Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.

Effect of interferon alpha2b plus ribavirin treatment on selected growth factors in respect to inflammation and fibrosis in chronic hepatitis C

AIM: Growth factors (GF) that participate in regeneration and apoptosis have an important role in chronic liver diseases. We analyzed serum GF concentration during antiviral treatment and correlated it with morphological liver failure in chronic hepatitis C. METHODS: The levels of GF were determined in sera by ELISA method in 0,16,32 and 48 wk of therapy in 40 patients treated with IFNα2b (9 MU sc/wk) and RBV (1.2 g/d) and in 25 healthy subjects. Blind liver biopsies were done before treatment with histological grading and staging examination. RESULTS: The hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were markedly elevated prior the treatment and decreased during the therapy, although they did not reach the normal level. In non-responding (NR) patients, HGF and EGF were higher than that in responders (R), however differences were not significant. Before the treatment thrombopoietin (TPO) level was significantly lower in R than in NR (P<0.03). Platelet-derived growth factor (PDGF) concentration was lower in chronic hepatitis C than in healthy subjects and decreased during the treatment. A significant positive correlation was observed between inflammatory activity in the liver tissue and the concentration of HGF (in R: r= 0.4, in NR: r= 0.5), TPO (R: r= 0.6), and a significant negative correlation between this activity and EGF (R: r = -0.6) and PDGF (R: r= -0.5). Serum HGF concentration was higher in more advanced fibrosis (R: r = 0.5, P<0.05; NR: r=0.4, P<0,03). CONCLUSION: The decrease in PDGF can be an effective prognostic marker of the treatment and HCV elimination. Decreasing HGF, EGF, and PDGF can influence the inhibition of inflammatory and fibrotic processes in the liver during the antiviral treatment.

干扰素α-1b联合恩替卡韦治疗高病毒载量慢性乙型肝炎疗效评价

目的探讨干扰素α-1b联合恩替卡韦(ETV)治疗高病毒载量慢性乙型肝炎(CHB)患者的临床疗效。方法 92例高病毒载量(血清HBV DNA≥1×107 IU/ml)CHB患者被分为观察组48例和对照组44例。对照组采用干扰素α-1b治疗,观察组采用干扰素α-1b联合ETV治疗,疗程48 w。比较两组治疗后第12、24、48 w血清丙氨酸氨基转移酶(ALT)复常率、HBV DNA不可检出率、HBe Ag阴转率和HBe Ag转换率。采用ELISA法检测血清乙型肝炎病毒标记物;使用自动生化分析仪检测肝功能指标;采用荧光定量PCR法检测HBV DNA。结果在治疗第24 w和48 w时,观察组血清ALT复常率分别为68.8%和91.7%,显著高于对照组的34.1%和63.6%(P<0.01);在治疗第12 w、24 w和48 w时,观察组血清HBV DNA不可检测率分别为45.8%、72.9%和87.5%,显著高于对照组的11.4%、31.8%和47.7%(P<0.01);在治疗第48 w时,观察组HBe Ag阴转率和HBe Ag转换率分别为67.6%和62.2%,显著高于对照组的42.9%和37.1%(P<0.05)。结论干扰素α-1b联合ETV治疗血清高病毒载量的CHB患者疗效优于单用干扰素α-1b。

聚乙二醇干扰素α-2a与恩替卡韦辅治慢性乙型肝炎的临床疗效及安全性比较

目的比较聚乙二醇干扰素α-2a与恩替卡韦治疗慢性乙型肝炎患者的疗效与安全性。方法将60例慢性乙型肝炎患者随机分为干扰素组30例和恩替卡韦组30例;2组均常规护肝治疗。干扰素组给予聚乙二醇干扰素α-2a,恩替卡韦组另予恩替卡韦,观察治疗30周后2组患者的临床疗效。结果治疗后,2组丙氨酸氨基转肽酶(ALT)、天冬氨酸氨基转肽酶(AST)及总胆红素(TBIL)与治疗前比较,肝功能均有所改善(P<0.05);恩替卡韦组的ALT复常率(53.3%)、TBIL复常率(33.3%)和HBV-DNA转阴率(36.7%)明显高于干扰素组的ALT复常率(46.7%)、TBIL复常率(30.0%)和HBV-DNA转阴率(20.0%),差异有统计学意义(P<0.05);干扰素组(43.3%)的不良反应发生率高于恩替卡韦组(10.0%),差异有统计学意义(P<0.05)。结论恩替卡韦用于慢性乙型肝炎的抗病毒疗效明显优于聚乙二醇干扰素α-2a,且不良反应发生率小。

α-2-HS-糖蛋白对聚乙二醇干扰素alfa-2b治疗慢性乙型肝炎患者e抗原血清转换预测作用的研究

利用干扰素治疗慢性乙型肝炎仅在约1/3的患者中取得了满意的治疗效果.采用基于双向电泳的血清蛋白质组学技术,寻找慢性乙型肝炎患者干扰素治疗时发生e抗原血清学转换的预测标志物.对发生/未发生血清学转换组的患者基线和治疗24周血清进行差异蛋白的筛选和鉴定,并对筛选得到的α-2-HS-糖蛋白在训练组和验证组患者个体中进行了基线和第4周的进一步验证实验.结果发现,α-2-HS-糖蛋白从治疗基线至治疗第4周的变化趋势对慢性乙型肝炎患者干扰素alfa-2b治疗过程中e抗原血清学转换具有预测意义.

干扰素与胸腺肽联合治疗慢性乙型肝炎前C区变异株感染的疗效观察

目的 了解干扰素联合胸腺肽治疗慢性乙型肝炎前C区变异株感染的疗效。方法 6 3例患者随机分为A、B两组。A组用干扰素α 2b 3 0× 10 6U ,肌注 ,每日 1次 ,14d后改隔日 1次至 6个月 ,胸腺肽 40～ 5 0mg ,静滴 ,每日 1次 ,1～ 2月后改肌注或口服至 3个月。B组单用干扰素α 2b ,方法同A组。比较两组血清HBVDNA、HBsAg阴转率和ALT复常率。结果 A、B两组治疗结束时HBVDNA阴转率分别为 45 16 %和 43 75 % (P >0 0 5 ) ,9个月后分别为77 42 %和 5 3 13 % (P <0 0 5 ) ,远期疗效联合治疗组优于单用干扰素组。两组治疗结束时均无HBsAg阴转者。ALT复常率A组为 48 39% ,B组为 5 0 % ,两组差异无显著性。结论 干扰素α 2b联合胸腺肽治疗乙型肝炎病毒前C区变异株感染远期疗效优于单用干扰素组 ,但疗效仍不够理想。

Efficacy of Sishen Wan(四神丸) on dinitrobenzene sulfonic acid-induced ulcerative colitis and its effect on toll-like receptor 2/interleukin-1 receptor-associated kinase-4/nuclear factor-κB signal pathway

OBJECTIVE:To investigate the therapeutic effect of Sishen Wan(四神丸,SSW)on ulcerative colitis(UC)induced by dinitrobenzene sulfonic acid and its effect on toll-like receptor 2/interleukin-1 receptor-associated kinase-4/nuclear factor-κB(TLR2/IRAK4/NF-κB)signaling pathway in colonic tissue.METHODS:In this study,120 Sprague–Dawley rats were randomly divided into blank and model groups.The experimental UC model in rats was established by subcutaneous injection of hydrocortisone+senna gavage for 21 d+dinitrobenzene sulfonic acid(DNBS)/ethanol solution enema.The successful model rats were randomly divided into the model group;mesalazine(0.36 g/kg)group;and high-,medium-,and low-dose SSW(24,12,and 6 g/kg)groups.The model and blank groups were gavaged with equal volumes of distilled water once a day for 21 d.The general condition of the rats was observed,and the body mass,fecal properties,and occult blood were recorded for calculating the disease activity index(DAI)score.The colonic tissue of the rats was collected,and its general morphology and pathological form were noted for obtaining the colonic mucosal injury index(CMDI)score.Hematoxylin-eosin staining was used to view the pathological changes of the colon tissue in each group,apoptosis of the cells was detected using terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling staining,and quantitative real-time polymerase chain reaction was used to measure the expressions of TLR2,myeloid differentiation primary response gene 88(My D88),IRAK4,and NF-κB p65 mRNA in the colon tissue.The expressions of TLR2,My D88,IRAK4,and NF-κB p65 protein were detected using western blotting and immunohistochemistry assay,and the levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the colon tissue were determined using enzyme linked immunosorbent assay.RESULTS:Compared with the blank group,the general condition of the model group was relatively poor.The DAI and CMDI scores of the model group increased significantly(P<0.01),the glands and intestinal mucosa disappeared partially,and several inflammatory cells infiltrated and gathered in the mucosal layer and base layer of the rats in the model group.Furthermore,the cell apoptosis and expression levels of TLR2,My D88,IRAK4,and NF-κB p65 mRNA and protein in the colon tissue of rats in the model group increased significantly(P<0.01).The levels of IL-1βand TNF-αincreased significantly in the colon tissue of rats in the model group(P<0.01).After treatment with SSW,compared with the model group,the general condition of the UC rats improved.Moreover,the DAI and CMDI scores of the UC rats decreased significantly(P<0.05),and the pathological changes in the colon tissue of the UC rats tended to be normal.The cell apoptosis and expression levels of TLR2,My D88,IRAK4,and NF-κB p65 mRNA and protein in the colon tissue of the UC rats decreased gradually(P<0.01),and the levels of IL-1βand TNF-αdecreased significantly(P<0.01).CONCLUSION:SSW can improve the general condition and alleviate the intestinal mucosal injury of UC model rats.Additionally,SSW can inhibit the TLR2/IRAK4/NF-κB signaling pathway,but further studies are required to confirm it.

IFN替换或加IFN方案治疗核苷(酸)类似物耐药的慢性乙型肝炎患者疗效比较

目的:比较IFN替换或加IFN两种方案治疗核苷(酸)类似物(NAs)耐药的慢性乙型肝炎(CHB)患者的疗效及安全性。方法:选择我院85例对NAs耐药的CHB患者,随机分为两组,IFNα-2b组(40例)肌肉或皮下注射600万U IFNα-2b,隔日1次;IFNα-2b+NAs组(45例)在原NAs治疗基础上,肌肉或皮下注射600万U IFNα-2b,隔日1次,疗程均为12个月。治疗前和治疗后3、6、12个月检测各组患者肝功能(AST、ALT、TBil、ALB)、血清HBV DNA和HBV标志物定量,并观察不良反应。结果:与IFNα-2b组比较,治疗3个月后,IFNα-2b+NAs组AST、ALT、TBil水平降低,治疗6个月和12个月后,AST、ALT水平降低,差异均有统计学意义(P<0.05或P<0.01),两组HBV DNA水平、ALT复常率、HBV DNA不可测率、HBe Ag阴转率和HBe Ag转换率差异无统计学意义(P>0.05)。治疗期间IFNα-2b不良反应发生率高,但不严重,安全性良好。结论:IFNα-2b对NAs耐药的CHB患者具有一定疗效,安全性好;与NAs联合在改善患者肝功能方面优于IFNα-2b单药。