Delić Dragan
Klinicki centar Srbije, Beograd, Institut za infektivne i tropske bolesti.
Med Pregl. 2006 Sep-Oct;59(9-10):415-9. doi: 10.2298/mpns0610415d.
Chronic hepatitis C remains a formidable threat to world health. Progression of chronic hepatitis C is associated with significant morbidity: cirrhosis, hepatic failure and hepatocellular carcinoma. The introduction of combined therapy with pegylated interferons and ribavirin has increased the sustained virologic response (SVR) in the much higher percentage than with previous treatment options, while the level of adverse effects has not changed significantely. The aim of this study was to assess the efficacy and safety of combined therapy (peginterferon alfa-2a + ribavirin) in Serbian population.
Patients with genotypes 1 and 4 received a 48-week course of therapy of peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). Patients with genotypes 2 and 3 received the same doses of both drugs, but during 24 weeks. All patients were scheduled for follow-up visit 24 weeks after the end of treatment. Physicians were instructed to adjust the dose of both drugs if adverse events occurred. Standard PCR tests were used for qualitative and quantitative detection of viral RNA, as well as for determination of patients' genotypes.
A total of 95 patients were enrolled in the sutdy. The majority of patients were male (65.26%), aged 40 or under (52.63%), with genotype 1 (63.15%). The average duration of infection was 2.81 + 4.89 years, but still, the majority of patients (51.58%) had HCV infection for less than 2 years. Fibrosis was present in 69.47 % of patients, and cirrhosis in 21.06%. The most common mode of infection was through i.v. drug use (29.48%), but it was unknown in 32.63% of patients. The mean ALT value was 100.44 + 70.26, with the total of 93.68% of patients having elevated ALT level. At the end of treatment (EoT) time point, data were collected from 66 patients (69.47%), while at the end of follow-up (EoFU), data were collected from 68 patients (71.58%). This unusuall drop-out rate of 28.42% was mainly caused by losing contact with patients (14.74%) and premature termination of therapy (13.68%). The primary parameter of efficacy SVR at the EoFU was achieved in 59 out of 68 patients (86.76%), while the secondary efficacy parameter (SVR at the EoT) was achieved in 77.27% of patients. Multiple regression anlysis has established the initial level of ALT, patient's age and fibrosis level as main parameters statistically significantely impacting the outcome of treatment. Although without statistical significance, the trend of better outcomes was associated with early therapy (within 2 years from infection), and while the disease has not progressed (patients with fibrosis achieved SVR at the EoFU in 89.19% vs. 75.00% in patients with cirrhosis). The safety record was good, the most common adverse effects including cytopenia, rash and local reactions at the site of administration.
Combination therapy with peginterferon alfa-2a and ribavirin is safe and well tolerated, with SVR achieved in 86.76% of patients.
慢性丙型肝炎仍然是对世界健康的一个巨大威胁。慢性丙型肝炎的进展与显著的发病率相关：肝硬化、肝衰竭和肝细胞癌。聚乙二醇化干扰素和利巴韦林联合疗法的引入使持续病毒学应答（SVR）率比以往的治疗方案有了显著提高，而不良反应水平并未显著改变。本研究的目的是评估联合疗法（聚乙二醇化干扰素α-2a + 利巴韦林）在塞尔维亚人群中的疗效和安全性。
基因1型和4型患者接受为期48周的聚乙二醇化干扰素α-2a（180微克/周）和利巴韦林（1000 - 1200毫克/天）治疗。基因2型和3型患者接受相同剂量的两种药物，但疗程为24周。所有患者在治疗结束后24周安排随访。如果发生不良事件，医生会被指示调整两种药物的剂量。标准PCR检测用于病毒RNA的定性和定量检测，以及患者基因型的测定。
共有95名患者纳入研究。大多数患者为男性（65.26%），年龄在40岁及以下（52.63%），基因1型（63.15%）。平均感染持续时间为2.81 ± 4.89年，但仍有大多数患者（51.58%）感染HCV不到2年。69.47%的患者存在纤维化，21.06%的患者存在肝硬化。最常见的感染途径是静脉吸毒（29.48%），但32.63%的患者感染途径不明。平均ALT值为100.44 ± 70.26，共有93.68%的患者ALT水平升高。在治疗结束（EoT）时间点，从66名患者（69.47%）收集了数据，而在随访结束（EoFU）时，从68名患者（71.58%）收集了数据。这种异常的28.42%的脱落率主要是由于与患者失去联系（14.74%）和治疗过早终止（13.68%）。在EoFU时，68名患者中有59名（86.76%）达到了主要疗效参数SVR，而次要疗效参数（EoT时的SVR）在77.27%的患者中实现。多元回归分析确定ALT的初始水平、患者年龄和纤维化水平是对治疗结果有统计学显著影响的主要参数。虽然无统计学意义，但较好结果的趋势与早期治疗（感染后2年内）相关，并且在疾病未进展时（纤维化患者在EoFU时达到SVR的比例为89.19%，而肝硬化患者为75.00%）。安全性记录良好，最常见的不良反应包括血细胞减少、皮疹和给药部位的局部反应。
聚乙二醇化干扰素α-2a和利巴韦林联合疗法安全且耐受性良好，86.76%的患者实现了SVR。
