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Background Late relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by the rebound in liver enzymes and non-specific clinical manifestations around 30-60 days after YF symptom onset. Methods Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais, and were followed-up at 30-, 45- and 60- days post symptom onset (dps). Results From 46 up to 60 dps, 16% of YF patients (n=36/221) exhibited a rebound of transaminases (AST or ALT >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF. Conclusions These findings provide new data on the clinical course of late relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

Authors' contribution: MLM, MCFS-M and DGC performed study conception and design. MLB and FAG enrolled the patients and collected their samples. MAR and ALA designed patients' clinical data and ALA collected them. MLM, MCFS-M, IRO, LSMFB, HMM and DGC performed laboratory tests. MLM, MCFS-M and DGC performed data analysis and prepared the manuscript, and EFB-S performed its critical evaluation. All authors read and approved the final manuscript.

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