Papatheodoridis George V, Sypsa Vana, Dalekos George N, Yurdaydin Cihan, Van Boemmel Florian, Buti Maria, Calleja Jose Luis, Chi Heng, Goulis John, Manolakopoulos Spilios, Loglio Alessandro, Voulgaris Theodoros, Gatselis Nikolaos, Keskin Onur, Veelken Rhea, Lopez-Gomez Marta, Hansen Bettina E, Savvidou Savvoula, Kourikou Anastasia, Vlachogiannakos John, Galanis Kostas, Idilman Ramazan, Esteban Rafael, Janssen Harry L A, Berg Thomas, Lampertico Pietro
Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece.
J Hepatol. 2020 Jun;72(6):1088-1096. doi: 10.1016/j.jhep.2020.01.007. Epub 2020 Jan 22.
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting.
Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5.
In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups.
In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy.
In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.
慢性乙型肝炎（CHB）患者即使经过5年的口服治疗仍可能发生肝细胞癌（HCC），且难以预测。我们评估了这种情况下HCC发生的预测因素以及HCC监测的必要性。
在纳入PAGE - B队列的1951例成年白种CHB患者中，1427例（73%）在治疗后完成了超过5年的随访，到第5年时未发生HCC。从治疗开始的中位随访时间为8.4年。建立了基于积分的风险评分来预测第5年后的HCC风险。
在第5 - 12年，1427例患者中有33例（2.3%）被诊断为HCC，8年、10年和12年的累积发病率分别为2.4%、3.2%和3.8%。年龄较大或年龄>50岁、基线肝硬化以及第5年时肝脏硬度（LSM）≥12 kPa与HCC风险增加独立相关。在基线无肝硬化且第5年LSM < 12的患者中，HCC发病率低于有肝硬化的患者；在基线有肝硬化的患者中，第5年LSM < 12的患者HCC发病率低于LSM≥12 kPa的患者。CAGE - B评分基于第5年的年龄、基线肝硬化以及与第5年LSM的关系，SAGE - B评分仅基于第5年的年龄和LSM（c指数 = 0.809 - 0.814，自抽样验证后为0.805 - 0.806）。两种评分在其低风险组中对HCC发生的阴性预测值均为100%。
在白种CHB患者中，抗病毒治疗的前5年后HCC风险取决于年龄、基线肝硬化状态以及第5年时的LSM。CAGE - B评分，尤其是SAGE - B评分，是治疗5年后HCC预测和监测的简单可靠风险评分。
在慢性乙型肝炎的白种人中，恩替卡韦或替诺福韦治疗的前5年后肝细胞癌的风险取决于年龄、基线肝硬化状态以及第5年时的肝脏硬度，这可为治疗5年后的肝细胞癌预测和监测提供简单可靠的风险评分。在基线有肝硬化的患者中，第5年肝脏硬度<12 kPa与较低的HCC风险相关，但仍可能需要监测。
