Which patients with nonalcoholic fatty liver disease should undergo liver biopsy?

NONINVASIVE TESTING

Since liver biopsy is associated with procedure-related morbidity, mortality, and cost, researchers have been developing noninvasive markers of steatohepatitis and fibrosis.¹²

The NAFLD fibrosis score—based on patient age, body mass index, hyperglycemia, platelet count, albumin, and ratio of aspartate aminotransferase to alanine aminotransferase—has been shown to have an area under the receiver operating curve of 0.85 for predicting advanced fibrosis, with a negative predictive value of 88% to 93% and a positive predictive value of 82% to 90%.¹³ The NAFLD fibrosis score can be used to identify patients who may have fibrosis or cirrhosis and can help direct the use of liver biopsy in patients who would benefit from prognostication and potential treatment.

Of note, the NAFLD fibrosis score is only slightly less accurate than the imaging techniques of magnetic resonance elastography and transient elastography, particularly when the relative costs are considered.¹⁴

INDICATIONS FOR LIVER BIOPSY

There are two clear indications for liver biopsy in NAFLD.

Before starting any pharmacologic therapy for NAFLD. Most NAFLD patients have steatosis without NASH or fibrosis and do not require medical therapy. Importantly, the available treatments have significant adverse effects—prostate cancer with vitamin E, bladder cancer and weight gain with pioglitazone, and nausea with pentoxifylline.

Diagnosis. Up to 30% of patients have elevated serum ferritin and autoantibodies, including ANA, ASMA, and AMA. Liver biopsy is often needed to exclude hemochromatosis or autoimmune hepatitis.¹⁵ Occasionally, a possible confounding drug-induced liver injury may necessitate a liver biopsy.

LIFESTYLE MODIFICATION

The first step in managing patients who have NAFLD is to treat components of the metabolic syndrome, including obesity, dyslipidemia, and type 2 diabetes.

In a randomized controlled trial in 31 obese patients with biopsy-proven NASH,¹⁶ intensive lifestyle modification (consisting of diet, behavior modification, and 200 minutes of exercise weekly for 48 weeks) was shown to improve histologic NAFLD Activity Scores, including degrees of steatosis, necrosis, and inflammation. As a result, weight loss of 7% to 9% is generally recommended for patients with NAFLD.

DRUG THERAPIES

Much research has been directed toward identifying risk factors for progression of fibrosis and toward developing new therapies for patients with NAFLD. A 2015 meta-analysis concluded that pentoxifylline and obeticholic acid improve fibrosis, while vitamin E, thiazolidinediones, and obeticholic acid improve necroinflammation associated with NASH.¹⁷

Long-term studies are needed to determine the impact of these drugs on NASH-related morbidity, mortality, and need for liver transplant.

TAKE-AWAY POINTS

• NAFLD is the leading cause of chronic liver disease in the United States and is increasing as a reason for liver transplant.
• NASH is associated with the metabolic syndrome and can progress to fibrosis, cirrhosis, and end-stage liver disease. Noninvasive markers such as the NAFLD Activity Score can be useful in identifying patients who may have advanced fibrosis and can select patients who should be directed to liver biopsy for definitive diagnosis.^8,9
• Liver biopsy is the gold standard for diagnosing steatohepatitis and fibrosis and is the only diagnostic tool used in clinical trials to direct pharmacotherapy for NASH.
• Liver biopsy should be reserved for patients suspected of having NASH or fibrosis and who might benefit from therapy.
• Liver biopsy is also indicated for those NAFLD patients who have confounding laboratory findings such as an elevated ferritin level and autoantibodies including ANA, ASMA, and AMA.