Non-Alcoholic Fatty Liver Disease (NAFLD)

The prevalence of Non-alcoholic fatty liver disease (NAFLD) is higher in PLWH (30- 40% in the US) than in the general population [17]

Nearly half of the PLWH who undergo evaluation for unexplained liver test abnormalities are found to have NAFLD. The diagnosis of NAFLD requires the exclusion of both secondary causes and of a daily alcohol consumption ≥ 30 g for men and ≥ 20 g for women

Spectrum of NAFLD

Often associated with components of the metabolic syndrome:

  • NAFLD is defined as:
    • hepatic steatosis involving > 5% of hepatocytes
    • often associated with components of metabolic syndrome
    • exclusion of both secondary causes and of alcoholic fatty liver disease (defined as a daily alcohol consumption ≥ 30 g for men and ≥ 20 g for women)
  • Non-Alcoholic SteatoHepatitis (NASH)
    • Early NASH: no or mild (F0-F1) fibrosis
    • Fibrotic NASH: significant (≥ F2) or advanced (≥ F3, bridging) fibrosis
    • NASH-cirrhosis (F4)
    • HCC (can occur in the absence of cirrhosis and histological evidence of NASH)
  • Most common concurrent diseases
    • AFLD-alcoholic fatty liver disease
    • Drug-induced fatty liver disease
    • HCV-associated fatty liver (GT 3)

ARV Drug Considerations

  • Consider use of lipid neutral regimens in individuals at risk of or with NAFLD


  • Ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD
  • Whenever imaging tools are not available or feasible, serum biomarkers
    and scores are an acceptable alternative for the diagnosis
  • Where available and in experienced centres, transient elastography with controlled attenuation parameter could be used to diagnose HIV-associated NAFLD, although no optimal cut-off has been established yet
  • A quantitative estimation of liver fat can only be obtained by MRS as well as MRI-PDFF. This technique is of value in clinical trials and experimental studies, but is expensive and not recommended in the clinical setting.
  • NASH has to be diagnosed by a liver biopsy showing steatosis, hepatocyte ballooning and lobular inflammation


  • Lifestyle modification and weight reduction is the cornerstone of treatment
  • Dietary restriction PLUS Progressive increase in aerobic exercise/resistance training: Calorie restriction (500-1,000 /day) targeting 7-10% weight loss target in persons with central obesity and/or overweight; 150-200 min/ week of moderate intensity aerobic physical activities in 3-5 sessions
  • Pharmacotherapy should be reserved for individuals with NASH, particularly for those with significant fibrosis ≥ F2 and individuals with less severe disease, but at high risk of faster disease progression (i.e. with diabetes, metabolic syndrome, persistently increased ALT, high necroinflammation)
  • Management and treatment of NASH should be discussed with hepatologists. Options with proven efficacy include pioglitazone, vitamin E and bariatric surgery, although no specific studies are available in the context of HIV infection
  • Statins may be safely used but have demonstrated no impact on liver disease. The same is true for n-3 polyunsaturated fatty acids


Diagnostic Flow-chart to Assess and Monitor Disease Severity in Case of Suspected NAFLD and Metabolic Risk Factors


These recommendations are largely inspired by the EASL–EASD–EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease: European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity [18]

  1. NAFLD, Non-alcoholic fatty liver disease
  2. FIB-4 = Age ([years] x AST [U/L]) / ([platelet [109/L]) x ALT [U/L])
  3. NFS, Non-alcoholic fatty liver disease Fibrosis Score = -1.675 + 0.037 x age (years) + 0.094 x BMI (kg/m2) + 1.13 x impaired fasting glucose/diabetes mellitus(iv) (yes=1/no=0) + 0.99 x AST/ALT ratio-0.013 x platelet (x109)-0.66 x albumin(g/dL)
  4. ELFTM test, Enhanced Liver Fibrosis Test is a blood test that provides an estimate of liver fibrosis severity by measuring Hyaluronic Acid (HA), Amino-terminal propeptide of type III procollagen (PIIINP), Tissue inhibitor of metalloproteinase 1 (TIMP-1)
  5. ARFI elastography, Acoustic Radiation Force Impulse