Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors

Abstract

Background: Bodybuilding supplements can cause a profound cholestatic syndrome.

Aim: To describe the drug-Induced liver injury network's experience with liver injury due to bodybuilding supplements.

Methods: Liver injury pattern, severity and outcomes, potential genetic associations, and exposure to anabolic steroids by product analysis were analysed in prospectively enrolled subjects with bodybuilding supplement-induced liver injury with causality scores of probable or higher.

Results: Forty-four males (mean age 33 years) developed liver injury with a median latency of 73 days. Forty-one per cent presented with hepatocellular pattern of liver injury as defined by the R > 5 ([Fold elevation of ALT] ÷ [Fold elevation of Alk Phos] (mean, range = 6.4, 0.5-31.4, n = 42) despite all presenting with clinical features of cholestatic liver injury (100% with jaundice and 84% with pruritus). Liver biopsy (59% of subjects) demonstrated a mild hepatitis and profound cholestasis in most without bile duct injury, loss or fibrosis. Seventy-one per cent were hospitalised, and none died or required liver transplantation. In some, chemical analysis revealed anabolic steroid controlled substances not listed on the label. No enrichment of genetic variants associated with cholestatic syndromes was found, although mutations in ABCB11 (present in up to 20%) were significantly different than in ethnically matched controls.

Conclusions: Patients with bodybuilding supplements liver injury uniformly presented with cholestatic injury, which slowly resolved. The ingested products often contained anabolic steroids not identified on the label, and no enrichment in genetic variants was found, indicating a need for additional studies.

Figure 1.. Median total bilirubin (mg/dL) (uMol) or Alk Phos and ALT activity in U/L plotted over time in weeks after presentation.

The lines connect the median values over time for each serum test. The numbers of subjects at different time period for ALT are as follows (with about +/− 1 for others): 44 at onset (day 0); 36 at Week 1; 31 at Week 2; 35 for Week 3–4; 29 for Week 5–6; 22 for Week 7–8; 23 for Week 8–12; 36 for > 12 Weeks 36. Mean values are depicted as symbols inside the box with the top and bottom of the box representing the 25 and 75 percentiles, respectively.

Figure 2.. Histological findings in anabolic steroid DILI.

Anabolic androgenic steroid liver injury is classically associated with bland cholestasis. There is canalicular and hepatocellular cholestasis with little or no lobular inflammation (A) and portal areas have a normal appearance without inflammation (B). (H&E, 600× and 400× respectively). Most of the cases in this report had mild degree of inflammation. Multiple small foci of lobular inflammation (arrowheads) are seen along with canalicular cholestasis (arrows) (C). The portal areas of this case also show inflammation (D).