MKSAP quiz: Elevated liver chemistries

This month's quiz asks readers to evaluate a 35-year-old woman with type 2 diabetes mellitus, hypertension, hyperlipidemia, obesity, and the metabolic syndrome.


A 35-year-old woman comes to the office to discuss recent laboratory test results. She is asymptomatic. Medical history includes type 2 diabetes mellitus, hypertension, hyperlipidemia, obesity, and the metabolic syndrome. The patient has a sedentary lifestyle. She does not smoke cigarettes and drinks one alcoholic beverage weekly. Her current medications include metformin and lisinopril. Atorvastatin was initiated 3 weeks ago.

Physical examination findings, including vital signs, are normal. BMI is 32.

On laboratory testing, aspartate aminotransferase level is 76 U/L and alanine aminotransferase level is 83 U/L. These results are unchanged from 3 months ago. Results of serologies for antinuclear antibody and viral hepatitis infection are negative; transferrin saturation is 20%.

In addition to aggressive lifestyle intervention, which of the following should be done next?

A. Antimitochondrial antibody measurement
B. C-reactive protein measurement
C. Evaluation for nonalcoholic steatohepatitis
D. HFE genotyping

Reveal the Answer

MKSAP Answer and Critique

The correct answer is C. Evaluation for nonalcoholic steatohepatitis. This item is available to MKSAP 18 subscribers as item 6 of extension set 1 in the Gastroenterology and Hepatology section. More information about MKSAP 18 is available online.

This patient should be evaluated for nonalcoholic steatohepatitis (NASH). The American Diabetes Association recommends that patients with type 2 diabetes or prediabetes and elevated alanine aminotransferase level or fatty liver on ultrasound should be evaluated for presence of NASH and liver fibrosis. There are no noninvasive tests that can diagnose NASH as a cause of chronically elevated liver chemistries. Patients with elevated liver chemistries, a negative serological evaluation for alternative causes, clinical features of the metabolic syndrome, and characteristic abdominal imaging are presumed to have NASH. The NAFLD fibrosis score (www.nafldscore.com) uses clinical data to identify patients at risk for severe disease. Transient elastography can be used to determine whether patients with NASH have developed significant hepatic fibrosis. Liver biopsy is indicated when the diagnosis is in doubt, or if the presence of hepatic fibrosis cannot otherwise be determined.

Antimitochondrial antibody testing is helpful in establishing the diagnosis of primary biliary cholangitis (PBC), an autoimmune disease affecting the small and medium bile ducts. PBC can present with fatigue and pruritus, but many patients are asymptomatic, with the diagnosis suggested by elevated alkaline phosphatase levels. Diagnosis does not require liver biopsy when the alkaline phosphatase level is at least 1.5 times the upper limit of normal and the result of antimitochondrial antibody testing is positive. This patient's presentation is not consistent with cholestatic liver disease and testing for antimitochondrial antibody is unnecessary.

The metabolic syndrome has been associated with pro-inflammatory markers such as elevated levels of C-reactive protein (CRP) and increased risk for cardiovascular mortality. However, the presence of inflammatory markers explains only a small part of the association between metabolic syndrome and increased cardiovascular mortality. Current guidelines emphasize that the predictive ability of CRP is uncertain, and measurement in patients with metabolic syndrome is optional.

The diagnosis of hemochromatosis is suggested by the presence of chronic, unexplained elevations of aminotransferase levels. Transferrin saturation elevated to greater than 45% is often used as a screening threshold for the disease; diagnosis is confirmed through genetic testing for the HFE genotype. This patient's transferrin saturation is normal and further testing for hemochromatosis is unnecessary.

Key Point

  • The American Diabetes Association recommends that patients with type 2 diabetes or prediabetes and elevated alanine aminotransferase levels or fatty liver on ultrasound should be evaluated for presence of nonalcoholic steatohepatitis and liver fibrosis.