Risk of liver-related death linked to increased fibrosis stage in NAFLD

Increasing fibrosis stage was associated with an exponential increase in risk for liver-related death in patients with nonalcoholic fatty liver disease (NAFLD), a recent study found.

Researchers performed a systematic review and meta-analysis in order to quantify the risk for all-cause and liver-related death according to fibrosis stage in patients with NAFLD. Retrospective or prospective cohort studies published from inception to November 2016 that reported mortality in relation to fibrosis stage in adult patients with confirmed NAFLD were included. Fibrosis stage 0 was used as the reference population. The study results were published online March 31 and will appear in the May Hepatology.

Five studies of 1,495 adult patients with NAFLD were included, encompassing 17,452 patient-years of follow-up. Over half (53.5%) of patients were men, and the mean age was 49.3 years. Obesity prevalence in the cohorts was 40% (range across cohorts, 25.8% to 50%). A total of 38.1% of patients had stage 0 fibrosis, 28.9% had stage 1, 13.6% had stage 2, 12.0% had stage 3, and 7.4% had stage 4. Patients with NAFLD who had fibrosis at any stage were at higher risk for all-cause mortality than NAFLD patients with stage 0 fibrosis. This risk appeared to increase by fibrosis stage, with all-cause mortality rate ratios of 1.58 (95% CI, 1.19 to 2.11) for stage 1, 2.52 (95% CI, 1.85 to 3.42) for stage 2, 3.48 (95% CI, 2.51 to 4.83) for stage 3, and 6.40 (95% CI, 4.11 to 9.95) for stage 4. The increase in risk by fibrosis stage was much higher for liver-related death, particularly in later stages (stages 2 to 4), with mortality rate ratios of 1.41 (95% CI, 0.17 to 11.95) for stage 1, 9.57 (95% CI, 1.67 to 54.93) for stage 2, 16.69 (95% CI, 2.92 to 95.36) for stage 3, and 42.30 (95% CI, 3.51 to 510.34) for stage 4.

The authors acknowledged that they were not able to adjust for comorbid conditions such as diabetes or for demographic characteristics such as age that are known to have an effect on progression of fibrosis in NAFLD. In addition to other limitations, they also pointed out that they were not able to obtain patient-level data on exact cause of death for all of the included studies. However, they concluded that risk of mortality, especially liver-related mortality, increases exponentially with increasing fibrosis stage in patients with NAFLD. “These data suggest that benefits of regression of fibrosis even by one stage may be more profound in patients with cirrhosis (stage 4) or in patients with bridging fibrosis (stage 3) than in earlier stages of fibrosis,” the authors wrote. They said their results could aid shared decision-making with patients and help inform future trials of therapeutic interventions.