A 60-year-old man is evaluated at follow-up for elevated aminotransferase levels noted on laboratory testing for asymptomatic hepatomegaly. He has type 2 diabetes mellitus, hypertension, and hyperlipidemia. Current medications are metformin, hydrochlorothiazide, losartan, and atorvastatin. He consumes one to two alcoholic beverages weekly.
On physical examination, blood pressure is 143/80 mm Hg; other vital signs are normal. BMI is 37. Abdominal examination reveals hepatomegaly, no tenderness to palpation, and no splenomegaly.
Alkaline phosphatase level is 180 U/L, alanine aminotransferase level is 64 U/L, and aspartate aminotransferase level is 42 U/L. Platelet count is 250,000/µL (250 × 109). Serum albumin, and serum total bilirubin are normal.
Ultrasound shows a normal gallbladder without stones; normal-size bile ducts; and an enlarged, echogenic liver.
Which of the following is the most appropriate next step in management?
A. Alcohol cessation
B. Discontinuation of atorvastatin
C. Initiation of pioglitazone
D. Weight loss
MKSAP Answer and Critique
The correct answer is D. Weight loss. This item is available to MKSAP 19 subscribers as item 35 in the Gastroenterology and Hepatology section. More information about MKSAP is online.
The most appropriate next step in management is weight loss (Option D). This patient likely has nonalcoholic fatty liver disease (NAFLD) given the presence of diabetes, obesity, hypertension, and hyperlipidemia. Diabetes is associated with the development of NAFLD, including its more severe manifestations of nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma. Elevations of hepatic aminotransferase concentrations are associated with higher BMI, waist circumference, and triglyceride levels and lower HDL cholesterol levels. Patients with type 2 diabetes or prediabetes and elevated liver enzyme levels or fatty liver on ultrasound should be evaluated for presence of NASH and liver fibrosis. An NAFLD fibrosis score calculator or fibrosis-4 (FIB-4) score is used to identify patients at risk for severe disease. Patients with low fibrosis scores are classified as low risk and are managed with weight loss and lifestyle modifications. Patients with indeterminate fibrosis scores should undergo liver stiffness measurement with transient elastography; patients with low liver stiffness are managed as low risk, whereas patients with indeterminate or high-risk stiffness should be managed by a hepatologist. Patients with a high NAFLD fibrosis score or FIB-4 score should be referred to hepatology for consideration of liver stiffness measurement or liver biopsy. The mainstay of NAFLD management for all patients is weight loss. Weight loss of at least 5% improves steatosis, whereas weight loss of 8% to 10% improves steatohepatitis and fibrosis. No specific diet for NAFLD is recommended. Bariatric surgery and concomitant weight loss improve inflammation and fibrosis associated with NAFLD.
This patient does not excessively use alcohol, so alcohol cessation (Option A) is unlikely to resolve his steatosis. No amount of alcohol use is safe in patients with liver disease.
Statins are safe in most patients with NAFLD and should not be discontinued (Option B). Cardiovascular disease is the leading cause of death in patients with NAFLD, and initiation of therapy with statins should be considered in patients with NAFLD at high risk for cardiovascular events. There is no relationship between statin use and steatosis in NAFLD.
No drugs have been approved by the FDA for the treatment of NAFLD. Pioglitazone (Option C) and vitamin E treatment of biopsy-proven nonalcoholic steatohepatitis improve liver histology, but effects on longer-term clinical outcomes are not known and routine use for NAFLD is not recommended.
- Patients with type 2 diabetes or prediabetes and elevated liver enzymes or fatty liver on ultrasound should be evaluated for presence of nonalcoholic steatohepatitis and liver fibrosis.
- The mainstay of management of nonalcoholic fatty liver disease is weight loss.