J Hepatol
Virginia Commonwealth University School of Medicine, Richmond, United States.
Published: November 2022
Background & Aims: Liver fibrosis is a key prognostic determinant for clinical outcomes in non-alcoholic steatohepatitis (NASH). Current scoring systems have limitations, especially in assessing fibrosis regression. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses provides standardized evaluation of NASH features, especially liver fibrosis and collagen fiber quantitation on a continuous scale. This approach was applied to gain in-depth understanding of fibrosis dynamics after treatment with tropifexor (TXR), a non-bile acid farnesoid X receptor agonist in patients participating in the FLIGHT-FXR study (NCT02855164).
Method: Unstained sections from 198 liver biopsies (paired: baseline and end-of-treatment) from 99 patients with NASH (fibrosis stage F2 or F3) who received placebo (n = 34), TXR 140 μg (n = 37), or TXR 200 μg (n = 28) for 48 weeks were examined. Liver fibrosis (qFibrosis®), hepatic fat (qSteatosis®), and ballooned hepatocytes (qBallooning®) were quantitated using SHG/TPEF microscopy. Changes in septa morphology, collagen fiber parameters, and zonal distribution within liver lobules were also quantitatively assessed.
Results: Digital analyses revealed treatment-associated reductions in overall liver fibrosis (qFibrosis®), unlike conventional microscopy, as well as marked regression in perisinusoidal fibrosis in patients who had either F2 or F3 fibrosis at baseline. Concomitant zonal quantitation of fibrosis and steatosis revealed that patients with greater qSteatosis reduction also have the greatest reduction in perisinusoidal fibrosis. Regressive changes in septa morphology and reduction in septa parameters were observed almost exclusively in F3 patients, who were adjudged as 'unchanged' with conventional scoring.
Conclusion: Fibrosis regression following hepatic fat reduction occurs initially in the perisinusoidal regions, around areas of steatosis reduction. Digital pathology provides new insights into treatment-induced fibrosis regression in NASH, which are not captured by current staging systems.
Lay Summary: The degree of liver fibrosis (tissue scarring) in non-alcoholic steatohepatitis (NASH) is the main predictor of negative clinical outcomes. Accurate assessment of the quantity and architecture of liver fibrosis is fundamental for patient enrolment in NASH clinical trials and for determining treatment efficacy. Using digital microscopy with artificial intelligence analyses, the present study demonstrates that this novel approach has greater sensitivity in demonstrating treatment-induced reversal of fibrosis in the liver than current systems. Furthermore, additional details are obtained regarding the pathogenesis of NASH disease and the effects of therapy.
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http://dx.doi.org/10.1016/j.jhep.2022.06.018 | DOI Listing |
BMC Infect Dis
January 2025
Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte, Minas Gerais, Brazil.
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Brussels Health Campus, Department of Gastroenterology and Hepatology, University Hospital Brussels (UZ Brussel), Brussels, Belgium.
The incidence of hepatocellular carcinoma (HCC) is rising, with a shift towards Metabolic Dysfunction-associated Steatotic Liver Disease becoming the dominant risk factor in Western countries. Significant advances in treatment have broadened the range of available therapeutic options. For this reason, clinical decision-making, along with a multidisciplinary team approach, plays a crucial role in improving patient outcomes.
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January 2025
Department of Internal Medicine 1, Shimane University Faculty of Medicine, Japan.
We herein report a 56-year-old man with severe hypocalcemia during ruxolitinib therapy for myelofibrosis transitioning from JAK2 mutation-positive polycythemia vera. Blood transfusions were administered every one to two weeks for ruxolitinib-induced anemia. Blood tests revealed hypocalcemia with low TRACP-5b, 25-hydroxyvitamin D (25 (OH) D), and 1,25-dihydroxyvitamin D (1,25 (OH) D) levels within the lower reference range.
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January 2025
Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address:
Background: Patients after kidney transplantation (KTx) in childhood show a high prevalence of cardiac complications, but the underlying mechanism is still poorly understood. In adults, myocardial fibrosis detected in cardiac magnetic resonance (CMR) imaging is already an established risk factor. Data for children after KTx are not available.
View Article and Find Full Text PDFBioorg Chem
January 2025
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201 China; University of Chinese Academy of Sciences, Beijing 100049 China. Electronic address:
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction- associated with fatty liver disease (MAFLD), is one of the most prevalent chronic liver diseases globally. NAFLD is characterized by the accumulation of liver fat unrelated to excessive alcohol consumption. Non-alcoholic steatohepatitis (NASH) is the disease progression of NAFLD and could develop into cirrhosis and hepatocellular carcinoma.
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