Both all-cause and liver-related mortality rates increase exponentially with an increase in fibrosis stage for patients with nonalcoholic fatty liver disease, according to results of a systematic review published in Hepatology.
“We observed that all-cause and liver-related mortality increased exponentially with increasing fibrosis stage, and NAFLD patients were at an increased risk even at early stages of fibrosis,” Rohit Loomba, MD, MHSc, director of the NAFLD Research Center, UC San Diego Health, and professor of medicine at UC San Diego School of Medicine, and colleagues wrote.
“The risk of liver mortality increases exponentially as the stage of fibrosis increases, suggesting that societal benefits of therapies to treat nonalcoholic steatohepatitis would be significantly higher with higher stage and therefore willingness to pay would also be higher for stage 3 and stage 4 disease,” Loomba told Healio.com/Hepatology.
The researchers accessed the Medline, EMBASE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews databases and reviewed cohort studies of NAFLD patients that reported mortality.
The review included five studies comprising 1,495 patients and 17,452 patient years of follow-up. Median age of patients was 49.3 years; 53.5% were men. Researchers considered patients with no fibrosis, or stage 0, (38.1%) as the reference population, which they compared with patients at stage 1 (28.9%), stage 2 (13.6%), stage 3 (12%) or stage 4 (7.4%).
The crude all-cause mortality rate for stage 0 patients was 15.2 per 1,000 patient years of follow-up, compared with 17.1 for stage 1, 27.9 for stage 2, 36 for stage 3 and 45.8 for stage 4. The mortality rate ratio increased per stage from 1.58 for stage 1 (95% CI, 1.19-2.11), to 2.52 for stage 2 (95% CI, 1.85-3.42), 3.48 for stage 3 (95% CI, 2.51-4.83) and 6.4 for stage 4 (95% CI, 4.11-9.95).
Similarly, liver-related morality rates increased per stage. The fibrosis stage 0 patients had a crude mortality rate of 0.3 per 1,000 patient years of follow-up, compared with 0.64 for stage 1, 4.28 for stage 2, 7.92 for stage 3 and 23.3 for stage 4. The mortality ratio rates increased from 1.41 for stage 1 (95% CI, 0.17-11.95), to 9.57 for stage 2 (95% CI, 1.67-54.93), 16.69 for stage 3 (95% CI, 2.92-95.36) and 42.30 for stage 4 (95% CI, 3.51-510.34).
“These data have important implications for understanding health utility of patients in the respective stage of disease and economic impact of benefits of improvement in the stage of fibrosis in the setting of a treatment modality,” the researchers concluded. “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 stage of fibrosis.” – by Talitha Bennett
Disclosures: The researchers report no relevant financial disclosures.