A 41-year-old HIV-infected man, successfully treated with antiretroviral drugs for 8 years, with a history of syphilis and viral hepatitis type C, was admitted to our hospital on January 19, 2022 because of nausea, vomiting, and upper abdominal pain. Physical examination did not reveal any abnormalities.

Laboratory investigations showed elevated levels of liver enzymes with alanine transaminase (ALT) at 88 U/l (reference range [RR], 10–50 U/l), aspartate transaminase (AST) at 54 U/l (RR, 0–38 U/l), alkaline phosphatase (ALP) at 156 U/l (RR, 40–129 U/l), and gamma-glutamyl transferase (GGTP) at 80 U/l (RR, 10–71 U/l). Total bilirubin level was normal. HIV viremia was below detection limit. T CD4+ count was 758 cells/µl. HBV DNA and HCV RNA were undetectable. The patient denied using any hepatotoxic drugs. However, rapid plasma reagin test (RPR) titer was 1:4.

Ultrasound examination of the liver showed multiple hypoechoic areas in the liver parenchyma. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple focal lesions in both lobes of the liver. The lesions were indistinctly contoured; the largest was approximately 23 mm × 21 mm × 16 mm in size. Based on ultrasound, CT, and MRI results (Figure 1), the most probable diagnosis seemed a malignant neoplasm (most likely liver metastases), and a series of further tests were performed to identify the primary focus. Colonoscopy, gastroscopy, ultrasound of the scrotum, CT scan of the chest, histopathologic examination of alveolar scrapings, ultrasound of the neck, and MRI of the head were done but no primary focus was found.

Figure 1. Magnetic resonance imaging of the patient’s liver

The liver biopsy was then performed, and 4 specimens of the liver lesions were sampled for histopathologic examination. It revealed inflammatory nature of the lesions, that is, large zones of necrosis with margins of marked granulomatous hepatitis, with giant cell masses, and no signs of malignancy. Laboratory tests were performed to determine the reason of the hepatic lesions. Tuberculosis, brucellosis, toxoplasmosis, lambliasis, amebiasis, and autoimmune hepatitis were tentatively excluded. Considering the positive result of RPR, a diagnosis of syphilitic hepatitis was suggested.

The patient was treated with benzathine penicillin (2 400 000 IU intramuscularly, 3 times at 7-day intervals), and soon we observed resolution of all clinical symptoms. After administration of the second dose of the antibiotic, ultrasound examination of the liver showed almost complete disappearance of the lesions. They were fewer, smaller, and mainly hyperechoic. Laboratory tests showed normalization of ALT, AST, ALP, and GGTP levels. The Veneral Disease Research Laboratory test, performed 2 months after the treatment, was negative.

The diagnostic criteria for syphilitic hepatitis proposed in 2004 include abnormal levels of liver enzymes, serological evidence for Treponema pallidum infection, exclusion of other causes of increased levels of liver enzymes, and their normalization after antibiotic therapy.1 An atypical hepatic manifestation of T. pallidum infection is estimated to be very rare in all cases of syphilis, affecting between 0.2% and 2.7% of patients.2 A systematic review of 144 patients revealed that approximately 89% of such manifestations develop in early syphilis and 6% at late stages.3