Emricasan for Improving Liver Function in Patients with Cirrhosis
Atif Zaman, MD, MPH reviewing Frenette CT et al. Clin Gastroenterol Hepatol 2018 Jun 15
This promising pan-caspase inhibitor appeared to improve biomarkers and liver function in some patients with cirrhosis.
Caspases, a family of cysteine proteases, mediate apoptosis and inflammation, which are associated with many chronic liver diseases that lead to hepatic fibrosis. Emricasan, a pan-caspase inhibitor, has been shown to reduce serum markers for apoptosis and inflammation in chronic liver disease.
In this manufacturer–sponsored and designed, multicenter, double-blind, randomized, placebo-controlled study in patients with Child-Pugh A or B cirrhosis, patients randomly received emricasan 25 mg or placebo twice daily for 3 months. Thereafter, all patients received open-label emricasan for an additional 3 months. The primary endpoint was a change from baseline in levels of serum keratin 18 (CK-18) at 3 months. Secondary endpoints included model for end-stage liver disease (MELD) and Child-Pugh score changes from baseline.
Serum levels of full-length CK-18, but not cleaved CK-18, decreased significantly in the emricasan but not in the placebo group. Although MELD and Child-Pugh score changes were similar in both groups, emricasan group patients with baseline MELD ≥15 had significant decreases in both MELD and Child-Pugh scores. These improvements endured or increased during the open-label phase. Adverse events were similar between the two groups.
Comment
In this small study, emricasan appeared to improve caspase-related biomarkers, such as CK-18. More importantly, it improved liver function in patients with cirrhosis and MELD >15. Liver function improvement could possibly occur in lower-MELD-score patients, but the small sample size likely obscured the treatment effect. Further studies with larger sample sizes, powered to have MELD as the primary outcome, and including a diverse cirrhosis population, are needed to determine its value in clinical practice.
Editor Disclosures at Time of Publication
Disclosures for Atif Zaman, MD, MPH at time of publication
Grant/Research support:
Merck
Citation(s):
Frenette CT et al. Emricasan improves liver function in patients with cirrhosis and high model for end-stage liver disease scores compared with placebo. Clin Gastroenterol Hepatol 2018 Jun 15; [e-pub]. (https://doi.org/10.1016/j.cgh.2018.06.012)