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- Buzzetti, Elena, et al.
(author)
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Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease
- 2019
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In: Alimentary Pharmacology and Therapeutics. - : WILEY. - 0269-2813 .- 1365-2036. ; 49:9, s. 1214-1222
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Journal article (peer-reviewed)abstract
- Background Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis. Aim To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD. Methods We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and x4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients. Results Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis. Conclusions CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.
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| 3. |
- Mozes, Ferenc E., et al.
(author)
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Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis
- 2023
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In: The Lancet Gastroenterology & Hepatology. - : ELSEVIER INC. - 2468-1253. ; 8:8, s. 704-713
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Journal article (peer-reviewed)abstract
- Background Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score >= 15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs >= 20 kPa; FIB-4: <1<middle dot>3 vs 1<middle dot>3 to <= 2<middle dot>67 vs >2<middle dot>67; NFS: <-1<middle dot>455 vs -1<middle dot>455 to <= 0<middle dot>676 vs >0<middle dot>676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.Findings Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44<middle dot>7%] were female, median age was 54 years [IQR 44-63), and 1161 [46<middle dot>1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5<middle dot>8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0<middle dot>0001 for all comparisons). The tAUC at 5 years were 0<middle dot>72 (95% CI 0<middle dot>62-0<middle dot>81) for histology, 0<middle dot>76 (0<middle dot>70-0<middle dot>83) for LSM-VCTE, 0<middle dot>74 (0<middle dot>64-0<middle dot>82) for FIB-4, and 0<middle dot>70 (0<middle dot>63-0<middle dot>80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.Interpretation Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.
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| 5. |
- Polyzos, Stergios A., et al.
(author)
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Review article: non-alcoholic fatty liver disease and cardiovascular diseases: associations and treatment considerations
- 2021
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In: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 54:8, s. 1013-1025
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Research review (peer-reviewed)abstract
- Background There are increasing data on the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). Aim To summarise evidence on the association between NAFLD and CVD in the clinical setting and provide potential therapeutic implications. Methods We searched PubMed. Evidence was primarily derived from meta-analyses. and then, if data were insufficient, from clinical trials, and then from observational studies. Results NAFLD has been linked to arterial hypertension, arterial stiffness, atherosclerosis, coronary artery disease, atrial fibrillation and aortic valvular sclerosis. Advanced liver fibrosis is a crucial prognostic factor for end-stage liver disease and for cardiovascular and overall mortality. Weight loss through lifestyle modifications (diet and exercise) remains the cornerstone of the management of both NAFLD and CVD, but is difficult to achieve and possibly more difficult to sustain long term. Therefore, pharmacological management of NAFLD seems to be important, although no licenced medication currently exists. Pioglitazone, proposed for non-alcoholic steatohepatitis (NASH) by most guidelines, increases weight and should be avoided in congestive heart failure. Statins should not be avoided in NAFLD patients at risk for CVD. Glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter-2 inhibitors, two classes of anti-diabetic drugs, have shown promising results in NAFLD and CVD, but more studies with hard end points are needed. Obeticholic acid, a promising medication for NASH under investigation, should be carefully considered, owing to its adverse effect on lipid profile. Conclusions NAFLD is associated with CVD, which may have certain clinical and therapeutic implications.
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- Shribman, Samuel, et al.
(author)
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Plasma Neurofilament Light as a Biomarker of Neurological Involvement in Wilson's Disease.
- 2021
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In: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 36:2, s. 503-508
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Journal article (peer-reviewed)abstract
- Outcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end-organ damage.To identify a biomarker for neurological involvement in WD.Neuronal and glial-specific proteins were measured in plasma samples from 40 patients and 38 age-matched controls. Patients were divided into neurological or hepatic presentations and those with recent neurological presentations or deterioration associated with non-adherence were subcategorized as having active neurological disease. Unified WD Rating Scale scores and copper indices were recorded.Unlike copper indices, neurofilament light (NfL) concentrations were higher in neurological than hepatic presentations. They were also higher in those with active neurological disease when controlling for severity and correlated with neurological examination subscores in stable patients.NfL is a biomarker of neurological involvement with potential use in guiding chelation therapy and clinical trials for novel treatments. © 2020 University College London. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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