Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Ung thư biểu mô tế bào gan trong viêm đường mật xơ hóa nguyên phát và viêm đường mật nguyên phát: một nghiên cứu lâm sàng và bệnh lý trong một môi trường ít gặp nhưng đang nổi lên
Archiv für pathologische Anatomie und Physiologie und für klinische Medicin - Tập 479 - Trang 1131-1143 - 2021
Tóm tắt
Viêm đường mật xơ hóa nguyên phát (PSC) và viêm đường mật nguyên phát (PBC) là những bệnh lý đường mật có nguy cơ cao mắc ung thư biểu mô tế bào gan (HCC), mặc dù HCC thường liên quan nhiều hơn đến viêm gan virus và viêm gan nhiễm mỡ. Phân tầng nguy cơ HCC trong các quần thể PBC/PSC có thể giúp lựa chọn bệnh nhân cho việc giám sát. Chúng tôi giả thuyết rằng các chẩn đoán liên quan đến hội chứng chuyển hóa và bệnh gan nhiễm mỡ không do rượu (NAFLD) đi kèm có thể là các yếu tố nguy cơ cho HCC ở bệnh nhân PBC và PSC. Chúng tôi đã tiến hành một nghiên cứu so sánh trường hợp đa cơ sở về PSC (19 trường hợp, 38 đối chứng) và PBC (39 trường hợp và đối chứng) với tổn thương xơ hóa nặng, được ghép nối theo các yếu tố nguy cơ HCC đã biết về tuổi và giới tính, những người có mẫu phẫu thuật gan tự nhiên. Trong quần thể PSC, nguy cơ HCC có liên quan đáng kể đến nhiều chẩn đoán liên quan đến hội chứng chuyển hóa (OR 13, p = 0.02), tăng lipid máu (OR 29, p = 0.03) và béo phì (OR 6.8, p = 0.01). Trong nhóm PBC, chỉ có bệnh tiểu đường típ 2 là yếu tố nguy cơ cho HCC (OR 4.7, p = 0.03). Trong nhóm PSC, các vách xơ dày có liên quan đến nguy cơ HCC (OR 3.4, p = 0.04). Không có các đặc điểm bệnh lý khác của gan không u bướu nào có liên quan đáng kể đến HCC, bao gồm các đặc điểm của NAFLD như thoái hóa mỡ lớn, xơ hóa quanh tế bào và viêm gan nhiễm mỡ. Các chẩn đoán liên quan đến hội chứng chuyển hóa, cụ thể là bệnh tiểu đường típ 2 ở bệnh nhân PBC, có liên quan đến nguy cơ HCC ở bệnh nhân xơ gan loại đường mật. Tuy nhiên, chúng tôi không tìm thấy bằng chứng cho rằng nguy cơ HCC liên quan đến NAFLD đi kèm, cho thấy một cơ chế biệt lập trong khả năng gây ung thư liên quan đến hội chứng chuyển hóa ở những quần thể này.
Từ khóa
#ung thư biểu mô tế bào gan #viêm đường mật xơ hóa nguyên phát #viêm đường mật nguyên phát #hội chứng chuyển hóa #bệnh gan nhiễm mỡ không do rượuTài liệu tham khảo
Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome–a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 23:469–480. https://doi.org/10.1111/j.1464-5491.2006.01858.x
Ali AH, Tabibian JH, Nasser-Ghodsi N, Lennon RJ, DeLeon T, Borad MJ, Hilscher M, Silveira MG, Carey EJ, Lindor KD (2018) Surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis. Hepatology 67:2338–2351. https://doi.org/10.1002/hep.29730
Altman DG (1991) Practical statistics for medical research. Chapman and Hall, London, New York
Bosch DE, Yeh MM (2017) Primary sclerosing cholangitis is protective against nonalcoholic fatty liver disease in inflammatory bowel disease. Hum Pathol 69:55–62. https://doi.org/10.1016/j.humpath.2017.09.008
Bowlus CL, Lim JK, Lindor KD (2019) AGA clinical practice update on surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis: expert review. Clin Gastroenterol Hepatol 17:2416–2422. https://doi.org/10.1016/j.cgh.2019.07.011
Brunt EM (2005) Pathology of hepatic iron overload. Semin Liver Dis 25:392–401. https://doi.org/10.1055/s-2005-923311
Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA, (CRN) NCRN, (2011) Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 53:810–820. https://doi.org/10.1002/hep.24127
Caballería L, Parés A, Castells A, Ginés A, Bru C, Rodés J (2001) Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis. Am J Gastroenterol 96:1160–1163. https://doi.org/10.1111/j.1572-0241.2001.03695.x
Cavazza A, Caballería L, Floreani A, Farinati F, Bruguera M, Caroli D, Parés A (2009) Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: comparative analysis from two centers. Hepatology 50:1162–1168. https://doi.org/10.1002/hep.23095
Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, Gores GJ, Diseases AAftSoL, (2010) Diagnosis and management of primary sclerosing cholangitis. Hepatology 51:660–678. https://doi.org/10.1002/hep.23294
Cheung KS, Seto WK, Fung J, Lai CL, Yuen MF (2017) Epidemiology and natural history of primary biliary cholangitis in the chinese: a territory-based study in Hong Kong between 2000 and 2015. Clin Transl Gastroenterol 8:e116. https://doi.org/10.1038/ctg.2017.43
Cheung KS, Seto WK, Fung J, Mak LY, Lai CL, Yuen MF (2017) Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis. World J Gastroenterol 23:7863–7874. https://doi.org/10.3748/wjg.v23.i44.7863
Debes JD, Boonstra A, de Knegt RJ (2020) NAFLD-related hepatocellular carcinoma and the four horsemen of the apocalypse. Hepatology 71:774–776. https://doi.org/10.1002/hep.31170
Deutsch M, Papatheodoridis GV, Tzakou A, Hadziyannis SJ (2008) Risk of hepatocellular carcinoma and extrahepatic malignancies in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 20:5–9. https://doi.org/10.1097/MEG.0b013e3282f163ed
Doycheva I, Zhang T, Amjad W, Thuluvath PJ (2020) Diabetes and hepatocellular carcinoma: incidence trends and impact of liver disease etiology. J Clin Exp Hepatol 10:296–303. https://doi.org/10.1016/j.jceh.2019.11.004
Dragasevic S, Stankovic B, Kotur N, Sokic-Milutinovic A, Milovanovic T, Lukic S, Milosavljevic T, Srzentic Drazilov S, Klaassen K, Pavlovic S, Popovic D (2020) Metabolic syndrome in inflammatory bowel disease: association with genetic markers of obesity and inflammation. Metab Syndr Relat Disord 18:31–38. https://doi.org/10.1089/met.2019.0090
Efe C, Torgutalp M, Henriksson I, Alalkim F, Lytvyak E, Trivedi H, Eren F, Fischer J, Chayanupatkul M, Coppo C, Purnak T, Muratori L, Werner M, Muratori P, Rorsman F, Onnerhag K, Nilsson E, Heurgué-Berlot A, Demir N, Semela D, Kıyıcı M, Schiano TD, Montano-Loza AJ, Berg T, Ozaslan E, Yoshida EM, Bonder A, Marschall HU, Beretta-Piccoli BT, Wahlin S (2020) Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome. J Gastroenterol Hepatol. https://doi.org/10.1111/jgh.15214
Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43:S99–S112. https://doi.org/10.1002/hep.20973
Fung BM, Lindor KD, Tabibian JH (2019) Cancer risk in primary sclerosing cholangitis: Epidemiology, prevention, and surveillance strategies. World J Gastroenterol 25:659–671. https://doi.org/10.3748/wjg.v25.i6.659
Giles DA, Moreno-Fernandez ME, Stankiewicz TE, Cappelletti M, Huppert SS, Iwakura Y, Dong C, Shanmukhappa SK, Divanovic S (2016) Regulation of inflammation by IL-17A and IL-17F modulates non-alcoholic fatty liver disease pathogenesis. PLoS ONE 11:e0149783. https://doi.org/10.1371/journal.pone.0149783
Gossard AA, Lindor KD (2014) Hepatocellular carcinoma: low risk of HCC in patients who have PSC and cirrhosis. Nat Rev Gastroenterol Hepatol 11:276–277. https://doi.org/10.1038/nrgastro.2014.47
Horsley-Silva JL, Rodriguez EA, Franco DL, Lindor KD (2017) An update on cancer risk and surveillance in primary sclerosing cholangitis. Liver Int 37:1103–1109. https://doi.org/10.1111/liv.13354
Hosonuma K, Sato K, Yanagisawa M, Kakizaki S, Takagi H, Hirato J, Mori M (2013) Incidence, mortality, and predictive factors of hepatocellular carcinoma in primary biliary cirrhosis. Gastroenterol Res Pract 2013:168012. https://doi.org/10.1155/2013/168012
Imam MH, Silveira MG, Sinakos E, Gossard AA, Jorgensen R, Keach J, DeCook AC, Lindor KD (2012) Long-term outcomes of patients with primary biliary cirrhosis and hepatocellular carcinoma. Clin Gastroenterol Hepatol 10:182–185. https://doi.org/10.1016/j.cgh.2011.09.013
Janmohamed A, Trivedi PJ (2018) Patterns of disease progression and incidence of complications in primary biliary cholangitis (PBC). Best Pract Res Clin Gastroenterol 34–35:71–83. https://doi.org/10.1016/j.bpg.2018.06.002
Kim MY, Cho MY, Baik SK, Park HJ, Jeon HK, Im CK, Won CS, Kim JW, Kim HS, Kwon SO, Eom MS, Cha SH, Kim YJ, Chang SJ, Lee SS (2011) Histological subclassification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical stage and grade of portal hypertension. J Hepatol 55:1004–1009. https://doi.org/10.1016/j.jhep.2011.02.012
Kim SU, Oh HJ, Wanless IR, Lee S, Han KH, Park YN (2012) The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis. J Hepatol 57:556–563. https://doi.org/10.1016/j.jhep.2012.04.029
Kim SU, Jung KS, Lee S, Park JY, Kim DY, Ahn SH, Choi GH, Kim KS, Choi JS, Han KH, Park YN (2014) Histological subclassification of cirrhosis can predict recurrence after curative resection of hepatocellular carcinoma. Liver Int 34:1008–1017. https://doi.org/10.1111/liv.12475
Kuiper EM, Hansen BE, Adang RP, van Nieuwkerk CM, Timmer R, Drenth JP, Spoelstra P, Brouwer HT, Kuyvenhoven JP, van Buuren HR, Group DPS (2010) Relatively high risk for hepatocellular carcinoma in patients with primary biliary cirrhosis not responding to ursodeoxycholic acid. Eur J Gastroenterol Hepatol 22(1495):1502. https://doi.org/10.1097/MEG.0b013e32834059e7
Kumar M, Sakhuja P, Kumar A, Manglik N, Choudhury A, Hissar S, Rastogi A, Sarin SK (2008) Histological subclassification of cirrhosis based on histological-haemodynamic correlation. Aliment Pharmacol Ther 27:771–779. https://doi.org/10.1111/j.1365-2036.2008.03653.x
Liang Y, Yang Z, Zhong R (2012) Primary biliary cirrhosis and cancer risk: a systematic review and meta-analysis. Hepatology 56:1409–1417. https://doi.org/10.1002/hep.25788
Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M (2019) Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 69:394–419. https://doi.org/10.1002/hep.30145
Liu X, Xu H, Zhan M, Niu J (2019) The Potential effects of diabetes mellitus on liver fibrosis in patients with primary biliary cholangitis. Med Sci Monit 25:6174–6180. https://doi.org/10.12659/MSM.916107
Loomba R, Lim JK, Patton H, El-Serag HB (2020) AGA clinical practice update on screening and surveillance for hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: expert review. Gastroenterology 158:1822–1830. https://doi.org/10.1053/j.gastro.2019.12.053
Ludwig J, Dickson ER, McDonald GS (1978) Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Arch A Pathol Anat Histol 379:103–112. https://doi.org/10.1007/BF00432479
Nagula S, Jain D, Groszmann RJ, Garcia-Tsao G (2006) Histological-hemodynamic correlation in cirrhosis-a histological classification of the severity of cirrhosis. J Hepatol 44:111–117. https://doi.org/10.1016/j.jhep.2005.07.036
Nakanuma Y, Zen Y, Harada K, Sasaki M, Nonomura A, Uehara T, Sano K, Kondo F, Fukusato T, Tsuneyama K, Ito M, Wakasa K, Nomoto M, Minato H, Haga H, Kage M, Yano H, Haratake J, Aishima S, Masuda T, Aoyama H, Miyakawa-Hayashino A, Matsumoto T, Sanefuji H, Ojima H, Chen TC, Yu E, Kim JH, Park YN, Tsui W (2010) Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement. Pathol Int 60:167–174. https://doi.org/10.1111/j.1440-1827.2009.02500.x
Natarajan Y, Tansel A, Patel P, Emologu K, Shukla R, Qureshi Z, El-Serag HB, Thrift AP, Kanwal F (2020) Incidence of hepatocellular carcinoma in primary biliary cholangitis: a systematic review and meta-analysis. Dig Dis Sci. https://doi.org/10.1007/s10620-020-06498-7
Piscaglia F, Sagrini E (2008) Malignancies in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 20:1–4. https://doi.org/10.1097/MEG.0b013e3282f16436
Razumilava N, Gores GJ, Lindor KD (2011) Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology 54:1842–1852. https://doi.org/10.1002/hep.24570
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 48:132–141. https://doi.org/10.1007/s12016-015-8483-x
Sabino J, Vieira-Silva S, Machiels K, Joossens M, Falony G, Ballet V, Ferrante M, Van Assche G, Van der Merwe S, Vermeire S, Raes J (2016) Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD. Gut 65:1681–1689. https://doi.org/10.1136/gutjnl-2015-311004
Salomao M, Yu WM, Brown RS, Emond JC, Lefkowitch JH (2010) Steatohepatitic hepatocellular carcinoma (SH-HCC): a distinctive histological variant of HCC in hepatitis C virus-related cirrhosis with associated NAFLD/NASH. Am J Surg Pathol 34:1630–1636. https://doi.org/10.1097/PAS.0b013e3181f31caa
Salomao M, Remotti H, Vaughan R, Siegel AB, Lefkowitch JH, Moreira RK (2012) The steatohepatitic variant of hepatocellular carcinoma and its association with underlying steatohepatitis. Hum Pathol 43:737–746. https://doi.org/10.1016/j.humpath.2011.07.005
Silveira MG, Suzuki A, Lindor KD (2008) Surveillance for hepatocellular carcinoma in patients with primary biliary cirrhosis. Hepatology 48:1149–1156. https://doi.org/10.1002/hep.22458
Suzuki A, Lymp J, Donlinger J, Mendes F, Angulo P, Lindor K (2007) Clinical predictors for hepatocellular carcinoma in patients with primary biliary cirrhosis. Clin Gastroenterol Hepatol 5:259–264. https://doi.org/10.1016/j.cgh.2006.09.031
Tabibian JH, Ali AH, Lindor KD (2018) Primary sclerosing cholangitis, part 2: cancer risk, prevention, and surveillance. Gastroenterol Hepatol (N Y) 14:427–432
Tomiyama Y, Takenaka K, Kodama T, Kawanaka M, Sasaki K, Nishina S, Yoshioka N, Hara Y, Hino K (2013) Risk factors for survival and the development of hepatocellular carcinoma in patients with primary biliary cirrhosis. Intern Med 52:1553–1559. https://doi.org/10.2169/internalmedicine.52.0010
Trivedi PJ, Lammers WJ, van Buuren HR, Parés A, Floreani A, Janssen HL, Invernizzi P, Battezzati PM, Ponsioen CY, Corpechot C, Poupon R, Mayo MJ, Burroughs AK, Nevens F, Mason AL, Kowdley KV, Lleo A, Caballeria L, Lindor KD, Hansen BE, Hirschfield GM, Group GPS (2016) Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study. Gut 65(321):329. https://doi.org/10.1136/gutjnl-2014-308351
Vlăduţ C, Ciocîrlan M, Bilous D, Șandru V, Stan-Ilie M, Panic N, Becheanu G, Jinga M, Costache RS, Costache DO, Diculescu M (2020) An overview on primary sclerosing cholangitis. J Clin Med 9(3):754. https://doi.org/10.3390/jcm9030754
Xiang Z, Chen YP, Ma KF, Ye YF, Zheng L, Yang YD, Li YM, Jin X (2013) The role of ursodeoxycholic acid in non-alcoholic steatohepatitis: a systematic review. BMC Gastroenterol 13:140. https://doi.org/10.1186/1471-230X-13-140
Zeng N, Duan W, Chen S, Wu S, Ma H, Ou X, You H, Kong Y, Jia J (2019) Epidemiology and clinical course of primary biliary cholangitis in the Asia-Pacific region: a systematic review and meta-analysis. Hepatol Int 13:788–799. https://doi.org/10.1007/s12072-019-09984-x
Zenouzi R, Weismüller TJ, Hübener P, Schulze K, Bubenheim M, Pannicke N, Weiler-Normann C, Lenzen H, Manns MP, Lohse AW, Schramm C (2014) Low risk of hepatocellular carcinoma in patients with primary sclerosing cholangitis with cirrhosis. Clin Gastroenterol Hepatol 12:1733–1738. https://doi.org/10.1016/j.cgh.2014.02.008
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 21:3554–3563. https://doi.org/10.3748/wjg.v21.i12.3554