Diagnosis and Management of Non-Alcoholic Fatty Liver Disease

Publication Date: September 1, 2017
Last Updated: March 14, 2022

Guidance Statements


1. Ongoing or recent alcohol consumption >21 standard drinks on average per week in men and >14 standard drinks on average per week in women is a reasonable threshold for significant alcohol consumption when evaluating patients with suspected NAFLD.

2. Patients with unsuspected HS detected on imaging who have symptoms or signs attributable to liver disease or have abnormal liver chemistries should be evaluated as though they have suspected NAFLD and worked up accordingly.

3. Patients with incidental HS detected on imaging who lack any liver-related symptoms or signs and have normal liver biochemistries should be assessed for metabolic risk factors (e.g., obesity, diabetes mellitus, or dyslipidemia) and alternate causes for HS such as significant alcohol consumption or medications.

4. Routine Screening for NAFLD in high-risk groups attending primary care, diabetes, or obesity clinics is not advised at this time because of uncertainties surrounding diagnostic tests and treatment options, along with lack of knowledge related to long-term benefits and cost-effectiveness of screening.

5. There should be a high index of suspicion for NAFLD and NASH in patients with type 2 diabetes. Clinical decision aids such as NFS or fibrosis-4 index (FIB-4) or vibration controlled transient elastography (VCTE) can be used to identify those at low or high risk for advanced fibrosis (bridging fibrosis or cirrhosis).

6. Systematic screening of family members for NAFLD is not recommended currently.

7. When evaluating a patient with suspected NAFLD, it is essential to exclude competing etiologies for steatosis and coexisting common CLD.

8. In patients with suspected NAFLD, persistently high serum ferritin, and increased iron saturation, especially in the context of homozygote or heterozygote C282Y HFE mutation, a liver biopsy should be considered.

9. High serum titers of autoantibodies in association with other features suggestive of autoimmune liver disease (>5 ULN aminotransferases, high globulins, or high total protein to albumin ratio) should prompt a work-up for autoimmune liver disease.

10. Initial evaluation of patients with suspected NAFLD should carefully consider the presence of commonly associated comorbidities such as obesity, dyslipidemia, IR or diabetes, hypothyroidism, polycystic ovary syndrome, and sleep apnea.

11. In patients with NAFLD, MetS predicts the presence of SH, and its presence can be used to target patients for a liver biopsy.

12. NFS or FIB-4 index are clinically useful tools for identifying NAFLD patients with higher likelihood of having bridging fibrosis (stage 3) or cirrhosis (stage 4).

13. VCTE or MRE are clinically useful tools for identifying advanced fibrosis in patients with NAFLD.

Abbreviations: AASLD, American Association for the Study of Liver Diseases; ACG, American College of Gastroenterology; AIH, autoimmune hepatitis; ALT, alanine aminotransferase; APRI, AST to platelet ratio index; AST, aspartate aminotransferase; AUROC, area under the receiver operating curve; BMI, body mass index; CI, confidence interval; CLD, chronic liver disease; CT, computed tomography; CVD, cardiovascular disease; ELF, Enhanced Liver Fibrosis; FDA, U.S. Food and Drug Administration; FIB-4, fibrosis-4 index; FLD, fatty liver disease; GFR, glomerular filtration rate; GLP-1, glucagon-like peptide-1; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDL, high-density lipoprotein; HF, hepatic fibrosis; HS, hepatic steatosis; ICD-10, International Classification of Diseases, Tenth Revision; IR, insulin resistance; LDL, low-density lipoprotein; LT, liver transplantation; METs, metabolic equivalents; MetS, metabolic syndrome; MR, magnetic resonance; MRE, MR elastography; MRI, magnetic resonance imaging; NAFL, nonalcoholic fatty liver; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD activity score; NASH, nonalcoholic fatty liver disease; NASH CRN, NASH Clinical Research Network; NFS, NAFLD fibrosis score; NIAAA, National Institute on Alcohol Abuse and Alcoholism; OCA, obeticholic acid; PNPLA-3, patatin-like phospholipase domain-containing protein 3; PPAR, peroxisome proliferator-activated receptor gamma; RCT, randomized controlled trial; SAF, Steatosis Activity Fibrosis; SH, steatohepatitis; T2DM, type 2 diabetes mellitus; TE, transient elastography; TG, triglyceride; TONIC, treatment of nonalcoholic fatty liver disease in children; UDCA, ursodeoxycholic acid; ULN, upper limit of normal; VCTE, vibration controlled transient elastography; WD, Wilson’s disease.



Diagnosis and Management of Non-Alcoholic Fatty Liver Disease

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