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Interferon Therapy (interferon + therapy)
Selected AbstractsRelationship of health-related quality of life to treatment adherence and sustained response in chronic hepatitis C patientsHEPATOLOGY, Issue 3 2002David Bernstein Interferon therapy may exacerbate health-related quality of life (HRQL) deficits associated with hepatitis C virus (HCV) early in the course of therapy. Treatment with polyethylene glycol,modified interferon (peginterferon) alfa-2a (40 kd) provides improved sustained response over interferon alfa-2a, but its effect on HRQL is unknown. The objective of this study was to (1) evaluate the effect of sustained virologic response on HRQL in patients with HCV and (2) determine whether impairment of HRQL during treatment contributes to early treatment discontinuation. Data consisted of a pooled secondary analysis of patients (n = 1,441) across 3 international, multicenter, open-label, randomized studies that compared peginterferon alfa-2a (40 kd) with interferon alfa-2a. ANCOVA was used to examine the effect of sustained virologic response on HRQL. Repeated-measures mixed-models ANCOVA was used to compare Fatigue Severity Scale (FSS) and SF-36 scores during treatment by treatment group. Logistic regression analysis was used to examine the association between changes at baseline in on-treatment HRQL and early treatment discontinuation. Sustained virologic response was associated with marked improvements from baseline to end of follow-up in all subjects, including patients with cirrhosis. During treatment, patients receiving peginterferon alfa-2a (40 kd) had statistically significantly better scores on both the SF-36 and FSS. Baseline to 24-week changes in fatigue and SF-36 mental and physical summary scores significantly predicted treatment discontinuation. In conclusion, sustained virologic response is associated with improvements in quality of life in patients with or without advanced liver disease. This parameter may be an important consideration in maximizing treatment adherence. [source] Hepatitis C virus infection and interferon therapy in patients with Down syndromePEDIATRICS INTERNATIONAL, Issue 1 2008Yoko Miyoshi Abstract Background: The clinical features of hepatitis C virus (HCV)-associated liver diseases, or the efficacy of interferon (IFN) therapy in children with Down syndrome (DS) remain to be elucidated. The purpose of the present paper was to survey the features of liver diseases in this subset of children and evaluate the efficacy of IFN treatment in those patients. Methods: A questionnaire was sent to 41 members of the Japan Society of Pediatric Hepatology. Ten of them reported on 11 patients with DS who had concomitant chronic HCV infection, providing information on liver disease and the response to IFN treatment. Results: Interferon therapy of 24 weeks duration using natural IFN-, was instituted in six of the 11 patients with DS, but none of the six patients cleared HCV-RNA from their serum. Among 12 age- and sex-matched control children who were treated with IFN using the same regimen against chronic HCV infection, half of them had a favorable response to IFN therapy with a sustained clearance of HCV-RNA from their serum. The major baseline features including alanine aminotransferase levels, HCV genotype and viral load were not apparently different between the six patients with DS and the 12 controls. Conclusions: IFN therapy for HCV infection in patients with DS may be unfavorable as compared with non-DS children. [source] Therapy of other viral infections: herpes to hepatitisDERMATOLOGIC THERAPY, Issue 6 2004Arun Chakrabarty ABSTRACT:, Over the past several years, there has been an increase in knowledge pertaining to the diagnosis and management strategies for the herpes family (Types 1,8), the pox viruses, mumps, measles, rubella, and parvovirus B19 as well as the viral etiologies of hepatitis. Various antiviral treatments, such as nucleoside analogs and interferon therapy, have been available to reduce the signs and symptoms of these common viral infections. This article summarizes the preferred treatment strategies to be employed for each of the viruses for reducing severity, duration, recurrences (notably in the herpes family), transmission rates, as well as preventive alternatives. The majority of the therapeutic options attenuate the course of disease. Treatment decisions are driven by knowledge of the natural history and often are tailored to incorporate clinical circumstances for individual patients. Promotion of community awareness and the development of vaccines should be emphasized in the battle against these common viruses, particularly the herpes simplex viruses, the pox viruses, and hepatitis B. [source] Bell's palsy during interferon therapy for chronic hepatitis C infection in patients with haemorrhagic disordersHAEMOPHILIA, Issue 2 2000Ogundipe Two adult patients with life-long severe haemorrhagic disorders commenced on interferon-,2b therapy for chronic hepatitis C infection. Both developed Bell's palsy several weeks after commencing therapy, They were started on steroids and, in addition, the first patient discontinued interferon-,2b therapy while the second patient elected to continue with therapy. In both cases facial paralysis improved over the ensuing weeks. Bell's palsy is often idiopathic but has been reported. in association with herpesviruses. It is not a recognised complication of chronic hepatitis B or C infection, or interferon-,2b therapy. However, the interferons are associated with numerous adverse reactions including various neuropsychiatric manifestations and neurological syndromes. There are several reports of nerve palsies, including optic tract neuropathy, occurring during interferon therapy, and immune-based mechanisms are thought to play a role in the aetiopathogenesis. No reports of Bell's palsy in association with interferon therapy were identified in our literature search, although one possible case has been reported to the Committee of Safety in Medicine. Although Bell's palsy in our patients may have occurred by chance, a neuropathic effect of interferon-,2b on the facial nerve cannot be excluded and we urge physicians using interferons to be aware of this potential side-effect. [source] Benefits and risks of interferon therapy for hepatitis B,HEPATOLOGY, Issue S5 2009Robert Perrillo Alpha interferon is the only licensed drug for hepatitis B with immunomodulatory as well as viral inhibitory properties. Potential advantages of interferon compared to nucleoside analogs include a lack of drug resistance, a finite and defined treatment course, and a higher likelihood for hepatitis B surface antigen (HBsAg) clearance. Approximately 30% of hepatitis B e antigen (HBeAg)-positive and 40% of HBeAg-negative cases have a sustained virological response (when defined as HBeAg seroconversion and/or hepatitis B virus (HBV) DNA levels below 20,000 copies/mL, respectively) 6 months after completion of a 48-week course of peginterferon alfa-2a These responses remain durable in 80% and 50% of cases, respectively, when evaluated several years later. Recent studies have shown that changes in HBsAg and HBeAg concentration during treatment predict sustained virological response and serial monitoring of HBsAg is helpful in predicting HBsAg clearance. HBeAg-positive patients with genotype A have higher rates of HBeAg and HBsAg clearance, whereas HBeAg-negative patients with genotype D have the lowest rate of response to interferon therapy. Long-term follow-up of virological responders to either standard alpha interferon or peginterferon has demonstrated a progressive increase in the rate of HBsAg clearance, particularly in patients who were initially HBeAg-positive. Future studies need to address if specific virological benchmarks during therapy can be used to tailor treatment duration. Conclusion: Peginterferon alfa has a place as first-line therapy of hepatitis B in patients who are carefully selected on the basis of pretreatment serum HBV DNA and aminotransferase levels, safety considerations, and viral genotype. (HEPATOLOGY 2009;49:S103,S111.) [source] Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta,,HEPATOLOGY, Issue 3 2006Grazia Anna Niro Therapy of chronic hepatitis delta with standard interferon therapy has met with limited efficacy. This study was designed to examine the efficacy and safety of peginterferon with or without ribavirin. Thirty-eight serum hepatitis B surface antigen- and HDV RNA-positive patients with alanine aminotransferase (ALT) more than 1.5 times the upper normal limit received peginterferon alpha-2b (1.5 ,g/kg) alone as monotherapy (n = 16) or in combination with ribavirin (n = 22), for 48 weeks. Thereafter, all the patients were maintained on peginterferon for 24 weeks and followed for 24 weeks off therapy. The primary end point studied was the virological and biochemical response at the end of follow-up. HDV RNA was determined by single or nested polymerase chain reaction assays. Twenty-seven patients (71%), 11 receiving monotherapy and 16 receiving the combination treatment, completed the follow-up. At the end of treatment, a virological response was observed in 3 of the patients treated with peginterferon (19%) and in 2 of the patients treated with combination therapy (9%), and a biochemical response was observed in 6 (37.5%) and 9 patients (41%), respectively. In nonresponders, ALT diminished from a mean of 174 ± 53 to 86 ± 41 IU/L. At the end of follow-up, serum HDV RNA was negative in 8 patients (21%), and a biochemical response was detected in 10 patients (26%). Treatment was discontinued in 25% of the patients, and dosing was modified in 58%. In conclusion, a prolonged course of peginterferon alpha-2b resulted in clearance of serum HDV RNA and ALT normalization in a fifth of patients with chronic hepatitis D, while ribavirin had no effect on the viral clearance rate. Overall tolerance of therapy was poor. (HEPATOLOGY 2006;44:713,720.) [source] Long-term follow-up after successful interferon therapy of acute hepatitis CHEPATOLOGY, Issue 1 2004Johannes Wiegand Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-,-2b) prevents chronicity in almost all patients. So far, no data are available on the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The aim of this study was to assess the clinical, virological, and immunological long-term outcome of 31 successfully treated patients with acute hepatitis C infection who were followed for a median of 135 weeks (52-224 weeks) after end of therapy. None of the individuals had clinical evidence of liver disease. Alanine aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C virus (HCV) RNA was negative throughout follow-up, even when investigated with the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5-10 IU/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear cells (PBMC) of 15 cases tested. The patients' overall quality-of-life scores as determined by the SF-36 questionnaire did not differ from the German reference control cohort. Ex vivo interferon gamma (IFN-,) ELISPOT analysis detected HCV-specific CD4+ T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8+ T-cell responses were found in 4 of 5 HLA -A2,positive individuals. Anti-HCV antibody levels decreased significantly during and after therapy in all individuals. In conclusion, early treatment of symptomatic acute hepatitis C with IFN-,-2b leads to a long-term virological, biochemical, and clinical response. Waning of anti-HCV humoral immunity and presence of HCV-specific CD8+ (but not CD4+) T cells highlights the complexity of T-cell and B-cell memory to HCV, which might be significantly altered by IFN treatment. (HEPATOLOGY 2004;40:98,107.) [source] Validity of FibroScan values for predicting hepatic fibrosis stage in patients with chronic HCV infectionJOURNAL OF DIGESTIVE DISEASES, Issue 2 2009Ryosuke TAKEMOTO OBJECTIVE: The aim of this study was to validate the FibroScan system compared with liver histology and serum markers for the diagnosis of hepatic fibrosis. We also tried to determine the cut-off levels and assess the feasibility of using FibroScan values to predict the fibrosis stage. METHODS: In 44 patients with HCV infection, liver stiffness was evaluated by FibroScan, serum fibrosis markers and a liver biopsy. Associations between these indices were also analyzed. RESULTS: FibroScan values showed a good correlation with serum levels of type IV collagen, hyaluronic acid and procollagen-III-peptide, and with the platelet count. Compared with liver histology, the FibroScan values increased proportionally with the progression of the histological fibrosis stage. Advanced fibrosis (F3 or F4) could be efficiently predicted by a FibroScan cut-off value of 15 kPa. The FibroScan sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 100%, 73.9%, 77.8%, 100%, and 86.4%, respectively. CONCLUSION: FibroScan values gave a good correlation with various markers of fibrosis and increased proportionally with the progression of the hepatic fibrosis stage. A FibroScan value of 15 kPa was found to be a significant separation limit for differentiating advanced fibrosis stages (F3 and F4) from the milder stages (F0,F2). FibroScan values are clinically useful for predicting the fibrosis stages and helpful in managing interferon therapy in patients with chronic hepatitis C. [source] Prospective study of short-term peginterferon-,-2a monotherapy in patients who had a virological response at 2 weeks after initiation of interferon therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2008Soocheol Jeong Abstract Background and Aims:, Long-term interferon (IFN) therapy is effective in eliminating hepatitis C virus (HCV). However, it carries the risk of adverse effects and reduced quality of life. To assess whether short-term IFN therapy effectively eliminates HCV, we performed a prospective pilot study of pegylated (peg)IFN-,-2a therapy for 8 or 24 weeks. Methods:, After excluding patients with high titers of genotype-1, 55 HCV patients received pegIFN-,-2a. Patients who became negative for HCV-RNA at week 2 were allocated to either an 8-week (n = 19) or 24-week (n = 15) course of IFN. We evaluated the efficacy of and tolerance to IFN therapy. Results:, The sustained virological response rate was excellent in the two groups (8 weeks, 89.5% [17/19]; 24 weeks, 100% [15/15], respectively,). IFN dose reduction was required in one patient of the 8-week group, but in six patients of the 24-week group (P = 0.028). Treatment was completed by all patients of the 8-week group, but discontinued in five patients of the 24-week group (P = 0.011). Conclusions:, The 8-week IFN therapy is more tolerable than the 24-week therapy and had similar outcomes. Excluding the patients with high titers of genotype-1, we recommend switching to an 8-week course of pegIFN-, monotherapy once patients show an ultra rapid virological response at week 2 from the start of IFN therapy. [source] Effect of interferon therapy on Japanese chronic hepatitis C virus patients with anti-liver/kidney microsome autoantibody type 1JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2001Yoshihiko Iijima Abstract Aim: The aim of this study was to determine the prevalence of anti-liver/kidney microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. Methods: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/kidney microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. Results: Anti-liver/kidney microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. Conclusion: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease. [source] Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following ,-interferon therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2001Ichiro Shimizu Abstract Background: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with ,-interferon (IFN-,) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. Methods and Results: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. Conclusions: These findings suggest that IFN-, treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C. [source] Influence of RNA titre and amino acid changes in the NS5A region of GB virus C/hepatitis G virus on the effectiveness of interferon therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2000Tomoki Fujisawa Abstract Background: A relationship between the pretreatment RNA titre of GB virus C/hepatitis G virus (GBV-C/HGV) and the effectiveness of interferon (IFN) therapy has been reported previously. However, the influence of changes in the amino acid sequence of the NS5A region of GBV-C/HGV on the effectiveness of IFN therapy has not been examined, although this influence has been explored in patients with chronic hepatitis caused by hepatitis C virus. We examined the relationship between changes in the amino-acid sequence of the NS5A region and the effectiveness of IFN therapy. Methods: The subjects were 10 patients with chronic hepatitis C coinfected with GBV-C/HGV and treated with IFN. The pretreatment level of GBV-C/HGV-RNA (copies/mL) in their sera was measured by real-time detection polymerase chain reaction (PCR) assay. At 6 months after cessation of therapy, four of 10 patients had become negative for GBV-C/HGV-RNA (CR, complete response) and six patients were still positive for GBV-C/HGV-RNA (NR, non-response). We determined the nucleotide sequence of the NS5A region (amino acid residues 1865,2279; NS5A1865,2279) of pretreatment GBV-C/HGV-RNA by direct sequencing. Results: The pretreatment GBV-C/HGV-RNA level of CR patients (7.8 × 104,6.2 × 105, mean 3.30 × 105) was significantly lower than that of NR patients (6.3 × 107,7.2 × 108, mean 3.55 × 108; P < 0.01). The number of amino acid substitutions in NS5A1865,2279 was five to seven (mean 5.8 ± 1.0) in CR patients, and four to eight (mean 6.8 ± 1.6) in NR patients, a difference that is not significant. Moreover, there were no amino acid substitutions or sites of substitution in NS5A1865,2279 that were specific to either group. Conclusions: The effectiveness of IFN therapy for GBV-C/HGV is strongly related to the pretreatment GBV-C/HGV-RNA level, but is not related to changes in NS5A1865,2279. [source] Predictors of the efficacy of interferon therapy for patients with chronic hepatitis C before and during therapy: how does this modify the treatment course?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2000Yasushi Shiratori Antiviral therapy for hepatitis C virus (HCV) infection should be based on the natural history of HCV infection; there is a sequential, but slow, progression from chronic hepatitis to cirrhosis, leading to death from either liver failure or hepatocellular carcinoma (HCC). The risk of HCC development increases in association with the advance of fibrosis, and antiviral therapy can reduce this risk. More than 30 indices have been proposed as ,predictors' of favourable response to IFN therapy: host factors (age, gender, duration of HCV-infection, alcohol intake, hepatic iron stores, platelet count, histological staging of the liver disease), viral factors (HCV RNA levels in serum, HCV subtype, diversity of the hypervariable region, mutation of non-structure 5A gene), and IFN factors (dose, duration of treatment, type, treatment regimens i.e. every day vs three times a week, escalating dose regimen). Before starting IFN therapy, HCV subtype and pretreatment HCV RNA load, as well as the fibrotic stage of the liver, should be determined. The response to IFN therapy should be monitored by the HCV RNA status in serum during therapy, and the treatment regimen modified, or discontinued as required. A sustained virological response should be checked at more than 3 months after the completion of therapy. Even though the risk of HCC is markedly reduced in sustained responders, it is possible to develop HCC several years after completion of IFN therapy. [source] Barriers to Treatment of Hepatitis C in HIV/HCV-Coinfected Adults with Alcohol ProblemsALCOHOLISM, Issue 9 2006David Nunes Background: Alcohol use and human immune deficiency virus (HIV) infection are both associated with accelerated progression of hepatitis C virus (HCV) disease and reduced response rates to interferon therapy. In this study, we assessed the prevalence of barriers to interferon treatment in a population of HIV/HCV-coinfected patients with current or past alcohol problems and the extent to which they received treatment to address the barriers. Methods: This is a cross-sectional, descriptive analysis of baseline data from a prospective study assessing the impact of HCV and alcohol use on HIV disease progression. Using consensus guidelines, subjects were categorized as having absolute, relative, or no contraindications to interferon therapy for HCV. Absolute contraindications to treatment included heavy alcohol use, decompensated liver disease, CD4 cell count <100 cells/,L, recent needle sharing, and suicidal ideation. Relative contraindications included moderate alcohol use, recent injection drug use, depressive symptoms, and CD4 cell count from 100 to 199 cells/,L. Results: Of 401 HIV-infected subjects, 200 were HCV RNA-positive. Fifty-three percent had an absolute contraindication to interferon therapy, 35% a relative but no absolute contraindication, and only 12% had no contraindication. Of those with an absolute contraindication, 61% reported heavy drinking and the majority (88%) had multiple contraindications. These contraindications were present despite the fact that over 50% were in receipt of substance abuse and mental health treatment. Conclusions: Continued alcohol and drug use as well as depressive symptoms are the major barriers to interferon therapy in HCV/HIV-coinfected subjects and these barriers persist despite high treatment rates for these problems. Therefore, more intensive treatments of alcohol, drug, and mental health issues are needed to improve HCV treatment eligibility in HCV/HIV-coinfected persons. [source] Interferon-induced retinopathy and its risk in patients with diabetes and hypertension undergoing treatment for chronic hepatitis C virus infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009J. D. PANETTA Summary Background, Ocular complications are amongst many side-effects of interferon based therapy for hepatitis C virus (HCV) infection. Some suggest that diabetic and hypertensive patients are at increased risk of these complications. Aim, To determine the frequency of ophthalmological complications related to interferon use. Methods, Retrospective analysis of patients undergoing HCV treatment with pegylated interferon ,-2a, ,-2b or consensus interferon plus ribavirin between 2005 and 2007. All patients underwent a baseline eye examination and any visual complaints during treatment prompted a repeat examination. Data recorded included HCV genotype, treatment duration, interferon type, pre-treatment and on treatment visual complaints, known ocular pathology, and retinal findings at baseline and at follow-up. Results, Of 183 patients, 29 (16%) had diabetes and 85 (46%) had hypertension. Seventy-one (38%) received interferon ,-2a, 100 (55%) ,-2b, and 12 (7%) consensus interferon. Seven (3.8%) had retinal changes on follow-up and treatment was discontinued in 3 (1.6%). Of seven with ocular changes two had hypertension and one had both hypertension and diabetes. Conclusion, The incidence of symptomatic retinopathy in HCV patients undergoing interferon therapy appears low and treatment cessation is rarely needed. Furthermore, patients with hypertension and diabetes may not be at higher risk for interferon-induced retinopathy. [source] Influence of HFE gene polymorphism on the progression and treatment of chronic hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 2 2004P. Lebray Summary., We analysed liver histology findings in a large cohort of patients with chronic hepatitis C and in roughly half of them their response to interferon- , -based on iron parameters and HFE status. Histological activity and virological response to antiviral therapy (n = 146) were analysed in 273 immunocompetent and nonalcoholic patients with chronic hepatitis C, in terms of serum iron load, intrahepatic iron load (n = 110) and HFE mutations. Patients who were heterozygous for the C282Y and H63D mutations exhibited higher iron serum parameters than subjects without these mutations. The intrahepatic iron load was higher in H63D patients only. No association was observed between HFE mutations and histological activity. Increased iron parameters were associated with liver disease severity by univariate analysis only. Genotype 1 and ferritinaemia were associated with a poor response to antiviral therapy, whereas the H63D mutation emerged as a positive predictive factor for end of treatment and sustained antiviral response. Therefore, in chronic hepatitis C patients serum and intrahepatic iron levels were weakly correlated with histological activity, while HFE mutations were not. As for the response to interferon- ,, elevated ferritinaemia constituted a negative predictive factor whereas the H63D mutation was a positive one. The H63D mutation might form part of an immunogenetic profile influencing the response to interferon therapy. [source] In vivo immunization following virus suppression: a novel approach for inducing immune control in chronic hepatitis B,JOURNAL OF VIRAL HEPATITIS, Issue 1 2003D. Sprengers summary. Antiviral treatment of patients with active chronic hepatitis B may lead to significant reduction in morbidity and mortality. However, after stopping nucleoside therapy, relapse rates are high in those without acquired specific immunity. We have treated two chronic hepatitis B patients with in vivo immunization. In vivo immunization aims to optimize conditions for an effective immune response: following rapid and profound virus suppression by interferon-lamivudine combination therapy, lamivudine is withdrawn intermittently for 4 weeks during continued interferon therapy. In both patients with profound virus suppression a rapid rebound in viral replication was observed after lamivudine withdrawal; despite continued interferon. These periods of renewed viral replication were followed by rises in hepatitis activity. After re-introduction of lamivudine HBV DNA became undetectable by PCR followed by normalization of serum ALT. These observations are a stimulus to further explore the concept of in vivo immunization as a novel therapeutic approach for chronic hepatitis B. [source] Predictors of a sustained virological response in patients with genotype 4 chronic hepatitis CLIVER INTERNATIONAL, Issue 8 2008Rita Raafat Gad Abstract Objectives: To determine the clinical, biological, virological and histological predictive factors associated with a sustained virological response (SVR) to combined interferon therapy among Egyptian patients infected by genotype 4 hepatitis C virus (HCV). Patients and Methods: Individual data from 250 patients with genotype 4 chronic hepatitis C, treated with different regimens of combined interferon, were analysed. The primary end point was SVR defined as undetectable HCV RNA by polymerase chain reaction (PCR) 24 weeks after the end of treatment. Multivariate logistic regression analysis was performed to select the independent prognostic parameters associated with SVR. Results: A sustained virological response was achieved among 137/250 (54.8%) patients. Baseline factors independently and negatively associated with SVR were serum ,-fetoprotein (AFP) level (above 0.3 upper limit of normal) [odds ratio (OR)=0.5, 95% confidence interval (CI): 0.2,0.8], severe fibrosis (Metavir score >F2) (OR=0.4, 95% CI: 0.2,0.8), presence of steatosis (OR=0.5, 95% CI: 0.3,0.97) and standard interferon treatment (OR=0.4, 95% CI: 0.2,0.8). Conclusions: Among genotype 4 chronic hepatitis C patients, severe fibrosis, severe steatosis, treatment with standard interferon and a high serum AFP level were all negatively associated with SVR. Pretreatment serum AFP level should be considered in the routine assessment of factors predictive of a treatment response. [source] Pegylated interferons: chemical and clinical differencesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2004G. R. Foster Summary Pegylated interferon therapy for the treatment of chronic hepatitis C virus provides significant increases in sustained virological response rates compared with standard interferons. Two pegylated interferons are now available and are used in conjunction with ribavirin to maximize response rates in infected patients. The two pegylated interferons, peginterferon, -2a and peginterferon, -2b, differ substantially in terms of their chemical and structural characteristics, pharmacokinetic and pharmacodynamic properties, and dosing and administration. A full understanding of the differences between the two drugs is important to maximize the clinical benefits. Controlled studies designed to characterize the effects of the two drugs on viral kinetics and sustained virological response rates are emerging and may help to shed additional light on the use of these compounds in patients with chronic hepatitis C. [source] Raised serum ferritin predicts non-response to interferon and ribavirin treatment in patients with chronic hepatitis C infectionLIVER INTERNATIONAL, Issue 3 2002S Distante Abstract: Background/Aim: Previous studies have indicated that response to interferon therapy is inversely proportional to the amount of body iron stores. We have studied the relationship between serum ferritin, transferrin saturation, liver iron, presence of HFE-C282Y gene mutation and response to treatment in patients with chronic hepatitis C infection. Methods: Two hundred and fifty-six naive, HCV-RNA positive patients (60% males, median age 38 years, range 21,70) were treated with interferon and ribavirin for 6 months. Iron indices and the presence of the C282Y mutation were measured. In 242 (94%) patients iron deposition were determined by Perls staining method. Patients with negative HCV-RNA at 6 months after the end of treatment were defined as sustained viral responders. Results: Non-responders (n = 127) had significantly higher median s-ferritin values compared with sustained viral responders (130 µg/L vs. 75 µg/L P < 0.001). There was no difference in transferrin saturation among the two response groups. Only 23% (4/7) of patients with Perls grade 1 in liver biopsies responded to treatment vs. 54% (122/225) patients without iron deposition (P = 0.02), however, 10/13-non-responders had HCV genotype one. Two patients (0.8%) were homozygous for the C282Y mutation, 36 patients were heterozygous (14%). Among mutation carriers 26/38 achieved sustained response compared with 102/216 non-carriers (68% vs. 48%, P = 0.02). In a multivariate analysis s-ferritin (P = 0.030) and C282Y carrier status (P = 0.012) remained independent predict of sustained response. Conclusions: Raised s-ferritin values predicate non-response to interferon-ribavirin therapy in hepatitis C patients. Response rate in C282Y mutation carriers seems greater than in non-carriers. [source] A prospective study of interferon therapy modified by pre-treatment viral load in cirrhotic patientsLIVER INTERNATIONAL, Issue 4 2000Yasushi Shiratori Abstract:Background/Aims: The relative role of hepatitis C virus (HCV) load and subtype as predictors of the efficacy of interferon therapy has been clarified in patients with chronic hepatitis C, but the effectiveness of interferon therapy in cirrhotic patients is still unclear. Methods: To resolve this issue, we undertook a multicenter, randomized, and prospective study of 114 cirrhotic patients with hepatitis C virus infection. The patients were selected to undergo two different periods (6 or 12 months) of IFN therapy according to viral load. Patients with "low" viral load (,105.8 copies/ml serum) were randomly divided into three groups, receiving 6 or 9 million units (MU) interferon three times a week for 6 months (total dose: 468 or 702 MU), or of a modified regimen using 6MU of IFN over 6 months (total dose 564 MU), while patients with "high" viral load (,106.3 copies/ml serum) were also randomly divided into two groups of 6 or 9 MU of IFN three times a week for 12 months (total dose: 936 or 1404 MU). Results: HCV-RNA negativity rate at the completion of treatment with 6 or 9 MU IFN was 65% in patients with "low" viral load, in contrast to 14% in patients with "high" viral load. Sustained virological response was found in 40% of patients with "low" viral load irrespective of the three different regimens, in contrast to only 1 out of 35 patients (3%) with "high" viral load. Viral eradication was found in approximately 50% of patients having a low virus load (,104.3 copies/ml) and with HCV subtype 2a. Univariate and multivariate analysis revealed that pretreatment viral load was a significant factor contributing to efficacy of IFN therapy. Conclusions: Sustained response was scarcely achieved in cirrhotic patients with high viral loads even after a 12-month course of intensive IFN therapy. This result indicates that there is a certain cut-off level of HCV RNA load which can not be eradicated. [source] Outcomes 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] Hepatitis C virus infection and interferon therapy in patients with Down syndromePEDIATRICS INTERNATIONAL, Issue 1 2008Yoko Miyoshi Abstract Background: The clinical features of hepatitis C virus (HCV)-associated liver diseases, or the efficacy of interferon (IFN) therapy in children with Down syndrome (DS) remain to be elucidated. The purpose of the present paper was to survey the features of liver diseases in this subset of children and evaluate the efficacy of IFN treatment in those patients. Methods: A questionnaire was sent to 41 members of the Japan Society of Pediatric Hepatology. Ten of them reported on 11 patients with DS who had concomitant chronic HCV infection, providing information on liver disease and the response to IFN treatment. Results: Interferon therapy of 24 weeks duration using natural IFN-, was instituted in six of the 11 patients with DS, but none of the six patients cleared HCV-RNA from their serum. Among 12 age- and sex-matched control children who were treated with IFN using the same regimen against chronic HCV infection, half of them had a favorable response to IFN therapy with a sustained clearance of HCV-RNA from their serum. The major baseline features including alanine aminotransferase levels, HCV genotype and viral load were not apparently different between the six patients with DS and the 12 controls. Conclusions: IFN therapy for HCV infection in patients with DS may be unfavorable as compared with non-DS children. [source] Longitudinal course of depression, fatigue, and quality of life in patients with high risk melanoma receiving adjuvant interferonPSYCHO-ONCOLOGY, Issue 8 2004Peter C. Trask Purpose: Treatment of malignant melanoma with interferon- , has been associated with a variety of side effects ranging from fatigue to depression, and a concomitant impact on quality of life (QOL), in a variety of case reports and cross-sectional clinical trials. Few, if any, studies have been conducted with the express purpose of assessing the longitudinal course of depression, fatigue, and QOL before and during interferon therapy. Description of study: The current study reports on 16 patients who were assessed at 6 points in time: baseline, post high dose, and 1, 2, 3, and 6 months post high dose treatment with interferon- , with the Brief Symptom Inventory, Beck Depression Inventory, Revised Piper Fatigue Scale, and Functional Assessment of Cancer Therapy-Biological Response Modifiers. Results: Results revealed consistent changes from baseline through 6 month assessment. Specifically, increased somatic complaints, depression, and fatigue were observed on the BSI, BDI, and RPFS, respectively. Additional reductions in QOL on the FACT-BRM were also identified. Clinical implications: The findings suggest that IFN has a significant effect on QOL, but that it may be the somatic symptoms of fatigue that contribute to changes on measures of mood. Limiting the amount of fatigue and depression would appear to be significant if individuals are to successfully complete IFN therapy. Copyright © 2003 John Wiley & Sons, Ltd. [source] Splenectomy and preemptive interferon therapy for hepatitis C patients after living-donor liver transplantationCLINICAL TRANSPLANTATION, Issue 6 2005Yoji Kishi Abstract:, Recurrent hepatitis C after liver transplantation is a major cause of graft failure. We routinely perform preemptive interferon and ribavirin therapy in patients after living-donor liver transplantation indicated for hepatitis C-related cirrhosis. One of the obstacles for the therapy includes blood cytopenia. To overcome this problem, we recently performed splenectomy concurrently with liver transplantation. Thirty-five patients underwent liver transplantation and received preemptive therapy for hepatitis C. They were divided into two groups: those with splenectomy (group A, n = 21) and those without (group B, n = 14). There was no significant difference in the frequency of morbidity between the groups. Platelet counts were well maintained in group A patients during the therapy, and cytopenia led to the discontinuation of the therapy in one group B patient. The results of the preliminary study warrant a randomized control trial to examine the feasibility of splenectomy and preemptive viral therapy during liver transplantation for hepatitis C. 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