In patients with hepatitis E virus (HEV) infections, extrahepatic, particularly renal and hematological manifestations, are increasingly reported in the medical literature but have never been studied compared to a control cohort. We retrospectively analyzed medical records of consecutive patients that were diagnosed with acute hepatitis E (AHE) (n = 69) or acute hepatitis A (AHA) (n = 46) at the University Medical Center Hamburg Eppendorf from January 2009 to August 2019 for demographical, clinical, and laboratory information. Patients with AHE had significantly lower median levels of ALAT (798 U/L) and total bilirubin (1.8 mg/dL) compared to patients with AHA (2326 U/L; p < 0.001 and 5.2 mg/dL; p < 0.001), suggesting a generally less severe hepatitis. In contrast, patients with AHE had significantly higher median serum creatinine levels (0.9 mg/dL vs. 0.8 mg/dL; p = 0.002) and lower median estimated glomerular filtration rate (eGFR) (91 mL/min/1.73 m2 vs. 109 mL/min/1.73 m2; p < 0.001) than patients with AHA. Leucocyte, neutrophil and lymphocyte count, hemoglobin, platelets, red cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), and RDW to lymphocyte ratio (RLR) did not differ between patients with AHE and those with AHA. Our observations indicate that renal but not hematological interference presents an underrecognized extrahepatic feature of AHE, while inflammation of the liver seems to be more severe in AHA.