运用AS-PCR方法及SOE技术研究猪α干扰素

采用AS PCR方法和SOE技术相结合的策略 ,通过找出猪α干扰素基因内部的特异位点 ,设计引物扩增出两个DNA片段并将其连接为全长基因。所得片段编码序列长 5 0 1bp ,共编码 16 6个氨基酸。与已知PoIFN α1基因有 5个碱基差别 ,导致

一种小鼠新α干扰素亚型基因的发现、序列测定与表达

用引物测序法从小鼠cDNA库的克隆中发现一种小鼠新型α干扰素(简称mIFN-αB),其结果与已知基因库中所有的小鼠α干扰素不同.以后对其编码区及5’和3’端非翻译区的核苷酸序列共1.2kb进行了全顺序测定.结果申请加入了基因库.将此α干扰素基因装入表达载体中,在大肠杆菌中得到了很好的表达.

聚乙二醇干扰素α-2a联合乙肝疫苗治疗慢性乙型肝炎疗效观察

目的探讨聚乙二醇干扰素α-2a(PEG-IFNα-2a)联合乙肝疫苗治疗慢性乙型肝炎(CHB)的临床疗效及安全性。方法随机将172例CHB患者分为观察组和对照组,每组86例。对照组应用PEG-IFNα-2a治疗,观察组应用PEG-IFNα-2a联合乙肝疫苗治疗。比较两组在治疗6 m、12 m和随访6 m时HBV DNA阴转率、HBeAg阴转率和ALT复常率。结果在治疗12 m和随访6 m时,观察组HBV DNA阴转率、HBeAg阴转率和ALT复常率分别为81.4%、53.5%和82.6%,和93.0%、64.0%和95.3%,均显著高于对照组水平(67.4%、38.7%和68.6%,和75.6%、46.5%和77.9%,P<0.05);在治疗6 m、12 m和随访6 m时,观察组ALT和AST水平分别为(93.5±43.1)U/L和(86.0±50.6)U/L、(40.8±25.1)U/L和(50.7±28.6)U/L、(36.5±11.3)U/L和(43.2±15.7)U/L,均显著低于对照组(116.4±58.6)U/L和(105.3±52.8)U/L、(50.6±26.2)U/L和(59.5±25.4)U/L、(46.0±24.4)U/L和(52.6±23.9)U/L,P<0.05。结论 PEG-IFNα-2a联合乙肝疫苗治疗CHB可有效地提高干扰素的临床疗效。

聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的疗效观察

目的:探讨聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的临床疗效及安全性。方法:选取2014年1月—2017年1月嘉应学院医学院附属医院收治的慢性丙型肝炎患者100例,以计算机随机数字分组法分为对照组和观察组,每组50例。对照组采用普通干扰素α-1b联合利巴韦林治疗,观察组采用聚乙二醇干扰素α-2a联合利巴韦林治疗,比较两组患者的临床疗效、病毒学应答率、肝功能及不良反应发生情况。结果:观察组患者的总有效率为84%(42/50),明显高于对照组的62%(31/50);观察组患者的快速病毒学应答率、早期病毒学应答率和治疗终点病毒学应答率明显高于对照组,差异均有统计学意义(P<0.05)。治疗后,两组患者的丙氨酸氨基转移酶、天门冬氨酸氨基转移酶和碱性磷酸酶等肝功能指标水平均明显低于本组治疗前,且观察组患者明显低于对照组,差异均有统计学意义(P<0.05);两组患者不良反应发生率的差异无统计学意义(P>0.05)。结论:聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎,疗效显著,安全可靠。

大剂量干扰素辅助治疗国人口腔粘膜恶性黑色素瘤的临床研究

目的：探讨大剂量干扰素辅助治疗口腔粘膜恶性黑色素瘤的疗效和安全性。方法回顾性分析2004年5月至2012年11月我科经治的Ⅲ～ⅣA期口腔粘膜恶性黑色素瘤患者的治疗及预后情况。在经治的117例患者中，73例术后接受了大剂量干扰素α-2b治疗，其中有58例完成了治疗计划，设为治疗组，另15例中途停止；其余44例未采用大剂量干扰素治疗者作为对照组。比较两组患者的总生存期（ OS）和无复发生存期（ RFS）以及相关不良反应的发生情况。结果117例患者的中位OS为40个月（95％CI：33～62个月）。治疗组与对照组中Ⅲ期患者的中位OS（69个月vs．65个月）和RFS（50个月vs．34个月）的差异均无统计学意义（P＞0.05），治疗组与对照组中ⅣA期患者的中位OS（37个月 vs．20个月）和中位RFS（33个月 vs．10个月）的差异均有统计学意义（ P＜0.05），治疗组与对照组中Ⅳ期伴颈淋巴结转移患者的中位OS（40个月vs．20个月）和中位RFS（33个月 vs．10个月）的差异均有统计学意义（P＜0.05）。大剂量干扰素治疗的常见血液学毒性为骨髓抑制，包括白细胞减少和血小板减少；非血液性不良反应包括流感样症状、恶心呕吐、肝功能损害等。全组患者不良反应以1～2级为主，仅有7例出现3～4级毒副反应，给予对症治疗后均能缓解，无治疗相关性死亡。结论术后大剂量干扰素辅助治疗能显著提高ⅣA期口腔粘膜恶性黑色素瘤患者的OS和RFS，且治疗的不良反应可耐受。

长效与短效α-干扰素治疗慢性丙型肝炎疗效观察

目的：对比长效干扰素联合利巴韦林与普通干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效及安全性。方法回顾性分析60例慢性丙型肝炎患者的临床资料，其中长效干扰素组采用聚乙二醇干扰素α-2a （PEG-INFα-2a）联合利巴韦林进行抗病毒治疗（n=30例），普通干扰素组采用普通IFNα-2a联合利巴韦林治疗（n=30例），均分别于治疗4、12、24、48w及治疗结束后24w评价疗效，并观察药物的不良反应。结果长效干扰素组持续病毒学应答率（SVR）为90.0%，显著高于普通干扰素组的56.7%（P〈0.01）；两组药物不良反应均有发热、肌肉酸痛、脱发及中性粒细胞、血小板下降等，但长效干扰素组发生发热和肌肉酸痛比率分别为36.7%和33.3%，显著低于普通干扰素组（90.0%和93.3%，P〈0.01）；长效干扰素组中性粒细胞下降明显高于普通干扰素组，在4～24w尤其明显。结论长效干扰素联合利巴韦林治疗方案疗效显著优于普通干扰素联合利巴韦林，且未增加不良反应。

Physicochemical Characters of rPoIFN-α and Its Antiviral Activity in vitro

[Objective]The research aimed to test and identify the physicochemical characters and antiviral activity in vitro of semi-finished product of the recombinant porcine rPoIFN-α. [Method]HEp-2/VSV system was used to test the antiviral activity of three batches of rPoIFN-α. Using recombinant human IFN-α as reference,the titer of interferon was measured. The semi-finished product of rPoIFN-α with the known titer were treated with 0.25% trypsin,HCl and mouse anti-porcine IFN-α monoclonal antibody. And the anti-viral activity of each batch of rPoIFN-α was detected. The physicochemical characters of rPoIFN-α were evaluated. The inhibition of induced cytopathic effect of rPoIFN-α on PPV （Porcine parvovirus） and PRV （Porcine pseudorabies） on swine kidney cell （PK-15） was determined. And the antiviral activity of rPoIFN-α in vitro was observed. [Result]The titers of semi-finished products of rPoIFN-α titrated by HEp-2/VSV system could reach 1.5×105 IU/ml,with the specific activity of 1.1×106 IU/mg. The residual rate of the tier of rPoIFN-α treated by 0.25% trypsin at 37 ℃ for 1 h was less than 1%. And that treated with HCl （pH of 2.0） for 72 h was up to 95%. And that treated at 56 ℃ for 30 min and that treated by mouse anti-porcine IFN-α monoclonal antibody at 37 ℃ for 1 h were higher than 47% and about 1% respectively. The antiviral test in vitro showed that 50 and 500 IU/ml rPoIFN-α could inhibit the induced cytopathic effect of PRV and PPV on PK-15 cell lines. [Conclusion]rPoIFN-α had the basic physicochemical characters of IFN-α. And it could inhibit the induced cytopathic effect of PRV and PPV on PK-15 cell lines,but there was dosage difference.

Effects of Downregulation of Inhibin α Gene Expression on Apoptosis and Proliferation of Goose Granulosa Cells

Inhibin a is one of the candidate genes that control the ovulation in poultry. To study the genetic effects of inhibin a on apoptosis and proliferation of goose granulosa cells cultured in vitro, two RNA interference （RNAi） expression vectors, psiRNA-INHal and psiRNA-INHα2, were constructed to knock down inhibin α gene expression. After 48 h of transfection, the efficiency of these two RNAi expression vectors was examined by fluorescence microscopy. Meanwhile, inhibin protein expression levels, apoptosis indexes （AI） and proliferation indexes （PI） of granulosa cells were analyzed by flow cytometry. In addition, the supernatants were collected to assay the concentrations of estrogen （E2） and progesterone （P） by radioimmunoassay. The results showed that the expression level of inhibin a in the RNAi group were decreased 30%--40% than those in the control groups （P 〈0.05） and the apoptosis indexes and proliferation indexes in the RNAi groups were significantly higher than those in the control groups （P 〈0.05）. However, the E2 concentrations in the RNAi groups were lower than those in the control groups （P 〈0.05）. These results indicate that inhibin a has antagonistic effect on granulosa cell apoptosis.

Inhibitory Effects of INF-α and Curcumin on the Proliferation of Raji Cells

Objective： To investigate the inhibitory effect of interferon-α （IFN-α） and curcumin on proliferation of Raji cells （B-NHL） and its mechanism. Methods： The morphological, changes of Raji cells were observed in culture medium with IFN-α （500, 1000, 2000, 3000 U/L） and various concentrations of curcumin （6.25, 12.5, 25 μmol/L） for different time in vitro. The inhibitory ratio was measured by MTT assay. Apoptosis was detected by flow cytometry （FCM）. The expression of caspase 6, caspase 8 and caspase 9 in Raji cells treated with IC5025 μmol/L curcumin with IFN-α was examined using Western blot. Results： IFN-α and curcumin could significantly inhibit the growth and induce apoptosis of RAji cells with synergistic effects. They could increase the expression of caspase 6, caspase 8 and caspase 9 in Raji cells in a dose- and time-dependent manner. Conclusion： The combined use of IFN-α and curcumin can inhibit the proliferation of B-NHL Raji cells apparently in vitro. Promotion of the expression of caspase 6, caspase 8, caspase 9 and induction of apoptosis might be one of the important mechanisms.

Effect of interferon in combination with ribavirin on the plus and minus strands of HCV RNA in patients with chronic hepatitis C

AIMS To probe the effect of interferon in combination with rib- avirin on the plus and minus strands of hepatitis C virus RNA (HCV RNA). METHODS Twenty-three cases diagnosed as chronic hepatitis C (CHC) according to positive HCV RNA/anti-HCV,fluctuating levels of aminotransferase activities (>1 year) and absence of other hepatitis virus marker,were studied. Among them,13 pa- tients received combined antiviral therapy (subcutaneous injection of 3MU of interferon-α three times per week for 3 months and intra- venous drip of 1 g of ribavirin per day during the first month of treatment with interferon) and 10 patients received single interfer- on therapy (the same as above-mentioned) as control. The plus and minus strands of HCV RNA in sera and peripheral blood mononuclear cells (PBMCs) of these patients were tested by means of nested reverse transcription-polymerase chain reaction (nested RT-PCR). RESULTS At the end of therapy,the abnormal ALT levels de- creased to normal range in 9 (69.23%) cases in the combined antiviral group. Of them,5 (55.56%)experienced post-therapy relapse and 4 (44.44%) were complete responders. In the inter- feron group,the ALT decreased to normal in 6 (60%) cases,of which,4 (66.67%) had post-therapy relapse and 2 (33.33%) were complete responders. The differences between the two groups were nonsignificant (P>0.05). At the end of therapy,the positive rate of the plus strand in sera decreased from 92.3% to 38.46% (P<0.05) and that of the minus strand in PBMCs,from 76.92% to 38.46% (P<0.05) in the combined antiviral group; and in the interferon group,the former decreased from 100% to 50% (P<0.05) and the latter,from 90% to 40% (P<0.05). Again,no significant differences were found between groups (P >0.05). The relapse occurred in patients whose plus strand HCV RNA in PBMCs remained positive before and after treatment. CONCLUSIONS Ribavirin could not enhance the antiviral effect of interferon. The absence of HCV RNA in serum does not mean complete clearance of HCV,and its value for evaluating the an- tiviral effect and prognosis is limited. Therefore,it is essential to measure the plus and minus strands of HCV RNA in sera and PBM- Cs simultaneously.

RNA interference mediated silencing of α-synuclein in MN9D cells and its effects on cell viability

Objective To silence the expression of α-synuclein in MN9D dopaminergic cells using vector mediated RNA interference （RNAi） and examined its effects on cell proliferation and viability. Methods We identified two 19-nucleotide stretches within the coding region of the α-synuclein gene and designed three sets of oligonucleotides to generate doublestranded （ds） oligos. The ds oligos were inserted into the pENTR^TM/Hl/TO vector and transfected into MN9D dopaminergic cells, α-Synuclein expression was detected by RT-PCR, real-time PCR, immunocytochemistry staining and Western blot. In addition, we measured cell proliferation using growth curves and cell viability by 3-（4, 5）-dimethylthiahiazo （-z-y 1）-3, 5-diphenytetrazoliumromide （M＇FF）. Results The mRNA and protein levels of α-synuclein gene were significantly down-regulated in pSH2/α-SYN-transfected cells compared with control MN9D and pSH/CON-transfected MN9D cells, while pSHI/α-SYN- transfected cells showed no significant difference. Silencing α-synuclein expression does not affect cell proliferation but may decrease cell viability. Conclusion Our results demonstrated pSH2/α-SYN is an effective small interfering RNA （siRNA） sequence and potent silencing of mouse α-synuclein expression in MN9D cells by vector-based RNAi, which provides the tools for studying the normal function of α-synuclein and examining its role in Parkinson＇s disease （PD） pathogenesis. α-Synuclein may be important for the viability of MN9D cells, and loss of α-synuclein may induce cell injury directly or indirectl

Intraocular complications of IFN-α and ribavirin therapy in patients with chronic viral hepatitis C

We report a panel of severe inflammatory and vascular intraocular disorders occurring during interferon-alpha （IFN-α） treatment in eight hepatitis C virus （HCV）- infected patients. These events include three cases of Vogt-Koyanagi-Harada like （VKH） disease （an association of panuveitis, retinal detachment, ear and meningeal detachment and skin and hair changes）, two cases of central retinal vein occlusion, one case of central retinal artery occlusion, one case of severe hypertensive retinopathy and one case of bilateral ischemic optic neuropathy with severe visual impairment. Rare as they are, such severe ophthalmological complications require a close follow-up of HCV-infected patients under IFN-α breabnent with ophthalmological monitoring if any ocular manifestation occurs.

Expression of interferon-alpha/beta receptor protein in liver of patients with hepatitis C virus-related chronic liver disease

ABM: To study the expression of interferon-alpha/beta (IFN-α/β) receptor protein in liver of patients with hepatitis C virus (HCV)-related chronic liver disease and its clinical significance. METHODS: A total of 181 patients with HCV-related chronic liver disease included 56 with HCV-related liver cirrhosis (LC) and 125 with chronic hepatitis C (CHC). CHC patients were treated with five megaunits of interferon-α1b six times weekly for the first 2 weeks and then every other day for 22 wk. The patients were divided into interferon (IFN) treatment-responsive and non-responsive groups, but 36 patients lost follow-up shortly after receiving the treatment. The expression of IFN-α/β receptor (IFN-α/βR) protein in liver of all patients was determined with immunofluorescence. RESULTS: In liver of patients with HCV-related chronic liver disease, the expression of IFN-α/βR protein in liver cell membrane was stronger than that in cytoplasm and more obvious in the surroundings of portal vein than in the surroundings of central vein. Moreover, it was poorly distributed in hepatic lobules. The weak positive, positive and strong positive expression of IFN-α/βR were 40% (50/125), 28% (35/125), 32% (40/125), respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56), respectively in LC group. The positive and strong positive rates were higher in CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8% (10/36) showed weak positive expression; 72.2% (26/36) showed positive or strong positive expression. In the non-responsive group, 71.7% (38/53) showed weak positive expression; 28.3% (15/53) showed positive or strong positive expression. The expression of IFN-α/βR protein in liver was more obvious in IFN treatment responsive group than in non-responsive group. CONCLUSION: Expression of IFN-α/βR protein in liver of patients with HCV-related chronic liver disease is likely involved in the response to IFN treatment.

Pegylated IFN-α2b added to ongoing lamivudine therapy in patients with lamivudine-resistant chronic hepatitis B

AIM： To investigate the role of pegylated-interferon （IFN）α-2b in the management of patients with lamivudineresistant chronic hepatitis B. METHODS： Twenty consecutive anti-HBe positive patients were treated with pegylated IFN α-2b （100 IJg sc once weekly） for 12 mo. There was no interruption in lamivudine therapy. Hematology, liver biochemistry, serum HBV DNA levels were detected by PCR, and vital signs were also assessed. Liver histology was assessed in some patients at entry and at wk 52 for comparison. RESULTS： Nine patients （45%） had a partial virological end-treatment response; seven patients （35%） showed complete virological end-treatment response. Eight patients （40%） showed biochemical end-treatment response. There was a trend for higher virological response rates in patients who had previously responded to IFN and relapsed compared to IFN non-responders （four out of seven patients vs none out of six patients, respectively; P=0.1）. Patients without virological endtreatment response showed significant worsening of fibrosis [median score 2 （range, 1 to 3） vs median score 3 （range, 1 to 4）], in the first and second biopsy respectively （P=0.014）, whereas necroinflammatory activity was not significantly affected. Patients with complete or partial virological end-treatment response did not show any significant changes in histological findings, possibly due to the small number of patients with paired biopsies （n = 5）. Nevertheless, after 12 mo of follow-up, only onepatient （5%） showed sustained virological response and only 2 patients （10%） showed sustained biochemical response. Two patients （10%） discontinued pegylated ]FN both after 6 mo of treatment due to flu-like symptoms. CONCLUSION： Pegylated IFNα-2b, when added to ongoing lamivudine therapy in patients with lamivudineresistant chronic hepatitis B, induces sustained responses only in a small minority of cases.

Effect of interferon alpha and ribavirin treatment on serum levels of transforming growth factor-β1,vascular endothelial growth factor,and basic fibroblast growth factor in patients with chronic hepatitis C

AIM： To assess the role of transforming growth factor-β1 （TGF-β1）, vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF） in the pathogenesis of fibrosis associated with chronic hepatitis C （CHC） and to evaluate the influence of the antiviral therapy on above parameter levels depending on the treatment results （complete response or no response）. METHODS： Study group included 100 patients with CHC, in whom fibrosis in liver specimens was assessed （Scheuer fibrosis score： 1-4 points）. Control group included 30 subjects with antibodies anti-HCV present and persistently normal ALT level, without fibrosis （Scheuer fibrosis score： 0 points）. Concentration of studied parameters was assayed in the serum by immunoenzymatic method before and after the therapy with interferon alpha-2b and ribavirin. RESULTS： TGF-β1 levels were significantly higher in the study group compared to the control group （35.89 vs 32.37 ng/mL; P= 0.023）. Such differences were not found in VEGF and bFGF levels. In patients showing complete response （negative HCV RNA and normal ALT level）, significant increase in VEGF （112.8 vs 315.03 pg/mL; P〈 0.05） and bFGF （2.51 vs 15.79 pg/mL; P=0.04） levels were found. Significant decrease in TGF-β1 level was observed both in responders （37.44 vs 30.02 ng/mL; P=0.05）, and in non-responders （38.22 vs 30.43 ng/mL; P=0.043）. bFGF levels before the treatment were significantly lower （2.51 vs 5.94 pg/mL; P=0.04）, and after the treatment significantly higher （15.79 vs 4.35 pg/mL; P=0.01） in patients with complete response response. CONCLUSION： Among the analyzed parameters TGF-β1 seems to play the most important role in the pathogenesis of fibrosis in CHC. Levels of this factor are significantly lower in subjects who do not have fibrosis developed in them. Good therapeutic effect in CHC patients is associated with significant changes in TGF-β1, VEGF, and bFGF levels, bFGF seems to have the highest usefulness in the prognosis of treatment efficacy.

Characterization of the antiviral effects of interferon-α against a SARS-like coronoavirus infection in vitro

Interferon （IFN）-αs bind to and activate their cognate cell surface receptor to invoke an antiviral response in target cells. Well-described receptor-mediated signaling events result in transcriptional regulation of IFN sensitive genes, effectors of this antiviral response. Results from a pilot study to evaluate the clinical efficacy of IFN-α treatment of SARS patients provided evidence for IFN-inducible resolution of disease. In this report we examined the contribution of IFN-inducible phosphorylation-activation of specific signaling effectors to protection from infection by a SARS-related murine coronavirus, MHV-1. As anticipated, the earliest receptor-activation event, Jakl phosphorylation, is critical for IFN-inducible protection from MHV-1 infection. Additionally, we provide evidence for the contribution of two kinases, the MAP kinase p38MAPK, and protein kinase C （PKC） 5 to antiviral protection from MHV-1 infection. Notably, our data suggest that MHV^I infection, as for the Urbani SARS coronoavirus, inhibits an IFN response, inferred from the lack of activation ofpkr and 2 ＇5 ＇-oas, genes associated with mediating the antiviral activities of IFN-as. To identify potential target genes that are activated downstream of the IFN-inducible signaling effectors we identified, and that mediate protection from coronavirus infection, we examined the gene expression profiles in the peripheral blood mononuclear cells of SARS patients who received IFN treatment. A subset of differentially regulated genes were distinguished with functional properties associated with antimicrobial activities.

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2:A project of the Kyushu University Liver Disease Study Group

AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed. METHODS： In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS： The overall sustained virological response （SVR）, defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, （146/173） by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin （46.9% vs 92.9 %）, but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment （34.8 % vs 92.0 %）. CONCLUSION： The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16

Histological outcome of chronic hepatitis B in children treated with interferon alpha

AIM： To evaluate the effect of interferon alpha （IFN-α） treatment on the liver histology in children with chronic hepatitis B and to evaluate the usefulness of various histological scoring systems of liver histology in this group of patients. METHODS： Fibrosis stage and inflammation grade were assessed according to Batts and Ludwig, Ishak et al., and IETAVIR （only fibrosis stage） before and 12 mo after IFN-α treatment termination in 93 children aged 2-16 years with chronic hepatitis B. RESULTS： None of the three numerical scoring systems for liver fibrosis showed statistically significant differences in liver fibrosis, while evolution of inflammatory activity revealed statistically significant improvement in the whole group of children with chronic hepatitis B treated with IFN-α and in responders. Significantly positive correlations were found between fibrosis stage and inflammation grade in the respective scoring systems. CONCLUSION： Treatment with IFN-α did not improve histological fibrosis but decreased inflammatory activity in children with chronic hepatitis B. The three semiquantitative scoring systems seem to be comparable in the estimation of the inflammation grade and fibrosis stage in this group of children.

Psychiatric side effects of pegylated interferon alfa-2b as compared to conventional interferon alfa-2b in patients with chronic hepatitis C

AIM: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional interferon.METHODS: Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98patients; 5 MIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 μgpeginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1 200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R).RESULTS: Therapy with pegylated interferon alfa-2bproduces comparable scores for depression (ANOVA:P = 0.875) as compared to conventional interferon.Maximums of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy subgroups.CONCLUSION: Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. Monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.

Interferon-伪 plus lamivudine vslamivudine reduces breakthroughs, but does not affect sustained response in HBeAg negative chronic hepatitis B

AIM： To investigate the efficacy of combination treatment of IFN-α and lamivudine compared to lamivudine monotherapy, after 24 mo of administration in HBeAgnegative hepatitis B patients. METHODS： Fifty consecutive patients were randomly assigned to receive IFN-α-2b （5 MU thrice per week, n = 24） plus lamivudine （100 mg daily） or lamivudine only （n = 26） for 24 mo. Patients were followed up for further 6 mo. The primary outcome was the proportion with sustained virological response （undetectable serum HBV DNA concentrations） and or sustained biochemical response （transaminase levels within normal range） at 30 mo （6 mo after the end of therapy）. Secondary end-points were timed from initial virological （biochemical） response to VBR （BBR, respectively） and the emergence of YMDD mutants across the two arms. RESULTS： Five of twenty-four （21%） patients in the combination arm vs 3/26 （12%） in the lamivudine arm had sustained response （i.e., normal serum transaminase levels and undetectable HBV DNA by PCR assay） 6 mo after treatment discontinuation. A reduction in the emergence of YMDD mutants and in the development of virological breakthroughs was observed in patients receMng combination treatment （10% vs46% , P= 0.01 and 14% vs46% , P= 0.03, respectively）. Time from initial virologic response to virologic breakthrough （VBR） was greater among initial responders receiving combination treatment compared to those receiving lamivudine （22.9 mo vs 15.9 mo, respectively; P = 0.005）.CONCLUSION： Our results demonstrate that IFN-α plus lamivudine combination therapy does not increase the sustained response, compared to lamivudine. However, combination therapy reduces the likelihood of VBR due to YMDD mutants and prolongs the time period until the breakthrough development.