Biomarkers for primary biliary cholangitis: current perspectives

Kouroumalis, Elias; Samonakis, Demetrius; Voumvouraki, Argyro

doi:10.2147/hmer.s135337

Cited by 17 publications

(13 citation statements)

References 118 publications

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“…The co-localization of Sp100 and PML in nuclear dots suggests association of both proteins in multi-subunit complexes. ANAs are a relevant tool for diagnosis of PBC, especially in AMA-negative patients, and their high specificity for PBC has been confirmed in several reports [ 22 , 28 , 29 ]. The existence of anti-Sp100 antibodies in PBC patients was related with a negative course of the disease [ 8 ].…”

Section: Introductionmentioning

confidence: 84%

Analysis of Autoantibodies against Promyelocytic Leukemia Nuclear Body Components and Biochemical Parameters in Sera of Patients with Primary Biliary Cholangitis

et al. 2021

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Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by immune-mediated destruction of intrahepatic bile ducts and the presence of specific antibodies. The aim of the study was to examine the diagnostic significance of antibodies against promyelocytic leukemia nuclear body (PML NB) components such as Sp100, Sp140, and PML in a cohort of PBC patients and compare the results with biochemical and histological parameters. Serum samples were collected from 93 PBC patients. Anti-Sp100 and anti-PML antibodies were assessed using commercially available kits, anti-Sp140 using developed “in-house” ELISA test. Anti-Sp140, anti-Sp100, and anti-PML antibodies were present in 25 (27%), 37 (40%), and 29 (31%) PBC patients, respectively. Anti-PML NB positive patients also showed increased concentration of bilirubin and alkaline phosphatase (p < 0.05). In the group with the presence of at least two types of these antibodies, more frequent deaths or transplantations were observed. A correlation between the presence of antibodies and histological grade (OR = 2.55 p = 0.039) was established. Patients with bilirubin > 1.1 mg/dL at the time of diagnosis had a significantly shorter time of survival than patients with bilirubin ≤ 1.1 mg/dL (HR 5.7; 95% C.I., 2.7, 12.3; p < 0.001). Our data confirm very high specificity of anti-PML NB antibodies, which can expand the laboratory diagnostic capabilities of PBC. We found an association between positive reactivity of autoantibodies directed against components of PML nuclear bodies and higher concentrations of bilirubin and alkaline phosphatase, but the main prognostic marker of survival remains serum bilirubin.

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Section: Introductionmentioning

confidence: 84%

Analysis of Autoantibodies against Promyelocytic Leukemia Nuclear Body Components and Biochemical Parameters in Sera of Patients with Primary Biliary Cholangitis

et al. 2021

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“…However, we found that these scores could not determine early or advanced stage fibrosis. [ 5 , 22 ] Among the studies, sample size, distribution differences for patients according to the fibrosis stage, and variations in the general patient characteristics may affect the diagnostic performance of these non-invasive indicators.…”

Section: Discussionmentioning

confidence: 99%

“…The aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis index based on four factors (Fib-4), and RDW-to-platelet ratio (RPR) are models that were proposed to detect the fibrosis stage in PBC patients. [ 5 ] In addition, there are models that have no literature data in PBC but that were reported to have a better diagnostic performance in chronic hepatitis B than APRI and Fib-4 scores. One of these models is the S-Index, which is calculated using gamma-glutamyltransferase (GGT) and albumin levels and the platelet count.…”

Section: Introductionmentioning

confidence: 99%

Can simple non-invasive fibrosis models determine prognostic indicators (fibrosis and treatment response) of primary biliary cholangitis?

et al. 2021

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Objective: The fibrosis stage during diagnosis and the response to ursodeoxycholic acid in the 1 st year of treatment are considered to be prognostic indicators in primary biliary cholangitis (PBC). Determining these indicators with non-invasive models can enable the risk of liver failure to be monitored with continuous variables from the moment of diagnosis. The aim of this study was to evaluate the diagnostic performance of non-invasive models for determining the prognostic indicators in patients with PBC. Materials and Methods: Data from patients with PBC were screened retrospectively. Patients were divided into early (≤2) and advanced (≥3) fibrosis groups. In addition, treatment response status according to the Paris-II criteria and liver failure risk (LFR) according to the UK-PBC score were determined. The S-Index consisting of gamma-glutamyltransferase (GGT), platelets (PLT), and albumin, (S-index: 1000×GGT÷[PLT×Albumın 2 ]), other non-invasive models were calculated. The diagnostic effectiveness of non-invasive indicators to determine the fibrosis stage, response to treatment, and low LFR was analyzed. Results: Fifty-three patients were included in the study. The overall mean age at diagnosis was 49.6±13.6 years and 86.8% of the patients ( n =46) were female. The S-Index was able to determine fibrosis stage, treatment responded, and patients with low LFR (AUC: 0.747, 0.823, and 0.752; p =0.006, <0.001, and 0.0007, respectively). Furthermore, S-Index found to superior to other non-invasive indicators in terms diagnosis of prognostic indicators of PBC. Conclusion: S-index is a practical and inexpensive non-invasive model that can identify liver fibrosis and treatment response in patients with PBC. It can be used as a continuous variable prognostic model in PBC.

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“…(2) Regardless of the differences, both PBC and PSC are progressive diseases and orthotopic liver transplantation (OLT) is eventually required in many patients. (3,4) Despite some recent progress, PSC and PBC still lack reliable noninvasive prognostic biomarkers, (5) hampering the prediction of disease outcomes and assessment of the effect of therapy. (6) To address this unmet need, we have utilized an assay designed to detect liver-speci c circulating cell-free DNA (cfDNA) in plasma as a potential prognostic biomarker for PBC and PSC.…”

Section: Introductionmentioning

confidence: 99%

Liquid Biopsy in Cholestatic Liver Disease Using Hepatocyte-Specific Methylation Markers

Punia

Juran

Ali

et al. 2021

Preprint

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Background: Quantification of circulating organ-specific cell-free DNA (cfDNA) provides a sensitive measure of ongoing cell death that could benefit evaluation of the cholestatic liver diseases primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), which lack reliable non-invasive biomarkers. Our goal in this pilot study was to determine whether liver-specific cfDNA levels are increased in PBC and PSC patients relative to controls and in advanced versus early disease, to evaluate their potential as novel disease biomarkers.Methods: Peripheral blood derived bisulfite-treated DNA was PCR amplified from patients with PBC (n=48), PSC (n=48) and controls (n=96) to evaluate methylation status at 16 CpG sites reported to be specifically unmethylated in liver tissue near the genes IGF2R, ITIH4 and VTN. Amplicons were used to prepare paired end libraries which were sequenced on a MiSeq sequencer. Trimmed reads were aligned and used to determine unmethylation ratios and to calculate concentration of liver-specific cfDNA. Comparisons between groups were performed using the two-tailed Mann-Whitney Test and relationships between variables were evaluated using Pearson’s Correlation. Results: Levels of liver-specific cfDNA, as measured at the 3 genetic loci, were increased in PBC and PSC patients relative to controls and in late-stage relative to early-stage patients. As well, cfDNA levels were correlated with levels of alkaline phosphatase, a commonly used biochemical test to evaluate disease severity in liver disease, in patients, but not in controls. Conclusions: cfDNA offers promise as a non-invasive liquid-biopsy to evaluate liver-specific cell-death in patients with cholestatic liver diseases.

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Biomarkers for primary biliary cholangitis: current perspectives

Cited by 17 publications

References 118 publications

Analysis of Autoantibodies against Promyelocytic Leukemia Nuclear Body Components and Biochemical Parameters in Sera of Patients with Primary Biliary Cholangitis

Analysis of Autoantibodies against Promyelocytic Leukemia Nuclear Body Components and Biochemical Parameters in Sera of Patients with Primary Biliary Cholangitis

Can simple non-invasive fibrosis models determine prognostic indicators (fibrosis and treatment response) of primary biliary cholangitis?

Liquid Biopsy in Cholestatic Liver Disease Using Hepatocyte-Specific Methylation Markers

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