聚乙二醇化干扰素α-2a、聚乙二醇化干扰素α-2b和干扰素α-2b联合利巴韦林治疗慢性丙型肝炎的疗效

Curative effect of ribavirin combined with pegylated(Peg) interferon(IFN) α-2a, PegIFN-α-2b and IFN-α-2b for patients with chronic hepatitis C

目的观察聚乙二醇化干扰素(PegIFN)α-2a、PegIFN-α-2b和干扰素(IFN)α-2b联合利巴韦林治疗慢性丙型肝炎(CHC)患者的疗效。方法回顾性观察278例CHC患者的临床资料,分为接受PegIFN-α-2a、PegIFN-α-2b和IFN-α-2b联合利巴韦林抗病毒治疗组。比较患者治疗前、治疗第4、12、24、48周时各组患者HCV基因分型、HCV RNA载量、ALT和AST的变化。分析各组患者治疗期间ALT/AST复常率、病毒学应答,不同基因型或HCV RNA载量与病毒学应答的相关性。结果停药后随访24周时,各治疗组患者肝功能复常率差异具有统计学意义(χ~2=23.06、P<0.001),以PegIFN-α-2a(180μg)组与PegIFN-α-2b(80μg)组患者复常率较高(分别为76.7%和83.0%)。各治疗组患者快速病毒学应答(RVR)、治疗结束时病毒学应答(ETVR)及持续病毒学应答(SVR)差异均具有统计学意义(χ~2=9.79、P=0.04,χ~2=11.33、P=0.02,χ~2=11.99、P=0.02),以PegIFN-α-2a(180μg)组与PegIFN-α-2b(80μg)组患者较高(分别为62.8%、88.4%、64.0%和64.2%、83.0%、65.1%)。普通IFN-α-2b(600万单位)组、PegIFN-α-2a(180μg)组、PegIFN-α-2b(80μg)组患者依次有13例、54例和68例获得RVR,依次有11例(84.6%)、50例(92.6%)和62例(91.2%)最终获得SVR。入组患者中1b基因型患者243例,其RVR、完全早期病毒学应答(cE VR)和SVR均优于非HCV 1b基因型患者(χ~2=8.23、P<0.001,χ~2=46.26、P=0.01,χ~2=10.22、P<0.001)。普通IFN-α-2b(600万单位)组、PegIFN-α-2a(180μg)组、PegIFN-α-2b(80μg)组低病毒载量(HCV RNA<6.0 Log_(10)拷贝/ml)患者的SVR均优于高病毒载量患者(χ~2=4.10、P=0.04,χ~2=20.89、P<0.001,χ~2=19.60、P<0.001)。结论聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎具有较好疗效,早期RVR对SVR的获得具有很强的预测作用,非基因HCV 1b型和低病毒载量患者疗效优于HCV 1b基因型和高病毒载量患者。

Objective To investigate the curative effect of ribavirin in combination with pegylated （Peg） interferon （IFN） α-2a, PegIFN-α-2b and IFN-α-2b for patients with chronic hepatitis C （CHC）, respectively. Methods Total of 278 CHC patients were administered through combined therapy of ribavirin with PegIFN-α-2a, PegIFN-α-2b and IFN-α-2b, respectively. Genotyping and viral load of hepatitis C virus （HCV） , levels of alanine aminotransferase （ALT） and aspartate aminolransferase （AST） of 278 cases were detected at the 4th, 12th, 24th, and 48th week. The correlation between the normalization rates of ALT/AST, virological response,different genotypes or HCV RNA loads with virological response were analyzed, respectively. Results The biochemical response showed the normalization rates of liver function signifcantly different at 24-week follow-up among different treatment groups （χ2 = 23.06, P 〈 0.001）, patients in Peg-IFNα-2a （180 μg） group and Peg-IFNα-2b （80 μg） group were with higher normalization rates （76.7% and 83.0%, respectively）. The rapid virological response （RVR）, end-of-treatment virological response （ETVR） and sustained virological response （SVR） of patients among different treatment groups were signifcantly different （χ2 = 9.79, P = 0.04; χ2 = 11.33, P = 0.02; χ2 = 11.99, P = 0.02）, patients in PegIFN-α-2a （180 μg） group and PegIFN-α-2b （80 μg） group were with higher levels of the above indicators, which were 62.8%, 88.4%, 64.0% and 64.2%, 83.0%, 65.1%, respectively. In common IFN-α-2 （600 wIU） group, PegIFN-α-2a （180 μg） group and PegIFNα-2b （80 μg） group, there were 13 cases, 54 cases and 68 cases achieved RVR, respectively, while 11 cases （84.6%）, 50 cases （92.6%） and 62 cases （91.2%） achieved SVR. Among the 278 patients, 243 cases were HCV 1bgenotype, whose RVR, complete early virological response （cEVR） and SVR were higher than those of non-HCV 1b genotype （χ2 = 8.23, P 〈 0.001; χ2 = 46.26, P = 0.01; χ2 = 10.22, P 〈 0.001）. In common IFNα-2 （600 wIU） group, PegIFN-α-2a （180 μg） group and PegIFN-α-2b （80 μg） group, the condition of SVR of patients with low viral load （HCV RNA 〈 6.0 log10 copies/ml） were signifcantly superior than those with high viral load （χ2 = 4.10, P = 0.04; χ2 = 20.89, P 〈 0.001; χ2 = 19.60, P 〈 0.001）. Conclusions Treatment of PegIFN-α combined with ribavirin on patients with CHC is effective. The occurrence of early RVR had predictive effect on SVR. The curative effect for patients with non-HCV 1b genotype and low HCV RNA load showed more effective than patients with HCV 1b genotype and high HCV RNA load.