Browsing by Author "Marciano, Sebastián"

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    High inherited risk predicts age-associated increases in fibrosis in patients with MASLD
    (2025) Díaz, Luis Antonio; Alazawi, William; Agrawal, Saaket; Arab, Juan Pablo; Arrese, Marco; Idalsoaga, Francisco; Barreyro, Fernando Javier; Gadano, Adrián; Marciano, Sebastián; Martínez Morales, Jorge; Villela Nogueira, Cristiane; Leite, Nathalie; Alves Couto, Claudia; Theodoro, Rafael; Dias Monteiro, Mísia Joyner de Sousa; Oliveira, Claudia P.; Pessoa, Mario G.; Reis Alvares-da-Silva, Mario; Madamba, Egbert; Bettencourt, Ricki; Richards, Lisa M.; Majithia, Amit R.; Khera, Amit V.; Loomba, Rohit; Ajmera, Veeral
    Background & AimsLimited data have prevented routine genetic testing from being integrated into clinical practice in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to quantify the effect of genetic variants on changes in fibrosis severity per decade in MASLD.MethodsThis cross-sectional study included prospectively recruited adults with MASLD aged 18–70 who underwent magnetic resonance elastography (MRE) and genotyping for PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13. A genetic risk score (GRS) was calculated as the sum of established risk alleles in PNPLA3 minus protective variants in HSD17B13 (0=low risk, 1=high risk). We also estimated the polygenic risk score-hepatic fat content (PRS-HFC) and the adjusted version (PRS-5). The primary endpoint was the age-related change in liver stiffness measurement (LSM) on MRE by GRS. Findings were validated using an external cohort from Latin America.ResultsAmong 570 participants, the median age was 57 [49–64] years, 56.8% were women, and 34.2% were Hispanic. Median MRE was 2.4 [2.1–3.0] kPa, and 51% had high GRS. High GRS was independently associated with increased LSM (β=0.28 kPa, 95%CI:0.12–0.44, p=0.001) per 10-year age increase, while the low GRS group showed no significant difference. Similar findings were observed using PRS-HFC and PRS-5. PNPLA3 genotype alone also predicted higher LSM (C/G: β=0.32 kPa, 95%CI:0.02–0.61, p=0.034; G/G: β=0.87 kPa, 95%CI:0.52–1.22, p<0.0001) and G/G genotype was associated with significantly higher LSM by age 44, which was consistent in the validation population.ConclusionGRS, PRS-HFC, PRS-5, and PNPLA3 genotypes alone are associated with greater fibrosis per decade, resulting in divergent disease trajectories starting in midlife. Assessing genetic risk in MASLD will identify high-risk patients who require more frequent monitoring."
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    Inherited Genetic Risk of Liver Fibrosis in Lean Versus Nonlean Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD)
    (John Wiley & Sons Ltd., 2025) Tesfai, Kaleb; Díaz Piga, Luis Antonio; Arab, Juan Pablo; Arrese, Marco; Idalsoaga, Francisco; Ayares, Gustavo; Agrawal, Saaket; Barreyro, Fernando Javier; Gadano, Adrian; Marciano, Sebastián; Martínez Morales, Jorge; Villela‐Nogueira, Cristiane; Leite, Nathalie; Salles, Gil; Regina Cardoso, Claudia; Alves Couto, Claudia; Theodoro, Rafael; Monteiro. Mísia Joyner de Sousa Dias; Oliveira, Claudia P.; Pessoa, Mario G.; Alvares‐da‐Silva, Mario Reis; Huang, Daniel Q.; Madamba, Egbert; Singh, Seema; Lokanadham, Snigdha; Bettencourt, Ricki; Richards, Lisa M.; Khera, Amit V.; Loomba, Rohit; Ajmera, Veeral
    Introduction Previous studies have revealed conflicting results regarding liver fibrosis risk in lean metabolic dysfunction–associated steatotic liver disease (MASLD). We aimed to compare the risk of significant fibrosis in lean versus nonlean MASLD and identify fibrosis-associated factors in lean MASLD. Methods The study was a cross-sectional analysis of prospectively enrolled adults with MASLD. Individuals with lean MASLD were age- and sex-matched with nonlean MASLD. Fibrosis assessment included vibration-controlled transient elastography, magnetic resonance elastography and liver biopsy. A genetic risk score (GRS), summating the effect alleles of PNPLA3 and TM6SF2 minus the protective HSD17B13 genotype, was estimated to consider inherited genetic risk across BMI categories. Results were validated in an external Latin American cohort.ResultsThe mean ( SD) age of 312 included participants with MASLD was 58.3  11.6 years and 69.2% were female. 44 (14.1%) individuals were lean, 90 (28.9%) were overweight, 90 (28.9%) had class I obesity and 88 (28.1%) had class II or greater obesity. The prevalence of significant fibrosis was 27.3% in lean and 31.1% in nonlean (p = 0.653). Individuals with a high GRS had a higher prevalence of significant fibrosis compared to patients with low GRS (36.5% vs. 25.2%, p = 0.043) and the prevalence of significant fibrosis was similar in lean and nonlean patients with high GRS (31.3% vs. 37.1%, p = 0.645). The Latin American cohort exhibited similar results. Conclusions The prevalence of significant fibrosis and the effect of GRS were similar in lean and nonlean MASLD, highlighting that lean MASLD patients may have a comparable risk to overweight and obese MASLD.
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    Latin American Association for the Study of the Liver (ALEH) guidance of preoperative care in liver transplantation: referral criteria, patient assessment, and waiting list management
    (2025) Mainardi, Victoria; Pages, Josefina; Menéndez, Josemaría; Zapata, Rodrigo; Díaz Piga, Luis Antonio; Marciano, Sebastián; Cairo, Fernando; Padilla-Machaca, Martin; Tenorio, Laura; Urzúa, Álvaro; Navarro, Lucía; Domínguez, Nicolás; Coste, Pablo; Mendizábal, Manuel; Martínez, Jorge; López, Sergio; Varón, Adriana; Alfeu de Medeiros Fleck, jr; Abad Gonzáles, Jhon; Restrepo, Juan Carlos; Codes, Liana; Lisboa Bittencourt, Paulo; Pérez Figueroa, Norma Marlene; Castro-Narro, Graciela; Terrabuio, Débora Raquel B.; Pessoa, Mário Guimarães; Girala, Marcos; Schiavon, Leonardo Lucca; Aguilera, Edgard; Valenzuela Aguilera, Kenia; Samada, Marcia; Gerona, Solange; Villamil, Alejandra
    Liver transplantation (LT) is the standard of care therapy for patients with decompensated cirrhosis, early-stage hepatocellular carcinoma, acute liver failure, and other expanding indications. Latin America is a highly heterogeneous region characterized by an uneven distribution of socio-economic conditions and irregular access to health resources, and consequently LT activity varies across it. This current guidance of preoperative care in LT represents a collaborative effort to assess and standardize preoperative evaluation of liver transplant candidates in Latin America. It is the first position paper of the special interest group on LT of the Latin American Association for the Study of the Liver (ALEH), which draws evidence-based comprehensive recommendations regarding who to refer, the LT assessment and how to manage the patient on the waiting list, taking into consideration their applicability in Latin America.
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    MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis
    (Elsevier B.V., 2023) Diaz Piga, Luis Antonio; Fuentes Lopez, Eduardo; Ayares Campos, Gustavo Ignacio; Idalsoaga Ferrer, Francisco Javier; Arnold Álvarez, Jorge Ignacio; Valverde, María Ayala; Perez, Diego; Gómez, Jaime; Escarate, Rodrigo; Villalon Friedrich, Alejandro Andrés; Ramírez, Carolina A.; Hernández-Tejero, María; Zhang, Wei; Qian, Steve; Simonetto, Douglas; Ahn, Joseph C.; Buryska, Seth; Dunn, Winston; Mehta, Heer; Agrawal, Rohit; Cabezas, Joaquín; Garcia Carrera, Inés; Cuyas, Berta; Poca, Maria; Soriano, German; Sarin, Shiv K.; Maiwall, Rakhi; Jalal, Prasun K.; Abdulsada, Saba; Higuera de la Tijera, Fátima; Kulkarni, Anand V.; Rao, P. Nagaraja; Guerra Salazar, Patricia; Skladany, Lubomir; Bystrianska, Natália; Clemente Sánchez, Ana; Villaseca Gómez, Clara; Haider, Tehseen; Chacko, Kristina R.; Romero, Gustavo A.; Pollarsky Florencia D.; Restrepo, Juan Carlos; Castro Sánchez, Susan; Toro, Luis G.; Yaquich, Pamela; Mendizabal, Manuel; Garrido, María Laura; Marciano, Sebastián; Dirchwolf, Melisa; Vargas, Víctor; Jimenez, César; Louvet, Alexandre; Garcia Tsao, Guadalupe; Roblero, Juan Pablo; Abraldes, Juan G.; Shah, Vijay H.; Kamath, Patrick S.; Arrese Jimenez, Marco Antonio; Singal, Ashwani K.; Bataller, Ramón; Arab Verdugo, Juan Pablo
    © 2023 The Author(s)Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20–33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732–0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713–0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691–0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723–0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727–0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724–0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708–0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687–0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805–0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.