If you’ve never heard of NAFLD (Non-alcoholic Fatty Liver Disease), or MASLD (Metabolic dysfunction-Associated Steatotic Liver disease (MASLD), its equally non-catchy new name[1], you’re not alone. Yet this condition affects 30% of the global population.
Image: DALL-e
As an anesthesiologist working in the operating rooms of a large university medical center in Cleveland, Ohio in the 1990s and 2000s it was obvious that my patients were becoming heavier (42% of Americans are obese) and sicker. When I looked over the drapes into a surgically opened belly or on the monitor showing “keyhole” (laparoscopic) surgery, I could often see that the liver was not a normal, beefy brown colour but yellowish, pale, and swollen – signs of its infiltration by fat.
Healthy liver and fatty liver. Source: https://liverfoundation.org/liver-diseases/fatty-liver-disease/nonalcoholic-steatohepatitis-nash/nash-definition-prevalence/
Development and progression of MASLD
MASLD is linked to “Western” diets and lifestyle and rising levels of obesity (31% of South African males, 67% of females) and metabolic syndrome (11-24%)(diabetes, high blood pressure and obesity) which damages eyes, kidneys, heart, blood vessels, and nerves. The liver is injured by this metabolic mayhem, but liver dysfunction also helps make it happen.
Causative factors include refined carbohydrates, including fructose, and calorie excess, with less agreement on the contribution of saturated fats, ultra-processed food, and red meat. Genetics play a role, along with physical inactivity and stress.
In MASLD, as noted, excess fat accumulates in the liver cells. In the next stage, called MASH (Metabolic dysfunction-Associated Steato-Hepatitis), the real trouble begins – inflammation, cell death and fibrosis (scarring).
It’s not clear why only some people – about 10% – develop severe forms of the disease. This takes years. About 20% then progress to scar tissue, known as cirrhosis, also seen in patients with excess alcohol intake.
Late stage symptoms include fatigue, abdominal pain, nausea, loss of appetite, swelling from ascites (fluid in the belly), intestinal bleeding, itchy skin, mental confusion, shortness of breath, and leg swelling.
In its most severe form, the liver fails, which is fatal without a transplant. The risk of liver cancer, the fastest rising cancer in the US, Europe, China and India, is also increased.
Identifying and diagnosing MASLD
In its early development, MASLD is clinically silent (no symptoms), hence its low profile, but it’s now the commonest liver disease in the world, and not just in adults. The increasing prevalence in children is alarming: 3-10% overall, 40-70% among those who are obese, with boys affected more than girls, about 2:1. The quoted sub-Saharan Africa incidence of MASLD (13.5%) is likely an underestimate.
Clues to the diagnosis are risk factors like obesity, diabetes, high blood pressure and high cholesterol, confirmed by evidence from blood tests (e.g., raised levels of liver enzymes in the blood), imaging with ultrasound or MRI and/or a biopsy.
Effective but costly new treatment: Resmetirom
Until last month there was no approved drug treatment for MASLD or MASH. On March 14, the United States FDA granted accelerated approval for a medicine called resmetirom, following positive trial results. About a quarter of patients showed significant improvement in disease activity and the amount of fibrosis, compared to 14% in the placebo group.
Resmetirom (Rezdiffra: Madrigal Pharmaceuticals) could be the next blockbuster pharmaceutical, but with a $47,400 (ZAR890,000) price tag there might not be anything left in global health budgets when you’ve already spent $1,000 or more per month per person on GLP-1s (e.g., semaglutide) for patients with obesity and diabetes.
Can this pandemic be reversed?
Image: DALL-e
GLP-1s are very effective for obesity and diabetes, offering not just weight loss and blood sugar control but protection from heart, vascular and kidney damage, with positive effects on the liver too. Local experts, comparing this to the success of ARVs for controlling the HIV epidemic, are demanding lower prices and wide availability for these drugs.
Even if GLP-1 medications and drugs like resmetirom become affordable and available, what will happen to a population that continues with the same low-quality diet and unhealthy lifestyle? Medications for MASLD or for metabolic syndrome can’t be the whole story. Systemic and environmental factors got us here, including how we eat, exercise, sleep and work. Surely, we need to work harder on these things.
Dietary interventions, at population level, have a dismal overall track record so far but important successes have been achieved. We now know that diabetes and MASLD are not necessarily lifelong and progressive – if addressed within the first few years of onset.
Weight loss of 5-10% or more, achieved through calorie restriction, or specific diets, induces diabetes remission, (defined by patients staying off their medicines for at least 3 months), and reduces liver fat.
Metabolic (“bariatric”) weight loss surgery has similar and long-lasting benefits: diabetes remission and stores of liver fat reduce at the same time.
Nutrition is the most important focus for public health action. We need to study the benefits, costs, and types of “Food as Medicine” and test it use to limit the onset and progression of food-driven disease like MASLD.
Let’s compare the costs and effects of medical interventions with healthier food. $47,000 can buy a lot of healthy, tasty, and culturally acceptable food, and support farmers and the associated food production and supply chain.
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If you suspect you have MASLD or are at risk for MASLD due to factors like obesity, diabetes, high blood pressure, or high cholesterol, consult your doctor for an accurate diagnosis and treatment.
[1] The terms “non-alcoholic” and “fatty” were considered stigmatizing, therefore a change was agreed in 2023; steatotic means fatty.