Interferon Therapy For Hepatitis Research Articles

Comparative Analysis of Host and Virus-Driven Variables Affecting Response to Ribavirin and Interferon Therapy in Hepatitis C Patients

Current guidelines advocate for individualized treatment approaches for the management of Hepatitis C, that incorporate baseline assessments of viral genotype, host comorbidities, and socioeconomic factors to maximize therapeutic success. Objectives: To analyze the impact of host and virus-driven variables on treatment response in patients receiving ribavirin and interferon therapy. Methods: This prospective cohort study was conducted on 138 patients aged 18–65 with confirmed chronic HCV infection who were eligible for interferon and ribavirin therapy. The patients were followed up to a 24-week post-treatment to assess recovery measured in terms of sustained virological response (SVR). The host-driven factors included age, gender, BMI, and the presence of IL28B polymorphism while virus-driven factors included HCV genotype and baseline viral load. Results: The study sample predominantly consisted of male (55.1%), and genotype 3 virus accounted for 68.1% of participants. A high proportion (76.1%) of participants achieved SVR. Factors associated with better treatment outcomes included younger age (90.7% in the 31–45 age group), gender (89.5% of male), normal BMI (91.2% of those with a BMI of 18.5–24.9), and the favorable IL28B polymorphism CC genotype (91.8%). Low baseline viral load was observed in 60.1% of patients, and those with genotype 3 had better SVR rates. Conclusions: It was concluded that younger age, male gender, normal BMI, favorable IL28B polymorphism along with low baseline viral load, and genotype 3 were positively associated with achieving SVR.

Association of thrombotic microangiopathy with interferon therapy for hepatitis B: a case report

BackgroundThrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy.Case presentationWe report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient’s renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable.ConclusionsThis report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency.

A real-world observational study of drug utilization and clinical outcomes of direct-acting antivirals and interferon therapy for hepatitis C treatment in Taiwan

Objective In this study, we investigated the use of direct-acting antivirals (DAAs), medical expenses and clinical outcomes since the initiation of national health insurance coverage in Taiwan. Methods This was a retrospective observational study. We obtained claims data from Taiwan’s National Health Insurance Research Database in 2017. Patients diagnosed with hepatitis C with at least two physician visits or one hospitalization were included in the study. Cases were divided into three groups based on the treatment type: traditional treatment (interferon, INF), new drug treatment (DAA) and INF-experienced (INF followed by DAA). We compared the distributions of various cases based on individual demographic variables, hospital type and comorbidities. Trends in medical expenses by treatment type were estimated. We also analyzed clinical outcomes, including rehospitalization and liver function disorders, using a survival analysis method. Results Among patients with hepatitis C, the DAA group had a significantly higher proportion of females, a higher mean age and greater disease severity than the INF group. The growth rate of medical expenses was significantly lower in the DAA group. In addition, compared to the INF group, the DAA group and INF-experienced group had significantly lower rehospitalization rates, and the DAA group had a significantly lower risk of liver function disorders. Furthermore, the longer a patient received any form of treatment, the lower was their chance of rehospitalization and liver function disorders. Conclusions In conclusion, our results confirmed that insurance coverage of DAAs led to better clinical outcomes than INF, and this may reduce increases in medical expenses and the risks of rehospitalization and liver function disorders. What is known on this topic Interferon for hepatitis C has low efficacy with serious side effects, while the efficacy of new oral drugs (direct-acting antivirals, DAAs) is high. DAAs were approved for listing in Taiwan in December 2013, and they have been covered by National Health Insurance since January 2017. Little is known about DAA-related real-world evidence following the coverage of DAAs in Taiwan, including drug utilization, expenditures and safety. What this study adds This study explored three important issues related to DAAs: drug utilization, medical expenses and clinical outcomes following the insurance coverage by using the National Health Insurance Database. Cases were divided into three groups based on the treatment type: traditional treatment (interferon, INF), new drug treatment (DAA) and INF-experienced (INF followed by DAA). After the adjustment of various personal and hospital factors, the DAA group and INF-experienced group had significantly lower rehospitalization rates, and the DAA group had a significantly lower risk of liver function disorders, compared to the interferon group. There was a lower chance of rehospitalization and lower liver function disorder rates with longer treatment.

Residual low HDV viraemia is associated HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis delta: Results from the HIDIT-II study.

The role of low levels of HDV-RNA during and after interferon therapy of hepatitis D is unknown. We re-analysed HDV RNA in 372 samples collected in the HIDIT-2 trial (Wedemeyer et al, Lancet Infectious Diseases 2019) with the Robogene assay (RA; Jena Analytics). Data were compared with the previously reported in-house assay (IA). We detected HDV-RNA in one-third of samples previously classified as undetectable using the highly sensitive RA. Low HDV viraemia detectable at week 48 or week 96 was associated with a high risk for post-treatment relapse, defined as HDV RNA positivity in both assays at week 120. HDV RNA relapses occurred in 10/15 (67%) patients with detectable low HDV RNA at week 48 and in 10/13 (77%) patients with low viraemia samples at week 96. In contrast, the post-treatment relapse rate was lower in patients with undetectable HDV RNA in both assays during treatment.

Predictors of sustained functional cure in hepatitis B envelope antigen‐negative patients achieving hepatitis B surface antigen seroclearance with interferon‐alpha–based therapy

Hepatitis B surface antigen (HBsAg) loss is considered a functional cure in chronic hepatitis B (CHB). However, the durability of HBsAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen (HBeAg)-negative CHB patients. In this prospective study, 176HBeAg-negative CHB patients with functional cure were enrolled for 12weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus (HBV) biomarkers and clinical biochemical indicators were evaluated every 3months; liver imaging examinations were performed every 3-6months during the 48-week follow-up. The sustained functional cure was evaluated. After the 48-week follow-up, the sustained functional cure rate was 86.63%. The cumulative rates of HBsAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment≥12weeks after HBsAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HBsAg reversion than consolidation treatment<12weeks (76.19% vs 90.00%, P=0.022 and 23.81% vs 9.23%, P=0.014, respectively). Patients with hepatitis B surface antibody (HBsAb) had higher rate of sustained functional cure than patients achieving HBsAg loss but without HBsAb (89.86% vs 73.53%, P=0.012). Consolidation treatment≥12weeks (odds ratio [OR] 16.478; 95% confidence interval [CI], 2.135-127.151; P=0.007) and high HBsAb levels (OR 8.312; 95% CI, 1.824-37.881; P=0.006) were independent predictors of sustained functional cure. Results suggested that 12weeks of consolidation therapy after HBsAg clearance and elevated HBsAb levels help to improve functional cure.

Is Interferon Therapy for Hepatitis C Infection a Treatable Risk Factor for Parkinson Disease?

Is Interferon Therapy for Hepatitis C Infection a Treatable Risk Factor for Parkinson Disease?

IL-28β gene polymorphism determines virological response to PEGylated interferon therapy in hepatitis C virus genotype 4 Egyptian patients.

PEGylated interferon (PEG-IFN) in combination with ribavirin is the gold standard for chronic hepatitis C virus (HCV). The majority of patients received PEG-IFN/ribavirin achieve a sustained viral response (SVR), but few cases failed to respond. It was evident that host genetic factors determine the treatment-induced viral clearance as well as spontaneous response. In the current study, the rs12979860 polymorphism of IL28β gene was analyzed and its association with the virological response to PEG-IFNtreatment was determined. One hundred and fifty Egyptian patients with HCV genotype 4 treated with PEG-IFN/ribavirin were assessed at 12 and 24 weeks of therapy, the rs12979860 genotype was determined using TaqMan-based quantitative polymerase chain reaction. Although the CC genotype was the most frequent (58%), the higher SVR was achieved for patients with favorable CC genotype (93%) in contrast to CT and TT genotypes. we conclude that IL28B polymorphism is highly associated with SVR to therapy in the Egyptian population infected with HCV genotype 4 and patients who carry CC genotype have a higher chance of SVR.

Successful renal transplantation to a recipient with type II cryoglobulinemia: a case report

BackgroundRecurrence of glomerulonephritis is an important risk factor for renal graft dysfunction. Cryoglobulinemia is known as a relatively rare cause of renal failure, and doctors are usually hesitant to perform transplantation on a recipient with cryoglobulinemia because of the risk for graft loss. We present a case of renal transplantation on a patient with organ manifestations of type II cryoglobulinemia.Case presentationAt the age of 44 years, the patient developed acute kidney injury and purpura on the lower extremities with type II cryoglobulinemia after interferon therapy for hepatitis C virus. Cryoglobulinemic glomerulonephritis was suspected; however, despite immunosuppressive therapy combined with plasmapheresis, she eventually needed hemodialysis treatment. She was referred to us at the age of 49 years for renal transplantation. Cryocrit was 14% and the organ manifestations persisted, including the lower extremity purpura and neurologic symptoms. After monitoring and confirming sufficient suppression of cryoglobulin concentration by immunosuppressive treatment with prednisolone, cyclophosphamide, and rituximab combined with plasmapheresis, the operation was performed. After transplantation, the cryoglobulin concentration was continuously monitored, and plasmapheresis and rituximab infusion were performed as appropriate. Her graft function has remained stable for 2 years and 6 months.ConclusionOur case suggested that a patient with cryoglobulinemia and persistent organ manifestations can receive a renal graft if the cryoglobulin concentration is sufficiently controlled by pretransplant treatment.

Epstein–Barr virus and Interleukin-28B polymorphism in the prediction of response to interferon therapy in hepatitis C patients

Background and study aimsIn chronic hepatitis C virus (HCV), viral and host factors are known to be predictors for anti-viral therapy. IL-28B genotype strongly influences treatment outcome, while Epstein–Barr virus (EBV) co-infection could accelerate the course of chronic HCV infection. This study was conducted to assess whether EBV co-infection adds to the predictive value of IL-28B. Patients and methodsA total of 105 patients with chronic HCV were classified according to their response to treatment into two groups: 38 sustained virological responders (SVRs) and 67 nonresponders (NRs). Collected sera at baseline and follow-up (FUP) were used for assessing EBV antibodies by enzyme-linked immunosorbent assay (ELISA) and the expression of EBV genes (BNLF-1, BZLF-1, and EBER-2) by polymerase chain reaction (PCR). Collected peripheral blood was used for detecting IL-28B rs.12979860 single-nucleotide polymorphism. ResultsRegarding IL-28B genotype frequencies, a significant difference (p=0.003) was observed between SVRs (C/C=51.4%, C/T=48.6%, T/T=0%) and NRs (C/C=25%, C/T=55%, T/T=20%). On assessing EBV infection at baseline and FUP, it was found that 61% and 55% were positive, respectively, with no significant difference between SVRs and NRs. As for anti-viral capsid antigen (VCA) antibodies, the NRs had significantly higher baseline anti-VCA immunoglobulin M (IgM) levels than SVRs (p=0.01). While FUP anti-Epstein–Barr nuclear antigen-1 (EBNA-1) IgG reported a significant decline within SVR patients (p=0.02), neither baseline nor FUP anti-VCA IgG levels showed a statistically significant viral response. Finally, on comparing EBV markers with CC versus CT and TT genotypes, it was found that FUP anti-VCA IgG levels were significantly increased in CC genotype (p=0.003). ConclusionInterleukin-28B polymorphism could be a possible predictor of response to pegylated interferon/ribavirin therapy (PEG-IFN/RBV). Furthermore, co-infection with EBV did not affect the response to IFN-based therapy in HCV-infected patients.

Interferon therapy in hepatitis C leading to chronic type 1 diabetes.

To review the prevalence, clinical data and course of interferon- associated type 1 diabetes in chronic hepatitis C virus (HCV) infection. Search of all interferon (INF)-related type 1 diabetes mellitus (T1DM) cases published in the English literature from 1992 to December 2013 according to the key words: chronic hepatitis C infection, diabetes mellitus type 1, insulin dependent diabetes mellitus, and interferon treatment. We found 107 cases and analyzed their clinical and laboratory data and long-term follow-up. Due to the predominance of cases described in Japanese literature, we analyzed separately cases of Caucasian and Japanese origin. In addition we describe a representative case with HCV who developed INF-related T1DM. Our data show that INF treatment increases the risk of developing T1DM by 10-18 fold compared with the corresponding general population and the median age of onset was 43 years (range: 24-66 years) in Caucasians and 52 years (range: 45-63 years) in Japanese. Most patients developed T1DM during INF treatment, after a median time-period of 4.2 and 5.7 mo in Caucasian and Japanese groups, respectively. The clinical course was characterized by a fulminant course with abrupt severe hyperglycemia or ketoacidosis, a high titer of anti-islet autoantibodies and almost all patients (105/107) permanently required insulin therapy with a follow-up of up to 4 years. A substantial number of patients had evidence for other autoimmune disorders mainly thyroid diseases (25% and 31% in Caucasian and Japanese groups, respectively). INF-associated T1DM in HCV has a fulminant course, often associated with other autoimmune diseases, and results almost inevitably in permanent insulin therapy requirement.

Relationship between hepatitis B virus genotype B and C and response to interferon therapy in HBeAg positive chronic hepatitis B patients: A meta‐analysis

Previous studies examining the relationship between hepatitis B virus (HBV) genotype B and C and response to interferon therapy in Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients have yielded conflicting results. We aim to summarize data to reach firm conclusions on the role of HBV genotype B and C in response to interferon therapy. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant articles published up to March 2013. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by fixed- or random-effects models. Heterogeneity, sensitivity analysis, and publication bias were also assessed. Fifteen studies were identified. All studies except for those evaluating the rate of end-of-treatment HBeAg seroconversion exhibited significant heterogeneity. There were significant differences in rates of end-of-treatment alanine aminotransferase (ALT) normalization, HBV DNA negative, and HBeAg seroconversion between the genotype B and genotype C groups, but not in HBeAg clearance. The pooled results showed higher rates of sustained ALT normalization (OR = 2.24, 95%CI 1.53-3.27), HBV DNA negative (OR = 2.60, 95%CI 1.65-4.12), HBeAg clearance (OR = 2.13, 95%CI 1.29-3.52) and HBeAg seroconversion (OR = 1.95, 95%CI 1.27-2.98) in patients with genotype B than those with genotype C. The sensitivity analysis did not alter the effects observed in the primary analysis. There was no evidence of publication bias except for HBeAg clearance rate. The results of the current meta-analysis indicate that HBV genotype B patients receiving interferon therapy respond better to treatment compared with genotype C patients, but this needs to be further examined.

Role of a 48-week pegylated interferon therapy in hepatitis B e antigen positive HIV-co-infected patients on cART including tenofovir: EMVIPEG study

In hepatitis B e antigen (HBeAg) positive-HIV co-infected patients treated with combined antiretroviral therapy (cART), including tenofovir disoproxil fumarate (TDF), the rate of HBe seroconversion remains low. Whether adding pegylated interferon alfa (PegIFN) could increase the likelihood of HBeAg loss and HBe seroconversion has not been assessed. A 48-week PegIFN therapy was added to HBeAg positive-HIV co-infected patients on TDF and emtricitabine, or lamivudine for at least 6 months. The primary endpoint was HBV sustained response: HBe seroconversion with undetectable HBV DNA levels 24 weeks after completing PegIFN therapy (W72). Fifty-one patients (49 men, median age 46 years, range: 32-65), were included. Median duration of HIV, HBV infections and TDF therapy was 10.3 (0.6-22), 9.8 (0.5-16), and 3.3 (0.5-6.8)years, respectively. Median baseline CD4 count was 506 (175-1316)/mm(3). HIV viral load was <50 copies/ml in 49 (96%) patients. Nine (18%) patients stopped PegIFN prematurely. Ten (20%) patients experienced HBeAg loss at W72 and four (8%) patients had a HBV sustained response. No HBs seroconversion was observed. Only patients with more than 350 CD4/mm(3) at baseline achieved HBe loss. HBeAg level >10 PEIU/ml at W12 or a quantitative HBsAg decline <0.5 log IU/ml at W24 had 100% and 84% negative predictive values for response, respectively. 48-week PegIFN additional therapy to cART including TDF did not significantly increase the HBe seroconversion rate, despite an HBeAg loss in 20% of the patients. HBe and HBs kinetics may nevertheless be of help in tailoring and optimising this strategy.

Letter: do interferon lambda 3 polymorphisms predict the outcome of interferon therapy in hepatitis B infection? Authors' reply

1. Galmozzi E, Vigano M, Lampertico P. Systematic review with meta-analysis: do interferon lambda 3 polymorphisms predict the outcome of interferon-therapy in hepatitis B infection? Aliment Pharmacol Ther. 2014. Aliment Pharmacol Ther 2014; 39: 569–78. 2. Sonneveld MJ, Wong VW, Woltman AM, et al. Polymorphisms near IL28B and serologic response to peginterferon in HBeAgpositive patients with chronic hepatitis B. Gastroenterology 2012; 142: 513–20. 3. Wu X, Xin Z, Zhu X, et al. Evaluation of susceptibility locus for response to interferon-alpha based therapy in chronic hepatitis B patients in Chinese. Antiviral Res 2012; 93: 297–300. 4. Holmes JA, Nguyen T, Ratnam D, et al. IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-alpha. J Gastroenterol Hepatol 2013; 28: 861–6. 5. Lampertico P, Vigano M, Cheroni C, et al. IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigennegative patients with chronic hepatitis B. Hepatology 2013; 57: 890–6. 6. Mangia A., Santoro R., Mottola L., et al. Lack of association between IL28B variants and HBsAg clearance after interferon treatment. J Hepatol 2011; 54(S1): S525. 7. Papatheodoridis GV, Gatselis N., Goulis I, et al. IL-28B polymorphisms as predictors of response to peginterferon-alfa2a in HBeAg-negative chronic hepatitis B. Hepatology 2013; 58S: 686A [A993]. 8. Hadziyannis E, Laras A, Panopoulou E, et al. The IL28B polymorphism does not correlate with treatment-induced and spontaneous outcomes in chronic hepatitis B. Hepatology 2013; 58S: 633A [A897]. 9. Wei L, Wedemeyer H, Liaw YF, et al. No association between IL28B genotype and response to peginterferon alfa-2a (40KD) in HBe antigen-positive and HBe antigen-negative patients with chronic hepatitis B from three large randomized clinical studies. Hepatology 2013; 58S: 647A [A924].

EPA-0908 – Successful treatment with interferon therapy of hepatitis c positive opiate addicts who are in substitution maintenance therapy with buprenorphine/naloxone (suboxone®)

Hepatitis C is highly infected disease with long period of failure to recognize it, what leads to chronic liver damage and lower chances for complete cure if detected late. Intravenous (IV) opiate users are not aware when be infected from virus carriers using the same non-sterile equipment so they pass the infection to other IV drug users. By implementation of substitution treatment of opiate addicts with Buprenorphine/Naloxone (Suboxone) at the Department of Psychiatry in Tuzla on 27 July 2009 year, we made the obligatory serological tests for hepatitis B and C and HIV, as well as laboratory findings with liver function parameter analysis as a condition for starting substitution therapy. In this way we discovered 50/195 opiate addicts hepatitis C positive. Although faced with danger of the final result if not treated in time, addicts when became aware that they were hepatitis C positive, they avoid further needed procedures leading to the inclusion of specific therapy with pegylated interferon. In this paper, the authors presented the procedure of multidisciplinary approach of treatment of hepatitis C positive opiate addicts despite their resistances they do not occur on the continuation of the procedure detecting HCV genotypes, and the inclusion of specific therapy for the treatment of hepatitis C in the clinics for infectious or internal diseases. At the end, the authors present eleven clinical vignettes of successful treatment of hepatitis C in opiate addicts realized with multidisciplinary team. All of the treated individuals, after finished interferon treatment appeared hepatitis C negative.

C型肝炎IFN著効後に診断された肝細胞癌と胆管細胞癌の同時性重複癌の1例

C型肝炎IFN著効後に診断された肝細胞癌と胆管細胞癌の同時性重複癌の1例

Management of Depression Induced by Interferon Hepatitis Therapies

Treatment with interferon therapy for hepatitis can induce depression and/or recurrence of affective illness, which could result in cessation of interferon treatment. This article reviews treatment for interferon-induced depression, including antidepressant drugs that may diminish associated symptoms. English-language literature with no date restrictions on the treatment of interferon-induced depression was reviewed via PubMed and MEDLINE using the key words hepatitis, interferon, hepatitis C, interferon-induced depression, pharmacotherapy of interferon-induced depression, and depression prevention. Fourteen of the most pertinent references are cited. Escitalopram is the most prominently noted pharmaceutical prescribed for treating mood symptoms in hepatitis patients with interferon-induced depression. Other antidepressant medicines may have utility as well. Antidepressant drugs can be efficacious in diminishing mood disorders during hepatitis therapies. It remains controversial as to whether antidepressant medications can provide prophylaxis against newly developing interferon-induced depressions in individuals with no past history of a mood disorder. Antidepressant medicines can be effective at improving mood in patients undergoing interferon treatment for hepatitis.

Antiviral therapy after curative treatment of hepatitis B/C virus‐related hepatocellular carcinoma: A systematic review of randomized trials

Available published work on the benefit of adjuvant antiviral therapy after curative treatment of hepatocellular carcinoma (HCC) reports controversial results. The objective of this systematic review was to evaluate the effect of adjuvant antiviral therapy on recurrence and survival after curative treatment of HCC. We conducted an extensive search strategy. All randomized controlled trials comparing adjuvant antiviral therapy versus placebo or no treatment were considered for this review. Results were expressed as hazard ratio for time-to-event outcomes with 95% confidence intervals using RevMan 5. We included nine trials (three of low risk of bias and six of unclear risk of bias) with 954 patients. All the included studies used conventional interferon (IFN) as adjuvant antiviral therapy; none of them used pegylated IFN or nucleoside analogs. There were significant improvements for recurrence-free survival and overall survival in the adjuvant IFN group compared with the control group. Subgroup analysis also showed a significant difference favoring IFN therapy in hepatitis C virus (HCV)-related HCC patients, but for hepatitis B virus (HBV)-related patients, the difference failed to reach statistical significance. A dose reduction was needed in 28.3% of patients and discontinuation of IFN therapy happened in 8.2% of patients due to moderate to severe side-effects. Our study suggested potential benefits of adjuvant IFN therapy following curative treatment of HCC, especially for HCV-related HCC. Further high-quality randomized controlled trials of more effective adjuvant antiviral regimens, either used alone or in combination, for virus-related HCC, especially HBV-related HCC, are needed.

English

OBJECTIVE: To determine the frequency of hyperthyroidism in patients presenting with generalized anxiety disorder. MATERIAL AND METHODS: This prospective analytical study was carried out on 150 patients presenting with Generalized Anxiety disorder following the criteria of DSM-IV-TR presenting to the Medical OPD of Sri Aurobindo Institute of Medical Sciences, Indore (M.P) from Jan 2011 to Nov 2012 with symptoms of anxiety, worry, palpitations, sweating, tremors, anorexia, hot flushes, restlessness, difficulty in concentrating and weight loss and those experiencing periods of intense fear were enrolled. All those patients who had been diagnosed or were being treated for thyroid disease or had undergone thyroid surgery or radioablation of thyroid gland were excluded. In addition patients who had anxiety with concomitant medical disease as tuberculosis, hepatitis, diabetes or hypertension etc and those on anti-arrhythmic drug amiodarone and interferon therapy for hepatitis were also excluded from the study. After a detailed history and clinical examination, thyroid function tests, E.C.G was performed in all patients and those found thyrotoxic were subjected to thyroid scan and Thyroid Peroxidase antibodies (TPOAb) test to know cause of thyrotoxicosis. Results: Out of 150 patients, 108 (72%) were females and 42 (28%) were males. They were between 18 to 48 years of age. Mean age was 28.5 ± 4.2 years. Out of 150 patients, 19 patients (12.7%) were found to have elevated total and unbound thyroid hormone and low thyroid stimulating hormone levels and the rest 131 (87.3%) patients had normal thyroid function test. All of 19 thyrotoxic patients (15 females and 4 males) in thyroid scan showed increased tracer uptake. Out of 19 thyrotoxic patients six had Graves' disease, ten had toxic multinodular goiter and three had toxic thyroid adenoma. CONCLUSION: Thyrotoxicosis is a common cause of generalized anxiety, patients are misdiagnosed and are being treated with anxiolytics and antidepressants, so it is very important for the physician to explore fully and give early the tests for thyroid dysfunction if required, which today are relatively simple before the diagnosis of anxiety is made and treatment started.

Ischemic Colitis During Type I Interferon Therapy for Hepatitis C and Multiple Sclerosis

Ischemic Colitis During Type I Interferon Therapy for Hepatitis C and Multiple Sclerosis

Rapidly Generated Multivirus-specific Cytotoxic T Lymphocytes for the Prophylaxis and Treatment of Viral Infections

Severe and fatal viral infections remain common after hematopoietic stem cell transplantation. Adoptive transfer of cytotoxic T lymphocytes (CTLs) specific for Epstein–Barr virus (EBV), cytomegalovirus (CMV), and adenoviral antigens can treat infections that are impervious to conventional therapies, but broader implementation and extension to additional viruses is limited by competition between virus-derived antigens and time-consuming and laborious manufacturing procedures. We now describe a system that rapidly generates a single preparation of polyclonal (CD4+ and CD8+) CTLs that is consistently specific for 15 immunodominant and subdominant antigens derived from 7 viruses (EBV, CMV, Adenovirus (Adv), BK, human herpes virus (HHV)-6, respiratory syncytial virus (RSV), and Influenza) that commonly cause post-transplant morbidity and mortality. CTLs can be rapidly produced (10 days) by a single stimulation of donor peripheral blood mononuclear cells (PBMCs) with a peptide mixture spanning the target antigens in the presence of the potent prosurvival cytokines interleukin-4 (IL4) and IL7. This approach reduces the impact of antigenic competition with a consequent increase in the antigenic repertoire and frequency of virus-specific T cells. Our approach can be readily introduced into clinical practice and should be a cost-effective alternative to common antiviral prophylactic agents for allogeneic hematopoietic stem cell transplant (HSCT) recipients.