Metabolic risk factors in primary biliary cholangitis (PBC) have not been well described in China. Additionally, it is unclear whether these factors have an impact on the prognosis of PBC patients. Therefore, this study aimed to investigate the prevalence of main metabolic risk factors in PBC, and to evaluate their prognostic values for liver-related outcomes.

A cohort of 789 PBC patients was retrospectively studied between July 2008 and September 2019 by investigating the main metabolic risk factors and analyzing liver-related outcomes.

At presentation, 271 (34.3%) patients had concomitant hyperlipidemia, 126 (16.0%) had hypertension, 94 (11.9%) had type 2 diabetes mellitus (T2DM), and 17 (2.2%) had nonalcoholic fatty liver disease (NAFLD). Hyperlipidemia was found to be associated with the lower risk of liver-related death [P<0.0001, hazard ratio (HR): 0.397, 95% confidence interval (CI): 0.268-0.588] and adverse outcomes (P<0.0001, HR: 0.487, 95% CI:0.367-0.646), while hypertension was noted as a risk factor for liver-related death (P=0.001, HR: 1.788, 95% CI:1.268-2.521) and adverse outcomes (P=0.014, HR: 1.417, 95% CI:1.074-1.869). Moreover, age ≥ 55 years old (P=0.005) and cirrhosis (P<0.0001) had superimposition effects on hypertension as a risk factor for liver-related death, while only cirrhosis (P<0.0001) had an effect on hypertension as a risk factor for adverse outcomes. Additionally, anti-sp100 was associated with adverse outcomes (P=0.013) in PBC patients with hypertension in univariate Cox regression analysis.

Hyperlipidemia, hypertension, and T2DM were found as main metabolic risk factors in PBC in China. Hyperlipidemia indicated a benign clinical outcome of PBC, while hypertension indicated a poor outcome of PBC. Older age and cirrhosis had superimposition effects on hypertension for liver-related poor outcomes. Anti-sp100 might be associated with adverse outcomes, especially in PBC patients with hypertension.

Primary biliary cirrhosis (PBC) is frequently associated with hypercholesterolemia and with an increased cardiovascular morbidity and mortality. Statins lower serum cholesterol levels and may thus improve the cardiovascular risk in PBC patients. The aim of our study was to prospectively examine the efficacy of low-dose atorvastatin on cholestasis as well as cardiovascular risk markers such as dyslipidemia and vascular function in patients with PBC.

Nineteen patients with early-stage (biopsy proven and AMA positive) PBC and low-density lipoprotein cholesterol (LDL-C) above 130mg/dL were included in this single-center study and treated with atorvastatin 10mg per day for one year.

Concentrations of total cholesterol, LDL-C, LDL triglycerides, oxLDL, IgG and sVCAM-1 decreased significantly after 48 weeks of atorvastatin treatment. Flow-mediated dilation (FMD) of the brachial artery as an indicator of vascular function significantly increased, while carotid artery intima-media thickness and vascular wall stiffness did not progress under treatment. No statistical differences in liver enzymes were observed except a transient increase of alkaline phosphatase.

Treatment with low-dose atorvastatin is safe in early-stage PBC, effectively reduces total cholesterol, LDL-C, LDL triglycerides, oxLDL and sVCAM-1 and improves vascular function as reflected by FMD, without affecting cholestasis progression. Therefore, statin therapy should be considered in PBC patients with additional risk factors for cardiovascular disease.

Statin therapy may target both hypercholesterolemia and cholestasis in primary biliary cirrhosis (PBC). However, little is known about the efficacy and safety of statins in PBC. The aim of this single-center study was therefore to prospectively examine the effects of atorvastatin on serum markers of cholestasis, aminotransferases, and lipid and bile acid metabolism as well as inflammatory and immunological markers in patients with PBC. Fifteen patients with early-stage PBC and an incomplete biochemical response to ursodeoxycholic acid (UDCA) therapy (defined as alkaline phosphatase 1.5-fold above the upper limit of normal after 1 year) were treated with atorvastatin 10 mg/day, 20 mg/day, and 40 mg/day for 4 weeks, respectively. Serum levels of alkaline phosphatase increased during atorvastatin 20 mg and 40 mg (P < 0.05), whereas leucine aminopeptidase and gamma-glutamyltransferase remained unchanged. No statistical differences in overall serum ALT, AST, bilirubin, and IgM levels were observed. However, atorvastatin was discontinued in 1 out of 15 patients because of ALT 2-fold above baseline, and 2 patients showed ALT elevations 3-fold above the upper limit of normal at the end of the atorvastatin treatment period. Serum total cholesterol and low-density lipoprotein cholesterol levels decreased by 35% and 49%, respectively (P < 0.001). Precursors of cholesterol biosynthesis (lanosterol, desmosterol, lathosterol) showed a similar pattern. No changes in serum bile acid levels and composition were observed during treatment.

Atorvastatin does not improve cholestasis in PBC patients with an incomplete biochemical response to UDCA but effectively reduces serum cholesterol levels.

Primary biliary cirrhosis (PBC) is characterized by the presence of antimitochondrial antibodies (AMA). Autoantibodies specific for the mitochondrial M4 antigen can be detected by a complement fixation test (CFT) but not by immunoblotting. The aim of this study was to elucidate the identity of the M4 antigen.

M4 proteins were purified by affinity chromatography using IgG fractions of PBC marker sera being CFT positive (n=5) or negative (n=5) and identified by Western blotting, silver staining and sequence analysis. Further, a cohort of 57 PBC patients was tested for the reactivity to M4 and pyruvate dehydrogenase complex (PDC).

Two AMA patterns of the marker sera were visualized: CFT-positive sera were defined as PDC-E2(+)/E1(+) and the CFT-negative sera as PDC-E2(+)/E1(-). The major proteins in the M4 fraction could be related to the PDC-E1 subunits. A clear-cut association between anti-M4 reactivity in the CFT and the reactivity to both PDC subunits could also be documented in the cohort of 57 PBC patients showing anti-PDC-E1alpha and E1beta antibodies at a frequency of 74% and 67%.

CFT reactivity against M4 antigens could be preferentially identified as a reaction against PDC-E1. As PDC-E1 subunits as compared with PDC-E2 lack lipoyl-binding sites, they probably have to be considered as an independent and important target.

A 44-year-old woman developed jaundice and was diagnosed as stage II of primary biliary cirrhosis (PBC). She showed a severely high total cholesterol level. This article focuses on atypical presentations of PBC and the need to test the total cholesterol level of PBC patients.