Primary-hypercholesterolemia may increase risk of hepatic complications in general population: Study

While low LDL-C levels are known to reduce cardiovascular risk, the broader health implications remain contentious. In primary HBL, incidences of liver steatosis and cirrhosis have been occasionally reported. This study aimed to investigate the association between HBL and the risk of hepatic complications in the general population, specifically focusing on cirrhosis complications and primary liver cancer.

A cohort study was conducted using data from the French CONSTANCES cohort and the UK Biobank (UKBB) cohort. Participants with primary HBL (LDL-C <5th percentile for age and sex) were compared to those with normal LDL-C levels (40th-60th percentile). Those on lipid-lowering therapies were excluded. Incidence density ratios (IDRs) were calculated to compare follow-up events related to hepatic complications.

The study analyzed 34,653 participants from CONSTANCES and 94,666 from the UKBB, with median ages of 45 and 56 years, respectively. The mean LDL-C concentrations in the HBL group versus the control group were 71 mg/dl vs. 128 mg/dl in CONSTANCES and 86 mg/dl vs. 142 mg/dl in the UKBB, with follow-up durations of 5.0 and 11.5 years.

• Incidence of Hepatic Complications: In CONSTANCES, the HBL group had an incidence of 0.32/1,000 person-years compared to 0.07/1,000 person-years in the control group (IDR = 4.50, 95% CI 1.91-10.6).

• In the UKBB, the incidence was 0.69/1,000 person-years for the HBL group vs. 0.21/1,000 person-years for the control group (IDR = 3.27, 95% CI 2.63-4.06).

• Independence from Classical Risk Factors: The increased risk of hepatic complications in the HBL group was independent of obesity, alcohol consumption, diabetes, and viral hepatitis, as shown in a 5-year landmark analysis excluding early events.

The study underscores the independent association between HBL and an increased risk of hepatic complications, including primary liver cancer. This risk persists even when classical risk factors for liver disease are accounted for. Sensitivity analyses using apolipoprotein-B levels and genetically defined HBL showed consistent results, further validating the findings.

HBL should be recognized as a significant independent risk factor for liver diseases, necessitating specific prevention and screening strategies. Given the marked risk of hepatic complications in HBL patients, regular liver monitoring is crucial. The findings from this study reveal a critical need for targeted health interventions and continuous liver monitoring in individuals with hypobetalipoproteinemia. This approach could mitigate the elevated risk of liver disease complications associated with this lipid disorder.

Reference:

Wargny, M., Goronflot, T., Rimbert, A., Boursier, J., Kab, S., Henny, J., Lainé, A., Leux, C., Smati, S., Hadjadj, S., Le May, C., Goldberg, M., Zins, M., & Cariou, B. (2024). Primary hypocholesterolemia is associated with an increased risk of hepatic complications in the general population. Journal of Hepatology, 80(6), 846–857. https://doi.org/10.1016/j.jhep.2024.01.030