Alteraciones lipídicas y metabólicas tras la erradicación del virus de la hepatitis C mediante antivirales de acción directa

El virus de la Hepatitis C (VHC) provoca gran cantidad de cambios en el metabolismo del huésped, tanto por la afectación hepática que ocasiona, como de manera intrínseca a la infección. Desde la aparición del tratamiento con antivirales de acción directa (AAD), las tasas de erradicación han aumentado desde resultados claramente subóptimos hasta cifras por encima del 90%. Sin embargo, hay dudas acerca de los cambios y modificaciones en el metabolismo del paciente que pueden producirse tras la curación del virus, especialmente en el metabolismo lipídico. Se diseñó un estudio prospectivo, observacional, no intervencionista, llevado a cabo en las consultas externas del hospital Miguel Servet de Zaragoza. Se reclutaron todos los pacientes derivados para tratamiento con AAD por infección crónica por VHC. Se excluyeron pacientes con otras causas de enfermedad hepática, consumo abusivo de alcohol, tratamiento hipolipemiante o con insulina, tratamiento con neurolépticos y embarazo. También se excluyeron pacientes co-infectados por el VHB o el VIH. La resistencia a la insulina se evaluó mediante el índice HOMA. Las lipoproteínas se estudiaron mediante cromatografía líquida y espectroscopia de resonancia magnética nuclear. Se llevó a cabo un seguimiento analítico de un año y un seguimiento clínico de dos años.Se reclutaron un total de 167 pacientes, de los cuales menos del 10% presentaban cirrosis hepática. Se observaron niveles bajos de LDL colesterol y colesterol total antes del tratamiento erradicador, que aumentaron tras la curación del virus. También se observó un aumento de triglicéridos y de HDL colesterol (solo en hombres). En toda la cohorte se observó una mejoría en el índice HOMA. El metabolismo del hierro también mejoró, y se produjo un descenso significativo en los niveles de cianocobalamina circulantes. Mediante el análisis de las lipoproteínas se evidenció que las partículas virales se expulsaban a la circulación sistémica asociadas a VLDL ricas en APOE. No se observó un aumento desproporcionado de las partículas LDL de mayor riesgo aterogénico. Se ha constatado una reducción en el contenido en triglicéridos en las partículas HDL, que se correlaciona con la mejoría en el índice HOMA. La eliminación del VHC provoca un aumento en los niveles de colesterol total y LDL, pero sin conllevar un aumento del riesgo cardiovascular, probablemente debido a la mejora cualitativa de las lipoproteínas circulantes y a que no se produce un aumento desproporcionado de las subclases de mayor riesgo aterogénico. <br /

Valoración global de la cardiomiopatía cirrótica y su evolución después del trasplante hepático

HIPÓTESIS 1. En el paciente afecto de una hepatopatía en fase de CH existen unos cambios hemodinámicos y cardiológicos, que se caracterizan principalmente por la presencia de síndrome hiperdinámico y disfunción diastólica en reposo. Estas alteraciones se correlacionarán con el estadio de la hepatopatía. 2. La substitución del hígado cirrótico por uno sano comportará una normalización de las alteraciones hemodinámicas y cardiológicas. OBJETIVOS 1. Determinar la prevalencia, el grado y las características del trastorno cardiaco en la CH mediante estudio hemodinámico de corazón derecho, ecocardiograma y determinación de NT-proBNP y Cistatina C. 2. Determinar la prevalencia, el grado y las características del trastorno cardiaco en los pacientes trasplantados hepáticos. 3. Averiguar si el trastorno cardiaco es reversible y desaparece tras el TH comparando el estudio ecocardiográfico y los valores de NTproBNP y Cistatina C. 4. Investigar si dichas alteraciones cardiacas se correlacionan con el grado de insuficiencia hepática. 5. Investigar si la presencia de síndrome hiperdinámico comporta un mayor trastorno cardiaco. 6. Evaluar la utilidad del NT-proBNP y la Cistatina C en la cardiomiopatía cirrótica CONCLUSIONES 1. Un alto porcentaje de pacientes cirróticos presenta alteraciones en la función y en la estructura cardiaca, definidas mediante estudio hemodinámico, ecocardiograma y niveles de NT-proBNP. 2. Estas alteraciones cardiacas se correlacionan con el grado de deterioro hepático, definido por la clasificación de Child y el índice MELD. 3. Un alto porcentaje de pacientes trasplantados hepáticos presenta alteraciones en la función y en la estructura cardiaca, existiendo un empeoramiento respecto a los valores basales previos al trasplante hepático. 4. Los pacientes con síndrome hiperdinámico presentan una cirrosis más avanzada con un mayor índice cardiaco y un mayor desarrollo de hipertrofia ventricular izquierda. 5. Los niveles de NT-proBNP se correlacionan con la clase Child, el índice cardiaco y el índice de masa ventricular izquierda. 6. Los niveles de NT-proBNP presentan una especificidad elevada para el diagnóstico de insuficiencia cardiaca de alto gasto cardiaco. 7. Los niveles de Cistatina C se correlacionan con la clase Child, la creatinina sérica y la fracción de acortamiento ventricular izquierdo

Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B

COVID-19; Hepatitis B; TenofovirCOVID-19; Hepatitis B; TenofovirCOVID-19; Hepatitis B; TenofovirBackground and Aims HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). Methods Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. Results Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04–0.67, p = 0.01). Conclusion Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. No funding sources needed

Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression

Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis

Unraveling Adipose Tissue Dysfunction: Molecular Mechanisms, Novel Biomarkers, and Therapeutic Targets for Liver Fat Deposition

Adipose tissue (AT), once considered a mere fat storage organ, is now recognized as a dynamic and complex entity crucial for regulating human physiology, including metabolic processes, energy balance, and immune responses. It comprises mainly two types: white adipose tissue (WAT) for energy storage and brown adipose tissue (BAT) for thermogenesis, with beige adipocytes demonstrating the plasticity of these cells. WAT, beyond lipid storage, is involved in various metabolic activities, notably lipogenesis and lipolysis, critical for maintaining energy homeostasis. It also functions as an endocrine organ, secreting adipokines that influence metabolic, inflammatory, and immune processes. However, dysfunction in WAT, especially related to obesity, leads to metabolic disturbances, including the inability to properly store excess lipids, resulting in ectopic fat deposition in organs like the liver, contributing to non-alcoholic fatty liver disease (NAFLD). This narrative review delves into the multifaceted roles of WAT, its composition, metabolic functions, and the pathophysiology of WAT dysfunction. It also explores diagnostic approaches for adipose-related disorders, emphasizing the importance of accurately assessing AT distribution and understanding the complex relationships between fat compartments and metabolic health. Furthermore, it discusses various therapeutic strategies, including innovative therapeutics like adipose-derived mesenchymal stem cells (ADMSCs)-based treatments and gene therapy, highlighting the potential of precision medicine in targeting obesity and its associated complications

Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Na&iuml;ve Patients without History of Cardiovascular Disease

Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population