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Advanced Fibrosis Predicts Nonfatal CVD in NAFLD Patients

Key findings

  • In a prospective, biopsy-characterized cohort of 285 patients who had nonalcoholic fatty liver disease (NAFLD) and no cardiovascular disease (CVD), 9% experienced one or more incident CV events over a median follow-up of five years
  • Advanced fibrosis on biopsy, smoking, lower alanine aminotransferase levels and lower albumin levels were independent predictors of incident CVD
  • A noninvasive indicator of fibrosis, the NAFLD fibrosis score, was also a significant predictor of CVD
  • Fibrosis severity should be considered when assessing CV risk in patients with NAFLD, and statin therapy should be started if indicated

Nonalcoholic fatty liver disease (NAFLD) is well established as an independent risk factor for cardiovascular disease (CVD). What's not well understood is which patients with NAFLD are at highest risk for cardiovascular events or whether cardiovascular risk varies according to the severity of NAFLD.

In Alimentary Pharmacology & Therapeutics, Jacqueline B. Henson, MD, resident in the Department of Medicine at Massachusetts General Hospital, Kathleen E. Corey, MD, MPH, director of the Fatty Liver Center, and colleagues present evidence that advanced fibrosis on biopsy and higher NAFLD fibrosis score are independent predictors of nonfatal CVD.

Study Details

The researchers analyzed data on 285 adults with biopsy-proven NAFLD who were enrolled in the Mass General NAFLD tissue repository between 2011 and 2018. To be included, patients had to have at least six months of follow-up; not have pre-existing CVD, decompensated cirrhosis or prior bariatric surgery; and not have a cardiovascular event within six months of enrollment.

Follow-up ended on November 1, 2018. The primary outcome was incident of new-onset CVD, defined as a new diagnosis of coronary artery disease, congestive heart failure, peripheral vascular disease, stroke, transient ischemic attack or a major adverse cardiac event (myocardial infarction, coronary revascularization or cardiac-related death).

Incident CVD

During prospective follow-up lasting a median of 5.2 years, 26 patients (9%) experienced one or more CV events:

  • Coronary artery disease (CAD; n=17)
  • Congestive heart failure (CHF; n=2)
  • Both CAD and CHF (n=1)
  • Ischemic stroke (n=5)
  • Transient ischemic attack (n=1)

The median time to a cardiovascular event was 3.8 years (range, 0.5–8.7 years).

Incident CVD Predictors

In multivariable models, advanced fibrosis on biopsy, smoking, lower alanine aminotransferase levels and lower albumin levels were significant and independent predictors of incident CVD.

A separate model considered a noninvasive indicator of fibrosis, the NAFLD fibrosis score (NFS). The established cut-off for the presence of significant fibrosis, NFS >0.676, was associated with a 4.6 times greater risk of CVD. Conversely, NFS ≤1.5 was associated with 82% less risk.

Advanced Fibrosis, Cardiovascular Risk Scores and Incident CVD

When adjusted for the Framingham Risk Score and the Atherosclerotic Cardiovascular Disease Pooled Cohort Equations Risk Score, advanced fibrosis and the NFS remained significant predictors of CVD.

Overall, 20% of patients with advanced fibrosis on biopsy experienced a cardiovascular event versus 7% of those without advanced fibrosis (P=.01). Advanced fibrosis accounted for 67% of the attributable risk of CVD.

Applying Findings to Practice

Fibrosis severity, whether determined after biopsy or through the NFS, should be considered when assessing cardiovascular risk in patients with NAFLD because it seems to add prognostic value to cardiovascular risk scores.

CVD, not hepatic complications, is the most common cause of death among people with NAFLD. Therefore, ensuring appropriate statin use is important. Applying current guidelines retrospectively, 70% of patients with advanced fibrosis in this study should have been using a statin at baseline, but only 29% were. The idea that statins are hepatotoxic has been repeatedly disproven.

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