Nonalcoholic Fatty Liver Disease (NAFLD)

Educational Objectives

The goal of this program is to improve management of nonalcoholic fatty liver disease. After hearing and assimilating this program, the clinician will be better able to:

1. Perform a diagnostic workup for patients at high risk for nonalcoholic fatty liver disease (NAFLD).
2. Develop management strategies for NAFLD to reduce risk for progression to cirrhosis and hepatocellular carcinoma.

Summary

Overview: presence of metabolic syndrome and genetic risk factors decrease responsiveness of the hepatocytes to insulin, which leads to accumulation of triglycerides in the liver; ≈47% of patients with nonalcoholic fatty liver disease (NAFLD) progress to nonalcoholic steatohepatitis (NASH), in which oxidative injury and inflammation occur

Nonalcoholic steatohepatitis

Consequences of disease progression: if untreated, ≤50% of patients develop cirrhosis; identification and prevention of cirrhosis are important because hepatocellular carcinoma (HCC) can develop, ≤50% of patients require liver transplantation after 10 yr, and risk for liver-related mortality is high; higher stage of fibrosis is associated with a decrease in survival; early diagnosis can improve outcomes

Prevalence and trends: prevalence of advanced fibrosis, cirrhosis, and liver-related mortality is expected to increase by >100% by 2030; >50% of patients on the waitlist for liver transplantation have NASH and alcoholic liver disease; since 2016, NASH has become the most common indication for liver transplantation in women and second most common in men

Risk factors: include metabolic syndrome, central obesity, insulin resistance or type 2 diabetes, hyperlipidemia, and Latin American or Middle Eastern ethnicity

Epidemiology and sex distribution:polycystic ovarian syndrome (PCOS) — present in ≤10% of women of reproductive age; >50% of women with PCOS have NAFLD (usually undiagnosed); age and sex — NAFLD is more common in men among individuals <60 yr of age, at which point the prevalence among women starts to increase; NASH is less common but more severe in women; complications — women are at higher risk for cirrhosis and lower risk for HCC compared with men; cardiovascular complications are the leading cause of death in patients with NASH; estrogen does not appear to have a cardioprotective effect in women with NAFLD, and risk for ischemic cardiovascular events is higher in young women than in men with NAFLD

Noninvasive diagnosis of NAFLD: liver function tests — commonly used for screening but are normal in ≤80% of patients; elevation in alanine transaminase (ALT) is poorly correlated with histology; ALT often normalizes as disease progresses, and aspartate aminotransferase (AST) levels may be higher than ALT; important features — markers must be noninvasive, reproducible, cost-effective, and widely available; additional data on sex differences in biomarkers are needed

Scoring systems to identify high-risk patients: NAFLD Fibrosis Score and Fibrosis-4 Index for Liver Fibrosis use age, AST, ALT, platelet count, body mass index, albumin, and impaired fasting glucose to predict risk for advanced fibrosis and identify patients who should receive further treatment

Transient elastography (eg, FibroScan): used to diagnose and monitor advanced liver cirrhosis; other liver diseases should be ruled out prior to staging with biomarker scoring in patients at risk for NAFLD; elastography is recommended for patients at high risk for advanced fibrosis

Treatment:lifestyle modifications — weight loss of 10% was shown to improve scarring in ≈45% of patients; weight loss of 5% to 7% has been shown to improve NASH and inflammation related to hepatic steatosis; study showed that a 12-wk exercise program led to improvement in fibrosis on biopsy for a majority of patients; bariatric surgery — reversal of liver scarring was observed ≤5 yr after surgery in patients with NASH, particularly those with less scarring; study showed higher quality-of-life scores in patients who underwent surgery; overall approach — requires integrated care by hepatologists, dieticians, primary care physicians, endocrinologists, and cardiologists

Medications: use for NASH is considered off label; pioglitazone and vitamin E have strong evidence to support use; antidiabetes drugs — glucagon like peptide-1 receptor agonists (eg, liraglutide and semaglutide) and sodium glucose cotransporter 2 inhibitors are being studied; LEAN trial showed histologic improvement in resolution of NASH, weight loss, and ALT with liraglutide; obeticholic acid — REGENERATE study showed an improvement in scarring without worsening of NASH after 18 mo of use; elafibranor — thought to have a better safety profile than obeticholic acid and reduce oxidative injury, inflammation, and cholesterol in the liver; phase 2 trial showed improvement in NASH, liver tests, glucose profile, and cholesterol

Readings

Chandrakumaran A, Siddiqui MS. Implications of nonalcoholic steatohepatitis as the cause of end-stage liver disease before and after liver transplant. Gastroenterol Clin North Am. 2020; 49:165-178; doi: 10.1016/j.gtc.2019.09.005; Charatcharoenwitthaya P et al. Moderate-intensity aerobic vs resistance exercise and dietary modification in patients with nonalcoholic fatty liver disease: a randomized clinical trial. Clin Transl Gastroenterol. 2021; 12:e00316; doi: 10.14309/ctg.0000000000000316; Galvin Z et al. Predictors of de novo nonalcoholic fatty liver disease after liver transplantation and associated fibrosis. Liver Transpl. 2019; 25:56-67; doi: 10.1002/lt.25338; Perumpail BJ et al. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2017; 23:8263-8276; doi: 10.3748/wjg.v23.i47.8263; Shamsoddini A et al. Effect of aerobic and resistance exercise training on liver enzymes and hepatic fat in iranian men with nonalcoholic fatty liver disease. Hepat Mon. 2015; 15:e31434; doi: 10.5812/hepatmon.31434; Tesfay M et al. NASH: the emerging most common form of chronic liver disease. Mo Med. 2018; 115:225-229.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Halegoua-DeMarzio was recorded at the 2nd Annual Jefferson Women and Gastroenterology Health Symposium, held February 21, 2020, in Philadelphia, PA, and presented by Sidney Kimmel Medical College at the University of Thomas Jefferson. For information on future CME activities from this presenter, please visit cme.jefferson.edu. Audio Digest thanks the speakers and meeting presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

GE352201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.