Summary

AASLD 2023 Practice Guidance updates the 2018 NAFLD document, emphasizing noninvasive risk stratification (FIB-4, VCTE, ELF, MRE) to identify “at-risk” NASH (NASH with ≥F2 fibrosis) and management of metabolic comorbidities. It highlights newer therapeutics with potential NASH benefit (semaglutide, pioglitazone, vitamin E) while noting no agent is FDA-approved for NASH. Pediatric NAFLD and NAFLD-in-diabetes are addressed in separate documents.

Key Recommendations

Do not perform population-based NAFLD screening; screen high-risk groups (T2DM, medically complicated obesity, family history of NASH cirrhosis, >mild alcohol use) for advanced fibrosis.
Use FIB-4 as the first-line primary risk assessment in all patients with suspected NAFLD; repeat every 1–2 years if pre-DM/T2DM or ≥2 metabolic risk factors.
If FIB-4 ≥1.3, perform secondary risk assessment with VCTE, MRE, or ELF; refer to hepatology if intermediate/high risk or persistent ALT/AST elevation >6 months.
Prescribe statins for CVD risk reduction in NAFLD across the disease spectrum including compensated cirrhosis; use cautiously in decompensated cirrhosis.
Recommend Mediterranean-style diet with caloric deficit and individualized exercise; weight loss of ≥10% is generally required to improve NASH and fibrosis.
Counsel patients with ≥F2 fibrosis to abstain completely from alcohol; quantify alcohol intake at every visit.
Consider bariatric surgery in eligible patients with NASH without cirrhosis, as it resolves NASH and reduces CVD/malignancy mortality; avoid in decompensated cirrhosis.
Consider semaglutide in patients with NASH plus T2DM or obesity given cardiovascular benefit and NASH resolution; consider pioglitazone for NASH with T2DM.
Consider vitamin E 800 IU/day in select non-diabetic adults with biopsy-proven NASH after discussion of risks.
Do not use metformin, UDCA, DPP-4 inhibitors, statins (for NASH), or silymarin as NASH therapy — no meaningful histological benefit.
Screen all patients with NAFLD for T2DM, dyslipidemia, hypertension, and (if overweight/obese) obstructive sleep apnea.
In cirrhosis, perform biannual HCC surveillance and screen for esophageal varices; first-degree relatives of NASH cirrhosis patients should be screened for advanced fibrosis.

Thresholds & Doses

True normal ALT: 29–33 U/L (men), 19–25 U/L (women); chronic ALT/AST >30 U/L suggests injury.
NAFLD alcohol threshold: <20 g/day women, <30 g/day men; moderate 21–39 g (W)/31–59 g (M); heavy ≥40 g (W)/≥60 g (M).
FIB-4: <1.3 low risk; 1.3–2.67 intermediate; >2.67 high risk; use cutoff >2.0 if age >65; unreliable if <35.
VCTE liver stiffness: <8 kPa rules out advanced fibrosis; 8–12 kPa possible fibrotic NASH; >12 kPa advanced fibrosis; ≥20 kPa suggests cirrhosis (with FIB-4 >3.48).
MRE liver stiffness: ≥5 kPa suggests cirrhosis; <5/5–8/>8 kPa correspond to 1.6%/17%/19% 3-year decompensation risk.
ELF: ≥9.8 identifies progression risk; ≥11.3 predicts future liver-related events.
Weight loss targets: 3–5% improves steatosis; ≥7–10% improves NASH; >10% improves fibrosis.
Exercise: ≥150 min/week moderate activity (5 sessions); vigorous exercise may be needed to improve NASH/fibrosis.
Coffee: ≥3 cups/day associated with reduced NAFLD/fibrosis risk.
Vitamin E (rrr α-tocopherol) 800 IU daily for biopsy-proven NASH in non-diabetics (PIVENS regimen).
Semaglutide phase 2b: NASH resolution 59% (0.4 mg daily) vs 17% placebo at 72 weeks.
Severe hypertriglyceridemia >500 mg/dL: use fibrates ± omega-3/icosapent ethyl to reduce pancreatitis risk.
Bariatric surgery criteria: BMI ≥40 kg/m² or ≥35 kg/m² with comorbidities; NASH increasingly accepted as qualifying comorbidity.
MRI-PDFF: ≥30% relative decline associated with 5-fold higher odds of NASH resolution.
Liver biopsy: 16-G needle, ≥1.5 cm (preferably 2–2.5 cm) length.
Lean NAFLD BMI cutoff: <25 kg/m² (<23 kg/m² in Asian individuals).

Citations

Guidance statements 1–5 (Comorbid conditions) — statin use, hypertriglyceridemia management, T2DM screening.
Guidance statements 6–7 (Alcohol) — abstinence in ≥F2 fibrosis.
Guidance statements 9–16 (Screening/risk assessment) — FIB-4 use, screening high-risk populations, biopsy indications.
Figure 2 — Algorithm for evaluation across practice settings with FIB-4/VCTE/MRE cutpoints.
Guidance statements 17–19 and Table 5 — Noninvasive tests for steatosis and fibrosis.
Guidance statements 20–22 (Lifestyle/bariatric) — diet, exercise, bariatric surgery.
Guidance statements 23–28 (Pharmacotherapy) — semaglutide, pioglitazone, vitamin E; agents not to use.
Guidance statement 29 (Surrogate markers) — ALT and imaging response as surrogates.