Comment on HHS-OASH-2026-0232, HHS-OASH-2026-0232-0001, 2026-13608

Allison et al. (2022): Kratom (Mitragyna speciosa)-Induced Hepatitis This peer-reviewed case report should be considered evidence supporting a 0% allowable 7-hydroxymitragynine (7-OH) threshold rather than permitting products containing measurable concentrations of 7-hydroxymitragynine. The authors describe a 23-year-old man who developed severe drug-induced liver injury after consuming 30 grams of kratom per day for 14 days. One week after discontinuing kratom, he presented with progressive jaundice, diffuse pruritus, dark urine, pale stools, abdominal discomfort, fatigue, and easy bruising. Laboratory testing demonstrated marked cholestatic liver injury with a total bilirubin of 34.3 mg/dL, elevated alkaline phosphatase, and abnormal liver enzymes. Extensive diagnostic evaluation, including magnetic resonance cholangiopancreatography and liver biopsy, excluded structural biliary disease and demonstrated histopathologic findings consistent with kratom-induced liver injury. The patient’s Roussel Uclaf Causality Assessment Method (RUCAM) score of 6 supported a probable diagnosis of drug-induced liver injury attributable to kratom. Importantly, this publication does not report exposure to a commercially marketed concentrated 7-hydroxymitragynine product. The authors describe only the use of kratom and provide no evidence that the product contained elevated concentrations of 7-hydroxymitragynine or exceeded the proposed 0.05% threshold. This distinction is directly relevant to the proposed threshold. If the purpose of establishing a 7-hydroxymitragynine concentration limit is to distinguish products considered acceptably safe from those presenting unacceptable risk, this report provides no evidence that products below the proposed threshold are free from clinically significant toxicity. Instead, it documents severe biopsy-confirmed liver injury following use of a product described simply as kratom, without evidence that elevated 7-hydroxymitragynine concentrations were present. The histopathologic findings strengthen this conclusion. The liver biopsy demonstrated diffuse canalicular cholestasis, mixed portal inflammation, and prominent perivenular necrosis, with the authors identifying perivenular necrosis as a previously undescribed histologic finding in kratom-associated liver injury. They further reviewed prior published biopsy-confirmed cases and concluded that canalicular cholestasis is the most consistent histologic feature of kratom-induced liver injury. The authors also emphasize that kratom-induced liver injury typically develops within 1 to 8 weeks of initiating use and is characterized by fatigue, nausea, abdominal pain, dark urine, and jaundice. They conclude that kratom’s increasing availability and widespread marketing make understanding its toxicities increasingly important for clinicians. Accordingly, this publication does not support the conclusion that kratom products containing less than the proposed 0.05% 7-hydroxymitragynine threshold are inherently safe. Rather, it demonstrates severe, biopsy-confirmed liver injury following exposure to products marketed simply as kratom, without evidence that elevated 7-hydroxymitragynine concentrations were required. For these reasons, this case report should be considered evidence supporting a 0% allowable 7-hydroxymitragynine standard. A zero-tolerance standard provides greater protection for public health than allowing any measurable concentration of a pharmacologically active opioid receptor agonist in products marketed as kratom.