Liver Injury Associated with Turmeric-A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN]

Abstract

Background: Turmeric is a commonly used herbal product that has been implicated in causing liver injury. The aim of this case series is to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury cases enrolled the in US Drug-Induced Liver Injury Network (DILIN).

Methods: All adjudicated cases enrolled in DILIN between 2004 and 2022 in which turmeric was an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing.

Results: Ten cases of turmeric-associated liver injury were found, all enrolled since 2011, and 6 since 2017. Of the 10 cases, 8 were women, 9 were White, and median age was 56 years (range 35-71). Liver injury was hepatocellular in 9 patients and mixed in 1. Liver biopsies in 4 patients showed acute hepatitis or mixed cholestatic-hepatic injury with eosinophils. Five patients were hospitalized, and 1 patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper). HLA typing demonstrated that 7 patients carried HLA-B*35:01, 2 of whom were homozygous, yielding an allele frequency of 0.450 compared with population controls of 0.056-0.069.

Conclusion: Liver injury due to turmeric appears to be increasing in the United States, perhaps reflecting usage patterns or increased combination with black pepper. Turmeric causes potentially severe liver injury that is typically hepatocellular, with a latency of 1 to 4 months and strong linkage to HLA-B*35:01.

Keywords: Drug-induced liver injury; Hepatotoxicity; Herbal-induced liver injury; Turmeric.

Figure 1.. Year of Presentation of 10 Cases of Turmeric Liver Injury.

Shown are the years of the clinical presentation of 10 cases of turmeric liver injury reported in the DILIN Prospective Study. Cases with turmeric exposure only are shown in blue; those with combined turmeric and piperine exposure (based upon product label and chemical analysis) are shown in orange.

Figure 2.. Histological Changes Associated with Turmeric Liver Injury.

A. Case 3: Severe acute hepatitis with bridging necrosis spanning between a portal area and a central vein. (H&E, 200x). B. Case 3: Higher magnification shows clusters of plasma cells at the portal-parenchymal interface. (H&E, 600x). C. Case 4: Canalicular cholestasis (arrow) with mild lobular hepatitis. (H&E, 400x). D. Case 5: Moderate hepatitis with increased numbers of eosinophils (arrows) in the portal area (H&E, 400x).