The Increasing Predicament of NASH

Silent Yet Ever More Prevalent in Western Populations

Before we even talk about NASH, let’s talk about NAFLD: non-alcoholic fatty liver disease. This a condition in which excess fat is stored in your liver. As the name implies, the build-up of fat is not caused by heavy alcohol use (which is commonly known as alcoholic liver disease).

Now, there are two types of NAFLD: simple fatty liver and NASH. These conditions are separate from each other. People typically develop one type of NAFLD or the other, although sometimes people with one form are later diagnosed with the other form of NAFLD.

What is Simple Fatty Liver?

Simple fatty liver, also called non-alcoholic fatty liver (NAFL), or steatosis, is a form of NAFLD in which you have fat in your liver but little or no inflammation or liver cell damage. Simple fatty liver typically does not progress to cause liver damage or complications.

What is NASH?

NASH stands for non-alcoholic steatohepatitis. It is a type of non-alcoholic fatty liver disease (NAFLD). NAFLD is a condition in which excess fat is stored in your liver. This build-up of fat is not caused by heavy alcohol use (which causes actual alcoholic liver disease).

Trivia: Experts are not sure why some people with NAFLD have NASH while others have simple fatty liver.

The 4 Stages of NAFLD

There are 4 main stages of NAFLD:

1. Simple fatty liver (steatosis) – a build-up of fat in the liver cells, which is usually harmless. For the most part, simple fatty liver may only be diagnosed during tests carried out for another reason
2. Non-alcoholic steatohepatitis (NASH) – a more serious form of NAFLD, where the liver has become inflamed. This is difficult to diagnose
3. Fibrosis – persistent inflammation from the previous stage starts to cause scar tissue around the liver and nearby blood vessels. The liver is still able to function normally at this stage
4. Cirrhosis – the final and most severe stage that occurs after years of inflammation. The liver shrinks and becomes lumpy and scarred. At this stage, the damage is permanent and can lead to liver failure (where your liver stops working properly) and liver cancer

Most people will only ever develop steatosis, usually without realising it. In a small number of cases, it can progress and eventually lead to liver damage if not detected and managed. It can take years for patients to eventually develop fibrosis or cirrhosis.

What are the Symptoms?

There aren’t usually any symptoms that can be observed in the early stages of NAFLD. Occasionally, people with NASH or fibrosis (more advanced stages of NAFLD) may experience the following:

1. Dull or aching pain in the top right of the tummy (over the lower right side of the ribs)
2. Extreme tiredness
3. Unexplained weight loss
4. Weakness

In most cases, those who suffer simple fatty liver disease or NASH are advised to make various lifestyle changes to prevent the condition from getting worse. These include maintaining a healthy diet, exercising regularly, stopping smoking, and so on.

Prevalence Factors: What Leads to NAFLD & NASH?

A study of NAFLD prevalence was carried out on one of the largest databases in the United States (an estimated 12,317 individuals). It concluded that 34% of the general population in the United States were affected by NAFLD, amounting to at least 42 million adults.

On a global scale, the prevalence of NAFLD is estimated at 24%; the highest rates are reported from South America and the Middle East, followed by Asia, the USA, and Europe.

The two most prevalent factors were identified among patients suffering from NAFLD and NASH:

1. Obesity – NAFLD is highly prevalent in populations suffering from obesity. A study from more than 1,600 individuals who had bariatric surgery (a type of weight loss surgery) revealed a prevalence of 37% towards NASH. According to OECD projections, 47% of the adult population in the United States will suffer from obesity by 2030, compared to 37.7% in 2014.
2. Type 2 Diabetes – On a global scale, the rates of diabetes are expected to grow by 55% by the year 2035 according to the International Diabetes Federation. This means that the population at risk of NAFLD/NASH will increase dramatically in the coming decades.

Other prevalence factors include:

1. High blood pressure
2. Over 50 years old
3. High count in cholesterol
4. Metabolic syndrome
5. Smoking

Here’s something else to think about: NAFLD has been diagnosed in people without any of these risk factors, including young children.

Current Challenges

NASH is a silent disease, and remains difficult to diagnose, even though promising programs are currently in development. Recent trends, however, indicate that NAFLD is growing to become the most common chronic liver condition in Western populations.

This coincides with relation to obesity and type 2 diabetes epidemics. Therefore, the prevalence of NASH is expected to increase by 63% between 2015 and 2030.

NAFLD and NASH in children is a major health concern for the medical community. A study conducted in the United States with a sample of more than 8,500 individuals estimated that 10% of US adolescents were affected by NAFLD, and 3% by NASH.

There’s currently no specific medication to treat NAFLD (and NASH for that matter), but there are various medicines that can be used in managing the problems associated with the condition. For example, doctors may recommend medication to treat high blood pressure, high cholesterol, type 2 diabetes and/or obesity.

In cases where patients develop severe cirrhosis, or the liver ceases to function properly, the only option is to undergo a liver transplant.

NASH is expected to become the leading cause of liver transplantation by 2020.

Potential Cure & Market Outlook

Intercept Pharmaceuticals are developing an experimental drug (dubbed obeticholic acid), to help improve liver scarring in patients with NASH. This is, by far, the biggest milestone in the field of NASH treatments to date, as the drug has already undergone a large Phase 3 study, with positive results.

In addition, Nash Pharmaceuticals (a subsidiary of Breathtec Biomedical) has recently announced positive pre-clinical test results for their lead compound NP-135. This product candidate showed an 84.4% reduction of fibrosis in patients suffering from NASH.

There are currently no US FDA approved treatments for NAFLD or NASH.

According to a report published by Allied Market Research, the global NASH market was valued at USD 1.17 Billion in 2017. The market is forecast to be within the avenue of USD 21.4 billion by 2025 as populations with fatty diets increasingly fall victim to a condition with no approved treatments available.

Other notable companies that are also developing treatments for NASH include Pfizer, Bristol-Myers Squibb, Gilead Sciences and Allergan. Investors and key players are on the lookout for promising initiatives that can treat NASH effectively.

Sources:

1. https://www.globenewswire.com/news-release/2019/01/31/1708218/0/en/Nash-Pharmaceuticals-to-Present-Pre-Clinical-Data-on-Non-Alcoholic-Fatty-Liver-Disease-at-2nd-Global-NASH-Congress-in-London-UK.html
2. https://www.alliedmarketresearch.com/press-release/global-non-alcoholic-steatohepatitis-NASH-market-is-expected-to-reach-1-6-billion-by-2020-allied-market-research.html
3. https://www.biopharmadive.com/news/intercept-nash-drug-succeeds-in-fields-first-positive-phase-3-trial/548678/
4. https://www.the-nash-education-program.com/what-is-nash/key-figures/
5. https://www.nhs.uk/conditions/non-alcoholic-fatty-liver-disease/
6. https://www.nature.com/articles/nrgastro.2017.109