Spotlight on cholesterol and the liver

Two recent studies looked at the hepatic effects of abnormal cholesterol levels.

The first study, published by the Journal of Hepatology on Feb. 6, looked at the effects of very low low-density lipoprotein (LDL) cholesterol levels, or primary hypobetalipoproteinemia (HBL). Researchers used two population-based cohorts, one from France (CONSTANCES) and one from the U.K. Biobank (UKBB) with 34,653 and 94,666 patients, respectively. Mean LDL-C concentrations were 71 mg/dL and 86 mg/dL in the French and U.K. HBL patients, respectively, versus 128 mg/dL and 142 mg/dL in the general cohort populations. After mean follow-ups of 5.0 and 11.5 years, HBL patients had substantially higher incidence of hepatic complications than the general population, at 0.32 and 0.69 per 1,000 person-years versus 0.07 and 0.69 per 1,000, in the French and U.K. cohorts, respectively (incidence density ratios, 4.50 [95% CI, 1.91 to 10.6] and 3.27 [95% CI, 2.63 to 4.06]).

The association between HBL and liver disease was independent of traditional liver-disease risk factors, such as obesity, alcohol consumption, diabetes, and viral hepatitis, the study authors noted. However, they also said that the increase in risk was driven by cirrhosis and that, in fact, patients with HBL did not have a statistically significant increase in incidence of primary liver cancer. There is still reason for concern, though, they said. "Although the frequency of hepatic complications may appear low, it should be noted that the individuals included in these cohorts were relatively young (45 years on average in CONSTANCES and 56 years in UKBB)," the study authors added. "Altogether, these findings highlight the need for long-term liver monitoring in subjects with primary HBL."

The other study, published by Clinical Gastroenterology and Hepatology on Feb. 12, assessed the effects of hypercholesterolemia in patients with primary biliary cholangitis (PBC). It included 531 Chinese patients with PBC and no prior cirrhosis-related complications, randomized into derivation and validation cohorts. In total, 205 (38.6%) patients had total cholesterol levels above 5.2 mmol/L. After a median follow-up of 50 months, the primary outcome of liver-related death, liver transplantation, or cirrhosis-related complications had occurred in 98 (18.5%) patients, including 33 (6.2%) with liver-related death or transplantation. Untargeted lipidomics were also performed in 89 PBC patients and 28 healthy controls and indicated an upregulation of lipid families in high-risk patients.

The ability of total cholesterol to predict liver disease outcomes was stable over the years and comparable to that of the GLOBE score, the study authors observed. They found that a cutoff of 5.2 mmol/L "optimally divided patients into low- and high-risk groups," and that a combination of total cholesterol and GLOBE score provided the most accurate stratification of patients. "The present study data showed that hypercholesterolemia at baseline is a valuable predictive criterion of the likelihood of a poor prognosis, including liver-related death, [liver transplant], or complications," said the study authors. "These results strongly suggest that clinicians should pay more attention to patients with hypercholesterolemia, especially those with a Globe score below 0.3, who are easily neglected in clinical practice."