Ayurvedic Drug-Induced Liver Injury

Drug induced liver injury (DILI) is responsible for 50% of acute liver failure in developed countries. Ayurvedic (herbal) and homeopathic medicine have been linked to liver injury. Punarnaya mandur and Kanchnar guggulu are commonly used herbs in Eastern culture and both ironically report anti-inflammatory and hepatoprotective properties. They had not previously been associated with DILI. DILI is a diagnosis of exclusion and the use of multi-modalities tools including the ACG algorithms, causative assessment scales, histological findings, and imaging is recommended. A 44-year-old female presented to the ED for 2 weeks of painless jaundice, pale stools, and dark urine. She had a 6 month history of cholelithiasis diagnosed in India, and she began to use 3 different herbal and homeopathic medications for treatment. She denied any other mediation use, alcohol, or a history of infectious hepatitis. Her admission labs demonstrated an AST 1092 U/L, ALT 1185 U/L, total bilirubin 9.0 mg/dL, direct bilirubin 6.2, INR 1.8, and normal alkaline phosphatase of 118. All viral serologies and antibodies were negative. Right upper quadrant ultrasound reported gallbladder neck calculus, wall thickening, and nondilated hepatic and common bile duct. MRCP confirmed a gallbladder neck stone, but no choledocholelithiasis. There was heterogeneous T2 enhancement of liver with no signs of hepatic steatosis. Jaundice and LFTs improved within 3 weeks of stopping offending Ayurvedic medications. Later the patient had an outpatient elective cholecystectomy with liver biopsy. Liver biopsy demonstrated mild portal chronic inflammation, ballooning hepatocytes, and interface activity with grade 3 bridging fibrosis. Ceroid-laden Kupffer cells were present in portal tracts. Plasma cells were not seen, but eosinophils were conspicuous. Overall, the histologic pattern was suggestive of drug hypersensitivity reaction with resolving hepatitis. This describes the first documented case report of Punarnava mandur and Kanchnar guggulu causing drug induced liver injury. From the biopsy, the ceroid laden Kupffer cells and prominent eosinophils are highly suggestive of DILI. This nonspecific heterogeneous pattern T2 enhancement may be a unique, underutilized diagnostic clue for DILI secondary to herbal and homeopathic mediations. For herbal and homeopathic medications the early recognition is important with subsequent withdrawal of the medication.Figure: Prominent eosinophils suggests a drug reaction of the hypersensitivity type. (H&E X400)Figure: T2 weighted MRI Pancreas with contrast. The heterogeneous T2 enhancements (hyperintensities, white areas) are present throughout the liver parenchyma.