Long-term clinical outcomes in lysosomal acid lipase deficiency: Fibrosis regression with sebelipase alfa therapy
Bibliographic record
Abstract
Background: gene, leading to accumulation of cholesterol esters and triglycerides, particularly in the liver and spleen. The disease manifests as either severe infantile Wolman disease or the milder chronic cholesteryl ester storage disease (CESD). Enzyme replacement therapy (ERT) with sebelipase alfa (Kanuma) has shown potential in reducing hepatic and lipid abnormalities. Methods: We present a case of a 41-year-old female with biopsy-confirmed CESD and cirrhosis, diagnosed in childhood. She was enrolled in the 2015 phase 3 clinical trial for Kanuma and continued on biweekly ERT thereafter. Serial liver imaging and biopsies were performed between 2002 and 2023 to monitor fibrosis progression or regression. Results: Initial fibrosis staging progressed to cirrhosis (Metavir F4) by 2016. Despite persistently elevated lipid levels (LDL 3.81 mmol/L in 2025), MR elastography and liver biopsy in 2023 demonstrated regression of fibrosis to stage 1-2 and histologic signs of cirrhosis reversal while she was taking Kanuma. This occurred in the absence of significant hepatic steatosis or iron overload. Conclusions: This case highlights the potential for long-term Kanuma therapy to reverse liver fibrosis in LAL-D, even with ongoing dyslipidemia. While early initiation of ERT may optimize outcomes, this case supports its continued use in advanced disease stages. Further research is needed to assess the long-term metabolic and histologic benefits of ERT in LAL-D patients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".