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Hepatic fibrosis, not NAFLD, increased risk for cardiovascular-related death

Recent results indicate an independent association between mortality risk and advanced hepatic fibrosis, as defined by noninvasive markers, but not nonalcoholic fatty liver disease diagnosed via ultrasonography.

Researchers evaluated data on 11,154 patients collected from the National Health and Nutrition Examination Survey database between 1988 and 1994. The presence of nonalcoholic fatty liver disease (NAFLD) and hepatic fibrosis was determined, along with mortality rates, during a median follow-up of 14.5 years. From this, potential associations between NAFLD and increased mortality risk also were calculated. Among patients with NAFLD, fibrosis was assessed according to NAFLD fibrosis score (NFS), AST-platelet ratio index (APRI) and FIB-4 score.

NAFLD, defined as mild-to-severe steatosis measured via ultrasonography, was observed in 34% of cases. NFS consistent with a low probability of fibrosis (less than –1.455) was observed in 71.7% of cases, while a high likelihood of advanced fibrosis (NFS above 0.676) was present in 3.2%. Death occurred in 1,795 cases, including 1,016 patients without NAFLD and 779 with NAFLD. Cardiovascular causes (9.3% of deaths) and malignancy (5%) were the most common factors.

Investigators found no significant association between NAFLD and all-cause (adjusted HR=0.89; 95% CI, 0.78-1.02) or cause-specific mortality, including liver disease, malignancy or diabetes. An association between NAFLD and death from cardiovascular disease, however, approached significance (aHR=0.75; 95% CI, 0.56-1.01). Higher NFS was associated with increased mortality risk: Patients with high NFS scores were at greater risk than those with low scores (P=.02), as were patients with intermediate scores (P=.076). Cause-specific analysis indicated a particular increased in risk for death from cardiovascular causes among patients with high NFS scores (HR=3.46; 95% CI, 1.91-6.25) compared with patients with low scores. Similar results were observed when APRI or FIB-4 was used as fibrosis markers.

“It is clear that NAFLD without advanced fibrosis has little impact on mortality upon follow-up [for] up to two decades,” the researchers wrote. “However, NAFLD with advanced fibrosis is an independent predictor of increased mortality, mainly from cardiovascular causes. In those patients, rigorous interventions to modify cardiovascular risk factors as well as careful follow-up for progression of fibrosis may be warranted.”