Spotlight on NAFLD outcomes

Three studies published in the past month focused on clinical outcomes among patients with nonalcoholic fatty liver disease (NAFLD).

The first study found that the prevalence and severity of NAFLD were independently associated with coronary artery disease (CAD). Researchers conducted a cross-sectional study of 296 patients (59% female; mean age, 54 years) referred to the catheterization laboratory of an academic hospital in Iran for elective coronary angiography to investigate the presence and severity of CAD. All participants also had abdominal ultrasonography to detect NAFLD and its severity. Results were published April 27 by JGH Open.

Overall, 187 patients (63%) had CAD and 160 (54%) had NAFLD. Those with NAFLD had a significantly higher prevalence of obesity (odds ratio [OR], 1.047; 95% CI, 1.002 to 1.094), hypertension (OR, 1.909; 95% CI, 1.027 to 3.55), hyperlipidemia (OR, 3.474; 95% CI, 1.862 to 6.482), and CAD (OR, 2.009; 95% CI, 1.100 to 3.669). The percentage of patients with normal vessels was highest in the non-NAFLD group, followed by the group with mild and severe NAFLD (P<0.001). Single- and multi-vessel disease incidences among the non-NAFLD, mild, and severe NAFLD groups were 36.1%, 43.1%, and 63.7%, respectively. The percentage of patients with two-vessel stenosis was higher in patients with severe NAFLD than in those with mild or no NAFLD (P<0.001). “The results of this study may provide a beneficial background for future studies to modify the guidelines for the management of CAD patients,” the study authors wrote. “In addition, NAFLD patients would benefit from advice on lifestyle and risk factor modifications.”

The second study found that patients with NAFLD may be at increased risk of sarcopenia. Researchers conducted a cohort study of 52,815 patients ages 20 years and older (56% men; mean age, 49 years) who had at least two health check-up exams with bioelectrical impedance analysis and abdominal ultrasound imaging at a Korean center between August 2006 and July 2016. The researchers estimated the five-year change in appendicular skeletal muscle mass in participants with and without NAFLD and assessed severity of NAFLD using the NAFLD Fibrosis Score. Results were published May 19 by Hepatology.

The overall prevalence of NAFLD at baseline was 32%. Compared to participants without NAFLD, those with the disease had higher appendicular skeletal muscle mass at baseline (mean values, 22.3 vs. 19.2 kg; P<0.001). Over an average five years of follow-up, the estimated average changes in appendicular skeletal muscle mass in participants without and with NAFLD at baseline were −225.2 g (95% CI, −232.3 g to −218.0 g) and −281.3 g (95% CI, −292.0 g to −270.6 g), respectively (P<0.001). In adjusted analysis, those with NAFLD had a faster loss of appendicular skeletal muscle mass than those without (−39.9 g; 95% CI, −53.1 g to −26.8 g), both among men (−45.6 g; 95% CI, −61.1 g to −30.1 g) and women (−30.5 g; 95% CI, −52.8 g to −8.3 g). The association of NAFLD with muscle loss was stronger in younger adults than in those ages 50 years and older (P=0.047 for interaction), as well as in ever smokers and in moderate drinkers compared to never smokers and never drinkers (P=0.03 for interaction) and in those with diabetes and hyperlipidemia (P<0.01 for interaction). Limitations of the study include a lack of assessment of muscle function and the use of bioelectrical impedance, which has lower accuracy than dual-energy X-ray absorptiometry, the authors noted.

The third study found that risk of all-cause and liver-related mortality increases substantially with NAFLD fibrosis stage. Researchers performed a time-to-event meta-analysis of cohort studies reporting survival outcomes by fibrosis stage in patients with biopsy-proven NAFLD. They classified fibrosis into individual stages (F0, F1, F2, F3, and F4) and pooled survival estimates using reconstructed individual participant data. Results were published May 2 by Clinical Gastroenterology and Hepatology.

The analysis included 14 articles involving 17,301 patients with NAFLD. All-cause mortality at one, five, and 10 years for patients with F0 to F2 fibrosis was 0.1%, 3.3%, and 7.7% versus 0.3%, 20.6%, and 41.5% for those with F4 fibrosis. Compared to F0 fibrosis, all-cause mortality increased with fibrosis stage. Hazard ratios (HRs) were 1.46 (95% CI, 1.08 to 1.98) for F2, 1.96 (95% CI, 1.41 to 2.72) for F3, and 3.66 (95% CI, 2.65 to 5.05) for F4. Risk for liver-related mortality increased exponentially as fibrosis stage increased, with HRs of 4.07 (95% CI, 1.44 to 11.5) for F2, 7.59 (95% CI, 2.80 to 20.5) for F3, and 15.1 (95% CI, 5.27 to 43.4) for F4. Patients with F3 and F4 fibrosis had higher all-cause (HR, 3.32) and liver-related mortality (HR, 10.40) compared with those with F0 to F2 fibrosis, and those with F4 fibrosis had higher all-cause (HR, 2.67) and liver-related mortality (HR, 2.57) than those with F3 fibrosis. The study was limited by a relatively small sample size for liver-related mortality and sparse time-to-event data on non-liver-related mortality and cardiovascular-related mortality, the authors noted.