Interferon Alfa-2a Research Articles

The influence of hepatic steatosis on the success of antiviral therapy for chronic hepatitis C

Background/Aim. Chronic hepatitis C and liver steatosis often appear simultaneously in the same person, and steatosis can lead to worsening of liver disease and reducing the success of the treatment of chronic hepatitis C. Treatment of one disease can influence and cause favorable impact on treatment of other diseases. The aim of this study was to determine the incidence of liver steatosis in patients with chronic hepatitis C and to examine the impact of steatosis of the liver and other predictors on the success of antiviral therapy for chronic hepatitis C. Methods. The study included 123 patients with chronic hepatitis C treated with pegylated interferon alfa 2a in combination with ribavirin. The patients were divided into two groups based on the presence of cirrhosis: the group I consisted of 43 (34.9%) patients with steatosis and the group II consisted of 80 (65.1%) patients without liver steatosis. The success of the treatment was evaluated on the basis of the stable virological response. Results. The presence of steatosis was determined in 34.96% of the patients. The overall success of antiviral therapy was found in 74.79% of the patients. The success of antiviral therapy was present in 62.79% of the patients with hepatic steatosis, and in 81.25% the patients without steatosis (p < 0.05). The success of antiviral treatments was seen in 80.95% of the patients with hepatic steatosis and the genotype of hepatitis C virus 3. The predictors of antiviral therapy success for chronic hepatitis C in our study were patient's age, duration of infection, genotype 3, steatosis and severe fibrosis or cirrhosis. Conclusion. Liver steatosis is often present in patients with chronic hepatitis C. It has negative impact on the efficacy of antiviral therapy in patients with infection with genotype non-3 hepatitis C virus. Therefore, hepatic steatosis in these patients must be eliminated or treated prior to application of antiviral therapy.

EVALUATION OF EFFECTIVENESS OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C, CAUSED BY HCV GENOTYPE 6

Objectives: Evaluating the effectiveness of 2 therapeutic schemes for chronic hepatitis C (genotype 6) which combined sofosbuvir and ribavirin, one of them also included pegylated interferon. Materials and methods: The study included 110 patients with chronic hepatitis C (genotype 6), who have undergone antiviral therapy (HTP) in Hepatology Clinic inHo Chi Minh City,Vietnamfrom November 2015 to July 2016. 24 patients were treated by Pegylated interferon alfa-2a, ribavirin and sofosbuvir for 12 weeks, 86 patients – by sofosbuvir and ribavirin for 24 weeks. Non-interferon regimen was administered primarily to patients with contraindications to the use of interferon. To monitor the effectiveness of antiviral therapy, quantification of HCV RNA in serum was performed by PCR prior to treatment, at 4th, 12th or 24th week (depending on the observation group) from the starting of treatment and at 12th, 24th week after completion of treatment. Results: All patients, who were treated with pegylated interferon, ribavirin and sofosbuvir, completed the full course of treatment and 100% of them are registered with sustained virological response at 12th and 24th week after the end of antiviral therapy (SVR-12 and SVR-24, respectively). In the group of patients, who treated with ribavirin and sofosbuvir, 97,7% of patients completed full course of treatment (SVR-12 was registered in 93% of patients, and SVR-24 – in 91,9% of patients). Of 75 patients without a history of HCC, SVR24 was registered in 74 people (98,7%), of 11 patients with HCC – in 5 patients (45,5%). SVR-24 was registered in 98% of patients with cirrhosis (F4) without HCC. Conclusion: The results can serve as a justification for the use of these schemes of antiviral therapy for special groups of patients and/or conditions when it is impossible to follow the latest recommendations, which will help to expand the access of patients to effective antiviral therapy for chronic hepatitis C.

HBsAg clearance in chronic hepatitis B patients with add-on pegylated interferon alfa-2a to ongoing tenofovir treatment: A randomized controlled study.

Background/Aims:The ideal end point of treatment for chronic hepatitis B virus (HBV) infection is sustained off-therapy hepatitis B surface antigen (HBsAg) loss with or even without seroconversion to anti-HBs. We investigated the role of adding PEGylated interferon (PEG IFN) to ongoing tenofovir treatment in chronic HBV patients for achieving HBsAg clearance.Patients and Methods:In this randomized controlled trial, chronic HBV patients who have been receiving tenofovir for >6 months with HBV viral load <2000 IU/ml were randomized into two groups. One group (add-on therapy) was given subcutaneous PEG IFN 180 mcg weekly for 12 months in addition to tenofovir. Patients in the other group received only tenofovir 300 mg orally on a daily basis. Patients in both groups were followed up for a total of two years, and patients in both groups were given tenofovir 300 mg daily indefinitely until they developed HBsAg clearance.Results:Twenty-three patients were allocated to the PEG IFN and tenofovir (add-on therapy) group, and another 25 patients were recruited to the tenofovir monotherapy group. Before randomization, patients had received tenofovir for 1135 mean days (range203 to 1542 days). One patient (4.3%) in add-on therapy lost HBsAg and seroconverted. Within two years, mean HBsAg decreased significantly with add-on therapy (from 4753 IU/ml to 2402; P = 0.03); and it decreased from 5957 IU/ml to 4198; P = 0.09 in tenofovir monotherapy group. More patients in the add-on group developed serious side effects, with treatment discontinuation, and dose reductions (P = 0.3).Conclusion:PEG IFN and tenofovir add-on therapy was successful in achieving HBsAg clearance and seroconversion in 4.3% of the patients. Add-on therapy patients had a significant decrease in HBsAg levels in two years; and no significant decrease in HBsAg levels with the tenofovir monotherapy. With no significant HBsAg clearance, the utility of this combination regimen is questionable.

Role of HBsAg decline in patients with chronic hepatitis B HBeAg-negative and E genotype treated with pegylated-interferon

Treatment options for patients with chronic hepatitis B (CHB) and hepatitis B e antigen (HBeAg)-negative are pegylated interferon alfa-2a (PEG-IFN) for 48 weeks or nucleos(t)ide analogues (NAs). The choice of patients with higher chance of sustained response (SR) to PEG-IFN can be made with pre-treatment and on-treatment factors; recent studies evidenced the role of early drop of serum hepatitis B surface antigen (HBsAg) as predictor of SR. The aim of this study was the evaluation of early decrease of HBsAg on the SR in HBeAg-negative patients with E genotype.A retrospective analysis was performed on 72 patients affected by HBeAg-negative CHB with E genotype, treated for 48 weeks with PEG-IFN. HBsAg and HBV-DNA kinetics were evaluated. Decline of HBsAg (>0.5 logIU/mL) and HBV-DNA (≥2 logIU/mL) at 12 weeks was described according to observed chance of SR.After 96 weeks of follow-up, SR was observed in 10 patients (13.9%); HBsAg loss 6 (8.3%), HBsAg seroconversion in 3 (4.2%). No patients with HBsAg decline ≤0.5 log IU/mL and HBV-DNA<2 logIU/mL achieved SR (negative predictive value, NPV 100%). In multivariate analysis were significantly associated with SR the combined decline of HBsAg and HBV-DNA at 12 weeks (OR = 35.336; 95% CI: 4.668–112.226; p < 0.001) and the HBsAg≤7500 IU/mL at 24 weeks (OR = 51.824; 95% CI: 9.692–134.144; p < 0.001).Combining the HBsAg and HBV-DNA decline at 12 weeks we can identify patients without chance of SR who may stop PEG-IFN treatment. Stopping rule at 24 weeks using HBsAg≤7500 IU/mL is strong predictor of SR in HBeAg-negative patients with E genotype.

Dermatological Manifestations of Pegylated Interferon alfa2a and Ribavirin Combination Therapy in Chronic HCV Patients

Background and study aim: Dermatological adverse events are an existing concern during treatment of chronic hepatitis C virus infection. Pegylated Interferon (peg –IFN- alfa2a) and ribavirin combination therapy is associated with well-characterized dermatological lesions tending towards a uniform entity of dermatitis. A prospective observational study was designed to evaluate the frequency and clinical pattern of cutaneous side effects in a cohort of patients receiving combination therapy of (pegylated interferon alfa2a) and ribavirin for chronic hepatitis C infection. Patients and Methods: This study was carried out at Alahrar Center for treating chronic hepatitis C patients which is one of the centers of the national committee for treating chronic hepatitis C patients (HCV), Zagazig, Sharkia governorate, Egypt over a period of one year starting from January, 2014 to December 2014. A cohort of 116 consecutive, HCV-positive patients to be treated with pegylated interferon alfa2a and ribavirin with standard doses, were prospectively enrolled. After taking an informed consent, detailed history and cutaneous examination, before treatment and then monthly follow up for one year(during the course of treatment) were performed and recorded .All patients were subjected to throughout, routine laboratory investigations before enrollment including, CBC, random blood sugar, complete liver and renal function tests, TSH, Alfa fetoprotein, antibilharzial Ab titre, ANA, P.T, INR, quantitative PCR for HCV-RNA, pregnancy test was performed for the ladies. Results: 113/116 patients (97%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 69 cases (Session [CurrentTestPartTermID]%). Pigmented Oral lichen planus was noted in 50 cases (43%) and generalized pigmentation in 32 (27%). Hypertrichosis of eyelashes (trichomegaly) and eyebrows (synophyrs) was observed in 42 (36%) and 40 (34%) cases respectively. Pruritus occurred in 50 cases (43%), aphthous stomatitis was observed in 33 cases (38%), 19 patients (22%) either developed or had worsening of melasma and 23 (27%) developed urticaria. Brittle nails (10 cases), cheilitis (8 cases), glossitis (3 cases), actinic lichen planus (9 cases), greying of hair (3 cases), discoloration of moustache hair (1 case), and photo-sensitivity (3 cases) were also observed. Preexisting psoriasis (8 cases), and lichen planus (5 cases) aggravated. Eruptive seborrhoeic keratosis was reported in 1 case. Conclusion: 113/116 patients (97%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 69 cases (Session [CurrentTestPartTermID]%). Pigmented Oral lichen planus was noted in 50 cases (43%) and generalized pigmentation in 32 (27%). Hypertrichosis of eyelashes (trichomegaly) and eyebrows (synophyrs) was observed in 42 (36%) and 40 (34%) cases respectively. Pruritus occurred in 50 cases (43%), aphthous stomatitis was observed in 33 cases (38%), 19 patients (22%) either developed or had worsening of melasma and 23 (27%) developed urticaria. Brittle nails (10 cases), cheilitis (8 cases), glossitis (3 cases), actinic lichen planus (9 cases), greying of hair (3 cases), discoloration of moustache hair (1 case), and photosensitivity (3 cases) were also observed. Preexisting psoriasis (8 cases), and lichen planus (5 case) aggravated. Eruptive seborrhoeic keratosis was rep case).

Synergistic Effects of Jerusalem Artichoke in Combination with Pegylated Interferon Alfa-2a and Ribavirin Against Hepatic Fibrosis in Rats.

Complementary and alternative medicine has been highly appreciated as a supportive regimen for classical treatment strategies. Here we offer a nutrition-based adjuvant therapy for liver fibrosis, a major risk factor for cirrhosis and hepatocellular carcinoma. To evaluate the possible hepatoprotective effects of Jerusalem artichoke tubers (JAT) in combination with interferon and ribavirin. Twelve groups of rats were administered JAT, interferon and ribavirin either separately or in combination from day one of CCL4 administration until the end of the study. Animals were killed after 8 weeks of CCL4- induced hepatotoxicity. Hepatocytes from rats treated with triple combination of interferon, ribavirin, and JAT showed more less normal architecture compared to CCL4- treated rats. We also detected significantly higher hepatic protein expression levels of p53, BAX and transforming growth factor-β (TGF-β) in the CCl4- intoxicated group compared to normal controls, as evidenced by immunohistochemical staining and western blotting analyses. Addition of JAT as a supportive regimen improved response to ribavirin and interferon and effectively participated in retaining normal histopathological and biochemical criteria and significantly lowered protein expression of p53, BAX, and TGF-β. We suggest that addition of JAT as a supportive regimen to interferon and ribavirin effectively potentiates their anti-fibrotic effects.

Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: A randomized controlled study

Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B. In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180μg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF). For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively. Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy. Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment. NCT01086085.

Response to Pegylated Interferon in Chronic Hepatitis B, Effect of with and without Precore Mutant Stain: A Multicenter Tunisian Study

Background and Study Aims : To evaluate the effectiveness of pegylated interferon in patients with chronic hepatitis B infection in a real life setting. Patients and Methods : Fifteen hospitals in Tunisia were included in this study. Data from consecutively treated chronic hepatitis B (CHB) patients, who received pegylated interferon, were collected retrospectively. Baseline demographic and clinical data, on-treatment virological and serological responses and adverse events (AE) were recorded. Sustained virologic response (SVR) is defined as an hepatitis B virus (HBV) DNA concentration of less than 2,000 IU/mL six months after the completion of therapy. Results : A total of 351 CHB patients under peg interferon alfa-2a treatment were included in this multicenter, open label, non-interventional study. Thirty five HBeAg positive patients were identified (62% male, 23% advanced fibrosis). Six months after therapy, 24% had viral loads < 2000 IU/mL, 20% achieved HBeAg seroconversion and 5, 7% achieved HBs Ag loss. Three hundreds sixteen HBeAg negative patients were treated (72, 5% male, 24% advanced fibrosis). Six months post-treatment, 14 % had viral loads < 2000 IU/mL and 1, 2% achieved HBs Ag loss. Treatment was well tolerated in 92% of cases and was stopped in 5.2% of patients. In multivariate analysis, predictors of response to pegylated interferon were: age less than 50 years (P=0,04 IC [0,169-0,737]), precore mutant stain infection (p=0,04 IC [0,60-0,69]), a body mass index < 30kg/m 2 (P=0,05 IC [0,225-0,320]), and a pre-treatment serum HBV DNA level <20000IU/ml (P=0,03 IC [1,316-2,225]). Conclusion : PEG-IFN therapy in chronic hepatitis B (CHB) is well tolerated and can achieve a good response especially if we select good responders.

The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients

BackgroundThe hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries.ObjectivesThe aim of this study was to investigate the association of substitutions in the HCV subtype 1b (HCV-1b) core protein and the rs12979860 polymorphism in the interleukin 28B gene (IL28B) with the response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients.Patients and MethodsA total of fifty-one chronically HCV-1b-infected Azerbaijani patients were enrolled in this cross-sectional study from March 2010 to June 2015. After RNA extraction from pre-treatment plasma, the core region of the HCV genome was amplified using the nested reverse transcription (RT) polymerase chain reaction (PCR) method, followed by standard sequencing. In addition, genomic DNA was extracted from peripheral blood mononuclear cell (PBMC) specimens, and the rs12979860 single nucleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay.ResultsIn this study, a significant association was observed between the non-responders and relapsers to antiviral therapy and substitutions in the HCV-1b core region at positions 43 (R43K, P = 0.047), 70 (R70Q, P < 0.001), 91 (M91L, P = 0.037), and 106 (S106N, P = 0.018). Concerning the IL28B polymorphism, the results showed that sustained virological response was significantly associated with homozygous CC patients (P = 0.009) as compared with other genotypes, while homozygous TT subjects were associated with HCV relapse after therapy (P = 0.006).ConclusionsThe data of the present study suggest that amino acid substitutions at position 43, 70, 91, and 106 in the HCV-1b core protein are correlated with the response to the Peg-IFNα-2a/RBV treatment in Azerbaijani patients with chronic hepatitis C. Moreover, host genetic polymorphisms, such as those of the IL28B locus, might be useful for predicting the responsiveness to Peg-IFNα-2a/RBV combination therapy against HCV.

Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma.

Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1-2×10(6) IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy.

Efficient Source of Cells in Proximal Oviduct for Testing Non-Viral Expression Constructs in the Chicken Bioreactor Model and for Other in Vitro Studies.

This work shows the usefulness of chicken oviduct epithelial cells (COEC) in evaluating the efficacy of non-viral expression vectors carrying human therapeutic genes. Secondly, an efficient source of progenitor COEC for in vitro studies is described. Within the distal part of the oviduct, weak to moderate expression of a trans membrane glycoprotein (CD44) was observed. Single cells presenting only weak expression of CD44 were found in magnum sections. in vitro cultured oviduct cells originating from the distal oviduct were suitable for subculturing and showed a stable proliferation potential up to the 2nd passage. However, the pavimentous epithelial-like morphology of COEC was progressively lost over time and mainly a fibroblast-like monolayer was established in consecutive passages. Moreover, various commercial transfection agents including FuGENE6 and XtremeGENE9 DNA were used to optimize delivery of human interferon alfa-2a, (IFNα2a) a therapeutic protein gene under an ovalbumin promoter. The transfection efficiency of adherent COEC was estimated for up to 40% at a ratio of 6:1 of transfectant to pOVA5EIFN + GFP plasmid. Expression of IFNα2a was confirmed by western blotting in transformed COEC. In conclusion, the population of epithelial progenitor cells sourced from the distal oviduct can significantly contribute to in vitro culture of COEC, representing an efficient model to develop the production of avian bioreactors and other in vitro studies related to oviduct tissue.

The Efficacy of Add-on Telbivudine Versus Switching to Pegylated Interferon Alfa-2a in Chronic Hepatitis B Patients With Poor Responses to Adefovir

Background:There are limited options for chronic hepatitis B (CHB) patients who have poor responses to adefovir (ADV).Objectives:The aim of this study is to evaluate the effects of adding on telbivudine (LdT) or switching to pegylated interferon alfa-2a (PEG-IFN-α2a) as alternative rescue therapies for patients with poor responses to the initial ADV treatments.Patients and Methods:Ninety-seven CHB patients with HBV DNA > 2 log10 copies/mL 48 weeks after ADV monotherapy were included in this study. Fifty-nine of these patients were treated with a combination of LdT plus ADV (LdT + ADV) daily, while thirty-eight patients were switched to PEG-IFN-α2a subcutaneous injections weekly for 48 weeks.Results:Both rescue strategies were proven to be safe and the majority of patients tolerated the therapies well. LdT + ADV led to more rapid reductions in viral loads than PEG-IFN-α2a monotherapy, with 2.14 (LdT + ADV) and 0.98 (PEG-IFN-α2a) log10 copies/mL decreases 48 weeks after rescue treatments, respectively (P < 0.00001). The rates corresponding to virological and biochemical responses were also elevated in patients who received the LdT + ADV combination therapy at the end of the observation period (88.1 vs. 68.4% for virological response, P = 0.017; 83.3 vs. 47.2%, P = 0.00045). However, the decline in the hepatitis B surface antigen (HBsAg) was more pronounced in PEG-IFN-α2a treated patients. Moreover, the cumulative rates of serological responses were higher in patients who switched to the PEG-IFN-α2a therapy.Conclusions:Both add-on LdT and switching to PEG-IFN-α2a were satisfactory and optimal treatments for CHB patients with poor responses to ADV. Both rescue strategies resulted in significant reductions in serum viral load and ALT levels, and were associated with high rate of serological outcomes in our hospital.

ANTIVIRAL TREATMENT OF HEPATITIS C IN SERBIAN PRISON SETTING: MEDICAL TREATMENT OUTCOMES AND PATIENTS' ADHERENCE.

Seroprevlence of chronic hepatitis C viral infection in correctional facilities ranges from 16% to 49%. However, there are only very limited data available on the course of hepatitis C viral infection and outcomes oftreatment with pegylated interferon plus ribavirin in correctional settings. The aim ofthis study was to assess the feasibility and effectiveness of use of pegylated interferon plus ribavirin treatment in the Serbian correctional setting. The study sample consisted of the patients with hepatitis C hospitalized in the Special Hospital for Prisoners in Belgrade (Serbia) during 2007-2013. Health authorities approved treatment for 32 patients out of 76 treatment-naive patients referred to this institution. The patients (N=32) received 180 mcg pegylated interferon alfa-2a once a week plus oral ribavirin in dosage of 800 mg or 1000/1200 mg/day for 24 or 48-week treatment. All patients who completed therapy were assessed at the end of an additional 24-week treatment-free period for a sustained virological response. Sustained virological response was achieved in 53.8% of hepatitis C viral infection genotype I patients and in 73.3% and 66.6% of patients with hepatitis C viral infection genotype 3 and 4, respectively. One patient with mixed genotype (1, 2) did not achieve sustained virological response. The overall safety profile of the treatment regimen was very good. The incidence of influenza-like symptoms and depression were low A serious adverse event was recorded only in 6.4% of patients. The results showed that pegylated interferon alfa-2a plus ribavirin given once a week was well tolerated among prisoners and the regimen had the same adherence and effectiveness as in general population.

FRI-146 - Genetic Variation in FCER1A Gene Predicts Sustained HBsAg Clearance in East-Asian Patients Treated with Pegylated Interferon Alfa-2a (40kd): The “Peg-Be-Yond” Study

FRI-146 - Genetic Variation in FCER1A Gene Predicts Sustained HBsAg Clearance in East-Asian Patients Treated with Pegylated Interferon Alfa-2a (40kd): The “Peg-Be-Yond” Study

Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial.

To investigate the efficacy of pegylated interferon alfa (PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFNα alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed. The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFNα alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance. Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.

Durability of Response in Children Treated With Pegylated Interferon alfa [corrected] 2a ± Ribavirin for Chronic Hepatitis C.

No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C. This prospective, multicenter, long-term follow-up (LTFU) study aimed to assess long-term durability of sustained virological response (SVR), long-term safety and tolerability, and the association between IL28B genotype and treatment response, in children previously treated with PegIFN alfa-2a ± ribavirin (RBV) in the PEDS-C trial. A total of 93 patients were assessed for enrollment, and 38 enrolled in the study. Patients attended 2 study visits: 5 (mean 5.6, range 4.1-6.6) and 6 (6.6, 5.1-7.7) years after treatment cessation. Standardized medical history, physical examination, and laboratory testing were performed at these visits. Reminder telephone calls were conducted at 4 and 8 months after the initial visit. The LTFU cohort was the representative of the original PEDS-C cohort because both baseline and treatment characteristics were comparable. Of the 38 participants, 21 achieved SVR (responders) during the PEDS-C trial and 17 had not (nonresponders). All 21 responders maintained undetectable hepatitis C virus RNA during the LTFU (4.4-7.0 years after achieving SVR) in contrast to the nonresponders who demonstrated persistent viremia. IL28B CC genotype was associated with SVR (67% vs 30% in non-CC, P = 0.028). Long-term durability of SVR is excellent following PegIFN alfa-2a treatment in children with chronic hepatitis C; SVR is higher in those with IL28B CC versus non-CC.

Pegylated-Interferon Treatment Is Safe and Efficient for Pregnant Patients with Essential Thrombocythaemia

Essential thrombocythaemia (ET) is a rare (only 20% are diagnosed at child-bearing age), acquired clonal stem cell disorder. Pregnancy in patients with ET is associated with an increase in foetal (spontaneous abortion, stillbirth, intrauterine growth retardation) and maternal complications (thrombosis, hemorrhage, preeclampsia). Although Interferon alfa-2a (INF) therapy in ET patients has been associated with improved pregnancy outcomes, data regarding pegylated-interferon alfa-2a (PEG-INF) in pregnant ET patients is not available and its use is currently not recommended. PEG-INF has an increased half-life in comparison with INF, requiring less frequent injections, is associated with a better tolerance profile and is increasingly used outside of pregnancy. For those reasons, it is an interesting alternative for pregnant ET patients.This observational study is the first one focussing on use of PEG-INF during pregnancy. We included 7 pregnancies in 6 women with a diagnosis of ET treated with PEG-INF. Patients were identified through physician willingness to participate. In all pregnancies, PEG-INF was started before conception to control the platelet count. A specific questionnaire for data collection was sent to physicians. This study was performed in accordance with the Helsinki Declaration.Median age and platelet count at ET diagnosis were 22 years (range: 12 - 34 years) and 1647 x109/L (791 - 3265 x109/L), respectively. Median age at the beginning of pregnancy was 25 years (21 - 39 years). 5 women (83 %) had a prior documented history of 8 pregnancies with 2 (25 %) live births, 5 (63 %) miscarriages and 1 (13%) termination. On the 5 previous miscarriages, all women were on low-dose aspirin (AAS), 2 on low molecular weight heparin (LMWH) and 1 on INF. The rationale to introduce cytoreductive treatment was high-risk ET in 5 (83%) woman (4 with platelet count >1500x109/L at diagnosis, 1 with previous sagittal sinus thrombosis) and complications in previous pregnancy in 1 (17%) women (numbness of right face and arm). In addition to PEG-INF, all woman received AAS and 4 (66 %) LMWH (3 (50 %) had prophylactic dose and 1 (17 %) had therapeutic dose for previous sagittal sinus thrombosis).Median platelet count at conception was 520 x109/L (354 - 676 x109/L), 434 x109/L (254-570 x109/L) during the first trimester, 435 x109/L (225-469 x109/L) during the second trimester and 342 x109/L (183-428 x109/L) during the third trimester.4 woman experienced PEG-INF grade 1 adverse events (AEs) (2 reported hair loss, 1 had transient nausea, anorexia and abdominal pain, 1 had skin reaction, 1 had headaches). Neither grades 3-4 AEs nor drug discontinuation was reported.On the 7 pregnancies, 6 (86 %) live birth and 1 (14 %) miscarriage (at 7 weeks, platelet count of 492 x109/L) were reported. Median time of gestation at delivery was 39 weeks (range: 38+3-40+6 weeks) and median birthweight was 3.1 Kg (range: 2.8-4.1 kg). Delivery was vaginal for 7 (83%) and by caesarean for 1 (17%), with induction for 1 (17 %). Neither major bleeding nor thrombosis was reported during pregnancy, delivery or post-partum. There were no stillbirths nor infant malformations at birth. Patient's characteristics are summarised in the Table.Outcomes of pregnancies for these 6 woman were significantly better when treated with PEG-INF during pregnancy with more live births (6 with PEG-INF, 2 without) (p<0.05).In conclusion, PEG-INF improves outcomes of pregnancy in ET woman with significantly more live birth. Moreover it is efficient to control platelet count, with only few side effects and no infant complication reported. We report for the first time that PEG-INF seems a safe and interesting alternative treatment of ET in pregnancy. [Display omitted] DisclosuresOff Label Use: Peginterferon alfa-2a for cytoreduction in pregnant ET women. Harrison:Shire: Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

Efficacy and Safety of Pegylated Interferon Alpha-2a in Patients with Essential Thrombocythemia and Polycythemia Vera: Results after a Median 7-Year Follow-up of a Phase 2 Study

Introduction: It has been previously reported that pegylated interferon alpha-2a can induce hematologic and molecular responses in patients with essential thrombocythemia "ET" and polycythemia vera "PV", but the follow up in these studies were relatively short.Objective: We present longer-term efficacy and safety results of a prospective phase II study of pegylated interferon alpha-2a in patients with ET and PV after a median follow up of 82.5 months (range, 8-107).Methods: Patients with a diagnosis of ET or PV, in a need of therapy, either newly diagnosed or previously treated, were eligible for this study. Median interferon starting dose of 180 mcg/week SQ (range, 450-90; 39% started on 90mcg/week) was modified in majority of the patients based on toxicity or lack of efficacy. Clinical and molecular responses were assessed every 3 to 6 months.Results: Among 83 enrolled patients (43 PV, 40 ET), 32 patients (39%) are still on study (but in 8 therapy is on hold: 5 due to toxicity, and 3 for financial reasons). Median age was 53 years (range, 19-78). Overall 37% of patients did not receive prior cytoreductive treatment. The overall median exposure to therapy was 87 months (range, 58-107) and was no different for patients still enrolled on the study and those who stopped study participation. Nine (28%) patients still on study are currently on a dose equal or higher than 90 mcg/week and 15 (47%) are on dose equal or smaller than 45mcg/week. JAK2 status or allele burden had no impact on achievement of response (clinical or molecular), time to response or duration of therapy. 55 of 59 (71%) JAK2V617F positive patients were evaluable for molecular response (Figure); 8 patients carried CARL mutation, 3 carried MPL and in 13 were triple negative. Median duration of hematologic and molecular response was 66 and 53 months, respectively; and directly correlated with treatment length and type of response (CMR had the longest duration of response). Overall yearly discontinuation rate were gradually decreasing for first 5 years, from 17% to 5%, and slowly increasing afterward to 10%. Of the 51 patients not on the study anymore, 27 (35% of the total) discontinued therapy primarily due to treatment toxicity. New late (≥24 months from start of therapy) G3/4 toxicity occurred in 17% of patients. Among patients in complete hematologic response treatment failure due to vascular adverse event or disease transformation was seen in 5 patients each. Three patients died on study (not related to therapy or disease), and 8 after stopping participation. Mean changes in allele burden over time in JAK2 positive patients are depicted in figure.Conclusions: Although pegylated interferon alpha-2a can induce significant hematologic and molecular responses; toxicity still limits its use over longer period of time and loss of response or transformation is encountered. TableResponseCharacteristicsFirst responseLast responseHem Resp, N. of patients (No), (%)CHR62 (76)25 (40)aPHR4 (5)1 (25)ORR66 (79)26 (39)aMol Resp, No, (%)CMR10 (18)9 (90)PMR20 (36)5 (25)*mMR5 (9)2 (40)ORR35 (74)16 (46)SafetyAny gradeGrade≥3Overall Adverse Events (AE), No, (%)any AE83 (100)57 (67)recurrent AE74 (89)13 (16)AE subtypes, No, (%)musculoskeletal73 (88)6 (8)neurological53 (64)2 (4)psychiatric38 (46)4 (11)gastrointestinal54 (65)11 (20)LFT elevation27 (33)5 (18)skin18 (22)2 (11)infection/fever26 (31)3 (12)respiratory23 (28)2 (9)cardiovascular13 (16)3 (23)metabolic16 (19)2 (13)neutropenia37 (45)21 (57)thrombocytopenia18 (22)a1 (6)anemia36 (43)1 (3)Autoimmune toxicity, No, (%)hepatitis1 (2.5)CNS vasculitis1 (2.5)lupus nephritis1 (2.3)Sjogren sy & dermatitis1 (2.5)Vascular AE (TEE/bleeding),Unprovoked6 (7)5 (83)No, (%)Provoked4 (5)3 (75)Disease transformation, No, (%)Myelofibrosis6 (7)AML1 (1)Safety over ≥24 months**Any gradeGrade≥3New AE, No (%)3th year10 (17)4 (40)4th year6 (11)4 (67)5th year5 (10)1 (20)≥ 6th year10 (24)1 (10)**Effective sample size for patients on therapy/year: Initial number of patients at risk at the beginning of period minus half of patients censored during that period*% calculated from 19 patientsastatistically significant differences by Fisher's exact testAbbr. CMR= complete molecular remission (undetectable JAK2 allele burden), PMR= partial molecular remission (>50% decrease in allele burden), mMR= minor molecular remission (20-49% decrease in allele burden) [Display omitted] DisclosuresOff Label Use: Pegylated Interferon alfa-2a used for patients with essential thrombocythemia and polycythemia vera. Cortes:Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding.

Safety of the Association of Pegylated Interferon and Ribavirin in the Treatment of Chronic Viral Hepatitis C in the Blacks: A Ten Year Observation

Background: Sub Saharan population are the most affected by chronic hepatitis C. The interferon- based regimen has been the only available treatment in the last decade. The announced direct acting antivirals will still be associated to the actual regimen. Reports on the safety of these protocols are so far Caucasians-based, and data from sub Saharan populations are lacking. Aim: To describe the secondary effects of the combination of Pegylated interferon and ribavirin I the treatment of chronic hepatitis C in black Africans. Methods: it was a multicenter study in which we included chronic hepatitis C patients, over ten years, treated by the association of Pegylated interferon-Inf and ribavirin, from all the centers of treatment in the country. Patients should be naive to this treatment, fulfill the condition of treatment according to manufacturer, namely Hoffmann La Roche. Side effects were recorded during follow up. The base line follow up biological tests included: Liver function tests; full blood count; TSH; kidney function test. Results: All the patients reported at least one adverse event, related to treatment. The clinical adverse events were dominated by asthenia; flu-like syndrome; head ache and myalgia; we registered 6 cases of depression. The most biological adverse events were of hematologic origin. Conclusion: The adverse effects related to combination therapy using Pegylated interferon alfa-2a and ribavirin in the treatment of chronic HCV in the blacks, are similar to those indicated by the manufacturer. These adverse effects tend to be in relation the duration of treatment. Some of them can become intractable, alternative treatment or psychological support from patients association can be helpful.

Comparative Study on Selectivity and Kinetic Performance of Recent Reversed Phase Liquid Chromatography Columns in the Separation of Protein Variants

In this study, the impact of stationary phase chemistry was investigated for the analysis of large biomolecules. For this purpose, widepore state-of the-art C18, C3, diphenyl stationary phases as well as a new superficially porous material possessing a carbon core and nanodiamond-polymer shell (composite material) were tested. To evaluate the similarities and differences between these phases, two samples were considered, including i) oxidatively stressed and reduced recombinant interferon alfa-2A variants as well as ii) light chain and heavy chain fragments of a human IgG1 monoclonal antibody Belimumab. For both samples, the overall selectivity was found to be similar on all the silica-based stationary phases (e.g. α = 1.20 - 1.25 between the two oxidized forms of interferon), while it was somewhat different on the composite material (α = 1.12 between the two oxidized forms of interferon). On the other hand, the kinetic performance of the composite phase was somewhat lower (peak capacity between 70 and 80) than that of silica-based materials (peak capacity higher than 100), except in the presence of a relatively high concentration TFA (0.5% TFA) due to the reduction of ionic interactions. At the end, when separating closely eluting proteins variants in RPLC mode, minor differences in selectivity may be more important than kinetic efficiency and therefore, the composite material might also be of interest for biomolecules characterization. Keywords: Carbon/nanodiamond/polymer shell particles, kinetic performance, protein separation, reversed phase chromatography, selectivity.