A 42-year-old woman comes to the office for follow-up due to abnormal liver function studies. The patient reports no symptoms. Medical history is significant for primary hypertension, and she has been taking amlodipine for 5 years. Family history is negative for liver disease. The patient drinks a glass of wine 3 or 4 times a week but denies smoking or illicit drug use. Temperature is 37.5 C (99.5 F), blood pressure is 146/80 mm Hg, and heart rate is 80/min. BMI is 28 kg/m². Scleral icterus and palmar erythema are absent. Cardiopulmonary and abdominal examinations are both unremarkable. Laboratory studies are as follows: Initial testing 3 months ago showed similar results. Which of the following most likely explains this patient's persistent laboratory abnormalities?

Question

A 42-year-old woman comes to the office for follow-up due to abnormal liver function studies. The patient reports no symptoms. Medical history is significant for primary hypertension, and she has been taking amlodipine for >5 years. Family history is negative for liver disease. The patient drinks a glass of wine 3 or 4 times a week but denies smoking or illicit drug use. Temperature is 37.5 C (99.5 F), blood pressure is 146/80 mm Hg, and heart rate is 80/min. BMI is 28 kg/m². Scleral icterus and palmar erythema are absent. Cardiopulmonary and abdominal examinations are both unremarkable. Laboratory studies are as follows: Initial testing 3 months ago showed similar results. Which of the following most likely explains this patient's persistent laboratory abnormalities?

Quizplus · Accepted Answer

11ec25c8_d2df_ec6c_bc81_d9a0a61012ab_MD0003_00 This woman with persistent asymptomatic elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and a large gamma gap (total protein − albumin = >4 g/dL) has autoimmune hepatitis (AIH). AIH is thought to be triggered by environmental exposure in susceptible individuals; it occurs most commonly in women with comorbid autoimmune disease (eg, autoimmune thyroiditis, vitiligo). The initial presentation is variable, with most patients presenting with constitutional symptoms (eg, fatigue, weight loss), abdominal pain, pruritus, and, possibly, cirrhosis (eg, jaundice, ascites). However, approximately 25% are asymptomatic and identified by routine blood work demonstrating a hepatocellular pattern of liver injury, with predominant elevations in AST and ALT and normal or mildly elevated alkaline phosphatase and bilirubin. High levels of autoantibodies (typically IgG) result in hypergammaglobulinemia and a gamma gap, a helpful characteristic feature (not seen in all cases). Positive serology (eg, anti-smooth muscle, anti-liver/kidney microsomal type 1, antinuclear antibodies) or hypergammaglobulinemia confirms the diagnosis. (Choice A) Alcoholic hepatitis also causes a hepatocellular pattern of injury, but an AST/ALT ratio of >2:1 is expected, and transaminases rarely exceed 300 U/L. In addition, patients typically have heavy alcohol use (5 or 6 drinks/day), fever, and jaundice. A gamma gap would be atypical. (Choice B) Alpha1-antitrypsin deficiency (AATD) is an autosomal codominant condition leading to emphysema (typically presenting in patients in their 40s) and liver disease (eg, chronic hepatitis, cirrhosis). This patient does not have manifestations of emphysema (eg, cough, dyspnea) or a family history of liver disease, and a protein gap would not occur with AATD. (Choice D) Although amlodipine can cause hepatotoxicity, this adverse effect is exceedingly rare, typically develops within weeks to months (rather than after >5 years), and is generally associated with a cholestatic pattern. An elevated gamma gap would not occur. (Choice E) Hepatitis A causes a hepatocellular pattern of injury, but it typically presents with vomiting, fever, and abdominal pain; transaminases are generally >1,000 U/L and would be expected to normalize after 3 months. (Choice F) Primary biliary cholangitis is an autoimmune disorder characterized by elevated antimitochondrial antibodies. Although PBC can be asymptomatic and mild AST and ALT elevation can be seen, a cholestatic picture is expected, with marked elevations in alkaline phosphatase (≥1.5x the upper limit of normal). Educational objective: Autoimmune hepatitis is characterized by a hepatocellular pattern of liver injury (elevations in aspartate aminotransferase and alanine aminotransferase with normal alkaline phosphatase and bilirubin), as well as high levels of autoantibodies, resulting in elevated serum globulins and a gamma gap. Positive serology (eg, anti-smooth muscle, anti-liver/kidney microsomal type1, antinuclear antibodies) or hypergammaglobulinemia confirms the diagnosis. References: Diagnosis and management of autoimmune hepatitis: current status and future direction (http://www.ncbi.nlm.nih.gov/pubmed/26934884)

A 42-Year-Old Woman Comes to the Office for Follow-Up Due