A 41-year-old woman comes to the office for follow-up of abnormal liver function test results. The patient has a 3-year history of hypercholesterolemia treated with a statin medication that was discontinued 6 months ago when a moderate elevation in hepatic transaminases was noted. She has no jaundice, abdominal pain, or nausea. Medical history is also notable for type 2 diabetes mellitus. Current medications include metformin and lisinopril, both of which she has taken for several years. The patient drinks 1-2 glasses of wine on weekends and does not use tobacco or illicit drugs. There is no family history of liver disease. Vital signs are normal. BMI is 36 kg/m². Examination shows mild hepatomegaly. Laboratory results are as follows: Which of the following is the most likely diagnosis in this patient?

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11ec25c8_d272_36e5_bc81_09594f58d8d7_MD0003_00 This patient with persistent mild aminotransferase elevation and hepatomegaly has comorbid obesity, diabetes mellitus, and hyperlipidemia. In the absence of significant alcohol use, this presentation suggests nonalcoholic fatty liver disease (NAFLD). NAFLD is defined as hepatic steatosis in the absence of other causes of secondary hepatic fat accumulation (eg, alcohol). The incidence has risen along with the increase in obesity, with nearly half of obese patients demonstrating some degree of steatosis on liver biopsy. Most patients with NAFLD have hepatomegaly, but other stigmata of chronic liver disease are rarely seen. Liver markers typically show mild elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, with an AST/ALT ratio <1. Alkaline phosphatase levels may also be elevated; however, albumin and bilirubin levels are typically normal. Diagnosis is often made based on laboratory and imaging findings (eg, hyperechoic texture on ultrasound) but can be confirmed with liver biopsy. Management includes weight loss and control of metabolic risk factors. (Choice A) Alcoholic liver disease is characterized by AST predominance (AST/ALT ratio 2:1) in contrast to the parallel rise in NAFLD. In addition, alcoholic liver disease is unlikely with light to moderate alcohol intake (<15 drinks/week for men, <10/week for women). (Choice B) Autoimmune hepatitis causes elevations in transaminase levels but typically causes a more marked elevation in AST and ALT (eg, hundreds to thousands) and bilirubin levels. It is often associated with arthralgias, anorexia, and fatigue. (Choice C) Hemochromatosis can cause a transaminitis and diabetes, but it typically presents after menopause in women because menstruation slows iron accumulation. In addition, skin hyperpigmentation, arthralgias, and fatigue are common. (Choice D) Hepatitis A typically causes a self-limited disease associated with nausea, vomiting, fever, abdominal pain, and jaundice. Aminotransferase levels are usually markedly elevated (>1000 U/L) with ALT predominance (ALT/AST ratio 2:1) and generally high bilirubin levels. (Choice F) Primary biliary cholangitis is characterized by destruction of the intrahepatic bile ducts, leading to a cholestatic disease (ie, markedly elevated alkaline phosphatase levels), fatigue, and pruritus. (Choice G) Statins are generally considered safe in patients with NAFLD. Furthermore, this patient's statins were discontinued 6 months ago and would be unlikely to cause further liver injury. Educational objective: Nonalcoholic fatty liver disease is characterized by hepatomegaly, with mild elevations in liver transaminase levels in the absence of other causes of secondary hepatic fat accumulation (eg, alcohol). It is most common in patients with obesity and diabetes. Management includes weight loss and control of metabolic risk factors. References: Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. (http://www.ncbi.nlm.nih.gov/pubmed/26226097) Nonalcoholic fatty liver disease and statins. (http://www.ncbi.nlm.nih.gov/pubmed/26234727)

A 41-Year-Old Woman Comes to the Office for Follow-Up of Abnormal