Pellicelli Adriano M, Vignally Pascal, Messina Vincenzo, Izzi Antonio, Mazzoni Ettore, Barlattani Angelo, Bacca Donato, Romano Mario, Mecenate Fabrizio, Stroffolini Tommaso, Furlan Caterina, Picardi Antonio, Gentilucci Umberto V, Gulminetti Roberto, Bonaventura Maria E, Villani Roberto, D'Ambrosio Cecilia, Paffetti Amerigo, Mastropietro Cristina, Marignani Massimo, Fondacaro Lucia, Cerasari Giuseppe, Andreoli Arnaldo, Barbarini Giorgio
Liver Unit Azienda Ospedaliera San Camillo Forlanini Rome, Italy.
Instituto Superiore Sanità Rome, Italy.
Ann Hepatol. 2014 Jul-Aug;13(4):376-85.
BACKGROUND AND RATIONALE OF THE STUDY: Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded.
HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003).
Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeA-gnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.
研究背景与原理：在真实队列中，长期核苷/核苷酸（NUC）对HBeAg阴性D基因型患者肝细胞癌（HCC）发病率的影响尚未得到充分研究。我们的目的是评估肝纤维化和其他变量对该患者群体中HCC发病率的影响。在745例慢性乙型肝炎（CHB）患者中，选择306例HBeAg阴性D基因型患者纳入本研究。所有患者接受NUC治疗至少18个月。纳入CHB或代偿期肝硬化患者。排除在NUC治疗的前18个月内或之前被诊断为HCC的患者。
2例CHB患者（1.0%）和23例肝硬化患者（20%）被诊断为HCC（OR = 24.41，95%CI 5.40 < OR < 153.2；p < 0.0001）。多因素分析显示，HCC风险与年龄≥60岁（OR = 6.45，95%CI 1.22至34.0；p = 0.02）和肝硬化（OR = 12.1，95%CI 1.39至106.2；p = 0.02）独立相关，但与病毒学应答（VR）、既往对NUC的耐药性或挽救治疗无关。肝硬化患者的多因素分析显示，只有年龄≥60岁是与HCC相关的独立危险因素（p = 0.003）。
肝硬化和年龄≥60岁是D基因型HBeAg阴性患者发生HCC的更强危险因素。挽救治疗后实现VR的患者既往对NUC的耐药性不是HCC的预测因素。当患者已进展为肝硬化时，VR似乎并未显著降低HCC的总体发病率。
