Severe liver fibrosis in the HCV cure era: Major effects of social vulnerability, diabetes, and unhealthy behaviors

Beo, Vincent Di; Barré, Tangui; Bureau, Morgane; Marcellin, Fabienne; Protopopescu, Camélia; Alric, Laurent; Bonnet, Delphine; Payssan-Sicart, Virginie; Pomes, Chloe; Maynard, Marianne; Bai, Roxane; Hucault, Lucie; Bailly, François; Raffi, François; Billaud, Éric; Boutoille, David; Lefèbvre, M.; André-Garnier, Élisabeth; Calès, Paul; Hubert, I.; Lannes, Adrien; Lunel, F.; Asselah, Tarik; Boyer, Nathalie; Giuily, Nathalie; Castelnau, Corinne; Scoazec, Giovanna; Rousseaud, Emilie; Vallet-Pichard, Anaı̈s; Sogni, Philippe; Foucher, Juliette; Hiriart, Jean‐Baptiste; M’Bouyou, Jancell; Irlès‐Depé, Marie; Ahmed, Si Nafa Si; Oulès, Valérie; Tran, Albert; Anty, Rodolphe; Gelsi, Ève; Truchi, Régine; Thabut, Dominique; Hammeche, Saloua; Moussali, Joseph; Causse, Xavier; Dieuleveult, Barbara De; Ouarani, Brahim; Labarrière, Damien; Ganne, Nathalie; Grando‐Lemaire, Véronique; Brulé, Séverine; Ulker, Betul; Guyader, Dominique; Jézéquel, Caroline; Brener, Audrey; Laligant, Anne; Rabot, Aline; Renard, Isabelle; Habersetzer, François; Baumert, Thomas F.; Doffoël, Michel; Mutter, Catherine; Simo-Noumbissie, Pauline; Razi, Esma; Bronowicki, Jean–Pierre; Barraud, Hélène; Bensenane, Mouni; Nani, Abdelbasset; Hassani-Nani, Sarah; Bernard, Marie-Albertine; Meszaros, Magda; Métivier, Sophie; Bureau, Christophe; Morales, Thibault; Péron, Jean Marie; Robic, Marie Angèle; Decaens, Thomas; Froissart, Bruno; Hilleret, Marie‐Noëlle; Costentin, Charlotte; Gerster, Théophile; Riachi, Ghassan; Goria, Odile; Paris, Fatima; Montialoux, Hélène; Leroy, Vincent; Amaddeo, Giuliana; Varaut, Anne; Simoes, Mélanie; Amzal, Rachida; Chazouillières, Olivier; Andréani, Tony; Angoulevant, Bénédicte; Chevance, Azeline; Serfaty, Lawrence; Vallée, Jean‐Charles Duclos; Samuel, Didier; Antonini, Térésa; Coilly, Audrey; Tateo, Mariagrazia; Abergel, Armand; Reymond, Maud; Brigitte, Chanteranne; Benjamin, Buchard; Muti, Leon; Geist, Claire; Conroy, Guillaume; Riffault, Raphaëlle; Rosa, Isabelle; Barrault, Camille; Laurent, Alexis; Hagège, Hervé; Loustaud‐Ratti, Véronique; Carrier, Paul; Debette‐Gratien, Maryline; Maury, Philippe; Lassailly, Guillaume; Lemaître, Elise; Canva, V.; Dharancy, Sébastien; Louvet, Alexandre; Minello, Anne; Latournerie, Marianne; Bardou, Marc; Mouillot, Thomas; d’Altéroche, Louis; Barbereau, Didier; Nicolas, Charlotte; Elkrief, Laure; Jaillais, Anaïs; Gournay, Jérôme; Chevalier, Caroline; Archambeaud, Isabelle; Habes, Sarah; Portal, Isabelle; Gelu-Siméon, Moana; Saillard, Eric; Lafrance, Marie-Josée; Catherine, Lucie; Chau, Frédéric; Goderel, Isabelle; Lusivika‐Nzinga, Clovis; Bellance, Marc-Antoine; Bellet, Jonathan; Monfalet, Priscilla; Chane-Teng, Jessica; Bijaoui, Sephora; Pannetier, Grégory; Téoulé, François; Nicol, Jérôme; Bekhti, Rafika; Nailler, Laura; Meut, Guillaume Le; Bourlière, Marc; Boursier, Jérôme; Carrat, Fabrice; Carrieri, Patrizia; Delarocque-Astagneau, Elisabeth; Lédinghen, Victor de; Dorival, Céline; Fontaine, Hélène; Fourati, Slim; Housset, Chantal; Larrey, Dominique; Nahon, Pierre; Pageaux, Georges‐Philippe; Petrov–Sanchez, Ventzislava; Pol, Stanislas; Bruyand, Mathias; Wittkop, Linda; Zoulim, Fabien; Zucman–Rossi, Jessica; L’hennaff, Marianne; Sizorn, Michèle; Boston, Anaïs; Diallo, Alpha; Cagnot, Carole; Bousselet, Alice; Caralp, Mireille

doi:10.1016/j.jhepr.2022.100481

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…The liver fibrosis stage was defined by histology and/or transient elastography, according to METAVIR classification [ 1 ]. Due to the intended balancing between all the different stages of liver disease, there was an obvious overrepresentation of the more advanced stages of fibrosis (and, consequently, of HCC) compared to what was expected a priori in a non-selected outpatient population (which would be around 30%) [ 22 ]. As reported in every HCV population, we found a high prevalence of metabolic diseases (such as diabetes, hypertension, or dyslipidemia) [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

Plasma Pattern of Extracellular Vesicles Isolated from Hepatitis C Virus Patients and Their Effects on Human Vascular Endothelial Cells

Grossini

Smirne

Venkatesan

et al. 2023

IJMS

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Hepatitis C virus (HCV) patients are at increased risk of cardiovascular disease (CVD). In this study, we aimed to evaluate the role of extracellular vesicles (EVs) as pathogenic factors for the onset of HCV-related endothelial dysfunction. Sixty-five patients with various stages of HCV-related chronic liver disease were enrolled in this case series. Plasma EVs were characterized and used to stimulate human vascular endothelial cells (HUVEC), which were examined for cell viability, mitochondrial membrane potential, and reactive oxygen species (ROS) release. The results showed that EVs from HCV patients were mainly of endothelial and lymphocyte origin. Moreover, EVs were able to reduce cell viability and mitochondrial membrane potential of HUVEC, while increasing ROS release. Those harmful effects were reduced by the pretreatment of HUVEC with the NLR family pyrin domain containing 3 (NLRP3)/AMP-activated protein kinase and protein kinase B blockers. In conclusion, in HCV patients, we could highlight a circulating pattern of EVs capable of inducing damage to the endothelium. These data represent a novel possible pathogenic mechanism underlying the reported increase of CVD occurrence in HCV infection and could be of clinical relevance also in relation to the widespread use of antiviral drugs.

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Section: Resultsmentioning

confidence: 99%

Plasma Pattern of Extracellular Vesicles Isolated from Hepatitis C Virus Patients and Their Effects on Human Vascular Endothelial Cells

Grossini

Smirne

Venkatesan

et al. 2023

IJMS

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“…[95] Yet, even among patients with high sustained virological response, unemployment and low educational attainment were associated with severe liver fibrosis. [97] Addressing these disparities in DAA treatment could help decrease the LT indication for HCV. [93] NAFLD/NASH NAFLD/NASH is the fastest-growing cause of HCC in LT candidates and recipients [98] and is expected to surpass ALD as the leading indication for LT in all patients within the next few years.…”

Section: Geographic Disparities By Liver Disease Etiologymentioning

confidence: 99%

“…Solutions to address these urban-rural differences in DAA treatment include the use of telehealth to educate rural primary care providers about prescribing DAAs 95 . Yet, even among patients with high sustained virological response, unemployment and low educational attainment were associated with severe liver fibrosis 97 . Addressing these disparities in DAA treatment could help decrease the LT indication for HCV 93 …”

Section: Geographic Disparities By Liver Disease Etiologymentioning

confidence: 99%

Geographic disparities in access to liver transplantation

Yilma

Dalal

Wadhwani

et al. 2023

Liver Transplantation

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Since the Final Rule regarding transplantation was published in 1999, organ distribution policies have been implemented to reduce geographic disparity. While a recent change in liver allocation, termed acuity circles, eliminated the donor service area as a unit of distribution to decrease the geographic disparity of waitlisted patients to liver transplantation, recently published results highlight the complexity of addressing geographic disparity. From geographic variation in donor supply, as well as liver disease burden and differing model for end-stage liver disease (MELD) scores of candidates and MELD scores necessary to receive liver transplantation, to the urban-rural disparity in specialty care access, and to neighborhood deprivation (community measure of socioeconomic status) in liver transplant access, addressing disparities of access will require a multipronged approach at the patient, transplant center, and national level. Herein, we review the current knowledge of these disparities—from variation in larger (regional) to smaller (census tract or zip code) levels to the common etiologies of liver disease, which are particularly affected by these geographic boundaries. The geographic disparity in liver transplant access must balance the limited organ supply with the growing demand. We must identify patient-level factors that contribute to their geographic disparity and incorporate these findings at the transplant center level to develop targeted interventions. We must simultaneously work at the national level to standardize and share patient data (including socioeconomic status and geographic social deprivation indices) to better understand the factors that contribute to the geographic disparity. The complex interplay between organ distribution policy, referral patterns, and variable waitlisting practices with the proportion of high MELD patients and differences in potential donor supply must all be considered to create a national policy strategy to address the inequities in the system.

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“…However, it becomes clear that virus-induced disease cannot be fully eliminated because of multifactorial reasons including underlying liver fibrosis, comorbidities, and socioeconomic status. 3 , 4 , 5 Epigenetic imprinting by chronic infection and injury is associated with persistent pro-oncogenic transcriptional pattern, an important driver of persistent HCC-risk post-HCV cure. Epigenetics represents the genomic memory of environmental conditions in the past.…”

mentioning

confidence: 99%