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Interferon Alfa (interferon + alfa)
Selected AbstractsOutcomes of acute rejection after interferon therapy in liver transplant recipientsLIVER TRANSPLANTATION, Issue 7 2004Sammy Saab Interferon alfa has been increasingly used against recurrent hepatitis C (HCV) disease in post-liver transplant (LT) recipients. A serious potential adverse effect is acute rejection. We reviewed our experience using interferon-based therapy (interferon or pegylated interferon with or without ribavirin) for treating recurrent HCV in LT recipients. Forty-four LT recipients were treated with interferon for recurrent HCV. Five of the 44 patients developed acute rejection during interferon-based therapy. These 5 patients started treatment of 42.4 ± 33.89 months (mean ± SD) after LT. Mean (± SD) histological activity index and fibrosis scores before initiating antiviral therapy were 8.8 (± 1.92) and 2.6 (± 0.55), respectively. Patients were treated for 3.3 ± 2.28 months (mean ± SD) prior to rejection. At the time of rejection, HCV load was not detectable in 4 of the 5 recipients. All 5 patients had tolerated interferon therapy, and none had stopped therapy because of adverse effects. The rejection was successfully treated in 3 patients. In 2 of those 3 patients, cirrhosis eventually developed. In the 2 patients who did not respond to rejection treatment, immediate graft failure occurred, leading to re-LT in 1 patient and death from sepsis in the other. In conclusion, the results indicate that further studies are needed to assess the safety of interferon in LT recipients. Interferon-based therapy may lead to acute rejection and subsequent graft loss and should therefore be used with caution. Treated recipients may also develop progressive cirrhosis despite achieving a sustained virological response. (Liver Transpl 2004;10:859,867.) [source] Treatment planning in cutaneous T-Cell lymphomaDERMATOLOGIC THERAPY, Issue 4 2003Eric C. Vonderheid ABSTRACT:, Effective long-term management of cutaneous T-cell lymphoma (CTCL) requires administration of skin-directed therapies such as topically applied nitrogen mustard or photochemotherapy to achieve a complete response in clinically early disease (patch and thin-plaque-phase mycosis fungoides, MF) and often the concomitant administration of well-tolerated drugs with systemic effects such as interferon alfa, bexarotene, methotrexate or extracorporeal photopheresis in more advanced, but not highly aggressive/nontransformed disease (thick plaque or tumor phase MF or erythrodermic CTCL). The author's approach is provided as a guide for dermatologists in private practice. [source] Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders,,HEPATOLOGY, Issue 6 2009Vinod K. Rustgi Merimepodib (MMPD) is an orally administered, inosine monophosphate dehydrogenase inhibitor that has shown antiviral activity in nonresponders with chronic hepatitis C (CHC) when combined with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) and ribavirin (RBV). We conducted a randomized, double-blind, multicenter, phase 2b study to evaluate the antiviral activity, safety, and tolerability of MMPD in combination with Peg-IFN-alfa-2a and RBV in patients with genotype 1 CHC who were nonresponders to prior therapy with Peg-IFN and RBV. Patients received 50 mg MMPD, 100 mg MMPD, or placebo every 12 hours, in addition to Peg-IFN-alfa-2a and RBV, for 24 weeks. Patients with a 2-log or more decrease from baseline or undetectable hepatitis C virus (HCV) RNA levels at week 24 were then eligible to continue Peg-IFN-alfa-2a and RBV for a further 24 weeks, followed by 24 weeks of follow-up. The primary efficacy endpoint was sustained virological response (SVR) rate at week 72 in all randomized patients who received at least one dose of study drug and had a history of nonresponse to standard therapy. A total of 354 patients were randomized to treatment (117 to placebo; 119 to 50 mg MMPD; 118 to 100 mg MMPD), and 286 completed the core study. The proportion of patients who achieved SVR was similar among the treatment groups: 6% (6/107) for 50 mg MMPD, 4% (5/112) for 100 mg MMPD, and 5% (5/104) for placebo (P = 0.8431). Adverse-event profiles for the MMPD combination groups were similar to that for Peg-IFN-alfa and RBV alone. Nausea, arthralgia, cough, dyspnea, neutropenia, and anemia were more common in patients taking MMPD. Conclusion: The addition of MMPD to Peg-IFN-alfa-2a and RBV combination therapy did not increase the proportion of nonresponder patients with genotype 1 CHC achieving an SVR. (HEPATOLOGY 2009.) [source] Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response,HEPATOLOGY, Issue 1 2008Olav Dalgard A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA,positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon ,-2b (1.5 ,g/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, ,0.1 to +13.9). Conclusion: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks. (HEPATOLOGY 2007.) [source] Alcohol potentiates hepatitis C virus replicon expressionHEPATOLOGY, Issue 1 2003Ting Zhang Alcohol consumption accelerates liver damage and diminishes the anti-hepatitis C virus (HCV) effect of interferon alfa (IFN-,) in patients with HCV infection. It is unknown, however, whether alcohol enhances HCV replication and promotes HCV disease progression. The availability of the HCV replicon containing hepatic cells has provided a unique opportunity to investigate the interaction between alcohol and HCV replicon expression. We determined whether alcohol enhances HCV RNA expression in the replicon containing hepatic cells. Alcohol, in a concentration-dependent fashion, significantly increased HCV replicon expression. Alcohol also compromised the anti-HCV effect of IFN-,. Investigation of the mechanism(s) responsible for the alcohol action on HCV replicon indicated that alcohol activated nuclear factor ,B (NF-,B) promoter. Caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-,B, abolished alcohol-induced HCV RNA expression. In addition, naltrexone, an opiate receptor antagonist, abrogated the enhancing effect of alcohol on HCV replicon expression. In conclusion, alcohol, probably through the activation of NF-,B and the endogenous opioid system, enhances HCV replicon expression and compromises the anti-HCV effect of IFN-,. Thus, alcohol may play an important role in vivo as a cofactor in HCV disease progression and compromise IFN-,-based therapy against HCV infection. [source] A pilot study of interferon alfa and ribavirin combination in liver transplant recipients with recurrent hepatitis CHEPATOLOGY, Issue 5 2002A. Obaid Shakil Although interferon alfa (IFN-,) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. We conducted a pilot study to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFN-, 3 million units 3 times a week subcutaneously and ribavirin 800 mg daily by mouth for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy but 16 withdrew due to adverse effects, including 2 with myocardial infarction. Median age was 50 years; 74% were men, and 91% had genotype 1. The median interval between transplantation and enrollment was 23 months. On an intention-to-treat basis, 7 patients (18%) had a biochemical and 5 (13%) had a virologic response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5%) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. In conclusion, IFN-, and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. Adverse effects occur commonly, requiring dose reductions and treatment withdrawal. [source] A randomized 4-arm multicenter study of interferon alfa,2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon aloneHEPATOLOGY, Issue 1 2001Giorgio Saracco To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n = 139) received 3 million units (MU) IFN-,2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n = 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n = 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n = 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P = .04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P = .03; group 1 = 9%, group 4 = 12%, P = not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 = 32%, group 2 = 30%, group 3 = 30%, group 4 = 35%, P = NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if re-treated by 5 MU t.i.w. IFN plus ribavirin 1,000 mg/d for 1 year. Patients with genotype 1 should receive a high dosage of IFN plus ribavirin for 12 months, whereas therapy for patients with genotype 2 or 3 should be less aggressive. [source] Long-term follow-up of interferon alfa treatment in chinese patients with chronic hepatitis B infection: The effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complicationsHEPATOLOGY, Issue 1 2001Man-Fung Yuen The long-term effect of interferon alfa (IFN-,) in Chinese patients with chronic hepatitis B infection is unknown. A total of 411 chronic hepatitis B patients (208 treated with IFN-, and 203 as control) were followed up for hepatitis B serology and the development of hepatoma and other cirrhosis-related complications. The hepatitis B e antigen (HBeAg) seroconversion rate in the IFN-,,treated group, though significantly greater at 6 and 24 months, was comparable with the control group on subsequent follow-up, irrespective of pretreatment alanine transaminase (ALT) levels. HBeAg seroreversion rate was higher in the IFN-, group compared with the control group (21.1% vs. 2.2%; P = .001). Loss of hepatitis B surface antigen (HBsAg) occurred in 2.4% of the IFN-,,treated patients and 0.49% of the control patients (P = NS). Around 90% of the anti-HBe,positive patients in both groups were still hepatitis B virus (HBV)-DNA,positive by polymerase chain reaction (PCR) assay. Two patients suffered from hepatic reactivation during the course of treatment. Nine (4.3%) patients in the IFN-, group and 2 (1.0%) in the control group developed complications of cirrhosis and hepatoma (P = .062). In Chinese HBsAg carriers, IFN-, was of no long-term benefit in inducing HBeAg seroconversion or in the prevention of hepatoma and other cirrhosis-related complications. [source] Expression of hepatitis C virus NS5A natural mutants in a hepatocytic cell line inhibits the antiviral effect of interferon in a PKR-independent mannerHEPATOLOGY, Issue 6 2001Philippe Podevin The impact of hepatitis C virus NS5A protein mutations on interferon alfa (IFN-,) signaling pathway, cell proliferation, and viability is an important issue that is still under debate. We have therefore combined transient and stable expression in a human hepatocytic cell line (Huh7) of 3 full-length NS5A sequences, isolated from patients with or without response to IFN-, therapy. Expression of all 3 NS5A-reduced IFN-, global antiviral activity on both vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) replication. We did not show, however, an effect of these 3 NS5A proteins on double-stranded RNA,dependent kinase (PKR) expression and activity as well as colocalization and coimmunoprecipitation between NS5A and PKR. We also failed to show an effect of the 3 NS5A mutants tested on cell proliferation and viability. Overall, our results support an important role of NS5A in controlling IFN-, antiviral activity; they show, however, that PKR-independent mechanisms are implicated, at least in liver-derived cells. [source] Diffuse cutaneous eruption due to interferon alfa and ribavirin treatment of chronic hepatitis CJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2005E Avk [source] Recurrent hepatitis C after liver transplantation: On-treatment prediction of response to peginterferon/ribavirin therapyLIVER TRANSPLANTATION, Issue 1 2008Ibrahim A. Hanouneh Sustained virologic response (SVR) in the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) remains suboptimal. We evaluated efficacy of pegylated interferon alfa (PEG) and ribavirin (RBV) (PEG/RBV) combination therapy in LT recipients with recurrent HCV and predictive values of rapid virological response (RVR) and early virologic response (EVR). Between January 2001 and October 2005, LT recipients with recurrent HCV were intended to be treated for 48 weeks with PEG/RBV combination therapy independent of genotype or virologic response [53 patients (79% genotype 1)]. On-treatment predictor of response at week 4 (RVR) was defined as undetectable HCV RNA, and at week 12 (EVR) as undetectable HCV RNA or a >2 log10 drop from pretreatment viral load. SVR was seen in 19 (35%) patients. Patients with genotype 2/3 were more likely to achieve SVR than those with genotype 1 (87% versus 23%; P = 0.001). The highest rate of SVR was seen in patients with RVR [specificity and positive predictive value (PPV) = 100%] while the highest rate of treatment failure was seen in those who did not have EVR [sensitivity and negative predictive value (NPV) = 100%]. The NPV of RVR to identify those who will not achieve SVR was also very high (88%). EVR had low PPV (63%) to identify those with SVR. In conclusion, PEG/RBV combination therapy is effective in the treatment of post-LT recurrent HCV. On-treatment virologic monitoring is highly predictive of SVR and may optimize the virologic response and minimize toxicity. Given its high PPV and NPV, RVR appears to be the most appropriate decision time point for continuation of therapy. Liver Transpl 14:53,58, 2008. © 2007 AASLD. [source] Treatment of recurrent hepatitis B infection in liver transplant recipientsLIVER TRANSPLANTATION, Issue 10B 2002Norah A. Terrault MD 1Therapeutic decisions are guided by a patient's clinical status (severity of disease and presence of comorbidities) and previous drug-exposure history. 2Lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B virus (HBV) infection caused by wild-type virus or failure of hepatitis B immunoglobulin therapy. Lamivudine resistance, developing in approximately 25% after 12 months of therapy, is its main limitation. 3Famciclovir is safe in liver transplant recipients; however, virological and clinical responses are less consistent than with lamivudine. Thus, lamivudine is favored over famciclovir as first-line therapy in transplant recipients with no previous exposure to nucleoside analogues. 4Although limited in availability, adefovir dipivoxil appears safe and effective in treating liver transplant recipients with lamivudine-resistant HBV disease. Close monitoring of renal function is recommended, with dose adjustment in patients with reduced creatinine clearances. 5Limited data suggest that intravenous ganciclovir, tenofovir disoproxil fumarate, and interferon alfa may be useful as rescue therapies for patients with lamivudine- or famciclovir-resistant HBV disease. 6Antiviral therapy with two or more suitable agents may minimize the chance for viral resistance; therefore, future therapeutic strategies likely will use combination therapy in the long-term management of recurrent HBV disease. [source] Diffuse inflammatory lesions in patients treated with interferon alfa and ribavirin for hepatitis C: a series of 20 patientsBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2002O. Dereure Summary Background Cutaneous side-effects of treatment with interferon alfa or interferon alfa plus ribavirin in patients with hepatitis C have already been reported but they are mostly local with inflammation and, much less frequently, necrosis at the injection points. By contrast, very few data are available with regard to distant skin reactions, particularly inflammatory lesions on other parts of the body. Objectives To assess the clinical and histological pattern of inflammatory skin lesions outside the injection points in patients treated with interferon alfa and ribavirin for chronic hepatitis C. Methods Twenty patients attending a University Hospital in Southern France (secondary referral centre) were evaluated regard to clinical history, type and localization of lesions, progression and histology. Skin testing was performed in some patients and the relevance of the results was evaluated. Results Eczema-like skin lesions were mainly distributed on the extremities, sometimes associated with photosensitivity. They usually occurred between 2 and 4 months of treatment. Histology was nonspecific, with a dermal, mainly perivascular, mononuclear infiltrate. Skin testing was poorly informative and was not predictive of relapse. Treatment had to be interrupted in half the patients, of whom two of three relapsed on resuming therapy. Conclusions The incidence of inflammatory skin lesions at a distance from injection sites in patients treated with interferon alfa and ribavirin for chronic hepatitis C is currently unknown, but this adverse event must be taken into consideration as it may lead to the transient or definitive interruption of treatment. [source] Blue rubber bleb nevus syndromeACTA PAEDIATRICA, Issue 4 2010M Agnese Abstract Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare condition characterized by multiple venous malformations involving the skin and internal organs. The gastrointestinal tract is always involved and intestinal haemorrhage is the most frequent clinical manifestation associated with iron deficiency anaemia. We describe a 10-year-old girl who, since birth, presented numerous venous malformations all over her body and a lymphangioma in the right leg. At the age of 5 years, she also had a severe episode of gastric bleeding requiring a blood transfusion. From this episode, she is suffering from chronic anaemia and this is the reason for admission into our hospital. The endoscopic examination of the gastrointestinal tract revealed multiple giant venous malformations in the oesophagus, stomach, duodenum and in all visible sections of the colon. Endoscopy is the gold standard technique for the diagnosis of BRBNS with GI lesions and also allows immediate therapeutic measures such as argon plasma coagulation, laser photocoagulation, sclerotherapy or band ligation. In addition, pharmacological treatments based on corticosteroids, interferon alfa, vincristine or octreotide have been described for BRBNS. Conclusion:, Blue Rubber Bleb Nevus Syndrome is a congenital cutaneous and gastrointestinal haemangiomatosis. Its morbidity and mortality depends on involvement of visceral organs and particularly on GI bleeding. The treatment is based on pharmacological or surgical therapy. Overall, the most important step is the follow-up to the presence and the evolution of GI lesions and the possible bleeding. [source] | ||||||||||