This decision is based on a reassessment of the current need for this study, impracticality of opening study sites in outpatient clinics due to administrative and legal constraints.

A multicenter real-world observational study of the prevalence, diagnostic pathways, and clinical characteristics of lysosomal acid lipase deficiency in pediatric and adolescent risk groups in the Russian Federation (HELIOS)

Inclusion Criteria

Age 12 months to 18 years (infantile form is out of scope for the analytical component);

Patients not previously evaluated for LAL-D (test-naïve);

Presence of at least one (1) of the following major criteria:

Unexplained hepatomegaly and/or splenomegaly persisting ≥3 months;

Persistent hypertransaminasemia: ALT or AST ≥ 1.5× upper limit of normal (ULN) after exclusion of common metabolic/infectious causes;

Atherogenic dyslipidemia: elevated total cholesterol (TC), elevated LDL-C and/or reduced HDL-C (LDL-C >95th percentile for age and sex or HDL-C <5th percentile); triglycerides not markedly elevated.

Presence of at least two (2) of the following minor criteria:

Chronic diarrhea or intermittent unstable bowel movements;

Abdominal pain and/or bloating;

Loss of appetite;

Nausea, vomiting;

Belching, heartburn;

Weight loss, growth deceleration (height/weight lag behind peers);

Weakness, easy fatigability;

Recurrent aphthous stomatitis (oral mucosal ulcers);

Splenomegaly (if not counted as a major criterion);

Anemia and/or thrombocytopenia;

Evidence of steatosis/fibrosis by ultrasound/elastography/ liver examination by MRI;

Suboptimal response to lipid-lowering therapy: after ≥3 months of optimized therapy (maximally tolerated statin ± ezetimibe with documented adherence), LDL-C reduction <50% from baseline OR on-treatment LDL-C remains above guideline targets (e.g., ≥3.4 mmol/L without very high risk or ≥2.6 mmol/L in very-high-risk settings), despite therapy [12].

Family history of FH-like dyslipidemia without typical FH genetic markers (if available).

Provision of signed and dated written informed consent by parent(s)/legal guardian(s) (and the child, where applicable).

Exclusion Criteria

Confirmed alternative etiology fully explaining liver disease/dyslipidemia (e.g., hepatitis A/B/C, autoimmune hepatitis by diagnostic criteria) without grounds to suspect LAL-D;

Wolman disease;

Long-term use of systemic corticosteroids which is defined as oral or parenteral continuous administration during ≥14 days in the last 6 months prior to the inclusion.

Pediatric participants (aged 12 months to 18 years) identified by predefined pediatric red flags for LAL-D and undergoing a standardized diagnostic workflow will be enrolled in in pediatric hepatology, gastroenterology, and cardiology/lipid clinics.

The study population is planned to comprise 1,200 participants in approximately 50 pediatric clinical centers across multiple regions of the Russian Federation. Eligible patients will be enrolled consecutively at each site to minimize selection bias at each site.

Enrollment will occur only after the parent(s)/legal guardian(s) (and the child, where applicable) provide informed consent/assent following a detailed explanation of the study objectives and procedures by the study physician.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.