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A practical clinical approach to liver fibrosis.

ABSTRACT: Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.

SUBMITTER: Kumar R

PROVIDER: S-EPMC6301869 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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A practical clinical approach to liver fibrosis.

Kumar Rahul R Teo Eng Kiong EK How Choon How CH Wong Teck Yee TY Ang Tiing Leong TL

Singapore medical journal 20181201 12

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with hi ...[more]

PMID: 30631885

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Project description:Bayesian analysis is firmly grounded in the science of probability and has been increasingly supplementing or replacing traditional approaches based on P values. In this review, we present gradually more complex examples, along with programming code and data sets, to show how Bayesian analysis takes evidence from randomized clinical trials to update what is already known about specific treatments in cardiovascular medicine. In the example of revascularization choices for diabetic patients who have multivessel coronary artery disease, we combine the results of the FREEDOM trial (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) with prior probability distributions to show how strongly we should believe in the new Class I recommendation ("should be done") for a preference of bypass surgery over percutaneous coronary intervention. In the debate about the duration of dual antiplatelet therapy after drug-eluting stent implantation, we avoid a common pitfall in traditional meta-analysis and create a network of randomized clinical trials to compare outcomes after specific treatment durations. Although we find no credible increase in mortality, we affirm the tradeoff between increased bleeding and reduced myocardial infarctions with prolonged dual antiplatelet therapy, findings that support the new Class IIb recommendation ("may be considered") to extend dual antiplatelet therapy after drug-eluting stent implantation. In the decision between culprit artery-only and multivessel percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction, we use hierarchical meta-analysis to analyze evidence from observational studies and randomized clinical trials and find that the probability of all-cause mortality at longest follow-up is similar after both strategies, a finding that challenges the older ban against noninfarct-artery intervention during primary percutaneous coronary intervention. These examples illustrate how Bayesian analysis integrates new trial information with existing knowledge to reduce uncertainty and change attitudes about treatments in cardiovascular medicine.

Project description:Background/Aim: We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Results: NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. Conclusion: Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease.

Dataset Information

A practical clinical approach to liver fibrosis.

Publications

A practical clinical approach to liver fibrosis.

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