Interpreting Liver Function Abnormalities in Returned Travelers: Clinical Context Matters More Than Pathogen-Specific Signatures.

Liver function test abnormalities (LFTA) are frequently observed in ill-returned travelers, yet their diagnostic value remains uncertain. To gain more insights, a retrospective cohort study of 2,957 consecutive ill-returned travelers presenting to a national reference center for tropical diseases between 2012 and 2015 was conducted. The associations between clinical presentation, broad etiologic categories (viral, bacterial and parasitic infections) and the presence, severity and type of LFTA (parenchymatous, cholestatic or mixed) were evaluated using chi-square analysis, Cramér's V and standardized residuals. Pathogen-level analyses assessed variability in the frequency and severity of liver involvement. LFTA were present in 40% of patients and were predominantly mild with a mixed biochemical pattern. Clinical presentation was strongly associated with the presence, severity and type of LFTA. Febrile illness was associated with a higher likelihood of LFTA and with more severe and mixed-type abnormalities, whereas gastrointestinal and cutaneous presentations were associated with milder abnormalities. Broad etiologic categories were associated with the presence and severity of LFTA but showed no clinically meaningful association with biochemical pattern. Pathogen-level analyses revealed substantial heterogeneity in liver involvement. LFTA were prevalent but mainly non-specific in returning travelers. Clinical presentation offered more diagnostic insight than classification in viral, bacterial and parasitic etiology when interpreting liver involvement. LFTA should be evaluated within the clinical context, rather than as specific indicators of pathogens.