The clinical and laboratory features associated with cancer in patients with primary biliary cholangitis: a longitudinal survey–based study
Tóm tắt
To analyze the clinical and laboratory features of primary biliary cholangitis (PBC) patients complicated with cancer, and explore the potential factors associated with cancer. We consecutively enrolled PBC patients from January 2002 to February 2016 in Peking Union Medical College Hospital and performed a structured interview, systemic rheumatologic evaluation, and laboratory tests. The risk factors associated with cancer were analyzed with univariate and multivariable logistic regression and proportional hazard model. Among the 580 PBC patients enrolled, 51 cancers were identified in 51 patients (8.8%), including 45 (88.2%) solid tumors and 6 (11.8%) hematologic malignancies. Patients with cancer were older (62.1 ± 9.6 vs. 55.4 ± 11.6 years, p < 0.01) than patients without cancer. Additionally, positive anti-centromere antibody (ACA) was more frequently observed in patients without cancer (25.9% vs 4.3%, p = 0.019) compared with patients with cancer diagnosed after establishing PBC. The median follow-up after the diagnosis of PBC was 4 years (IQR 2.0–6.6). Furthermore, multivariable logistic regression confirmed that older age was associated with cancer in PBC patients (odds ratio (OR) = 1.045, 95% confidence interval (CI): 1.006–1.085), and positive ACA was a protective factor (OR = 0.116, 95% CI: 0.015–0.876). Additionally, proportional hazard model analysis revealed that age was a risk factor (hazard ratio = 1.045, 95% CI: 1.012–1.080), and positive ACA was a protective factor (hazard ratio = 0.232, 95% CI: 0.055–0.977) for cancer. Both solid tumor and hematologic malignancy were prevalent in PBC patients. Older age was associated with cancer, and positive ACA was a protective factor of cancer in PBC patients.
Tài liệu tham khảo
Carey EJ, Ali AH, Lindor KD (2015) Primary biliary cirrhosis. Lancet. 386(10003):1565–1575
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66(2):115–132
Hemminki K, Sundquist K, Sundquist J, Ji J (2015) Risk of cancer of unknown primary after hospitalization for autoimmune diseases. Int J Cancer 137(12):2885–2895
Fang YF, Wu YJ, Kuo CF, Luo SF, Yu KH (2016) Malignancy in dermatomyositis and polymyositis: analysis of 192 patients. Clin Rheumatol 35(8):1977–1984
Trivedi PJ, Lammers WJ, van Buuren HR, Pares A, Floreani A, Janssen HL et al (2016) Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study. Gut. 65(2):321–329
Zhang XX, Wang LF, Jin L, Li YY, Hao SL, Shi YC, Zeng QL, Li ZW, Zhang Z, Lau GK, Wang FS (2015) Primary biliary cirrhosis-associated hepatocellular carcinoma in Chinese patients: incidence and risk factors. World J Gastroenterol 21(12):3554–3563
Jones DE, Metcalf JV, Collier JD, Bassendine MF, James OF (1997) Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes. Hepatology. 26(5):1138–1142
Harada K, Hirohara J, Ueno Y, Nakano T, Kakuda Y, Tsubouchi H, Ichida T, Nakanuma Y (2013) Incidence of and risk factors for hepatocellular carcinoma in primary biliary cirrhosis: national data from Japan. Hepatology. 57(5):1942–1949
Liang Y, Yang Z, Zhong R (2012) Primary biliary cirrhosis and cancer risk: a systematic review and meta-analysis. Hepatology. 56(4):1409–1417
Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ, American Association for Study of Liver Diseases (2009) Primary biliary cirrhosis. Hepatology. 50(1):291–308
Heathcote EJ (2000) Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. Hepatology. 31(4):1005–1013
Harada K, Nakanuma Y (2014) Prevalence and risk factors of hepatocellular carcinoma in Japanese patients with primary biliary cirrhosis. Hepatol Res 44(2):133–140
Su CW, Hung HH, Huo TI, Huang YH, Li CP, Lin HC, Lee PC, Lee SD, Wu JC (2008) Natural history and prognostic factors of primary biliary cirrhosis in Taiwan: a follow-up study up to 18 years. Liver Int 28(9):1305–1313
Deutsch M, Papatheodoridis GV, Tzakou A, Hadziyannis SJ (2008) Risk of hepatocellular carcinoma and extrahepatic malignancies in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 20(1):5–9
van der Deure WM, Lugtenburg EP, Dwarkasing RS, Biermann K, Tjwa ET (2015) Malignancy presenting as multiple lesions in a cirrhotic liver: not always hepatocellular carcinoma. J Gastrointest Liver Dis 24(1):7
Kaneko H, Endo T, Saitoh H, Katsuta Y, Aramaki T, Hayakawa H (1993) Primary biliary cirrhosis associated with multiple myeloma. Intern Med 32(10):802–805
Rodriguez-Leal GA, Moran-Villota S, Arista-Nasr J, Uribe-Esquivel M (1997) Case report of multiple myeloma and hypothyroidism in primary biliary cirrhosis. Rev Investig Clin Organo Hosp Enferm Nutr 49(3):215–220
Blade J, Montserrat E, Bruguera M, Aranalde J, Granena A, Cervantes F et al (1981) Multiple myeloma in primary biliary cirrhosis. Scand J Haematol 26(1):14–18
Rong G, Wang H, Bowlus CL, Wang C, Lu Y, Zeng Z, Qu J, Lou M, Chen Y, An L, Yang Y, Gershwin ME (2015) Incidence and risk factors for hepatocellular carcinoma in primary biliary cirrhosis. Clin Rev Allergy Immunol 48(2-3):132–141
Cavazza A, Caballeria L, Floreani A, Farinati F, Bruguera M, Caroli D et al (2009) Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: comparative analysis from two centers. Hepatology. 50(4):1162–1168
Pawelec G, Derhovanessian E, Larbi A (2010) Immunosenescence and cancer. Crit Rev Oncol Hematol 75(2):165–172
Shah AA, Hummers LK, Casciola-Rosen L, Visvanathan K, Rosen A, Wigley FM (2015) Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma. Arthritis Rheum 67(4):1053–1061
Liaskos C, Marou E, Simopoulou T, Barmakoudi M, Efthymiou G, Scheper T, Meyer W, Bogdanos DP, Sakkas LI (2017) Disease-related autoantibody profile in patients with systemic sclerosis. Autoimmunity. 50(7):414–421
Liberal R, Grant CR, Sakkas L, Bizzaro N, Bogdanos DP (2013) Diagnostic and clinical significance of anti-centromere antibodies in primary biliary cirrhosis. Clin Res Hepatol Gastroenterol 37(6):572–585
Lee KE, Kang JH, Lee JW, Wen L, Park DJ, Kim TJ, Park YW, Lee SS (2015) Anti-centromere antibody-positive Sjogren's syndrome: A distinct clinical subgroup? Int J Rheum Dis 18(7):776–782
Hamaguchi Y (2010) Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis. J Dermatol 37(1):42–53
Iniesta Arandia N, Simeon-Aznar CP, Guillen Del Castillo A, Colunga Arguelles D, Rubio-Rivas M, Trapiella Martinez L et al (2017) Influence of antibody profile in clinical features and prognosis in a cohort of Spanish patients with systemic sclerosis. Clin Exp Rheumatol 35(Suppl 106(4)):98–105
Freeman S (2012) Scleroderma malignancy risk linked to antinuclear antibodies
Higuchi M, Horiuchi T, Ishibashi N, Yoshizawa S, Niho Y, Nagasawa K (2000) Anticentromere antibody as a risk factor for cancer in patients with systemic sclerosis. Clin Rheumatol 19(2):123–126
Fuschiotti P, Medsger TA Jr, Morel PA (2009) Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosis. Arthritis Rheum 60(4):1119–1128
Liu H, Liu Y, Wang L, Xu D, Lin B, Zhong R, Gong S, Podda M, Invernizzi P (2010) Prevalence of primary biliary cirrhosis in adults referring hospital for annual health check-up in Southern China. BMC Gastroenterol 10:100