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Abstract BACKGROUND Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) fibrosis may prevent liver-related morbidity and mortality. We investigated the effectiveness of multiple 2-step approaches for detecting at-risk advanced MASLD fibrosis, defined as a hierarchical clinical score comprising liver histology and VCTE depending on availability, in primary and hospital outpatient care. METHODS Patients at […]

Abstract BACKGROUND Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease characterised by systemic inflammation and lung tissue damage. In injured lungs, fibroblast activity increases in response to tissue insult and has been shown to be prognostic in fibrotic disease. This study investigated whether fibroblast activity is associated with mortality in severe COVID-19. METHOD […]

Abstract Extracellular matrix (ECM) turnover and neutrophil protease activity contribute to chronic obstructive pulmonary disease (COPD) pathobiology, but the prognostic value of circulating neoepitopes for acute exacerbations (AECOPD) is uncertain. In a prospective cohort from the CORTICO-COP trial, the biomarkers C5M and C6M (type V/VI collagen degradation), ELP-3 (proteinase 3-generated elastin fragment), and CPa9-HNE (neutrophil […]

Abstract BACKGROUND AND AIMS Betaine, 20 g/day for 12 months, reduced liver injury in several trials in non-alcoholic steatohepatitis (NASH). Our aim was to determine the safety and efficacy of lower doses of betaine in clinically diagnosed metabolic dysfunction-associated steatotic liver disease (MASLD) and an elevated ALT. APPROACH AND RESULTS We performed 3 pilot trials in […]

Abstract BACKGROUND Chronic hepatitis C (CHC) infection remains a global health burden, contributing to the risk of long-term complications such as progressive fibrosis, cirrhosis, and hepatocellular carcinoma, particularly in undiagnosed or untreated individuals. Novel biomarkers for the assessment of disease progression and prognosis are required for fibroinflammatory chronic liver disease. Our study population from the […]

Abstract BACKGROUND & AIMS Drug development for metabolic and alcohol-related liver disease and alcohol-related liver disease is emerging, but designing clinical trials remains challenging due to unknown disease progression rates and a lack of validated surrogate endpoints. We studied fibrosis progression rates and determinants of progression using dual liver biopsies and compared the prognostic performance […]

Abstract RATIONALE Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease driven by nodules containing “LAM cells” and recruited LAM-associated fibroblasts. Although rapamycin reduces lung function loss, some patients continue to decline, meaning additional therapies are needed. OBJECTIVES To investigate how the LAM nodule environment affects LAM cell proliferation and the response to rapamycin. METHODS Proteins […]

Abstract BACKGROUND Idiopathic pulmonary fibrosis (IPF) is characterized by an increase in proteolytic enzymes, including matrix metalloproteinases that degrade the extracellular matrix and markers of localized inflammation. Protein fragments (neoepitopes) are detectable in the circulation. RESEARCH QUESTION Can short-term trajectories of neoepitopes after initiation of antifibrotic treatment predict therapy-related outcomes, including mortality, in patients with […]

Abstract BACKGROUND & AIMS Alcohol is a key driver of liver-related mortality, and phosphatidylethanol (PEth) is a direct biomarker of alcohol intake. We investigated the prognostic performance of PEth with noninvasive liver fibrosis tests (NITs) for predicting hepatic decompensation in an alcohol-related liver disease (ALD) at-risk population. METHODS Prospective cohort study with 411 at risk […]