中国肝癌早筛策略专家共识

摘要/Abstract

摘要： 原发性肝细胞癌是全世界常见的恶性肿瘤之一,每年一半的新发肝癌发生在中国。大量临床研究和实践证明早筛和早诊可有效降低肝癌的5 年总病死率。因此探索建立适合中国国情的肝癌筛查策略极其迫切。全国多中心前瞻性肝癌极早期预警筛查项目(Prospective suRveillance for very Early hepatoCellular cARcinoma,PreCar)专家组基于国内外主要相关指南、临床实践和PreCar 项目研究最新进展,提出了中国早期肝癌筛查策略和具体流程,旨在为早期肝癌筛查和诊断提供实际方法,提高我国防控水平。

全国多中心前瞻性肝癌极早期预警筛查项目(PreCar)专家组. 中国肝癌早筛策略专家共识[J]. 肝脏, 2021, 26(8): 825-831.

参考文献

[1] Global Burden of Disease Liver Cancer Collaboration.The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol, 2017, 3: 1683-1691.
[2] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68: 394-424.
[3] 安澜, 曾红梅, 郑荣寿, 等.2015 年中国肝癌流行情况分析. 中华肿瘤杂志, 2019, 41: 721-727.
[4] Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391: 1023-1075.
[5] 中国临床肿瘤学会(CSCO). 原发性肝癌诊疗指南(2020). 人民卫生出版社, 2020.
[6] Sung H, Ferlay J, Siegel R, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71: 209-249.
[7] Park JW, Chen MS, Colombo M, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int, 2015, 35: 2155-2166.
[8] Mu XM, Wang W, Jiang Y, et al. Patterns of comorbidity in hepatocellular carcinoma: a network perspective. Int J Environ Res Public Health, 2020, 17: 3108.
[9] Forner A, Reig M, Bruix J.Hepatocellular carcinoma. Lancet, 2018, 391: 1301-1314.
[10] 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019 年版). 中华肝脏病杂志, 2019, 27:938-961.
[11] Baffy G, Brunt EM, Caldwell SH.Hepatocellular carcinoma in nonalcoholic fatty liver disease: an emerging menace. J Hepatol, 2012, 56: 1384-1391.
[12] Huang DQ, EL-Serag HB, Loomba R.Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol, 2021, 18: 223-238.
[13] Xiao J, Wang F, Wong NK, et al. Global liver disease burdens and research trends: analysis from a Chinese perspective. J Hepatol, 2019, 71: 212-221.
[14] 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019 年版). 中华肝脏病杂志, 2020, 28: 112-128.
[15] Kudo M, Matsui O, Izumi N, et al. JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the Liver Cancer Study Group of Japan. Liver Cancer, 2014, 3: 458-468.
[16] Kudo M.Management of hepatocellular carcinoma in Japan as a world-leading model. Liver Cancer, 2018, 7: 134-147.
[17] Sharma SA, Kowgier M, Hansen BE, et al. Toronto HCC risk index: a validated scoring system to predict 10-year risk of HCC in patients with cirrhosis. J Hepatol, 2018, 68: 92-99.
[18] Yang HI, Yuen MF, Chan HLY, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B(REACH-B): development and validation of a predictive score. Lancet Oncol, 2011, 12: 568-574.
[19] Fan C, Li M, Gan Y, et al. A simple AGED score for risk classification of primary liver cancer: development and validation with long-term prospective HBsAg-positive cohorts in Qidong, China. Gut, 2019, 68: 948-949.
[20] Papatheodoridis G, Dalekos G, Sypsa V, et al. PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy. J Hepatol, 2016, 64: 800-806.
[21] Kim JH, Kim YD, Lee M, et al. Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy. J Hepatol, 2018, 69: 1066-1073.
[22] Papatheodoridis GV, Sypsa V, Dalekos GN, et al. Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B. J Hepatol, 2020, 72: 1088-1096.
[23] Raimondi S, Bruno S, Mondelli MU, et al. Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis. J Hepatol, 2009, 50: 1142-1154.
[24] 中华医学会肝病学分会, 中华医学会感染病学分会. 丙型肝炎防治指南(2019 年版). 中华肝脏病杂志, 2019, 27: 962-979.
[25] Monica P, Sergio RT, Juan IE, et al. Non-invasive prediction of liver-related events in patients with HCV-associated compensated advanced chronic liver disease after oral antivirals. J Hepatol, 2020, 72: 472-480.
[26] Fanv R, Papatheodoridis G, Sun J, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol, 2020, 73: 1368-1378.
[27] Wu HC, Yang HI, Wang Q, et al. Plasma DNA methylation marker and hepatocellular carcinoma risk prediction model for the general population. Carcinogenesis, 2017, 38: 1021-1028.
[28] 中华预防医学会肝胆胰疾病预防与控制专业委员会, 中国研究型医院学会肝病专业委员会, 中华医学会肝病学分会, 等. 原发性肝癌的分层筛查与监测指南(2020 版). 中华肝脏病杂志, 2021, 29: 25-40.
[29] Johnson PJ, Pirrie SJ, Cox TF, et al. The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers. Cancer Epidemiol Biomarkers Prev, 2014, 23: 144-153.
[30] Yang JD, Addissie BD, Mara KC, et al. GALAD score for hepatocellular carcinoma detection in comparison with liver ultrasound and proposal of GALADUS score. Cancer Epidemiol Biomarkers Prev, 2019, 28: 531-538.
[31] Berhane S, Toyoda H, Tada T, et al. Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients. Clin Gastroenterol Hepatol, 2016, 14: 875-886.e6.
[32] Zhang HX, Zhu JZ, Xi LT, et al. Validation of the Toronto hepatocellular carcinoma risk index for patients with cirrhosis in China: a retrospective cohort study. World J Surg Oncol, 2019, 17: 75.
[33] 李秀华, 郝新, 邓永红, 等. 应用aMAP 评分评估基层医院慢性肝病人群的肝癌发生风险. 中华肝脏病杂志, 2021, 29: 332-337.
[34] Chen L, Abou-Alfa GK, Zheng B, et al. Genome-scale profiling of circulating cell-free DNA signatures for early detection of hepatocellular carcinoma in cirrhotic patients. Cell Res, 2021, 31: 589-592.
[35] Harris PS, Hansen RM, Gray ME, et al. Hepatocellular carcinoma surveillance: an evidence-based approach. World J Gastroenterol, 2019, 25: 1550-1559.
[36] Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology, 2018, 68: 723-750.
[37] European Association for the Study of the Liver.EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol, 2018, 69: 182-236.
[38] Taketa K, Endo Y, Sekiya C, et al. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection fo hepatocellular carcinoma. Cancer Res, 1993, 53: 5419-5423.
[39] Choi JG, Kim GA, Han SB, et al. Longitudinal assessment of three serum biomarkers to detect very early-stage hepatocellular carcinoma. Hepatology, 2019, 69: 1983-1994.
[40] Kokudo N, Hasegawa K, Akahane M, et al. Evidence-based clinical practice guidelines for hepatocellular carcinoma: the Japan Society of Hepatology 2013 update (3rd JSH-HCC guidelines). Hepatol Res, 2015, 45: 123-127.
[41] Tzartzeva K, Obi J, Rich NE, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology, 2018, 154:1706-1718.
[42] Jeong WK.Surveillance of hepatocellular carcinoma: is only ultrasound enough?. Clin Mol Hepatol, 2017, 23: 222-223.
[43] Nault JC, Martin Y, Caruso S, et al. Clinical impact of genomic diversity from early to advanced hepatocellular carcinoma. Hepatology, 2020, 71: 164-182.
[44] Kobayashi M, Ikeda K, Hosaka T, et al. Dysplastic nodules frequently develop into hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosis. Cancer, 2006, 106: 636-647.
[45] Sato T, Kondo F, Ebara M, et al. Natural history of large regenerative nodules and dysplastic nodules in liver cirrhosis: 28-year follow-up study. Hepatol Int, 2015, 9: 330-336.
[46] Roberts LR, Sirlin CB, Zaiem F, et al. Imaging for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Hepatology, 2018, 7: 401-421.
[47] Guo J, Seo Y, Ren S, et al. Diagnostic performance of contrastenhanced multidetector computed tomography and gadoxetic acid disodium-enhanced magnetic resonance imaging in detecting hepatocellular carcinoma: direct comparison and a meta-analysis. Abdom Radiol (NY), 2016, 41: 1960-1972.
[48] Renzulli M, Biselli M, Brocchi S, et al. New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and highgrade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: a new diagnostic algorithm. Gut, 2018, 67: 1674-1682.
[49] Kim SY, An J, Lim YS, et al. MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma. JAMA Oncol, 2017, 3: 456-463.
[50] Ichikawa T, Sano K, Morisaka H. Diagnosis of pathologically early HCC with EOB-MRI: experiences and current consensus. Liver Cancer, 2014, 3: 97-107.
[51] Inchingolo R, Faletti R, Grazioli L, et al. MR with Gd-EOB-DTPA in assessment of liver nodules in cirrhotic patients. World J Hepatol, 2018, 10: 462-473.
[52] Snyder MW, Kircher M, Hill AJ, et al. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell, 2016, 164: 57-68.
[53] Jiang PY, Sun K, Peng WL, et al. Plasma DNA end-motif profiling as a fragmentomic marker in cancer, pregnancy, and transplantation. Cancer Discov, 2020, 10: 664-673.
[54] Mouliere F, Chandrananda D, Piskorz AM, et al. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med, 2018, 10: eaat4921.
[55] Cristiano S, Leal A, Phallen J, et al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature, 2019, 570: 385-389.
[56] Xu RH, Wei W, Krawczyk M, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater, 2017, 16: 1155-1161.
[57] Kisiel JB, Dukek BA, Kanipakam R, et al. Hepatocellular carcinoma detection by plasma methylated DNA: discovery, phase I pilot, and phase II clinical validation. Hepatology, 2019, 69: 1180-1192.
[58] Chalasani NP, Bhattacharya A, Book A, et al. Algorithm for bloodbased panel of methylated DNA and protein markers to detect early-stage hepatocellular carcinoma with high specificity. J Clin Oncol, 2020, 38: 4577.
[59] Cai JB, Chen L, Zhang Z, et al. Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a noninvasive approach for early detection of hepatocellular carcinoma. Gut, 2019, 68: 2195-2205.
[60] Liao WJ, Yang HY, Xu HF, et al. Noninvasive detection of tumorassociated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing. Oncotarget, 2016, 7: 40481-40490.
[61] Zhou J, Yu L, Gao X, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol, 2011, 29: 4781-4788.
[62] Tomimaru Y, Eguchi H, Nagano H, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol, 2012, 56: 167-175.
[63] Yin HM, Peng XG, Ren P, et al. MicroRNAs as a novel class of diagnostic biomarkers in detection of hepatocellular carcinoma: a meta-analysis. Tumour Biol, 2014, 35: 12317-12326.
[64] Amr KS, Atia HAE, Elbnhawy RAE, et al. Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma. Genes Dis, 2017, 4: 215-221.
[65] Li L, Chen JG, Chen X, et al. Serum miRNAs as predictive and preventive biomarker for pre-clinical hepatocellular carcinoma. Cancer Lett, 2016, 373: 234-240.
[66] Xue XF, Zhao YB, Wang XN, et al. Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma. J Cell Biochem, 2019, 120: 135-142.
[67] Sheng LQ, Li JR, Qin H, et al. Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis. World J Gastrointest Oncol, 2020, 12: 1195-1208.
[68] 中华医学会肝病学分会. 原发性肝癌二级预防共识(2021 年版). 中华肝脏病杂志, 2021, 29: 216-226.