Syphilitic Hepatitis Presenting As Cholestatic Liver Injury: A Case Report

An estimated 8.0 million new adult syphilis infections occurred worldwide in 2022, according to World Health Organization figures cited in a case report published on October 13, 2026, by Cureus, highlighting a sexually transmitted infection that can involve virtually any organ system, including the liver. While liver involvement remains an uncommon manifestation, physicians note it typically presents with a distinct pattern of injury that can easily be mistaken for other hepatobiliary conditions.

Cholestatic Liver Injury Patterns in Secondary Syphilis

The Cureus case details a 61-year-old man admitted with a 15-day history of fatigue, bilateral leg edema, dry cough, odynophagia, weight loss, and conjunctivitis of the right eye. Laboratory testing revealed a cholestatic pattern of liver injury. Alkaline phosphatase reached 895 U/L and gamma-glutamyl transpeptidase climbed to 981 U/L, levels that were disproportionately elevated compared to alanine aminotransferase at 103 U/L and aspartate aminotransferase at 84 U/L. Total bilirubin registered at 3.16 mg/dL.

PMC.ncbi.nlm.nih.gov published parallel case analyses demonstrating similar diagnostic puzzles, noting that syphilitic hepatitis incidence ranges from 0.2% to 38% among diagnosed patients. One PMC report described a 28-year-old male presenting with right-sided abdominal tenderness, aspartate aminotransferase of 169 U/L, alanine transaminase of 271 U/L, and alkaline phosphatase of 377 U/L. A separate PMC account detailed an incarcerated 36-year-old female presenting with seizures and multiple liver lesions.

Differential Diagnosis and Diagnostic Challenges

Syphilis is caused by the spirochete Treponema pallidum and has historically earned the moniker the great imitator because its dissemination affects diverse organ systems. The Cureus report points out that hepatic involvement is frequently overlooked because presenting symptoms are non-specific and a cholestatic profile with jaundice more readily suggests biliary obstruction, malignancy, or drug-induced liver injury.

In the Cureus case, viral hepatitis panels for A, B, C, and E, along with cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus tests, returned negative results. The Venereal Disease Research Laboratory test proved reactive at a titer of 1/128, and anti-Treponema pallidum IgG tested positive, leading to a diagnosis of secondary syphilis with hepatic involvement. PMC reports emphasize that diagnosis relies on combining non-treponemal tests with specific assays after excluding alternative causes of hepatic dysfunction.

Antimicrobial Treatment and Clinical Resolution

Management for secondary syphilis with hepatic involvement relies on standard antimicrobial therapy. The patient described in the Cureus report received a single intramuscular dose of 2.4 million IU of benzathine penicillin G. Following this intervention, symptoms resolved completely and liver biochemical parameters largely normalized within six months.

PMC reporting mirrors this therapeutic response, noting that the 28-year-old male patient experienced complete symptom resolution and normalization of liver function tests one week after receiving the same 2.4 million-unit benzathine penicillin G regimen. Both publications stress that prompt recognition prevents disease progression to fulminant hepatic failure.

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