Background: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood.
Patients and Methods: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis.
Results: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5– 4.7) for DAA and 9.3 years (IQR: 6.6– 12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20– 18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤ 0.001, depending on covariates). A HR of 6.62 (CI: 2.01– 21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups.
Conclusion: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.



中文翻译：

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使用直接抗病毒药物治疗慢性丙型肝炎后肝细胞癌的发生率仍然很高：来自瑞士肝移植中心的分析

背景：直接作用抗病毒药物 (DAA) 彻底改变了慢性丙型肝炎 (CHC) 的治疗，并取代了以前的 PEG-干扰素/利巴韦林 (PEG-IFN/RBV) 治疗。CHC 和晚期肝病患者患肝细胞癌 (HCC) 的风险增加。然而，基于 DAA 的 CHC 治疗对后续 HCC 发病率的影响仍然知之甚少。
患者和方法：这项回顾性单机构队列研究包括 243 名接受 PEG-IFN/RBV 治疗的连续患者和 263 名接受 DAA 治疗的患者。多变量原因特异性 Cox 比例风险模型用于比较治疗类型之间发生 HCC 的时间，审查在竞争事件发生时死亡或接受原位肝移植 (OLT) 的患者。年龄、性别、BMI、病毒载量、肝硬化、纤维化阶段、糖尿病、病毒基因型和既往 PEG-IFN/RBV（在 DAA 之前）被用作协变量。此外，我们进行了倾向得分匹配分析。
结果：DAA 治疗后观察到 19 例 HCC，而 PEG-IFN/RBV 治疗后观察到 18 例。DAA 患者的中位随访时间为 4.1 年（IQR：3.5-4.7），PEG-IFN/RBV 组为 9.3 年（IQR：6.6-12.4）。在未经调整的 Cox 模型中，估计 DAA 与 PEG-IFN/RBV 后 HCC 的风险比 (HR) 为 6.40（CI：2.20–18.61，p=0.006）。在多变量 Cox 比例风险模型中，年龄和肝硬化被确定为进一步的 HCC 风险因素，但 DAA 与 PEG-IFN/RBV 的 HR 估计值仍然表明与 DAA 治疗相关的风险显着增加（HR 在 7.23 和 11.52 之间，p≤0.001 ，取决于协变量）。在倾向评分匹配分析中估计 DAA 与 PEG-IFN/RBV 的 HR 为 6.62（CI：2.01-21.84，p=0.002）。
结论：在一项来自三级医院的队列研究中，与 PEG-IFN/RBV 治疗相比，开始 DAA 治疗后 HCC 的发生率更高。我们的数据强化了在成功治疗 CHC 后应继续监测的建议。