6533b855fe1ef96bd12b0afe
RESEARCH PRODUCT
Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study
Francesco AngelicoStefano Ginanni CorradiniDaniele PastoriSilvia FargionFracanzani Anna LudovicaMario AngelicoLuigi BolondiGiulia TozziPietro Luigi PujattiGiancarlo LabbadiaGino Roberto CorazzaMaurizio AvernaFrancesco PerticoneGiuseppe CroceMarcello PersicoTommaso BucciFrancesco BarattaLicia PolimeniMaria Del BenFrancesco VioliFrancesco VioliFrancesco AngelicoDaniele PastoriFrancesco BarattaMaria Del BenLicia PolimeniGiancarlo LabbadiaStefania BasiliValeria RaparelliLaura NapoleoneStefano Ginanni CorradiniFlaminia FerriPellone MonicaMonica MischitelliParlati LuciaGiulia TozziJessica D'amicoMarina ColziPaola AndreozziFrancesco PerticoneBenedetto CaroleoGino Roberto CorazzaMasotti MichelaBergamaschi GaetanoDavid SacerdotiSilvia BroccoMario AngelicoFrancesco SantopaoloSimona FranciosoPietro Luigi PujattiAlessandra FaedoAngelo AndriulliAntonio M. IppolitoLuigi BolondiFrancesco TovoliSilvia FargionAnna Ludovica FracanzaniGiovanni DavìDario Di MicheleGiuseppe CroceMaurizio AvernaAntonina GiammancoMarcello PersicoTommaso BucciLuigi IulianoMarco Ciacciarellisubject
Liver CirrhosisMaleCryptogenic cirrhosis; Liver disease; Lysosomal acid lipase; PathogenesisCirrhosisCryptogenic cirrhosisCryptogenic cirrhosis; Liver disease; Lysosomal acid lipase; Pathogenesis; Cardiology and Cardiovascular MedicineComorbidityPathogenesisLysosonal acid lipase; non-alcoolic fatty liver disease; cirrhosis030204 cardiovascular system & hematologyGastroenterologyLiver disease0302 clinical medicineModel for End-Stage Liver DiseasePathogenesiRisk FactorsPrevalenceProspective cohort studyMultivariate AnalysiSettore MED/12 - GastroenterologiaMiddle AgedItalyCohortLinear Model030211 gastroenterology & hepatologyFemaleCardiology and Cardiovascular MedicineLiver diseaseHumanmedicine.medical_specialtyLiver CirrhosiDown-Regulation03 medical and health sciencesInternal medicineCryptogenic cirrhosis; Liver disease; Lysosomal acid lipase; Pathogenesis; Aged; Biomarkers; Chi-Square Distribution; Comorbidity; Cross-Sectional Studies; Down-Regulation; Dried Blood Spot Testing; Female; Humans; Italy; Linear Models; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Platelet Count; Prevalence; Risk Factors; Sterol EsterasemedicineLysosonal acid lipaseHumansnon-alcoolic fatty liver diseaseAgedCross-Sectional StudieChi-Square Distributionbusiness.industryPlatelet CountcirrhosisRisk FactorBiomarkerCholesterol ester storage diseaseHepatologySterol Esterasemedicine.diseaseCross-Sectional StudiesMultivariate AnalysisLysosomal acid lipaseLinear ModelsDried Blood Spot TestingSteatohepatitisbusinessCryptogenic cirrhosiBiomarkersdescription
Background and aims Blood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis. Methods This is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2. Results Overall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic + viral, 7 autoimmune). Mean age was 64.2 ± 13.4 years, and 28.5% were women. Patients with CC were older compared to other aetiology-cirrhosis, with a lower Child-Turcotte-Pugh (CTP, p=0.003) and MELD (p=0.009) score, and a higher prevalence of cardio-metabolic risk factors and previous ischemic events. In the whole cohort, median LAL activity value was 0.58 nmol/spot/h, 0.49 and 0.65 in the groups of CC and known-aetiology cirrhosis, respectively (p=0.002). The difference remained significant after adjustment for white blood cells count (p=0.001). Multivariable linear regression analysis showed that CC (vs. known aetiology, Beta = â0.144, p=0.018), platelet count (Beta = 0.398, p < 0.001) and CTP score (Beta = â0.133, p=0.022) were associated with log-LAL activity. Similar results were found using MELD as covariate. Conclusions We found a marked reduction of LAL activity in patients with cryptogenic cirrhosis compared to the other known aetiologies. A prospective study will clarify the role of LAL in chronic liver diseases.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-01 |