During outpatient follow-up with Gastroenterology 2 days after discharge, the patient’s liver transaminases and bilirubin continued to trend upward (to a maximum ALT of 871 U/L; AST, 1097 U/L; alkaline phosphatase, 122 U/L; and bilirubin, 2.9 µmol/L). Immunoglobulin G was 1342 mg/mL (normal range, 694-1618 mg/mL).
An ultrasound-guided liver biopsy was performed; it demonstrated lobular, portal, and periportal hepatitis with focal bridging necrosis, consistent with a diagnosis of autoimmune hepatitis. Mild-to-moderate focal cholestasis was demonstrated, consistent with cholestatic hepatitis.
DISCUSSION
Autoimmune hepatitis is characterized by inflammation of the liver, secondary to the presence of circulating antibodies or hypergammaglobulinemia. The pathogenesis is thought to involve a T-cell–mediated immune attack on the liver. Based on case reports,the use of minocycline is associated with risk for liver injury, although the incidence is rare.1-4 Use of this medication may be associated with autoimmune disease in patients who are predisposed to autoimmune tendencies or who have genetic predeterminants.
Diagnosis is typically made based on abnormalities in aminotransferases (AST, ALT), elevation in serum immunoglobulins, and positive auto-antibody titers including ANA, smooth muscle antibodies, and anti-liver kidney microsomal type 1 antibodies. Although clinical presentations tend to differ, the confirmatory diagnosis is typically made histologically, with the presence of lobular and perivenular necro-inflammatory changes and plasma cell infiltration.5
Other infectious and metabolic causes of hepatitis should be excluded. Many medications and herbal agents have been noted to cause autoimmune hepatitis or similar syndromes that mimic the condition.
Medication history. Review of the case patient’s medication list identified ethinyl estradiol/norethindrone acetate and minocycline as potential culprits. Ethinyl estradiol/norethindrone acetate is a low-dose combination oral contraceptive pill (OCP). Although earlier formulations of OCPs were associated with hepatobiliary complications, these adverse effects are noted to be rare in the absence of predisposing conditions.6 In some cases, OCPs have been linked to cholestasis, chronic hepatocellular carcinoma, or hepatic adenomas, but studies have shown that these medications do not affect the course of acute liver failure.7
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