significant fibrosis Fibrosis stage F2 or F3 as defined histologically.5,19* is a strong predictor of liver-related mortality in NASH1,2

Fibrosis progression can be rapid and unpredictable, often resulting in cirrhosis.3,4

  • According to claims data from a retrospective real-world cohort study of 19,419 patients with noncirrhotic NASH at baseline, 22% (4235) progressed to end-stage liver disease over an average of ~3 years4†
    • ~50%‡ of patients progressed within 1 year to cirrhosis, decompensated cirrhosis, liver transplant, or liver cancer4
    • ~80%‡ of progressors advanced directly to decompensated cirrhosis4
  • This nature of progression makes early diagnosis and active management critical4,5

Once a patient develops significant fibrosis, Fibrosis stage F2 or F3 as defined histologically.5,19 the risk of liver-related mortality increases substantially1,2

  • For some patients, time to development of severe liver disease may substantially accelerate with each stage of fibrosis progression starting at F26§‖

In NASH, impairment of hepatic thyroid hormone signaling is a factor that drives fibrosis progression7-10

NASH with fibrosis is a complex, progressive liver disease driven by multiple factors such as genetics, environment, other conditions, and disease site dynamics.11,12

  1. In NASH, there can be disruption of hepatic thyroid hormone signaling mediated via thyroid hormone receptor-β (THR-β), which is found predominately in the liver7,9
  2. THR-β signaling disruption can cause mitochondrial dysfunction and impaired lipid metabolism, and is a factor that can worsen hepatic lipotoxicity that drives NASH and fibrosis progression7-10
  3. As a result, hepatic stellate cells lay down scar tissue (fibrosis) in the liver, which can progress to cirrhosis, decompensated liver disease, and an increased risk of liver-related mortality1,2,8,9,13

For more information, please visit the FAQs below.

What is the role of the thyroid hormone signaling pathway in the liver?

Thyroid hormone plays a central role in hepatic lipid metabolism and processing. The effects of thyroid hormone on hepatic lipid homeostasis are primarily exerted through thyroid receptor‐β (THR‐β), the predominant isoform expressed in the liver.7

  • In a healthy liver, hepatic thyroid hormone signaling activates lipid metabolism and contributes to normal liver function7
  • In NASH, studies have shown 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 species8,14‐16
  • Impairment of hepatic thyroid hormone signaling mediated through THR-β worsens hepatic lipotoxicity, driving progression of liver fibrosis in NASH7‐10

What do current clinical guidelines recommend regarding the treatment goal or goals for NASH?

According to current clinical guidelines, the treatment goal in NASH is to resolve the underlying inflammation and steatohepatitis that drive disease progression, in addition to halting and reversing fibrosis. Evidence of fibrosis reversal or halting as well as NASH resolution are considered the best surrogate endpoints to likely predict clinical benefit and correlate to improved disease outcomes.5,17

Why is it important to actively manage NASH?

It’s important to manage NASH because the rates of fibrosis progression and hepatic decompensation vary significantly for each patient. Once a patient develops stage F2, the progression of fibrosis can accelerate unpredictably and the risk of liver-related mortality can increase substantially.3,6,9,18

*Fibrosis stage F2 or F3 as defined histologically.5,19
†Based on US health insurance claims data from large commercial and Medicare Advantage health plans. Patients were identified based on first captured MASH diagnosis within a 6-month period, and may not necessarily reflect first-ever diagnosis (epidemiological data).
‡Percentage of the 4235 patients who progressed to end-stage liver disease.4
§Cirrhosis, liver failure, liver decompensation, or hepatocellular carcinoma.
‖The lower end of the 95% CI for the 10th percentile.
NASH=nonalcoholic steatohepatitis; T3=triiodothyronine; T4=thyroxine.

Noninvasive tests (NITs) can be used for
disease identification and staging.20-22

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