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The risk for cancer in patients with nonalcoholic fatty liver disease (NAFLD) was highest among those with early-onset disease and declined at later ages of diagnosis, a matched cohort study found.

Examining more than 60,000 participants from a prospective Chinese dataset revealed that the increased risk of malignancy with NAFLD was highest among patients diagnosed before the age of 45 (average hazard ratio [AHR] 1.52, 95% CI 1.09-2.12), reported Hanping Shi, MD, PhD, of Beijing Shijitan Hospital Capital Medical University, and colleagues.

The increased risk in this age group was primarily driven by malignancies of the digestive system (AHR 2.00, 95% CI 1.08-3.47) and lungs (AHR 2.14, 95% CI 1.05-4.36), according to the findings in .

"The increasing incidence of NAFLD among younger populations highlights the underestimation of harmful outcomes associated with this condition," wrote Shi and colleagues. "Our findings suggest that early control and intervention against NAFLD progression may be crucial to reduce the occurrence of NAFLD-related cancers and lessen the burden on public health."

One-third of liver disease-related deaths occur in people who had been diagnosed with NAFLD before the age of 30, they noted. Even children and young adults are diagnosed with NAFLD, putting them at .

"Unfortunately, NAFLD is usually insidious in onset, asymptomatic at presentation, and may only be identified in the early stages by aminotransferase elevation," said Andrew Talal, MD, MPH, of the University at Buffalo in New York, who was not involved in the research.

"Healthcare providers, including pediatricians and those in primary care, need to be alert for the diagnosis," he told MedPage Today.

While multiple prior studies have linked NAFLD with an increased risk for cancer, as well as liver decompensation, it's been unclear whether the age of NAFLD onset factored into the degree of cancer risk.

In their study, Shi and colleagues found that 17.83% (95% CI 4.92-29.86) of the cancer risk among NAFLD patients under age 45 could be attributed to their fatty liver disease, a number that declined with age.

"Mechanically, as NAFLD progresses, lipid accumulation in liver cells leads to oxidative damage and DNA mismatch repair, which act as driving factors for cancer," they explained. "Our research highlights the dangers associated with early exposure to NAFLD. Patients with NAFLD in their early stage of life may experience metabolic disorders with sustained liver damage."

Talal noted that "inflammation is another potential contributor that can place stress on hepatocytes, causing them to age, which can lead to fat accumulation promoting liver fibrosis and liver cancer."

He added that from a public health perspective, "screening and surveillance programs might be considered especially amongst young individuals with additional risk factors for NAFLD."

For their study, the researchers initially identified 46,100 participants with new-onset NAFLD enrolled in the Chinese Kailuan Cohort Study from 2006 to 2021, matching 31,848 of them by age and sex with an equal number of controls.

In the NAFLD group, the largest share had their NAFLD diagnosed from ages 45 through 54 years (n=10,271), followed by those under 45 years (n=8,984), those 55 to 64 (n=8,585), and those 65 and over (n=4,008).

Matched participants had an average age of 51 years, the vast majority were men (83%), about a fifth were current smokers, and 10% had diabetes. A slightly higher proportion of NAFLD patients had hypertension versus controls (46% vs 39%), and the NAFLD patients had a greater body mass index, a larger waist circumference, and were less likely to exercise regularly. They also had higher levels of cholesterol, triglycerides, and alanine aminotransferase.

Over a median follow-up of 10.16 years, cancer was diagnosed in 2,415 patients, with 53% of the cancers occurring in the NAFLD group. The bulk of the cancers (69%) occurred in people ages 45 to 64 years, with 32% located in the digestive tract (mostly colorectal, liver, and stomach) and 29% in the lungs.

Increased risk for cancer among the NAFLD patients appeared similarly high for those ages 45 to 54 years, but then declined with increasing age (P<0.001 for interaction):

• 45-54 years: AHR 1.50 (95% CI 1.15-1.97)
• 55-64 years: AHR 1.13 (95% CI 0.97-1.33)
• ≥65 years: AHR 0.75 (95% CI 0.45-1.27)

Looking at digestive cancers specifically showed similar results (P<0.001 for interaction):

• 45-54 years: AHR 1.94 (95% CI 1.46-2.74)
• 55-64 years: AHR 1.13 (95% CI 0.85-1.51)
• ≥65 years: AHR 0.71 (95% CI 0.50-1.02)

Study limitations included that the Kailuan cohort primarily consists of male workers, that NAFLD was diagnosed by ultrasound rather than liver biopsy, and that researchers lacked details on the extent of NAFLD and liver fibrosis. Also, some cancers were diagnosed in small numbers, which limited analyses by age.

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