{
  "abstract": "We thank Dr Amjad and Dr Thomas for their interest in our recent study on statin use in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).1 2 Their letter raises several thoughtful concerns about the study’s design, interpretation and broader implications. Our cohort was a liver-specific population, comprising patients with MASLD undergoing serial vibration-controlled transient elastography assessments. Randomised controlled trials (RCTs) typically include more selectively defined populations and have shorter follow-up durations. Second, we acknowledge that adjusting for atherosclerotic cardiovascular disease (ASCVD) risk scores is a valid approach. However, since ASCVD is a composite of overlapping cardiometabolic factors, adjusting for both the composite score and individual variables may introduce collinearity. This issue is particularly relevant in liver-specific cohorts, where such scores are not routinely used as covariates. Third, we acknowledge the potential for immortal time bias. To mitigate this, we excluded patients with under 12 months of follow-up and defined statin exposure by sustained use. However, these challenges are inherent in retrospective pharmacoepidemiology and complicated by real-world medication use. Fourth, while statin users often have hyperlipidaemia or high ASCVD risk, the independent impact of these factors on liver-related outcomes in MASLD is unclear. It is plausible that the potential adverse effects of these risks were attenuated or even outweighed by the therapeutic benefits of statins. Therefore, the lower event rates among statin users likely reflect treatment effects rather than reverse causality or selection bias. Fifth, while comparing new statin users to non-users with proper time-zero alignment would improve causal inference, this was not feasible due to many patients already using statins at baseline. Although RCTs offer definitive evidence, withholding statins from high-risk patients poses ethical issues. Future studies emulating target trials may provide a practical solution.",
  "authors": [
    {
      "affiliations": [
        "MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China",
        "Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China"
      ],
      "name": "Xiao-Dong Zhou"
    },
    {
      "affiliations": [
        "Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China",
        "State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China"
      ],
      "name": "Vincent Wai-Sun Wong"
    },
    {
      "affiliations": [
        "MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China",
        "Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China"
      ],
      "name": "Ming-Hua Zheng"
    }
  ],
  "title": "Reconsidering statins in MASLD: beyond cardiovascular protection to multisystem benefit",
  "uid": "a6bb5be9-1456-5e74-b91a-9dd0fc44ec20"
}