Response to Primary Biliary Cholangitis Treatment: Influencing Factors and the Role in Prognosis Prediction

LIU Yifeng , FAN Xiaoli, SHEN Yi, MEN Ruoting, GUO Yuxin, YANG Li

Abstract

To examine the influencing factors and prognostic features of poor response to ursodeoxycholic acid (UDCA) treatment in primary biliary cholangitis (PBC) patients with dyslipidemia.   Methods  A retrospective study was conducted, covering 512 patients who had a confirmed diagnosis of PBC, and who received treatment at West China Hospital, Sichuan University between January 2009 and March 2022. According to their actual response to UDCA treatment, patients were divided into two groups, UDCA full-response group (n=305) and UDCA non-responding group (n=207). The data from the two groups were compared to predict the adverse factors influencing patient response and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, identify the cut-off value of total cholesterol (TC), and analyze the differences in baseline laboratory test findings and the rate of responses to treatment. According to the TC cut-off value, patients were divided into a group with TC≥5.415 mmol/L and another group with TC<5.415 mmol/L. In addition, differences in the prognosis of the two groups were assessed by comparing the UK-PBC and GLOBE scores.   Results  The baseline data, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), triglycerides (TG), TC, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were significantly increased in the UDCA non-responding group compared to those in the full-response group (all P<0.005), while the albumin level of the UDCA non-responding group was decreased compared to that of the full-response group (P=0.012). Findings of multi-factor logistic regression analysis suggested that TC (odds ratio [OR]=1.501, 95% confidence interval [CI]: 1.275-1.767, P<0.01) and ALP (OR=1.005, 95% CI: 1.003-1.006, P<0.01) were independent risk factors influencing patient response. The ROC curve analysis suggested worse prognosis for patients with TC≥5.415 mmol/L (AUC: 0.727, 95% CI: 0.680-0.775, 63.8% sensitivity, 76.4% specificity). In addition, the UK-PBC risk score at 1 year of treatment was higher in the high-TC group (TC≥5.415 mmol/L) than that in the low-TC group (TC<5.415 mmol/L) (P<0.05).   Conclusions  Hypercholesterolemia is an independent risk factor for poor response to UDCA in PBC patients. When the baseline TC is equal to or higher than 5.415 mmol/L, PBC patients have a relatively poor response to UDCA and poor prognosis.


Keywords: Primary cholestatic cholangitis, Ursodeoxycholic acid, Biochemical response, Hypercholesterolemia.


 

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References


GULAMHUSEIN A F， HIRSCHFIELD G M. Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol，2020，17(2): 93–110. doi: 10.1038/s41575-019-0226-7.

CAREY E J， ALI A H， LINDOR K D. Primary biliary cirrhosis. Lancet， 2015，386(10003): 1565–1575. doi: 10.1016/s0140-6736(15)00154-3.

CRIPPIN J S， LINDOR K D， JORGENSEN R ， et al. Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? Hepatology，1992，15(5): 858–862. doi: 10.1002/hep. 1840150518.

CASH W J， O'NEILL S， O'DONNELL M E， et al. Randomized controlled trial assessing the effect of simvastatin in primary biliary cirrhosis. Liver Int，2013，33(8): 1166–1174. doi: 10.1111/liv.12191.

LONGO M， CROSIGNANI A， BATTEZZATI P M， et al. Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis. Gut，2002，51(2): 265–269. doi: 10.1136/gut.51.2.265.

ALLOCCA M ， CROSIGNANI A， GRITTI A， et al. Hypercholesterolaemia is not associated with early atherosclerotic lesions in primary biliary cirrhosis. Gut，2006，55(12): 1795–1800. doi: 10.1136/gut.2005.079814.

FLOREANI A， VARIOLA A， NIRO G， et al. Plasma adiponectin levels in primary biliary cirrhosis: a novel perspective for link between hypercholesterolemia and protection against atherosclerosis. Am J Gastroenterol，2008，103(8): 1959–1965. doi: 10.1111/j.1572-0241.2008.01888.x. STOJAKOVIC T，

CLAUDEL T， PUTZ-BANKUTI C， et al. Low-dose atorvastatin improves dyslipidemia and vascular function in patients with primary biliary cirrhosis after one year of treatment. Atherosclerosis， 2010，209(1): 178–183. doi: 10.1016/j.atherosclerosis.2009.08.052.

SURAWEERA D， FANOUS C， JIMENEZ M， et al. Risk of cardiovascular events in patients with primary biliary cholangitis--systematic review. J Clin Transl Hepatol，2018，6(2): 119–126. doi: 10. 14218/jcth.2017.00064.

MOUSTAFA T， FICKERT P， MAGNES C， et al. Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury. Gastroenterology，2012，142(1): 140–151.e12. doi: 10.1053/j.gastro.2011.09.051.

SHAH R A， KOWDLEY K V. Current and potential treatments for primary biliary cholangitis. Lancet Gastroenterol Hepatol，2020，5(3): 306–315. doi: 10.1016/s2468-1253(19)30343-7.

European Association for the Study of the Liver. EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol，2017，67(1): 145–172. doi: 10.1016/j.jhep. 2017.03.022.

GARCIA-TSAO G， ABRALDES J G， BERZIGOTTI A， et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology，2017，65(1): 310–335. doi: 10.1002/hep.28906.

SCHUPPAN D， AFDHAL N H. Liver cirrhosis. Lancet，2008，371(9615): 838–851. doi: 10.1016/s0140-6736(08)60383-9.

CHEN S， DUAN W， YOU H， et al. A brief review on prognostic models of primary biliary cholangitis. Hepatol Int，2017，11(5): 412–418. doi: 10. 1007/s12072-017-9819-9.

LAMMERS W J， Van BUUREN H R， HIRSCHFIELD G M， et al. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. Gastroenterology，2014，147(6): 1338–49.e5; quiz e15. doi: 10.1053/j.gastro.2014.08.029.

BARRON-MILLAR B， OGLE L， MELLS G， et al. The serum proteome and ursodeoxycholic acid response in primary biliary cholangitis. Hepatology，2021，74(6): 3269–3283. doi: 10.1002/hep.32011.

BOBERG K M， CHAPMAN R W， HIRSCHFIELD G M， et al. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol，2011，54(2): 374–385. doi: 10.1016/j.jhep.2010.09.002.

CORPECHOT C， CHAZOUILLÈRES O， ROUSSEAU A， et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N Engl J Med，2018，378(23): 2171–2181. doi: 10.1056/NEJMoa1714519.

FIORUCCI S， DISTRUTTI E， CARINO A， et al. Bile acids and their receptors in metabolic disorders. Prog Lipid Res，2021，82: 101094. doi: 10.1016/j.plipres.2021.101094.

ALGER H M， BROWN J M， SAWYER J K， et al. Inhibition of acyl-coenzyme A: cholesterol acyltransferase 2 (ACAT2) prevents dietary cholesterol-associated steatosis by enhancing hepatic triglyceride mobilization. J Biol Chem，2010，285(19): 14267–14274. doi: 10.1074/jbc. M110.118422.

ARAB J P， KARPEN S J， DAWSON P A， et al. Bile acids and nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives. Hepatology，2017，65(1): 350–362. doi: 10.1002/hep.28709. SCHAFFNER F， POPPER H. Clinical-pathologic relations in primary biliary cirrhosis. Prog Liver Dis，1982，7: 529–554.


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