The gamma‐glutamyl transpeptidase‐to‐platelet ratio predicts liver fibrosis and cirrhosis in HBeAg‐positive chronic HBV infection patients with high HBV DNA and normal or mildly elevated alanine transaminase levels in China

The gamma‐glutamyl transpeptidase‐to‐platelet ratio (GPR) is a new serum diagnostic model, which is reported to be more accurate than aspartate transaminase‐to‐platelet ratio index (APRI) and fibrosis index based on the four factors (Fib‐4) for the diagnosis of significant fibrosis and cirrhosis in chronic HBV infection (CHBVI) patients in West Africa. To evaluate the performance of the GPR model for the diagnosis of liver fibrosis and cirrhosis in HBeAg‐positive CHBVI patients with high HBV DNA (≥5 log₁₀ copies/mL) and normal or mildly elevated alanine transaminase (ALT) (≤2 times upper limit of normal (ULN)) in China. A total of 1521 consecutive CHBVI patients who underwent liver biopsies and routine laboratory tests were retrospectively screened. Of these patients, 401 treatment naïve HBeAg‐positive patients with HBV DNA≥5 log₁₀ copies/mL and ALT≤2 ULN were included. The METAVIR scoring system was adopted as the pathological diagnosis standard of liver fibrosis. Using liver histology as a gold standard, the performances of GPR, APRI, and Fib‐4 for the diagnosis of liver fibrosis and cirrhosis were evaluated and compared by receiver operating characteristic (ROC) curves and the area under the ROC curves (AUROCs). Of 401 patients, 121 (30.2%), 49 (12.2%) and 17 (4.2%) were classified as having significant fibrosis (≥F2), severe fibrosis (≥F3) and cirrhosis (=F4), respectively. After estimating the AUROC to predict significant fibrosis, the performance of GPR (AUROC=0.66, 95% CI 0.60–0.72) was higher than APRI (AUROC=0.58, 95% CI 0.52–0.64, P=.002) and Fib‐4 scores (AUROC=0.54, 95% CI 0.47–0.60, P<.001). After estimating the AUROC to predict severe fibrosis, the performance of GPR (AUROC=0.71, 95% CI 0.63–0.80) was also higher than APRI (AUROC=0.65, 95% CI 0.56–0.73, P=.003) and Fib‐4 scores (AUROC=0.67, 95% CI 0.58–0.75, P=.001). After estimating the AUROC to predict cirrhosis, the performance of GPR (AUROC=0.73, 95% CI 0.56–0.88) was higher than APRI (AUROC=0.69, 95% CI 0.54–0.83, P=.041) and Fib‐4 scores (AUROC=0.69, 95% CI 0.55–0.82, P=.012) too. The GPR is a new serum model for the diagnosis of liver fibrosis and cirrhosis and shows obvious advantages in Chinese HBeAg‐positive patients with HBV DNA≥5 log₁₀ copies/mL and ALT≤2 ULN compared with APRI and Fib‐4, thus warranting its widespread use for this specific population.     

The gamma‐glutamyl transpeptidase‐to‐albumin ratio predicts significant fibrosis and cirrhosis in chronic hepatitis B patients

Background/Aim Simple, inexpensive and clinically available noninvasive liver fibrosis tests are highly needed. We aimed to develop a novel noninvasive index for predicting significant fibrosis and cirrhosis in chronic hepatitis B (CHB) patients. Methods Using liver histology as gold standard, we developed a novel index to predict significant fibrosis and cirrhosis in CHB patients and then compared the diagnostic accuracy of the novel index, aspartate transaminase‐to‐platelet ratio index (APRI), and fibrosis index based on four factors (FIB‐4) in a training set (606 patients) and a validation set (216 patients) from the same patient catchment area. Results Of 606 CHB patients in the training set, 33.2% had significant fibrosis and 11.4% had cirrhosis. In multivariable analysis, gamma‐glutamyl transpeptidase (GGT) (OR=1.032, p<0.001) and albumin (OR=0.953, p=0.048) were independent predictors of significant fibrosis. Consequently, a GGT‐to‐albumin ratio (GAR) was developed. In the training set, the area under the receiver operating characteristic curve (AUROC) of GAR was significantly higher than that of APRI and FIB‐4 to predict ≥F2 (0.82, 0.70, and 0.68, respectively), ≥F3 (0.86, 0.76, and 0.75, respectively), and F4 (0.88, 0.75, and 0.73, respectively), respectively. In the validation set, the AUROC of GAR was also better than APRI and FIB‐4 for predicting ≥F2 (0.81, 0.63 and 0.61, respectively), ≥F3 (0.88, 0.78, and 0.76, respectively) and F4 (0.92, 0.85, and 0.78, respectively), respectively. Conclusions GAR is a more accurate noninvasive index than APRI and FIB‐4 to stage significant fibrosis and cirrhosis in CHB patients and represents a novel noninvasive alternative to liver biopsy.     

Evaluation and comparison of thirty noninvasive models for diagnosing liver fibrosis in chinese hepatitis B patients

The limitations of liver biopsy have led to the development of indirect noninvasive models for liver fibrosis assessment. We aimed to evaluate and compare the performance of 30 noninvasive models to predict fibrosis stage in treatment‐naïve and treated chronic hepatitis B (CHB) patients. A total of 576 Chinese treatment‐naïve CHB patients and 236 treated CHB patients who had undergone percutaneous liver biopsy were included in the analysis. Histological grading and staging was assessed by the Ishak scoring system. The diagnostic accuracies of 30 noninvasive models were assessed by area under the receiver operating characteristic curves (AUROCs). In treatment‐naïve CHB patients, the AUROCs of the 30 noninvasive models for discriminating significant fibrosis (SF) were less than 0.800, and only the AUROC of the PP score for diagnosing advanced fibrosis (AF) was more than 0.800, while the AUROCs of FIB‐4, FibroQ, HB‐F, Lok index, PHP score and PP score for predicting cirrhosis were greater than 0.800. In treated CHB patients, only the AUROCs of APRI, GUCI, King's score and Wang I for identifying cirrhosis were more than 0.800. The Spearman correlation analysis identified that only the changes in FCI and Virahep‐C model values were weakly correlated with changes in Ishak fibrosis scores before and after treatment (r = 0.206, p = 0.008; r = 0.187, p = 0.016, respectively). In conclusion, in Chinese CHB patients, the 30 existing noninvasive models were not suitable for assessing each stage of fibrosis except cirrhosis before and after antiviral therapy, especially in gauging progression and regression of liver fibrosis following therapy.     

Plateletcrit as a potential index for predicting liver fibrosis in chronic hepatitis B

Noninvasive tests (NITs) for liver fibrosis are highly needed for chronic hepatitis B (CHB) patients. We aimed to investigate whether plateletcrit (PCT) could be used as a NIT in predicting liver fibrosis for CHB patients. Five hundred and sixty‐seven treatment‐naïve CHB patients with available liver biopsies were included. Patients were randomly divided into a derivation cohort (n = 378) and a validation cohort (n = 189). The diagnostic accuracy of PCT was evaluated using receiver operating characteristic (ROC) curves. In the derivation cohort, PCT in CHB patients with S2‐S4 (0.14%), S3‐S4 (0.13%) and S4 (0.12%) was lower than patients with S0‐S1 (0.17%, P < .001), S0‐S2 (0.17%, P < .001) and S0‐S3 (0.16%, P < .001), respectively. PCT was an independent predictor of significant fibrosis (≥S2), advanced fibrosis (≥S3) and cirrhosis (S4). The area under the ROC curve (AUROC) of PCT in predicting significant fibrosis, advanced fibrosis and cirrhosis was 0.645, 0.709 and 0.714, respectively. The AUROC of PCT was higher than the aspartate transaminase to platelet ratio index (APRI) in identifying advanced fibrosis and cirrhosis, while this was comparable with APRI in identifying significant fibrosis. The diagnostic value of PCT was comparable with fibrosis‐4 score (FIB‐4) in predicting significant fibrosis, advanced fibrosis and cirrhosis. In the validation cohort, PCT could also identify significant fibrosis, advanced fibrosis and cirrhosis with similar diagnostic accuracy as in the derivation cohort. PCT represents a simple and inexpensive indictor for liver fibrosis in CHB patients. PCT is just as good or better than other more complex tools for staging liver fibrosis in CHB patients.     

APRI and FIB‐4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS)

We aim to determine the predictive ability of APRI, FIB‐4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2–F4) from none to minimal fibrosis (F0–F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0–4 equivalent fibrosis stage. Mean APRI and FIB‐4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut‐offs, the AUROCs in distinguishing F2–F4 from F0 to F1 were 0.81 (0.76–0.87) for APRI, 0.81 (0.75–0.86) for FIB‐4 and 0.56 (0.49–0.64) for AST/ALT ratio. APRI and FIB‐4 distinguished F2–F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis.     

A novel index using routine clinical parameters for predicting significant liver inflammation in chronic hepatitis B

Identifying the degree of liver inflammation is critical for therapeutic judgement of patients with chronic hepatitis B (CHB). However, we lack indexes which can accurately predict significant liver inflammation in patients with CHB. This study aimed to develop a simple predictive index for liver inflammation in CHB using routine clinical parameters. A total of 519 patients with CHB who underwent liver biopsy were enrolled and randomly divided into training (n = 346) and validation cohorts (n = 173). Based on routine clinical parameters, gamma‐glutamyl transpeptidase (GGT; P = 0.031) and platelets (PLT; P < 0.001) were identified as independent predictors of significant inflammation by multivariable analysis in the training cohort. Accordingly, the GGT to PLT ratio (GPR) was developed to amplify the opposing effects for predicting liver inflammation. In the training cohort, the AUCs of GPR in predicting significant inflammation were 0.791 (95% CI: 0.742‐0.839), 0.783 (95% CI: 0.717‐0.849) and 0.791 (95% CI: 0.716‐0.867) in the entire patients with CHB, HBeAg‐positive CHB patients and HBeAg‐negative CHB patients, respectively. The diagnostic performance of GPR for significant inflammation was significantly superior to that of alanine aminotransferase (ALT), aspartate transaminase (AST) and GGT in all patients with CHB and HBeAg‐positive CHB patients, but was comparable with ALT, AST and GGT in HBeAg‐negative CHB patients. In the validation cohort, the diagnostic performance of GPR in assessing significant liver inflammation was also superior to other indexes in all patients with CHB and HBeAg‐positive CHB patients, but was comparable with GGT in HBeAg‐negative CHB patients. Thus, GPR can be a novel and simple index for predicting significant liver inflammation in CHB, especially for HBeAg‐positive CHB.     

Alanine aminotransferase influencing performances of routine available tests detecting hepatitis B‐related cirrhosis

The performances of routine tests such as FIB‐4 and APRI in detecting cirrhosis and significant fibrosis in chronic hepatitis B (CHB) have been shown to be discrepant between studies. Novel tests such as red cell distribution width‐platelet ratio (RPR), γ‐glutamyl transpeptidase to platelet ratio (GPR) and easy liver fibrosis test (eLIFT) are introduced recently. To evaluate the aminotransferase influence on the performance of these routine tests, a total of 1005 CHB patients who underwent liver biopsies and routine tests were retrospectively analysed. The diagnostic cut‐offs referring to likelihood ratio were determined for excluding or including cirrhosis diagnosis and also for ruling in significant fibrosis diagnosis. The performances of RPR, FIB‐4, eLIFT and APRI in detecting cirrhosis seemed improved at higher ALT levels, while GPR was conversely impaired. The likelihood ratio was ∝ for APRI cut‐off 2 diagnosing cirrhosis in ALT < 2 upper limit of normal (ULN), 14.6 for APRI cut‐off 1.5 determining significant fibrosis in ALT ≤ 5ULN and 20.6 for FIB‐4 cut‐off 3.2 diagnosing ≥ F3 in the total cohort, respectively. The optimal cut‐offs for cirrhosis diagnosis were increased with higher ALTs by tests which included aminotransferase, but not for RPR. The proportions of patients classified as having cirrhosis or no cirrhosis stratified by ALT level cut‐offs were superior. Stepwise applying RPR, GPR and eLIFT would determine 60% of patients as having cirrhosis or no cirrhosis with an accuracy of 93.0%. In conclusion, the performance of aminotransferase comprising tests in detecting cirrhosis in CHB were influenced by ALT levels. Thus, ALT stratified cut‐offs may be a preferred alternative. In resource‐limited settings, stepwise applying routine tests could be recommended as a preferred measurement for cirrhosis detection.     

Delayed viral suppression during antiviral therapy is associated with increased hepatocellular carcinoma rates in HBeAg‐positive high viral load chronic hepatitis B

The treatment option in chronic hepatitis B (CHB) patients with persistent low‐level viremia despite entecavir or tenofovir monotherapy is unclear. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B e antigen (HBeAg)‐positive high viral load CHB patients, according to the time needed to achieve complete viral suppression. A total of 325 HBeAg‐positive CHB patients with high viral load who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were divided into 2 groups with 4 separate criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3 or 4 years of therapy initiation. The outcomes were development of HCC and cirrhosis. The cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03‐19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24‐9.23; P = .018), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04‐3.66; P = .037) or 2 years (HR, 2.44; 95% CI, 1.41‐4.22; P = .001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2 years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development.     

Comparison of FIB‐4 and APRI in Chinese HBV‐infected patients with persistently normal ALT and mildly elevated ALT

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.     

Use of simple noninvasive biomarkers to predict liver fibrosis in HIV/HCV coinfection in routine clinical practice

Background

Simple noninvasive tests to predict fibrosis, as an alternative to liver biopsy (LB), are needed. Of these, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the Forns index (FI) have been validated in HIV/hepatitis C virus (HCV) coinfection. However, these indexes may have lower diagnostic value in situations other than the circumscribed conditions of validation studies. We therefore examined the value of the APRI and FI in HIV/HCV‐coinfected patients for the detection of significant fibrosis in real‐life conditions.

Patients and methods

HIV/HCV‐coinfected patients who had participated in a multicentre cross‐sectional retrospective study were selected if they had undergone an LB within 24 months before the last visit. The predictive accuracy of the APRI and FI was measured using the areas under receiver‐operating‐characteristic curves (AUROCs). Diagnostic accuracy was determined using the positive (PPV) and negative (NPV) predictive values.

Results

A total of 519 coinfected individuals were included in the study. The AUROC [95% confidence interval (95% CI)] of the APRI was 0.67 (0.66–0.71) and that of the FI was 0.67 (0.62–0.71). The PPV of the APRI was 79% and its NPV was 66%. The PPV of the FI was 74% and its NPV was 64%. LB length was available and was ≥15 mm in 120 individuals. In this group, the PPV of the APRI was 85%, and that of the FI was 81%. Using these indexes, 22% of patients could be spared LB. Applying both models sequentially, 30% of patients could be spared LB.

Conclusions

In HIV/HCV‐coinfected patients, the diagnostic accuracy of the APRI in real‐life conditions was similar to that in the validation studies. The FI performed less well. However, combining the two indexes to make decisions on anti‐HCV therapy may prevent a significant proportion of patients from having to undergo LB.     

Estimation of liver fibrosis by noncommercial serum markers in comparison with transient elastography in patients with chronic hepatitis C virus infection receiving direct‐acting antiviral treatment

Treatment decisions are based on extent of fibrosis in patients with chronic hepatitis C (HCV) infection. Noninvasive diagnostic tools may help to avoid liver biopsy. We investigated the diagnostic accuracy of noncommercial serum scores in comparison with transient elastography (TE). Data analysis was undertaken based on 2458 patients enrolled in the German Hepatitis C Registry, in a prospective, observational study. Aspartate aminotransferase‐to‐platelet ratio index (APRI), FORNS index and FIB‐4 score were calculated and the diagnostic accuracy was compared to TE. As estimated by TE, 955 (38.9%) patients had absence of significant fibrosis (SF), 736 (29.9%) patients had SF, and 767 (31.2%) patients were shown to have cirrhosis. Patients with absence of SF had a sustained virological response (SVR) rate of 97.9%, whereas SVR was attained in 96.2% and 92.2% in those with SF and cirrhosis, respectively (P < 0.0001). The area under the receiver operator characteristic curve (AUROC), sensitivity and specificity in discriminating of SF were 0.789, 0.596 and 0.939 by APRI; 0.838, 0.852 and 0.748 by FORNS index; and 0.828, 0.658 and 0.946 by FIB‐4 score. AUROCs for the prediction of cirrhosis, sensitivity and specificity were 0.881, 0.851 and 0.854 by APRI; 0.846, 0.948 and 0.628 by FORNS index; and 0.907, 0.907 and 0.848 by FIB‐4 score. In conclusion, in the present multicentre real‐world cohort, SF and cirrhosis were predicted with high accuracy with noncommercial serum markers using TE as reference. Further prospective long‐term follow‐up is necessary to compare biomarkers with TE concerning liver‐related outcome and overall mortality.     

Diagnostic potential of serum direct markers and non‐invasive fibrosis models in patients with chronic hepatitis B

Aim: Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the disadvantages of liver biopsy, many studies related to non‐invasive biomarkers and scores have been performed. In this study, we aimed to assess the diagnostic value of serum direct markers and non‐invasive fibrosis models to predict liver fibrosis in the treatment‐naive chronic hepatitis B (CHB) patients and to compare their diagnostic performance. Methods: This study included 58 patients with a diagnosis of CHB virus infection and 30 healthy controls. Hyaluronic acid, tissue inhibitor of matrix metalloproteinase 1 and amino‐terminal propeptide of type III procollagen were measured by enzyme‐linked immunosorbent assay; and the Original European Liver Fibrosis panel, the Enhanced Liver Fibrosis (ELF) panel, PP score, aspartate aminotransferase to platelet ratio index (APRI) and FIB‐4 indexes were calculated using the formulas taken from previous publications. Fibrosis stage was determined using Ishak's scoring system. Results: The fibrosis stages identified upon liver biopsy was F0 in 12 patients (20.7%), F1–2 in 36 (62.1%) and F3–5 in 10 (17.2%). The diagnostic value of all the non‐invasive indices was low to detect mild fibrosis. We demonstrated that the diagnostic accuracy of HA is the best for predicting fibrosis of F3 or more (area under the receiver–operator curve, 0.902). In our study, the results from a combination of tests showed that ELF and APRI had the highest diagnostic value sensitivity of 90%, specificity of 100%, positive predictive value of 100% and negative predictive value of 96.4% for detection of fibrosis of F3 or more. Conclusion: In CHB patients, combination of ELF and APRI has a better diagnostic value in predicting fibrosis of F3 or more.     

Validation of FIB‐4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus‐infected patients

Backgrounds: To optimize management and predict long‐term clinical courses in patients with chronic hepatitis B (CHB), noninvasive tests to determine the degree of hepatic fibrosis have been developed. Aims: This study aimed to validate a simple, noninvasive FIB‐4 index, which was first derived from an HCV–HIV‐co‐infected population, in patients with CHB and to compare it with other noninvasive tests for predicting cirrhosis. Methods: From 2006–2008, a total of 668 consecutive CHB patients who underwent liver biopsies were enrolled. The fibrosis stage was assessed according to the Batts and Ludwig system by a single pathologist blinded to patients' data. Results: For prediction of significant (F≥2) and severe (F≥3) fibrosis, and cirrhosis (F=4), the area under the receiver‐operating characteristic curves were 0.865, 0.910 and 0.926 respectively. In predicting cirrhosis, it demonstrated diagnostic values comparable to the age–spleen platelet ratio index (0.937, P=0.414) and age–platelet index (0.928, P=0.888), and better outcomes than spleen–platelet ratio index (0.882, P=0.007), aspartate aminotransferase (AST)–platelet ratio index (0.731, P<0.001) and AST–alanine aminotransferase ratio index (0.730, P<0.001). FIB‐4 cut‐offs of 1.6 and 3.6 provided 93.2% negative predictive value and 90.8% positive predictive value for detection of cirrhosis respectively. Based on these results, liver biopsy could be avoided in 70.5% of the study population. These cut‐offs were validated internally using bootstrap resampling methods, showing good agreement. Conclusions: FIB‐4 is a simple, accurate and inexpensive method of predicting cirrhosis, with outcomes comparable to other noninvasive tests and may reduce the need for liver biopsy in the majority of CHB patients.     

Stepwise application of fibrosis index based on four factors,red cell distribution width–platelet ratio,and aspartate aminotransferase–platelet ratio for compensated hepatitis B fibrosis detection

Background and Aim

Fibrosis index based on four factors (FIB‐4) and aspartate aminotransferase–platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width–platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB‐4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis.

Methods

A total of 246 compensated CHB patients who underwent liver biopsies, transient elastography, and routine blood tests including complete blood count were included. Dual cut‐offs were determined to exclude or include cirrhosis diagnosis. Performance of stepwise combining routine biomarkers including RPR, FIB‐4, and APRI were statistically analyzed.

Results

The Metavir F0, F1, F2, F3, and F4 were identified in 2.4%, 22.0%, 32.1%, 24.0%, and 19.5% of the eligible patients, respectively. The area under receiver operating characteristics curves for detecting significant fibrosis and cirrhosis were 0.853 and 0.883 for transient elastography; 0.719 and 0.807 for FIB‐4; 0.638 and 0.791 for RPR; 0.720 and 697 for APRI; and 0.618 and 0.760 for mean platelet volume–platelet ratio, respectively. The proportion of patient determined as cirrhosis or non‐cirrhosis was 65.9% by transient elastography, 36.9% by FIB‐4, 30.5% by RPR, and 19.5% by APRI, respectively. These numbers for determining significant fibrosis were 49.6%, 24.2%, 21.5%, and 23.6% in the same order. Detected by stepwise application of FIB‐4, RPR, and APRI, 41.5% and 52.8% of patients could be determined the state of significant fibrosis and cirrhosis, respectively.

Conclusions

In source‐limited settings without transient elastography, stepwise applying FIB‐4, RPR, and APRI could free nearly half of CHB patients from liver biopsies in detecting significant fibrosis and cirrhosis.     

Noninvasive assessment of liver fibrosis in children with chronic hepatitis C: Shear wave elastography and APRI versus liver biopsy

Background and study aimsHepatitis C virus (HCV) is a major cause of chronic hepatitis. Although liver histopathological examination remains the reference standard for liver fibrosis assessment, noninvasive means of assessment such as shear wave elastography (SWE) and aspartate aminotransferase–platelet ratio index (APRI) have been developed to reduce the need for biopsy. We evaluated the efficacy of SWE and APRI versus liver biopsy for liver fibrosis assessment in children with chronic HCV infection.Patients and methodsFibrosis staging was performed in 46 children (35 boys, 11 girls; mean age: 15.52 ± 2.71 years) with liver biopsy-proven chronic HCV infection according to the METAVIR system. SWE was performed within 6 months of liver biopsy. APRI scores were calculated using data collected on the day of biopsy.ResultsEighteen children had no or mild fibrosis (<F2, 39.1%) and 28 had significant fibrosis (≥F2, 60.9%), with a significant difference between the corresponding mean APRI scores (0.43 ± 0.23 vs 1.26 ± 1.24; p = 0.043). The APRI scores exhibited a significant correlation with the METAVIR stage (r = 0.630; p < 0.001). The SWE values were significantly higher in those with significant fibrosis than in those with no or mild fibrosis (10.43 vs 4.26 kPa; p < 0.000). These values exhibited significant correlations with the METAVIR stage and APRI score (r = 0.863 and 0.544, respectively; both p < 0.001). For differentiating significant fibrosis, the sensitivity, specificity and positive and negative predictive values for an APRI cutoff value of 0.62 were 46.43%, 94.4%, 92.9% and 53.1%, respectively, and these values for an SWE cutoff value of 7.6 kPa were 55.88%, 100%, 100% and 44.4%, respectively.ConclusionIn the clinical assessment of children, the APRI score and SWE can help differentiate between no or mild fibrosis and significant fibrosis. The routine use of SWE and APRI may help decrease the number of liver biopsies performed.     

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBV RNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg‐positive and HBeAg‐negative CHB patients. In this study, 85 HBeAg‐positive and 25 HBeAg‐negative patients who have never received antiviral therapy were included. Among HBeAg‐positive patients, HBcrAg was correlated positively with HBsAg (r = 0.564, P < 0.001) and HBV RNA (r = 0.445, P < 0.001), and HBV RNA was also correlated positively with HBsAg (r = 0.323, P = 0.003). Among HBeAg‐negative patients, no significant correlation was observed between HBcrAg, HBsAg and HBV RNA. By multivariable linear regression, HBcrAg (β = ?0.563, P < 0.001), HBsAg (β = ?0.328, P < 0.001) and HBV RNA (β = 0.180, P = 0.003) were all associated with cccDNA levels among HBeAg‐positive patients, but only serum HBcrAg was associated with cccDNA level (β = 0.774, P = 0.000) among HBeAg‐negative patients. HBcrAg was better correlated with cccDNA as compared to HBsAg and HBV RNA, irrespective of HBeAg status. Among HBeAg‐positive patients, though HBcrAg level was influenced by hepatic inflammatory activity and HBV DNA levels, the good correlations of HBcrAg with cccDNA persisted after stratification by inflammatory activity and HBV DNA levels. In conclusion, correlations of serum HBcrAg, HBV RNA and HBsAg levels differ significantly between HBeAg‐positive and HBeAg‐negative patients, but serum HbcrAg correlates with cccDNA levels better than HBV RNA and HBsAg, irrespective of HBeAg status.     

Loss of intrahepatic HBsAg expression predicts sustained response to peginterferon and is reflected by pronounced serum HBsAg decline

There is a lack of knowledge regarding the effect of peginterferon (PEG‐IFN) on the expression of intrahepatic hepatitis B core and surface antigen (HBcAg and HBsAg) in chronic hepatitis B (CHB) and its relation with response to therapy. Fifty‐two HBeAg‐positive and 67 HBeAg‐negative CHB patients with paired liver biopsies taken at baseline and after 1 year of PEG‐IFN therapy were studied. After PEG‐IFN therapy, HBeAg‐negative patients showed a significant reduction in both intrahepatic HBcAg (P = 0.04) and HBsAg expression (P < 0.001). In contrast, a reduction in intrahepatic HBcAg expression was not observed in HBeAg‐positive patients, while a trend in reduction of intrahepatic HBsAg staining was found (P = 0.09). Post‐treatment, 7 (13%) HBeAg‐positive and 9 (14%) HBeAg‐negative patients had no expression of intrahepatic HBsAg. Patients without any intrahepatic HBsAg expression post‐treatment were more likely to achieve a combined response (HBeAg loss with hepatitis B virus (HBV) DNA <2000 IU/mL for HBeAg ‐positive and HBV DNA <2000 IU/mL and normal alanine aminotransferase for HBeAg‐negative CHB): 71% vs 5% for HBeAg‐positive (P < 0.001) and 60% vs 16% for HBeAg‐negative patients (P = 0.004), respectively. Moreover, a more profound decline of serum HBsAg was observed in patients with absence of intrahepatic HBsAg staining (3.1 vs 0.4 log IU/mL, P < 0.001 and 1.7 vs 0.4 log IU/mL, P = 0.005 for HBeAg‐positive and HBeAg‐negative CHB, respectively). In conclusion, PEG‐IFN reduces expression of intrahepatic HBsAg. Loss of HBsAg as assessed by immunohistochemistry from the liver predicts a sustained response and is reflected in a pronounced serum HBsAg decline.     

Aspartate transaminase to platelet ratio index in hepatitis C virus and Schistosomiasis coinfection

AIM: To assess the diagnostic accuracy,of aminotransferase-to-platelet ratio index(APRI) alone and with antischistosomal antibody(Ab) in patients with hepatitis C virus(HCV) and schistosomiasis coinfection. METHODS: This retrospective study included medical records of three hundred and eighty three Egyptianmen patients who had undergone percutaneous liver biopsy between January 2006 to April 2014 in tertiary care hospital in Qatar for diagnosis or monitoring purpose were selected. Data of patients 18 years of age were included in the study. The values of HCV RNA titer and antischistosomal antibody titer were also taken into consideration. Patients were excluded from the study if they had any other concomitant chronic liver disease,including; history of previous antiviral or interferon therapy,immunosuppressive,therapy,chronic hepatitis B infection,human immunodeficiency virus co-infection,autoimmune hepatitis,decompensated liver disease,hepatocellular carcinoma,prior liver transplantation,and if no data about the liver biopsy present. RESULTS: Median age of patients was 46 years. About 7.1% had no fibrosis,whereas 30.4%,37.5%,20.4%,and 4.6% had fibrosis of stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ respectively. In bivariate analysis,APRI score,levels of AST,platelet count and age of patient showed statistically significant association with liver fibrosis(P 0.0001); whereas antischistosomal antibody titer(P = 0.52) and HCV RNA titer(P = 0.79) failed to show a significant association. The respective AUC values for no fibrosis,significant fibrosis,severe fibrosis and cirrhosis of APRI score were 63%,73.2%,81.1% and 88.9% respectively. This showed good sensitivity and specificity of APRI alone for grading of liver fibrosis. But the inclusion of anti-Schistosoma antibody did not improve the prediction of fibrosis stage. CONCLUSION: The study results suggest that noninvasive biochemical markers like APRI are sensitive and specific in diagnosing the degree of fibrosis and cirrhosis in patients with coinfection of HCV and schistosomiasis as compared to biopsy. The addition of antischistosomal Ab to APRI did not improve sensitivity for predicting the degree of cirrhosis.     

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large‐sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)‐positive chronic HBV infection (n = 588), HBeAg‐positive chronic hepatitis B (n = 596), and HBeAg‐negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%‐90% confidence interval: 3.52 log10 IU/mL‐4.99 log10 IU/mL]) in patients with HBeAg‐positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg‐positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg‐negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg‐positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg‐negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.     

Prospective comparison of transient elastography,point shear wave elastography,APRI and FIB‐4 for staging liver fibrosis in chronic viral hepatitis

Ultrasound‐based elastography and serum indexes have been individually validated as noninvasive methods for staging liver fibrosis in chronic viral hepatitis. We aimed to compare the accuracy of transient elastography (TE), shear wave elastography (SWE), aspartate aminotransferase to platelet index (APRI) and Fibrosis‐4 index (FIB‐4) with the METAVIR liver fibrosis staging in viral hepatitis patients. We enrolled 121 treatment‐naïve chronic hepatitis B and C monoinfected patients. All underwent liver biopsy had biochemistry tests and liver stiffness measurements by TE using M and XL probes followed by point SWE performed on the same day. The accuracy of each method for predicting different fibrosis stages was demonstrated as an area under the receiver operating characteristic (AUROC) curves. The AUROCs of TE using M and XL probes, SWE, APRI and FIB‐4 were 0.771, 0.761, 0.700, 0.698 and 0.697, respectively, for significant fibrosis; 0.974, 0.973, 0.929, 0.738 and 0.859, respectively, for advanced fibrosis; and 0.954, 0.949, 0.962, 0.765 and 0.962, respectively, for cirrhosis. TE using the M probe was comparable to the XL probe in detecting all fibrosis stages. TE was superior to SWE for assessing significant fibrosis and advanced fibrosis. For cirrhosis, the performances of TE, SWE and FIB‐4 were similar. APRI was least accurate in liver fibrosis staging. To conclude, for patients with viral hepatitis, TE using either M or XL probe is an effective noninvasive test for assessing liver fibrosis, particularly advanced fibrosis and cirrhosis, while SWE and FIB‐4 possess an excellent accuracy in predicting cirrhosis.