Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD), where excess fat in the liver is accompanied by inflammation and cell damage. This distinguishes it from the simpler form of NAFLD where there is fat but minimal inflammation. This inflammation can cause scarring, known as fibrosis, which impairs the liver’s ability to function. The global prevalence of NASH is rising, linked to increasing rates of obesity and type 2 diabetes, and its progressive nature can lead to severe complications like cirrhosis and liver cancer.
Foundational Therapeutic Approaches
The initial management of NASH centers on lifestyle modifications, with sustained weight loss as a primary goal. Losing at least 7-10% of total body weight has been shown to significantly reduce liver fat, inflammation, and even fibrosis. The emphasis is on gradual and sustainable loss.
Dietary changes are a fundamental component. Adopting a Mediterranean-style diet, rich in fruits, vegetables, whole grains, and healthy fats, is frequently recommended. Patients are also advised to limit their intake of fructose, found in sugary drinks and processed foods, and to reduce consumption of saturated and trans fats.
Regular physical activity complements dietary efforts. A combination of aerobic exercise and resistance training is encouraged. Aerobic activities like brisk walking or cycling help with weight management and improve insulin sensitivity, while resistance training builds muscle to help regulate glucose. Guidelines suggest at least 150 minutes of moderate-intensity activity per week.
Approved Pharmacological Treatments
A significant advancement in NASH treatment came with the approval of Rezdiffra (resmetirom), the first medication specifically for this condition. It offers a targeted pharmacological option for patients who have not achieved sufficient results with diet and exercise alone.
Rezdiffra functions as a thyroid hormone receptor-beta (THR-beta) agonist. This receptor is highly expressed in the liver and plays a part in regulating metabolism. By selectively activating THR-beta, resmetirom helps increase the breakdown of fat in the liver, reducing the steatosis that is a hallmark of NASH.
The medication is approved for adults who have NASH with moderate to advanced liver fibrosis (stages F2 or F3). Clinical trial data demonstrated that treatment with resmetirom can lead to both the resolution of NASH and an improvement in liver fibrosis without the condition worsening.
Emerging and Investigational Therapies
The pipeline for NASH treatments is robust, with numerous investigational therapies being evaluated in clinical trials that target the complex biological pathways of the disease.
One prominent class of drugs under investigation is glucagon-like peptide-1 (GLP-1) receptor agonists. These medications, already used for type 2 diabetes and weight management, have demonstrated benefits for liver health. They help improve insulin sensitivity, promote weight loss, and have been shown in studies to reduce liver fat and inflammation.
Other therapies in development focus on the inflammatory and fibrotic processes that cause progressive liver damage. Anti-inflammatory agents aim to quell chronic inflammation, while anti-fibrotic therapies are designed to halt or reverse the accumulation of scar tissue in the liver.
Given the multiple factors driving NASH, combination therapy will likely become a future standard of care. This strategy involves using multiple drugs that target different aspects of the disease simultaneously, such as reducing liver fat, controlling inflammation, and combating fibrosis.
Managing Related Health Conditions
A comprehensive treatment strategy for NASH extends beyond therapies aimed directly at the liver. Because NASH is closely intertwined with metabolic syndrome, managing associated health conditions is an integral part of patient care.
Controlling type 2 diabetes is a priority, as insulin resistance is a major driver of fat accumulation in the liver. Medications such as metformin are often used to improve insulin sensitivity and lower blood sugar levels. Effective glucose control can significantly lessen the metabolic stress on the liver.
Managing high cholesterol, or hyperlipidemia, is also important to reduce the high risk of cardiovascular disease in NASH patients. Statins are commonly prescribed to lower LDL cholesterol levels and are considered safe and effective for most patients with liver disease.
Similarly, controlling high blood pressure (hypertension) is another component of managing NASH. Lifestyle modifications like a low-sodium diet and regular exercise are recommended, often alongside antihypertensive medications to lower blood pressure and reduce strain on the cardiovascular system.