Sebelipase alfa normalizes liver size and eliminates abdominal pain in patients with lysosomal acid lipase deficiency (LAL-D), Dr. Florence Lacaille reported in an editorial published in the Journal of Hepatology and based on her clinical experience. Liver biopsy is the ideal method for tracking the evolution of liver fibrosis, she wrote.

LAL-D causes cholesteryl esters to accumulate in the lysosomes of tissues, primarily in the liver, that play a role in the endocytosis and degradation of lipoproteins. Myofibroblast proliferation or cholesteryl ester crystals stimulate liver fibrosis, which can activate inflammasomes.

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The first-line treatment for LAL-D is enzyme replacement therapy, namely sebelipase alfa. Lacaille wrote, “This highly efficient treatment has been used for more than 10 years; however, treated children remain susceptible to digestive and hepatic symptoms; thus, the metabolic defect is corrected to an acceptable, but not normal level.” 

Lacaille cited a landmark study that established the safety and efficacy of sebelipase alfa. The study found that sebelipase alfa treatment stabilized or improved liver disease in the 59 patients studied. The cohort is large, considering that LAL-D is a rare disease, and two-thirds of the patients were aged less than 18 years. 

The study demonstrated improvements in dyslipidemia and transaminases, with MRI showing reduced hepatic fat content. Liver biopsies of 12 patients, with a 1-year interval, showed stabilization or improvement in liver fibrosis. 

Lacaille argued that standard criteria are needed to measure the efficacy of sebelipase alfa treatment, since it is expensive and administered bimonthly in a hospital setting.

“Therefore, before initiating this difficult, life-long therapy, which aims to slow or stop the progression of fibrosis, we need criteria for assessing disease progression, particularly in young people,” she wrote. “We strongly suggest performing a liver biopsy: if the fibrosis is absent or mild, a re-assessment should be considered 3 to 5 years later, to evaluate the rate of progression.”


Lacaille F. When deficient lysosomes make the liver fatty and the arteries greasy: how to treat, whom and whenJ Hepatol. 2021;S0168-8278(21)02240-6. doi:10.1016/j.jhep.2021.12.002