Dataset Information

Identification and Validation of Novel Serum Autoantibodies Biomarkers for Staging Liver Fibrosis in Patients With Chronic Hepatitis B.

ABSTRACT: Aim: Liver fibrosis monitoring is essential in patients with chronic hepatitis B (CHB). However, less robust, noninvasive diagnostic methods for staging liver fibrosis, other than liver biopsy, are available. Our previous study demonstrated a panel of cellular proteins recognized by autoantibodies that may have potential value in discrimination of CHB and liver cirrhosis. We aim to assess the diagnostic value of these serum autoantibodies for staging liver fibrosis. Methods: Candidate autoantigens were screened and assessed by microarray analysis in 96 healthy controls and 227 CHB patients with pre-treatment biopsy-proven METAVIR fibrosis score, comprising 69, 115, and 43 cases with S0-1, S2-3, and S4 stages, respectively. Autoantibodies with potential diagnostic value for staging liver fibrosis were verified by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristic curve was conducted to evaluate autoantibody performance. Results: Microarray analysis identified autoantigens CENPF, ACY1, HSPA6, and ENO1 with potential diagnostic value for liver fibrosis staging, among which CENPF and ACY1 were validated using ELISA. CENPF and ACY1 autoantibodies had area under the curve values of 0.746 and 0.685, 58.14 and 74.42% sensitivity, and 88.41 and 60.87% specificity, respectively, for discriminating liver fibrosis stages S4 and S0-1. The prevalence of CENPF and ACY1 autoantibodies was not correlated with age, sex or level of inflammation. Conclusions: Autoimmune responses may be elicited during progression of liver fibrosis, and serum autoantibodies may be a valuable biomarker for staging liver fibrosis deserving of further study.

SUBMITTER: Qi S

PROVIDER: S-EPMC8764302 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Chronic hepatitis B (CHB) virus continues to be a leading cause of morbidity and mortality worldwide. The diagnosis of liver fibrosis has a key role in selecting patients with CHB for antiviral treatment. However, serum biomarkers demonstrate limited diagnostic utility. The present study aimed to compare the performances of fibrosis biomarkers for diagnosing significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB and to identify the most appropriate biomarker for these patients. The current study included 96 antiviral-naïve patients with CHB who underwent liver biopsy. METAVIR scoring system was used to assess liver fibrosis and necroinflammation. The diagnostic performances were evaluated of the platelet (PLT) count; the levels of hyaluronan, serum 7S domain of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer (M2BPGi) and N-terminal type III collagen propeptide (Pro-C3); the fibrosis index based on four factors; the aspartate aminotransferase-to-platelet ratio index; and enhanced liver fibrosis score for identifying significant liver fibrosis [?fibrosis stage 2 (F2)]. All fibrosis biomarkers, except the Pro-C3 level, correlated with the fibrosis stage. M2BPGi was better than other biomarkers for diagnosing ?F2, with the highest area under the curve of 0.902. M2BPGi demonstrated a higher diagnostic accuracy for significant fibrosis than mild/severe fibrosis or cirrhosis. However, no significant correlation was observed between the M2BPGi level and fibrosis stage in patients with CHB having significant liver necroinflammation defined as ? necroinflammatory activity 2. The M2BPGi level and PLT count were exclusively correlated with the fibrosis stage in 73 patients without significant liver necroinflammation. M2BPGi demonstrated the highest diagnostic performance for significant fibrosis in patients having significant liver fibrosis with no significant liver necroinflammation. In conclusion, the M2BPGi level can accurately diagnose significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB.

Project description:Chronic hepatitis B virus (CHB) infection is one of the primary risk factors associated with the development of hepatocellular carcinoma (HCC). Despite having been extensively studied, diagnosing early-stage HCC remains challenging, and diagnosed patients have a poor (3-5%) survival rate. Identifying new approaches to detect changes in the serum metabolic profiles of patients with CHB and liver cirrhosis (LC) may provide a valuable approach to better detect HCC at an early stage when it is still amenable to treatment, thereby improving patient prognosis and survival. In the present study, we, therefore, employed a liquid chromatography-mass spectrometry (LC-MS)-based approach to evaluate the serum metabolic profiles of 30 CHB patients, 29 LC patients, and 30 HCC patients. We then employed appropriate statistical methods to identify those metabolites that were best able to distinguish HCC cases from LC and CHB controls. A mass-based database was then used to putatively identify these metabolites. We then confirmed the identities of a subset of these metabolites through comparisons with the MS/MS fragmentation patterns and retention times of reference standards. The serum samples were then reanalyzed to quantify the levels of these selected metabolites and of other metabolites that have previously been identified as potential HCC biomarkers. Through this approach, we observed clear differences in the metabolite profiles of the CHB, LC, and HCC patient groups in both positive- and negative-ion modes. We found that the levels of taurodeoxy cholic acid (TCA) and 1,2-diacyl-3-β-d-galactosyl-sn-glycerol rose with the progression from CHB to LC to HCC, whereas levels of 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid were gradually reduced with liver disease progression in these groups. The ROC analysis showed that taurodeoxy cholic acid (TCA), 1,2-diacyl-3-β-d-galactosyl-sn-glycerol, 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid had a diagnosis performance with liver disease progression. These four metabolites have a significant correlation with alpha fetal protein (AFP) level and age. Our results highlight novel metabolic biomarkers that have the potential to be used for differentiating between CHB, LC, and HCC patients, thereby facilitating the identification and treatment of patients with early-stage HCC.

Project description:BackgroundNon-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs.AimTo clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir.MethodsThis prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls.ResultsLevel of HBcrAg correlated negatively with liver fibrosis staging (γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively.ConclusionHBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.

Dataset Information

Identification and Validation of Novel Serum Autoantibodies Biomarkers for Staging Liver Fibrosis in Patients With Chronic Hepatitis B.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets