Elsa Sola

All Publications

• Infections in decompensated cirrhosis: Pathophysiology, management, and research agenda. Hepatology communications Ferguson Toll, J., Solà, E., Perez, M. A., Piano, S., Cheng, A., Subramanian, A. K., Kim, W. R. 2024; 8 (10)

  Abstract

  Bacterial infections in patients with cirrhosis lead to a 4-fold increase in mortality. Immune dysfunction in cirrhosis further increases the risk of bacterial infections, in addition to alterations in the gut microbiome, which increase the risk of pathogenic bacteria. High rates of empiric antibiotic use contribute to increased incidence of multidrug-resistant organisms and further increases in mortality. Despite continous advances in the field, major unknowns regarding interactions between the immune system and the gut microbiome and strategies to reduce infection risk and improve mortality deserve further investigation. Here, we highlight the unknowns in these major research areas and make a proposal for a research agenda to move toward improving disease progression and outcomes in patients with cirrhosis and infections.

  View details for DOI 10.1097/HC9.0000000000000539

  View details for PubMedID 39365139

• Prospective validation of the EASL management algorithm for acute kidney injury in cirrhosis. Journal of hepatology Ma, A. T., Sole, C., Juanola, A., Escude, L., Napoleone, L., Avitabile, E., Perez-Guasch, M., Carol, M., Pompili, E., Gratacos-Gines, J., Soria, A., Rubio, A. B., Cervera, M., Moreta, M. J., Morales, M., Sola, E., Poch, E., Fabrellas, N., Graupera, I., Pose, E., Gines, P. 2024

  Abstract

  BACKGROUND AND AIMS: The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice.METHODS: Prospective cohort study of consecutive hospitalized patients with cirrhosis and AKI. EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥ stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). Primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy.RESULTS: A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in 1/3 of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with ATN being the most common phenotype. Response rate in patients not meeting criteria of HRS-AKI was 70%. Only 30 patients met the diagnostic criteria HRS-AKI, and response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While urinary neutrophil gelatinase-associated lipocalin (uNGAL) could differentiate acute tubular necrosis (ATN) vs other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema.CONCLUSIONS: The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy.

  View details for DOI 10.1016/j.jhep.2024.03.006

  View details for PubMedID 38479614

• γδ T cell antigen receptor polyspecificity enables T cell responses to a broad range of immune challenges. Proceedings of the National Academy of Sciences of the United States of America Guo, J., Chowdhury, R. R., Mallajosyula, V., Xie, J., Dubey, M., Liu, Y., Li, J., Wei, Y. L., Palanski, B. A., Wang, C., Qiu, L., Ohanyan, M., Kask, O., Sola, E., Kamalyan, L., Lewis, D. B., Scriba, T. J., Davis, M. M., Dodd, D., Zeng, X., Chien, Y. H. 2024; 121 (4): e2315592121

  Abstract

  γδ T cells are essential for immune defense and modulating physiological processes. While they have the potential to recognize large numbers of antigens through somatic gene rearrangement, the antigens which trigger most γδ T cell response remain unidentified, and the role of antigen recognition in γδ T cell function is contentious. Here, we show that some γδ T cell receptors (TCRs) exhibit polyspecificity, recognizing multiple ligands of diverse molecular nature. These ligands include haptens, metabolites, neurotransmitters, posttranslational modifications, as well as peptides and proteins of microbial and host origin. Polyspecific γδ T cells are enriched among activated cells in naive mice and the responding population in infection. They express diverse TCR sequences, have different functional potentials, and include the innate-like γδ T cells, such as the major IL-17 responders in various pathological/physiological conditions. We demonstrate that encountering their antigenic microbiome metabolite maintains their homeostasis and functional response, indicating that their ability to recognize multiple ligands is essential for their function. Human γδ T cells with similar polyspecificity also respond to various immune challenges. This study demonstrates that polyspecificity is a prevalent feature of γδ T cell antigen recognition, which enables rapid and robust T cell responses to a wide range of challenges, highlighting a unique function of γδ T cells.

  View details for DOI 10.1073/pnas.2315592121

  View details for PubMedID 38227652

• AASLD Practice guidance on Acute-on-chronic liver failure and the management of critically Ill patients with cirrhosis. Hepatology (Baltimore, Md.) Karvellas, C. J., Bajaj, J. S., Kamath, P. S., Napolitano, L., O'Leary, J. G., Solà, E., Subramanian, R., Wong, F., Asrani, S. K. 2023

  View details for DOI 10.1097/HEP.0000000000000671

  View details for PubMedID 37939273

• Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis. Gut Juanola, A., Ma, A. T., de Wit, K., Gananandan, K., Roux, O., Zaccherini, G., Jimenez, C., Tonon, M., Sole, C., Villaseca, C., Uschner, F. E., Graupera, I., Pose, E., Moreta, M. J., Campion, D., Beuers, U., Mookerjee, R. P., Francoz, C., Durand, F., Vargas, V., Piano, S., Alonso, S., Trebicka, J., Laleman, W., Asrani, S. K., Soriano, G., Alessandria, C., Serra-Burriel, M., Morales-Ruiz, M., Torres, F., Allegretti, A. S., Krag, A., Caraceni, P., Watson, H., Abraldes, J. G., Sola, E., Kamath, P. S., Hernaez, R., Gines, P., LiverHope Investigators, Aban, M., Andrade, R., Angeli, P., Avitabile, E., Bassegoda, O., Bernardi, M., Carol, M., Cervera, M., Chiappa, M. T., Esnault, V., Fabrellas, N., Farres, J., Ferstl, P., Gratacos-Gines, J., Joyera, M., Korenjak, M., Martinez, S., Montagnese, S., Napoleone, L., Nicolao, G., Palacio, E., Pavesi, M., Perez-Guasch, M., Pich, J., Rubio, A. B., Schulz, M., Simon-Talero, M., Vives, A. 2023

  Abstract

  BACKGROUND: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications.METHODS: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not.RESULTS: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46).CONCLUSION: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.

  View details for DOI 10.1136/gutjnl-2023-329923

  View details for PubMedID 37884354

• Editorial: composite kidney outcomes in studies with patients with cirrhosis and AKI-Are we ready to "MAKE" the switch? Alimentary pharmacology & therapeutics Ma, A. T., Sola, E. 2023; 57 (12): 1473-1474

  View details for DOI 10.1111/apt.17527

  View details for PubMedID 37243463

• NK-like CD8+ γδ T cells are expanded in persistent Mycobacterium tuberculosis infection. Science immunology Roy Chowdhury, R., Valainis, J. R., Dubey, M., von Boehmer, L., Sola, E., Wilhelmy, J., Guo, J., Kask, O., Ohanyan, M., Sun, M., Huang, H., Huang, X., Nguyen, P. K., Scriba, T. J., Davis, M. M., Bendall, S. C., Chien, Y. H. 2023; 8 (81): eade3525

  Abstract

  The response of gamma delta (γδ) T cells in the acute versus chronic phases of the same infection is unclear. How γδ T cells function in acute Mycobacterium tuberculosis (Mtb) infection is well characterized, but their response during persistent Mtb infection is not well understood, even though most infections with Mtb manifest as a chronic, clinically asymptomatic state. Here, we analyze peripheral blood γδ T cells from a South African adolescent cohort and show that a unique CD8+ γδ T cell subset with features of "memory inflation" expands in chronic Mtb infection. These cells are hyporesponsive to T cell receptor (TCR)-mediated signaling but, like NK cells, can mount robust CD16-mediated cytotoxic responses. These CD8+ γδ T cells comprise a highly focused TCR repertoire, with clonotypes that are Mycobacterium specific but not phosphoantigen reactive. Using multiparametric single-cell pseudo-time trajectory analysis, we identified the differentiation paths that these CD8+ γδ T cells follow to develop into effectors in this infection state. Last, we found that circulating CD8+ γδ T cells also expand in other chronic inflammatory conditions, including cardiovascular disease and cancer, suggesting that persistent antigenic exposure may drive similar γδ T cell effector programs and differentiation fates.

  View details for DOI 10.1126/sciimmunol.ade3525

  View details for PubMedID 37000856

• A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2. Nature materials Yin, Q., Luo, W., Mallajosyula, V., Bo, Y., Guo, J., Xie, J., Sun, M., Verma, R., Li, C., Constantz, C. M., Wagar, L. E., Li, J., Sola, E., Gupta, N., Wang, C., Kask, O., Chen, X., Yuan, X., Wu, N. C., Rao, J., Chien, Y., Cheng, J., Pulendran, B., Davis, M. M. 2023

  Abstract

  The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

  View details for DOI 10.1038/s41563-022-01464-2

  View details for PubMedID 36717665

• Assessment of kidney function in cirrhosis: Are we moving closer to accurate estimation of glomerular filtration rate? Liver international : official journal of the International Association for the Study of the Liver Ma, A. T., Juanola, A., Sola, E. 2022; 42 (5): 957-959

  View details for DOI 10.1111/liv.15238

  View details for PubMedID 35447007

• Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis. Hepatology communications Pose, E., Sola, E., Lozano, J. J., Juanola, A., Sidorova, J., Zaccherini, G., de Wit, K., Uschner, F., Tonon, M., Kazankov, K., Jimenez, C., Campion, D., Napoleone, L., Ma, A. T., Carol, M., Morales-Ruiz, M., Alessandria, C., Beuers, U., Caraceni, P., Francoz, C., Durand, F., Mookerjee, R. P., Trebicka, J., Vargas, V., Piano, S., Watson, H., Abraldes, J. G., Kamath, P. S., Davis, M. M., Gines, P., investigators of the LIVERHOPE Consortium, Schulz, M., Ferstl, P., Giovo, I., Roux, O., Simon-Talero, M., Perez-Guasch, M., Rubio, A. B., Cervera, M., Martinez, S., Fabrellas, N., Pich, J., Vives, A., Avitabile, E., Graupera, I., Sole, C., Bassegoda, O., Gratacos-Gines, J., Joyera, M., Palacio, E., Aban, M., Lanzillotti, T., Nicolao, G., Chiappa, M. T., Esnault, V., Andrade, R., Pavesi, M., Korenjak, M., Farres, J., Serra-Burriel, M., Angeli, P. 1800

  Abstract

  Patients with decompensated cirrhosis, particularly those with acute-on-chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n=42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE-SAFETY randomized, double-blind, placebo-controlled trial treated with simvastatin 20mg/day plus rifaximin 1,200mg/day (n=12) or matching placebo (n=13) for 3months. Plasma samples were analyzed using ultrahigh performance liquid chromatography-tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan-kynurenine and carnitine beta-oxidation pathways. An ACLF-specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan-kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

  View details for DOI 10.1002/hep4.1881

  View details for PubMedID 34964311

• Distinct phenotype of CD4+ T cells driving celiac disease identified in multiple autoimmune conditions. Nature medicine Christophersen, A., Lund, E. G., Snir, O., Sola, E., Kanduri, C., Dahal-Koirala, S., Zuhlke, S., Molberg, O., Utz, P. J., Rohani-Pichavant, M., Simard, J. F., Dekker, C. L., Lundin, K. E., Sollid, L. M., Davis, M. M. 2019

  Abstract

  Combining HLA-DQ-gluten tetramers with mass cytometry and RNA sequencing analysis, we find that gluten-specific CD4+ T cells in the blood and intestines of patients with celiac disease display a surprisingly rare phenotype. Cells with this phenotype are also elevated in patients with systemic sclerosis and systemic lupus erythematosus, suggesting a way to characterize CD4+ T cells specific for disease-driving antigens in multiple autoimmune conditions.

  View details for PubMedID 30911136