A 53-year-old woman with a history of asthma, depression and moderate-to-heavy consumption of alcohol had presented to the emergency department with a three-month history of increasing fatigue and jaundice. She had reported consuming three or four beers on a regular basis and a few glasses of wine three times weekly. Over the past three months, she had been taking six prescription medications (Table 1)1–3 and seven natural health products (Table 2).4–12 Her bilirubin level had been elevated (281 [normal 3.4–22] μmol/L), as had her liver enzyme levels (alanine transaminase 755 [normal 8–56] U/L and alkaline phosphatase 273 [normal 42–98] U/L). An ultrasound of her abdomen had been consistent with cirrhosis, and the presumptive diagnosis had been cirrhotic liver disease. She had been advised to stop using alcohol and all of the natural health products.
Despite taking this advice, the patient’s jaundice and fatigue worsened. She presented to the emergency department 12 days later, at which time she was admitted to hospital. Her physical exam showed asterixis, spider nevi and ascites, and she seemed mildly confused. A test showed that she was immune to hepatitis B. A blood test for hepatitis C was negative. Her levels of ceruloplasmin, α-1 antitrypsin, antimitochondrial antibodies, antinuclear antibody, and antismoothmuscle antibody were normal. Her immunoglobulin levels were elevated (immunoglobulin G 20.4 [normal 6.94–16.18] g/L, immunoglobulin A 6.11 [normal 0.70–4.00] g/L and immunoglobulin M 3.15 [normal 0.60–3.00] g/L). Her liver function tests remained abnormal (bilirubin 441 μmol/L, alanine transaminase 317 U/L and alkaline phosphatase 247 U/L), and a repeat ultrasound of her abdomen was still consistent with cirrhosis. There was no evidence of thrombosis in the hepatic or portal veins and no biliary dilatation. A transjugular biopsy of the liver showed submassive necrosis without the features of alcoholic hepatitis (Figure 1).
The differential diagnosis was submassive hepatic necrosis causing hepatic encephalopathy, due to either autoimmune hepatitis or drug toxicity. Liver injury as a result of alcohol use was considered unlikely because of the patient’s very high level of alanine transaminase and the results of the biopsy of her liver. A timeline showing the patient’s use of prescription and nonprescription medications is shown in Figure 2.
The patient’s condition eventually improved with treatment that included diuretics, lactulose and prednisone, followed by azathioprine.
The case of this patient was evaluated through the multicentre Pharmacy Study of Natural Health Product Adverse Reactions (SONAR).13 We concluded that the entire combination of drugs, natural products and alcohol taken by our patient was possibly related to her hepatic symptoms. A single causative agent could not be isolated.