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-analysisMed Univ Vienna, Austria; Med Univ Vienna, Austria.
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2023 (English)In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 8, no 8, p. 704-713Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
ELSEVIER INC , 2023. Vol. 8, no 8, p. 704-713
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:liu:diva-199261DOI: 10.1016/S2468-1253(23)00141-3ISI: 001084590000001PubMedID: 37290471OAI: oai:DiVA.org:liu-199261DiVA, id: diva2:1813969
Note
Funding Agencies|Innovative Medicines Initiative 2 (IMI2) Joint Undertaking [777377]; EU; EFPIA; Fonds de Recherche du Quebec-Sante [296306]; Wellcome Trust [221805/Z/20/Z]; Royal Society [221805/Z/20/Z]; KHIDI - Ministry of Health Welfare, Korea [HI14C1135]; Newcastle NIHR Biomedical Research Centre
2023-11-222023-11-222024-09-09