Clinical Features and Outcomes of Complementary and Alternative Medicine Induced Acute Liver Failure and Injury

Abstract

OBJECTIVES The increasing use of complementary and alternative medicines (CAMs) has been associated with a rising incidence of CAM-induced drug-induced liver injury (DILI). The aim of this study was to examine the clinical features and outcomes among patients with acute liver failure (ALF) and acute liver injury (ALI) enrolled in the Acute Liver Failure Study Group database, comparing CAM-induced with prescription medicine (PM)-induced DILI. METHODS A total of 2,626 hospitalized patients with ALF/ALI of any etiology were prospectively enrolled between 1998 and 2015 from 32 academic transplant centers. Only those with CAM or PM-induced ALI/ALF were selected for analysis. RESULTS A total of 253 (9.6%) subjects were found to have idiosyncratic DILI, of which 41 (16.3%) were from CAM and 210 (83.7%) were due to PM. The fraction of DILI-ALF/ALI cases due to CAM increased from 1998–2007 to 2007–2015 (12.4 vs. 21.1%, P=0.047). There was no difference in the type of liver injury—hepatocellular, cholestatic, or mixed—between groups as determined by R score (P=0.26). PM-induced DILI showed higher serum alkaline phosphatase levels compared with the CAM group (median IU/L, 171 vs. 125, P=0.003). The CAM population had fewer comorbid conditions (1.0 vs. 2.0, P<0.005), higher transplantation rates (56 vs. 32%, P<0.005), and a lower ALF-specific 21-day transplant-free survival (17 vs. 34%, P=0.044). CONCLUSIONS CAM-induced DILI is at least as severe in presentation as that observed due to PM with higher rates of transplantation and lower transplant-free survival in those who progress to ALF. This study highlights the increasing incidence of CAM-induced liver injury and emphasizes the importance of early referral and evaluation for liver transplantation when CAM-induced liver injury is suspected.

Ayurvedic and herbal medicine-induced liver injury: It is time to wake up and take notice

“…Furthermore, the incidence of CAMinduced severe liver injury in the USA has almost doubled from 12.4% in the last decade to 21% now [6]. This has resulted in a higher rate of liver transplantation, and a lower transplant-free survival, highlighting the increased morbidity and mortality from these agents [6]. Similar studies are unavailable in India, although final results of the study by the Indian Network of Drug-Induced Liver Injury are awaited.…”

“…Although prescription drugs are an important cause of liver injury, the contribution of herbal and botanical medicationinduced liver injury has increased over the years and has varied considerably across the world ranging anywhere from 17% in Japan [2], 20% in the USA [3], and 31% in China [4] to 70% in Korea [5]. Furthermore, the incidence of CAMinduced severe liver injury in the USA has almost doubled from 12.4% in the last decade to 21% now [6]. This has resulted in a higher rate of liver transplantation, and a lower transplant-free survival, highlighting the increased morbidity and mortality from these agents [6].…”

Herbal and Dietary Supplement–Induced Liver Injury

“…(15) Among patients presenting with acute liver failure, those whose disease was attributed to HDS use are more likely to undergo liver transplantation than those associated with prescription medicines (56.1 vs. 31.9%, P <0.005). (16)…”

Drug-induced liver injury

“…The HDS group had higher transplantation rates (56% versus 32%, p<0.005) and lower transplant-free survival (17% versus 34%, p=0.044) compared with those receiving conventional drugs. 39 Specifically in hepatocellular DILI, a serum bilirubin of ≥3 times ULN in the absence of biliary obstruction or Gilbert's syndrome is associated with a mortality of approximately 10% (range 5-50%). 40 This is also known as Hy's law, in recognition of the pioneering work done by Hyman Zimmerman -an American hepatologist.…”