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Background and purpose of the study <p>Liver inflammation and fibrosis are the key determinants of long-term adverse outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, identifying progressive forms of MASLD is crucial. Lysosomal acid lipase (LAL), a central enzyme in intracellular lipid hydrolysis, has been reported to be reduced in MASLD and linked to liver injury.</p> Aim <p>To evaluate whether baseline LAL activity predicts long-term progression of MASLD.</p> Methods <p>We prospectively followed up 144 adults with biopsy-proven MASLD for a minimum of 5&#xa0;years (median 8.1). All patients underwent a FibroScan® at baseline and follow-up and 94 of them also had paired liver biopsies. LAL activity (expressed as LAL/platelet-LAL/ptls) was measured on dried blood spots. Liver disease progression was defined by meeting of the histological endpoint at follow-up (i.e., development of MASH and/or NAS worsening ≥ 1 point and/or fibrosis progression ≥ 1 stage) or by liver stiffness measurement (LSM) worsening at Fibroscan.</p> Results <p>Among the 94 biopsied patients, 26% met the composite histological endpoint and had significantly lower baseline LAL/ptls ratio, higher HOMA-IR, CAP and LSM. In particular, lower LAL/ptls was strongly related to the worsening of inflammation. In multivariate analysis, lower ln-transformed LAL/ptls ratio independently predicted histological progression (OR 0.51, 95% CI 0.04–0.60, <i>p</i> = 0.018). No association emerged between baseline LAL/ptls ratio and non-invasive progression by FibroScan.</p> Conclusions <p>Lower LAL/ptls ratio identifies MASLD patients at increased risk of histological progression and complements non-invasive tools by reflecting biological pathways linked to inflammation.</p> Graphical Abstract <p>Progression of MASLD and levels of Lysosomal acid lipase activity</p> <p></p>

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Low lysosomal acid lipase activity is associated with histological progression of metabolic dysfunction-associated steatotic liver disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月22日

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  • Rosa Lombardi,
  • Felice Cinque,
  • Annalisa Cespiati,
  • Cristina Bertelli,
  • Giuseppina Pisano,
  • Giovanna Oberti,
  • Erika Fatta,
  • Jaqueline Currà,
  • Emma Calzavara,
  • Francesca Alletto,
  • Carola Garavaglia,
  • Giulia Cincotto,
  • Anna Ludovica Fracanzani,
  • Monica Gomaraschi

摘要

Background and purpose of the study

Liver inflammation and fibrosis are the key determinants of long-term adverse outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, identifying progressive forms of MASLD is crucial. Lysosomal acid lipase (LAL), a central enzyme in intracellular lipid hydrolysis, has been reported to be reduced in MASLD and linked to liver injury.

Aim

To evaluate whether baseline LAL activity predicts long-term progression of MASLD.

Methods

We prospectively followed up 144 adults with biopsy-proven MASLD for a minimum of 5 years (median 8.1). All patients underwent a FibroScan® at baseline and follow-up and 94 of them also had paired liver biopsies. LAL activity (expressed as LAL/platelet-LAL/ptls) was measured on dried blood spots. Liver disease progression was defined by meeting of the histological endpoint at follow-up (i.e., development of MASH and/or NAS worsening ≥ 1 point and/or fibrosis progression ≥ 1 stage) or by liver stiffness measurement (LSM) worsening at Fibroscan.

Results

Among the 94 biopsied patients, 26% met the composite histological endpoint and had significantly lower baseline LAL/ptls ratio, higher HOMA-IR, CAP and LSM. In particular, lower LAL/ptls was strongly related to the worsening of inflammation. In multivariate analysis, lower ln-transformed LAL/ptls ratio independently predicted histological progression (OR 0.51, 95% CI 0.04–0.60, p = 0.018). No association emerged between baseline LAL/ptls ratio and non-invasive progression by FibroScan.

Conclusions

Lower LAL/ptls ratio identifies MASLD patients at increased risk of histological progression and complements non-invasive tools by reflecting biological pathways linked to inflammation.

Graphical Abstract

Progression of MASLD and levels of Lysosomal acid lipase activity