Why aspirin in MASLD is on clinicians radar

Metabolic dysfunction-associated steatotic liver disease is prevalent, progressive in a subset of patients, and tightly linked to cardiometabolic comorbidities. For many, the first question is whether MASLD itself is a reason to start Aspirin, or whether its role remains confined to well-established cardiovascular indications. A recent multi-institutional analysis available on PubMed associates aspirin use alone with reduced all-cause mortality and fewer liver-related events over approximately three years. The design is observational, so confounding by indication and other biases are possible, and causation cannot be claimed. Decisions should be anchored in the patient in front of you, not in population-level associations alone.

The biological plausibility of benefit exists but does not substitute for causal evidence. Platelet activation, microthrombosis in the hepatic microcirculation, and sterile inflammation are implicated in steatohepatitis and fibrogenesis, and antiplatelet effects could theoretically modulate these pathways. Chemopreventive signals related to Hepatocellular Carcinoma have also been discussed in other contexts, though heterogeneity in populations and exposure definitions limits generalization. Importantly, bleeding risk is not uniform and often concentrates among those with advanced fibrosis, portal hypertension, or concomitant anticoagulation. Clinicians must weigh possible long-term hepatic benefits against near-term bleeding harms.

In practice, this means maintaining a clear distinction between hepatic and cardiac drivers of therapy. Aspirin is a cornerstone of secondary prevention for atherosclerotic cardiovascular disease and remains a consideration for select primary prevention scenarios when net benefit is favorable. In MASLD, the liver signal may be additive to cardiovascular value for some patients, but it should not eclipse core safety checks. The intention should be to refine risk stratification so that any decision aligns with both hepatic stage and the patient’s cardiovascular risk profile. Ultimately, the care plan should be co-produced with the patient, reflecting preferences and tolerance for bleeding risk.

What the analysis signals

The multi-institutional dataset reports that aspirin use alone was linked to fewer liver-related events and lower all-cause mortality over a three-year horizon. While the direction of effect is encouraging, observational signals are susceptible to healthy-user effects, differential surveillance, and residual confounding. Dose, adherence, and indication are not always fully captured, and competing risks can complicate interpretation. Association is not proof of benefit, but it can guide hypothesis generation and frame pragmatic conversations with patients who already have reasons to consider aspirin for their cardiovascular profile. The key is to translate the signal into decisions that guard against foreseeable harm.

Several clinically relevant details stand out for translation. First, the benefit signal does not tell us who, within MASLD, is most likely to gain net benefit from aspirin when bleeding risk is nontrivial. Second, time-related biases, such as immortal time bias or depletion of susceptibles, may inflate apparent benefits if not tightly addressed in the analysis. Third, bleeding outcomes are often rarer but clinically weighty, so even small absolute increases can materially alter net value. Finally, the pathway from platelet inhibition to fewer liver-related complications is plausible but remains an inference rather than a demonstrated causal chain in MASLD.

Populations who may benefit now

Where aspirin is already indicated for secondary prevention of atherosclerotic events, the question shifts from whether to initiate to whether to continue, given hepatic context. Many MASLD patients carry high burden of cardiometabolic risk, and a careful accounting of Cardiovascular Disease status is essential. For Secondary Prevention, benefit generally outweighs bleeding risk in the absence of advanced portal hypertension or recent major gastrointestinal bleeding. In primary prevention, the calculus is more nuanced, especially in older adults or those with multiple bleeding risk factors. Any hepatic signal should be considered supportive but not determinative in this setting.

For Primary Prevention, age, blood pressure control, diabetes status, and baseline bleeding risk deserve close attention. The presence of advanced fibrosis or known varices should trigger a pause and a deeper conversation before starting aspirin for primary prevention alone. If baseline bleeding risk is high, postponing initiation or selecting alternative cardiometabolic risk-reduction strategies is prudent. On the other hand, patients with low bleeding risk, no features of advanced liver disease, and high predicted cardiovascular risk may find the balance more favorable. The process should be anchored in Shared Decision-Making that integrates values, goals, and risk tolerance.

How this interacts with liver care plans

Beyond the decision to use aspirin, MASLD care plans should continue to prioritize weight reduction, glycemic control, blood pressure targets, and statin therapy when indicated. Statins are safe across the spectrum of hepatic steatosis and remain underused despite proven cardiovascular benefit. Fibrosis staging guides surveillance, hepatocellular carcinoma screening, and portal hypertension evaluation, and these pathways operate independently of aspirin. Integrating aspirin into the plan should not disrupt these core elements of MASLD management. Rather, it should complement them where appropriate and recede where bleeding risk dictates caution.

Coordination among primary care, endocrinology, and hepatology improves the safety net for patients navigating both hepatic and cardiovascular risks. When aspirin is continued for cardiovascular reasons, the hepatology care plan can proactively address bleeding modifiers, including Helicobacter pylori testing and eradication, alcohol use counseling, and gastroprotective strategies where indicated. Communication about planned endoscopic procedures or biopsy can prevent avoidable complications. Conversely, if aspirin is withheld, documentation of the rationale and a plan to revisit the decision after staging or risk factor modification preserves clinical flexibility. The guiding principle is to avoid irreversible harms while remaining responsive to new information.

Bleeding risk and cirrhosis context

Bleeding risk is the hinge on which many aspirin decisions turn in MASLD. Age, prior gastrointestinal bleeding, renal dysfunction, uncontrolled hypertension, concomitant anticoagulants, and history of peptic ulcer disease raise risk meaningfully. Cirrhosis amplifies this baseline risk through hemodynamic changes, variceal formation, and coagulopathy. In many cases, the presence of clinically significant portal hypertension shifts the balance against aspirin for primary prevention. A structured approach can identify patients who face a high near-term bleeding risk that outweighs any plausible hepatic benefit signal.

Risk is not binary, and multiple levers can lower it without forfeiting potential benefit. Dyspepsia management, Helicobacter pylori eradication when present, and careful blood pressure control reduce upper gastrointestinal bleeding. Minimizing concurrent nonsteroidal anti-inflammatory drug exposure further decreases risk. For selected patients with clear indications for antiplatelet therapy, gastroprotection with Proton Pump Inhibitors can be considered after weighing benefits and risks. Even with these strategies, advanced hepatic disease remains a strong cautionary signal for aspirin use.

Cirrhosis, portal hypertension, and varices

Staging cirrhosis and assessing for Portal Hypertension are central to aspirin decisions in MASLD. The presence of varices, recent variceal bleeding, or decompensation events like ascites or encephalopathy heavily disfavors initiation for primary prevention and may even prompt reevaluation of ongoing therapy. In patients with compensated advanced chronic liver disease, noninvasive markers and elastography help determine whether to proceed with endoscopic screening. When varices are present, nonselective beta-blockers or endoscopic band ligation take precedence, and any antiplatelet therapy requires careful multidisciplinary coordination. A conservative stance is justified until hepatic hemodynamics are adequately characterized.

Laboratory and noninvasive staging

Baseline laboratory data and noninvasive assessment inform bleeding and progression risk. Simple scores such as FIB-4 help triage patients into low, indeterminate, or high fibrosis risk categories and can trigger elastography or hepatology referral. Thrombocytopenia, often a surrogate marker for portal hypertension, flags increased bleeding risk; the finding of Thrombocytopenia should prompt more cautious decision-making. Coagulation indices, transaminases, albumin, and bilirubin provide additional context for both hepatic function and procedure planning. Together, these data points refine the risk-benefit calculus for aspirin.

• Confirm MASLD and stage fibrosis with noninvasive tools before attributing risk to the liver alone.
• Screen for portal hypertension and varices when advanced disease is suspected or confirmed.
• Characterize bleeding risk factors systematically, including prior bleeding and concomitant medications.
• Reassess cardiovascular indications at each step to avoid therapeutic inertia or overcorrection.
• Document the decision and the plan to revisit as new information emerges.

Medication review and alternatives

A thorough medication review often reveals modifiable contributors to bleeding risk. Over-the-counter NSAIDs, dual antiplatelet therapy without a current indication, or unrecognized anticoagulant use can tilt the balance against aspirin. Where cardiovascular risk reduction is needed, optimizing statins, blood pressure control, SGLT2 inhibitors or GLP-1 receptor agonists for diabetes, and smoking cessation should be prioritized. Gastroprotection strategies can be considered when antiplatelet therapy is essential, but they do not erase the risks associated with varices or decompensation. The safest net benefit emerges when the full therapeutic ecosystem is aligned.

From association to decision: a pragmatic framework

Translating observational signals into individual care plans requires a disciplined, repeatable process. Start by separating the hepatic signal from the cardiovascular indication question, then layer in bleeding risk and patient values. The objective is to converge on the choice that yields the highest probability of benefit at the lowest acceptable risk, given current information. Recognize that uncertainty remains, and build a plan that is reversible, monitorable, and ready to incorporate new evidence. The framework below supports consistent, patient-centered decisions.

Risk stratification steps

• Assess cardiovascular indications first: if secondary prevention is present, default toward continuation unless bleeding risk is prohibitive; in primary prevention, estimate absolute risk and consider alternatives.
• Stage liver disease: use noninvasive tests, elastography, and, if needed, hepatology referral to determine fibrosis stage and portal hypertension risk.
• Characterize bleeding risk: prior gastrointestinal bleeding, peptic ulcer history, age, renal function, blood pressure control, thrombocytopenia, and concomitant antithrombotics are key inputs.
• Address modifiable risks: treat H. pylori when present, minimize NSAIDs, optimize blood pressure and glycemic control, and consider gastroprotection when appropriate.
• Co-produce the decision: discuss expected benefits, potential harms, uncertainties, and how the plan will be monitored and revised.

This stepwise approach shifts the focus from the population signal to the individual risk profile. It encourages attention to changeable factors and avoids reflexive prescribing or deprescribing. It also clarifies when more information is needed before deciding, such as pending elastography or endoscopy. By anchoring to structured steps, clinicians reduce variability and improve transparency. Patients can see how their specific risks and goals shape the recommendation.

Communicating uncertainty and values

Patients deserve direct, jargon-free explanations of what the association means and does not mean. A balanced script might say that aspirin was linked with fewer liver-related events and lower mortality in people like them, but it has not been proven to cause these benefits and can increase bleeding. Because their personal bleeding risk depends on liver stage and other factors, the team will check those and revisit the decision. The plan can also emphasize that many effective liver and cardiovascular strategies do not involve aspirin. This framing fosters partnership and prevents false certainty.

Monitoring and follow-up

For patients who use aspirin, monitoring protects against preventable harm. Reinforce early recognition of melena, hematemesis, syncope, or symptomatic anemia and provide clear instructions on when to seek urgent care. Periodic review of hemoglobin, iron indices if indicated, and liver-related labs supports safety and disease tracking. Scheduled reassessment of hepatic staging and cardiovascular risk ensures that the plan evolves with the patient’s profile. If bleeding complications occur, deprescribing should be prompt and coordinated, with re-evaluation once risks are stabilized.

What evidence would change practice

Practice-changing evidence would come from randomized trials in MASLD that compare low-dose aspirin with placebo, stratified by fibrosis stage and portal hypertension status. Primary endpoints should include liver-related events and all-cause mortality, with rigorous bleeding outcome capture and adjudication. Dose, duration, and discontinuation strategies matter, as does clarifying interaction with gastroprotective measures and variceal prophylaxis. Pragmatic trial designs embedded in routine care could accelerate answers while reflecting real-world patients and adherence patterns. Until then, observational associations should inform but not dictate prescribing.

In synthesis, aspirin’s association with fewer liver-related events and lower mortality in MASLD is a meaningful signal that sits alongside, not above, established cardiovascular indications and individual bleeding risk. The safest path is to maintain aspirin where cardiovascular benefit is clear, to defer initiation when bleeding risk is high or hepatic staging is uncertain, and to co-create decisions through structured risk assessment and shared decision-making. As evidence matures, clinicians should remain ready to recalibrate. For now, a pragmatic, patient-centered framework is the most reliable way to translate this emerging signal into better outcomes.