A 42-year-old female developed
fulminant hepatic failure after having ingested an undetermined quantity of a herbal product over a period of approximately four months prior to the onset of her illness. Clinically, the cause of
liver failure was assessed to be
drug-induced and she eventually underwent total
hepatectomy, with porto-caval shunting, in anticipation of a living-unrelated
liver transplant. Unfortunately, her condition deteriorated and she died less than 48 hours post-operatively, approximately three weeks post-admission. An autopsy showed that the subject was deeply jaundiced and severely obese (BMI: 47.1 kg m(-2)), with evidence of diffuse haemorrhage, including the presence of 1.35 l of blood in the peritoneal cavity. The liver had been removed and was later recovered as a
formalin-fixed specimen which was markedly contracted, comprising multiple micronodules interspersed with extensive areas of dense fibrotic tissue. Histologically, there was massive
necrosis of the hepatic parenchyma, such that the residual hepatocytes were disposed as nodules displaying variable cellular regeneration and ballooning degeneration, attended by florid ductal proliferation and mixed inflammatory infiltrates. Infective, autoimmune, metabolic, vascular, neoplastic and most other natural causes of massive hepatocellular
necrosis were effectively excluded. Analysis of the post-mortem blood samples yielded
fluconazole,
metronidazole,
frusemide,
lignocaine and
tramadol, (therapeutic agents administered to the patient during her last illness). Subsequent analysis of the residual capsules revealed that they were adulterated by
fenfluramine, N-
nitrosofenfluramine (1.3-1.6 mg per
capsule),
nicotinamide (13.3-15.6 mg per
capsule) and thyroid extract. None of the herbal ingredients is currently known to be hepatotoxic and much the same applies to
fenfluramine,
nicotinamide (except when taken in mega-doses) and thyroid extract. However, as
nitrosamines are known to be variably hepatotoxic, it would be reasonable to surmise that, in the absence of a more plausible cause of liver damage, N-
nitrosofenfluramine was the likely cause of massive hepatocellular
necrosis in this instance.