NASH: Present and Emerging Treatments
Nonalcoholic steatohepatitis (NASH) is the second leading cause of liver transplantation in the United States. Since available therapeutic options remain limited, developing new therapies that can change the disease outcomes for people living with NASH is vital. This brief article will look at the current NASH management options and discuss new drugs in development.
What is NASH?
Nonalcoholic steatohepatitis (NASH) is a condition marked by a buildup of fat in the liver, chronic inflammation, and scarring. It often develops from a less severe condition called nonalcoholic fatty liver disease (NAFLD). NASH is very similar to liver damage caused by long-term drinking. Still, it occurs in people who don’t abuse alcohol.
Risk factors include high body weight, high blood sugar and fats levels, type 2 diabetes, insulin resistance, older age, etc. The exact cause is unclear, and scientists still don’t understand why some people develop NASH, and some don’t.
What are the Symptoms of NASH?
Common symptoms of NASH include:
- Weakness and fatigue
- Intense itching
- Yellow skin and eyes
- Pain or discomfort in the upper right abdomen
- A swollen stomach
- Visible spider-like blood vessels beneath the skin
- Unexplainable weight loss
The condition may progress for several years before it causes symptoms.
People with NASH are more likely to develop other health problems, such as:
- Cirrhosis
- Liver cancer (called hepatocellular carcinoma)
- Liver failure
- Heart problems
- Type 2 diabetes
How is NASH Treated?
Although there are no approved drugs to cure NASH at present, symptoms can improve through a combination of:
- Lifestyle changes
- Medications, such as vitamin E and pioglitazone
Please note that it is important to talk with your doctor before starting or taking any medications or supplements.
Lifestyle Changes
Weight loss is the first line of treatment for NASH patients. Losing 3 to 5% of body weight can reduce the fat buildup in the liver, while losing 5 to 10% of body weight may also lower inflammation. Weight loss typically can be achieved through:
- Having a balanced diet
- Cutting down on calories
- Regular exercise
- Limiting the intake of salt and sugar
Vitamin E
Vitamin E is a powerful antioxidant that may reduce inflammation and fat accumulation in the liver. These benefits come with an increased risk of intracranial bleeding and prostate cancer. Vitamin E is recommended by US, European, and Japanese guidelines for biopsy-proven NASH patients who don’t have type 2 diabetes. Talking with your doctor before starting or taking any medications or supplements is important.
Pioglitazone
Pioglitazone is a drug that works by binding to the peroxisome proliferator-activated receptor (PPAR) ?. It may improve insulin sensitivity and limit fat buildup in liver cells by increasing fat accumulation in fat cells. According to current guidelines, patients with or without type 2 diabetes can use it, although it may cause weight gain. Pioglitazone has also been associated with bladder cancer and bone loss.
Emerging Therapies
NAFLD is an increasingly widespread issue likely to be the primary cause of chronic liver disease in the next decade. Many drugs have been tested but have not been approved by the FDA. Vitamin E and pioglitazone have been used to treat NASH but have only improved inflammation and not fibrosis. Consequently, diet changes and weight loss have been the basis of NASH treatment and have been proven to improve histological activity and fibrosis.
Ultimately, most of the available therapeutic options for NASH fail to reduce liver fibrosis. Due to this unmet need, several clinical trials are working on developing new effective medications for NASH. Some of them are described in the sections below.
As always, if you are considering participating in a clinical trial, you should talk to your doctor about the potential risks and benefits of an investigational treatment and if the trial may be a good fit for you.
Farnesoid X Receptor Agonists
In 2023, certain drugs currently in clinical trials are showing promise in reducing the risk and negative effects of NASH. Obeticholic acid may improve inflammation, fibrosis, and insulin sensitivity. The medication is also associated with increased blood fat levels and itching. It is currently approved for the treatment of primary biliary cholangitis. This chronic and progressive condition causes inflammation and, eventually, the destruction of the bile ducts that run through your liver. Additionally, the US Food and Drug Administration (FDA) granted it a New Drug Application (NDA) on January 19, 2023. This put this class of drugs on its way to possible FDA approval for use in patient care.
Thyroid ß Receptor Agonists
Treatment with resmetirom has been found to decrease hepatic fat and is associated with mild adverse events such as diarrhea and nausea.
Peroxisome Proliferator-Activated Receptor (Ppar) Agonists
In addition to pioglitazone, PPAR agonists such as elafibranor and lanifibranor have been found to reduce fat accumulation, inflammation, and liver fibrosis.
C-C Motif Chemokine Receptor Type 2 and 5 (Ccr2/Ccr5 Chemokine) Antagonists
CCR2/CCR antagonist cenicriviroc may reduce fibrosis by counteracting cells that form scar tissue. The drug is considered very safe and well-tolerated.
Glucagon-Like Peptide-1 (Glp-1) Agonists
GLP-1 agonists such as liraglutide and semaglutide may reduce fibrosis and have cardiovascular benefits. While these drugs are becoming widely popular for weight loss, their use for NASH is experimental. They may cause adverse gastrointestinal symptoms such as reduced appetite and nausea.
The Significance of Clinical Trials
The only way to develop new treatments for NASH is by conducting clinical trials with volunteer participants. Would you consider joining a clinical trial?
Volunteering is the best way to contribute to developing new drugs for treating NASH patients. Participate by talking to your healthcare provider or search for a clinical trial at ClinicalTrials.gov.