Efficacy of low dose peginterferon alpha-2b with ribavirin on chronic hepatitis C

AIM: To assess the effi cacy of peginterferon alpha 2b at doses of 50 μg weekly and 80 μg weekly (based on body weight) plus ribavirin in HCV genotype 2 and genotype 3 chronic hepatitis C patients. METHODS: During the study period of Jan 2002 to Dec 2003, all patients diagnosed as chronic hepatitis C or HCV related compensated cirrhosis were treated with peginterferon alpha 2b 50 μg S/C weekly (body weight < 60 kg) or 80 μg S/C weekly (body weight > 60 kg) plus ribavirin 800 mg/d for 24 wk. RESULTS: Overall 28 patients, 14 patients in each group (based on body weight) were treated during the period. Out of 28 patients, 75% were genotype 3, 18% were genotype 2 and 7% were genotype 1. The mean dose of peginterferon alpha 2b was 0.91 μg/kg in group 1 and 1.23 μg/kg in group 2 respectively. The end of treatment and sustained virologic response rates were 82% and 78% respectively. Serious adverse effects were seen in 3.5% patients. CONCLUSION: Low dose peginterferon alpha 2b in combination with ribavirin for 24 wk is effective in HCV genotype 2 and 3 chronic hepatitis C patients.

长链非编码RNA alpha-2-巨球蛋白反义RNA 1靶向微小RNA-106b-5p调控氧化型低密度脂蛋白诱导的人脑微血管内皮细胞损伤

目的探讨长链非编码RNA(lncRNA)alpha-2-巨球蛋白反义RNA 1(A2M-AS1)靶向微小RNA(miR)-106b-5p对氧化型低密度脂蛋白(ox-LDL)诱导的人脑微血管内皮细胞损伤的影响。方法用ox-LDL诱导人脑微血管内皮细胞设为ox-LDL组,正常培养细胞为对照(Ctrl)组;A2M-AS1过表达(pcDNA-A2M-AS1组)、空载体(pcDNA组)、miR-106b-5p抑制剂(anti-miR-106b-5p组)、阴性对照(anti-miR-NC组)、pcDNA-A2M-AS1与对照mimic NC(miR-NC组)、pcDNA-A2M-AS1与miR-106b-5p模拟物(miR-106b-5p mimics组)转染细胞后加ox-LDL处理,n=9;Real-time PCR检测A2M-AS1与miR-106b-5p表达;试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)水平;流式细胞术及TUNEL法检测细胞凋亡;双荧光素酶报告基因实验检测A2M-AS1与miR-106b-5p靶向关系;Western blotting检测Bcl-2和Bax蛋白表达量。结果与Ctrl组比较,ox-LDL组A2M-AS1表达水平、SOD和CAT活性、Bcl-2蛋白水平降低,miR-106b-5p表达水平、MDA水平、凋亡率、Bax蛋白水平升高(P<0.05);过表达A2M-AS1或干扰miR-106b-5p降低ox-LDL诱导细胞后MDA水平、凋亡率与Bax蛋白水平,升高SOD、CAT活性和Bcl-2蛋白水平(P<0.05);A2M-AS1靶向miR-106b-5p;上调miR-106b-5p逆转过表达lncRNA A2M-AS1对ox-LDL诱导的人脑微血管内皮细胞损伤的作用。结论A2M-AS1通过靶向miR-106b-5p减轻ox-LDL诱导的人脑微血管内皮细胞损伤。

CHOP-like Regimen in Combination with Rituximab and Peginterferon Alpha-2b in Newly-diagnosed Diffuse Large B-cell Non-Hodgkin＇s Lymphoma： Experience in a Chinese Center

OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin＇s lymphoma （DLBCL）.METHODS From January 2003 to July 2008, 51 patients received CHOP-like chemotherapy （cyclophosphamide 750 mg/m2, epirubicin 80 mg/m2, vindesine 2.8 mg/m2 on day 1, and prednisolone 100 mg/day on day 1 to day 5）. Thirty-one patients received CHOPR-like treatment （rituximab 375 mg/m2 1 day before CHOP-like chemotherapy）. Twenty patients received CHOP-like regimen in combination with peginterferon （pegIFN） （1μg/kg on day 5） and rituximab （on day 6）.RESULTS -The CR （complete remission） rate in the CHOPR-like （with or without pegIFN） group and in the CHOP-like group was 78.4% and 45.1% （P = 0.005）, respectively. The estimated mean time of overall survival （OS） in the CHOPR-like group and CHOP- like group was 58.7 ± 2.8 and 36.4 ±3.4 months, respectively （P = 0.002）. The rates of CR and OR （overall remission） in CHOPR- like with IFN arm were 85.0% and 95.0%, and the rates of those in CHOPR-like without IFN arm were 74.2% and 87.0% （P 〉 0.05）. The estimated mean time of 4-year-PFS （progression- free survival） in CHOPR-like with IFN arm and in CHOPR-like without IFN arm was 62.9 ±3.0 months and 51.0 ± 4.6 months （P = 0.092）, respectively. In the CHOPR-like with IFN arm, no patient relapsed after achieving CR, while the estimated rate of 4-year- DFS （disease-free survival） in the patients who reached CR in the CHOPR-like without IFN arm was （63.4 ± 19.3）% （P = 0.061）. CONCLUSION Rituximab combined with CHOP-like chemotherapy improved the prognosis of DLBCL patients. The IFN may help to improve the quality and duration of response of DLBCL patients treated with rituximab and CHOP-like regimen.

三角帆蚌alpha-2巨球蛋白cDNA全长的克隆及表达特征

alpha-2巨球蛋白是河蚌体内重要的天然免疫因子,参与广泛的免疫防御和调节。通过RACE法克隆了三角帆蚌α2M全长cDNA序列,提交Genbank,获得核苷酸序列登陆号:DQ993157.1。同时,采用生物信息学方法对alpha-2巨球蛋白进行了系统分析。该基因cDNA全长5124bp,其中编码区4836bp,5′端非编码区35bp,3′端非编码区为253bp(含polyA尾31bp),该基因能编码1611个氨基酸,其中前23个氨基酸残基为信号肽序列,成熟蛋白分子量为177571.8u,等电点为5.49。蛋白的不稳定系数为39.53,表明该蛋白是稳定的。在此基础上,以18S作为内标,利用半定量RT-PCR法检测α2M基因在三角帆蚌不同组织和不同生理状态下的表达情况。结果表明,alpha-2巨球蛋白仅在血细胞中有表达,而在外套膜、闭壳肌、肠和性腺中没有表达。经注射大肠杆菌和嗜水气单胞菌12h后,三角帆蚌体内α2M的表达水平都有一定量的升高,证明α2M是三角帆蚌基础免疫系统中的组成部分。本研究丰富了软体动物免疫学研究内容,为三角帆蚌抗病机理提供理论资料。

三角帆蚌alpha-2巨球蛋白活性测定及不同组织的表达

alpha-2巨球蛋白(alpha-2 Macroglobulin,α2M)是一种蛋白酶结合蛋白,是重要的天然免疫因子。利用α2M的作用原理,用三角帆蚌血浆保护胰蛋白酶,后用大豆蛋白酶抑制剂抑制未被保护的胰蛋白酶。利用Na-benzoyl-DL-arg-nine-p-nitroanilide(BAPNA)作为酶底物检测被保护的蛋白酶活性的方法,首次证明了三角帆蚌体内α2M的存在。在此基础上,克隆了α2M基因保守区受体结合区片段,进一步证明了α2M在三角帆蚌体内的存在。同时,还进行了α2M不同组织的表达检测,结果显示,α2M基因在血细胞中有表达,而在外套膜、闭壳肌、肠和性腺中没有表达。

双氢青蒿素对C2株蓝氏贾第鞭毛虫Alpha-7.3giardin基因mRNA表达水平的影响

目的观察双氢青蒿素(dihydroartemisinin,DHA)对C2株蓝氏贾第鞭毛虫(Giardia lamblia)Alpha-7.3giardin(α-贾第素)基因mRNA表达水平的影响,探讨其对蓝氏贾第鞭毛虫骨架蛋白的损伤作用。方法用双氢青蒿素浓度为100μg/mL、200μg/mL的改良TYI-S-33培养基分别培养C2株蓝氏贾第鞭毛虫2h、4h、8h、12h后,以不含药物组为对照,实时荧光定量RT-PCR检测药物作用后Alpha-7.3giardin基因mRNA表达水平的变化。结果双氢青蒿素作用虫体后Alpha-7.3giardin基因mRNA表达水平明显低于对照组,二者有显著性差异。结论双氢青蒿素对C2株蓝氏贾第鞭毛虫Alpha-7.3giardin基因mRNA的表达具有明显的抑制作用,抑制效果与药物浓度和作用时间相关,提示双氢青蒿素对蓝氏贾第鞭毛虫骨架蛋白具有损伤作用。

Alpha-2-HS糖蛋白遗传多态性的研究进展

Heremans最早发现人类α2-HS-糖蛋白（α2-HS-glycoprotein）,称为α2-Z-球蛋白（α2-Z-globulin）。Schmid及Burg继续研究,将其命名为Baα2-糖蛋白（Baα2-glycoprotein）。Schultze等根据这种蛋白质的电泳迁移率（α2）将其命名为α2-HS-糖蛋白。H与S分别是Heremans与Schmid姓氏的第一个字母。α2HS的分子量是49000道尔顿,由A、B两条多肽链组成,两链以二硫链共价结合。A链含282个氨基酸,有4个连接糖的部位,B链含27个氨基酸,只有1个连接糖的部位,即第6个氨基酸残基丝氨酸;与B链连接的糖侧链由涎酸、半乳糖及N-乙酰胺基半乳糖组成,用神经氨酸酶（ncuraminidase,NANA）脱涎酸,可使α2HS的等电点由pH4.5～5.0提高至pH5.5,最近才报道。α2HS的分离与纯化及其生化特征。

Serum proteins in chronic hepatitis B patients treated with peginterferon alfa-2b

AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.

The Predictive Value of Baseline HBs Ag Level and Early Response for HBs Ag Loss in Patients with HBe Ag-positive Chronic Hepatitis B during Pegylated Interferon Alpha-2a Treatment

Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators （HBs Ag, anti-HBs, HBe Ag, and anti-HBe） were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks （7-273 weeks）, and 74.38% （90 cases） of the patients needed extended treatment （〉 48 weeks）. The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant （B = 14.465, t = 2.342, P = 0.021）. Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss （B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005）. Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

Peginterferon alfa-2a for the treatment of chronic hepatitis C in the era of direct-acting antivirals

BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS: PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION: In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.

Alpha-2-macroglobulin as a radioprotective agent: a review

Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin（α2M） possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi？ et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.

Combination Therapy with Pegylated Interferon alpha-2b and Adefovir Dipivoxil in HBeAg-positive Chronic Hepatitis B versus Interferon Alone: A Prospective, Randomized Study

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.

Protracted anaphylaxis developed after peginterferon α-2a administration for chronic hepatitis C

Peginterferon is a key drug used to treat chronic viral hepatitis that is known for causing various side effects.Side effects occurring immediately after administration include headache, nausea, and influenza-like symptoms, such as fever and joint pain.However, reports of anaphylactic shock are extremely rare.Here we report a patient with protracted anaphylaxis who suffered shock symptoms after peginterferon α-2a administration for chronic hepatitis C.Although the patient improved temporarily with shock treatment, symptoms of anaphylaxis recurred.As peginterferon is often administered on an outpatient basis, it is important to recognize life-threatening side effects that may develop in a protracted manner.

Treatment of Hepatitis C with Pegylated Interferon Alpha-2a and Ribavirin:Experience from Benin

Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effectiveness and safety of treatment with classic dual interferon pegylated alpha-2a (IFN) and ribavirin therapy in Benin, and 2) to present problems related to financial accessibility to this treatment. Methods: This was a cross-sectional, descriptive and analytical study, with a retrospective collection of data from November 1, 2010 to December 31, 2015 and prospective collection from January 1, 2016 to July 31, 2016 (7 months). We included all patients treated with IFN + ribavirin for hepatitis C at CNHU/HKM. Sustained virological response (SVR) was defined as undetectable viral load C 6 months after stopping treatment. Safety was appreciated by the search for clinical and hematological adverse effects. Results: One hundred and six patients were followed for HCV, of whom 58 (54.7%) undergoing treatment (26 under standard dual therapy and 32 under direct-acting antivirals). Of the 26 patients under-conventional dual therapy, 12 (46.1%) were genotype 1, 13 (50%) genotype 2 and one (3.9%) genotype 4. In conventional dual therapy, SVR was achieved in 15 (57.7%) patients, including the genotype 4 patient, 4 out of 12 (33.3%) genotype 1 patients, and 10 out of 13 (76.9%) for genotype 2 patients. The most common side effects with this treatment were severe asthenia (23 cases), flu-like symptoms (22 cases), weight loss (21 cases) and neutropenia (22 cases), anemia and thrombocytopenia (20 of 26 cases). The overall cost of treatment per patient was 11,800,624 FCFA for genotypes 1 and 4;and 7,835,048 FCFA for genotype 2. Conclusion: The treatment of HCV with IFN + ribavirin in Benin is effective for genotype 2. But its adverse effects are manifold and its cost is high. The switch to direct-acting antivirals (more effective, better tolerated and less expensive) was therefore necessary.

Pain-Relief Effects of Aroma Touch Therapy with <i>Citrus junos</i>Oil Evaluated by Quantitative EEG Occipital Alpha-2 Rhythm Powers

Aroma touch therapy is widely used in clinical fields for alleviating pain-related symptoms;however, few studies have reported the pain-relief mechanisms. The present study aimed to elucidate the analgesic effects of aroma touch therapy with Citrus junos oil based on the quantitative evaluation of deep brain network (DBN) activity using electroencephalogram (EEG) occipital alpha-2 rhythm (10-13 Hz) powers. Experimental investigations were performed with 13 healthy volunteers using the cold pressor task for simulating chronic pain in three different sessions: a baseline session with no therapies, a control session with a touch therapy, and an aroma touch therapy. We have found for the first time that the interviewed pain ratings represented by Numeric Rating Scale (NRS) scores were strongly correlated with a DBN activity index, which was derived from the slow fluctuation components of occipital EEG alpha-2 rhythm powers. The correlation was characterized by a V-shaped curve in the DBN activity index versus the pain rating, i.e., the NRS score, which provided the complete analgesic states (NRS = 0) for some subjects under aroma touch therapy at an appropriate DBN activity index. Such analgesic states were not so strongly correlated with emotional valence. In conclusion, aroma touch therapy may directly modulate DBN activity so that pain-induced outcomes are minimized.

Appropriate leucine-richα-2 glycoprotein cut-off value for Japanese patients with ulcerative colitis

BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease.In particular,the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis(UC)has become a matter of interest.AIM To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with UC.METHODS This was a cross-sectional,single-center,observational study of Japanese patients with UC.Among 213 patients with UC,in whom LRG was measured from September 2020 to February 2022,we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein(CRP)were performed on the same day.We retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices,including the Mayo endoscopic subscore and UC endoscopic index of severity.RESULTS Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant(r=0.754,P<0.0001;r=0.778,P<0.0001,respectively).There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity(r=0.599,P=0.0005;r=0.563,P=0.0012,respectively),although the correlation coefficients were higher for LRG.The LRG cutoff value for predicting endoscopic remission was 13.4μg/mL for a Mayo endoscopic subscore of 0[area under the curve(AUC):0.871;95%confidence interval(CI):0.744-0.998],and 13.4μg/mL for an UC endoscopic index of severity of 0 or 1(AUC:0.904;95%CI:0.792-1.000).CONCLUSION LRG may be a surrogate marker for endoscopic activity in UC,with a cut-off value of around 13.4μg/mL for endoscopically inactive disease.

聚乙二醇干扰素α-2a联合胸腺肽α_1治疗HBeAg阳性慢性乙型肝炎

目的:探讨聚乙二醇α-2a干扰素(PEG INFα-2a)和胸腺肽α_1(Tα_1)联合治疗HBeAg阳性慢性乙型肝炎的疗效和安全性。方法:按随机对照原则选择80例HBV DNA、HBeAg阳性的慢性乙型肝炎患者,按1:1随机分配进入单一PEG INFα- 2a组和PEG INFα-2a联合Tα_1治疗组。结果:治疗6个月时,PEG INFα-2a+Tα_1组HBeAg血清转换率(62.5%)明显高于PEG INFα-2a组(40.0%),P<0.05。停药6个月后,持续的HBeAg血清转换率分别为57.5%(23/40)和35.0%(14/40),P<0.05。治疗6个月时,PEG INFα-2a+Tα_1组HBV DNA阴转率(65.0%)明显高于PEG INFα-2a组(42.5%),P<0.05。停药6个月后,持续的HBV DNA阴转率分别为62.5%(25/40)和40.0%(16/40),P<0.05。治疗6个月时和停药6个月后,两组的丙氨酸转氨酶(ALT)复常率差异有显著性。治疗6个月,联合治疗组完全应答率(62.5%)明显高于PEG INFα-2a组(40.0%),停药后6个月,持续应答率分别为57.5%(23/40)和35.0%(14/40)。联合治疗组有4例患者HBsAg阴转,而PEG INFα-2a组仅有2例患者HBsAg阴转。两组有相似的不良反应,不良反应间差异无显著性,两组治疗过程中均无发生重要的不良事件。结论:Tα_1与PEG INFα-2a联合治疗HBeAg阳性的慢性乙型肝炎不良反应少,疗效优于PEG INFα-2a单一用药。

聚乙二醇干扰素α-2a治疗慢性丙型肝炎疗效观察

目的：观察聚乙二醇干扰素α-2a（PEG-IFNα-2a）治疗慢性丙型肝炎的临床疗效和安全性。方法：85例慢性丙型肝炎患者随机分为两组，观察组（43例）予PEG-IFNα-2a180μg，皮下注射，每周1次，同时口服利巴韦林900～1200mg·d-1；对照组（42例）接受普通干扰素α-2b500MU，皮下注射，1周3次，利巴韦林用法同观察组。48周治疗结束后随访24周，检测基线及治疗4，12，48周及治疗结束后24周时的血清HCVRNA和ALT水平，比较两组快速病毒学应答（RNA）率、早期病毒学应答（EVR）率、治疗终点病毒学应答（ETVR）率、持续病毒学应答（SVR）率以及ALT复常率与不良反应。结果：EVR、ETVR、SVR观察组分别为76.7%、86.0%和79.1%，明显高于对照组的54.8%、66.7%和57.1%，差异有统计学意义（P＜0.05）。观察组治疗12周及48周时ALT复常率分别为81.4%和90.7%，明显高于对照组（P＜0.05）。观察组白细胞计数下降和血小板减少的发生率高于对照组（P＜0.05），中性粒细胞计数减少的发生率明显高于对照组（P＜0.01），其他不良反应两组相近，未出现与聚乙二醇干扰素α-2a相关的新的不良反应。结论：PEG-IFNα-2a对慢性丙型肝炎患者的疗效优于普通干扰素，并具有较好的安全性和耐受性。