Guide to manage NONalcoholic fatty liver disease

As a clinical pharmacist, you will see more focus on managing nonalcoholic fatty liver disease (NAFLD), partly due to new guidelines. It’s being called a “sleeper epidemic” About 1 in 4 patients have this steatosis, but most don’t have symptoms. NAFLD often goes hand in hand with cardiovascular (CV) risk factors, such as insulin resistance or diabetes, obesity and dyslipidemia. And at least 1 in 7 of these patients have nonalcoholic steatohepatitis (NASH), a more aggressive form of NAFLD that can lead to liver fibrosis, cirrhosis, or liver cancer.

Screen high-risk patients (diabetes, obesity, etc) with the FIB-4 index. It’s calculated using the patient’s age, AST, ALT, and platelet count and helps define their risk of fibrosis. The tough part is that there’s not good evidence that medications decrease the risk of cirrhosis, liver transplant, or death. Reinforce that weight loss is the most important treatment. A loss of over 5% reduces liver fat, over 10% can reverse fibrosis. Optimize medications for diabetes, dyslipidemia and hypertension. Reassure that statins are safe in NAFLD, even in NASH.

For NASH, consider pioglitazone (Actos) or injectable semaglutide (Ozempic, Wegovy). These reduce steatosis and slow fibrosis progression, regardless of type 2 diabetes. Use pioglitazone up to 30 mg/day, higher doses don’t add benefit. But caution about edema and weight gain, and avoid it in heart failure. Otherwise, titrate Ozempic or Wegovy toward max doses. There’s not much evidence with other GLP-1 agonists. But consider downsides, such as GI side effects and rare pancreatitis. Be aware, SGLT2 inhibitors (Jardiance, etc) reduce steatosis in type 2 diabetes, but there aren’t data on liver fibrosis.

Tell patients not to rely on milk thistle (Legalon) to help NAFLD. And don’t jump to vitamin E. Taking 800 IU/day might reduce steatosis and inflammation in patients with NASH withOUT diabetes, but there’s no evidence in other patients. Plus some evidence suggests that doses of 400 IU/day or above are linked with CV risk.

References

• Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022 May;28(5):528-562. Available at: https://www.endocrinepractice.org/article/S1530-891X(22)00090-8/fulltext

  Pradhan R, Yin H, Yu O, Azoulay L. Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Nonalcoholic Fatty Liver Disease Among Patients With Type 2 Diabetes. Diabetes Care. 2022 Apr 1;45(4):819-829. Available at: https://diabetesjournals.org/care/article-abstract/45/4/819/141054/Glucagon-Like-Peptide-1-Receptor-Agonists-and?redirectedFrom=fulltext