Having cirrhosis, diabetes, or substance use disorder increased the odds of treatment discontinuation in type 1 hepatitis C virus infection, whereas use of growth factor drugs correlated with treatment persistence, reported Dr. Lauren A. Beste and colleagues in the November issue of Clinical Gastroenterology and Hepatology.

The investigators looked at 11,019 patients in the U.S. Veterans Administration health care system with hepatitis C genotype 1 who received at least two prescriptions for pegylated interferon and ribavirin between Jan. 1, 2002 and Dec. 31, 2007.

Patients who completed at least 80% (38.4 weeks) of the standard 48-week treatment regimen were considered to have completed treatment; overall, 5,795 patients (52.6%) reached this goal (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.07.012]).

Although “no indications currently exist for discontinuing treatment [before 12 weeks] due to lack of response,” a total of 1,184 patients (roughly 10% of the total cohort) did just that, the authors said. Patients who stopped therapy before 12 weeks were significantly more likely to have cirrhosis, compared with patients who persisted with therapy (adjusted odds ratio [AOR] 1.42; P less than .01), and also were more likely to have diabetes (AOR, 1.25; P = .02) and pretreatment substance use disorder, or SUD (AOR, 1.24; P = .01).

They were also half as likely to use growth factor as were their counterparts who continued with therapy (AOR, 0.56; P less than .01). The growth factors included erythropoietin, darbepoetin, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor.

The authors also assessed patients who discontinued treatment between 12 and 24 weeks of therapy (including 317 patients with known early virologic response who discontinued despite their response). These patients were more likely to have pretreatment depression (AOR, 1.59; P less than .01), were slightly less likely to have other mental illnesses (AOR, 0.65; P = .02), and – once again – were nearly half as likely to use growth factor as were patients who persisted with the therapy (AOR, 0.64; P less than .01).

Finally, the authors looked at patients who discontinued therapy before 38.4 weeks. “No variables significantly predicted discontinuation in this time period in bivariate or multivariate analyses,” wrote Dr. Beste, of the Veterans Affairs Puget Sound Healthcare System in Seattle, Washington, and her coauthors.

Regarding SUD as a predictor of discontinuation, the authors wrote that “patients with history of substance abuse may benefit from early support and intervention during treatment in order to continue antiviral therapy.”

Of the pretreatment depression that emerged as a predictor in the 12-24 week discontinuation group, they wrote: “Prior studies report that the depressive side effects of interferon peak by week 25, which may explain the observed association between depression and discontinuation midtreatment.”

And regarding the links between cirrhosis and diabetes and discontinuation, they pointed to other studies showing that these patients “may be more susceptible to treatment side-effects.” However, they also speculated that blood glucose derangements in diabetic patients receiving treatment may lead to discontinuation.

Finally, Dr. Beste and her colleagues commented on the use of growth factor, which correlated with reduced risk of discontinuation both before 12 weeks and from weeks 12 to 24. They speculated that growth factor use “leads to improvement in low blood counts, allowing providers to continue treatment when otherwise it would be stopped.”

Therefore, “appropriate use of growth factors should be prospectively evaluated as a modifiable means to prevent treatment discontinuation,” they recommended.

Dr. Beste and her colleagues had no relevant financial disclosures. The study was supported by the Department of Veterans Affairs and the U.S.-based Northwest Hepatitis C Resource Center.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

一项研究表明，对1型丙型肝炎病毒感染者而言，存在肝硬化、糖尿病、物质使用障碍(SUD)等疾病会促使患者停止治疗， 而使用生长因子类药物却能使患者坚持更长时间的治疗。

 

研究者从美国退伍军人管理局医疗保健系统中选取了11,019例1型丙型肝炎患者，这些患者在2002年1月~2007年12月31日间均接受过至少2个疗程的聚乙二醇干扰素和利巴韦林治疗。持续治疗时间达到标准疗程(48周)80%(38.4周)以上的患者被认为完成了全部治疗。共有5,795例(52.6%)患者达成了这一目标(Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.07.012])。研究中使用的生长因子类药物包括促红细胞生成素、阿法达贝伯丁、粒细胞集落刺激因子、粒细胞巨噬细胞集落刺激因子。

 

在治疗前12周，有1,184例(约占队列总人数的10%)患者因治疗无效而停止治疗。与坚持治疗的患者相比，这些患者肝硬化发病率更高[校正后的比值比(AOR)为1.42；P＜0.01]，糖尿病(AOR=1.25；P = 0.02)和SUD(AOR=1.24；P = 0.01)的发病率也更高。此外，这些患者使用生长因子类药物的几率仅相当于坚持治疗者的一半(AOR=0.56；P＜0.01)。对治疗12~24周停止治疗的患者(包括317例出现早期病毒学应答但仍停止治疗的患者)进行的评估表明，这些患者患治疗前抑郁症的风险更高(AOR=1.59；P＜0.01)，但患其他精神疾病的风险更低(AOR=0.65；P= 0.02)，其使用生长因子类药物的几率同样仅相当于坚持治疗者的一半(AOR=0.64；P＜0.01)。对治疗前38.4周停止治疗的患者进行双因素或多因素分析表明，在这一时间段内，无任何一种变量可对患者停止治疗做出准确预测。

 

鉴于SUD是患者停止治疗的预测因素之一，为了保证存在物质滥用史的患者能坚持抗病毒治疗，应对此类患者提供早期支持和干预。肝硬化和糖尿病患者更易停止治疗的原因可能在于其对治疗相关不良反应更加易感，此外，糖尿病患者存在的血糖紊乱症状会增大其停止治疗的几率。使用生长因子类药物与患者在治疗前12周和12~24周停药风险的降低存在关联，该类药物有助于提高患者血细胞计数，对于那些本可能停止治疗的患者而言，这一效应有助于他们坚持下去。

 

研究者表示无相关经济利益披露。本研究由美国退伍军人事务部和美国西北丙型肝炎资源中心赞助。

 

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