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After two decades of research that helped lead to a cure for hepatitis C, Ira M. Jacobson, MD, who joined �ٺ���Ƶ Health in 2017 as director of hepatology in the , has embarked on a new crusade: defeating nonalcoholic fatty liver disease (NAFLD). Caused by the excess buildup of fat in the liver and closely linked to the rising incidence of obesity and type 2 diabetes, NAFLD affects an estimated 30 percent of American adults. Left unchecked, it can be as damaging to the liver as excessive drinking, elevating the risk for liver cancer and liver failure, as well as cardiovascular disease. Despite its prevalence, NAFLD is a largely silent epidemic, with insufficient awareness among patients and, surprisingly, even many physicians. Here, Dr. Jacobson sheds light on this complex, poorly understood disease.

1. The Causes Are Unclear, but There Are Clues

Doctors don’t know why some people who drink little to no alcohol are prone to NAFLD and others aren’t. That’s not the only mystery. While some cases of NAFLD don’t advance—a version known as simple fatty liver, or steatosis—others cause inflammation and cell damage, leading to a more severe form called nonalcoholic steatohepatitis (NASH). At that point, it can lead to scarring, or fibrosis, which in its late stage is called cirrhosis. Up to 40 percent of patients with fatty liver disease have NASH, which greatly increases the risk of progressive scarring, liver cancer, liver failure, and, potentially, the need for a liver transplant. Those most susceptible to developing NASH are obese, have type 2 diabetes, or have been diagnosed with metabolic syndrome—a cluster of conditions that includes hypertension, insulin resistance, excess abdominal fat, and high levels of cholesterol or triglycerides.

2. Pinpointing Damage to the Liver Is Tricky

A precise diagnosis for NAFLD is elusive, and screening for it is challenging. “The dilemma,” explains Dr. Jacobson, “is that liver disease rarely exhibits any specific symptoms until the damage is done.” While liver enzymes are tested during routine blood workups, some people within the normal range can still develop or have advanced disease. Beyond this, many private and hospital labs use reference ranges that are not yet aligned with new clinical guidelines that significantly lower the threshold for abnormal levels. Dr. Jacobson believes that the key to early detection is vigilance. “Clinicians must be on high alert for fatty liver disease, especially in patients who fit the high-risk profile,” he says. “An elevation of liver enzymes, however slight, is often the first sign that the patient has a liver condition.”

3. A New Imaging Tool Is Changing the Game

If a patient’s liver enzymes are elevated, their doctor may order imaging tests, such as ultrasound, to confirm the presence and assess the extent of fat buildup, along with lab tests to check for other types of liver disease. If the initial findings are inconclusive, the most definitive way to assess inflammation and scarring is to perform a liver biopsy. But biopsies are invasive, painful, and carry the risk of complications, so Dr. Jacobson favors a recently developed diagnostic tool called transient elastography, a noninvasive ultrasound-based technique that can not only estimate liver scarring by measuring the organ’s degree of stiffness, but also quantify the amount of fat in the liver. “This tool has transformed the practice of hepatology,” he notes. “Blood markers can also be used to help identify patients at high risk for developing NASH and liver scarring.” Dr. Jacobson adds that even when a radiology report includes an incidental finding of fat in the liver that is deemed “clinically insignificant,” the physician should consider referring the patient to a liver specialist.

4. Lifestyle Changes Can Make Nonalcoholic Fatty Liver Disease a Nonissue

While patients tend to focus on reversing NAFLD, Dr. Jacobson emphasizes that as long as the disease is detected early enough, it doesn’t need to be cured—just stopped in its tracks. “In people who are sedentary, simply starting to exercise reduces the amount of fat in the liver—even just taking long walks regularly,” he says. For patients who are overweight or obese, weight loss is central to managing the disease. “Trimming body weight by as little as 3 percent can decrease the degree of fat deposition in the liver, a 5 percent to 7 percent loss can reduce inflammation, and a 10 percent drop can actually start to reverse scarring,” he explains. A diet high in healthy fats and low in carbohydrates has also been shown to reduce the amount of fat in the liver.

5. Treatments May Be on the Horizon

Developing a singularly effective medication for NAFLD has been challenging because the disease is rooted in multiple underlying mechanisms, both genetic and environmental. Still, researchers could be on the verge of a breakthrough. Along with other important clinical trials for this disease, Dr. Jacobson and his colleagues recently initiated a multicenter phase 3 clinical trial at �ٺ���Ƶ that combines three drugs aimed at reducing fat buildup, inflammation, and scarring in the liver at the same time. “Combination therapies that target several disease pathways at once will be a major step forward,” explains Dr. Jacobson. “The liver is a remarkable organ, the only one that can regenerate when a piece is removed. It can even dissolve its own scar tissue—if we stop the processes that caused the scarring in the first place.”