Liver disease can progress rapidly in LAL-D, unlike progression in patients with NAFLD/NASH.⁵

In a meta-analysis, in patients with NAFLD or NASH, the average progression of fibrosis from stage 0 to stage 1 took 14.3 years [95% CI, 9.1-50.0 years] and 7.1 years [95% CI, 4.8-14.3 years], respectively.^5,e

NOTE: These studies represent individual publications using different populations of patients. Data are not directly comparable.

^a Clinical study of patients with LAL-D (N=66; age range, 4-58 years; mean age, 16 years). Graph shows data from biopsied patients (n=32 of 66), and includes patients with a baseline Ishak score ≥3.^2,4,6

^b Clinical study (N=67; age range, 5.5-11.3 years) and retrospective longitudinal cohort study (N=66; age range, 3.2-19.6 years) in pediatric patients with NAFLD. Graph shows data from biopsied patients (n=96 of 133), and includes patients with stage 2-3 fibrosis or cirrhosis.^6-8

^c Case review (N=135; age range, 1-82 years at last report) and observational study (N=48; age range, 6-48 years at time of consent) of pediatric and adult patients with LAL-D.^1,2,9

^d No instances of liver transplant were reported for 1 of the studies.⁹

^e Systemic review and meta-analysis of the rate of fibrosis progression in adult patients with biopsy-proven NAFLD (N=81) or NASH (N=21) and stage 0 fibrosis at baseline who underwent paired biopsies ≥1 year apart.⁸

^a Adjusted RR for incidence of CHD by lipid category in the pooled Framingham Heart Study dataset (n=3101 women, mean age 49 years; n=2693 men, mean age 48 years).⁵

^b CHD is defined in the Framingham Heart Study as fatal and nonfatal myocardial infarction, acute coronary insufficiency, and sudden cardiovascular death.⁵

^c Mean data from patients aged 31 to 58 years (n=6) in a clinical study of patients with LAL-D (N=66).⁶

^d RR compared with LDL-c <3.4 mmol/L and HDL-c ≥1.6 mmol/L, which correspond to an RR of 1.00.⁶

^e RR (95% CI) for each parameter were as follows: for LDL-c ≥4.1 mmol/L: women, RR 2.45 (1.37-4.39); men, RR 2.04 (1.44-2.90); for HDL-c <1.0 mmol/L: women, RR 4.93 (2.53-9.59); men, RR 3.25 (1.69-6.26).⁶

While CHD risk estimate is assessed in patients under the age of 30 years, dyslipidemia often starts from a young age in patients with LAL-D^5,9

Progression of atherosclerosis in patients with LAL-D can begin to manifest at a young age, as also reported for other disorders with high cardiovascular risk, such as HeFH^3,12         

• Mean LDL-c was 5.4 mmol/L in patients with LAL-D (mean age, 16.1 years), compared with 6.1 mmol/L in patients with HeFH (mean age, 12.9 years)^2,13,iii,iv

• Mean ApoB, the main protein constituent of LDL-c and non-HDL-c, was 1.7 g/L in patients with LAL-D, compared with 1.4 g/L in patients with HeFH^{2,13,14,iii,iv}