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Expanded Dengue and the Digestive System: A Systematic Review and Meta-Analysis
Daniel Peñaherrera-Vásquez1,2, Alison Reina3, Gabriela Zambrano-Sánchez1,4
1Unidad de Revisiones Sistemáticas y Metaanálisis-URMA, Facultad de Ciencias Médicas, Universidad Central del Ecuador, Quito 170403, Ecuador.
Abstract:
Background Expanded dengue syndrome represents a severe and atypical spectrum of dengue virus infection characterized by multisystem involvement beyond classic manifestations. While mild gastrointestinal symptoms are common in classic dengue, expanded dengue syndrome may present with clinically significant digestive organ involvement, including hepatitis, fulminant hepatic failure, pancreatitis, and acute acalculous cholecystitis. These manifestations often resemble primary gastrointestinal diseases, leading to diagnostic delays and inappropriate management. Despite increasing recognition, the true frequency of digestive system involvement remains poorly defined due to heterogeneous reporting and limited quantitative evidence. Methodology/Principal Findings A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251270772). MEDLINE, Scopus, Web of Science, Embase, CENTRAL, Scielo, and BIREME were searched from inception to December 10, 2025. Primary studies reporting laboratory-confirmed dengue infection with atypical digestive system involvement and sufficient quantitative data were included. Seven studies comprising 1774 participants met eligibility criteria. Random-effects meta-analyses were performed to estimate pooled frequencies of gastrointestinal manifestations. The pooled frequency of hepatic involvement was 7% (95% confidence interval: 0-21), including fulminant hepatic failure (3%) and hepatitis (33%), with substantial heterogeneity. Acute pancreatitis occurred in 3% (95% confidence interval: 0-11) of cases. Acute acalculous cholecystitis was the most frequent manifestation, with a pooled frequency of 21% (95% confidence interval: 3-48). All included studies were classified as low risk of bias.
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