Middle-aged Woman With Abnormal Liver Enzyme Levels
A 58-year-old woman is evaluated after routine blood tests revealed elevated transaminase levels. She is asymptomatic and reports no complaints.
HISTORY
Several years earlier, mild hypercholesterolemia was diagnosed, and she has been taking simvastatin ever since. There are no other major medical diagnoses or medications. She drinks a glass of wine several nights a week. She has no history of blood transfusion, and she has been married to her only sex partner for 35 years.
PHYSICAL EXAMINATION
The patient is moderately obese with a body mass index (BMI) of 31 kg/m2. Vital signs are normal. Sclerae are non-icteric, and no skin stigmata of cirrhosis are noted. The liver is neither tender nor enlarged, and the spleen is not palpable.
LABORATORY RESULTS
The hemogram is normal. The basic metabolic panel reveals a random blood glucose level of 129 mg/dL, but the other results are normal. A comprehensive metabolic panel shows normal bilirubin and alkaline phosphatase levels. The aspartate aminotransferase (AST) level is 47 U/L, and the alanine aminotransferase (ALT) level is 72 U/L. Results of repeated studies are similar.
Which of the following statements regarding this case is false?
A. This syndrome is now the most common cause of elevated transaminase levels in the United States.
B. This patient can and should continue to use statins if indicated for the treatment of dyslipidemia.
C. A liver biopsy will be required in most patients with this syndrome.
D. Currently, no proven pharmacologic therapy improves morbidity and lowers mortality in this syndrome.
Answer and discussion on next page
CORRECT (FALSE) ANSWER: C
This case is typical of non-alcoholic fatty liver disease (NAFLD), formerly called non-alcoholic steatohepatitis. This condition is now the most common cause of elevated liver enzyme levels in the United States; thus, choice A is true.
Epidemiology. The epidemiology of this condition parallels that of the increasingly prevalent metabolic syndrome. NAFLD becomes more common with increasing body weight: it affects roughly two-thirds of persons with a BMI of greater than 30 kg/m2 and more than 90% of those with a BMI of greater than 39 kg/m2.1,2 Other epidemiologic risk factors include diabetes/glucose intolerance and hypertriglyceridemia, which were present in this case.
Clinical features. The typical presentation is the asymptomatic elevation of transaminase levels in an obese patient. Frequently, a battery of studies to exclude other causes of hepatitis are performed, including serologic testing for hepatitis B and C; serum iron studies for hemochromatosis; and immunologic assays, such as antinuclear antibody/antimitochondrial antibody for the autoimmune hepatitis syndromes.
A careful history taking is required to exclude toxic causes—medications and particularly alcohol. In fact, the diagnosis of NAFLD requires that daily alcohol intake be less than 20 g/d for women and 30 g/d for men (less than 1.5 and less than 2 standard drinks, respectively).3
The pattern of laboratory results yields clues to the likelihood or not of NAFLD. In alcoholic liver disease, the AST/ALT ratio is typically greater than 2, while in NAFLD the ratio is less than 1, as in this case. As a rule, elevations are moderate, 1 to 4 times normal; higher elevations suggest other diagnoses or, less typically, more severe liver damage from NAFLD.
Further workup. Additional diagnostic studies include a liver ultrasound examination, which identifies fat in the liver with a specificity of about 85% and a sensitivity of greater than 90%.3 Liver biopsy is “controversial” in a majority of studies. Biopsy is the only reliable method to definitively diagnose NAFLD and to ascertain extent of pathology, presence of cirrhosis, and prognosis.2,3 However, on the negative ledger are the benign course of NAFLD in most patients, the lack of proven therapies in any event, and the small but not inconsequential risk associated with biopsy.2,3 The consensus is that most patients do not require biopsy, particularly early in the workup, making choice C the correct one here. Exceptions may include patients who have risk factors for cirrhosis, such as morbid obesity (BMI of greater than 39 kg/m2), AST/ALT ratios greater than 1,2,3 and persistent enzyme elevations despite appropriate lifestyle. None of these risk factors is present here.
Management. To date, there is no specific, effective therapy for NAFLD. Appropriate lifestyle changes are the first step. Thus, exercise and slow, controlled weight loss to achieve a BMI of 25 kg/m2 and avoidance of concordant risk factors such as alcohol consumption are indicated not only to ameliorate NAFLD but also to lessen general cardiovascular risk as well.
Metformin, the glitazones, and various statins have been shown to lower liver enzyme levels. Vitamins and antioxidants can also reduce transaminase levels and even improve liver biopsy histologic findings. However, to date no intervention has demonstrated improvement in morbidity or mortality in controlled trials.
With regard to statins (choice B), the hepatic metabolism of these agents and the occasional liver toxicity they cause have given some investigators and clinicians pause about their use in patients with NAFLD. Experience and at least one good trial4 have shown that statins can be safely used in patients with NAFLD when indicated; moreover, the American College of Cardiology guidelines advise that statins should be used when indicated in patients with mild to moderate NAFLD (liver enzyme levels of less than 3 times normal) with careful clinical and laborator y monitoring.5
Outcome of this case. The patient was counseled to cease alcohol intake and to continue her statin therapy. Weight loss was advised, but at 6-month follow-up her BMI has not changed. Her liver enzyme levels remain elevated but stable. No biopsy is planned at present, but she will be closely monitored.
THE TAKE-HOME MESSAGE:
NAFLD is the most common cause of elevated transaminases in the United States. Obesity, diabetes, and elevated triglycerides are risk factors. Prognosis overall is good, although a minority of patients progress to cirrhosis. Liver biopsy is not required in most patients.
1. Clark JM, Diehl AM. Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA. 2003;289:3000-3004.
2. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221-1231. 3. Bayard M, Holt J, Boroughs E. Nonalcoholic fatty liver disease. Am Fam Phys. 2006;73:1961-1968.
4. Chalasani N, Aljadhey H, Kesterson J, et al. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology. 2004;126:1287-1292.
5. Pasternak RC, Smith SC, Bairey Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the use and safety of statins. Stroke. 2002;33:2337-2341.