NP
Nurse Practitioner

Nonalcoholic Fatty Liver Disease

August 01, 2024.
Amanda Chaney, DNP, APRN, FAANP, AF-AASLD,, Senior Director of Advanced Practice Services, Cleveland Clinic

Educational Objectives

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

Cite potential clinical outcomes of NAFLD and nonalcoholic steatohepatitis (NASH).
Develop management strategies for obesity, NAFLD, and NASH.
Refer patients with NAFLD to specialists when appropriate.
Identify emerging medications and interventions that may have potential for management of NAFLD.
Manage comorbidities commonly associated with NAFLD.

Summary

Nonalcoholic fatty liver disease (NAFLD) and potential outcomes: associated with increased mortality; third most common cause of hepatocellular carcinoma (HCC) in the United States (US); nonalcoholic steatohepatitis (NASH) is the second most common cause of liver transplantation; obesity is a predictor of NASH-related cirrhosis; long-term mortality is associated with degree of fibrosis (advanced fibrosis is associated with poor outcomes)

Spectrum of NAFLD: nonalcoholic fatty liver — describes fat in liver cells (hepatic steatosis); alcohol can cause increased fat in the liver; NASH — describes the presence of inflammation in the liver; although liver can repair itself, ongoing inflammation and injury make this difficult; progression — disease can progress to fibrosis and then cirrhosis, at which point the condition is no longer reversible (reversibility is possible with advanced fibrosis if offending factors are removed); patients with cirrhosis are more likely to develop HCC and should be screened regularly

Changes in nomenclature (2023): NAFLD and NASH are classified under the umbrella term of steatotic liver disease (SLD); metabolic dysfunction-associated steatotic liver disease (MASLD) describes liver disease related to metabolic dysfunction; metabolic dysfunction-associated steatotic liver disease with increased alcohol intake describes disease caused by metabolic dysfunction and alcohol consumption; alcohol-associated liver disease (ALD) and cryptogenic SLD are also included; NASH is replaced with metabolic dysfunction-associated steatohepatitis (MASH)

Pathophysiology: complex processes; excess fat in the liver causes cell inflammation and injury; increase in fatty acid storage and decrease in fat oxidation increases size of liver cells, causing an enlarged, fatty appearance and increased injury of the liver; poor control of cardiometabolic conditions (eg, diabetes, hypertriglyceridemia) further increases fat into the liver cells, and it has a more difficult time leaving; this causes increased activation of inflammatory factors and liver damage, resulting in fibrosis and cirrhosis

Two-hit hypothesis: increase in fat in hepatocytes and inflammation in proinflammatory factors provide a “double hit”; presence of inflammation (steatohepatitis) causes fibrosis of scar tissue, and enlarged liver shrinks to a smaller-than-normal size; hepatic blood flow and production of clotting factors and digestive enzymes are reduced; hepatocytes are fragile and become unstable; increased inflammation causes mitochondrial dysfunction and cell death; fibrotic tissue leads to changes in structural design

Contributing factors: include genetics, dietary choices, diabetes, hyperlipidemia; lifestyle modifications can address many of these factors; alcohol consumption does not preclude diagnosis of NAFLD

Signs and symptoms of NAFLD: asymptomatic in most cases; often found during imaging for another reason; hepatomegaly is present in early stages, but liver is smaller and more fibrotic or cirrhotic in later stages

Initial evaluation: exclude other causes by performing laboratory tests, discussing medical history, and identifying other comorbidities; liver biopsy is the gold standard for diagnosis but is rarely performed because of high cost and potential for procedure error and risk for complications

Assessment of NAFLD: degree of fibrosis — risk factors for fibrosis include diabetes, uncontrolled hyperlipidemia, older age; severity can be assessed using NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4) calculator, BARD score, and aspartate aminotransferase-platelet ratio; NAFLD severity — scoring tools include Enhanced Liver Fibrosis Test, FIB-4, NFS; transient elastography (eg, FibroScan) is noninvasive tool and increasingly used for assessment

Complications of NAFLD: hyperlipidemia — statins should be given and reduce liver inflammation; cardiovascular disease (CVD) — NAFLD is an independent risk factor; stress testing and cardiac catheterization (as warranted) are recommended for symptomatic patients; hypertension — angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be considered if the patient does not have cirrhosis and ascites (which can be worsened by these drugs); obstructive sleep apnea — sleep study is recommended; consider continuous positive airway pressure to control symptoms; chronic kidney disease — patients with long-standing uncontrolled diabetes, dyslipidemia, hypertension are prone to more severe disease

Obesity: weight discussion is often avoided in clinic; <5% of primary care provider (PCP) visits are for weight management; >70% of adults in the US have a body mass index (BMI) >25; <1% of eligible patients use behavioral counseling for weight management that is covered by Medicare; diagnosis — BMI (>30 for obesity) is screening but not diagnostic, and is a core measure for documentation; waist circumference ≥35 in women and ≥40 in men; consider presence of risk factors; cutpoints for BMI and waist circumference differ for people of Asian ethnicity (BMI >23 and >26 for overweight and obesity, respectively)

NASH-related cirrhosis: prevalence of CVD is high; screen for esophageal varices (≤3 mo of diagnosis and every 6-12 mo thereafter) and HCC (ultrasonography and alpha fetoprotein every 6 mo); routine repeat biopsy is not recommended; referral to transplant center is recommended for patients with decompensated cirrhosis; monitor for metabolic issues in the post-transplantation setting; immunosuppression medications can worsen metabolic syndrome

Malnutrition and obesity: related to poor nutrition quality; sarcopenia is common and associated with poor outcomes in the post-transplantation setting; patients with NASH are most likely to be sarcopenic; nutrition consultation and encouraging increased consumption of high-protein foods and decreased consumption of high-fat and high-carbohydrate foods are recommended; prescribe physical therapy to increase muscle conditioning

Perceptions and barriers: avoid the term “obese patient” (labels the patient, which introduces a barrier to rapport and trust); address obesity as a disease that needs to be treated

Nonpharmacologic treatment of NAFLD: weight loss — reduce calorie intake by 500 to 1000 kcal/day; incorporate moderate-intensity exercise (150-200 min/wk); fibrosis regression occurs with weight loss ≥3%; avoid new liver injury — vaccinate for hepatitis A and B; avoid alcohol consumption; aggressive modification of CVD risk factors — manage diabetes, obstructive sleep apnea, dyslipidemia

Lifestyle therapy: counsel patients about ways to make changes; emphasize permanent lifestyle changes over temporary interventions; set reasonable goals; refer to dietician; support groups can be helpful; have a positive focus and encourage small, sustainable changes; plan to eat — should be individualized; increases in fruit, vegetables, lean protein, and decrease in red meat are recommended; movement — aerobic exercise with some resistance training is recommended; behaviors — smart goals (sustainable, small, realistic, timely, with a deadline) are recommended

Approaches for patient counseling: ABC approach — ask for permission to discuss weight; be systematic in discussing weight history, barriers, social determinants of health, medications; counsel patients and provide support by providing a wide range of dietary patterns and discussing physical activity; determine health status, comorbidities, and physical limitations; consider medications for patients with an eligible BMI; refer to an obesity specialist if eligible for bariatric surgery; discuss goals and follow up with the patient; “5 A’s” counseling framework — assess comorbidities and BMI, advise on weight loss, agree on goals, assist in accomplishing goals, and arrange for follow-up; use ADAPT (attitude, define problem, alternative solutions, predict consequences, try out solutions) mnemonic when assisting patients in their goals

Centers for Medicare and Medicaid Services reimbursement for behavioral therapy: offers weekly in-person visits during the first month, biweekly visits during 2 to 6 mo, monthly visits during 7 to 12 mo; visits are contingent on patient meeting a 3-kg weight loss during the first 6 mo of treatment; visits are 10 to 15 min (maximum of 22 visits); only PCPs are reimbursed

Pharmacologic treatments: none are approved by the US Food and Drug Administration for treatment of NASH; medications for diabetes, eg, metformin, may improve NASH by improving diabetes control; vitamin E improves histology for people with NASH and without diabetes; ursodeoxycholic acid has been tested but is not recommended; omega-3 fatty acids may help with hypertriglyceridemia but not recommended for NASH and NAFLD; pharmaceutical goals — improve liver-related outcomes with minimal side effects and reduce CVD risk; therapies are targeted toward people with high risk for disease progression

Future implications: emerging medications target metabolic issues, resulting inflammation, and progression to fibrosis; glucagon-like peptide-1 receptor agonists promote weight loss and insulin production, which reduces proinflammatory cytokines; thyroid hormone receptor β agonist is in phase 3 trials

Semaglutide: Newsome et al (2021) found that resolution of NASH without worsening of fibrosis (primary endpoint) occurred in a greater proportion of patients who received semaglutide compared with placebo

Bariatric surgery: Lassailly et al (2020) found that resolution of NASH and reduction of fibrosis occurred in 84% and 74%, respectively, of people who underwent bariatric surgery; Lee et al (2019) found that NASH resolution and reduction of fibrosis occurred in 66% and 40%, respectively, of people who underwent bariatric surgery

Readings

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Ms. Chaney has received royalties from APEA, PESI, and Springer Publishing. The planning committee reported nothing relevant to disclose.

Acknowledgements

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 0.00 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 0.00 CE contact hours.

Lecture ID:

NP240802

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.

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