A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores

Vincentis, Antonio De; Tavaglione, Federica; Jamialahmadi, Oveis; Picardi, Antonio; Incalzi, Raffaele Antonelli; Valenti, Luca; Romeo, Stefano; Vespasiani‐Gentilucci, Umberto

doi:10.1016/j.cgh.2021.05.056

Cited by 74 publications

(68 citation statements)

References 28 publications

(39 reference statements)

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“…These notions are corroborated by the slight but consistent outperforming of NFS by the much simpler FIB-4 ( 45 , 50 ). Recent data also suggest that, at the general population level, the ability of NFS to predict incident severe liver disease is inferior to that of FIB-4 among the obese ( 51 ). In addition to age, FIB-4 only includes the aspartate-to-alanine aminotransferase ratio as well as platelets, which are among the best indicators of advanced fibrosis and cirrhosis in routine laboratory tests ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease

Qadri

Ahlholm

Lønsmann

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity. Objective To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD. Design Cross-sectional cohort study comparing simple fibrosis scores (FIB-4, NFS, APRI, BARD, HFS) and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or CK-18 (MACK-3). Setting Tertiary referral center. Patients We recruited overweight/obese patients from endocrinology (n=307) and hepatology (n=71) clinics undergoing a liver biopsy (median BMI 40.3 [IQR 36.0–44.7] kg/m 2). Additionally, we studied 859 less obese patients with biopsy-proven NAFLD to derive BMI-adjusted cut-offs for NFS. Main Outcome Measures Biomarker AUROC, sensitivity, specificity, and predictive values to identify histological stage ≥F3 fibrosis or nonalcoholic steatohepatitis with ≥F2 fibrosis (fibrotic NASH). Results The scores with an AUROC >0.85 to identify ≥F3 fibrosis were ADAPT, FIB-4, FIBC3, and HFS. For fibrotic NASH, the best predictors were MACK-3 and ADAPT. The specificities of NFS, BARD, and FIBC3 deteriorated as a function of BMI. We derived and validated new cut-offs for NFS to rule in/out ≥F3 fibrosis in groups with BMIs <30.0, 30.0–39.9, and ≥40.0 kg/m 2. This optimized its performance at all levels of BMI. Sequentially combining FIB-4 with ADAPT or FIBC3 increased specificity to diagnose ≥F3 fibrosis. Conclusions In obese patients, the best-performing fibrosis biomarkers are ADAPT and the inexpensive FIB-4, which are unaffected by BMI. The widely used NFS loses specificity in obese individuals, which may be corrected with BMI-adjusted cut-offs.

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Section: Discussionmentioning

confidence: 99%

Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease

Qadri

Ahlholm

Lønsmann

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…The loci comprising the current risk score are also implicated in the risk for developing cirrhosis of diverse aetiologies. Using similar polygenic risk scores (PRS) in non-alcoholic fatty liver disease (NAFLD) revealed that combining genetic and clinical features refines the predictive utility of the algorithm for identifying those at higher risk of severe liver disease [32][33][34] . Given the many shared genetic and metabolic risks between alcohol-related liver disease and NAFLD, the predictive algorithm defined here may have a wider scope across these diseases for risk stratification of those at higher risk of cirrhosis.…”

Section: Scope Of Risk-scorementioning

confidence: 99%

A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers

Whitfield

Schwantes‐An

Darlay

et al. 2022

Journal of Hepatology

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“…Moreover, hepatitis virus can inhibit bone marrow megakaryocytes, which impairs platelet production, thereby reducing platelet count and their ability to aggregate, and increasing mean platelet volume and width. 42,43 Liver damage is associated with increases in the serum activities of AST and ALT, and these are commonly used as markers of hepatocyte injury. 44,45 These parameters are also used as a means of diagnosing NAFLD early, and the identification of a high-normal serum ALT activity is of great significance for the early prevention of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Use of GP73 in the diagnosis of non-alcoholic steatohepatitis and the staging of hepatic fibrosis

Yang

et al. 2021

J Int Med Res

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Objective To evaluate the utility of Golgi protein 73 (GP73) in the diagnosis of non-alcoholic steatohepatitis (NASH) and hepatic fibrosis (HF) staging. Methods Ninety-one patients with non-alcoholic fatty liver disease (NAFLD) were allocated to NAFL (n = 46) and NASH (n = 45) groups according to their NAFLD activity score (NAS), and there were 30 healthy controls. Serum GP73 was measured by ELISA, GP73 protein expression was evaluated using immunohistochemistry, and FibroScan was used to determine liver hardness. Results The serum GP73 concentrations of the NAFL and NASH groups were significantly higher than those of controls. GP73 expression in the liver of the patients gradually progressed from absent or low to moderate or high. Serum GP73 positively correlated with liver expression, and the serum and liver GP73 of the patients positively correlated with FibroScan value and HF stage. There was a strong positive correlation of the combination of alanine aminotransferase, gamma glutamyl transferase and GP73 with NASH. The combination of serum GP73 and FibroScan value was found to predict NASH (NAS > 4) and advanced HF (stage ≥2) in patients with NAFLD using receiver operating characteristic analysis. Conclusion Serum GP73 may be useful in the diagnosis of NASH and the staging of HF.

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A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores

Cited by 74 publications

References 28 publications

Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease

Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease

A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers

Use of GP73 in the diagnosis of non-alcoholic steatohepatitis and the staging of hepatic fibrosis

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