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The liver’s role in metabolic disease

Martin Grajower, MD
Conditions
December 8, 2025
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If you’re managing metabolic disease for your patients, you’re also dealing with liver disease, whether you realize it or not. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 70 percent of patients who have type 2 diabetes or obesity, yet reliable, routine screening for liver disease is anything but commonplace.

I often wonder why that is. After all, the liver is arguably the most sensitive barometer of metabolic dysfunction, one that can give us the gift of early intervention. Unfortunately, liver disease is typically viewed as a downstream complication and the domain of hepatologists concerned about cirrhosis and cancer. The reality is that most patients with steatotic liver disease are more likely to die from cardiovascular disease or diabetes than from cirrhosis. While the risk for cirrhosis is real, it affects only about 3-5 percent of patients with MASLD, whereas the risk for atherosclerotic disease or progression to diabetes is present in nearly all cases. MASLD doubles the risk of a cardiovascular event and increases the risk of progression from prediabetes to diabetes two- to threefold.

Furthermore, there is a widely held misconception among clinicians that fat in the liver is a benign condition. The science tells a different story: The liver both mirrors and magnifies metabolic dysfunction. Said another way: Fat in the liver is not merely a result of insulin resistance; it drives it. Excess hepatic fat interferes with the liver’s ability to regulate glucose and lipids, fueling the very insulin resistance that caused it in the first place. This results in a vicious cycle:

  • As insulin resistance worsens, more fat accumulates in the liver.
  • As hepatic fat increases, systemic inflammation and insulin resistance worsen.
  • That feedback loop accelerates the onset and worsens existing diabetes, hypertension, and cardiovascular disease.

In other words, the liver is not collateral damage; it’s an active driver of metabolic disease progression.

I often tell my peers that if you’re waiting for the A1C to rise, you’ve already missed the first signal. Hepatic steatosis may be the earliest measurable sign of insulin resistance, appearing before changes in glucose, HDL, or triglycerides.

Part of the problem with early diagnosis is that standard liver function blood tests like ALT and AST are unreliable for early detection. Up to 80 percent of patients with MASLD and nearly 60 percent with metabolic dysfunction-associated steatohepatitis (MASH) will have “normal” ALT levels. The result is that the most critical determinant of long-term outcomes (fibrosis) often goes undetected until it reaches an irreversible stage. In fact, approximately one in 20 people have MASH, yet it is estimated that nine out of 10 cases are undiagnosed.

Accurately detecting and quantifying the amount of steatosis and fibrosis is critical, and it can be done non-invasively with vibration-controlled transient elastography (VCTE). VCTE can quickly and reliably measure liver fat (steatosis score) and scarring (fibrosis score) at the point of care, providing you and your patients with the objective data needed to inform clinical decisions and lifestyle changes.

Patients want this data. They are genuinely afraid of their livers. When you show them their steatosis and fibrosis scores, you will see real fear and motivation in a way you wouldn’t during an abstract conversation. Quantitative data also makes discussions about their care plan and lifestyle changes more concrete, actionable, and measurable over time to document improvements resulting from these changes. I’ve had patients who were, for a long time, resistant to medication, exercise, or dietary changes finally comply with recommendations I had been making for years. The fact is that before they were shown the data, they did not realize or appreciate the silent burden their liver was carrying, and that is not their fault. It’s our responsibility as clinicians to make the invisible visible and provide that wake-up call.

Of course, our duty doesn’t end with a diagnosis. Liver health must be monitored and managed just like any other chronic condition. Following patients’ liver metrics every 6-12 months fosters accountability, strengthens relationships, and builds trust: the foundation of effective long-term care. It also allows us to adapt treatment plans based on objective evidence rather than assumptions. Over time, that data-driven partnership transforms how patients understand and engage with their own metabolic health.

Steatotic liver disease often isn’t easy to manage, for the provider or the patient. It’s about more than weight loss or BMI. In fact, there is no linear relationship between MASLD/MASH and weight; genetics, biology, and likely other unknown factors contribute to the disease and the response to different therapies. I’ve had many patients who appear to be the picture of health (triathletes even) develop MASLD. That’s why frontline providers must be vigilant and seek all the data we can from the liver, which, studies have shown, is often the most sensitive and earliest manifestation of metabolic dysfunction.

When we know better, we can do better. As providers, we are beginning to recognize the liver’s role in metabolic disease, but awareness alone isn’t enough. The tools to detect, quantify, and track liver health already exist. It’s time to make them routine, so our patients can know better, do better, and ultimately live better.

Martin Grajower is an endocrinologist.

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