| 1. |
- De Vincentis, Antonio, et al.
(författare)
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A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores.
- 2022
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Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 20:3, s. 658-673
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Tidskriftsartikel (refereegranskat)abstract
- A polygenic risk score based on well-known genetic variants in PNPLA3, TM6SF2, MBOAT7 and GCKR predicts hepatic fat content (PRS-HFC). Here we hypothesize that the addition of PRS-HFC to clinical fibrosis scores may improve risk stratification and prediction of severe liver disease (SLD).We used data from 266,687 individuals in the UK Biobank, evaluating the incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation during a median follow-up of 9 years. NAFLD fibrosis score (NFS), FIB-4, APRI, BARD and Forns scores, and PRS-HFC, were computed. All analyses were stratified according to the presence of diabetes, obesity and positive fatty liver index (FLI≥60).Unfavorable genetics (PRS-HFC≥0.396) further stratified the risk of SLD in subjects in intermediate/high risk classes of fibrosis scores, with higher effect in those with metabolic risk factors, and the prediction was improved by integrating PRS-HFC (AUROCs increased for all scores with p∼10-2-10-4, except for APRI in the overall population and in subjects with obesity. PRS-HFC improved diagnostic accuracies and positive predictive values for SLD in intermediate-high clinical score risk classes. Risk stratification and prediction were not/poorly affected by unfavorable genetics in subjects without metabolic risk factors.Integration of genetics with clinical fibrosis scores refines individual risk and prediction for SLD, mainly in individuals at risk for NAFLD. These data provide first evidence from a prospective cohort that common genetic variants capture additional prognostic insights not conveyed by validated clinical/biochemical parameters.
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| 2. |
- Tavaglione, Federica, et al.
(författare)
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Accuracy of controlled attenuation parameter for assessing liver steatosis in individuals with morbid obesity before bariatric surgery.
- 2022
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Ingår i: Liver international : official journal of the International Association for the Study of the Liver. - : Wiley. - 1478-3231. ; 42:2, s. 374-383
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Tidskriftsartikel (refereegranskat)abstract
- The ultrasound-based controlled attenuation parameter (CAP) is a non-invasive tool widely validated for assessing liver steatosis across different etiologies. However, few studies, with liver biopsy available, have investigated its performance in individuals with morbid obesity. Herein, we aimed to evaluate the diagnostic accuracy of CAP in participants with morbid obesity from the MAFALDA study before bariatric surgery.A total of 120 individuals with valid examinations within three months from bariatric surgery were included. Clinical, laboratory, FibroScan® (XL probe), and liver biopsy data were collected using standardized procedures. The overall accuracy of CAP for detecting liver steatosis was estimated by the area under the receiver-operating characteristics curve (AUROC). Optimal cut-offs were chosen at points with the highest Youden index.The AUROCs of CAP for detecting S≥S1, S≥S2, and S=S3 were 0.91 (95% CI 0.86-0.97), 0.83 (95% CI 0.76-0.90), and 0.86 (95% CI 0.79-0.94), respectively. The best CAP cut-offs for S≥S1, S≥S2, and S=S3 were 300dB/m (95% CI 275-316), 328dB/m (95% CI 296-345), and 344dB/m (95% CI 343-352), respectively. CAP values were independently influenced by steatosis grade (estimate 20.60, 95% CI 12.70-28.40, P=1.05×10-6 ). The AUROC of FibroScan-AST (FAST) score for detecting progressive non-alcoholic steatohepatitis was 0.76 (95% CI 0.66-0.86).In individuals with morbid obesity, CAP measured by XL probe is an accurate non-invasive tool for grading liver steatosis. Measurement of liver fat content by CAP may help identify those eligible for bariatric procedures and estimate the effect of bariatric surgery on hepatic steatosis.The ultrasound-based controlled attenuation parameter (CAP) by using the XL probe has an excellent performance for grading liver steatosis among individuals with morbid obesity. CAP may represent an accurate tool for the non-invasive assessment of liver steatosis among individuals with morbid obesity before and after bariatric surgery.
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| 3. |
- Tavaglione, Federica, et al.
(författare)
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Development and Validation of a Score for Fibrotic Non-Alcoholic Steatohepatitis.
- 2023
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Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 21:6, s. 1523-1532
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive assessment of histological features of non-alcoholic fatty liver disease (NAFLD) has been an intensive research area over the last decade. Herein, we aimed to develop a simple non-invasive score using routine laboratory tests to identify, among individuals at high risk for NAFLD, those with fibrotic non-alcoholic steatohepatitis (NASH) defined as NASH, NAFLD activity score (NAS) ≥4, and fibrosis stage ≥2.The derivation cohort included 264 morbidly obese individuals undergoing intraoperative liver biopsy in Rome, Italy. The best predictive model was developed and internally validated using a bootstrapping stepwise logistic regression analysis (2000 bootstrap samples). Performance was estimated by the area under the receiver operating characteristic curve (AUROC). External validation was assessed in three independent European cohorts (Finland, n=370; Italy n=947; England n=5,368) of individuals at high risk for NAFLD.The final predictive model, designated as Fibrotic NASH Index (FNI), combined aspartate aminotransferase (AST), high-density lipoprotein (HDL) cholesterol, and hemoglobin A1c (HbA1c). The performance of FNI for fibrotic NASH was satisfactory in both derivation and external validation cohorts (AUROCs 0.78 and 0.80-0.95, respectively). In the derivation cohort, rule-out and rule-in cut-offs were 0.10 for sensitivity ≥0.89 (negative predictive value [NPV] 0.93) and 0.33 for specificity ≥0.90 (positive predictive value [PPV] 0.57), respectively. In the external validation cohorts, sensitivity ranged from 0.87 to 1 (NPV 0.99-1) and specificity from 0.73 to 0.94 (PPV 0.12-0.49) for rule-out and rule-in cut-off, respectively.FNI is an accurate, simple, and affordable non-invasive score which can be used in primary healthcare to screen for fibrotic NASH individuals with dysmetabolism.
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| 4. |
- Tavaglione, Federica, et al.
(författare)
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Inborn and acquired risk factors for severe liver disease in Europeans with type 2 diabetes from the UK Biobank.
- 2021
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Ingår i: JHEP reports : innovation in hepatology. - : Elsevier BV. - 2589-5559. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is a major driver of fatty liver disease and its long-term complications. The aim of this study was to investigate the individual contribution of inborn and acquired risk factors for severe liver disease in individuals with type 2 diabetes from the UK Biobank study.A total of 22,812 UK Biobank participants of European descent without clinical history of liver disease and liver cancer were prospectively followed for the development of severe liver disease, defined as a composite diagnosis of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and/or liver transplantation from the National Health Service records. The contribution of inborn and acquired risk factors to the risk of incident severe liver disease was assessed by Cox proportional hazards models.During a median follow-up of 8.9 years (IQR 8.1-9.6), there were 279 individuals with severe liver disease, including 255 with cirrhosis and/or decompensated liver disease, 47 with hepatocellular carcinoma, and 5 with liver transplantation; death from severe liver disease occurred in 83 individuals. Risk factors independently associated with increased risk of incident severe liver disease included abnormal aspartate aminotransferase (adjusted hazard ratio [aHR] 4.85, 95% CI 2.76-8.54), decrease in serum albumin (aHR 2.39, 95% CI 1.76-3.24) and platelet count (aHR 1.12, 95% CI 1.09-1.16), cardiovascular disease (aHR 1.86, 95% CI 1.23-2.79), microalbuminuria (aHR 1.55, 95% CI 1.04-2.30), PNPLA3 rs738409 (aHR 1.67, 95% CI 1.27-2.18) and TM6SF2 rs58542926 (aHR 1.63, 95% CI 1.12-2.39), while the net effect of male sex was protective (aHR 0.49, 95% CI 0.26-0.94).These findings may help in clinical care to identify individuals with type 2 diabetes at risk of severe liver disease, in turn leading to personalised risk prediction and prevention strategies.Type 2 diabetes is a key driver of severe liver disease, namely cirrhosis, hepatocellular carcinoma, and liver-related mortality. In Europeans with type 2 diabetes from the prospective UK Biobank study, abnormal liver function, cardiovascular disease, microalbuminuria, and genetic variants in PNPLA3 and TM6SF2 genes are the major independent risk factors for severe liver disease. These findings may contribute in clinical care to identify and closely monitor individuals with type 2 diabetes at risk of developing severe liver disease, requiring more intensive follow-up strategies.
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