Obesity v.s Hepatitis C

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[B]Obesity Predicts Poor Response to Hepatitis C Treatment [/B] By Laurie Barclay, MD Medscape Medical News Sept. 26, 2003 — Obesity is an independent negative predictor of response to treatment for chronic hepatitis C virus (HCV), according to the results of a retrospective review published in the September issue of Hepatology. "Although the efficacy of antiviral therapy in chronic hepatitis C has improved since standard interferon (IFN) monotherapy was introduced, nonresponse to the current therapies remains common," write Brian L. Bressler, from the University of Toronto in Ontario, Canada, and colleagues. "Several factors have been shown to influence response; these include viral factors (particularly genotype) and host factors, which may be genetic (sex, HLA type, cytokine polymorphisms), and others such as age, presence of cirrhosis, and race..... Obesity, a modifiable risk factor, may have a deleterious effect on treatment response to both pegylated and standard IFN monotherapy." From 1989 to 2000, 253 patients at a single center were treated for chronic HCV with either IFN monotherapy or IFN in combination with ribavirin. A sustained response was defined as either negative polymerase chain reaction for HCV RNA and/or normal alanine aminotransferase (ALT) level, only in those treated before availability of HCV RNA testing, six months after completion of therapy. Normal weight was defined as body mass index (BMI) less than 25 kg/m2; overweight as BMI 25 to 30 kg/m2; and obesity as BMI greater than 30 kg/m2. Logistic regression with adjustments for age, sex, history of alcohol consumption greater than 50 g/day, cirrhosis on pretreatment biopsy, and BMI revealed significant differences in response to treatment according to BMI group (P = .01), genotype (P < .01), and cirrhosis (P < .01). Compared with patients with genotype 1, those with genotypes 2 or 3 had an odds ratio (OR) for treatment success of 11.7, and cirrhotic patients had an OR of 0.15 compared with noncirrhotic patients. Compared with normal and overweight patients, obese patients had an OR of 0.23 for treatment success. Hepatic steatosis was not an independent predictor of response to antiviral treatment. "Obese patients as judged by their BMI, independent of genotype and cirrhosis, had approximately an 80% lower chance of a sustained response to therapy compared with normal or overweight patients," the authors write. "The mechanism whereby obesity may affect the antiviral response to treatment is not completely understood." In an accompanying editorial, Arthur J. McCullough, MD, from Case Western Reserve University in Cleveland, Ohio, discusses the interrelationship of body fat mass and hepatic steatosis with the presence and progression of fibrosis in HCV. Despite the limitations inherent in a retrospective design, as well as other methodological shortcomings, "the two important observations in the current study appear valid," he writes. "Weight loss in obese patients may improve the efficacy of HCV treatment.... HCV's resistance to treatment is being nurtured by obesity, a 'terrain' that reflects the excesses of an affluent society." Sept. 26, 2003--根據一篇發表於九月號Hepatology回溯性評論的結果，肥胖對於治療慢性c型肝炎病毒(HCV)是一個獨立性陰性反應的預測指標。 　　 　　加拿大安大略的多倫多大學學士Brian L.及其同僚表示，自從採用標準干擾素(IFN)單一療法後，抗病毒藥物治療對於慢性c型肝炎的功效已獲得改善，但是目前無效的治療方法仍屬常見。 　　 　　其中某些因素會影響反應，包括了病毒性因素(特別是基因型)和遺傳學上的宿主性因素 (性別、HLA 類型、生長激素多型性)，及其他如年齡、肝硬化、和人種等，而可更改性的危險因子-肥胖，對於使用長效型及標準干擾素單一療法，兩者皆可能對治療反應產生有害的影響。 　　 　　從1989至2000年，醫學中心內共253位病人以干擾素單一療法或是以干擾素併用雷巴威林治療慢性HCV，只有在檢測到HCV RNA前，接受完整治療六個月後，其HVC RNA聚合酵素連鎖反應(PCR)呈陰性和/或是氨基丙氨酸(ALT)濃度正常化才被定義為持續有效反應。 　　 　　標準體重定義為身體質量指數(BMI)小於25 kg/m2； BMI在25到30 kg/m2為過重； BMI 超過30 kg/m2則為肥胖。 　　 　　在調整年齡、性、飲酒史超過50g/天，治療前的切片檢查為肝硬化，和BMI後，邏輯式迴歸顯示，不同BMI群(P=.01)，基因型態(<.01)，及肝硬化(P<.01)，其治療反應有顯著性差異。 　　 　　與基因型1的病患相比，基因型2或3的病患其成功治癒之勝算比(OR)為11.7，而肝硬化病患與無肝硬化病患相比，其OR為0.15，與體重標準及過重的病患相比，肥胖的病患治癒成功的ORj為0 .23，另外脂肪肝則不是抗病毒藥物治療反應的獨立性預測指標。 　　 　　作者表示，根據其BMI、基因型及肝硬化的不同，肥胖的病患比起正常的或過重的病患降低了約80%持續有效反應的機率，但是對於肥胖影響抗病毒藥物治療反應的機制尚未完全了解。 　　 　　在一篇同行文章中，美國俄亥俄州克利夫蘭凱斯西儲大學的Arthur J. McCullough博士則探討身體脂肪質量與脂肪肝合併HCV纖維化的相互關係。 　　 　　儘管受限於回顧性研究的本身及其他方法的不足，Arthur J. McCullough表示，現行研究中最重要的且有根據的兩項發現，一為肥胖病患減重後可增進HCV的治療功效，而反映出富裕社會中飲食過度的表徵，肥胖則會培育出HCV的抗藥性。