Finkelmeier Fabian, Dultz Georg, Peiffer Kai-Henrik, Kronenberger Bernd, Krauss Franziska, Zeuzem Stefan, Sarrazin Christoph, Vermehren Johannes, Waidmann Oliver
Schwerpunkt Gastroenterologie und Hepatologie, Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
Gastroenterologie, Hepatologie, Allgemeine Innere Medizin, Herz-Jesu-Krankenhaus Fulda, Fulda, Germany.
Liver Cancer. 2018 May;7(2):190-204. doi: 10.1159/000486812. Epub 2018 Mar 1.
The aim of the study was to evaluate the risk of hepatocellular carcinoma (HCC) development after treatment with direct-acting antivirals (DAAs) and to compare HCC occurrence in these patients with that among patients treated with interferon (IFN)-based therapies.
We analyzed a large cohort with chronic hepatitis C virus patients for the onset of new HCC after DAA treatment. A historical IFN-treated cohort was investigated for comparison.
A total of 819 patients were included in the DAA group. The median follow-up period was 263 days (0-1,001). Twenty-five patients (3.6 HCCs/100 person-years; 3.1%) were diagnosed with de novo HCC within the time of observation. No patient without cirrhosis had developed HCC. Patients with newly diagnosed HCC were mostly male, older, and treatment-experienced and had a lower 12-week sustained virologic response (SVR12) rate and higher levels of liver inflammation markers. The median time to HCC was 312 days (0-880). Investigation of the subcohort of 269 cirrhotic patients yielded an HCC rate of 8.9 HCCs/100 person-years. In this cohort, non-SVR12 was an independent risk factor for de novo HCC (HR 4.48; 95% CI 1.51-13.12; = 0.007). Twenty-four patients (96%) with new HCC were Child-Pugh class A and 17 (68%) were diagnosed in early BCLC stage A. For the IFN-treated patients, we calculated an overall risk of HCC occurrence of 1.3/100 person-years (19 patients out of 351; 5.4%). The median time to diagnosis was 38.8 months (0-113).
The de novo HCC rates did not differ between the DAA-treated patients and those who received IFN. Achievement of SVR is of utmost importance for HCC prevention.
本研究旨在评估直接作用抗病毒药物（DAA）治疗后肝细胞癌（HCC）发生的风险，并比较这些患者与接受基于干扰素（IFN）治疗的患者中HCC的发生率。
我们分析了一大群慢性丙型肝炎病毒患者，以观察DAA治疗后新发性HCC的发病情况。对一个接受过IFN治疗的历史队列进行了调查以作比较。
DAA组共纳入819例患者。中位随访期为263天（0 - 1001天）。在观察期内，25例患者（3.6例HCC/100人年；3.1%）被诊断为新发HCC。无肝硬化患者未发生HCC。新诊断为HCC的患者大多为男性、年龄较大且有治疗史，12周持续病毒学应答（SVR12）率较低且肝脏炎症标志物水平较高。发生HCC的中位时间为312天（0 - 880天）。对269例肝硬化患者亚组的调查显示，HCC发生率为8.9例HCC/100人年。在该队列中，未达到SVR12是新发HCC的独立危险因素（风险比4.48；95%置信区间1.51 - 13.12；P = 0.007）。24例（96%）新发HCC患者为Child-Pugh A级，17例（68%）在BCLC早期A期被诊断。对于接受IFN治疗的患者，我们计算出HCC发生的总体风险为1.3/100人年（351例中有19例；5.4%）。诊断的中位时间为38.8个月（0 - 113个月）。
接受DAA治疗的患者与接受IFN治疗的患者新发HCC率无差异。实现SVR对预防HCC至关重要。
