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.

Methods

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.

Results

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.

Conclusions

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.

Lay summary

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.

中文翻译：

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无非特征性结节的晚期肝病患者 HCV 治愈后的肝癌风险

背景与目标

在直接作用抗病毒药物 (DAA) 之前识别非特征性肝结节 (NCLN) 与 HCV 患者的肝细胞癌 (HCC) 风险增加相关。在开始 DAA 之前和持续病毒学应答 (SVR) 之前已排除 NCLN 的 F3/F4 患者的 HCC 风险尚未确定。本研究旨在估计该人群的 HCC 发病率。

方法

我们进行了一项前瞻性研究，纳入了 F3/F4 纤维化、无 HCC 病史且在 DAA 后实现 SVR 的 HCV 感染患者。只有在 SVR 后 30 天内接受了排除 HCC/NCLN 存在的超声成像的患者才被纳入。所有患者每 6 个月接受一次评估，直至发展为原发性肝癌、死亡或撤回知情同意。HCC 发病率以每 100 患者年 (/100PY) 表示。前 48 个月每 6 个月计算一次筛查计划的依从性。

结果

共纳入 185 名患者（63/122，F3/F4）。在肝硬化患者中，92% 为 Child-Pugh A 型，42.7% 为临床上显着的门静脉高压症 (CSPH)。白蛋白-胆红素评分分别在 84.9% 和 15.1% 的患者中为 1 分和 2 分。中位临床和影像学随访时间分别为 52.4 个月和 48 个月。10 名患者发生 HCC：整个队列的 HCC 发病率为 1.46/100PY (95% CI 0.79-2.71)，仅 F4 为 2.24/100PY (95% CI 1.21-4.17)，3.63/100PY (95% CI 1.95-6.74)在 CSPH 患者中。F3 患者未登记 HCC。SVR 和 HCC 发生之间的中位时间为 28.1 个月；还发现了 12 种非原发性肝癌。

结论

SVR 时无 NCLN 的肝硬化患者仍有发生 HCC 的风险。F3 患者不存在 HCC 增加了他们的边缘癌症风险，但需要前瞻性研究将他们排除在筛查计划之外。

总结

HCV 相关肝硬化患者在持续病毒学应答下没有非特征性肝结节，尽管病毒治愈，但仍有发生肝细胞癌的风险。然而，在没有非特征性肝结节的 F3 纤维化患者中，成功进行直接抗病毒治疗后的癌症风险微乎其微。如果在更大的前瞻性研究中得到证实，则可能需要在这组患者中重新审视当前的筛查建议。