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Fraction of Liver Injuries From Dietary Supplements Rising in US
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AASLD 2023, The Liver Meeting, November 10-14, 2023, Boston
Mark Mascolini
Reported and confirmed herb and dietary supplement-induced liver injury (HILI) peaked in 2010-2011 in the US Drug-Induced Liver Injury Network (DILIN) at 310 cases then retreated to 118 cases in 2020-2021 [1]. But from 2004-2005 to 2020-2021, the proportion of HILI cases attributed to non-body building agents jumped from 6% of all drug-induced liver injuries reported to 21%. In contrast the proportion of drug-induced liver injuries attributed to body-building agents slipped from a high of 9% in 2012-2013 to 3% in 2020-2021.
Victor Navarro from Philadelphia's Einstein Jefferson Hospital and colleagues set out to track clinical features and outcomes of HILI since the DILIN began in 2004. A case can enter the DILIN with an ALT or AST liver enzyme level more than 5 times the upper limit of normal (ULN) or an alkaline phosphatase more than 2 times ULN on consecutive occasions, or total bilirubin above 2 mg/dL. In this study a structured causality assessment with expert opinion determined DILI cases and whether they were caused by body-building or non-body building agents. The analysis included only high-confidence cases (definite, highly likely, or probable).
Among 1780 high-confidence DILI cases counted from 2004 to 2023, 325 (18%) were HILI. Since 2004 nearly three quarters of these 325 HILI (239 of 325, 73%) could be traced to non-body building agents. The number and proportion of body-building HILI dropped significantly since 2010 (P < 0.001) while the number and proportion of non-body building HILI rose significantly (P = 0.03).
Comparing 88 cases of body-building HILI, 239 cases of non-body building HILI, and 1455 cases of drug-induced liver injury, the researchers found a significantly lower median age in the body-building group (32 vs 46 vs 54, P < 0.001). Proportions of females in the body-building group were profoundly lower than in the non-body building group or the drug-induced group (4% vs 60% vs 61%, P < 0.001). People taking body-building drugs were more likely to be white (83% vs 73% vs 79%) and less likely to be black (9% vs 10% vs 14%) (P < 0.001). A higher proportion of Hispanics took non-body building supplements than took body-building agents or drugs that cause liver injury (21% vs 12% vs 8%, P < 0.001).
Median latency (time from starting drug to liver injury onset) was longer with body-building HILI and non-body building HILI than with drug-induced liver injury (70 vs 68 vs 41 days, P < 0.001). Median peak ALT was lowest with body-building HILI, highest with non-body building HILI, and intermediate with drug-induced liver injury (218 vs 1103 vs 602 U/L, P < 0.001). Median peak total bilirubin was highest with body-building agents than with non-body building supplements or drug-induced liver injury (25.0 vs 12.4 vs 7.5 mg/dL, P < 0.001).
No one in the body-building HILI group had a liver transplant, died, or went on to chronic drug-induced liver injury, compared with 7%, 2%, and 12% in the non-body building HILI group, and 3%, 3%, and 10% in the drug-induced liver injury group (P = 0.033 for chronic DILI and P = 0.001 for transplant and death).
The researchers concluded that the proportion of HILI caused by non-body building herbs and dietary supplements has been climbing since 2004 and that non-body building agents cause more severe disease and unwanted outcomes. Navarro and coworkers suggested that "changes in HILI may reflect US population characteristics and changing patterns of herbal and dietary substance" use.
Reference
1. Navarro VJ, Ahmad J, Barnhart H, et al. Characteristics and outcomes of liver injury due to herbal and dietary supplements in the U.S. AASLD 2023, The Liver Meeting, November 10-14, 2023, Boston.
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