Cavalletto Luisa, Bertoli Eleonora, Mescoli Claudia, Aliberti Camillo, Quaranta Maria Giovanna, Kondili Loreta, Chemello Liliana
UOC Clinica Medica 5, Regional Center for Liver Disease Outpatient Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
Unit of Emergency Medicine, Department of Systems Medicine-DIDAS, University of Padova, 35128 Padova, Italy.
Cancers (Basel). 2025 Apr 30;17(9):1528. doi: 10.3390/cancers17091528.
Novel direct antiviral-acting (DAA) molecules significantly improved efficacy and ameliorated outcomes of patients with chronic hepatitis C (CHC). The extensive use of DAA from 2015, due to large access to therapy, maximized rates of viral eradication with a safety profile in the majority of cases.
We evaluated risk factors and the incidence of related clinical events and hepatocellular carcinoma (HCC) in cases with sustained virologic response (SVR) after DAA. We also aimed to apply a score assessment to identify the individual patient with unfavorable outcomes during an average follow-up (FU) of five years.
In total, 470 cases consecutively recruited with CHC have been compared by non-invasive tests (NIT), as APRI, FORNS, FIB-4, LSPS, and transient elastography (TE) liver stiffness measurement (LSM), to identify cutoff related to major event onset.
Grouping of cases without or with related events development of both types hepatic (HE) (i.e., HCC or further cirrhosis decompensation or/with hospitalized septic state) or extrahepatic (EHE) (i.e., other tumors, bleeding, or thrombotic episodes and other organs pathologic conditions not liver related)allowed us to select the parameters to propose a novel risk stratification system (RISS) for the identification of the remnant individual patient's risk for HCC occurrence, orthotopic liver transplant (OLT) need, or death during long-term follow-up (FU).
Patients with cirrhosis and portal hypertension (PH) maintained a higher LSM mean value (>25 kPa), showed the lowest reduction of NIT scores, and developed events in 80/108 (74%) cases (67 and 13 of HE and EHE type), even after long-term successful DAA therapy. Furthermore, cases with RISS score ≥ 8 demonstrated a significant incidence of HCC (37/46, 80.4%) and a reduction in survival rate to 65.4% at 5-year FU.
新型直接抗病毒（DAA）分子显著提高了慢性丙型肝炎（CHC）患者的疗效并改善了预后。自2015年起，由于大量患者能够接受治疗，DAA的广泛使用在大多数情况下使病毒根除率最大化且具有良好的安全性。
我们评估了接受DAA治疗后获得持续病毒学应答（SVR）的患者的危险因素以及相关临床事件和肝细胞癌（HCC）的发生率。我们还旨在应用一种评分评估方法，以识别在平均五年的随访（FU）期间预后不良的个体患者。
通过非侵入性检测（NIT），如APRI、Forns、FIB-4、LSPS以及瞬时弹性成像（TE）肝脏硬度测量（LSM），对总共470例连续招募的CHC患者进行比较，以确定与主要事件发生相关的临界值。
对未发生或发生了肝脏相关（HE）（即HCC、进一步的肝硬化失代偿或/和住院脓毒症状态）或肝外相关（EHE）（即其他肿瘤、出血或血栓形成事件以及其他与肝脏无关的器官病理状况）两种类型事件的病例进行分组，使我们能够选择参数来提出一种新的风险分层系统（RISS），用于识别个体患者在长期随访（FU）期间发生HCC、需要原位肝移植（OLT）或死亡的残余风险。
即使在长期成功的DAA治疗后，肝硬化和门静脉高压（PH）患者的LSM平均值仍较高（>25 kPa），NIT评分降低幅度最小，且在80/108（74%）例患者中发生了事件（HE型和EHE型分别为67例和13例）。此外，RISS评分≥8的患者HCC发生率显著（37/46，80.4%），且在5年随访时生存率降至65.4%。
