Interferon Alpha-2b Treatment Research Articles

Therapeutic Effectiveness of Interferon Alpha 2b Treatment for COVID-19 Patient Recovery.

A previous report on 814 patients who were coronavirus disease 2019 (COVID-19) positive provided preliminary therapeutic efficacy evidence with interferon-α2b (IFN-α2b) in Cuba, from March 11 to April 14, 2020. This study re-evaluates the effectiveness of IFN-α2b during the period from March 11 to June 17, 2020. Patients received a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN-α2b. The primary endpoint was the proportion of patients discharged from the hospital; the secondary endpoint was the case fatality rate, and several outcomes related to time variables were also evaluated. From March 11 to June 17, 2,295 patients had been confirmed to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive in Cuba, 2,165 were treated with Heberon® Alpha R, and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with the non-IFN-treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases. Benefits of IFN were significantly supported by time variables analyzed. This second report confirmed our preliminary evidence about the therapeutic effectiveness of IFN-α2b in SARS-CoV-2 infection and postulated Heberon Alpha R as the main component within antiviral drugs used in the Cuban protocol COVID-19.

Topical Interferon Alpha 2b in the Treatment of Refractory Diabetic Macular Edema

PurposeTo report the efficacy of topical interferon alpha 2b in the treatment of refractory diabetic macular edema.MethodsIn this retrospective interventional case series, five eyes of three individuals with diabetic macular edema resistant to multiple intravitreal injections of anti-vascular endothelial growth factor drugs and macular photocoagulation were included.ResultsAll studied eyes had undergone multiple intravitreal injections including bevacizumab, combination of bevacizumab and triamcinolone and aflibercept, and macular laser photocoagulation before being included in this study. Two intravitreal ranibizumab injections had also been performed in both eyes of one patient. Two eyes had undergone pars plana vitrectomy, one for diabetic macular edema and the other for rhegmatogenous retinal detachment. After a discussion regarding the experimental topical interferon alpha 2b treatment, all patients agreed to start interferon alpha 2b drops four times a day. One month after the treatment, optical coherence tomography demonstrated a significant improvement in macular structure and thickness which was stable or improved at the three-month follow-up visit. Visual acuity in all eyes was stable or improved throughout the three-month follow-up period. Conjunctival injection and follicular conjunctivitis were the side effects of topical interferon alpha 2b and were treated with lubrication and steroids.ConclusionThis case series demonstrated the potential efficacy of interferon alpha 2b in the treatment of refractory diabetic macular edema. It might be an option in patients with contraindications for intravitreal injections.

Role of Tumor Necrosis Factor alpha promoter polymorphisms in interferon related side effects in chronic hepatitis B patients under interferon alpha 2b treatment

Objective(s). Interferon alpha therapy is associated with series of adverse effects leading premature discontinuation of treatment. Here we aimed to determine the effects of Tumor necrosis alpha promoter polymorphisms on interferon related side effects during interferon alpha 2b treatment in chronic hepatitis B patients
 Material and Method(s). This observational study enrolled 50 chronic hepatitis B patients, who were treated with interferon alpha 2b 10 tiw plus lamivudine 100mg/day at Selçuk University Meram Medical Faculty Department of Infectious Diseases and Clinical Bacteriology between 2006-2007. Patients were followed-up with complete blood count, transaminases and amylase monthly at out patient clinics of our department. All patients were asked to fill a questionnaire to evaluate the interferon related side effects at every visit. Tumor necrosis factor alpha -238 and -308 polymorphisms were investigated with PCR-Restriction fragment length polymorphisms.
 Result(s) and Conclusion Arthralgia was present in 93.8% of patients. Exhaustion, loss of appetite, mount dryness and fever are the leading complaints of the patients. Median complaint scores were 9, 9.5, 11 and 5 at 4th, 12th, 24th and 48th week visits, respectively. Thrombocytopenia and leucopenia were detected in 8 (16%) and 5 (10%) patients, respectively. One-third of the patients reported depressive mood however, depression was diagnosed in 5 (10%) patients. TNF alpha promoter 238GG and 308GG allele was present in 42/50 and 43/50 patients, respectively. No association was found between TNF promoter allele and certain patient-reported side effect, complaint score, hematological and psychological adverse effects. TNF alpha promoter polymorphisms do not contribute to occurrence of IFN alpha treatment related side effects.

Osteopontin as a marker for response to pegylated interferon Alpha-2b treatment in Chronic HCV Saudi patients.

Many recent studies support the idea that osteopontin (OPN) can be used to predict the success of pegylated interferon (PEG IFN) alpha-2b/ribavirin therapy in chronic HCV patients. Our aim was to investigate the role of plasma OPN and its gene polymorphism at nt - 443 in response to PEG IFN in Saudi patients with chronic HCV. Blood was collected from 87 patients with chronic hepatitis C before treatment, then patients received PEG IFN α2b plus ribavirin combination therapy. Another 25 healthy subjects, matched for age and sex to patients, were enrolled as controls. Single nucleotide polymorphism (SNP) in OPN at nt - 443 and its blood level were analyzed. The frequency of patients who reached sustained virological response (SVR) was increased in patients with T/T at nt - 443 than in those with C/C or C/T. Also the frequency of T allele was increased in responders than in non-responders. However, this increase was not statistically significant. The blood level of OPN was significantly increased in non-responders (Mean±SD=37.21±3.9) in comparison to responders (Mean±SD=33.22±4.1). Osteopontin blood level can be considered as a reliable predictor to PEG IFN α2b plus ribavirin therapy in chronic HCV Saudi Patients.

Surgical versus Medical Treatment of Ocular Surface Squamous Neoplasia: A Cost Comparison

The objective of this study was to compare the cost associated with surgical versus interferon-alpha 2b (IFNα2b) treatment for ocular surface squamous neoplasia (OSSN). A matched, case-control study. A total of 98 patients with OSSN, 49 of whom were treated surgically and 49 of whom were treated medically. Patients with OSSN treated with IFNα2b were matched to patients treated with surgery on the basis of age and date of treatment initiation. Financial cost to the patient was calculated using 2 different methods (hospital billing and Medicare allowable charges) and compared between the 2 groups. These fees included physician fees (clinic, pathology, anesthesia, and surgery), facility fees (clinic, pathology, and operating room), and medication costs. Time invested by patients was calculated in terms of number of visits to the hospital and compared between the 2 groups. Parking costs, transportation, caregiver wages, and lost wages were not considered in our analysis. Number of clinic visits and cost of therapy as represented by both hospital charges and Medicare allowable charges. When considering cost in terms of time, the medical group had an average of 2 more visits over 1 year compared with the surgical group. Cost as represented by hospital charges was higher in the surgical group (mean, $17 598; standard deviation [SD], $7624) when compared with the IFNα2b group (mean, $4986; SD, $2040). However, cost between the 2 groups was comparable when calculated on the basis of Medicare allowable charges (surgical group: mean, $3528; SD, $1610; medical group: mean, $2831; SD, $1082; P = 1.00). The highest cost in the surgical group was the excisional biopsy (hospital billing $17 598; Medicare allowable $3528), and the highest cost in the medical group was interferon ($1172 for drops, average 8.0 bottles; $370 for injections, average 5.4 injections). Our data in this group of patients previously demonstrated equal efficacy of surgical versus medical treatment. In this article, we consider costs of therapy and found that medical treatment involved two more office visits, whereas surgical treatment could be more or equally costly depending on insurance coverage.

Recombinant Interferon Alpha (rIFN) May Retard Progression Of Early Myelofibrosis By Reducing Splenomegaly and By Decreasing Marrow Fibrosis

▪ IntroductionLimited effect of JAK2 inhibitors in treating myelofibrosis (MF), either primary (PM) or secondary to polycythemia vera (PV-MF) or essential thrombocythemia (ET-MF), and the limited survival experienced with stem cell transplantation, prompted us to use interferon (rIFNα) in early stage MF (eMF), i.e. low or intermediate-1 disease. rIFNα effects megakaryopoiesis, decreasing megakaryocyte (MK) density and size, inhibiting thrombopoietin-induced signaling, and reducing levels of platelet derived growth factor, which play a major role in the pathogenesis of MF. Moreover, rIFNα affects stem cells in PV. Results we previously reported in eMF showed remission, clinical improvement (CI) or stable disease (SD) in 80% of 17 patients (pts.) with PM (Silver RT et al. Blood. 2011; 117(24):6669-72). Based on this encouraging experience, we expanded our trial with rIFNα to include PV-MF and ET-MF. We now report the results of 32 pts. with eMF. MethodsPts. were seen regularly in our clinic, evaluating symptoms, physical findings, signs of toxicity, routine blood counts and chemistries and JAK2 determinations. Bone marrow biopsies (BMBs) were encouraged annually to evaluate status of disease. The dose of recombinant interferon alpha-2b (rIFNα-2b) treatment was initiated at 500,000 – 1,000,000 units thrice weekly (18) or pegylated interferon alpha-2a (PEG-IFNα-2a), 45 mcg weekly (9). Results17 women and 15 men, median age 57 years (range: 34-72) were treated. Median duration of disease prior to treatment was 3.4 months. Median values for hematocrit, hemoglobin, and platelet count at baseline were 38.8%, 12.9 g/dL, and 345,000/uL, respectively. 12 pts. (37.5%) met the criteria for PM, 7 (22%) for PV-MF and 11 (34%) for ET-MF. Two (6.3%) PV pts. had continuing phlebotomy requirements and progressive splenomegaly, and marrow fibrosis in the absence of other WHO criteria. Risk categories were assigned based on the IWG-MRT DIPSS-PLUS. Twenty-two pts. were low-risk, 4 intermediate-1, and 6 intermediate-2 (the latter group emerged solely due to incorporation of cytogenetic data; prior to DIPSS-PLUS, the 6 pts. categorized as intermediate-1). The IWG-MRT risk categories were correlated with response (Table). Of 32 pts., 3 (9.4%) had complete remission (CR), 12 (37.5%) partial remission (PR), 3 (9.4%) CI and 7 (22%) SD - an overall response rate of 78%. Three (9.4%) pts. (1: intermediate-1, 2: intermediate-2) died of progressive disease (PD), one of whom was rIFNα non-compliant. Of 32 pts., 10 had no splenomegaly at onset of rIFNα, and 9 remained unchanged during treatment. In 10 pts. initially with slight splenomegaly (< 3 cm below the LCM), the spleen became non-palpable in 8. Of 3 pts. with moderate (>3 – 9 cm BLCM) spleens, and 9 (> 9 cm BLCM) with marked splenomegaly, there was a more variable response (1 – 16 cm decrease). Follow-up BMBs were possible in 22 pts.; in 12, reduction in cellularity occurred after a median treatment period of 2 years. Of 15 pts. with reduction in splenomegaly and evaluable BMBs, 7 had reduction in cellularity, 3 showed significantly improved MK morphology, marrow architecture, and striking reduction of reticulin and collagen fibrosis (grade 3 to 1); 3 showed no change in morphology, but nevertheless, experienced reduction in spleen size. Of the 32 pts., 23 (71.8%) were JAK2V617F (+). Of 19 follow-up specimens, 7 had a median allelic burden decrease of 44%., the remainder were unchanged Abnormal cytogenetics did not influence response.All pts. initially experienced the usual side effects of rIFNα which were mild in degree (grade 1-2) and subsided with time or dose adjustment; including mild depression, dry skin, cough, myalgia, fatigue and asthenia. Seventeen pts. developed increasing anemia (13: grade 1; 4: grade 2); one had grade 3 thrombocytopenia. In these cases, the dose was temporarily reduced or interrupted until cytopenias resolved. One pt. developed hyperthyroidism and treatment was discontinued. ConclusionsIn this eMF, single-arm study, we conclude that rIFNα prevents disease progression and can induce remission with acceptable toxicity, improving marrow morphology which usually, but not always, correlates with reduction in splenomegaly, warranting an expanded phase 3 trial, currently underway. [Display omitted] IWG-MRT treatment response stratified by DIPSS-PLUS risk at baseline. Disclosures:Silver:Sanofi: Consultancy; Sanofi: Research Funding; Sanofi: Honoraria. Off Label Use: The use of recombinant and pegylated interferon alpha in the treatment of myelofibrosis. Feldman:Tragara Pharmaceuticals: Consultancy.

P279 Reduction of hepatocellular carcinoma recurrence by pegylated interferon alpha-2b plus ribavirin treatment for chronic hepatitis C patients

P279 Reduction of hepatocellular carcinoma recurrence by pegylated interferon alpha-2b plus ribavirin treatment for chronic hepatitis C patients

Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: A prospective, multicenter study

The effects of pegylated interferon (PegIFN) α and ribavirin (RBV) treatment of chronic hepatitis C on the incidence of hepatocellular carcinoma (HCC) have not been well established. This study investigated the impact of treatment outcome on the development of HCC by chronic hepatitis C patients treated with PegIFNα2b and RBV. This large-scale, prospective, multicenter study consisted of 1013 Japanese chronic hepatitis C patients with no history of HCC (non-cirrhosis, n=863 and cirrhosis, n=150). All patients were treated with PegIFNα2b and RBV and the follow-up period started at the end of the antiviral treatment (median observation period of 3.6 years). The cumulative incidence rate of HCC was estimated using the Kaplan-Meier method, according to treatment outcome. Forty-seven patients (4.6%) developed HCC during the observation period. In the non-cirrhosis group, the 5-year cumulative incidence rates of HCC for the sustained virological response (SVR) (1.7%) and transient virological response (3.2%) (TVR: defined as relapse or breakthrough) groups were significantly lower than those of the non-virological response (NVR) group (7.6%) (p=0.003 and p=0.03, respectively). A significantly low rate of incidence of HCC by TVR patients in comparison with NVR patients was found for patients aged 60 years and over, but not for those under 60 years of age. In the cirrhosis group, the 5-year cumulative incidence rates of HCC for the SVR (18.9%) and TVR groups (20.8%) were also significantly lower than those of the NVR group (39.4%) (p=0.03 and p=0.04, respectively). SVR and complete viral suppression during treatment with relapse (TVR) were associated with a lower risk of HCC development when compared with NVR.

Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1

Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR=5.97, 95% CI 2.15-16.55, p=0.0006) and the baseline HOMA-IR (OR=0.65, 95% CI 0.48-0.87, p=0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC=0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC=0.772, HOMA-IR cut-off value: 1.55). For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.

The Efficacy of Topical Interferon Alpha 2b Treatment in Refractory Vernal Keratoconjunctivitis

Purpose: This study aimed to investigate the efficacy and safety of a 2-month topical interferon alpha 2b treatment in patients with refractory vernal keratoconjunctivitis.Methods: Twelve (10 male, 2 female) patients with refractory vernal keratoconjunctivitis received topical treatment with one million IU/mL interferon alpha 2b 4 times a day for 2 months. Symptom and ophthalmological examination scores were assessed at baseline and during follow-up.Results: No significant complications or side effects associated with the use of topical interferon alpha 2b were observed. Symptom scores for itching, tearing, photophobia, and total symptom score, and objective scores for corneal lesion, hyperemia, chemosis, papillary hypertrophy, secretion, and total examination score significantly improved during the 2-month treatment. Improvements were maintained after discontinuation of the treatment for most parameters.Conclusions: Topical interferon alpha 2b treatment seems to offer a safe and effective alternative for the treatment of refractory vernal keratoconjunctivitis for a brief period.

Risk score based PEG Interferon alpha 2b and Ribavirin treatment response estimation model for genotype 1 chronic hepatitis C patients

Attempt to create simple practical algorithm for prospective assessment of PEG interferon/ribavirin related treatment response in individuals with chronic hepatitis C (CHC) basing on the risk factors defined prior to the treatment initiation. Retrospective assessment of 45 female and 39 male previously untreated CHC patients aged 20 to 73 years, with genotype 1, undergoing standard treatment with PEG-IFNa2b+RBV was performed. For the final analysis 78 patients were included (38 effectively treated and 40 treatment failures). Thirty-six sustained virological response (SVR) related factors, which were routinely measured before treatment initiation were compared (including physical, biochemical, serologic and histopathologic). From this group the risk factors of the highest predictive value for treatment failure were selected. Cut-off values for statistical significance were defined for each parameter, with risk score (RS) calculated and compared in the group with and without SVR. Seven factors related to treatment failure were identified: HCV>600000 IU/L, blood platelet count <150000/ul, GGTP>45 IU/ml, total serum protein<7.8 g/dl, glycaemia>105 mg/dl, detectable HBc IgG antibodies and cirrhosis. In the group with RS 1 the likelihood of SVR was 70% (p<0.028), while in patients with RS 3 the response was reduced to 23.8% (p<0.016), with no SVR achieved among patients with RS >3. Low risk score (0-2) is associated with high probability of treatment success with scores >3 predictive for treatment failure. The presented model is a simple tool for prediction of treatment success for clinical use before PegIFN/RBV treatment initiation among genotype 1 CHC patients.

Common biostructure of the colonic microbiota in neuroendocrine tumors and Crohnʼs disease and the effect of therapy

The aims were to comparatively investigate the biostructure of colonic microbiota in patients with neuroendocrine tumors and Crohn's disease (CD) and to study the response of the microbiota to therapy. Sections of fecal cylinders from 66 patients with neuroendocrine tumors (NET; 25 foregut, 30 midgut, 11 hindgut), 50 patients with CD (Crohn's Disease Activity Index [CDAI] ≥150), and 30 patients with chronic idiopathic diarrhea seen at the Charité Hospital and 25 healthy controls were investigated using fluorescence in situ hybridization with probes specific for five bacterial groups: Faecalibacterium prausnitzii, Clostridium group XIVa / Roseburia group, Bacteroides, Enterobacteriaceae, and Bifidobacteriaceae. We found a striking F. prausnitzii (Fprau) depletion in the stool of patients with NET of the midgut and patients with CD. The changes of the microbiota in the two other NET groups were uncharacteristic and similar to those observed in patients with chronic idiopathic diarrhea. Fprau depletion was reversible with chemotherapy and with interferon alpha-2b treatment in patients with midgut NET. Somatostatin analogs had no influence on Fprau concentrations. Patients with NET and CD show similarities in their abnormalities of the fecal biostructure. Interferon alpha and systemic chemotherapy significantly improved the fecal biostructure in patients with midgut NET.

Abbott RealTime PCR assay is useful for evaluating virological response to antiviral treatment for chronic hepatitis C

This study was done to evaluate the utility of the Abbott RealTime PCR assay (ART) for the monitoring of chronic hepatitis C patients. The serum samples of 183 patients infected with hepatitis C virus (HCV) genotype 1b who had completed a 48-week period of pegylated interferon (PEG-IFN) alpha-2b plus ribavirin treatment were prospectively analyzed. Serum HCV RNA levels were measured both by ART and by the Roche COBAS Amplicor Monitor test, version2.0 (CAM) at baseline and at weeks 4, 12, 24, 36, and 48 of treatment, and at 24weeks after the end of treatment (EOT). A significant positive correlation of pretreatment HCV RNA levels was found between ART and CAM (r=0.595, P<0.0001). Of the 183 patients, 66 (36.0%) achieved a sustained virological response (SVR). The logarithmic decline of the HCV RNA level from the pretreatment level determined by ART in SVR patients was significantly higher than that in non-SVR patients at all time points tested. The logarithmic decline determined by CAM in SVR patients was significantly higher than that in non-SVR patients only at week 4, but there was no significant difference at other weeks. Of 124 patients who were HCV RNA-negative at EOT by ART, 58 (46.8%) had a relapse of viremia at 24weeks after EOT, whereas 77 of 143 patients (53.8%) who were HCV RNA-negative at EOT by CAM had a relapse. The relapse rate was lower when determined by ART than by CAM, but not significantly so. ART is more useful than CAM for evaluating the virological response to antiviral treatment for chronic hepatitis C.

Pegylated Interferon Alpha 2b for Treatment of Ocular Surface Squamous Neoplasia: A Pilot Study

Purpose: To conduct a pilot study of pegylated interferon alpha 2b (PEGIFNα2b) for treatment of ocular surface squamous neoplasia (OSSN).Methods: Three patients with histologically proven OSSN were studied prospectively. Patients were given subconjunctival/perilesional injections of 1 μg/kg of PEGIFNα2b (PEG Intron, Schering-Plough, Kenilworth, NJ) until the tumor resolved. Patients were followed clinically and photographically for evidence of tumor resolution and recurrence.Results: All patients had clinical resolution of the tumor. The mean time to resolution was 47 days. During the follow-up time after resolution of the lesion (mean 41 months), one patient had disease recurrence 7 months after clinical resolution. This was successfully treated with one further injection.Conclusion: PEGIFNα2b may be a viable medical alternative for the treatment of OSSN. Future studies will be needed to evaluate whether PEGIFNα2b is as effective as recombinant interferon alpha 2b.

Excellent superiority and specificity of COBAS TaqMan HCV assay in an early viral kinetic change during pegylated interferon alpha-2b plus ribavirin treatment

BackgroundAn early virological response (EVR) after the start of interferon (IFN) treatment for chronic hepatitis C leads to a successful virological outcome. To analyze an association between sustained virological response (SVR) and EVR by comparing TaqMan with Amplicor assays in HCV genotype 1-infected patients treated with pegylated (PEG)-IFN alpha-2b plus ribavirin (RBV).MethodsWe retrospectively analyzed a total of 80 HCV genotype 1 patients (39 SVR and 41 non-SVR patients), who received an enough dosage and a complete 48-week treatment of PEG-IFN alpha-2b plus RBV. Serum HCV RNA levels were measured by both TaqMan and Amplicor assays for each patients at Weeks 2, 4, 8 and 12 after the start of the antiviral treatment.ResultsOf the 80 patients with undetectable HCV RNA by Amplicor, 17 (21.3%) patients were positive for HCV RNA by TaqMan at Weeks 12. The quantification results showed that no significant difference in the decline of HCV RNA level between TaqMan and Amplicor 10-fold method assays within the initial 12 weeks of the treatment was found. However, the qualitative analysis showed significant differences of the positive predictive rates for SVR were found between TaqMan (100% at weeks 4 and 100% at weeks 8) and Amplicor (80.0% and 69.6%, respectively).ConclusionsThe COBAS TaqMan HCV assay is very useful for monitoring HCV viremia during antiviral treatment to predict a SVR in HCV genotype 1 patients.

Neuropsychiatric Complications Associated with Interferon - Alpha -2b treatment of Malignant Melanoma

Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

The longitudinal quantitative assessment by transient elastography of chronic hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin

The aim of this study was to assess the association between liver stiffness measured by transient elastography (FibroScan ®) and the efficacy of pegylated interferon alpha-2b plus ribavirin combination treatment for patients with chronic hepatitis C virus (HCV) infection. We prospectively studied 145 Japanese patients with chronic HCV infection. FibroScan was done at baseline, at the end of treatment, and at 48 and 96 weeks after the end of treatment. The FibroScan values were significantly decreased for sustained virological response (SVR) patients (the mean rate of change; −16.2%, −32.2% and −43.5%) in comparison with non-SVR patients (−7.2%, −2.1% and +17.3%) at the end of treatment ( P = 0.0127), and 48 weeks ( P < 0.0001) and 96 weeks ( P < 0.0001) after the end of treatment. Among the non-SVR patients, the FibroScan values were significantly decreased for patients with biochemical response (BR) (−17.9%, −30.0% and −27.1%) in comparison with non-BR (−4.1%, +6.4% and +30.6%) at the end of treatment ( P = 0.0270), and 48 weeks ( P < 0.0001) and 96 weeks ( P < 0.0001) after the end of treatment. The FibroScan values may predict a progressively better clinical outcome for patients with successful virological and biochemical responses.

Mumps: a resurgent disease with protean manifestations

Mumps has re-emerged as an infection in the developed world. Its epidemiology has changed, with the majority of cases now primarily affecting adolescents and adults. While mumps is easily suspected if parotitis is present, parotitis is absent in 10%-30% of symptomatic cases. Mumps is a systemic infection with a variety of extra-parotid complications. In Australia, mumps diagnosis is confirmed by antibody testing and reverse transcriptase-polymerase chain reaction techniques. Suitable specimens for testing are serum, saliva, urine and cerebrospinal fluid. Treatment is generally supportive, although intravenous immunoglobulin therapy may have a future role in mumps management. Interferon alpha-2b treatment may be considered specifically for mumps epididymo-orchitis. Mumps vaccine is included in the measles-mumps-rubella (MMR) vaccine. In Australia, this vaccine is routinely administered at the ages of 1 and 4 years. Serious reactions to the mumps components of the MMR vaccine are rare.

ALT and viral load decline during PEG-IFN alpha-2b treatment for HBeAg-positive chronic hepatitis B

Background Alanine aminotransferase (ALT) is one of the main indicators for inflammatory activity in chronic hepatitis B. During interferon-based therapy, approximately 25%–40% of patients exhibit an ALT flare. Objectives and study design To analyze the relation between ALT and HBV-DNA during pegylated interferon alpha-2b (PEG-IFN) treatment and compare different patterns of on-treatment viral load decline with the occurrence of ALT flares. Results Of the 123 patients included in this study 31 (25%) exhibited an ALT flare during treatment or follow-up. Six out of 8 (75%) host-induced flares, i.e. ALT flares which were followed by a HBV-DNA decrease associated with a favorable treatment outcome, occurred in patients with a delayed HBV-DNA decline pattern (delayed vs. non-delayed decline, p = .022); 5 of these 8 patients exhibited HBeAg loss and 4 even HBsAg loss at the end of follow-up. The prediction of ALT normalization was possible using on-treatment viral load. Based on the difference from baseline, the evolution of viral load and ALT level were strongly interrelated during treatment and follow-up. With a joint model we estimated a correlation coefficient of 0.38 ( p < 0.001) during the first 4 weeks of the treatment and of 0.72 ( p < 0.0001) thereafter. Conclusion There was a strong relation between ALT and viral load in HBeAg-positive chronic hepatitis B patients treated with PEG-IFN alpha-2b, especially after 4 weeks of treatment. Patients with a delayed decline in viral load often exhibited a host-induced flare associated with a favorable outcome.

Peginterferon &alpha;-2b・Ribavirin併用療法における0-2/0-4 ratioを用いた超早期治療効果予測

To optimize early identification of patients with chronic hepatitis C who will fail to achieve sustained viral response (SVR) with pegylated interferon alpha-2b plus ribavirin treatment, we investigated the dynamics of hepatitis C virus (HCV) RNA levels during initial 4 weeks of the treatment. We defined '0-2 ratio' as HCV RNA quantitative decrease at week 2 in comparison with the amount of HCV RNA just before the treatment, and '0-4 ratio' as that at week 4. We found that patients who showed 0-2 ratio of less than 1/2 or with 0-4 ratio of less than 2-log10 could not achieve SVR at week 24 after the treatment. We concluded that 0-2/0-4 ratios were novel predictors for non-SVR patients.