Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis
Open accessAbstract
Background: Primary biliary cirrhosis (PBC), a chronic cholestatic liver disease, is frequently associated with severe hypercholesterolaemia but the clinical significance of this finding is unclear. Aims: To characterise changes in serum lipid profile over time and to assess the risk of cardiovascular disease in PBC. Subjects and methods: We studied a cohort of 400 PBC patients for 6.2 years (range 4 months to 24 years) by serial determinations of serum lipid levels and registration of all cardiovascular events. Subjects included in an Italian prospective population based study served as controls. Results: At presentation, 76% of patients had serum cholesterol levels >5.2 mmol/l. Hyperbilirubinaemic patients had higher total cholesterol and lower high density lipoprotein (HDL) cholesterol levels (p<0.001). With time, disease progression was associated with a reduction in total (p<0.001) and HDL (p<0.05) cholesterol. The incidence of cardiovascular events was similar to that of the general population (cerebrovascular events: standardised ratio 1.4; 95% confidence interval 0.5–3.7; coronary events: 2.2; 0.9–4.3). Hypertension was associated with an increased risk of cardiovascular events (3.8; 1.6–8.9). Association with moderate hypercholesterolaemia was of borderline significance (3.8; 0.9–17) whereas severe hypercholesterolaemia was not associated with increased risk (2.4, 0.5–11). Conclusions: In PBC, serum cholesterol levels markedly increase with worsening of cholestasis, and decrease in the late disease stages, despite a severe reduction in biliary secretion. Marked hypercholesterolaemia, typical of severe longstanding cholestasis, is not associated with an excess risk of cardiovascular disease while less advanced patients with moderate hypercholesterolaemia are exposed to an increased cardiovascular risk. Putative protective factors in PBC patients with severe hypercholesterolaemia should be assessed.
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Retrospective studies indicate no elevated cardiovascular disease risk in PBC patients with hypercholesterolemia.
“retrospective studies suggest that there is no increased risk of cardiovascular disease in patients with PBC and hypercholesterolemia. (84,(244)(245)(246)”
From Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases (2019) · cites this paper as [244]
The introduction says earlier retrospective studies did not demonstrate increased cardiovascular mortality in PBC, but they did not assess non-fatal events. The Abstract further distinguishes severe hypercholesterolaemia, which was not associated with excess cardiovascular risk, from moderate hypercholesterolaemia, which was associated with increased risk. The claim is therefore too broad for patients with PBC and hypercholesterolaemia as a whole. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPatients with primary biliary cholangitis typically have hyperlipidemia, with elevated levels of HDL cholesterol and LDL cholesterol; this profile is not associated with increased cardiovascular risk.
“Patients with primary biliary cholangitis typically have hyperlipidemia, with elevated levels of HDL cholesterol and LDL cholesterol; this profile is not associated with increased cardiovascular risk. 31”
From A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis (2016) · cites this paper as [31]
The Results report that 76% of patients had elevated total cholesterol at presentation and that HDL and LDL levels were not associated with increased cardiovascular events. But the paper does not establish that both HDL and LDL are typically elevated: the Discussion describes elevated HDL with *modified LDL composition* in cholestasis-related hypercholesterolaemia, while HDL fell with disease progression. Its conclusion also distinguishes severe hypercholesterolaemia, which was not associated with excess cardiovascular risk, from moderate hypercholesterolaemia in less advanced patients, which carried increased risk. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPatients with PBC have not been robustly reported to have an associated increased cardiac risk.
“However, patients with PBC have not been robustly reported to have an associated increased cardiac risk [49,50].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [49]
Serum lipids can be elevated in up to 80% of PBC patients.
“Serum lipids can be elevated in up to 80% of patients with PBC [49]; the underlying mechanism of hyperlipidaemia is different from that in other conditions.”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [49]
PBC patients are not at increased risk of death from atherosclerosis, unlike patients with increased serum lipids without PBC.
“It is clinically significant that HDL cholesterol is elevated whilst LDL cholesterol is not, and patients with PBC are not at increased risk of death from atherosclerosis, which is the case for patients with increased serum lipid levels without PBC [49,50].”
From EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. (2017) · cites this paper as [49]
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- Authors
- Longo, M., Crosignani, A., Battezzati, P. M., Squarcia Giussani, C., Invernizzi, P., Zuin, M., & Podda, M.
- Affiliations
- University of Milan (IT)
- Division of Internal Medicine, Department of Medicine, Surgery, and Dentistry, San Paolo School of Medicine, University of Milan, Italy
- Corresponding author
- Podda, M
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2002-08
- Volume
- 51
- Issue
- 2
- Pages
- 265-269
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1773333
- OpenAlex
- W2170438544
- Semantic Scholar
- 4e5a1be10130c46eb36b8b2b0b92bab71593bf4a
- Cited by
- 190
- References
- 35
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 10 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 12 · 2018: 15 · 2017: 13 · 2016: 5 · 2015: 9 · 2014: 10 · 2013: 4 · 2012: 2
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- primary biliary cirrhosis, hypercholesterolemia, lipid profile, cardiovascular risk, HDL cholesterol, total cholesterol, hyperbilirubinemia, cholestasis, hypertension, disease progression, cardiovascular events
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Chronic Disease, Female, Humans, Hypercholesterolemia, Hypertension, Cholesterol, HDL, Liver Cirrhosis, Biliary, Male, Middle Aged, Prospective Studies, Risk, Case-Control Studies
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