Individuals with Primary Biliary Cholangitis Benefit from Statin Therapy

Hyperlipidemia complicates the course of primary biliary cholangitis (PBC) by increasing the burden of cardiovascular and metabolic disease, which may be underrecognized in this population, according to a retrospective analysis presented at The Liver Meeting 2025, in Washington, D.C. 

Hyperlipidemia is a common extrahepatic manifestation of PBC, which has been shown to affect up to 80% of patients with biliary cholestasis (Sorokin A et al. Atherosclerosis 2007;194:293-9). Historically, hyperlipidemia has been considered benign in the context of PBC, mainly because high-density lipoprotein cholesterol levels are disproportionally elevated in this population. Findings from a multi-center, retrospective cohort study including adults diagnosed with PBC between 2012 and 2024 may help overturn this assumption, and may prompt clinicians to reevaluate the impact of hyperlipidemia on cardiovascular outcomes in their patients with PBC. 

Using the TriNetX collaborative database, researchers at the Thomas Jefferson University in Philadelphia selected a cohort of 7,299 patients with PBC treated at various institutions who had documented hyperlipidemia, and compared their cardiometabolic outcomes to those of 7,299 patients with PBC without elevated lipid levels. Individuals with coexisting chronic liver diseases, pre-existing cardiovascular conditions, or prior statin use were excluded from the analysis. After propensity score matching, the investigators found that patients with PBC and hyperlipidemia had significantly higher rates of adverse cardiovascular and metabolic events, including ischemic heart disease, stroke, transient ischemic attack, peripheral arterial disease, heart failure, hypertension, and type 2 diabetes, than their counterparts without hyperlipidemia. Although all-cause mortality rates were lower in the group with hyperlipidemia, these patients had a slightly higher risk of hospitalization compared with the group without elevated lipid levels. 

“These findings challenge the long-standing belief that hyperlipidemia in PBC is benign and highlight the need to re-evaluate cardiovascular risk assessment and management in this population,” Tinsae Anebo, MD, and colleagues noted. “Despite a lower all-cause mortality and reduced liver-related complications, the significantly increased burden of cardiovascular and metabolic comorbidities in PBC patients with hyperlipidemia underscores the importance of more personalized and proactive cardiovascular monitoring. Traditional lipid parameters may not fully reflect risk in PBC, and as the disease progresses, integrating metabolic risk profiling into routine care may be essential for improving long-term outcomes.” 

A separate analysis presented at The Liver Meeting 2025 suggested that statins have the potential to improve survival in patients with PBC and protect them against decompensation - defined as variceal bleeding, hepatic encephalopathy, or ascites requiring diuretics or paracentesis. In a retrospective cohort study that included all patients with PBC who were treated at two hospital systems in Dallas, Texas between 2002 and 2023, the investigators analyzed the effects of statins on alkaline phosphatase levels, decompensation, and liver-related events in patients with PBC. Major liver-related events included decompensation, liver transplantation, hepatocellular carcinoma, and liver-related death. 

While patients who received statins and those who did not had comparable alkaline phosphatase levels at baseline (258 vs 204 IU/L), the analysis showed that statins were associated with an improvement in this key biomarker for cholestasis. After one year on statin therapy, alkaline phosphatase levels decreased in patients who took statins (-17.0%), while those who did not take statins followed a less favorable trajectory (+17.3%). Statins were used for an average of 6.25 years, with only two patients discontinuing use due to muscle aches. 

Multivariable regression analysis showed that statins protected against liver-related events and decompensation when accounting for the effects of alkaline phosphatase levels, total bilirubin levels, and platelet levels at 1 year, as well as those of a baseline diagnosis of cirrhosis and concurrent metabolic dysfunction-associated steatotic liver disease. The analysis also showed that statins improved decompensation-free survival and demonstrated a trend toward improved liver event-free survival. 

“Statins were associated with an improvement in alkaline phosphatase and were not associated with significant adverse events,” the authors concluded. “This should be further examined in a large, diverse population of patients with PBC, such as the Global PBC Study Group. With historical concerns about the use of fibrates and statins, safety analysis will be needed with the increasing use of PPAR-agonists in [the treatment of] patients with PBC.”