聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型慢性丙型肝炎临床观察

目的：观察聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型慢性丙型肝炎（CHC）的疗效及不良反应。方法40例基因1b 型 CHC 患者应用聚乙二醇干扰素α-2a 联合利巴韦林治疗,疗程48周,随访24周,观察病毒学应答情况及药物不良反应。结果获得快速病毒学应答（RVR）、完全早期病毒学应答（cEVR）、治疗结束时病毒学应答（ETVR）和持续病毒学应答（SVR）比例分别为65．0％、82．5％、90．0％、82．5％,获得 RVR 者均获得 SVR;合并脂肪肝者获得 SVR 的比例低于无脂肪肝者（P ＜0．05）;治疗过程中聚乙二醇干扰素α-2a 减量者8例,利巴韦林减量者6例。结论聚乙二醇干扰素α-2a 联合利巴韦林治疗基因1b 型 CHC 疗效良好;合并脂肪肝患者疗效低于无脂肪肝患者;治疗中不良反应普遍,但均能耐受。     

解读2011年美国肝脏病学会关于基因1型慢性丙型肝炎治疗指南的更新

慢性丙型肝炎病毒（HCV）感染的标准抗病毒治疗方案是聚乙二醇化干扰素-α（Peg-IFN-α）2a或Peg-IFN-α2b联合利巴韦林（RBV）治疗。基因1型慢性丙型肝炎初治患者48周持续病毒学应答（sustained virologic response,SVR）为40％～54％,     

聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型肝炎的随机对照临床研究

目的评价小剂量聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型病毒性肝炎的疗效和安全性.方法192例慢性丙型肝炎患者随机分为两组：聚乙二醇干扰素α-2b 0.5μg/kg每周一次联合利巴韦林750～1050 mg/d,或普通干扰素α-2b 3 MIU每周3次联合利巴韦林750～1050 mg/d.疗程48周,治疗结束后随访24周.结果聚乙二醇干扰素α-2b联合利巴韦林治疗的持续病毒学应答率为53.8%,而普通干扰素α-2b联合利巴韦林治疗的持续病毒学应答率为58.1%,两组持续病毒学应答率相当（P=0.966）.聚乙二醇干扰素α-2b治疗组的药物相关性不良反应发生率为100%,而普通干扰素α-2b治疗组的不良反应发生率为95.2%,两组间差异有统计学意义（P=0.033）.但是没有与干扰素α-2b聚乙二醇化相关的特有的新的不良反应发生.结论小剂量聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型肝炎的疗效和安全性与普通干扰素α-2b联合利巴韦林治疗的疗效和安全性相当.     

基因1型慢性丙型肝炎初治患者获得持续病毒学应答的相关因素研究

目的研究接受长效干扰素和利巴韦林治疗的基因1型慢性丙型肝炎患者获得持续病毒学应答的预测因素。方法 73例基因1型慢性丙型肝炎患者接受干扰素α-2a联合利巴韦林治疗24周或48周,随访6个月。结果 47.9%患者获得早期病毒学应答,38.4%患者获得持续病毒学应答;分析表明治疗前低病毒载量（小于8×105IU/ml）、体重指数低于25kg/m2和出现早期病毒学应答者更容易获得持续病毒学应答。结论病毒载量、体重指数和是否出现早期病毒学应答与基因1型慢性丙型肝炎初治患者获得持续病毒学应答相关。     

基因3型慢性丙型肝炎患者经济化治疗的临床观察

目的研究丙型肝炎病毒(HCV)基因3型感染者对普通干扰素和利巴韦林联合治疗的疗效。方法对2012年5月-2015年6月在我院就诊的抗-HCV和HCV RNA双阳性的1677例HCV患者进行基因分型,将其中2012年6月至2013年12月的120例HCV 3型初治患者采用普通干扰素(皮下注射IFN-α1b 5 MU/d,连续15 d;此后1次/隔日)联合利巴韦林(RBV 15 mg/kg·d)抗病毒治疗48周的方案;20例HCV 3型初治患者采用PegIFN-α2b(80μg/周)联合利巴韦林(RBV 15 mg/kg·d)治疗24周作为对照组。将普通干扰素联合利巴韦林抗病毒治疗获得快速病毒学应答(RVR)的患者,按照病毒载量分两组:≤1×10~5 IU/L(低病毒载量),A1组;1×10~5 IU/L(高病毒载量),A2组;获得早期病毒学应答(EVR),B组;未获得早期病毒学应答,C组。治疗前后和随访中检测患者血浆HCV RNA水平作为疗效评价的指标。结果在1677份标本中,检测到5种基因型,其中HCV基因lb型有263例,HCV基因2a型195例,HCV基因3a型314例,HCV基因3b型697例,HCV基因6a型67例,不能确定型别141例;其中基因3型(3a和3b)占总数的60.3%。治疗组112例患者完成既定治疗方案,92例(76.7%)患者获得SVR;其中A1组37例患者,33例(89.1%)获得SVR;A2组34例患者,28例(82.3%)获得SVR;B组(EVR)41例,31例(75.6%)获得SVR;C组(未获得EVR)8例:3例患者将普通干扰素调整为PegIFN,5例患者终止治疗。对照组20例均完成既定治疗方案:18例获得SVR,SVR率为90%,A1、A2组与对照组差异无统计学意义(P0.05)。结论(1)昆明地区慢性丙型肝炎患者以基因3型为主。(2)普通干扰素联合利巴韦林治疗获得RVR的3型慢性丙型肝炎患者疗效好。     

普通干扰素1b联合利巴韦林治疗非1b型慢性丙型肝炎患者临床观察

目的探讨不同基因型HCV感染者对普通干扰素联合利巴韦林治疗的疗效。方法应用型特异性探针杂交法检测106例慢性丙型肝炎患者HCV基因型。应用普通干扰素联合利巴韦林治疗,观察病毒学应答情况。结果在106例患者中,以HCV 3b（45.3%）、1b（20.8%）和3a（18.9%）型为主,6a（9.4%）和2a（5.7%）型次之;在22例1b型感染者,只有9例接受本治疗方案,82例非1b型感染者完成治疗。非1b型患者的RVR和EVR分别为50%和86.6%;在1b型HCV感染者,22.2%（2/9）获得SVR,而非1b型HCV感染者,76.8%（63/82）获得SVR。结论普通干扰素联合利巴韦林治疗非1b型慢性丙型肝炎患者疗效较好。     

普通干扰素与聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

目的研究干扰素α-1b或聚乙二醇化干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的效果、安全性、耐受性及经济-效益比。方法 86例慢性丙型肝炎患者接受干扰素α-1b联合利巴韦林治疗48周;另26例接受聚乙二醇干扰素联合利巴韦林治疗48周。结果在治疗4周和12周时,干扰素α-1b治疗患者病毒学应答率分别为18.6%和61.6%,显著低于聚乙二醇干扰素治疗组的38.5%和84.6%(P﹤0.05);在治疗48周和治疗结束后随访48周时,干扰素α-1b治疗患者病毒学应答率分别为79.1%和76.7%,与聚乙二醇干扰素组的92.3%和84.6%比,无明显差异性(P﹥0.05);干扰素α-1b治疗组成本/效果比为13959.6,显著低于聚乙二醇干扰素组的54241.1;治疗期间两组ALT复常率无明显差异性(P﹥0.05);干扰素α-1b治疗的副作用相对轻于聚乙二醇干扰素。结论在我国目前国情下,干扰素α-1b联合利巴韦林治疗慢性丙型肝炎有效、安全。     

丙型肝炎患者IL28B基因型和HCV基因型对抗病毒治疗的影响

目的:研究丙型肝炎患者IL28B基因相关的rs12979860基因型和HCV基因型对聚乙二醇干扰素α和利巴韦林联合抗病毒治疗疗效的影响.方法:对干扰素α联合利巴韦林治疗后获得持续病毒学应答(SVR)和无应答(NR)的各30例丙型肝炎患者的血液样品样进行检测,采用PCR反向斑点杂交法进行HCV基因分型,采用聚合酶链-连接...     

慢性丙型肝炎干扰素治疗后复发患者干扰素联合利巴韦林再治疗

目的 探讨干扰素（IFN）治疗后复发的慢性丙型肝炎（CHC）患者对IFN联合利巴韦林再治疗的应答情况及影响因素。方法 100例IFN治疗后复发的CHC患者中，50例使用聚乙二醇干扰素α-2a（PEG—IFNα-2a），50例使用重组人干扰素α-1b（CIFNα—1b），均联合利巴韦林再治疗，联合治疗48周，停药随访24周，分析HCVRNA载量、病毒基因型、药物种类对联合治疗疗效的影响。结果 100例复发患者联合再治疗后，36．00％取得持续病毒学应答（SVR），其中PEG-IFNα-2a组48．00％取得SVR，显著高于CIFNα—1b组（24．00％，P〈0．05）。56例低病毒载量（HCV-RNA〈1×10^5拷贝／mL）患者中，PEG—IFNα-2a组28例，其中57．14％取得SVR，显著高于CIFNα—1b组（25．00％，P〈0．05）。HCV非基因1（2a或2b）型组29例，其中55．17％取得SVR，显著高于基因1型组（28．20％，P〈0．05）；在CIFNα—1b治疗组，病毒非基因1型17例患者，其中47．06％取得SVR，明显高于基因1型患者（12，12％，P〈0．01）；在基因1型组，PEG—IFNα-2a组38例，其中42．11％取得SVR，显著高于CIFNα—1b组（12．12％，P〈0.01）。结论 IFN治疗后复发的CHC患者IFN联合利巴韦林再治疗存在部分患者无应答；对于HCV病毒载量低、基因1型的复发患者，聚乙二醇干扰素联合利巴韦林再治疗疗效明显优于普通干扰素的联合治疗。     

聚乙二醇干扰素联合利巴韦林治疗获极快速病毒学应答的初治基因1型慢性丙型肝炎患者疗效观察

目的观察获得极快速病毒学应答的初治基因1型慢性丙型肝炎患者,在继续接受36 w聚乙二醇干扰素α-2a联合利巴韦林治疗后的疗效。方法将基线HCV RNA水平〉400000 IU/ml、接受聚乙二醇干扰素α-2a（180μg/w）联合利巴韦林（1000～1200 mg/d）治疗2 w后HCV RNA阴转的基因1型慢性丙型肝炎初治患者,随机分为两组,分别接受36 w和48 w治疗,在停药后随访24 w,观察疗效。结果本研究共纳入40例患者,两组各20例。治疗36 w患者在治疗结束时病毒学应答（ETVR）、持续病毒学应答（SVR）和复发率分别为100%（20例）、90%（18例）和10%（2例）,治疗48 w患者ETVR、SVR和复发分别为95%（19例）、90%（18例）和5.3%（1例）,两组比较无统计学差异（P〉0.05）;在40例患者,基线HCV RNA水平与SVR呈负相关（OR=0.422,95%CI为0.05～0.29,P=0.007）;在治疗36 w患者,基线HCV RNA〈6×10^7IU/ml患者SVR显著高于HCV RNA≥6×10^7IU/ml患者（P=0.005）,但在治疗48 w患者,未发现这种差异（P=0.063）。结论对于基线HCV RNA水平〉400000 IU/ml的基因1型慢性丙型肝炎初治患者,接受聚乙二醇干扰素α-2a联合利巴韦林治疗,如在2 w时获得病毒学应答,治疗36 w疗程与48 w疗程的SVR相当。     

Efficacy of pegylated interferon plus ribavirin combination therapy for hepatitis C patients with normal ALT levels: a matched case�Ccontrol study

Background

The antiviral effect of pegylated interferon (Peg-IFN) plus ribavirin combination therapy in chronic hepatitis C (CHC) patients with normal alanine aminotransferase (ALT) levels (N-ALT) has been reported to be equivalent to that for patients with elevated ALT levels (E-ALT). However, the actual antiviral effect in N-ALT patients remains obscure because efficacy can be overestimated in patients with an advantageous background.

Methods

In this study, 386 patients were extracted, for a matched case?Ccontrol study, from 1320 CHC patients treated with Peg-IFN alpha-2b plus ribavirin combination therapy; 193 N-ALT patients [116 with hepatitis C virus genotype 1 (HCV-1), 77 with HCV genotype 2 (HCV-2)] were matched with 193 E-ALT patients by a propensity score method using the variables of age, sex, IFN treatment history, body mass index, and platelet counts.

Results

On multivariate analysis for sustained virological response (SVR) in N-ALT patients, younger age, low HCV RNA level at baseline, and HCV-2 were significant factors. The matched case?Ccontrol study showed that the SVR rates of N-ALT patients were equivalent to those of E-ALT patients; at 49 and 40% in the HCV-1 group (P?=?0.146), and 78 and 81% in the HCV-2 group (P?=?0.691). However, in N-ALT patients with non-SVR, approximately 40% showed ALT elevation at 24?weeks post-treatment.

Conclusion

Our findings indicate that the antiviral effect of Peg-IFN plus ribavirin therapy in N-ALT patients is comparable to that for E-ALT patients irrespective of their advantageous background; however, the application of this therapy for N-ALT patients, especially for those with HCV-1, should be considered carefully.     

Safety and efficacy of treatment with pegylated interferon alpha-2a with ribavirin in chronic hepatitis C genotype 4

The hepatitis C virus (HCV) genotype is an important predictive outcome parameter for pegylated interferon plus ribavirin therapy. Most published therapeutic trials to date have enrolled mainly patients with HCV genotypes 1, 2 and 3. Limited studies have focused on genotype 4 patients, who have had a poor representation in pivotal trials. Our aim was to evaluate the efficacy and safety of treatment with standard dose pegylated interferon alfa-2a in combination with weight-based ribavirin in patients with chronic hepatitis C genotype 4. In this prospective observational study, 198 patients with HCV-4 were included in this study from February 2004 to August 2005,188 patients who received at least 1 dose of drugs were included in the ITT analysis and they were treated with pegylated interferon alfa-2a and ribavirin for 48 weeks. Baseline and demographic characteristics, response to treatment at weeks 12, 48 and 72, and the nature and frequency of adverse effects were analyzed. Virological response at week 12 was achieved in 144 patients (76.6%). Virological response at the end of treatment was present in 110 patients (58.5%). At week 72, 99 patients presented SVR (52.7%). The reported adverse events were similar to those found in the literature for treatments of similar dose and duration. In conclusion, combined treatment with pegylated interferon alfa-2a and ribavirin was well tolerated and effective in chronic hepatitis C genotype 4, yielding response rates between those reported for genotype 1 and those of genotypes 2-3.     

Early virologic response after peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin treatment in patients with chronic hepatitis C

Patients infected with hepatitis C virus (HCV) genotype 1 and with serum HCV RNA concentrations over 800 000 IU/mL have relatively low rates of virologic response to pegylated interferons. The 2 forms of pegylated interferon have different pharmacokinetic profiles, and pilot studies comparing them have yielded varying results. We compared the virologic response to 12 weeks of treatment with peginterferon alpha-2a plus ribavirin vs peginterferon alpha-2b plus ribavirin in 380 patients who were infected with HCV genotype 1 and had high viral loads. We observed no between-group differences in viral load reduction over time and no differences in the percentage of patients treated with peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin who achieved early virologic response (EVR), defined as >/=2-log reduction in HCV RNA concentration or undetectable HCV RNA at 12 weeks (66%vs 63%). Serum levels of interferon were more frequently below the level of quantitation in patients treated with peginterferon alpha-2b plus ribavirin (58-68%) than in those treated with peginterferon alpha-2a plus ribavirin (1-2%). Patients treated with peginterferon alpha-2b plus ribavirin had higher rates of discontinuation for safety reasons (6%vs 1%). In conclusion, a substantial percentage of patients infected with HCV genotype 1 and high viral load can achieve EVR when treated with peginterferon and ribavirin. The 2 pegylated interferons showed comparable anti-HCV activity during the first 12 weeks of treatment when combined with the same doses of ribavirin (1000-1200 mg/day), but discontinuations for safety reasons were higher in the patients treated with peginterferon alpha-2b plus ribavirin.     

Detection of specific antibodies to HCV-ARF/CORE+1 protein in patients treated with pegylated interferon plus ribavirin

Hepatitis C virus (HCV) infection is a major cause for chronic liver disease and hepatocellular carcinoma. The HCV-ARF/core+1 protein is an alternative product of HCV core-encoding sequence of unknown biological function. Highly purified HCV core and ARF/core+1 recombinant proteins from HCV genotype 1a and HCV-ARF/core+1 recombinant protein from HCV genotype 3a were expressed in Escherichia coli. Using an enzyme-linked immunosorbent assay, we assessed the prevalence of anti-ARF/core+1 antibodies in 90 chronic hepatitis C patients infected with HCV genotypes 1a/1b or 3a, treated with pegylated interferon (Peg-IFN-a-2a) plus ribavirin. Samples derived from 92 healthy blood donors were used as negative controls. All HCV-RNA-positive serum samples reacted with core 1a antigen, while 15 (37.5%) of 40 and 14 (28%) of 50 patients infected with HCV-1a/1b and HCV-3a, respectively, were found to have anti-ARF/core+1 antibodies into their serum before treatment initiation. These antibodies were persistently present during treatment follow-up and linked to elevated levels of HCV-RNA at baseline.     

Efficacy and tolerability of pegylated interferon alpha 2b and ribavirin in chronic hepatitis C--a report from eastern India.

AIM: To study the efficacy and tolerability of pegylated interferon alpha 2b and ribavirin therapy in a cohort of chronic hepatitis C patients. METHODS: In a prospective, open label, uncontrolled trial pegylated interferon alpha 2b (Viraferon Peg) 1.5 microgram/ kg subcutaneously weekly plus daily ribavirin 800mg for 24 weeks in genotypes 2 & 3 and 1000mg for 48 weeks in genotypes 1 and 4 was administered to 16 patients of chronic hepatitis C. The primary end point was the sustained viral response. Therapy was prolonged by 3 months if the end of therapy response was not attained. Drug dosage was modified or temporarily discontinued if anaemia or bone marrow suppression developed. RESULTS: Both virological end of therapy response and sustained viral response were seen in 75% cases but not every patient who achieved end of therapy response had a sustained viral response. Relapse was seen in 31% cases and a pattern of delayed response was seen in 2 patients who later experienced a sustained viral response. Biochemical and virological responses were similar. A lower baseline viral load, genotype 3, a high ALT and the parenteral mode of viral acquisition were associated with higher sustained viral response rates. A good response was also seen in men, those over 50 years of age and those with normal baseline ALT. Most relapses occurred in genotype 3 patients whose age was less than 50 years; however the relapsing viral load was very low. 66% of previous interferon and ribavirin non-responders achieved sustained viral response. Treatment was well tolerated; temporary dose modification was required in 3 patients. CONCLUSION: In Indian patients, a combination of peginterferon alpha 2b and ribavirin is safe and effective both as initial treatment of chronic hepatitis C and for use in previous non-responders.     

Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4

BACKGROUND: The hepatitis C virus (HCV) genotype is an important predictive parameter for the success of pegylated interferon plus ribavirin therapy. To date, most published therapeutic trials have enrolled patients infected mainly with HCV genotypes 1, 2, and 3. Data regarding the responsiveness of genotype 4, the predominant type of HCV in the Middle East, are very limited. OBJECTIVE: To assess the efficacy of peginterferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis caused by HCV genotype 4. METHODS: Sixty-six treatment-naive patients infected with HCV genotype 4 were enrolled in this open label, prospective study. Cohort characteristics included the following: 48 M/18 F, mean age 45 +/- 9 years, and mean weight 74 +/- 8 kg. All patients had raised alanine aminotransferase (ALT) and were compensated. The mean pretreatment HCV-RNA level was 4.2 x 10(6) copies/ml (8.4 x 10(5) iu/ml) and median was 2.15 x 10(6) copies/ml. Twenty patients (29%) exhibited cirrhosis or severe fibrosis on pretreatment liver biopsy specimens. Participants were to receive peginterferon alfa-2b, 1.5 mcg/kg/wk plus ribavirin 1,000-1,200 mg/day for 48 wk. Patients were followed up for 24 wk after completing therapy. End of treatment viral response and sustained viral response (SVR) were defined as the absence of HCV-RNA from serum (<100 copies/ml) at 48 wk of treatment and at the end of follow-up, respectively. Data were analyzed on an intention-to-treat basis. RESULTS: End of treatment and sustained virologic response were 77% and 68%, respectively. Among patients with pretreatment HCV-RNA > or =2 x 10(6) SVR was 55% compared with SVR of 86% among patients with HCV-RNA < 2 x 10(6) (p= 0.05). Patients with cirrhosis or severe fibrosis had significantly lower SVR rate compared to those with mild or no fibrosis (29 vs 84%; p < 0.0002). Three patients (4%) discontinued therapy because of severe flu-like symptoms. Four patients developed hypothyroidism. Dose reduction of ribavirin and peginterferon alfa-2b was necessary in 15% and 6% of the patients, respectively. CONCLUSION: Peginterferon alfa-2b in combination with ribavirin is effective in the treatment of HCV genotype 4. The treatment was well tolerated by most of the patients.     

Impact of NS5A sequences of Hepatitis C virus genotype 1a on early viral kinetics during treatment with peginterferon- alpha 2a plus ribavirin

BACKGROUND. Hepatitis C virus (HCV) genotype 1 is the most prevalent genotype in Western countries, and treatment with pegylated interferon (pegIFN) plus ribavirin fails in 50%-60% of patients. Genetic variability within the NS5A dsRNA-dependent protein kinase binding domain (PKRbd) of HCV-1b has been associated with responsiveness to IFN- alpha . Little is known about NS5A sequences of HCV-1a. We investigated whether genetic variability of HCV-1a NS5A correlates with the early HCV kinetics during treatment. METHODS: Twenty-four treatment-naive, HCV-1a-infected patients were treated with standard doses of pegIFN- alpha 2a plus ribavirin. HCV viremia was quantitated at days 0, 1, 2, and 3 and weeks 1, 2, 4, 8, and 12 of treatment. According to HCV kinetics, patients were classified as early rapid responders, early moderate responders, or early slow responders. The full-length HCV NS5A was sequenced at baseline and at week 1. RESULTS: At baseline, variability of the NS5A C terminus (concentrated in the PKRbd) is associated with interferon efficacy but not with the second phase of the early viral decline that has been associated with a sustained virologic response. Comparisons between baseline and week-1 full-length sequences did not show significant increases in mutations. CONCLUSIONS: Genetic variability of HCV-1a NS5A does not predict responsiveness to IFN- alpha . Differences in early kinetics during combination therapy are not due to selection of IFN-resistant HCV strains.     

Sustained Viral Response to Pegylated Interferon α-2b and Ribavirin in Chronic Hepatitis C Refractory to Prior Treatment

Hepatitis C virus (HCV) infection refractory to previous therapy is common. Treatment of patients with refractory disease is difficult and less studied. Pegylated interferon α-2b plus ribavirin is used for treatment of HCV patients naïve to therapy. We conducted a randomized study for refractory HCV patients using a high- vs. a low-dose pegylated interferon α-2b and ribavirin protocol. Our aim was (1) to determine the efficacy of pegylated interferon α-2b plus ribavirin to eradicate HCV in previously treated individuals and (2) to compare a low-dose to a high-dose regimen. One hundred fifty-two patients were initiated in the study, 112 (74%) were male and 40 (26%) female. Nineteen percent of patients obtained a sustained viral response (SVR) in the high-dose arm. Prior relapsers had the highest SVR rates: 50% in non-genotype 1 and 34% in genotype 1. The odds of achieving a SVR were six times higher in previous relapsers. The rate of SVR in genotype 1 patients who were nonresponders to prior therapy was only 8%. All patients who achieved a SVR had no detectable virus at week 24. However, only half of those who had undetectable viral titers at week 24 achieved a SVR. In conclusion, retreatment of patients with refractory hepatitis C infection with interferon α-2b and ribavirin combination therapy is well tolerated and gives modest response rates. The most important factor in predicting response to therapy is the manner of response to previous treatment. The likelihood of response to treatment can be predicted from the viral titers at 24 weeks.     

IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection

Polymorphisms near the IL28B gene, which code for interferon (IFN)-λ3, predict response to pegylated interferon-α (PEG-IFN) and ribavirin treatment in hepatitis C virus (HCV) genotype 1 infected patients. Follow-up studies of the effect of IL28B gene in HCV non-genotype 1 infected patients have almost always used predominantly HCV genotype 2-infected or mixed genotype 2/3-infected cohorts with results partly conflicting with HCV genotype 1. We performed a retrospective analysis of 281 patients infected with HCV genotype 3 for association of response to therapy with IL28B polymorphisms. We found that the HCV genotype 1 responder genotypes at rs12979860 and rs8099917 did not associate with sustained virological response to PEG-IFN/ribavirin therapy. However, the responder genotypes of both SNPs showed association with rapid viral response measured at 4 weeks (rs12979860, P = 3 × 10(-5) ; rs8099917, P = 3 × 10(-4) ). In multivariate analysis, age (<40 years), baseline viral load (<4 × 10(5) IU/mL) and the responder genotypes of SNPs rs12979860 or rs8099917 remained significant independent predictors of rapid viral response to therapy. Furthermore, we show that IL28B polymorphisms are associated with relapse in patients who achieve rapid viral response to PEG-IFN/ribavirin therapy. The responder genotypes also showed association with markers of stage and activity of liver disease, namely high aspartate aminotransferase platelet ratio index (APRI, rs12979860, P = 0.018; rs8099917, not significant) and high alanine aminotransferase (ALT, rs12979860, P = 0.002; rs8099917, P = 0.001), in addition to a high baseline viral load (rs12979860, P = 1.4 × 10(-5) ; rs8099917, P = 7.3 × 10(-6) ). CONCLUSION: Polymorphisms near the IL28B gene show association with rapid viral response but not sustained viral response to PEG-IFN/ribavirin therapy in HCV genotype 3-infected patients.