“But they appeared to be so healthy, so full of life …”

How often have we heard this — or perhaps even said it — upon receiving a grieving phone call or reading a death notice in The Royal Gazette? What we tend to call “sudden” death might be a heart attack or a stroke or maybe liver disease. But while the resultant death is definitely sudden, the root cause will often have been lingering for years or decades.

However, if you are a patient who takes serious responsibility for your health and communicates regularly with your GP, most chronic illnesses can be detected and resolved early or even prevented entirely.

Despite the huge leaps in medical and pharmaceutical research, there remain some terminal diseases that simply do not warn you of their existence until it’s too late to avoid the consequences.

These are the silent killers. One such condition is hepatic steatosis, more commonly called fatty liver. As the name suggests, it is an excessive accumulation of fat on the liver, and most of us find comfort in the belief that it occurs only in obese people and/or heavy drinkers. But in fact it also attacks those with chronic problems such as high cholesterol.

This different path to the same outcome is called MASLD — that’s metabolic dysfunction-associated steatotic liver disease — and it is one of the most frequent causes of chronic liver diseases globally.

The natural history of MASLD ranges from isolated steatosis (fatty accumulation in the liver) to steatohepatitis (inflammation of the liver caused by fat), liver fibrosis (scan tissue), and cirrhosis (complete destruction of the liver structures with damage of its function). The sad thing is that you will have symptoms or feel unwell only when 80 per cent of the liver is already destroyed, and the only treatment at this stage would be a liver transplant.

Particular interest has been focused on MASH — metabolic dysfunction-associated steatohepatitis — as well as advanced liver fibrosis, as these have been linked to disease progression and mortality.

As for the drinking aspect, recent research has shown that hepatic steatosis can arise even at lower doses than those previously attributed to alcohol-associated liver disease.

Thus, hepatic steatosis is currently defined as a continuum of disease that is predominantly driven by metabolic dysfunction or alcohol use, or both of them.

Alcohol exerts a direct toxic effect on hepatocytes and, through its byproducts, promotes and amplifies liver damage in individuals with significant alcohol intake.

And, due to the intricate relationship between MASLD and common cardiometabolic risk factors, hepatic steatosis is frequently identified in individuals with excess weight, diabetes, arterial hypertension, and dyslipidemia.

A chilling message

But all the complicated medical words can’t mask the chilling message here for every Bermuda household:

If you or anyone you care about could lose a few pounds of weight, drinks too much, suffers from diabetes, high blood pressure or just about any of the other usual suspects, please keep reading.

We don’t have any such figures for Bermuda, but a recent US study of middle-aged people — some in primary-care and others at random — showed a prevalence of liver steatosis around 75 per cent, while advanced fibrosis and cirrhosis were estimated at 10.8 per cent and 4.5 per cent respectively. In particular, 90 per cent of liver steatosis cases were attributed to MASLD, highlighting the high burden of disease among individuals with excess weight.

In another US study — this time of previously-diagnosed diabetic adults aged around 50 — the MASLD prevalence was estimated at 65 per cent, while 14 per cent of diabetics had advanced fibrosis and 6 per cent cirrhosis. European countries and other Western regions face a similar plight, with MASLD prevalence up by 38.7 per cent in the last two decades.

It is pretty disturbing, but there are genuine positives to be found, here and now. Screening for MASLD and fibrosis is recommended in individuals with abnormal liver biochemistries and/or radiological signs of hepatic steatosis, as well as those with type 2 diabetes mellitus or excess weight, especially those aged over 50.

Currently, liver fibrosis staging is the most important method to stratify risk, monitor disease progression, and guide therapeutic interventions. Liver stiffness measurement by a breakthrough system called Transient Elastography assesses the velocity of a shear wave generated by a mechanical pulse. This technology is now available in Bermuda and not only measures the degree of fibrosis or existence of cirrhosis, but also the degree of fat accumulation in the liver.

As mentioned before, patients with active MASH and significant fibrosis are at higher risk of liver fibrosis progression. This particular population has been named at-risk MASH and is defined by a significant liver fibrosis, and elevated NAFLD activity score. The identification of patients with at-risk MASH is key for decision-making, being the population that could benefit most from pharmacological therapies.

This critical identification used to require a liver biopsy, but now the same can be achieved in a few minutes by the effortless ultrasound-like Transient Elastograph.

Healthy diets help to reduce condition

Dietary modification is a key component of the non-pharmacological management of MASLD. Several dietary patterns have been studied for their impact on liver health, with the Mediterranean diet emerging as one of the most beneficial. This diet is not only effective in reducing hepatic steatosis but also can reduce major cardiovascular events, which are particularly important given the high prevalence of cardiovascular disease in patients with MASLD.

Another dietary approach is the low-carbohydrate diet, which restricts the intake of refined carbohydrates and sugars, particularly fructose, which is strongly associated with liver fat accumulation. Reducing the intake of sugary beverages, processed foods, and high-fructose corn syrup is recommended to decrease hepatic fat content. Additionally, reducing overall caloric intake and avoiding foods high in saturated fats and trans fats can further support weight loss and liver health. In the absence of other medical contraindications, coffee intake is safe and evidence suggests it could even reduce the development of MASLD.

Weight loss is the most effective non-pharmacological approach for managing MASLD, producing a significant decrease in liver fat content, steatohepatitis, and liver fibrosis in a dose-dependent fashion. The recommended target weight loss is 7 per cent to 10 per cent of total body weight (10 per cent in at-risk MASH), as this degree of weight reduction is associated with a significant improvement in liver histology.

In addition, those with lean MASLD could benefit from a weight loss of 3 per cent to 5 per cent. Regular physical activity is another critical component of the non-pharmacological treatment of MASLD as well as lowering all-cause mortality.

Alcohol use has been proved to increase the risk of liver fibrosis in a dose-dependent fashion, exhibiting a supra-additive interaction with cardiometabolic risk factors. Given the potential role of alcohol in exacerbating MASH, contributing to fibrosis progression, and the increase in risk of liver cancer, complete alcohol abstinence should be recommended for all patients with MASLD and at least significant fibrosis.

Cigarette smoking negatively affects the progression of MASLD, and increases risk of liver cancer, and major cardiovascular events. In consequence, all patients with MASLD who are active cigarette smokers should be advised and assisted to quit smoking.

As for medication, your GP can guide you through the options that include drugs to reduce hepatic fat content and liver stiffness to medications which reduce cholesterol and those that help with weight loss.

Liver cancer is a significant concern in patients with MASLD, as the risk of developing hepatocarcinoma is elevated even in the absence of cirrhosis, which traditionally has been considered a prerequisite for liver cancer. In fact, 20 per cent to 30 per cent of liver cancer in MASLD occurs in individuals without cirrhosis.

The pathogenesis of liver cancer in MASLD is multifactorial, involving chronic hepatic inflammation, oxidative stress, and the accumulation of genetic and epigenetic alterations that promote carcinogenesis. The metabolic abnormalities associated with MASLD, such as insulin resistance, obesity, and hyperlipidemia, further contribute to the oncogenic process by creating a pro-inflammatory and pro-fibrogenic hepatic environment. In terms of chemoprevention, a prior systematic review evidenced that aspirin and statins could decrease HCC risk over time, making them attractive therapies to be tested in future clinical trials involving patients with MASLD.

Most important, please remember how it feels when someone you love dies unexpectedly. What you have discovered here and what you can do about it might just have ensured that you won’t be the next awful shock.

• Suraia Boaventura Barclay MD, PhD, AGAF is a gastroenterologist and endoscopist