NASH with fibrosis—a progressive liver disease with severe consequences^1-5

NASH, the most severe form of nonalcoholic fatty liver disease (NAFLD), has a high prevalence that is on the rise^6,7

It is estimated that ~1.5 million people have been diagnosed with NASH^7,8

Of those, ~525,000 people are estimated to have significant fibrosis Fibrosis stage F2 or F3 as defined histologically.^12,20 without cirrhosis^7,8

The initial presentation of NASH is heterogeneous⁹

Patients may present with:
- Incidental evidence of excessive liver fat¹⁰
- Absence of symptoms or mild symptoms (including fatigue, upper right quadrant pain, and epigastric fullness)¹¹
- Severe liver-related conditions^10,11
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 level¹¹

NASH is associated with comorbidities^10,12

Patients with NASH often have other comorbidities, such as:
- Obesity
- Type 2 diabetes
- Dyslipidemia
- Hypertension
- Metabolic syndrome

Take a closer look at NASH pathophysiology in the liver

NASH can drive severe consequences including mortality^1-5

Cardiovascular disease (CVD)

NASH is an independent driver of CVD—even after controlling for confounding factors such as type 2 diabetes, obesity, and smoking.^2,4,13

CVD is the leading cause of mortality in patients with NASH^1,4
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)¹⁴

Cirrhosis and decompensated liver disease

NASH can lead to cirrhosis and liver decompensation in many patients.^15,16

~20%-50% of NASH patients will develop cirrhosis within 10 years¹⁷
~22% of NASH patients with fibrosis stage F3 progress to cirrhosis within 2 years¹⁶
~23% of NASH patients with cirrhosis progress to decompensated disease within 3 years¹⁶
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.^10,17

NASH is projected to soon become the leading cause for all liver transplantation¹⁰
NASH is also a leading etiology of liver disease among all candidates for liver transplantation¹⁸

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.¹⁹

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 NASH^7,19,20

Person checking weight on a sliding scale.

Weight loss (via lifestyle modifications and/or diet) is a key management strategy for NASH. Success can be very difficult for the majority of patients.^21,22
For NASH patients with fibrosis, the degree of weight loss required to impact NASH can be challenging to achieve and sustain over time²¹
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 fibrosis⁷Fibrosis stage F2 or F3 as defined histologically.^12,20:

F2will increase by82%

F3will increase by124%

*Fibrosis stage F2 or F3 as defined histologically.^12,20

In NASH, impairment of hepatic thyroid hormone signaling is a factor that worsens hepatic lipotoxicity, driving fibrosis progression.^22-26

NASH with fibrosis—a progressive 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

The initial presentation of NASH is heterogeneous9

NASH is associated with comorbidities10,12

NASH can drive severe consequences including mortality1-5