0000000000544311

AUTHOR

Benedikt Schaefer

showing 3 related works from this author

Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation

2019

Background & Aims Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. Methods We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234…

Liver CirrhosisMale0301 basic medicineALTLiver diseasechemistry.chemical_compound0302 clinical medicineLiver Function TestsRisk FactorsGenotypeRare Liver DiseaseAlpha 1-antitrypsin deficiencyHomozygoteAge FactorsGastroenterologyMiddle AgedEuropeEditorial CommentaryPhenotypemedicine.anatomical_structureLiverElasticity Imaging TechniquesFemale030211 gastroenterology & hepatologyTEAdultmedicine.medical_specialty610Mice Transgenic03 medical and health sciencesSex Factorsalpha 1-Antitrypsin DeficiencyInternal medicinemedicinePiAnimalsHumansGenetic Predisposition to DiseaseASTAgedLungHepatologyTriglyceridebusiness.industryLipid Metabolismmedicine.diseaseFatty Liver030104 developmental biologyEndocrinologychemistryCase-Control Studiesalpha 1-AntitrypsinMutationSteatosisTransient elastographybusinessGastroenterology
researchProduct

Dual proteotoxic stress accelerates liver injury via activation of p62‐Nrf2

2021

Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. We investigated the interaction of both proteotoxic stresses in humans and mice. Animals overexpressing both PiZ and HBs (HBs-PiZ mice) had greater liver injury, steatosis, and fibrosis. Later they exhibited higher hepatocellular carcinoma load and a more aggressive tumor subtype. Although PiZ and H…

0301 basic medicineCirrhosisNF-E2-Related Factor 2medicine.disease_causePathology and Forensic MedicineMice03 medical and health sciences0302 clinical medicineSDG 3 - Good Health and Well-beingStress PhysiologicalFibrosisSequestosome-1 ProteinmedicineAnimalsHumansLiver injuryHepatitis B Surface Antigensbusiness.industryLiver DiseasesAutophagyHepatitis Bmedicine.diseasedigestive system diseasesaggregate Hepatitis B Surface Antigens Humans Liver Diseases Mice NF-E2-Related Factor 2 Sequestosome-1 Protein Stress Physiological alpha 1-Antitrypsin cirrhosis inclusionlipophagy oxidative stress SERPINA1 Animals030104 developmental biologyalpha 1-Antitrypsin030220 oncology & carcinogenesisHepatocellular carcinomaCancer researchSteatosisbusinessOxidative stressThe Journal of Pathology
researchProduct

Dynamic α-Fetoprotein Response and Outcomes After Liver Transplant for Hepatocellular Carcinoma.

2021

IMPORTANCE: Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured. OBJECTIVE: To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated sco…

MaleOncologymedicine.medical_specialtyCarcinoma Hepatocellularmedicine.medical_treatment030230 surgeryLiver transplantationMilan criteriaRisk AssessmentDisease-Free Survival03 medical and health sciences0302 clinical medicinePredictive Value of TestsInternal medicinemedicineHumansCumulative incidenceAgedProportional Hazards ModelsRetrospective StudiesReceiver operating characteristicbusiness.industryLiver NeoplasmsRegression analysisMiddle Agedmedicine.diseaseRegressionLiver TransplantationSurvival RateTransplantationROC Curve030220 oncology & carcinogenesisHepatocellular carcinomaFemaleSurgeryalpha-Fetoproteinsbusiness
researchProduct