scholarly journals Comparison and Validation of APRI and FIB-4 for Evaluating Liver Fibrosis in Chinese Hepatitis B Virus-infected Patients with Persistently Normal ALT, Mildly and Significantly Elevated ALT

Author(s):  
Shanshan Chen ◽  
Yuhan Gong ◽  
Jie Li ◽  
Xuan Dai ◽  
Yueyue Zhao ◽  
...  

Abstract Background: Many noninvasive models based on serum markers composition are used for the assessment of liver fibrosis, reducing the need for liver biopsy. However, most of the models have rarely been validated in Chinese hepatitis B patients. We aim to evaluate and validate chronic hepatitis B(CHB) patients with normal ALT, mildly and significantly elevated ALT levels.Methods: This single-center retrospective study enrolled 285 patients with CHB who underwent liver biopsy. There were 156 patients in normal ALT group, 85 patients in mildly elevated ALT group, and 44 patients in significantly elevated ALT group. The diagnostic accuracy of APRI and FIB-4 was evaluated by areas under the characteristic curves (AUROC) using the histological assessment of the fibrosis stages of the biopsy specimens as the standards.Results: Among 285 patients with CHB, 156 patients had normal ALT level, of which 65 (41.7%) had significant fibrosis(S2-4). The evaluation of significant fibrosis, AUROC in APRI and FIB-4 were 0.608, 0.634, 0.708 and 0.638, 0.679, 0.734 in normal ALT, mildly and significantly elevated ALT, respectively. The assessment of advanced fibrosis, AUROC in APRI and FIB-4 were 0.636, 0.751, 0.708 and 0.652, 0.763, 0.734 in normal ALT, mildly and significantly elevated ALT groups, respectively. Conclusions: APRI and FIB-4 may not be ideal noninvasive markers for evaluating liver fibrosis in Chinese HBV-infected patients with normal ALT levels. Compared with HBV-infected patients with normal ALT, APRI and FIB-4 had high accuracies in diagnosing liver fibrosis in patients with mildly and significantly elevated ALT.

2005 ◽  
Vol 51 (10) ◽  
pp. 1867-1873 ◽  
Author(s):  
Leon A Adams ◽  
Max Bulsara ◽  
Enrico Rossi ◽  
Bastiaan DeBoer ◽  
David Speers ◽  
...  

Abstract Background: Staging hepatic fibrosis by liver biopsy guides prognosis and treatment of hepatitis C, but is invasive and expensive. We sought to create an algorithm of serum markers that accurately and reliably predict liver fibrosis stage among hepatitis C patients. Methods: Ten biochemical markers were measured at time of liver biopsy in 117 untreated hepatitis C patients (training set). Multivariate logistic regression and ROC curve analyses were used to create a predictive model for significant fibrosis (METAVIR F2, F3, and F4), advanced fibrosis (F3 and F4), and cirrhosis (F4). The model was validated in 104 patients from other institutions. Results: A model (Hepascore) of bilirubin, γ-glutamyltransferase, hyaluronic acid, α2-macroglobulin, age, and sex produced areas under the ROC curves (AUCs) of 0.85, 0.96, and 0.94 for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. In the training set, a score ≥0.5 (range, 0.0–1.0) was 92% specific and 67% sensitive for significant fibrosis, a score <0.5 was 81% specific and 95% sensitive for advanced fibrosis, and a score <0.84 was 84% specific and 71% sensitive for cirrhosis. Among the validation set, the AUC for significant fibrosis, advanced fibrosis, and cirrhosis were 0.82, 0.90, and 0.89, respectively. A score ≥0.5 provided a specificity and sensitivity of 89% and 63% for significant fibrosis, whereas scores <0.5 had 74% specificity and 88% sensitivity for advanced fibrosis. Conclusions: A model of 4 serum markers plus age and sex provides clinically useful information regarding different fibrosis stages among hepatitis C patients.


Author(s):  
Ludmia Taibi ◽  
Anders Boyd ◽  
Nelly Bosselut ◽  
Julie Bottero ◽  
Jérôme Guéchot ◽  
...  

Background Non-invasive methods for assessing liver fibrosis are increasingly used as an alternative to liver biopsy. Recently, a score-based biochemical blood test (Coopscore©) was developed in a cohort of patients chronically infected with hepatitis C virus, showing higher diagnostic performances than Fibrometer®, Fibrotest®, Hepascore® and Fibroscan™. Here, we assess its performance in patients co-infected with the human immunodeficiency virus and hepatitis B virus. Methods Ninety-seven human immunodeficiency virus/hepatitis B virus co-infected patients with liver biopsies were included from a previously described cohort. Histological fibrosis staging using METAVIR criteria was used as the reference. Coopscore©, Fibrotest®, Fibrometer®, Hepascore® and Zeng score were computed and compared with the Coopscore© using the Obuchowski index and area under the receiving operator characteristic curves. Results The distribution of liver fibrosis levels was as follows: F0–F1 ( n = 42), F2 ( n = 25), F3 ( n = 15) and F4 ( n = 15). The Obuchowski index was higher for Coopscore© (0.774) than Fibrometer® (0.668), Hepascore® (0.690) and Zeng scores (0.704) ( P < 0.05), reflecting a better ability to discriminate between fibrosis stages. Similarly, when predicting significant fibrosis (≥F2), the AUROC was significantly greater for the Coopscore© (0.836) than the Hepascore® (0.727) and Zeng scores (0.746), but not for the Fibrotest® (0.778, P = 0.14) or Fibrometer® (0.790, P = 0.19). The Coopscore© did not show a higher capacity than other scores to predict advanced fibrosis (≥F3) or cirrhosis (F4). Conclusions This study supports the diagnostic value of the Coospcore© in fibrosis staging among human immunodeficiency virus/hepatitis B virus co-infected patients, especially to predict significant fibrosis.


2020 ◽  
Vol 7 (7) ◽  
Author(s):  
Romuald Cruchet ◽  
Lorenza N C Dezanet ◽  
Sarah Maylin ◽  
Audrey Gabassi ◽  
Hayette Rougier ◽  
...  

Abstract Background Quantitative hepatitis B core-related antigen (qHBcrAg) or antihepatitis B core antibody (qAnti-HBc) could be useful in monitoring liver fibrosis evolution during chronic hepatitis B virus (HBV) infection, yet it has not been assessed in human immunodeficiency virus (HIV)-HBV-coinfected patients undergoing treatment with tenofovir (TDF). Methods One hundred fifty-four HIV-HBV-infected patients initiating a TDF-containing antiretroviral regimen were prospectively followed. The qHBcrAg and qAnti-HBc and liver fibrosis assessment were collected every 6–12 months during TDF. Hazard ratios (HRs) assessing the association between qHBcrAg/qAnti-HBc and transitions from none/mild/significant fibrosis to advanced fibrosis/cirrhosis (progression) and from advanced fibrosis/cirrhosis to none/mild/significant fibrosis (regression) were estimated using a time-homogeneous Markov model. Results At baseline, advanced liver fibrosis/cirrhosis was observed in 40 (26%) patients. During a median follow-up of 48 months (interquartile range, 31–90), 38 transitions of progression (IR = 7/100 person-years) and 34 transitions of regression (IR = 6/100 person-years) were observed. Baseline levels of qHBcrAg and qAnti-HBc were not associated with liver fibrosis progression (adjusted-HR per log10 U/mL = 1.07, 95% confidence interval [CI] = 0.93–1.24; adjusted-HR per log10 Paul-Ehrlich-Institute [PEI] U/mL = 0.85, 95% CI = 0.70–1.04, respectively) or regression (adjusted-HR per log10 U/mL = 1.17, 95% CI = 0.95–1.46; adjusted-HR per log10 PEI U/mL = 0.97, 95% CI = 0.78–1.22, respectively) after adjusting for age, gender, duration of antiretroviral therapy, protease inhibitor-containing antiretroviral therapy, and CD4+/CD8+ ratio. Nevertheless, changes from the previous visit of qAnti-HBc levels were associated with liver fibrosis regression (adjusted-HR per log10 PEIU/mL change = 5.46, 95% CI = 1.56–19.16). Conclusions Baseline qHBcrAg and qAnti-HBc levels are not associated with liver fibrosis evolution in TDF-treated HIV-HBV coinfected patients. The link between changes in qAnti-HBc levels during follow-up and liver fibrosis regression merits further study.


2006 ◽  
Vol 101 (11) ◽  
pp. 2537-2545 ◽  
Author(s):  
Mehdi Mohamadnejad ◽  
Ghodrat Montazeri ◽  
Atoosa Fazlollahi ◽  
Farhad Zamani ◽  
Jafar Nasiri ◽  
...  

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 239-240
Author(s):  
D H Little ◽  
S Fischer ◽  
S K Fung

Abstract Background Accurate assessment of liver fibrosis is important to identify patients with chronic hepatitis B (CHB) who require antiviral therapy. As liver biopsy is invasive and costly, non-invasive tests of liver fibrosis are increasingly being used. Aims We aimed to evaluate the performance of the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis 4 index (FIB-4), and transient elastography (TE) in predicting fibrosis in patients with CHB. Methods We retrospectively analyzed a prospectively enrolled cohort of consecutive adults with CHB who underwent liver biopsy for routine clinical indications (ALT &gt; ULN and HBV DNA &gt; 2,000 IU/ml) from January 2018 to December 2019. Demographic information, routine biochemistry, HBV serology including HBV DNA, abdominal ultrasound, fibrosis stage by liver biopsy and TE data were collected. Positive predictive values (PPV) and negative predictive values (NPV) were calculated using published cut-off values with liver biopsy as the reference standard. Results Fifty-five patients of Asian ethnicity (mean age 46 years, 65% male) were included. Most patients were HBeAg-negative (67%) and treatment-naïve (80%). Eleven (20%) patients had advanced fibrosis (F3-F4 METAVIR) and 4 (7%) patients had cirrhosis (F4). APRI &lt;0.50 had a NPV of 73% for significant fibrosis (F2-F4) and APRI &gt;1.50 had a PPV of 33% for significant. All 4 patients with cirrhosis were misclassified as having no cirrhosis with an APRI &lt;1. FIB-4 &lt;1.45 had a NPV of 90% for advanced fibrosis (F3-F4). No patient, including 11 patients with advanced fibrosis, had a FIB-4 above the cut-off value to detect advanced fibrosis (&gt;3.25). TE data was available for 38 patients. TE &lt;7.25 kPa had a NPV of 78% for significant fibrosis and TE &gt;12.4 kPa had a PPV of 50% for cirrhosis. Conclusions In Asian patients with CHB and a low prevalence of advanced fibrosis or cirrhosis, APRI, FIB-4, and TE performed well in excluding those with advanced fibrosis but were unable to accurately identify those with significant/advanced fibrosis and cirrhosis. Further studies with larger numbers of CHB patients are needed to confirm our results. Funding Agencies None


Author(s):  
Xiangyi Liu ◽  
Xiaohua Wan ◽  
Zhongwu Li ◽  
Changqing Lin ◽  
Yutao Zhan ◽  
...  

AbstractThis study was performed to quantify the expression of Golgi protein-73 (GP73) in healthy controls and in patients with liver disease, and to evaluate the correlations between GP73 and other serum markers in different liver diseases.Serum GP73 was measured in 478 healthy controls and 296 patients with different types of liver disease. Quantitative hepatitis B virus (HBV) DNA was determined in two chronic hepatitis B (CHB) groups. Other serum liver fibrosis markers were measured in the liver fibrosis group and α-fetoprotein (AFP) was measured in hepatocellular carcinoma (HCC) group. The correlations between GP73 and these markers were evaluated.The GP73 value in hepatitis B e antigen (HBeAg)-positive CHB group, HBeAg-negative CHB group, liver fibrosis group and HCC group was significantly higher (p<0.001) than that in healthy controls. GP73 showed significant correlation with other markers in the liver fibrosis group and with AFP in the HCC group.Compared with healthy controls, GP73 in patients with liver disease was significantly increased. With the progression of liver disease, GP73 showed a significantly increasing trend. These results suggest that GP73 might be used as a serum marker for the diagnosis of liver diseases and for monitoring disease progression.


2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Tobias Flecken ◽  
Marie-Anne Meier ◽  
Peter Skewes-Cox ◽  
David T. Barkan ◽  
Markus H. Heim ◽  
...  

ABSTRACTCovalently closed circular DNA (cccDNA) forms the basis for replication and persistence of hepatitis B virus (HBV) in the chronically infected liver. We have previously shown that viral transcription is subject to regulation by posttranslational modifications (PTMs) of histone proteins bound to cccDNA through analysis ofde novoHBV-infected cell lines. We now report the successful adaptation of this chromatin immunoprecipitation sequencing (ChIPseq) approach for analysis of fine-needle patient liver biopsy specimens to investigate the role of histone PTMs in chronically HBV-infected patients. Using 18 specimens from patients in different stages of chronic HBV infection, our work shows that the profile of histone PTMs in chronic infection is more nuanced than previously observed inin vitromodels of acute infection. In line with our previous findings, we find that the majority of HBV-derived sequences are associated with the activating histone PTM H3K4me3. However, we show a striking interpatient variability of its deposition in this patient cohort correlated with viral transcription and patient HBV early antigen (HBeAg) status. Unexpectedly, we detected deposition of the classical inhibitory histone PTM H3K9me3 on HBV-DNA in around half of the patient biopsy specimens, which could not be linked to reduced levels of viral transcripts. Our results show that currentin vitromodels are unable to fully recapitulate the complex epigenetic landscape of chronic HBV infection observedin vivoand demonstrate that fine-needle liver biopsy specimens can provide sufficient material to further investigate the interaction of viral and host proteins on HBV-DNA.IMPORTANCEHepatitis B virus (HBV) is a major global health concern, chronically infecting millions of patients and contributing to a rising burden of liver disease. The viral genome forms the basis for chronic infection and has been shown to be subject to regulation by epigenetic mechanisms, such as posttranslational modification of histone proteins. Here, we confirm and expand on previous results by adapting a high-resolution technique for analysis of histone modifications for use with patient-derived fine-needle liver biopsy specimens. Our work highlights that the situationin vivois more complex than predicted by currentin vitromodels, for example, by suggesting a novel, noncanonical role of the histone modification H3K9me3 in the HBV life cycle. Importantly, enabling the use of fine-needle liver biopsy specimens for such high-resolution analyses may facilitate further research into the epigenetic regulation of the HBV genome.


Hepatology ◽  
1991 ◽  
Vol 13 (5) ◽  
pp. 838-844 ◽  
Author(s):  
Daniel R. Ciocca ◽  
Arturo D. Jorge ◽  
Oliver Jorge ◽  
Carlos Milutín ◽  
Roberto Hosokawa ◽  
...  

2021 ◽  
Author(s):  
Zhiqiang Xu ◽  
Jinfang Zhao ◽  
Jiaye Liu ◽  
Yi Dong ◽  
Fuchuan Wang ◽  
...  

Abstract Background: This study aimed to investigate the effectiveness of transient elastography (TE) by comparing liver biopsies to assess liver fibrosis in children with chronic hepatitis B (CHB). Methods: A total of 157 CHB children aged 0 - 6 years in China were enrolled in this single-center prospective study. All patients underwent liver stiffness measurement (LSM) by TE and liver biopsy at an interval of less than a week. Results: LSM, aspartate aminotransferase (AST)-platelet ratio index (APRI), and fibrosis-4 score (FIB-4) positively correlated with activity grade and fibrosis stage in children with CHB. The area under receiver operating characteristic curves (AUCs) of LSM for identifying significant (F ≥ 2) and advanced fibrosis (F ≥ 3) were 0.732 and 0.94, the cut-off values were 5.6 kPa and 6.9 kPa, specificity of 75.7% and 91.5%, and sensitivity of 67.4% and 81.3%, respectively. Compared to LSM, the overall diagnostic performance of APRI and FIB-4 for significant and advanced fibrosis was suboptimal with low AUCs and sensitivity. Since LSM, platelet, and Log10HBsAg were independent factors with the fibrosis stages (F < 2 and F ≥ 2) on the liver biopsy, the LPS index was formulated to predict F ≥ 2 by combining LSM, platelet, and Log10HBsAg. The AUC of LPS for F ≥ 2 was increased to 0.792, which was higher than that of LSM (0.732, p < 0.05), with an improved sensitivity (76.6% vs 67.4%).Conclusions: TE represents a promising technology for the diagnosis of advanced fibrosis in CHB children aged 0 - 6 years.


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