Sometani Emi, Hikita Hayato, Murai Kazuhiro, Toyoda Hidenori, Tanaka Satoshi, Oze Tsugiko, Sung Jihyun, Shimoda Akiyoshi, Fukuoka Makoto, Shigeno Satoshi, Fukutomi Keisuke, Shirai Kumiko, Tahata Yuki, Saito Yoshinobu, Nishio Akira, Furuta Kunimaro, Kodama Takahiro, Sakamori Ryotaro, Tatsumi Tomohide, Mita Eiji, Umezawa Akihiro, Tanaka Yasuhito, Takehara Tetsuo
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
Hepatol Res. 2024 Sep 18. doi: 10.1111/hepr.14111.
Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C.
We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15.
Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86 ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB-4 index, alpha-fetoprotein and gamma-glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0 ng/mL, gamma-glutamyl transpeptidase ≥22 U/L, FIB-4 index ≥1.93, and GDF-15 ≥1.17 ng/mL groups. In patients with no or more than three of these five risk factors, the 10-year HCC cumulative incidence rates were 0% and 41.0%, respectively.
High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs.
慢性乙型肝炎（CHB）患者即使接受核苷（酸）类似物治疗，仍有发生肝细胞癌（HCC）的风险。我们评估了HCC发生的危险因素，包括血清乙型肝炎病毒（HBV）RNA、乙型肝炎核心相关抗原水平以及生长分化因子15（GDF15）水平，后者是慢性丙型肝炎患者HCC发生的一个预测指标。
我们收集了接受核苷（酸）类似物治疗1年以上且HBV DNA水平低于3.0 log IU/mL、无HCC病史的CHB患者的临床资料并储存其血清。我们检测了血清HBV RNA和GDF15水平。
在242例CHB患者中，57例可检测到HBV RNA，所有患者均对GDF15进行了定量检测。GDF15水平中位数为0.86 ng/mL。Cox比例风险分析显示，男性以及较高的GDF15、FIB-4指数、甲胎蛋白和γ-谷氨酰转肽酶是HCC的独立危险因素。高于定量下限的HBV RNA的存在不是一个危险因素。当我们根据约登指数设定临界值时，男性、甲胎蛋白≥3.0 ng/mL、γ-谷氨酰转肽酶≥22 U/L、FIB-4指数≥1.93以及GDF-15≥1.17 ng/mL组的HCC累积发病率显著更高。在无这五个危险因素或有超过三个危险因素的患者中，10年HCC累积发病率分别为0%和41.0%。
高血清GDF15是接受核苷（酸）类似物治疗的CHB患者发生HCC的独立危险因素。
