Sanduzzi-Zamparelli Marco, Mariño Zoe, Lens Sabela, Sapena Victor, Iserte Gemma, Pla Anna, Granel Núria, Bartres Concepció, Llarch Neus, Vilana Ramón, Nuñez Isabel, Darnell Anna, Belmonte Ernest, García-Criado Angeles, Díaz Alba, Muñoz-Martinez Sergio, Ayuso Carmen, Bianchi Luis, Fuster-Anglada Carla, Rimola Jordi, Forner Alejandro, Torres Ferran, Bruix Jordi, Forns Xavier, Reig Maria
BCLC Group. Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Barcelona, Spain.
Liver Unit, Hospital Clinic of Barcelona, IDIBAPS. CIBERehd, University of Barcelona, Spain.
J Hepatol. 2022 Apr;76(4):874-882. doi: 10.1016/j.jhep.2021.11.023. Epub 2021 Nov 29.
BACKGROUND & AIMS: Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population.
We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months.
A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified.
Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs.
Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.
在直接抗病毒药物（DAA）治疗前识别未定性肝结节（NCLN）与丙型肝炎病毒（HCV）患者肝细胞癌（HCC）风险增加相关。在开始DAA治疗前已排除NCLN且获得持续病毒学应答（SVR）的F3/F4期患者中，HCC风险尚未明确。本研究旨在评估该人群中HCC的发病率。
我们进行了一项前瞻性研究，纳入了F3/F4纤维化的HCV感染患者，这些患者无HCC病史且在接受DAA治疗后获得了SVR。仅当患者在SVR后30天内接受超声检查排除了HCC/NCLN存在时才纳入研究。所有患者每6个月评估一次，直至发生原发性肝癌、死亡或撤回知情同意。HCC发病率以每100患者年（/100PY）表示。在最初的48个月内，每6个月计算一次对筛查计划的依从性。
共纳入185例患者（63/122，F3/F4）。在肝硬化患者中，92%为Child-Pugh A级，42.7%有临床显著性门静脉高压（CSPH）。分别有84.9%和15.1%的患者白蛋白-胆红素评分是1分和2分。临床和影像学的中位随访时间分别为52.4个月和48个月。10例患者发生了HCC：整个队列中HCC发病率为1.46/100PY（95%CI 0.79 - 2.71），仅F4期患者中为2.24/100PY（95%CI 1.21 - 4.17），CSPH患者中为3.63/100PY（95%CI 1.95 - 6.74）。F3期患者未发生HCC。SVR与HCC发生之间的中位时间为28.1个月；还发现了12例非原发性肝癌。
SVR时无NCLN的肝硬化患者仍有发生HCC的风险。F3期患者未发生HCC强化了其较低的癌症风险，但需要前瞻性研究将他们排除在筛查计划之外。
HCV相关肝硬化患者在持续病毒学应答时无未定性肝结节，尽管病毒已治愈，但仍有肝细胞癌风险。然而，在无未定性肝结节的F3纤维化患者中，成功的直接抗病毒治疗后的癌症风险较低。如果在更大规模的前瞻性研究中得到证实，可能需要重新审视这组患者目前的筛查建议。
