Medicine · Liver Disease (Cirrhosis, Hepatitis, Autoimmune, Wilson's, Hemochromatosis)

In non-cirrhotic portal hypertension due to non-alcoholic steatohepatitis (NASH), which recent clinical trial (NASH-focused) demonstrated significant regression of hepatic fibrosis by at least one stage with an investigational agent?

  • A REGENERATE trial — obeticholic acid (OCA)
  • B RESOLVE-IT trial — elafibranor
  • C CENTAUR trial — cenicriviroc
  • D STELLAR-3 trial — selonsertib
Correct answer: A. REGENERATE trial — obeticholic acid (OCA)

Explanation

The REGENERATE trial (Phase 3) with obeticholic acid (OCA), a selective farnesoid X receptor [FXR] agonist, met its fibrosis improvement endpoint: a significantly higher proportion of OCA-treated patients achieved ≥1 stage improvement in fibrosis without NASH worsening compared to placebo. This is the best-studied drug achieving fibrosis regression in NASH to date. The RESOLVE-IT trial with elafibranor (PPAR-α/δ agonist) and the CENTAUR trial with cenicriviroc (CCR2/CCR5 antagonist) both failed to meet primary endpoints. Selonsertib (ASK1 inhibitor) also failed in the STELLAR-3 and STELLAR-4 trials for advanced fibrosis/cirrhosis.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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