LB as a reference for fibrosis evaluation. However, as previously reported, LB can over or underestimate the degree of liver fibrosis and has to be considered as an imperfect comparator [27]. Sampling variation can explain most of these difficulties: only 65% of biopsies relying on 15 mm samples afford correct fibrosis assessment [27]. In our study, in order to control sample bias, the size of sample used to assess fibrosis was 20 mm. All histological slides were retrieved and reread by one liver pathologist (L.X.) to avoid interobserver discrepancies. In addition, all slides were reread over a 6 week period to minimize intra-observer variability.

Comparisons between the FIB-4 index and APRI were performed in the second part of this study. The FIB-4 index was slightly more precise than the APRI to exclude severe fibrosis. However, to exclude significant fibrosis, the two models had the same efficiency. The important finding from current analysis is that both the FIB-4 index and APRI can accurately predict fibrosis in CHB patients with normal ALT. In fact, the AUROC, sensitivity and specificity and accuracy were greater for those patients with normal, rather than elevated ALT. Although neither model had a high PPV, the high negative predictive value of excluding significant fibrosis was slightly better using FIB-4 for patients with normal ALT. However, for the patients with mildly elevated ALT, the APRI had a higher negative predictive value of excluding significant fibrosis. Possible explanations for the low PPV for significant fibrosis in our findings was due to the low proportion of patients with severe fibrosis and high determinant value for the two models.

Identifying those patients, who actually had significant fibrosis, placed into ‘immune tolerant’ phase according to their ALT levels, is important. These individuals may benefit from antiviral therapy, but the extent of histological improvement after such therapy remains unknown. Because of the moderate PPV, although the FIB-4 and APRI are good tests to rule out significant fibrosis in those patients with a normal ALT, LB may still be needed for patients who have FIB-4 > 1.45 or APRI > 0.5.

The present study has several unique features. First, we recruited consecutive patients undergoing liver biopsies at our liver disease centre who met eligibility criteria. Many prior studies have recruited only patients enroled in treatment trials, which may have introduced selection bias. Our study included treatment naïve patients only because liver histology may improve after antiviral treatment. Secondly, our study population was of the same race. Our study was prospective in design, and all data extraction was performed by one investigator (H.W.). The key variables in our study were objective laboratory results, most of which were available in the hospital computer system. The consistency in data was ensured.

We acknowledge that there are limitations to our study. First, we defined normal ALT levels based on our laboratory values. Recent studies have suggested that these values are high and that normal ALT should be 30 U/L for men and 19 U/L for women [28]. Because only 11% had ALT < 30 U/L (men) or 19 U/L (woman), we were unable to perform the analysis using this value. We chose to stratify our subjects based on ALT rather than AST, because ALT is more liver specific. Secondly, the original study of APRI defined normal AST < 45 U/L; our laboratory defined normal AST as 52 U/L if we chose 45 U/L, our results may have differed. Finally, in this study, the HBV genotype of our patients had not been assessed. Genotype C HBV has been consistently shown to be associated with more active liver disease than Genotype B HBV in Asian patients [29]. However, the determination of HBV genotype is not a routine clinical practice in our centre.

In conclusion, a fair proportion of HBV-infected patients with normal ALT have active liver disease and both FIB-4 and APRI are useful in identifying those without significant fibrosis with >85% accuracy. Stratifying those with FIB-4 ≦ 1.45 or APRI ≦ 0.5 would have reduced the number of biopsies performed in the entire cohort by 72%. However, because prediction of significant fibrosis by both models is poor, LB should remain in the assessment of patients with FIB-4 > 1.45 and APRI > 0.5. As better noninvasive models such as the fibroscan that has high specificity for predicting severe fibrosis are developed, in combination with FIB-4 or APRI, will mean fewer patients will require LB.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References