The etiology of acute hepatic cytolysis is complex, and a thorough laboratory investigation is needed to find the causative agent and guide the clinician toward a specific treatment. Viral hepatitis A is a well-known cause of acute hepatitis, but other viruses and bacteria can lead to or contribute to liver damage. We report the case of a young male patient with triple infection with hepatitis A virus, Epstein–Barr virus, and Leptospira spp. To our knowledge, this is the first case of an HAV, EBV, and Leptospira triple infection, and it aims to bring awareness about the possibility of double or triple infection with such pathogens that are highly cytotoxic for the liver tissue since all three pathogens are known to cause or contribute to the onset of acute hepatitis. It was deduced that the source of the infection likely happened during a two-week visit to the countryside in Romania, returning 16 days before the onset of symptoms. The evolution was favorable receiving treatment with amoxicillin/clavulanic acid (1200 mg/8 h); glucose 5% 500 mL/day; 0.9% saline 500 mL/day; phenobarbital 1 tablet/day (200 mg); vitamins B1 and B6 and a complex of vitamin C and D3 and zinc. Lactulose syrup was also administered when the patient had no bowel movement for more than 24 h to prevent the onset of hepatic encephalopathy, and the patient was discharged after 20 days. This case suggests that a detailed anamnesis can raise suspicion about more uncommon causes of hepatic cytolysis and lead to a broader and more complex laboratory investigation, thus improving the quality of patient care. Yet, this is the only case previously reported to compare different management options and patient outcomes.
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