P1179 - Evaluating the Impact of Cenicriviroc in Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Systematic Review

Avneet Singh, DO¹, Alexander Garcia, DO¹, Fariha Hasan, MD², Fatima Laique, MBBS³, Mubashir Mohiuddin, MBBS³, Muhammad Haris, MBBS³, Zehara Abidi, BS, MS⁴, Queenzy Jover, BSN, RN⁵, Mina Awadallah, MD, MSc⁶, Ali Wakil, MD⁷, Tommy Nguyen, DO², Satyajeet Roy, MD^1
1Cooper University Hospital, Camden, NJ; ²Cooper University Hospital, Philadelphia, PA; ³Dow University of Health Sciences, Karachi, Sindh, Pakistan; ⁴Touro College of Osteopathic Medicine, New York, NY; ⁵Virtua Health System, Camden, NJ; ⁶Rutgers New Jersey Medical School, Newark, NJ; ⁷Brooklyn Hospital Center, Brooklyn, NY

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 25% of US adults, while an estimated 5% have metabolic dysfunction-associated steato-hepatitis (MASH). While treatment options are limited, cenicriviroc (CVC), a chemokine receptor, has shown potential as an anti-fibrotic intervention. In this systematic review we assess the safety and effectiveness of CVC for MASH treatment

Methods: Clinical trials on PubMed, Embase, and Cochrane Library were systematically searched as of May 13, 2024 yielding 118 results. Risk of bias assessment was performed using Cochrane's tool for evaluating the risk of bias. Histological improvements in liver fibrosis, alterations in liver enzymes, and treatment-emergent adverse events (TEAEs) were the main outcomes reviewed. Sub-Analyses and post-hoc assessments were also taken into account in the review to help clarify treatment responses.

Results: Three trials, including 2234 patients, were reviewed. Two studies were randomized control trials and one an open label rollover. The mean age and BMI of all participants was 55.49 ± 10.72 and 35.07 ± 6.87 kg/m², respectively. In total, 3.89% patients had MASH CRN stage 1 fibrosis, 21.17% stage 2 fibrosis, 39.75% stage 3 fibrosis, and 1.52 stage 4 fibrosis. Improvement in fibrosis > stage 1 and no worsening of steatosis was observed in 13.98% of the enrollees. The Centaur study reported a statistically significant improvement in fibrosis in the CVC group, while the AURORA phase III study found no significant difference in fibrosis. Safety assessments showed that CVC had a favorable adverse event profile and was generally well-tolerated. TEAEs were noted in 53.2% of cases, with 10.85% graded as high-severity. An increase in ALT levels was noted in 2.83% of cases, while mortality was observed in only 0.36% of patients.

Discussion: Our systematic review suggests that the anti-fibrotic and anti-steatotic effects of CVC are variable between the two major studies. A small percentage of the participants had an improvement in fibrosis staging and, overall, CVC appears to be a well tolerated drug with minimal severe side effects. Due to limited treatment modalities for MASH, larger scale randomized trials around CVC should be considered to better understand treatment responses. Furthermore, in MASH clinical trials, noninvasive biomarkers and alternative endpoints might improve the evaluation of treatment outcomes.


Disclosures:


Avneet Singh, DO¹, Alexander Garcia, DO¹, Fariha Hasan, MD², Fatima Laique, MBBS³, Mubashir Mohiuddin, MBBS³, Muhammad Haris, MBBS³, Zehara Abidi, BS, MS⁴, Queenzy Jover, BSN, RN⁵, Mina Awadallah, MD, MSc⁶, Ali Wakil, MD⁷, Tommy Nguyen, DO², Satyajeet Roy, MD¹. P1179 - Evaluating the Impact of Cenicriviroc in Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Systematic Review, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.