NASH and Liver Cancer: A Silent Epidemic
Liver cancer has long been associated with advanced cirrhosis, particularly due to hepatitis or alcohol-related liver disease. But a quiet revolution in hepatology is underway—one that should give all of us pause. An increasing number of patients are being diagnosed with hepatocellular carcinoma (HCC), the most common form of primary liver cancer, at younger ages and in the absence of cirrhosis. And the primary culprit? A condition that is rapidly becoming one of the world’s most common liver diseases: NASH—Non-Alcoholic Steatohepatitis or fatty liver.
What is NASH and why should we be concerned?
NASH is the advanced inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called NAFLD. It’s linked to obesity, diabetes, and insulin resistance—conditions that are growing epidemics in both the West and Israel.
What makes NASH particularly insidious is that it can quietly progress from fatty liver to fibrosis and cancer without producing symptoms. And now, researchers are discovering that HCC can arise directly from NASH, even in patients without cirrhosis, sometimes at relatively young ages.
Data that challenges old assumptions
Traditionally, cirrhosis was considered a prerequisite for liver cancer. But this dogma is changing. Several recent studies show:
Up to 50% of liver cancer cases related to NASH occur in non-cirrhotic patients .
In these patients, HCC can arise earlier in life—particularly troubling since these individuals may not be enrolled in any regular surveillance programs.
A 2018 meta-analysis found that 20% of NAFLD-related HCC cases developed without cirrhosis, and the risk of HCC in this group was 2.5 times higher than in other chronic liver diseases.
A diagnostic and public health blind spot
The implications are alarming. Because non-cirrhotic NASH patients are not considered high risk, they are not routinely screened. This results in late diagnoses—often when curative treatment is no longer an option. In fact, emerging Israeli data mirrors global trends: we are seeing HCC in patients without viral hepatitis, without alcohol abuse, and without cirrhosis. What they often share is metabolic syndrome, sedentary lifestyles, and silent inflammation.
Rethinking how we screen—and when
If NASH-related HCC can occur in non-cirrhotic patients, especially those with diabetes and obesity, our screening guidelines may need to be reimagined. Should diabetics with fatty liver be screened earlier? Should ALT levels and imaging be used more proactively?
Additionally, public awareness lags far behind the science. Most patients with fatty liver disease don’t know they have it—and those who do are often falsely reassured by the absence of symptoms or a “normal” liver stiffness reading.
A call to action for Israel—and beyond
In Israel, where Western dietary patterns and high rates of diabetes are increasingly common, the public health burden of NASH is growing quietly but dramatically. As a internal medicine specialist and healthcare consultant, I urge my colleagues in primary care and hepatology to take note of these emerging patterns. And for the lay public: if you or a loved one has metabolic syndrome, high triglycerides, or diabetes—ask your doctor about fatty liver and NASH.
Our collective medical thinking must catch up to the biology. Liver cancer should no longer be thought of as a disease of older patients with cirrhosis. It is a growing risk for younger, metabolically vulnerable individuals—including those who still feel perfectly well.
We ignore this shift at our peril.
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Reference:
Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18(4):223–238. doi:10.1038/s41575-020-00381-6
