Performance of noninvasive tools for identification of minimal liver fibrosis in patients with hepatitis B virus infection.
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ABSTRACT: Background
Various noninvasive liver fibrosis assessment tools are available. Here, we evaluated the performance of the asparagine aminotransferase-to-platelet ratio index (APRI), the fibrosis-4 index (FIB-4), transient elastography (TE), and the globulin-platelet (GP) ratio for identifying liver fibrosis in patients with hepatitis B virus (HBV) infection.Methods
A total of 146 patients were assessed using TE, FIB-4, APRI, the GP ratio, and liver biopsy. Three patient grouping methods were applied: any fibrosis (AF; F0 vs. F1/2/3/4); moderate fibrosis (MF; F0/1 vs. F2/3/4); and severe fibrosis (SF; F0/1/2 vs. F3/4). Receiver operating characteristic (ROC) curve analysis, univariate analyses, and multivariate logistic regression were conducted.Results
Regardless of patient-grouping method, the area under the curve (AUC) of TE and the GP ratio were similar. Using the AF grouping method, the GP ratio showed superior performance compared with APRI and FIB-4: the AUCs for the GP ratio, TE, APRI, and FIB-4 were 0.76, 0.75, 0.70, and 0.66, respectively. Using the MF grouping method, the GP ratio also showed superior performance compared with APRI and FIB-4: the AUCs for the GP ratio, TE, APRI, and FIB-4 were 0.66, 0.68, 0.57, and 0.53, respectively. Using the SF grouping method, the AUCs for the GP ratio, TE, APRI, and FIB-4 were not significantly different.Conclusion
Compared with FIB-4 and APRI, the GP ratio had higher accuracy for identifying liver fibrosis, especially early-stage fibrosis, in patients with HBV infection.
SUBMITTER: Zhang H
PROVIDER: S-EPMC8418491 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background & aimsLiver fibrosis is a significant concern for patients with hepatitis C virus/human immunodeficiency virus co-infection. Fibrosis staging by biopsy is accurate, but costly and invasive. Several fibrosis prediction models using noninvasive biomarkers have been developed but are suboptimal in co-infected patients. We compared results from different staging models and ordinal regression with biopsy data.MethodsData from the Adult Acquired Immune Deficiency Syndrome Clinical Trials Group protocol A5178 were used to evaluate 5 models of fibrosis staging; areas under receiver-operator characteristic curves (AUROC) were assessed. Individual covariates were assessed with univariable regression and then entered into an ordinal logistic regression model from which a stage-wise index was developed.ResultsData from 173 patients were evaluated; 85% were on antiretroviral therapy, 31.2% had severe fibrosis (F3/F4), and 14% had cirrhosis (F4). Differences in CD4+ cell and platelets counts and international normalized ratio values were observed between those with and without F3/F4. Among existing models, the FIB-4 index ([age x AST])/[platelet count x (ALT)(1/2)]) performed best, with 88% specificity for F4 and greater than 86% negative predictive values for F3/F4, although AUROC values were low (0.56 +/- 0.03 for F3/F4). By using patients' demographic, clinical, and laboratory data, the ordinal regression model outperformed others, with an AUROC of 0.85 (standard error, 0.03) for predicting stage F3/F4 and 0.89 (standard error, 0.05) for stage 3 alone.ConclusionsCurrent noninvasive methods of fibrosis assessment have poor discriminatory capacity in hepatitis C virus/human immunodeficiency virus co-infected patients. Ordinal regression analysis outperformed other noninvasive fibrosis prediction models. Longitudinal studies with paired biopsies will assist in refining the Ordinal Regression Index.
| S-EPMC3159915 | biostudies-literature
Project description:Knowing the rate of liver fibrosis progression in hepatitis C virus (HCV)-infected persons can help inform patients and providers (clinicians, medical institutions or organizations, and third-party payers) in making treatment decisions.To determine the rate and factors associated with liver fibrosis progression and hepatic decompensation in persons after acquiring HCV infection.Secondary data analysis of persons in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a national Veterans Affairs (VA) database, between 2002 and 2012. Among 610?514 persons in ERCHIVES (half were HCV positive), we identified those with an initial negative and subsequent positive test result for HCV antibody and positive HCV RNA test result (HCV+). Controls had 2 negative HCV antibody test results (HCV-) in a comparable time frame and were matched 1:1 on age (in 5-year blocks), race, and sex. We excluded persons with human immunodeficiency virus, hepatitis B, less than 24 months of follow-up, hepatocellular carcinoma, and cirrhosis at baseline.Progression of liver fibrosis as estimated by the Fibrosis-4 (FIB-4) index; development of cirrhosis, defined by a FIB-4 score greater than 3.5; and development of hepatic decompensation.The evaluable data set consisted of 1840 persons who were HCV+ and 1840 HCV- controls. The HCV+ persons were younger and had a lower mean (SD) body mass index (27.39 [5.51] vs 29.49 [6.16]; P?<?.001), a higher prevalence of alcohol and drug abuse and dependence diagnoses, and higher serum aminotransferase levels, but had a lower prevalence of diabetes and hypertension. Fibrosis progression started early after infection among HCV+ persons and tapered off after 5 years. A total of 452 cirrhosis and 85 hepatic decompensation events were recorded. After 10 years of follow-up, HCV+ persons were more likely to have a diagnosis of cirrhosis compared with HCV- controls (18.4% vs 6.1%). Nine years after diagnosis of cirrhosis, hepatic decompensation events were uncommon but had a higher rate in the HCV+ group (1.79% vs 0.33%).Persons who seroconverted for HCV have a more rapid progression of liver fibrosis and accelerated time to development of cirrhosis after seroconversion compared with HCV- controls. Fibrosis progression occurs early after infection; however, hepatic decompensation is uncommon after diagnosis of cirrhosis.
| S-EPMC5017246 | biostudies-literature
Project description:ObjectiveThe objective was to develop a multiparametric CT algorithm to stage liver fibrosis in patients with chronic hepatitis C virus (HCV) infection.Materials and methodsAbdominal CT and laboratory measures in 469 patients with HCV (340 men and 129 women; mean age, 50.1 years) were compared against the histopathologic Metavir fibrosis reference standard (F0, n = 49 patients; F1, n = 69 patients; F2, n = 102 patients; F3, n = 76 patients; F4, n = 173 patients). From the initial candidate pool, nine CT and two laboratory measures were included in the final assessment (CT-based features: hepatosplenic volumetrics, texture features, liver surface nodularity [LSN] score, and linear CT measurements; laboratory-based measures: Fibrosis-4 [FIB-4] score and aspartate transaminase-to-platelets ratio index [APRI]). Univariate logistic regression and multivariate logistic regression were performed with ROC analysis, proportional odds modeling, and probabilities.ResultsROC AUC values for the model combining all 11 parameters for discriminating significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (F4) were 0.928, 0.956, and 0.972, respectively. For all nine CT-based parameters, these values were 0.905, 0.936, and 0.972, respectively. Using more simplified panels of two, three, or four parameters yielded good diagnostic performance; for example, a two-parameter model combining only LSN score with FIB-4 score had ROC AUC values of 0.886, 0.915, and 0.932, for significant fibrosis, advanced fibrosis, and cirrhosis. The LSN score performed best in the univariate analysis.ConclusionMultiparametric CT assessment of HCV-related liver fibrosis further improves performance over the performance of individual parameters. An abbreviated panel of LSN score and FIB-4 score approached the diagnostic performance of more exhaustive panels. Results of the abbreviated panel compare favorably with elastography, but this approach has the advantage of retrospective assessment using preexisting data without planning.
| S-EPMC6945751 | biostudies-literature
Project description:Assessment of liver fibrosis is important in determining prognosis, disease progression and need for treatment in patients with chronic hepatitis B (CHB). Limitations to the use of liver biopsy in assessing fibrosis are well recognized, and noninvasive tests are being increasingly evaluated including transient elastography (TE) and serum markers such as the Enhanced Liver Fibrosis (ELF) test. We assessed performance of ELF and TE in detecting liver fibrosis with reference to liver histology in a cohort of patients with CHB (n = 182), and compared the performance of these modalities. Median age was 46 and mean AST 70 IU/L. Cirrhosis was reported in 20% of liver biopsies. Both modalities performed well in assessing fibrosis at all stages. Area under receiver operator characteristic (AUROC) curves for detecting METAVIR fibrosis stages F ? 1, F ? 2, F ? 3 and F4 were 0.77, 0.82, 0.80 and 0.83 for ELF and 0.86, 0.86, 0.90 and 0.95 for TE. TE performed significantly better in the assessment of severe fibrosis (AUROC 0.80 for ELF and 0.90 for TE, P < 0.01) and cirrhosis (0.83 for ELF and 0.95 for TE, P < 0.01). This study demonstrates that ELF has good performance in detection of liver fibrosis in patients with CHB, and when compared, TE performs better in detection of severe fibrosis/cirrhosis.
| S-EPMC4298014 | biostudies-literature
Project description:BACKGROUND: Chronic infection with hepatitis C virus (HCV) is a risk factor for liver diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. HCV genetic heterogeneity was hypothesized to be associated with severity of liver disease. However, no reliable viral markers predicting disease severity have been identified. Here, we report the utility of sequences from 3 HCV 1b genomic regions, Core, NS3 and NS5b, to identify viral genetic markers associated with fast and slow rate of fibrosis progression (RFP) among patients with and without liver transplantation (n = 42). METHODS: A correlation-based feature selection (CFS) method was used to detect and identify RFP-relevant viral markers. Machine-learning techniques, linear projection (LP) and Bayesian Networks (BN), were used to assess and identify associations between the HCV sequences and RFP. RESULTS: Both clustering of HCV sequences in LP graphs using physicochemical properties of nucleotides and BN analysis using polymorphic sites showed similarities among HCV variants sampled from patients with a similar RFP, while distinct HCV genetic properties were found associated with fast or slow RFP. Several RFP-relevant HCV sites were identified. Computational models parameterized using the identified sites accurately associated HCV strains with RFP in 70/30 split cross-validation (90-95% accuracy) and in validation tests (85-90% accuracy). Validation tests of the models constructed for patients with or without liver transplantation suggest that the RFP-relevant genetic markers identified in the HCV Core, NS3 and NS5b genomic regions may be useful for the prediction of RFP regardless of transplant status of patients. CONCLUSIONS: The apparent strong genetic association to RFP suggests that HCV genetic heterogeneity has a quantifiable effect on severity of liver disease, thus presenting opportunity for developing genetic assays for measuring virulence of HCV strains in clinical and public health settings.
| S-EPMC4120150 | biostudies-literature
Project description:BackgroundChronic hepatitis C is a major cause of liver fibrosis and cirrhosis. It is generally accepted that inflammation that occurs in response to hepatocyte infection by the hepatitis C virus (HCV) is the main mechanism that triggers myofibroblast differentiation and stimulation in chronic hepatitis C. The aim of this study was to determine if HCV might infect human liver myofibroblasts (HLMF) and directly stimulate their fibrogenic activities.MethodsWe evaluated the expression of the viral entry receptors, levels of HCV-RNA and HCV-protein and the expression of fibrosis markers in HLMF by using quantitative PCR, western blot and immunofluorescence analyses. Pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) were used to study the ability of HLMF to support viral entry, replication and fibrosis induction.ResultsWe showed that HLMF expressed all known molecules of the HCV receptor complex, i.e. CD81, LDL-R, scavenger receptor-BI, claudin-1 and occludin. These cells were also permissive to HCVpp entry. Inoculation with HCVcc caused short-term infection of these cells, as shown by their content in positive- and negative-strand HCV RNA, in core and NS3 viral proteins, and by their release of core protein levels in the culture supernatants. HCV infection stimulated myofibroblastic differentiation, proliferation and collagen production in these cells. In addition, evidence of in vivo infection was provided by the detection of positive- and negative-strand HCV RNA in preparations of HLMF obtained from HCV-infected patients.ConclusionThese findings indicate that HCV infection of HLMF can occur and trigger extracellular matrix overproduction, thereby contributing to the development of HCV-related liver fibrosis.
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Project description:OBJECTIVE:To examine the accuracy of noninvasive inflammatory markers in predicting liver fibrosis stage in patients with autoimmune hepatitis (AIH). PATIENTS AND METHODS:We enrolled 55 patients with AIH and 60 healthy controls in this study, and divided them into three groups: F0 (control); F1-F3 (noncirrhotic fibrosis); and F4 (cirrhosis). The following markers were analyzed for all participants: lymphocyte-to-neutrophil ratio (LNR); lymphocyte-to-platelet ratio (LPR); lymphocyte-to-monocyte ratio (LMR); immunoglobulin-to-platelet ratio (IGPR); aminotransferase-to-platelet ratio index (APRI); aspartate aminotransferase-to-alanine aminotransferase ratio (AAR); and fibrosis-4 score (FIB-4). The predictive accuracy of these noninvasive markers was assessed using area under the receiver operating characteristic curve. Multivariate ordinal logistic regression models were used to analyze associations between the noninvasive markers and liver fibrosis stage. RESULTS:AAR, LPR, LMR, IGPR, APRI, and FIB-4 were linked to liver fibrosis-stage (P < 0.05), with correlation indices of - 0.219, 0.258, - 0.149, 0.647, 0.841, and 0.704, respectively, but not LNR (P = 0.093). area under the receiver operating characteristic curves of LPR, IGPR, AAR, LMR, APRI, and FIB-4 for detecting cirrhosis (F4 vs. F0-F3) were 0.936 (95% confidence interval: 0.870-1.000, P < 0.001), 0.939 (0.875-1.000, P < 0.001), 0.528 (0.319-0.738, P = 0.768), 0.555 (0.409-0.700, P = 0.568), 0.798 (0.694-0.902, P = 0.002), and 0.881 (0.796-0.967, P < 0.001). Our multivariate ordinal regression analysis showed that LPR and IGPR were associated independently with liver fibrosis stage, with a coefficient of 0.385 (95% confidence interval: 0.103-0.667, P = 0.007) and 14.903 (2.091-27.786, P = 0.023), respectively. CONCLUSION:LPR and IGPR were associated independently with liver fibrosis stage in treatment-naive AIH, and were superior to APRI and FIB-4 in detecting cirrhosis.
| S-EPMC7333545 | biostudies-literature
Project description:Background: In more than 90% of chronic viral hepatitis C (HCV) patients treated with direct-acting antiviral agents (DAAs), a sustained viral response (SVR) was observed. Unfortunately, there are subgroups of subjects who display enduring liver fibrosis and are at high risk of developing hepatocellular carcinoma (HCC). Thus, liver fibrosis evaluation during the follow-up of these patients plays a pivotal role. The gold standard to evaluate hepatic fibrosis is liver biopsy, which is an invasive procedure. Imaging techniques and serum biomarkers have been proposed as safer and cheaper procedures. Objectives: In this study, we evaluated the concordance of transient elastography (TE) with ELF score ( enhanced liver fibrosis) in a cohort of patients with HCV before and after direct-acting antiviral (DAAs) treatment. ELF score has been validated in other chronic liver diseases; the evidence is not available in HCV patients treated with DAAs. Study design: We prospectively recruited all consecutive HCV patient candidates for DAAs therapy at the University of Naples "Federico II" between April 2015 and July 2016. TE and ELF scores were assessed at baseline, at SVR24, and at SVR48. Results: One-hundred-nineteen patients were treated with DAAs, and 94.1% of them reached SVR. A total of 55.5% of patients were males with a mean age of 64.7 ± 9.6 years. TE results revealed that 12 patients (10%) had F1-2 mild/moderate fibrosis, and 107 (90%) had F3-4 advanced fibrosis. At baseline, SVR24, and SVR48, the concordance between ELF test and TE was poor: 0.11 (p = 0.086), 0.15 (p = 0.124), and 0.034 (p = 0.002), respectively. However, at SVR24 and SVR48, both methods showed a significant amelioration of liver fibrosis compared to baseline (p < 0.001). In addition, both ELF index and TE were significantly associated with portal hypertension at baseline, but not with varices and ascites. Conclusions: Our findings suggested that ELF test could predict changes in liver fibrosis, independently of TE. In case of TE unavailability, ELF score could represent an appropriate tool. Notably, in the context of the COVID-19 pandemic, ELF testing should be encouraged to reduce unnecessary access to the hospital and prolonged physical contact.
| S-EPMC9428144 | biostudies-literature
Project description:AimTo analyze the association of the CD36 polymorphism (rs1761667) with dietary intake and liver fibrosis (LF) in chronic hepatitis C (CHC) patients.MethodsIn this study, 73 patients with CHC were recruited. The CD36 genotype (G > A) was determined by a TaqMan real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography (Fibroscan(®)) and APRI score was classified as mild LF (F1-F2) and advanced LF (F3-F4).ResultsOverall, the CD36 genotypic frequencies were AA (30.1%), AG (54.8%), and GG (15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase (AST) serum values were higher in AA genotype carriers compared to non-AA carriers (91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST (β = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG (OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes (OR = 3.52, 95%CI: 1.18-10.45, P = 0.02).ConclusionThis study suggests that the CD36 (rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients.
| S-EPMC5026998 | biostudies-literature
Project description:Background/aimsTo investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomarkers for differentiating S0-S2 (early fibrosis) from S3-S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection.MethodsOne hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative polymerase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0-S2 from S3-S4.ResultsSerum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis progressed from S0-S2 to S3-S4 (p<0.05), but not miR-16. The multivariate logistic regression analysis identified a panel of three miRNAs and platelets that were associated with a high diagnostic accuracy in discriminating S0-S2 from S3-S4, with an area under the curve of 0.936.ConclusionsThe levels of the studied miRNAs, with the exception of miR-16, varied with fibrosis progression. A panel was identified that was capable of discriminating S0-S2 from S3-S4, indicating that serum miRNA levels could serve as a potential noninvasive biomarker of fibrosis progression.
| S-EPMC5669603 | biostudies-literature