Simultaneous Activation of Beta‐Oxidation and De Novo Lipogenesis in MASLD‐HCC: A New Paradigm

Liver International, Journal Year: 2025, Volume and Issue: 45(2)

Published: Jan. 22, 2025

ABSTRACT Background and Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) is the most common cause of hepatocellular carcinoma (HCC). In this study, we combine metabolomic gene expression analysis to compare HCC tissues with non‐tumoural (NTT). Methods A non‐targeted strategy LC–MS was applied 52 pairs human MASLD‐HCC NTT separated into 2 groups according fibrosis severity F0F1‐F2 versus F3F4. The genes related de Novo lipogenesis (DNL) fatty acid oxidation (FAO) has been analysed by quantitative RT‐PCR and/or interrogation RNA‐seq datasets in 259 (MASLD‐HCC vs. VIRUS‐HCC). Results Metabolomic revealed that acylcarnitines were main discriminating metabolites when compared MASLD‐HCC‐F0F1‐F2 MASLD‐HCC‐F3F4 NTT. Based on these data, a panel 15 selected DNL FAO indicated there no difference between MASLD‐HCC. contrast same comparative aetiology HCC: VIRUS‐HCC showed both aetiologies shared upregulation involved DNL. However, five (HADHA, CRAT, CPT1, CPT2 PPARA) are upregulated exclusively This result indicates pathways simultaneously activated VIRUS‐HCC. Conclusions These results suggest that, involvement adaptive metabolic different depending HCC. Moreover, dogma simultaneous activation incompatible cancer would not apply

Language: Английский

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The Natural History of Hepatitis C Virus Infection and Disease in the Era of Curative Therapy with Direct-Acting Antivirals

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 319 - 319

Published: Feb. 26, 2025

The availability of highly effective direct-acting antivirals (DAAs) that cure individuals infected with HCV has changed completely the natural history infection and chronic hepatitis C. In sustained responders to DAAs, most common clinical-pathologic outcome become liver disease regression, cirrhosis re-compensation, de-listing transplant candidates. However, careful scrutiny cofactors predictors in treated patients is mandatory for an appropriate personalized surveillance residual risk hepatocellular carcinoma. Since successful treatment DAAs does not confer protective immunity against reinfection, vaccine critically needed control infection. Meanwhile, it enhance universal access test asymptomatic high-risk groups who are main source transmission, screen people inject drugs (PWID), men have sex (MSM), workers, assure safe medical procedures provision disposable needle syringes.

Language: Английский

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Diverse Subsets of γδT Cells and Their Specific Functions Across Liver Diseases

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2778 - 2778

Published: March 19, 2025

γδT cells, a distinct group of T lymphocytes, serve as link between innate and adaptive immune responses. They are pivotal in the pathogenesis various liver disorders, such viral hepatitis, nonalcoholic fatty disease (NAFLD), alcoholic (ALD), fibrosis, autoimmune diseases, hepatocellular carcinoma (HCC). Despite their importance, functional diversity regulatory mechanisms cells remain incompletely understood. Recent advances high-throughput single-cell sequencing spatial transcriptomics have revealed significant heterogeneity among cell subsets, particularly Vδ1+ Vδ2+, which exhibit immunological roles. mainly tissue-resident contribute to tumor immunity chronic inflammation, while Vδ2+ predominantly found peripheral blood, play roles systemic surveillance but may undergo dysfunction diseases. Additionally, γδT17 exacerbate inflammation NAFLD ALD, whereas IFN-γ-secreting antiviral antifibrotic These discoveries laid foundation for creation innovative solutions. cell-based immunotherapeutic approaches, adoptive transfer, checkpoint inhibition, strategies targeting metabolic pathways. Future research should focus on harnessing cells’ therapeutic potential through targeted interventions, offering promising prospects precision immunotherapy

Language: Английский

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FibroScan-AST Score vs Liver Stiffness for the Prediction of Liver Events After HCV Cure

Open Forum Infectious Diseases, Journal Year: 2025, Volume and Issue: 12(4)

Published: March 27, 2025

Abstract Background Liver stiffness (LS) predicts liver complication occurrence in patients with hepatitis C virus (HCV) infection after sustained virological response (SVR). The FibroScan-AST (FAST) score, which includes aspartate aminotransferase (AST) and controlled attenuation parameter (CAP; measured by FibroScan), may improve the prediction ability of isolated LS. Our aim was to compare predictive capacity LS vs FAST this setting. Methods Multicenter cohort study including individuals HIV/HCV coinfection or HCV monoinfection from Spain if they had (1) ≥9.5 kPa pretreatment, (2) SVR a direct-acting antiviral (DAA)–based regimen, (3) CAP measurement at SVR. Fatty disease (FLD) defined as ≥248 dB/m. primary outcome (decompensation hepatocellular carcinoma [HCC]) Results Three hundred were included; 213 (71%) HIV. At SVR, 131 (44%) FLD. score <0.35 182 (61%), 0.35–0.67 79 (27%), >0.67 34 (12%) patients. After median (Q1–Q3) follow-up 73 (53–83) months, 36 complications (15 [5%] HCC) occurred. independently associated an increased risk developing (sub–hazard ratio [sHR], 1.06; 95% CI, 1.04–1.08; P < .001). In separate model, ≥0.35 also greater (sHR, 8.12; 3.11–21.17; area under receiver operating characteristics curve model based on 0.83 (95% 0.76–0.91), that 0.80 0.72–0.88; = .158). Conclusions development events but does not alone time point.

Language: Английский

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The Role of Direct-Acting Antivirals in Enhancing Quality of Life Among Individuals with Chronic Hepatitis C

Healthcare, Journal Year: 2025, Volume and Issue: 13(8), P. 878 - 878

Published: April 11, 2025

Background: Chronic hepatitis C virus (HCV) infection significantly impairs health-related quality of life (HRQoL) and poses a substantial global health concern. Direct-acting antiviral (DAA) therapies have revolutionized HCV treatment, but their impact on HRQoL, particularly considering clinical psychological factors, requires further investigation. This study aimed to evaluate the influence DAA therapy HRQoL in Romanian patients with chronic infection, analyzing effects treatment role associated factors. Methods: A prospective, single-center was conducted 90 HCV-infected treated 12-week regimen (Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir). assessed at baseline (BSL), end (EOT), 12 weeks post-treatment (SVR) using WHOQOL BREF questionnaire. Clinical data, including fibrosis degree, prior PegIFN assessments (HADS, PSS), were collected. Statistical analyses examined trends associations parameters. Results: Significant improvements observed across all domains over time (p < 0.0001). Gender residence did not changes. Fibrosis severity had no significant progression. However, comorbidities such as anemia kidney disease moderated specific domains. Anxiety also affected while perceived stress depression show effects. Conclusions: enhances patients. While treatment-related factors limited influence, anxiety played moderating role. These findings underscore importance personalized care integrated mental management.

Language: Английский

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The Triglyceride-Glucose Index as a Biomarker for Insulin Resistance Following Hepatitis C Virus Eradication: A Prospective Cohort Study

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(9), P. 2963 - 2963

Published: April 25, 2025

Background: The triglyceride-glucose (TyG) index has emerged as a novel surrogate marker of insulin resistance, but its changes after hepatitis C virus (HCV) eradication remain unclear. This study aimed to evaluate in the TyG following direct-acting antiviral (DAA) treatment. Methods: HCV-infected patients achieving sustained virological response 12 weeks post-treatment (SVR12) were prospectively enrolled from May 2015 June 2023. Exclusion criteria included following: (1) failure achieve SVR12; (2) use anti-diabetes or anti-hyperlipidemia medications; and (3) B human immunodeficiency co-infection. Changes lipid profiles, index, homeostasis model assessment resistance (HOMA-IR) evaluated baseline SVR12. Insulin was defined HOMA-IR ≥ 2.5. optimal cut-off for predicting determined using Youden Index. Results: A total 111 (median age: 61.0 years; 45.9% male) included. correlated positively with (Pearson’s r = 0.32, p < 0.001). Among pre-existing significant improvements observed at SVR12 both (4.0 [IQR: 3.1–5.4] vs. 2.5 2.0–3.9]; 0.001) (8.47 8.08–8.68] 8.36 8.00–8.71]; 0.028). Using 8.27 cut-off, similar noted (2.8 2.0–4.3] 2.3 1.5–3.8]; 0.031) (8.62 8.46–8.83] 8.52 8.27–8.89]; 0.003). Conclusions: is valuable tool monitoring HCV eradication, particularly resistance.

Language: Английский

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Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis C Virus Infection

Biology, Journal Year: 2022, Volume and Issue: 12(1), P. 23 - 23

Published: Dec. 22, 2022

Hepatitis C virus (HCV) is a significant cause of chronic liver diseases worldwide and associated with negative consequences, including cirrhosis, hepatic decompensation, hepatocellular carcinoma, increased risk mortality. In addition to liver-related morbidities, HCV also several extrahepatic manifestations, mixed cryoglobulinemia, diabetes mellitus, cardiocerebrovascular disease, lymphoma, autoimmune diseases. These non-liver-related complications increase the complexity this disease can contribute economic burden, morbidity, quality life, mortality throughout world. Therefore, understanding how each manifestation worth investigating. Currently, advancement treatment advent direct-acting anti-viral agents (DAAs) has led high cure rate as result sustained virologic response tremendously reduced burden complications. However, HCV-associated manifestations remain relevant concern, review aims give an updated highlight prevalence, factors, burdens, options for these conditions.

Language: Английский

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Molecular pathogenesis: Connections between viral hepatitis-induced and non-alcoholic steatohepatitis-induced hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 15, 2022

Hepatocellular carcinoma(HCC) is the sixth most common cancer in world and usually caused by viral hepatitis (HBV HCV), alcoholic, non-alcoholic fatty liver disease(NAFLD). Viral accounts for 80% of HCC cases worldwide. In addition, With increasing incidence metabolic diseases, NAFLD now disease a major risk factor developed countries. This review mainly described specificity similarity between pathogenesis hepatitis(HBV HCV)-induced NAFLD-induced HCC. general, promotes development through specific encoded proteins. HBV can also exert its tumor-promoting mechanism integrating into host chromosome, while HCV cannot. hepatitis-related NASH-related differ terms genetic factors, epigenetic modifications (DNA methylation, histone modifications, microRNA effects). both them lead to progression abnormal lipid metabolism, persistent inflammatory response, immune intestinal microbiome dysregulation.

Language: Английский

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Hepatitis C virus eradication by direct‐acting antivirals causes a simultaneous increase in the prevalence of fatty liver and hyper low‐density lipoprotein cholesterolemia without an increase in body weight

Hepatology Research, Journal Year: 2023, Volume and Issue: 53(7), P. 595 - 606

Published: March 22, 2023

Hepatitis C virus (HCV) infection has been reported to cause liver steatosis. Thus, eradicating HCV with direct-acting antivirals (DAAs) is expected reduce We aimed clarify long-term changes in the prevalence of fatty and hyper-low-density lipoprotein (LDL) cholesterolemia their associations patients who achieve successful eradication using DAAs.This retrospective study included achieved sustained virologic response after interferon-free DAA analyzed diagnosed controlled attenuation parameter (CAP), hyper-LDL cholesterolemia, relationships at baseline (n = 100) 24 weeks (SVR24, n 100), 96 (SVR96, 144 (SVR144, 90) DAA.In 100 participants, (19% vs. 32%, p 0.0349) (6% 15%, 0.0379) significantly increased without body weight SVR96. Median total cholesterol, low-density cholesterol (LDL-C), small-dense-LDL (sdLDL) levels CAP values were greater SVR24, SVR96, SVR144 than baseline. Baseline negatively correlated every observation point: r -0.5305, < 0.0001 SVR24; -0.3617, 0.0005 SVR96; -0.4735, SVR144. A similar relationship was observed levels. Unlike baseline, positively LDL-C sdLDL-C all points DAAs.Direct-acting may an accompanying weight. As post-SVR steatosis could HCC, careful follow-up be required.

Language: Английский

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Immunotherapies for hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Current and developing strategies

Advances in cancer research, Journal Year: 2022, Volume and Issue: unknown, P. 367 - 413

Published: Jan. 1, 2022

Language: Английский

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