July 10, 2024
Hepatology (Baltimore, Md.)
TAKE-HOME MESSAGE
- This study assessed the safety and efficacy of treatment with phospholipid curcumin (Meriva®), a phospholipid formulation with ameliorated systemic curcumin absorption and delivery, in patients with NASH. A total of 52 patients with NASH (a majority of whom had fibrosis and chronic kidney disease) were randomized to receive Meriva or placebo for 72 weeks. The primary endpoint was NASH resolution without worsening of fibrosis.
- Approximately 62% of the patients receiving Meriva experienced NASH resolution without worsening of fibrosis compared with 12% of those receiving placebo, and 50% of patients receiving Meriva experienced ≥1-stage fibrosis improvement compared with 8% of those receiving placebo. In addition, 50% of the patients receiving Meriva showed chronic kidney disease regression. Adverse events were rare.
Written by Gertrude Arthur PhD Written by David E. Stec PhD
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction–associated steatotic liver disease (MASLD), can progress to NASH. NASH is associated with increased liver inflammation and fibrosis and can progress to liver cirrhosis if not properly treated. Both MASLD and NASH are associated with the development of cardiovascular and renal disease. More recently, MASLD and NASH have been linked to an increased risk of development of chronic kidney disease (CKD). Currently, there are no approved pharmacological treatments for NASH or any of the cardiovascular or renal complications associated with this disease. Curcumin is a natural polyphenol, the active ingredient in turmeric, and a common spice mainly grown in India.
In this study, Musso et al used a patented formulation of curcumin, Meriva®, in a randomized, double-blinded, placebo-controlled trial to determine its safety and efficacy in reducing liver and kidney disease markers in patients with biopsy-confirmed NASH. The dose and treatment duration with Meriva® were based on previous clinical trials. The authors report that Meriva® treatment resulted in a greater percentage of patients exhibiting resolution of NASH (as determined histologically), improvement in fibrosis, as well as changes in serum liver enzymes. Interestingly, patients treated with Meriva® exhibited a regression of CKD (glomerular filtration rate >90 mL/kg 1.73 m2 and an albumin excretion rate <30 mg/dL) and improvements in glomerular filtration rate compared with placebo-treated patients. Lastly, patients treated with Meriva® exhibited a significant downregulation in hepatic NF-κB, a proinflammatory transcription factor.
This study provides the first clinical evidence to support the safe use of a novel formulation of curcumin, Meriva®, which exhibits improved oral bioavailability in patients with NASH. However, several questions remain to be addressed. Do these improvements remain after the 72 weeks when patients stop the treatment, or does the disease regress? If the drug is administered for a longer period, will there be further improvements? One limitation of the study was the small sample size; therefore, a larger-scale trial would be useful to test the true efficacy of Meriva® in patients with NASH.
Abstract
BACKGROUND AIMS
Nonalcoholic steatohepatitis (NASH) confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva ® ) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed safety and efficacy of Meriva ® in NASH.
APPROACH
In this double-blind trial, 52 biopsy-proven NASH patients(71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a CKD) were randomized 1:1 to receive Meriva ® 2 g/day or placebo for 72 weeks. Primary end-point was NASH resolution with no worsening of fibrosis. Secondary end-points included: a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant(i.e. stage≥F2) fibrosis and of chronic kidney disease(CKD); improvement in renal, glucose, lipid and inflammatory parameters. We also explored treatment effect on hepatic activation of Nuclear Factor(NF)-kB, a key proinflammatory transcription factor and a major target of curcumin.
RESULTS
Fifty-one patients(26 on Meriva ® and 25 on placebo) completed the trial. Sixteen(62%) patients on Meriva ® vs. three(12%) patients on placebo had NASH resolution(RR=5.33[95%CI=1.76-12.13]; p=0.003). Thirteen(50%) patients on Meriva ® vs. 2(8%) patients on placebo had ≥1 stage fibrosis improvement(RR=6.50[(1.63-21.20]; p=0.008). Eleven(42%) patients on Meriva ® vs. 0(0%) on placebo had regression of significant liver fibrosis(RR=18.01[1.43-36.07]; p=0.02). Hepatic NF-kB inhibition predicted NASH resolution(AUC=0.90,95%CI=0.84-0.95) and fibrosis improvement(AUC=0.89,95%CI=0.82-0.96). Thirteen(50%) patients on Meriva ® vs. 0(0%) on placebo had CKD regression(RR=10.71[1.94-17.99)]; p=0.004). Compared with placebo, Meriva ® improved eGFR(difference in adjusted eGFR change: +3.59[2.96-4.11] mL/min/1.73 m 2 /year, p =0.009), fasting glucose(-17 mg/dL;95%CI=-22, -12), HbA1c(-0.62%;95%CI=-0.87%, -0.37%), LDL-C(-39 mg/dL; 95%CI=-45, -33), triglycerides(-36 mg/dL, 95%CI= -46, -26), HDL-C(+10 mg/dL; 95%CI=+8, +11) and inflammatory markers. Adverse events were rare, mild and evenly distributed.
CONCLUSION
In NASH patients, Meriva ® administration for 72 weeks was safe, well-tolerated, improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile.