Patrick Campbell is the editorial director of HCPLive. Patrick has spent years spearheading coverage surrounding cardiometabolic health and rheumatic disease for MJH Life Sciences. Before joining MJH Life Sciences in 2019, he spent time as a beat reporter and/or multimedia specialist with the Pocono Record, Star News Group, and NJ Advance Media. He is the executive producer for multiple HCPLive podcasts, including Diabetes Dialogue, Don't Miss a Beat, Kidney Compass, Medical Ethics Unpacked, The Medical Sisterhood, and Skin of Color Savvy. 


Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

Steven Nissen, MD
Credit: Cleveland Clinic

Pelacarsen, an antisense oligonucleotide targeting apolipoprotein(a), lowered lipoprotein(a) [Lp(a)] but did not reduce major adverse cardiovascular events (MACE) compared with placebo in patients with established 

 and elevated Lp(a) in the phase 3 Lp(a)HORIZON trial, presented at the American Heart Association (AHA) Scientific Sessions 2026 and published in the 

At 12 months, Lp(a) fell by 78.4% with pelacarsen and 3.2% with placebo (difference, 77.7 percentage points; 95% CI, 77.0–78.4). Over a median follow-up of 4.7 years, the primary MACE endpoint occurred in 12.3% (511/4157) of the pelacarsen group and 12.1% (503/4165) of the placebo group (hazard ratio [HR], 1.02; 95% CI, 0.90–1.15; 

Additional data presented at AHA 2026 indicated results were similar among patients with baseline Lp(a) of at least 90 mg/dL (HR, 1.00; 95% CI, 0.87–1.15; 

“I cannot avoid the disappointing conclusion – it didn’t work. Pelacarsen improved Lp(a) measures significantly – 78% lower; however, cardiovascular outcomes were unchanged. The neutral finding was unexpected and surprising to the medical community,” said Steven E. Nissen, MD, senior author and chief academic officer of the Miller Family Heart, Vascular & Thoracic Institute at the Cleveland Clinic in Cleveland, Ohio.


Pelacarsen is an investigational antisense oligonucleotide from Novartis targeting apolipoprotein(a) messenger RNA. In Lp(a)HORIZON, it was given as an 80-mg subcutaneous injection once monthly.


Pelacarsen lowered Lp(a) by 78.4% at 12 months, but MACE occurred in 12.3% vs 12.1% of patients over a median 4.7 years (HR, 1.02; 95% CI, 0.90–1.15; P = .76).

What safety signals were seen with pelacarsen?


Serious adverse events were similar (37.3% vs 41.1%), but influenza-like and injection-site reactions were more frequent with pelacarsen, and 19 patients had adjudicated anaphylaxis vs none with placebo.

Lp(a)HORIZON trial design and pelacarsen MACE results

The double-blind, placebo-controlled trial randomized 8350 patients aged 18 to 80 years at 797 sites in 42 countries from December 2019 through July 2022, with 8322 included in the efficacy analysis. Eligible patients had a prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral artery disease and an Lp(a) level of at least 70 mg/dL.

Patients received subcutaneous pelacarsen 80 mg or placebo monthly, and the primary endpoint was a composite of cardiovascular death, nonfatal MI, nonfatal ischemic stroke, or urgent coronary revascularization.

Mean age was 59.7 years, 27.0% of patients were women, and 76.6% had a previous MI. Median baseline Lp(a) was 235.8 nmol/L and median LDL cholesterol was 64.6 mg/dL, with 77.6% of patients receiving high-intensity statin therapy. At 12 months, median Lp(a) was 64.4 nmol/L with pelacarsen and 233.4 nmol/L with placebo.

None of the MACE endpoints favored pelacarsen.

 Three-component MACE occurred in 10.2% vs 10.1% of patients (HR, 1.01; 95% CI, 0.88–1.16), and the composite including death from coronary heart disease occurred in 9.4% vs 9.7% (HR, 0.97; 95% CI, 0.85–1.12). Death from any cause occurred in 5.7% vs 5.9% (HR, 0.98; 95% CI, 0.82–1.17), with no between-group differences in any prespecified subgroup.

Pelacarsen safety, tolerability, and discontinuation in Lp(a)HORIZON

Serious adverse events occurred in 37.3% (1553/4166) of patients receiving pelacarsen and 41.1% (1709/4154) receiving placebo.

 Influenza-like reactions (31.9% vs 5.8%) and injection-site reactions (25.6% vs 2.9%) were more common with pelacarsen, as were adverse events leading to permanent discontinuation (20.6% vs 7.5%).

Adjudicated anaphylaxis occurred in 19 patients receiving pelacarsen and none receiving placebo, and 8 hypersensitivity reactions led to hospitalization, with no deaths.

After a suspected case of anaphylaxis in March 2023, pelacarsen injections were moved to a medically supervised setting for 6 months before at-home dosing resumed. Premature discontinuation of the trial regimen occurred in 35.1% of the pelacarsen group and 18.3% of the placebo group.

The investigators noted differential discontinuation as a limitation, along with a predominantly male and White population and possible COVID-19 confounding.

“The results were completely neutral across multiple analyses. There was basically no effect on outcomes, not even a trend, even in subpopulations,” said Nissen. “However, this does not mean Lp(a) is irrelevant. It means we need more in-depth research to help us fully understand the underlying mechanisms of Lp(a), its interactions with other CVD risk factors and how it does or does not impact cardiovascular outcomes. So for anyone currently enrolled in an Lp(a) trial, don’t drop out because of these findings. Lp(a) is still an important piece of the overall cardiovascular disease puzzle, an important cause of morbidity and mortality worldwide.”

The investigators suggested short-term Lp(a) reduction may not confer the benefit linked to lifelong lower levels in mendelian randomization studies, and strict background risk-factor control may have limited any added benefit.

 Topline results showing the trial missed its primary end point were reported in September 2026.

Phase 3 outcome trials are ongoing for the small interfering RNA agents olpasiran and lepodisiran and the oral agent muvalaplin, which have lowered Lp(a) by more than 90% and approximately 85%, respectively, in earlier trials.

 Lepodisiran has also been studied for its effect on oxidized phospholipids carried on Lp(a).

Cho L, Nicholls SJ, Frndak S, et al. Pelacarsen and cardiovascular outcomes in patients with high lipoprotein(a). 

American Heart Association. Lp(a) HORIZON trial: Lp(a) fell by 78%, but cardiovascular outcomes unexpectedly neutral. Published November 7, 2026. Accessed November 7, 2026. 

https://newsroom.heart.org/news/lp-a-horizon-trial-lp-a-fell-by-78-but-cardiovascular-outcomes-unexpectedly-neutral

HCPLive. Pelacarsen misses primary endpoint in Lp(a)HORIZON phase 3 trial. 

https://www.hcplive.com/view/pelacarsen-misses-primary-endpoint-in-lp-a-horizon-phase-3-trial

. Published September 5, 2026. Accessed November 7, 2026.

HCPLive. Lepodisiran reduces OxPL tied to Lp(a), with Steven Nissen, MD. 

https://www.hcplive.com/view/lepodisiran-oxidized-phospholipids-lpa

. Published September 4, 2026. Accessed November 7, 2026.

Articles

Pelacarsen cut lipoprotein(a) by 78.4% at 12 months but did not reduce MACE vs placebo in 8322 patients with cardiovascular disease (HR, 1.02).

News

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Atherosclerotic Cardiovascular Disease

Dyslipidemia

Lp(a) HORIZON Shows Pelacarsen Lowers Lp(a) 78% But Not Cardiovascular Events

Paul Ridker, MD
Credit: Mass General Brigham

Ziltivekimab, an interleukin-6 (IL-6) inhibitor, did not reduce cardiovascular events compared with placebo in patients with 

 (ASCVD), chronic kidney disease (CKD), and inflammation in the phase 3 ZEUS trial, according to results presented at the 

American Heart Association (AHA) Scientific Sessions 2026

Ziltivekimab, a monoclonal antibody neutralizing the IL-6 ligand, lowered high-sensitivity C-reactive protein (hsCRP) and other inflammatory biomarkers in a phase 2 study of patients with CKD. The ZEUS rationale drew on mendelian randomization data implicating IL-6 signaling in atherosclerosis and on CANTOS, in which interleukin-1β inhibition with canakinumab lowered recurrent cardiovascular event rates.

“The findings from ZEUS illustrate why clinical trials are so important: We don’t yet have all of the answers and science is often about trial and error,” said Paul M. Ridker, MD, Center for Cardiovascular Disease Prevention, Mass General Brigham. “We already know from prior studies that targeting inflammation can reduce rates of heart attack and stroke. The critical question is which drug works best in which patients.”


Ziltivekimab is an investigational monoclonal antibody from Novo Nordisk targeting the IL-6 ligand. In ZEUS, it was given as a 15-mg subcutaneous injection once monthly.


Among 6376 patients with ASCVD, CKD, and hsCRP of at least 2 mg/L, ziltivekimab lowered IL-6 and hsCRP but did not reduce 3-point MACE vs placebo (17.6% vs 17.7%; HR, 0.99; P = .84).

What safety signals were seen with ziltivekimab?


Serious adverse event rates were similar between groups, but serious infections (20.4% vs 17.9%) and serious venous thromboembolism (1.6% vs 0.6%) were more frequent with ziltivekimab.

Ziltivekimab efficacy on major adverse cardiovascular events in ZEUS

ZEUS was a double-blind, placebo-controlled, event-driven trial conducted at 757 sites in 38 countries, with enrollment from September 2021 through December 2024. Eligible adults had ASCVD, hsCRP of at least 2 mg/L, and CKD, defined as an estimated glomerular filtration rate (eGFR) of 15 to less than 60 mL/min/1.73 m².

Patients with an eGFR of at least 60 mL/min/1.73 m² qualified with a urinary albumin-to-creatinine ratio of at least 200 mg/g.

Patients were randomized 1:1 to subcutaneous ziltivekimab 15 mg once monthly or placebo, and the full analysis population included 6376 patients, with 3184 receiving ziltivekimab and 3192 receiving placebo.

Mean age was 69.4 years, 27.5% were women, 65.8% had diabetes, and 42.2% had heart failure. Median baseline hsCRP was 4.5 mg/L, and mean eGFR was 44.5 mL/min/1.73 m².

At 24 months, the between-group difference in median percent change was −76 percentage points for free IL-6 and −64 percentage points for hsCRP. Over a median follow-up of 33 months, 3-point major adverse cardiovascular events (MACE) occurred in 17.6% (561/3184) of the ziltivekimab group and 17.7% (565/3192) of the placebo group. The hazard ratio (HR) was 0.99 (95% CI, 0.88–1.11; 

Secondary end points and safety of IL-6 inhibition with ziltivekimab

None of the confirmatory secondary end points favored ziltivekimab.

 The 4-point MACE end point occurred in 18.4% vs 18.5% of patients (HR, 0.99; 95% CI, 0.88–1.10), and death from any cause in 16.9% vs 17.0% (HR, 0.99; 95% CI, 0.88–1.12).

 The composite kidney end point occurred in 20.2% vs 19.3% (HR, 1.05; 95% CI, 0.94–1.17).

Serious adverse events occurred in 54.6% of the ziltivekimab group and 54.8% of the placebo group.

 Serious infections were more frequent with ziltivekimab (20.4% vs 17.9%), as were deaths from infection (3.2% vs 2.5%) and cellulitis (2.9% vs 1.0%).

 Serious venous thromboembolism occurred in 1.6% vs 0.6% of patients, and platelet counts below 100×10⁹/L in 7.4% vs 3.2%.

According to the investigators, established risk factors only partly explained the venous thromboembolism imbalance, and whether it reflects IL-6 pathway inhibition, the enrolled population, or chance remains uncertain.

 The press release from Mass General Brigham characterized safety as reassuring, with no adverse effect on total mortality.

“Given our neutral findings, one logical next step is to move upstream, instead of downstream, to find the right target,” said Ridker. “For example, there are multiple new agents in development that can inhibit the upstream NLRP3 inflammasome. At the same time, it remains quite possible that downstream IL-6 inhibition is in fact effective, but that ZEUS targeted the wrong patient population.”

ZEUS participants were about 10 years older than those in CANTOS and carried a heavier burden of CKD, diabetes, and heart failure.

 Placebo-group 3-point MACE incidence was 6.8 per 100 person-years in ZEUS vs 4.5 in CANTOS.

 The authors also noted genetic evidence points most consistently to 

 variants, while ligand inhibitors such as ziltivekimab do not block the IL-6 receptor.

Ziltivekimab remains under study in 2 additional trials: HERMES in heart failure with midrange or preserved ejection fraction and ARTEMIS in acute coronary ischemia. Ridker also described low-dose colchicine, approved by the US Food and Drug Administration to lower rates of myocardial infarction and stroke, as underused in patients with stable atherosclerosis.

Ridker PM, Lincoff AM, Marx N, et al. Interleukin-6 inhibition with ziltivekimab for atherosclerotic disease. 

Mass General Brigham. Heart researchers unpack neutral findings from ZEUS, an anti-inflammatory clinical trial. EurekAlert! Published November 7, 2026. Accessed November 7, 2026. 

https://www.eurekalert.org/news-releases/1150801

Despite lowering free IL-6 and hsCRP, monthly ziltivekimab did not reduce 3-point MACE vs placebo in 6376 patients with ASCVD and CKD.

Nephrology

The HCPLive nephrology page is a resource for medical news and expert insights on kidney disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in nephrology, and more.

Chronic Kidney Disease

ZEUS: Ziltivekimab Fails to Reduce Cardiovascular Events in ASCVD and CKD

Abigail Brooks is a strategic content lead overseeing 

She joined MJH Life Sciences in August 2023 shortly after graduating from Monmouth University where she earned her BA in Communication with a concentration in Public Relations/Journalism and later an MA in Interactive Digital Media. She enjoys traveling, running, and reading books. She can be reached at abrooks@mjhlifesciences.com.

Saroglitazar magnesium 4 mg resolved steatohepatitis without worsening of fibrosis in 39.1% of adults with 

metabolic dysfunction-associated steatohepatitis (MASH)

, compared with 13.7% receiving placebo, in the phase 2b EVIDENCES X trial presented at 

. The trial did not meet its secondary histologic endpoint of fibrosis improvement, though the 4 mg dose improved several noninvasive fibrosis markers.

"Many people with MASH and fibrosis also have type 2 diabetes or obesity, so we need options that address both the liver disease and the metabolic dysfunction that drives it," Naga Chalasani, MD, of Indiana University School of Medicine, said in a statement. "In this Phase 2b trial, more patients achieved resolution of steatohepatitis without worsening of fibrosis with saroglitazar than with placebo, along with improvements in lipid and glycemic parameters. These results support evaluating saroglitazar in larger, longer-term studies."

Chalasani and Arun Sanyal, MD, of Virginia Commonwealth University, served as co-principal investigators of the global trial, which Zydus Lifesciences first reported had met its primary endpoint in August 2026.

 Resmetirom and semaglutide 2.4 mg currently hold FDA accelerated approval for noncirrhotic MASH with moderate to advanced fibrosis, and several other agents remain in development.

How Did Saroglitazar Perform in EVIDENCES X?

Saroglitazar is a predominantly peroxisome proliferator-activated receptor (PPAR)-α agonist with moderate PPAR-γ activity.¹ In the multicenter, double-blind, placebo-controlled EVIDENCES X trial (NCT05011305), adults with MASH were randomized to saroglitazar magnesium 4 mg (n = 64), saroglitazar magnesium 2 mg (n = 63), or placebo (n = 62) once daily for 52 weeks. Analyses used the intention-to-treat population and were stratified by baseline diabetes status.

Among 189 participants, the mean age was 56 years, approximately 61% were women, mean body mass index was approximately 35 kg/m², and 59% had type 2 diabetes.

 The trial enrolled patients across the US, Turkey, and Argentina.

Steatohepatitis resolution without worsening of fibrosis occurred in 39.1% of patients receiving 4 mg and 32.4% receiving 2 mg, compared with 13.7% receiving placebo.¹ The treatment difference vs placebo was 24.9% (95% CI, 9.5-40.3; 

 = .002) for 4 mg and 16.5% (95% CI, 1.3-31.6; 

Fibrosis improvement of at least 1 stage without worsening of NAFLD Activity Score occurred in 34.8% of patients receiving 4 mg, 22.8% receiving 2 mg, and 24.6% receiving placebo. Neither dose differed significantly from placebo (4 mg: 10.2%; 95% CI, −6.3 to 26.6; 

 = .230; 2 mg: −0.9%; 95% CI, −16.7 to 14.9; 

Noninvasive fibrosis assessments favored the 4 mg dose. Compared with placebo, saroglitazar 4 mg was associated with treatment differences of −9.50 ng/mL (95% CI, −15.3 to −3.7) for PRO-C3, −0.35 (95% CI, −0.5 to −0.2) for APRI, −0.30 (95% CI, −0.5 to −0.1) for FIB-4, and −0.53 (95% CI, −1.0 to −0.1) for ADAPT.

The 4 mg dose also produced clinically meaningful improvements in liver enzymes, lipid and glycemic parameters, and insulin resistance, according to the investigators. Treatment was well tolerated, without significant weight gain or a drug-induced liver injury signal. The authors described the noninvasive fibrosis findings as encouraging.

Saroglitazar magnesium was approved in India in 2020 for MASH and metabolic dysfunction-associated steatotic liver disease but remains investigational in the US for these indications.

In primary biliary cholangitis, the US Food and Drug Administration granted Priority Review to the new drug application for saroglitazar, with a target action date of November 27, 2026, as previously reported by HCPLive.

Chalasani N, Lazas D, Casciato P, et al. Saroglitazar magnesium achieves resolution of steatohepatitis without worsening fibrosis in patients with MASH: results of a randomized, placebo-controlled phase 2b trial (EVIDENCES X). Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

Zydus Lifesciences. Zydus announces positive topline results from completed EVIDENCES-X phase II(b) clinical trial of saroglitazar Mg in MASH. Published August 31, 2026. Accessed November 6, 2026. 

https://www.zyduslife.com/investor/admin/uploads/21/83/Zydus-Announces-Positive-Topline-Results-from-Completed-EVIDENCES-X-Phase-II(b)-Clinical-Trial-of-Saroglitazar-Mg-in-MASH.pdf

Livingston R. FDA grants Priority Review to saroglitazar NDA for primary biliary cholangitis. HCPLive. Published May 28, 2026. Accessed November 6, 2026. 

https://www.hcplive.com/view/fda-grants-priority-review-to-saroglitazar-nda-for-primary-biliary-cholangitis

In the phase 2b EVIDENCES X trial, saroglitazar 4 mg resolved MASH without worsening fibrosis in 39.1% of patients vs 13.7% with placebo at 52 weeks.

Hepatology

MASH / MASLD

The HCPLive MASH & MASLD page is a comprehensive resource for clinical news and insights on metabolic dysfunction-associated steatotic liver disease and steatohepatitis. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for fatty liver disease, steatohepatitis, and more.

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Saroglitazar Resolves MASH Without Fibrosis Worsening: EVIDENCES X

David Singh, MBBChir, MA (Cantab), MRCP, MD, FBPhS, FERS, is a professor of Clinical Pharmacology & Respiratory Medicine at the University of Manchester and is the medical director of the Medicines Evaluation Unit (MEU).

Dave Singh, MB B.Chir, MA (Cantab), MRCP, MD, FBPhS, FERS

The 2027 GOLD report mostly refines existing guidance, adding more on the evidence and importance of mucus plugs.

Revised wording around early, mild, and pre-COPD aims to encourage earlier diagnosis and trials before major lung damage.

GOLD keeps unlicensed biologics such as tozorakimab out of its algorithm, so clinicians should follow their local licensing.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) presented its 2027 report at the GOLD 2026 COPD International Conference in Philadelphia, where Alvar Agustí, MD, and Claus F. Vogelmeier, MD, reviewed the annual update to its global strategy related to 

 diagnosis, management, and prevention.¹

The update comes about as late-stage biologic data outpace regulatory approval. Tozorakimab, an anti-interleukin (IL)-33 monoclonal antibody, reduced annualized moderate to severe exacerbations among former smokers by 29% and 34% compared with placebo in the replicate phase 3 OBERON and TITANIA trials, published in 

Results for astegolimab, an anti-ST2 monoclonal antibody blocking IL-33 signaling, were mixed. The phase 2b ALIENTO trial met its primary end point with a 15.4% reduction in annualized exacerbation rate, while the phase 3 ARNASA trial showed a numerical 14.5% reduction without statistical significance, according to Roche.³

Neither agent is licensed for COPD, creating a gap between published evidence and prescribing access for clinicians reading the 2027 report. Outside of biologic drugs, the report’s refinements touch on clinical questions common in practice, including the interpretation of mucus plugs and the definitions used for earlier forms of disease.

Dave Singh, MB BChir, MA (Cantab), MRCP, MD, FBPhS, FERS, known for his work as professor of clinical pharmacology and respiratory medicine at the University of Manchester and as a member of the GOLD Science Committee, has led more than 300 clinical trials of new treatments for asthma and COPD as medical director of the Medicines Evaluation Unit. Singh sat down with 

 to discuss the 2027 report’s key refinements and how clinicians should interpret biologic evidence GOLD acknowledges but does not yet recommend:

: What are your overall reflections on the GOLD 2027 updates?

 The GOLD 2027 updates have included, I think, in many cases a refinement of the information that could better help the clinician. Maybe not a groundbreaking advance based on studies in the last year, but a chance to better describe areas that are common in clinical practice. So, for instance, mucus plugging. There’s been more information on that, and we’ve had a chance to put more into the document about the evidence and importance of mucus plugs.

There’s obviously been some adjustment to the language around definitions of early, mild, and pre-COPD [UNCLEAR — please review]. This often causes confusion, and one of the reasons we focused on that relates to clinical trials, because we often do clinical trials in patients at later stages in the natural history of the disease, and we really want to move to younger ages, people who are at higher risk, and try to do these studies before there’s too much lung damage. So I personally think that’s an important area for people to pay attention to: to diagnose people earlier and to encourage the generation of more evidence.

: How should clinicians interpret biologic evidence GOLD acknowledges in the 2027 report text but excludes from the treatment algorithm pending approval?

 In terms of biologics, we, for example, have the data on astegolimab and tozorakimab. Those clinical trials are published, but those medicines don’t have a license. Tozorakimab has 2 positive phase 3 studies, and we hope it will get a license. But GOLD takes the approach of not putting them in the treatment algorithm until clinicians can prescribe them.

In terms of how clinicians should move forward, I think in your locality, you rely on your licensing procedure. So, for example, if tozorakimab becomes licensed in country X, then a clinician is able to use it according to the license.

Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Singh had no relevant financial disclosures of note.

Agustí A, Vogelmeier CF. 2027 GOLD report and review. Presented at: GOLD 2026 COPD International Conference; November 6, 2026; Philadelphia, PA.

Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to prevent COPD exacerbations. 

. Published online September 8, 2026. doi:10.1056/NEJMoa2606998

Roche. Roche provides update on astegolimab in chronic obstructive pulmonary disease. Published July 21, 2025. Accessed November 6, 2026. 

https://www.roche.com/media/releases/med-cor-2025-07-21

Dave Singh, MD, reflects on 2027 GOLD report refinements, from mucus plugs and early COPD to biologics awaiting regulatory approval.

COPD

COPD condition center page, resources on the topics of medical news and expert insight into chronic obstructive pulmonary disease can be found. Content includes articles, interviews, videos, podcasts, and breaking news on COPD research, treatment, and drug development.

Pulmonology

Infectious Disease condition center page is a comprehensive resource for clinical news and insights on respiratory health. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for asthma, COPD, interstitial lung disease, COVID-19, and more.

Q&A: Discussing 2027 GOLD Report Updates in COPD, With David Singh, MD

Zobair Younossi, MD, MPH, is chairman of the Global NASH/MASH Council and professor and chairman of Beatty Liver and Obesity Research at Inova Health System.

Resmetirom (Rezdiffra) was associated with modest improvements in disease-related worry and health distress among patients with compensated 

 cirrhosis, according to a post hoc analysis of the phase 3 MAESTRO-NAFLD-1 trial presented at 

Zobair Younossi, MD, MPH, chairman of the Global NASH/MASH Council, presented the findings and discussed them in an interview with 

. He described health-related quality of life (HRQL) as central to the comprehensive burden of MASH, alongside clinical and economic burden, and noted quality of life tends to worsen as liver disease advances.

Resmetirom and Quality of Life in MASH Cirrhosis

How Did Resmetirom Affect Quality of Life in MASH Cirrhosis?

The analysis included 160 patients with compensated MASH cirrhosis from MAESTRO-NAFLD-1 who completed HRQL assessments, including the Liver Disease Quality of Life (LDQoL), Chronic Liver Disease Questionnaire-MASH (CLDQ-MASH), CLDQ-MASH Symptom Questionnaire, and Work Productivity and Activity Impairment (WPAI) questionnaires.

 At baseline, sleep- and fatigue-related domains showed the greatest impairment.

After 52 weeks of resmetirom 80 mg, patients showed improvement in the CLDQ-MASH Worry domain (mean, +0.30; 

 = .001), with a trend toward improvement in LDQoL Health Distress (+3.44; 

 = .051). Improvements in both domains were more pronounced among patients with portal hypertension.

Patients achieving a relative decrease of at least 25% in liver stiffness by vibration-controlled transient elastography (VCTE) reported improvement in bleeding gums and joint pain symptoms. The authors concluded resmetirom was associated with modest but significant improvements in mental health distress and worry, as well as relief of specific symptoms.

Younossi noted the findings extend earlier analyses. Previous MAESTRO-NAFLD-1 data showed improvements in Worry and Health Distress scores among patients with and without cirrhosis. Additionally, prior MAESTRO-NASH data linked histologic response to HRQL gains in noncirrhotic MASH.

What Do PROs Add to MASH Treatment Decisions?

Younossi said the link between liver stiffness response and symptom improvement offers clinicians added confidence in the real-world benefit of fibrosis-directed therapy. He emphasized the goal of treatment extends beyond surrogate markers to how patients feel and how long they live.

“Patients should feel better and should live longer, right? So it’s about quality of life and quantity of life,” Younossi said.

He also highlighted the absence of worsening in HRQL domains without improvement as a signal of tolerability, contrasting resmetirom with interferon-based hepatitis C therapy, which substantially impaired quality of life. Younossi cautioned year-long trials remain short for capturing the full effect on patient-reported outcomes (PROs).

“These trials are short, even if they’re a year long. If you continue these drugs longer and you continue to improve fibrosis, I suspect the quality of life will improve even more,” he said.

In clinical practice, Younossi recommended a minimum symptom assessment focused on fatigue, distinguishing pathologic fatigue unrelieved by rest from normal fatigue. He also advised screening for comorbidities such as depression, which can overlap with fatigue.

Resmetirom is approved by the US Food and Drug Administration for adults with noncirrhotic MASH and moderate to advanced fibrosis (F2–F3). MAESTRO-NAFLD-1 was a 52-week phase 3 safety trial including an open-label cohort of patients with compensated MASH cirrhosis.

Editors’ Note: Younossi reports relevant disclosures with Intercept, Boehringer Ingelheim, Ipsen, BMS, GSK, Novo Nordisk, Madridgal, Merck, Aligos, Akero, Sanofi, and others.

Younossi Z, Nader F, Taub R, et al. Impact of resmetirom on health-related quality of life, work productivity, and disease-specific symptoms in compensated MASH cirrhosis. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

Younossi Z. Health-related quality of life improvements with resmetirom, with Zobair Younossi, MD, MPH. HCPLive. Published November 11, 2025. Accessed November 6, 2026. 

https://www.hcplive.com/view/health-related-quality-life-improvements-resmetirom-zobair-younossi-md-mph

Younossi Z. Zobair Younossi, MD, MPH: resmetirom’s impact on health-related quality of life in MASH. HCPLive. Published October 9, 2024. Accessed November 6, 2026. 

https://www.hcplive.com/view/zobair-younossi-md-mph-resmetirom-impact-health-related-quality-life-mash

Harrison SA, Taub R, Neff GW, et al. Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2023;29(11):2919-2928. doi:10.1038/s41591-023-02603-1

Videos

Zobair Younossi, MD, MPH, discusses MAESTRO-NAFLD-1 data linking resmetirom to improved worry and health distress scores in compensated MASH cirrhosis.

Quality of Life With Resmetirom in MASH Cirrhosis: Zobair Younossi, MD, MPH

Retrospective data show semaglutide 2.4 mg was linked to lower liver enzymes, weight, and HbA1c in MASH, including vs resmetirom in a real-world cohort.

Semaglutide Linked to Lower Liver Enzymes, Weight in Real-World MASH Data

Dr. Norah Terrault is a transplant hepatologist, the Neil Kaplowitz Professor of Medicine and Chief of Gastrointestinal and Liver Diseases Division at the Keck School of Medicine of University of Southern California in Los Angeles, California.


Quantitative HBsAg testing now determines which patients on antiviral therapy may qualify for bepirovirsen, a finite add-on treatment for chronic hepatitis B.

Hepatitis C

Hepatitis C page, resources on the topics of medical news and expert insight into HCV can be found. Content includes articles, interviews, videos, podcasts, and breaking news on hepatitis C virus research, treatment, and drug development.

Bepirovirsen Patient Selection in Hepatitis B: The Role of HBsAg Testing, With Norah Terrault, MD, MPH

Marlyn Mayo, MD, is a professor of internal medicine at UT Southwestern Medical Center.

Marlyn Mayo, MD, discusses long-term seladelpar data linking IL-31 reductions to PBC pruritus improvement and why the cytokine is not ready to guide treatment.

Cholangitis

cholangitis page, resources on the topics of medical news and expert insight into cholangitis can be found. Content includes articles, interviews, videos, podcasts, and breaking news on research, treatment, and drug development in PBC, PSC, and more!

Seladelpar Linked to Sustained IL-31 Reduction in PBC in New Study

ALA Spokesperson and professor at Baylor College of Medicine.

Francesca Polverino, MD, PhD, explains how oxidized and reduced IL-33 drive mucus dysfunction and inflammation in COPD, and why mucus plugs matter.

Q&A: Why IL-33 Matters for Mucus Plugs, Inflammation in COPD

Phase 2 ENHANCE and ENRICH data show BRII-179 plus elebsiran and peginterferon increased HBsAg loss in chronic HBV, with priming halving peginterferon use.

Triple Therapy More Than Doubles HBsAg Loss vs Peginterferon in HBV

Pooled phase 2 data show fazirsiran 200 mg cut intrahepatic Z-AAT by about 90% vs placebo in AATD liver disease, with stable lung function through the OLE.

Latest News

Lp(a) HORIZON Shows Pelacarsen Lowers Lp(a) 78% But Not Cardiovascular Events

ZEUS: Ziltivekimab Fails to Reduce Cardiovascular Events in ASCVD and CKD

Saroglitazar Resolves MASH Without Fibrosis Worsening: EVIDENCES X

Q&A: Discussing 2027 GOLD Report Updates in COPD, With David Singh, MD

Quality of Life With Resmetirom in MASH Cirrhosis: Zobair Younossi, MD, MPH