17
Prediction and Need for Surveillance
of Hepatocellular Carcinoma (HCC)
Development after the First 5 Years of Entecavir
(ETV) or Tenofovir Disoproxil Fumarate (TDF)
Therapy in Caucasian Chronic Hepatitis B
(CHB) Patients of the PAGE-B Cohort
George V. Papatheodoridis1, George N. Dalekos2, Cihan
Yurdaydin3, Vana Sypsa4, Florian van Bömmel5, Maria
Buti6, Jose Luis Calleja7, Heng Chi8, Ioannis Goulis9,
Spilios Manolakopoulos10,11, Alessandro Loglio12, Spyros
Siakavellas11, Nikolaos K. Gatselis13, Onur Keskin14, Rhea
Veelken15, Marta Lopez-Gomez16, Bettina E. Hansen8,17,
Savvoula Savvidou18, Anastasia Kourikou19, Ioannis
Vlachogiannakos1, Kostas Galanis13, Ramazan Idilman3,
Rafael Esteban20, Harry L. A. Janssen21, Thomas Berg22 and
Pietro Lampertico23, (1)Department of Gastroenterology,
Medical School of National & Kapodistrian University of Athens,
Laiko General Hospital, Athens, (2)Department of Medicine
and Research Laboratory of Internal Medicine, University
of Thessaly, (3)Gastroenterology, Ankara University, (4)
Department of Hygiene, Epidemiology & Medical Statistics,
Medical School of National and Kapodistrian University of
Athens, (5)Clinic for Gastroenterology and Rheumatology,
University Clinic Leipzig, (6)Hospital Universitari Vall
d’Hebron, Barcelona, Spain, (7)Hospital Universitario Puerta
De Hierro, (8)Department of Gastroenterology & Hepatology
Erasmus MC, University Medical Center, (9)4th Department
of Internal Medicine, Hippokratio Hospital, Aristotle University
of Thessaloniki, (10)2nd Academic Department of Internal
Medicine, Medical School of National & Kapodistrian University
of Athens, Hippokratio General Hospital of Athens, (11)
Department of Gastroenterology, Medical School of National
and Kapodistrian University of Athens, Laiko General Hospital
of Athens, (12)Division of Gastroenterology and Hepatology,
Fondazione Irccs Cà Granda Ospedale Maggiore Policlinico,
Università Degli Studi Di Milano, Italy, (13)Department of
Internal Medicine, Thessalia University Medical School, (14)
Department of Gastroenterology, University of Ankara Medical
School, (15)Section of Hepatology, Clinic for Gastroenterology
and Rheumatology, University Clinic Leipzig, (16)Hospital U
Puerta De Hierro, Idiphim Ciberehd, (17)Liver Clinic, Toronto
Western & General Hospital, University Health Network,
(18)4th Department of Internal Medicine, Αristotle University
of Thessaloniki Medical School, (19)2nd Department of
Internal Medicine, Medical School of National & Kapodistrian
University of Athens, Hippokratio General Hospital of
Athens, (20)Department of Internal Medicine/Liver Unit, Vall
D’hebron University Hospital, (21)Toronto Centre for Liver
Disease, University Health Network, (22)Department of
Gastroenterology and Rheumatology, Section of Hepatology,
University Hospital Leipzig, (23)CRC “AM e a Migliavacca”
Center for Liver Disease, Division of Gastrotnerology and
Hepatology, Fondazione Irccs Cà Granda Ospedale Maggiore
Policlinico, Università Degli Studi Di Milano
Background: We recently showed that the HCC incidence
is decreasing after 5 years of ETV/TDF, but HCC may still
develop and cannot be easily predicted. We assessed
predictors and need for HCC surveillance beyond year
5 of ETV/TDF in CHB patients. Methods: Of 1951 adult
Caucasians with CHB±compensated cirrhosis included in
the PAGE-B cohort, 1427 (73%) have completed followup
>5 years without HCC until year 5 (age at year 5:57±13
years, males:70%, baseline cirrhosis:26%). Mean followup
has been 8.1±1.6 (median:8.3) years from ETV/TDF
onset. The cumulative HCC incidence rates derived from
Kaplan-Meier estimates. Results: In years 5-13, HCC has
been diagnosed in 33/1427 (2.3%) patients with cumulative
incidence 0.7%,1.8%,2.4%,3.2%,3.8% at year 6,7,8,10,13,
respectively. In multivariable Cox regression analysis,
only age [RH:1.08 (1.04-1.13), P<0.001] and presence
of cirrhosis at baseline [RH:2.45 (1.03-5.86), P=0.043] or
year 5 [RH:2.90 (1.21-7.41), P=0.018] were independently
associated with HCC development in years 5-13. After year
5, HCC developed only in cases >50 years old (33/992, 3.3%)
and in none of 435 cases ≤50 years old at year 5 (P<0.001).
Cirrhosis at baseline or year 5 was present in 62/429 (15%)
or 8/254 (3%) of patients aged ≤50 and 308/963 (32%) or
70/676 (10%) of patients >50 years at year 5 and available
data (P<0.001). The 6,8,10-year HCC incidence was lower
in 658 non-cirrhotics at baseline (0.6%,1.7%,2.0%) than 206
patients with cirrhosis reversion (stiffness <12 kPa) at year
5 (1.0%,5.1%,8.0%; P=0.001) or 66 patients who maintained
cirrhosis (1.5%,7.0%,7.0%; P=0.005); HCC incidence did not
differ in the latter two subgroups (P=0.657). If cirrhosis was not
considered, HCC development was associated with age and
platelets <150x109/L at year 5 [RH:2.28 (1.07-4.85), P=0.032].
In patients >50 years old, the 6,8,10-year HCC incidence was
1.3%,5%,8.9% and 0.8%,3.1%,3.8% in cases with platelets
<150 and ≥150x109/L (P=0.037).
Conclusion: HCC after the
first 5 years of ETV/TDF therapy seems to develop exclusively
in patients older than 50 years. Elastographic reversion of
cirrhosis at 5 years does not appear to decrease the HCC
risk. Platelets are not useful for excluding patients from HCC
surveillance after year 5, as the annual HCC risk in any
platelet subgroup is >0.2%, the threshold for cost-effective
HCC surveillance. Thus, HCC surveillance should continue
in all patients >50 years old and probably in the few cirrhotics
≤50 years old.作者: StephenW 时间: 2018-10-4 21:51
17
预测和需要监督
肝细胞癌（HCC）
恩替卡韦前5年后的发展
（ETV）或替诺福韦地索普西富马酸盐（TDF）
白种人慢性乙型肝炎的治疗
（CHB）PAGE-B队列的患者
George V. Papatheodoridis1，George N. Dalekos2，Cihan
Yurdaydin3，Vana Sypsa4，FlorianvanBömmel5，Maria
Buti6，Jose Luis Calleja7，Heng Chi8，Ioannis Goulis9，
Spilios Manolakopoulos10,11，Alessandro Loglio12，Spyros
Siakavellas11，Nikolaos K. Gatselis13，Onur Keskin14，Rhea
Veelken15，Marta Lopez-Gomez16，Bettina E. Hansen8,17，
Savvoula Savvidou18，Anastasia Kourikou19，Ioannis
Vlachogiannakos1，Kostas Galanis13，Ramazan Idilman3，
Rafael Esteban20，Harry L. A. Janssen21，Thomas Berg22和
Pietro Lampertico23，（1）胃肠病学系，
雅典国立和卡波迪斯特拉大学医学院，
雅典莱科总医院（2）医学系
大学内科学研究室
of Thessaly，（3）Ankara University，Gastroenterology，（4）
卫生，流行病学和医学统计学系，
国立大学医学院和卡波迪斯特拉大学
雅典，（5）胃肠病学和风湿病学诊所，
大学诊所莱比锡，（6）瓦大学医院
d'Hebron，巴塞罗那，西班牙，（7）Universitario Universitario Puerta
De Hierro，（8）胃肠病学和肝病学系
Erasmus MC，大学医学中心，（9）第四部
内科学，Hippokratio医院，亚里士多德大学
塞萨洛尼基，（10）内部第二学术部
医学，国立和Kapodistrian大学医学院
雅典，Hippokratio雅典总医院，（11）
国立医学院消化内科
和莱科总医院的雅典卡波迪斯特拉大学
雅典，（12）胃肠病学和肝病学，
FondazioneIrccsCàGrandaOspedale Maggiore Policlinico，
意大利米兰德意大利米兰大学（13）
Thessalia大学医学院内科，（14）
安卡拉大学医学院消化内科
学校，（15）肝病学，消化内科诊所
莱比锡大学诊所和风湿病学，（16）U医院
Puerta De Hierro，Idiphim Ciberehd，（17）多伦多肝脏诊所
西部和总医院，大学健康网络，
（18）亚里士多德大学第四内科
塞萨洛尼基医学院，（19）第二系
内科，国立和Kapodistrian医学院
雅典大学，Hippokratio综合医院
雅典，（20）瓦尔内科/肝脏科
D'Hebron大学医院，（21）多伦多肝脏中心
疾病，大学卫生网，（22）系
胃肠病学和风湿病学，肝病学科，
莱比锡大学医院，（23）CRC“AM e a Migliavacca”
肝病中心，胃肠病学和
Hepatology，FondazioneIrccsCàGrandaOspedale Maggiore
Policlinico，UniversitàDegliStudi Di Milano
背景：我们最近发现了HCC的发病率
ETV / TDF 5年后逐渐减少，但HCC仍可能
发展，不容易预测。我们评估了
超过一年的HCC监测的预测因子和需求
CHB患者中有5例ETV / TDF。方法：1951年成人
患有CHB±代偿性肝硬化的高加索人包括在内
PAGE-B队列，1427（73％）已完成随访
> 5年无HCC直至第5年（第5年龄：57±13岁）
年，男性：70％，基线肝硬化：26％）。平均随访
ETV / TDF为8.1±1.6（中位数：8.3）年
发作。累积的HCC发病率来源于
Kaplan-Meier估计。结果：在5-13岁，HCC有
已确诊为33/1427（2.3％）累积患者
发病率分别为6,7,8,10,13，分别为0.7％，1.8％，2.4％，3.2％，3.8％，
分别。在多变量Cox回归分析中，
只有年龄[RH：1.08（1.04-1.13），P <0.001]和存在
基线时的肝硬化[RH：2.45（1.03-5.86），P = 0.043]或
第5年[RH：2.90（1.21-7.41），P = 0.018]是独立的
与5-13岁的HCC发展相关。一年之后
5，HCC仅在> 50岁的情况下开发（33 / 1992,3.3％）
并且在第5年≤35岁的435例患者中没有一例（P <0.001）。
基线或第5年的肝硬化出现在62/429（15％）
或8/254（3％）年龄≤50和308/963（32％）或
70/676（10％）患者在第5年> 50岁并且可用
数据（P <0.001）。 6，8，10年的HCC发病率较低
658例非基础肝硬化患者（0.6％，1.7％，2.0％）比206例
患者肝硬化逆转（僵硬<12 kPa）
5（1.0％，5.1％，8.0％; P = 0.001）或66名维持的患者
肝硬化（1.5％，7.0％，7.0％; P = 0.005）; HCC发病率没有
后两个亚组不同（P = 0.657）。如果没有肝硬化
考虑到，HCC的发展与年龄和年龄有关
血小板在第5年<150×109 / L [RH：2.28（1.07-4.85），P = 0.032]。
在> 50岁的患者中，6，8，10年的HCC发病率为
血小板病例为1.3％，5％，8.9％和0.8％，3.1％，3.8％
<150且≥150x109/ L（P = 0.037）。
结论：HCC后
ETV / TDF治疗的前5年似乎完全发展
在50岁以上的患者。 弹性成像的逆转
5年的肝硬化似乎不会降低HCC
风险。 血小板不能用于排除HCC患者
5年后的监测，作为每年的HCC风险
血小板亚组> 0.2％，具有成本效益的阈值
HCC监测。 因此，HCC监测应继续进行
在所有> 50岁的患者中，可能在少数肝硬化患者中
≤50岁。