NASH with fibrosis - a liver disease with severe consequences1-5

NASH, the most severe form of nonalcoholic fatty liver disease (NAFLD), has a high prevalence that is on the rise6,7

it is estimated that 5% to 6% of the adult population in the United States (US) have NASH7,8

That's ~22 million people living with NASH - many of whom remain undiagnosed7,9,10

Of those, 8 million people are estimated to have significant fibrosis* Fibrosis stage F2 or F3 as defined histologically.11,12 without cirrhosis7

The initial presentation of NASH is heterogeneous13

  • Patients may present with:
    • Incidental evidence of excessive liver fat14
    • Absence of symptoms or mild symptoms (including fatigue, upper right quadrant pain, and epigastric fullness)15
    • Severe liver-related conditions14,15
  • A normal or near-normal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level does not exclude NASH; however, many NASH patients are identified once they have an elevated ALT or AST level15

NASH is associated with comorbidities11,14

  • Patients with NASH often have other comorbidities, such as:
    • Obesity
    • Type 2 diabetes (T2D)
    • Dyslipidemia
    • Hypertension
    • Metabolic syndrome

Take a closer look at NASH pathophysiology in the liver

NASH can drive severe consequences including mortality1-5

Cardiovascular disease (CVD).

NAFLD and NASH are independent drivers of CVD - even after controlling for confounding factors such as T2D, obesity, and smoking.2,4,16

  • CVD is the leading cause of mortality in patients with NAFLD/NASH1,4
  • Patients with NASH have been shown to be twice as likely to die from CVD as the general population (15.5% vs 7.5% over a mean follow-up period of 13.7 years)17
Cirrhosis and decompensated liver disease.

NASH can lead to cirrhosis and liver decompensation in many patients.18,19

  • ~20-50% of NASH patients will develop cirrhosis within 10 years18
  • ~22% of NASH patients with fibrosis stage F3 progress to cirrhosis within 2 years19
  • ~23% of NASH patients with cirrhosis progress to decompensated disease within 3 years19
  • The incidence of liver decompensation is estimated to increase by 2.7 times between 2015 and 20307
Liver transplant.

In the US, NASH is the leading cause for liver transplantation in women and is the second leading cause for all liver transplantation.14,20

  • NASH is projected to soon become the leading cause for all liver transplantation14
  • NASH is also a leading etiology of liver disease among all candidates for liver transplantation21
Hepatocellular carcinoma (HCC).

It has been estimated that patients with non-cirrhotic NASH have about a 3-fold increased risk of HCC compared to those with liver disease of other etiologies.22

  • Projections suggest that the incidence of NASH-associated HCC could more than double between 2015 and 20307

Despite its significant clinical impact, there is no FDA-approved treatment for NASH7,23,24

Person checking weight on a sliding scale.
  • Weight loss (via lifestyle modifications and/or diet) is a key management strategy for NASH, but success can be very difficult for the majority of patients24,25
  • The significant weight loss required to impact NASH can be challenging to achieve and sustain over time24
  • Despite current management approaches, NASH prevalence is on the rise7
    • By 2030, estimates project an increase in cases of NASH at every stage of fibrosis, including significant fibrosisFibrosis stage F2 or F3 as defined histologically.7:
*Fibrosis stage F2 or F3 as defined histologically.

Lipotoxicity in the liver is a key driver of fibrosis26-30

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