Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 64-year-old man is evaluated in follow-up after recent abnormal findings on intraoperative liver biopsy. Two days ago he underwent right colon resection for a large villous adenoma with high-grade dysplasia. At the time of surgery, an abnormal-appearing liver was noted and biopsy was performed. His medical history is notable for type 2 diabetes mellitus, hypertension, and obesity. Medications are metformin and lisinopril. He drinks two cans of beer daily but does not use tobacco.

On physical examination, vital signs are normal; BMI is 38. No jaundice or spider angiomata are noted. Abdominal examination reveals healing laparoscopic scars and hepatomegaly. The spleen is not palpable, and there is no ascites. No peripheral edema is seen.

Laboratory studies:

Complete blood count	Normal
INR	Normal
Alanine aminotransferase	79 U/L
Aspartate aminotransferase	68 U/L
Albumin	Normal
Alkaline phosphatase	126 U/L
Total bilirubin	Normal
Ferritin	389 ng/mL (389 µg/L)
Iron	Normal
Total iron-binding capacity	Normal
Iron saturation	Normal

Liver biopsy demonstrates a mildly active steatohepatitis without fibrosis. An iron stain is negative.

Which of the following is the most appropriate management?

A. Bariatric surgery
B. Phlebotomy
C. Surveillance for hepatocellular carcinoma
D. Weight loss

MKSAP Answer and Critique

The correct answer is D. Weight loss.

The most appropriate management is weight loss. This patient has nonalcoholic fatty liver disease (NAFLD), and weight loss should be recommended. NAFLD is the most common cause of abnormal liver test results in the United States. Approximately 30% of the U.S. population has NAFLD, some of whom have normal liver enzyme levels. Most patients with NAFLD have insulin resistance associated with obesity, hypertriglyceridemia, and/or type 2 diabetes mellitus. Approximately 20% of patients with NAFLD have nonalcoholic steatohepatitis (NASH), which is characterized by hepatic steatosis accompanied by inflammation and often fibrosis. Although NASH requires a liver biopsy for accurate diagnosis, a presumptive diagnosis can be made in a patient with mild abnormalities of aminotransferase levels, risk factors for NAFLD (such as diabetes, obesity, and hyperlipidemia), and imaging features consistent with hepatic steatosis. This patient’s liver biopsy is consistent with steatohepatitis, and given his risk factors of obesity and diabetes mellitus, NAFLD is the most likely diagnosis.

Patients with NASH who have bariatric surgery and lose weight have improvement in hepatic histology, and bariatric surgery can be considered if conservative attempts at weight loss fail.

Patients with NAFLD may have abnormal iron tests, especially serum ferritin. The absence of iron on this patient’s liver biopsy excludes significant iron overload, and therefore phlebotomy is unnecessary.

Patients with NASH and cirrhosis are at significant risk for hepatocellular carcinoma, and surveillance with imaging should be performed every 6 months; however, surveillance is not necessary in the absence of cirrhosis.

Key Point

• A presumptive diagnosis of nonalcoholic steatohepatitis can be made in a patient with mild abnormalities of aminotransferase levels, risk factors for nonalcoholic fatty liver disease (such as diabetes mellitus, obesity, and hyperlipidemia), and imaging features consistent with hepatic steatosis.

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