significant fibrosis Fibrosis stage F2 or F3 as defined histologically.^3,4* is a strong predictor of liver-related mortality in NASH^1,2

Lipotoxicity in the liver is a key driver of fibrosis^5-9

• NASH is a form of hepatitis (liver inflammation) where the major inciting factor is lipotoxic fat accumulation in hepatocytes (liver cells). NASH is defined by the presence of:^10-15
  Hepatic
  steatosis

  Hepatocellular
  damage

  Lobular
  inflammation
• Lipotoxic fat within hepatocytes drives an ongoing inflammatory state characterized by hepatocellular injury/death and increased numbers and activity of a variety of inflammatory cells, including hepatic stellate cells^10-13
  • In the presence of lipotoxicity, hepatic thyroid function mediated through thyroid hormone receptor-β (THR-β) is disrupted, impacting lipid metabolism and fatty acid oxidation in the liver^16,17
  • In NASH, normal thyroid hormone conversion (prohormone T4 to active hormone T3) shifts to conversion of T4 to inactive reverse T3 (rT3) in the liver. This produces a localized dysfunction in hepatic thyroid hormone activity, resulting in the impairment of mitochondrial activity and lipid management, including the generation of proinflammatory lipid species^18,19
  • Hepatic thyroid dysfunction has no effect on the hormone's activity elsewhere in the body (systemic activity and the central thyroid axis are unaffected)¹⁸
• As a result of persistent lipotoxicity and inflammation, hepatic stellate cells lay down scar tissue in the liver (fibrosis)^10,11,20
  • Increasing fibrosis can lead to cirrhosis, decompensated liver disease (ascites, esophageal varices, encephalopathy) and liver-related mortality^1,2,21,22

Once a patient develops significant fibrosis, Fibrosis stage F2 or F3 as defined histologically.^3,4 the risk of liver-related mortality increases substantially^1,2

• For some patients, time to development of severe liver disease may substantially accelerate with each stage of fibrosis progression starting at F2^21§†

Once significant fibrosisFibrosis stage F2 or F3 as defined histologically.^3,4 develops, it is important to actively manage patients with NASH²³

• Due to the increased risks of morbidity and mortality, identification of patients with significant fibrosisFibrosis stage F2 or F3 as defined histologically.^3,4 is important to target efforts at preventing disease progression^2,3,24
• The absence of a validated approach to predict the speed of progression for any individual patient further underscores the need for active monitoring

Noninvasive tests (NITs) are changing what’s possible with diagnosis and staging^25-27

Stay in touch with what’s happening in NASH with fibrosis