Fatty liver disease may increase cancer risks

NAFLD Linked to Higher Incidence Rates of Cancer

Significantly associated with HCC, colon cancer in men, and breast cancer in women

Nonalcoholic fatty liver disease (NAFLD) was tied to an increased risk of hepatocellular carcinoma (HCC), colorectal cancer in men, and breast cancer in women, South Korean researchers found.

Adjusted results from an observational meta-analysis of a cohort of 25,947 patients showed that after a median follow-up of 7.5 years, the cancer incidence rate was 782.9 per 100,000 person-years in 8,721 patients (33.6%) with NAFLD compared with 592.8 per 100,000 person-years in those without NAFLD (hazard ratio 1.32, P<0.001), according to Gi-Ae Kim of the University of Ulsan College of Medicine in Seoul, and colleagues.

NAFLD was associated with 32% higher incidence rates of cancer in general (HR 1.32, P<0.001). Patients with NAFLD were also 16.73 times more likely than their non-NAFLD counterparts to develop HCC (P=0.008), they reported online in the Journal of Hepatology.

In addition, men with NAFLD were twice as likely to develop colorectal cancer (HR 2.01, P=0.02), and the risk of breast cancer was almost doubled in women with NAFLD (HR 1.92, P=0.01). These estimates were based on 14 incident cases of HCC, 76 incident cases of colorectal cancer, and 91 incident cases of breast cancer.

A high NAFLD fibrosis score of ≥-1.455 indicated an 87% increase in risk of all cancers, particularly HCC. Similarly, a high fibrosis-4 score of ≥1.45 predicted a 74% increase in cancer risk.

“These findings suggest that patients with NAFLD require multidisciplinary evaluation with attention given to the development of malignancy,” the researchers wrote. “Further studies are needed to specify which high-risk groups of patients with NAFLD carry a greater risk of developing cancers, including HCC, colorectal cancer, and breast cancer.”


Compared with patients without NAFLD, those with NAFLD were:

  • Older: mean age 50 versus 47, P<0.001)
  • More likely to be male: 71.1% versus 45.1% (P<0.001)
  • Smokers: 58.4% versus 38.5% (P<0.001)
  • Diabetic: 16.2% versus 4.4% (P<0.001)
  • Hypertensive: 32.3% versus 16.9% (P<0.001)
  • Have higher levels of fasting glucose: 102.8 versus 93.1 mg/dl (P<0.001)
  • Have higher total cholesterol: 200.7 versus 187.0 mg/dl (P<0.001)


In an accompanying editorial, Peter Jepsen, PhD, of Aarhus University Hospital in Denmark, and colleagues said the study “provides relevant and valid information on the association between NAFLD and cancer risk, and evidence of its strong association with HCC.”

However, the relative and absolute risk for patients “remains imprecisely quantified,” they pointed out, adding that a randomized trial needs to be conducted to determine whether screening for HCC reduces mortality in patients with NAFLD.

“It is unclear whether NAFLD increases the risk of colorectal cancer among men, and even less clear whether it increases the risk of breast cancer among women,” they wrote.

Inclusion of non-cancer mortality data would have strengthened the study “considerably,” the editorialists said, noting that participants with NAFLD had more risk factors for disease than those without NAFLD.

The higher BMI, fasting glucose, LDL cholesterol, and triglyceride, as well as a higher prevalence of hypertension and diabetes seen in NAFLD participants highlights the fact that NAFLD is a manifestation of the metabolic syndrome, Jepsen’s group said.

It also “calls into question” whether NAFLD caused cancer or whether cancer developed because of metabolic syndrome. “It is possible, likely in fact, that Kim et al’s patients with NAFLD have a higher rate of death without HCC than their non-NAFLD counterparts because of their higher prevalence of smoking, diabetes, high LDL cholesterol, etc,” they wrote.”If so, the higher rates of colorectal cancer and breast cancer in NAFLD patients might not result in higher risks of those cancers. For HCC, the difference in rates is so great that the absolute risk of HCC is likely be greater, too.”



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