New Drugs For Treating Fatty Liver Disease And Cirrhosis

Researchers believe fatty liver disease, also known as non-alcoholic fatty liver, affects an estimated 20% of Americans.¹

Fatty liver can progress to cirrhosis (advanced liver scarring), which harms your overall health and quality of life.

In this article, we cover non-alcoholic fatty liver disease, cirrhosis, risk factors, and the treatments available for both.

Understanding non-alcoholic fatty liver disease

As the name suggests, non-alcoholic fatty liver disease (NAFLD) is a condition where excess fat accumulates in the liver without significant alcohol consumption.²

This is different from the other main form of fatty liver disease — alcohol-induced fatty liver disease (AFLD). This condition is generally caused by significant alcohol consumption.³

NAFLD is divided into the following two types:

• Non-alcoholic fatty liver (NAFL), where there is excess fat in the liver without signs of marked inflammation or injury to the liver cells

• Non-alcoholic steatohepatitis (NASH), where there is fatty liver in addition to inflammation and signs of liver cell injury. This could present with or without fibrosis.

NASH is considered the more severe form of NAFLD. Liver cirrhosis is the condition’s final negative prognosis.

While most people with NAFLD are asymptomatic, potential symptoms include the following:

• Discomfort or pain in the upper right side of the abdomen

• Fatigue

If the condition becomes a severe form of NASH or cirrhosis, you may experience the following symptoms:

• Nausea and vomiting

• Jaundice (yellowing of the skin and eyes)

• Fatigue and weakness

• Abdominal pain

• Abdominal swelling (ascites)

• Edema of the legs

Numerous causes and risk factors may increase your chance of developing NAFLD.

Risk factors

• Being overweight or obese (the main risk factor for developing NAFLD)

• Type 2 diabetes or insulin resistance

• Menopause

• Asian or Hispanic ancestry

• High level of belly fat or metabolic syndrome

• High cholesterol or dyslipidemia (unhealthy blood fat levels)

• High blood pressure (hypertension)

• Obstructive sleep apnea

Other less common causes include the following:⁴

• Some medications, including tamoxifen, corticosteroids, and amiodarone (Cordarone, Pacerone)

• Hepatitis C infection

• Genetic causes, including lipid metabolism disorders (abetalipoproteinemia, familial combined hyperlipidemia, Weber–Christian disease)

• Severe surgical weight loss

• Starvation

New treatments for fatty liver disease

Obesity is the most common risk factor for developing NAFLD. As such, health professionals usually recommend weight loss and lifestyle changes as the first point of treatment. This usually includes a regular exercise routine, dietary changes, and behavioral changes via therapy.

Due to the complex development of NAFLD, many new treatments being investigated must adhere to a multidisciplinary approach. This means ensuring beneficial effects on multiple bodily processes, including lipid regulation and glucoregulation.⁵

Below are some new treatments that have been researched or are currently being studied.⁶

Vitamin E and probiotic supplements

Vitamin E is an antioxidant that has shown promise in animal and human studies.

Researchers have found it can effectively reduce oxidative stress, decrease inflammation, and potentially reduce NAFLD progression, particularly when combined with other therapies such as atorvastatin and vitamin C.⁷

Take vitamin E supplements with caution and follow your doctor’s advice. It should be used in moderation as long-term and/or high vitamin E consumption may cause negative side effects and increase the risk of developing certain conditions.

Some evidence also suggests that probiotics may benefit lipid profile management, weight loss, and NAFLD.⁸

Medications

Non-bile farnesoid X receptor agonists (FXRs), such as tropifexor, are thought to be able to reduce fat accumulated in the liver. They may also help lower liver enzyme serum levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT).

Cilofexor and nidufexor are two other FXR agonists being researched for their effect on NAFLD.

Glucagon-like peptide-1 (GLP-1) is a class of diabetes drugs that promote weight loss and improve insulin sensitivity.⁹ Other benefits of GLP-1 include the following:¹⁰

• Regulating plasma glucose levels

• Increasing satiety after eating

• Reducing gastric emptying time

Semaglutide is the new generation of this drug. It has recently been researched for use as a treatment for obesity and NASH. A 72-week, double-blind phase 2 trial published in 2021 demonstrated promising results from subcutaneous semaglutide use. It led to a higher percentage of NASH resolution in the study group than in the placebo group.¹¹

Sodium-glucose transport-2 inhibitors (SGLT-2) are a relatively new class of inhibitors. They lower glucose by inhibiting glucose reabsorption by the kidneys, bowels, and heart. Recent studies involving animal models suggest that SGLT-2 treatment had a beneficial effect on inflammation and liver steatosis.¹² ¹³

Lipogenesis inhibitors are another new type of drug being investigated for use in fatty liver disease. High cholesterol and triglyceride blood levels are key factors for liver injury. As such, inhibiting certain enzymes that contribute to lipid synthesis could be beneficial.

Stearoyl-CoA desaturase-1 (SCD-1) inhibitors (aramchol) and acetyl-CoA carboxylase (ACC) inhibitors (firsocostat) have also shown promise in reducing liver fat content and fibrosis.¹⁴ ¹⁵

Combination therapy 

Research indicates that there’s no single medication that successfully treats NAFLD. Combination therapy has therefore become an innovative treatment option for targeting multiple pathogenic contributors to NAFLD. These contributors include the following:¹⁶

• Diabetes

• Obesity

• Lipid dysmetabolism

• Oxidative stress

• Inflammation and apoptosis

• Gut microbiota dysbiosis

Combination therapy generally uses multiple treatment methods at once. These may include antioxidants, probiotics, or a combination of medications to target any of the contributing factors. For example, treating diabetes, insulin resistance, obesity, and/or dyslipidemia can have anti-inflammatory effects, improve your overall lipid profile, and reduce liver steatosis and fibrosis.

Your doctor will consider your individual profile to recommend the right combination therapy for you.

Cirrhosis explained

Cirrhosis is liver scarring resulting from long-term liver damage. It can develop from NAFLD and at the end stage of other liver diseases.

Cirrhosis can be serious and even life-threatening. Your doctor will recommend starting a treatment plan as soon as possible to slow its progression.

Symptoms may vary depending on the severity of the disease and how far it has progressed. They may include the following:¹⁷

• Fatigue or tiredness

• Unintentional weight loss

• Nausea, vomiting, and reduced appetite

• Pain or discomfort in the upper right side of the abdomen

• Bleeding or bruising

• Dark urine

• Itchy skin

• Jaundice (yellowing of the skin and eyes)

• Edema (swelling in the lower legs, ankles, or feet)

What causes cirrhosis also depends on whether you have had NAFLD, AFLD, or other liver diseases (like hepatitis) that lead to cirrhosis. Common causes include the following:

• Drinking excess alcohol over a long period

• NAFLD

• Chronic hepatitis B or C

• Inherited liver diseases

• Long-term use of certain medications

• Chronic heart failure

Emerging new drugs for cirrhosis treatment 

Cirrhosis itself cannot be cured with specific treatments. However, symptoms and underlying health conditions can usually be managed to slow the progression.¹⁸

Generally, treatment options for cirrhosis focus on treating the underlying condition that caused it. Lifestyle changes may also be recommended, including stopping smoking or drinking alcohol, losing weight, and establishing a regular exercise routine.

Doctors can also prescribe medications to reduce the severity of common symptoms, like medications to remove fluid from the body to reduce edema. Doctors may also use medications to manage cirrhosis complications, such as liver cancer or portal hypertension.

Some people need a liver transplant. This involves replacing the existing organ with a healthy donor liver. The current drug development landscape for cirrhosis is still progressing. Researchers are investigating the pathogenesis of cirrhosis and how new medicines can interact with this. 

Researchers are studying synthetic drugs for cirrhosis and some are in late-phase trials. These include:¹⁹

• Obeticholic acid (an FXR agonist)

• Cenicriviroc

• Pegbelfermin

• Efruxifermin

• Aldafermin

The lowdown

Non-alcoholic fatty liver disease is a complex health condition with numerous potential causes. Researchers are investigating new and emerging drugs that exert a range of effects to target multiple causes of the disease at once.

Cirrhosis, a condition characterized by scarring of the liver, can develop from NAFLD. This is a serious and potentially life-threatening disease. There is currently no cure, but treatment options to slow the progression and reduce the severity of symptoms are available.

This field of research is continuously progressing. Speak to your doctor for advice on the right treatment plan for you.

People also ask

Can you have cirrhosis and fatty liver disease at the same time?

Yes, cirrhosis can occur during late-stage fatty liver disease if left untreated or if treatment is not effective.

Generally, non-alcoholic fatty liver disease is seen in people who are overweight or obese. It is rarely harmful in the early stages, but cirrhosis can develop if it worsens.

Can you get better if you have cirrhosis of the liver?

There is currently no specific cure for cirrhosis of the liver. Your liver can keep working if you have cirrhosis, but the disease can also lead to liver failure and death in some cases.

However, several approaches can help manage symptoms and slow the disease’s progression. New drugs are currently being researched, too.

Why is fatty liver disease harmful?

High levels of fat in the liver are generally associated with many health conditions, including diabetes, cardiac issues, high blood pressure, and kidney disease.

Fatty liver disease can lead to cirrhosis. This is a serious and potentially fatal condition characterized by scarred liver tissue.