Non-alcoholic Fatty Liver Disease (NAFLD)

 

 

Definition:

–  NAFLD is characterized by excessive fat accumulation associated with insulin resistance and defined by the presence of steatosis in >5 % of hepatocytes according to histological analysis.

 Pathological types:

  • 1. Non-alcoholic fatty liver (NAFL)
  • 2. Non-alcoholic steatohepatitis
  •                  – Fibrosis
  •                  – Cirrhosis
  •                 – HCC
  • • Diagnosis requires exclusion of secondary causes and daily alcohol ingestion ≥ 30 g for men and ≥20 g for women. Alcohol consumption above this limits indicates alcoholic liver disease
  • • Patients consuming moderate amount of alcohol may be still predisposed to NAFLD if they have metabolic risk factors
  • • Definitive diagnosis requires liver biopsy

** If fibrosis present it is predominantly in zone 3 hepatocytes but it may extend to portal and peri-portal area

 

Primary NAFLD and risk factors/components of metabolic syndrome

  • – Waist circumference ≥ 94 / ≥80 cm for europid men/women
  • – Arterial pressure  ≥ 130/ ≥ 85 mm Hg or treated HTN
  • – HDL<40/50 mg/dl for men/women
  • – TG > 50 mg/dl

 

Secondary causes of NAFLD

  • – AFLD- alcoholic fatty liver disease
  • – Drug induced fatty liver disease
  • – Hepatitis C virus associated fatty liver disease (genotype3)
  • Others
  •            • Hemochromatosis
  •            • Autoimmune hepatitis
  •            • Celiac disease
  •            • Wilson’s disease
  •            • Hypopituitarism,
  •            • Hypothyroidism
  •            • Starvation
  •           • Parenteral nutrition
  •           • Inborn errors of metabolism
  • – Primary/ Secondary NAFLD may coexist
  • – NAFLD present in 7 % normal weight persons, more frequently in women at young age and normal liver enzymes, their liver disease may nonetheless progressive

Liver biopsy:

  • – Essential for the diagnosis of NASH
  • – Only test that reliably differentiates NAFL from NASH
  • – NAFL encompasses
  •         • Steatosis alone
  •         • Steatosis with lobular or portal inflammation without ballooning, or
  •         • Steatosis with ballooning but without inflammation

 

  • NASH encompasses
  •          – Steatosis + Ballooning + Lobular Inflammation
  •         – Other histological features of NASH that may present in NASH but not necessary
  •                             • Portal inflammation
  •                             • Polymorph nuclear infiltrate
  •                             • Mallory-denk bodies
  •                             • Apoptotic bodies
  •                            • Clear vacuolated nuclei
  •                            • Microvesicular steatosis
  •                            • Mega mitochondria

Non-invasive assessment:

  • – In clinical practice, quantification of fat content is not of interest, except as a surrogate of treatment efficacy and is therefore not generally recommended.
  • – USG has limited sensitivity and does not reliably detect steatosis when < 20% or in individuals with high BMI (>40 kg/m²)
  • – Despite inter-observer variation, USG (or CT scan) robustly diagnose moderate and severe steatosis and provides additional hepatobiliary information, hence it is the first line investigation
  • USG finding of NAFLD:
  •            – Bright liver of increased echogenicity- consistent with hepatic steatosis
  • CT finding of NAFLD:
  •             – Fatty liver is lower in density than spleen
  • MRI finding of NAFLD
  •            – Bright liver on T1 image
  •            – No imaging modality is able to distinguish simple steatosis from more advanced NAFLD

 

NASH

  • – Clinical, biochemical or imaging measures cannot distinguish NASH from steatosis
  • – NASH should be diagnosed by a liver biopsy showing steatosis, hepatocyte ballooning and LOBULAR inflammation
  • – Cytokeratin-18 (CK-18) which are generated during cell death or apoptosis have modest accuracy for the diagnosis of NASH
  • – CK-18 changes parallel the histological improvement but do not perform better than ALT in identifying histological responders
  • – To date, non-invasive tests are not validated for the diagnosis of NASH

Imaging to detect fibrosis

  • – Transient Elastography (TE) performs better for cirrhosis (F4) than for advanced fibrosis (F3)
  • – Elastography has a higher rate of false-positive results than negative results and has a higher negative predictive value than positive predictive value
  • Shortcomings of transient elastography
  •       – Unreliable results in the presence of
  •              • High BMI
  •              • Increased thoracic fold thickness
  •              • Narrow intercostal space
  •             • Extrahepatic cholestasis
  •             • Hepatic venous congestion
  •             • Acute inflammation
  • ** XL probe has been developed to increase diagnostic accuracy in these patients to reduce the failure rate
  • Other US based methods
  •             • Acoustic Radiation Force Impulse (ARFI)
  •             • MR elastography – better than TE in differentiating mild from moderate to severe fibrosis ( disadvantage- high cost, limited availability)

Monitoring of NAFLD patients

  • – NAFL patients without worsening of metabolic risk factors : monitor 2-3 year interval
  • – Patients with NASH and/or fibrosis: Monitor annually
  • – Patients with NASH cirrhosis : Monitor 6 monthly

Monitoring should include

  • – Routine biochemistry
  • – Assessment of comorbidities
  • – Non-invasive monitoring of fibrosis

 

                                             Treatment of NAFLD:

 

 


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