E-case #14-C

Audrey Young, M.D.

June 24-28, 2002

A healthy 43-year-old Caucasian female public relations executive presents with elevated transaminases that were checked as part of an employee physical.  On recheck, LFTs are still elevated, with ALT of 96 and AST of 83.  The patient denies all associated symptoms including abdominal pain, nausea, vomiting, and diarrhea.  She denies alcohol and IV drug use.  There is no family history of liver disease. Past medical history includes only borderline high blood pressure. She takes no medications. BP is 138/88, HR 82, BMI 32. Exam is remarkable for a nontender abdomen and a liver edge palpable just below the right costal margin.  No stigmata of end stage liver disease.

RUQ ultrasound shows a fatty infiltrates of the liver.

What's the diagnosis?  The prognosis?  Should she have a liver biopsy? What treatment should be pursued?

1. Diagnosis: The clinical picture of asymptomatic elevation in LFTs, obesity, and fatty liver suggests NASH, or nonalcoholic steatohepatitis. She does not have evidence of viral-, toxin-, or alcohol-mediated liver disease.  Autoimmune hepatitis should be considered because of age and gender; hemochromatosis should be considered because of age and ethnicity. Rule out these diagnoses with an ANA plus anti-smooth muscle antibody, and iron studies. Rule out primary biliary cirrhosis with an anti-mitochondrial antibody, since PBC is treatable.  The subacute presentation argues against Wilson's and Budd-Chiari syndrome, and there is nothing on history, exam, or imaging to suggest these diagnoses.

2. Prognosis: NASH is thought to remain stable or regress most of the time, but sometimes progresses.  In five combined studies of 257 patients, 28% progressed histologically with cirrhosis developing in several patients.  Prognosis correlates with liver histology.  Pure steatosis has the best prognosis and steatohepatitis or more advanced fibrosis has a worse prognosis.  Risk factors for advanced histologic stage include age above 45, obesity or type II diabetes, and AST to ALT ratio > 1.0.

3. Liver biopsy: Biopsy confirms the diagnosis and is used to follow response to treatment. Obtaining liver biopsy is an individualized decision.  In this patient's case, biopsy was put off and a therapeutic trial of weight loss was initiated.

4. Treatment: Fatty infiltration typically decreases with weight loss.  Weight loss of 1.6 kg per week is recommended in adults.  A faster rate of weight loss is thought to worsen hepatic necrosis and inflammation.  No medications have yet proven to reduce liver damage.

References

Nonalcoholic fatty liver disease. NEJM 2002: 346; 1221-1231.

Evaluation of abnormal liver-enzyme results in asymptomatic patients. NEJM 2000: 342;1266-1271.