S3058 Kratom Induced Acute Liver Injury: A Case Study and Systematic Review of Liver Injury Patterns Due to Kratom

Abstract

Introduction: Kratom is an herbal supplement derived from the Mitragyna speciosa tree leaves in Southeast Asia. It is currently banned in only 6 states, regulated in 8, and completely unregulated in the rest (Figure 1). Kratom is popular for its psychotropic and opioid-like activity. In addition to other side effects, it is associated with acute liver injury and in rare cases, acute liver failure. Here, we report a patient who presented with cholestatic liver injury after Kratom use. We compare this case to 53 other reports of Kratom-associated hepatotoxicity to better understand the safety of this drug. Case Description/Methods: A 47-year-old male with a history of peripheral neuropathy and hypertension presented with 15 lbs of unintentional weight loss over a month and jaundice for 5 days. For at least three weeks, he had taken Kratom for neuropathy and hip pain. Labs were notable for cholestatic injury with an R factor of 1.8 and a urine drug screen positive for tetrahydrocannabinol and benzodiazepines (Table 1). Other workups including HIV, acetaminophen, and hepatitis labs were negative. He improved with supportive care and was advised to discontinue Kratom. After discharge, the patient reported complete resolution of his symptoms. A literature search in PubMed, Cochrane, and Embase found 69 cases of Kratom-induced DILI. We excluded cases without laboratory values, leaving 53 cases. A majority of Kratom users report taking the drug for acute or chronic pain. Males were predominant (64%) and the majority had a cholestatic liver injury pattern (80%). Unfortunately, 5.6% of these cases resulted in liver transplants. Furthermore, 9.4% of these cases experienced acute renal injury, with 60% requiring hemodialysis. Some patients also experienced rhabdomyolysis (3.7%), reversible heart failure (3.7%), acute cholecystitis (3.7%), and undifferentiated shock (1.9%). One patient suffered from Salmonella-contaminated Kratom ingestion. (Figure) Discussion: Kratom is widely available throughout the United States with very minimal regulation. After a review of our patient’s case report, as well as those of 53 other patients, we have significant safety concerns for the use of Kratom in the general population. Caution is advised in patients with pre-existing liver disease. Though its chemical properties may have interesting applications worthy of investigation, we recommend further research on the risks and mechanism of liver injury of Kratom.Figure 1.: A map of the United States and locations of Kratom restrictions as of 2022. California: Kratom is legal, except in San Diego and Oceanside; Colorado: Kratom is legal, except in the towns of Monument and Parker; Florida: Kratom is legal, except in Sarasota country; Illinois: Kratom is legal for adults 18 years and older, except in Jerseyville and Alton; Mississippi: Kratom is legal, except in several counties; New Hampshire: Kratom is legal, except in Franklin city; North Carolina: Kratom is legal for adults 18 years and older; Tennesee: Kratom is legal for adults 21 and older. Table 1. - Laboratory test results Variable (normal range) Day of admission Day of discharge Bilirubin, Total mg/dL (0.0-1.2) 10.7 5.0 Bilirubin, Direct mg/dL (< = 0.5) 6.7 AST U/L (8-34) 64 53 ALT U/L (10-49) 168 87 Alk-Phos U/L (46-116) 265 279 GGT U/L (12-64) 376 INR (0.80-1.2) 1.04 Prothrombin time (9.3-12.4 seconds) 10.9 Lipase U/L (< 78) 36 CA 19-9 U/mL < 5.30 Acetaminophen ug/mL (0.0-10.0) 5.6 Ferritin ng/mL (11.0-307.0) 410.2 Iron ug/dL (65-175) 140 Ceruloplasmin mg/dL (16.0-31.0) 31.3 Copper ug/dL (72-166) 120 Antinuclear Antibody Negative Smooth Muscle Antibody U (0-19) 20 Anti-Mitochondrial Antibody units (0.0-20.0) < 20.0 Alpha-1 Antitrypsin mg/dL (90.0-200.0) 186.0 AST, aspartate transaminase; ALT, alanine transaminase; Alk-Phos, alkaline phosphatase; INR, International Normalization Ratio; aPTT, activated partial thromboplastin; GGT, Gamma-Glutamyl Transferase.