After the Storm: Persistent Molecular Alterations Following HCV Cure DOI Open Access

Coline Seurre,

Armando Andres Roca Suarez, Barbara Testoni

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7073 - 7073

Published: June 27, 2024

The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management this pathology, as their use allows viral elimination in a large majority patients. Nonetheless, HCV remains major public health problem due to multiple challenges associated with its diagnosis, treatment availability and prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk developing hepatic complications such hepatocellular carcinoma. In review, we aim summarize impact that infection on wide variety peripheral intrahepatic cell populations, alterations remain following DAA potential molecular mechanisms implicated long-term persistence. Finally, consider how recent developments single-cell multiomics could refine our understanding disease each specific population drive field explore new directions for chemo-preventive strategies.

Language: Английский

Pathophysiology of obesity and its associated diseases DOI Creative Commons
Xin Jin, Tingting Qiu, Li Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(6), P. 2403 - 2424

Published: Jan. 13, 2023

The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that strongly contributes to development cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on public health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia formation visceral fat in non-adipose tissues evoke disease, diseases. Adipose tissue can also secrete adipokines inflammatory cytokines affect local microenvironment, induce insulin resistance, hyperglycemia, activate associated signaling pathways. This further exacerbates progression obesity-associated Although some progress treatment been achieved preclinical clinical studies, pathogenesis obesity-induced are complex unclear. We still need understand their links better guide In this review, we review between with view improve future management its co-morbidities.

Language: Английский

Citations

176
EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma DOI
Bruno Sangro, Lorenza Rimassa, Maxime Ronot

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

23
Risk of Incident Type 2 Diabetes and Prediabetes in Patients With Direct Acting Antiviral‐Induced Cure of Hepatitis C Virus Infection DOI Open Access
Yu‐Ping Chang,

Ji‐Yuh Lee,

Chi‐Yi Chen

et al.

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

ABSTRACT Background Data regarding the risk of incident type 2 diabetes (T2D) and prediabetes among patients with hepatitis C virus (HCV) achieving direct‐acting antivirals (DAAs)‐induced sustained virologic response (SVR 12 ) remains limited. Methods A total 1079 patients, including 589 normoglycemia 490 prediabetes, who underwent biannual fasting glucose glycosylated haemoglobin (HbA1c) assessment for a median post‐SVR follow‐up 5.5 years, were enrolled. We reported crude (cIRs) age‐standardised incidence rates (ASIRs) T2D prediabetes. Factors associated assessed using Cox proportional hazards models. Results The cIRs 1.18 8.99 per 100 person‐years (PYFU), respectively. Additionally, ASIRs 1.09 (95% CI: 0.76–1.53) 8.47 7.23–9.90) PYFU. Prediabetes (adjusted hazard ratio [aHR]: 4.71; 95% confidence interval (CI): 2.55–8.70, p < 0.001), body mass index (BMI) kg/m increase (aHR: 1.17; 1.09–1.26, 0.001) liver stiffness measurement (LSM) kPa 1.05; 1.02–1.09, = higher T2D. Age year 1.02; 1.01–1.03, was Conclusion remain substantial after HCV eradication. Lifestyle modification, drug therapy regular monitoring glycemic status are crucial at developing following clearance.

Language: Английский

Citations

2
Single-cell landscape of functionally cured chronic hepatitis B patients reveals activation of innate and altered CD4-CTL-driven adaptive immunity DOI Creative Commons

Balakrishnan Chakrapani Narmada,

Atefeh Khakpoor, Niranjan Shirgaonkar

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(1), P. 42 - 61

Published: Feb. 28, 2024

Background & AimsHepatitis B surface antigen (HBsAg) loss or functional cure (FC), is considered the desirable therapeutic outcome for chronic hepatitis (CHB) patients. However, immune-pathological biomarkers and underlying mechanisms remain unclear. In this study we comprehensively interrogate disease-associated cell states (DACS) identified within intra-hepatic tissue matched PBMCs from either CHB FC patients, at resolution of single cells, to provide novel insights into putative FC.MethodsWe combined transcriptomics (scRNA-seq) with multiparametric flow cytometry-based immune phenotyping, multiplexed immunofluorescence elucidate immunopathological associated vs FC.ResultsWe find that environment patients displays specific identities molecular signatures are distinct those found in PBMCs. emergence an altered adaptive response marked by CD4 cytotoxic T lymphocytes (CD4-CTLs), activated innate represented liver-resident natural killer (LR-NK) Kupffer (KC) subtypes marginated neutrophils. Surprisingly, also characterized presence MHC class II-expressing hepatocytes low but persistent levels cccDNA pgRNA, which may play important role achieving HBV patients.ConclusionsOur provides conceptually immuno-pathological control cure, opens exciting new avenues clinical management, biomarker discovery interventions. We believe discoveries study, as it relates activation facilitate sustained, low-grade inflammation, have broader implications viral hepatitis.

Language: Английский

Citations

13
Associations of severe liver diseases with cataract using data from UK Biobank: a prospective cohort study DOI Creative Commons
Chao Chen, Ling Wei, Wenwen He

et al.

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 68, P. 102424 - 102424

Published: Jan. 21, 2024

Liver disease is linked to series of extrahepatic multisystem manifestations. However, little known about the associations between liver and eye diseases, especially cataract, global leading cause blindness. We aimed investigate whether severe including non-alcoholic fatty (NAFLD), alcoholic (ALD), viral hepatitis, fibrosis cirrhosis, were associated with an increased risk cataract.

Language: Английский

Citations

9
Hepatitis C virus and hepatocellular carcinoma: carcinogenesis in the era of direct-acting antivirals DOI Creative Commons

Felix Fiehn,

Claudia Beisel,

Marco Binder

et al.

Current Opinion in Virology, Journal Year: 2024, Volume and Issue: 67, P. 101423 - 101423

Published: June 25, 2024

Chronic hepatitis C virus (HCV) infection is a major cause of hepatic fibrosis and cirrhosis, with risk for the development hepatocellular carcinoma (HCC). Although highly effective direct-acting antivirals (DAAs) are available, incidence, morbidity, mortality HCV-associated HCC still high. This article reviews current knowledge mechanisms HCV-induced carcinogenesis special focus on those processes that continue after clearance outlines implications patient surveillance DAA treatment.

Language: Английский

Citations

9
Food inequity and insecurity and MASLD: burden, challenges, and interventions DOI
Shira Zelber‐Sagi, Patrizia Carrieri, Juan M. Pericàs

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(10), P. 668 - 686

Published: July 29, 2024

Language: Английский

Citations

8
Risk of de novo HCC in patients with MASLD following direct-acting antiviral-induced cure of HCV infection DOI
Chen‐Hua Liu, Pin‐Nan Cheng,

Yu‐Jen Fang

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

8
Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma DOI Creative Commons
Zhiyong Liu, Xiahui Lin, Hongying Guo

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(7), P. 2763 - 2778

Published: Jan. 1, 2024

Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer.However, a systematic evaluation ALDH alterations and their therapeutic relevance hepatocellular carcinoma (HCC) remains lacking.Herein, we found that 15 19 ALDHs were transcriptionally dysregulated HCC tissues compared to normal liver tissues.A four gene signature, ALDH2, ALDH5A1, ALDH6A1, ALDH8A1, robustly predicted prognosis defined high-risk subgroup exhibiting immunosuppressive features like regulatory T cell (Tregs) infiltration.Single-cell profiling revealed selective overexpression tumor necrosis factor receptor superfamily member 18 (TNFRSF18) on Tregs, upregulated patients.We identified ALDH2 as suppressor HCC, with three novel phosphorylation sites mediated by protein kinase C zeta enhanced enzymatic activity.Mechanistically, suppressed Tregs differentiation inhibiting β-catenin/TGF-β1 signaling HCC.Collectively, our integrated multi-omics analysis defines an ALDH-Tregs-TNFRSF18 axis contributes pathogenesis represents potential targets for this aggressive malignancy.

Language: Английский

Citations

6
Glutamine metabolic reprogramming in hepatocellular carcinoma DOI Creative Commons
Yanyan Ye,

Bodong Yu,

Hua Wang

et al.

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Aug. 11, 2023

Hepatocellular carcinoma (HCC) is a lethal disease with limited management strategies and poor prognosis. Metabolism alternations have been frequently unveiled in HCC, including glutamine metabolic reprogramming. The components of metabolism, such as synthetase, glutamate dehydrogenase, glutaminase, metabolites, metabolite transporters, are validated to be potential biomarkers HCC. Increased consumption confirmed which fuels proliferation by elevated dehydrogenase or upstream signals. Glutamine metabolism also serves nitrogen source for amino acid nucleotide anabolism. In addition, more converts glutathione an antioxidant HCC protect cells from oxidative stress. Moreover, reprogramming activates the mTORC signaling pathway support tumor cell proliferation. targeting therapy includes deprivation, related enzyme inhibitors, transporters inhibitors. Together, plays pivotal role identification, proliferation, progression.

Language: Английский

Citations

13