ORCID Profile
0000-0002-4426-6930
Current Organisation
KU Leuven
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Publisher: BMJ
Date: 04-02-2021
DOI: 10.1136/GUTJNL-2020-322564
Abstract: The full phenotypic expression of non-alcoholic fatty liver disease (NAFLD) in lean subjects is incompletely characterised. We aimed to investigate prevalence, characteristics and long-term prognosis of Caucasian lean subjects with NAFLD. The study cohort comprises 1339 biopsy-proven NAFLD subjects from four countries (Italy, UK, Spain and Australia), stratified into lean and non-lean (body mass index (BMI) /≥25 kg/m 2 ). Liver/non-liver-related events and survival free of transplantation were recorded during the follow-up, compared by log-rank testing and reported by adjusted HR. Lean patients represented 14.4% of the cohort and were predominantly of Italian origin (89%). They had less severe histological disease (lean vs non-lean: non-alcoholic steatohepatitis 54.1% vs 71.2% p .001 advanced fibrosis 10.1% vs 25.2% p .001), lower prevalence of diabetes (9.2% vs 31.4%, p .001), but no significant differences in the prevalence of the PNPLA3 I148M variant (p=0.57). During a median follow-up of 94 months ( 483 person-years), 4.7% of lean vs 7.7% of non-lean patients reported liver-related events (p=0.37). No difference in survival was observed compared with non-lean NAFLD (p=0.069). Caucasian lean subjects with NAFLD may progress to advanced liver disease, develop metabolic comorbidities and experience cardiovascular disease (CVD) as well as liver-related mortality, independent of longitudinal progression to obesity and PNPLA3 genotype. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD where the disease manifests at lower overall BMI thresholds. NAFLD may affect and progress in both obese and lean in iduals. Lean subjects are predominantly males, have a younger age at diagnosis and are more prevalent in some geographic areas. During the follow-up, lean subjects can develop hepatic and extrahepatic disease, including metabolic comorbidities, in the absence of weight gain. These patients represent one end of a wide spectrum of phenotypic expression of NAFLD.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.JHEP.2021.05.008
Abstract: Non-invasive scoring systems (NSS) are used to identify patients with non-alcoholic fatty liver disease (NAFLD) who are at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extrahepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain. The most common NSS (NFS, FIB-4, BARD, APRI) and the Hepamet fibrosis score (HFS) were assessed in 1,173 European patients with NAFLD from tertiary centres. Performance for fibrosis risk stratification and for the prediction of long-term hepatic/extrahepatic events, hepatocarcinoma (HCC) and overall mortality were evaluated in terms of AUC and Harrell's c-index. For longitudinal data, NSS-based Cox proportional hazard models were trained on the whole cohort with repeated 5-fold cross-validation, s ling for testing from the 607 patients with all NSS available. Cross-sectional analysis revealed HFS as the best performer for the identification of significant (F0-1 vs. F2-4, AUC = 0.758) and advanced (F0-2 vs. F3-4, AUC = 0.805) fibrosis, while NFS and FIB-4 showed the best performance for detecting histological cirrhosis (range AUCs 0.85-0.88). Considering longitudinal data (follow-up between 62 and 110 months), NFS and FIB-4 were the best at predicting liver-related events (c-indices>0.7), NFS for HCC (c-index = 0.9 on average), and FIB-4 and HFS for overall mortality (c-indices >0.8). All NSS showed limited performance (c-indices <0.7) for extrahepatic events. Overall, NFS, HFS and FIB-4 outperformed APRI and BARD for both cross-sectional identification of fibrosis and prediction of long-term outcomes, confirming that they are useful tools for the clinical management of patients with NAFLD at increased risk of fibrosis and liver-related complications or death. Non-invasive scoring systems are increasingly being used in patients with non-alcoholic fatty liver disease to identify those at risk of advanced fibrosis and hence clinical complications. Herein, we compared various non-invasive scoring systems and identified those that were best at identifying risk, as well as those that were best for the prediction of long-term outcomes, such as liver-related events, liver cancer and death.
Publisher: SAGE Publications
Date: 09-2010
Abstract: Background: Osteochondral injury of the talus can be challenging to treat because the damaged articular cartilage has a poor intrinsic reparative capability. Autologous Chondrocyte Implantation has become an effective means for treating persistent cartilage lesions that fail to respond to routine ankle arthroscopy. The purpose of this study was to assess the results of Matrix-induced autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the talar dome using a technique which does not require an osteotomy of the tibia or fibula. Materials and Methods: A prospective investigation of MACI was performed on ten patients with full-thickness lesions of the talus. The patients had a documented talus lesion on MRI, failure of conservative treatment and arthroscopic debridement/curettage, persistent ankle pain and swelling, the absence of tibiotalar arthritis and a stable ankle. Five males and five females, with an average of 1.7 previous procedures prior to Matrix-induced autologous implantation, were included in this study. All patients were available for followup at 1 and 2 years. Lesions were graded during the harvesting procedure using the Cheng-Ferkel grading system, the Outerbridge classification, and the International Cartilage Repair Society system. Clinical and functional evaluation was done preoperatively, and at 1 and 2 years postoperatively using the AOFAS hindfoot evaluation and the SF-36 Health Survey. Results: Preoperative AOFAS hindfoot scores were 61.2 (range, 42 to 76) which improved 1 year postoperatively to 74.7 (range, 46 to 87) ( p 0.05) and 2 years postoperatively to 73.3 (range, 42 to 90) ( p = 0.151). At both 1 and 2 years postoperatively, the results of the SF36 evaluation demonstrated a significant improvement in the Physical Functioning ( p = 0.002) and Bodily Pain ( p 0.001) components. Subjectively, all ten patients believed this procedure helped them. Conclusion: The results of this study suggest that MACI may be an effective way to treat full-thickness lesions of the talus using harvested chondrocytes from the talus without malleolar osteotomy. We recommend it for patients who do not respond to initial curettage and microfracture. Level of Evidence: IV, Retrospective Case Series
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-05-2020
DOI: 10.14309/AJG.0000000000000676
Abstract: We investigated the longitudinal impact of antinuclear antibody (ANA) on clinical outcomes and survival in nonalcoholic fatty liver disease (NAFLD). ANA were found in 16.9% of 923 biopsy-proven NAFLD patients, but none of them had histologic autoimmune hepatitis (AIH) or developed AIH after a mean follow-up of 106±50 months. Although ANA-positive cases had a higher prevalence of nonalcoholic steatohepatitis at baseline, the occurrence of liver-related events, hepatocellula carcinoma, cardiovascular events, extrahepatic malignancy, and overall survival were similar to ANA-negative. Once AIH has been ruled out, the long-term outcomes and survival are unaffected by the presence of ANA in patients with NAFLD.
Publisher: BMJ
Date: 17-05-2021
DOI: 10.1136/GUTJNL-2021-324243
Abstract: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the in idual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. In idual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed in idually and in sequential combinations. Data were included from 37 primary studies (n=5735 45% women median age: 54 years median body mass index: 30 kg/m 2 33% had type 2 diabetes 30% had advanced fibrosis). AUROCs of in idual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs ( .3 ≥2.67) followed by LSM-VCTE cut-offs ( .0 ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63–68) and 86% (84–87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs ( .3 ≥3.48) followed by LSM cut-offs ( .0 ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37–39) and specificity of 90% (89–91) with 19% needing biopsy. Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1038/MODPATHOL.2013.228
Abstract: In many human cancers, the epithelial-to-mesenchymal transition has an important role in the induction of cancer stem-like cells, and hence, in the causation of intratumoral heterogeneity. This process, also referred to as mesenchymal mimicry, is, however, only poorly understood in melanoma and histological correlation is still lacking. In an immunohistochemical analysis of a large prospective series of 220 primary and metastatic melanomas for the well-known epithelial-to-mesenchymal transition marker FN1, we observed melanoma cells with high FN1 expression in metastases with ischemic necrosis, but rarely or not at all in s les lacking evidence of hypoxia. In a blinded, retrospective series of 82 melanoma metastases with 10-year follow-up, the presence of clusters of these FN1(high) melanoma cells correlated significantly with shortened melanoma-specific survival, highlighting the prognostic value of their presence. We describe in detail the unique light- and electron-microscopic features of these FN1(high) melanoma cells, enabling their identification in routinely hematoxylin-and-eosin-stained sections. In addition, by laser microdissection and subsequent gene expression analysis and immunohistochemistry, we highlight their distinctive, molecular phenotype that includes expression of various markers of the epithelial-to-mesenchymal transition (eg, ZEB1) and of melanoma stem-like cells (eg, NGFR), and lack of immunoreactivity for the melanocytic marker MITF. This phenotype could be reproduced in vitro by culturing melanoma cells under hypoxic conditions. Functionally, the hypoxic microenvironment was shown to induce a more migratory and invasive cell type. In conclusion, we identified a novel clinically relevant FN1(high)MITF(low) cell type in melanoma associated with ischemic necrosis, and propose that these cells reside at the crossroad of the epithelial-to-mesenchymal transition and stem-like cell induction, plausibly triggered by the hypoxic environment.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Public Library of Science (PLoS)
Date: 22-02-2019
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Olivier Govaere.