Browsing by Author "Díaz Piga, Luis Antonio"
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- ItemClinical Trial to Assess the Safety and Tolerability of Anti-IL 23 Monoclonal Antibody Guselkumab in Patients With Alcohol-Associated Liver Disease(2025) Díaz Piga, Luis Antonio; Morris, Sheldon; Dave, Shravan; Kim, Susy M.; Sarik, Wathnita; Richards, Lisa; Madamba, Egbert; Bettencourt, Ricki; Fulinara, Christian; Pham, Thuy; Miller, Grant; Carvalho-Gontijo Weber, Raquel; Momper, Jeremiah D.; He, Feng; Jain, Sonia; Jamieson, Catriona; Kisseleva, Tatiana; Brenner, David; Loomba, RohitBackgroundThere are no FDA-approved therapies for alcohol-associated liver disease (ALD). Preclinical studies indicate that blocking IL-23/IL-17 signalling may reverse liver injury. Guselkumab, an IL-23-specific antibody approved for psoriasis, may be beneficial for ALD. AimsWe aimed to assess the safety and tolerability of guselkumab in patients with ALD. MethodsThis phase-1 dose-escalation study included patients with >= 2 DSM-5 criteria for alcohol use disorder, significant steatosis (MRI-PDFF >= 8%) and MRE < 3.63 kPa (to exclude advanced disease). Guselkumab was given subcutaneously on Days 1 and 29 in 30, 70 or 100 mg dose cohorts. Primary endpoints were adverse events (AEs) and dose-limiting toxicity. ResultsWe enrolled 13 patients (three 30 mg, three 70 mg, and seven 100 mg). Eleven completed the study and two early discontinued in the 100 mg group. Of them, 77% were men, and the median age was 53 [IQR 49-61] years. The median MRI-PDFF and MRE were 18.4% [IQR 8.4%-34.0%] and 2.5 [2.2-2.6] kPa, respectively. The most frequent AEs were hyperuricemia (13%, mild only) and elevated lipase (11%, mild and moderate). There were no serious adverse events or significant variations in liver enzymes. There was a suppression of peripheral interleukin (IL)-17, IL-23, IL-1b and TNF-alpha in the 70 and 100 mg groups, and a significant decrease in alcohol consumption over time (AUDIT-C: 6 [3-7] vs. 5 [1-6], p = 0.023). Conclusions Guselkumab is safe in doses up to 100 mg and may reduce inflammation markers in ALD. These findings support further phase 2 studies to evaluate the efficacy of guselkumab in ALD, particularly in patients with severe phenotypes.
- ItemInpatient Hepatology Consultation: A Practical Approach for Clinicians(2023) Díaz Piga, Luis Antonio; Pages, Josefina; Mainardi, Victoria; Mendizabal, Manuel
- ItemLetter: Optimising public health policies to combat alcohol-associated liver disease in youth—Authors' reply(2024) Danpanichkul, Pojsakorn; Tothanarungroj, Primrose; Díaz Piga, Luis Antonio; Arab Verdugo, Juan Pablo; Liangpunsakul, Suthat; Wijarnpreecha, Karn
- ItemMetabolic dysfunction and alcohol-related liver disease (MetALD): Position statement by an expert panel on alcohol-related liver disease(2025) Arab Verdugo, Juan Pablo; Díaz Piga, Luis Antonio; Rehm, Jürgen; Im, Gene; Arrese, Marco; Kamath, Patrick S.; Lucey, Michael R.; Mellinger, Jessica; Thiele, Maja; Thursz, Mark; Bataller, Ramon; Burton, Robyn; Chokshi, Shilpa; Francque, Sven M.; Krag, Aleksander; Lackner, Carolin; Lee, Brian; Liangpunsakul, Suthat; MacClain, Craig; Mandrekar, Pranoti; Mitchell, Mack C.; Morgan, Marsha Y.In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.e., phosphatidylethanol), use of validated questionnaires (i.e. AUDIT-C [alcohol use disorders identification test consumption]), and collateral information from friends and relatives could help facilitate differentiation between alcohol-related liver disease (ALD) per se and liver disease with both metabolic and alcohol-related components (MetALD). Heavy alcohol use can contribute to cardiometabolic risk factors such as high blood pressure, hypertriglyceridaemia, and hyperglycaemia. As a result, caution should be exercised in the application of only one metabolic dysfunction criterion to diagnose MASLD, as suggested in the 2023 nomenclature document, particularly in individuals exceeding weekly alcohol use thresholds of 140 g for women and 210 g for men. This is particularly important in those individuals with isolated high blood pressure, hypertriglyceridaemia, or hyperglycaemia, where the disease process may be driven by alcohol itself. Additionally, metabolic dysfunction and alcohol use should be reassessed over time, especially after periods of change in risk factor exposure. This approach could ensure a more accurate prognosis and effective management of SLD, addressing both metabolic and alcohol-related factors.
- ItemPrevention and control of risk factors in metabolic and alcohol-associated steatotic liver disease(2024) Desalegn, Hailemichael; Farias Siel, Renata Francisca; Hudson, David; Idalsoaga Ferrer, Francisco Javier; Cabrera, Daniel; Díaz Piga, Luis Antonio; Arab Verdugo, Juan PabloSteatotic liver disease (SLD), including metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), is the primary cause of illness and mortality. In particular, MASLD affects more than 30% of the global population, while ALD accounts for 5.1% of all diseases and injuries worldwide. The SLD spectrum includes a variety of clinical conditions, from mild fatty liver and inflammation to different stages of liver fibrosis. Additionally, both conditions (MASLD and ALD) can be complicated by hepatocellular carcinoma (HCC), while around one-third of ALD patients can also develop at least one alcohol associated hepatitis (AH) episode. Both of these diseases are also associated with multiple extrahepatic complications, such as cardiovascular disease, chronic kidney disease, and malignancies. In MASLD, the rapid rise in global obesity and type 2 diabetes mellitus (T2DM) prevalence due to Westernized lifestyles has led to an increase in the prevalence of MASLD. Thus, the prevention and control of cardiometabolic risk factors (CMRFs) are the cornerstone of its treatment. Hypertension and atherogenic dyslipidemia are also important CMRFs associated with MASLD. Susceptible individuals with MASLD are adversely affected by even a small amount of alcohol consumption (though there is no agreed definition of a small amount), increasing the risk of severe outcomes and a faster progression of liver disease. This review explores factors that play a role in the development of SLD, especially focusing on the management of CMRFs and levels of alcohol use to prevent liver disease progression.