Thyroid diseases associated with interferon α treatment for viral hepatitis

There are many complications during the interferon alpha (IFNα) treatment for viral hep-atitis,and thyroid disease is the most common side-effect in endocrine aspects. Thus, clinicians are drawing much attention to the interferon induced thyroiditis (IIT). Though the etiology is not clear,some factors may contribute to the susceptibility to IIT, such as genetic predisposition, gender,and hepatitis C virus (HCV) in-fection. The pathogenesis may be secondary to immune modulation by IFNα and/or by its direct effects on the thyroid. Autoimmune IIT may manifest as Graves' disease, Hashimoto's thyroiditis and the development of thyroid antibodies without clinical symptoms. Non-autoimmune IIT can manifest as destructive thyroiditis or hypothyroidism with negative thyroid antibodies. Screening for autoantibodies and serum thyroid-stimulating hormone(TSH)is recommended before, during and after IFNα treatment. Early detection and therapy of these conditions is important.     

Thyroid diseases associated with interferon α treatment for viral hepatitis

There are many complications during the interferon alpha (IFNα) treatment for viral hep-atitis,and thyroid disease is the most common side-effect in endocrine aspects. Thus, clinicians are drawing much attention to the interferon induced thyroiditis (IIT). Though the etiology is not clear,some factors may contribute to the susceptibility to IIT, such as genetic predisposition, gender,and hepatitis C virus (HCV) in-fection. The pathogenesis may be secondary to immune modulation by IFNα and/or by its direct effects on the thyroid. Autoimmune IIT may manifest as Graves' disease, Hashimoto's thyroiditis and the development of thyroid antibodies without clinical symptoms. Non-autoimmune IIT can manifest as destructive thyroiditis or hypothyroidism with negative thyroid antibodies. Screening for autoantibodies and serum thyroid-stimulating hormone(TSH)is recommended before, during and after IFNα treatment. Early detection and therapy of these conditions is important.     

Thyroid diseases associated with interferon α treatment for viral hepatitis

There are many complications during the interferon alpha (IFNα) treatment for viral hep-atitis,and thyroid disease is the most common side-effect in endocrine aspects. Thus, clinicians are drawing much attention to the interferon induced thyroiditis (IIT). Though the etiology is not clear,some factors may contribute to the susceptibility to IIT, such as genetic predisposition, gender,and hepatitis C virus (HCV) in-fection. The pathogenesis may be secondary to immune modulation by IFNα and/or by its direct effects on the thyroid. Autoimmune IIT may manifest as Graves' disease, Hashimoto's thyroiditis and the development of thyroid antibodies without clinical symptoms. Non-autoimmune IIT can manifest as destructive thyroiditis or hypothyroidism with negative thyroid antibodies. Screening for autoantibodies and serum thyroid-stimulating hormone(TSH)is recommended before, during and after IFNα treatment. Early detection and therapy of these conditions is important.     

Thyroid diseases associated with interferon α treatment for viral hepatitis

There are many complications during the interferon alpha (IFNα) treatment for viral hep-atitis,and thyroid disease is the most common side-effect in endocrine aspects. Thus, clinicians are drawing much attention to the interferon induced thyroiditis (IIT). Though the etiology is not clear,some factors may contribute to the susceptibility to IIT, such as genetic predisposition, gender,and hepatitis C virus (HCV) in-fection. The pathogenesis may be secondary to immune modulation by IFNα and/or by its direct effects on the thyroid. Autoimmune IIT may manifest as Graves' disease, Hashimoto's thyroiditis and the development of thyroid antibodies without clinical symptoms. Non-autoimmune IIT can manifest as destructive thyroiditis or hypothyroidism with negative thyroid antibodies. Screening for autoantibodies and serum thyroid-stimulating hormone(TSH)is recommended before, during and after IFNα treatment. Early detection and therapy of these conditions is important.     

Thyroid diseases associated with interferon α treatment for viral hepatitis

There are many complications during the interferon alpha (IFNα) treatment for viral hep-atitis,and thyroid disease is the most common side-effect in endocrine aspects. Thus, clinicians are drawing much attention to the interferon induced thyroiditis (IIT). Though the etiology is not clear,some factors may contribute to the susceptibility to IIT, such as genetic predisposition, gender,and hepatitis C virus (HCV) in-fection. The pathogenesis may be secondary to immune modulation by IFNα and/or by its direct effects on the thyroid. Autoimmune IIT may manifest as Graves' disease, Hashimoto's thyroiditis and the development of thyroid antibodies without clinical symptoms. Non-autoimmune IIT can manifest as destructive thyroiditis or hypothyroidism with negative thyroid antibodies. Screening for autoantibodies and serum thyroid-stimulating hormone(TSH)is recommended before, during and after IFNα treatment. Early detection and therapy of these conditions is important.     

Thyroid diseases associated with interferon α treatment for viral hepatitis

There are many complications during the interferon alpha (IFNα) treatment for viral hep-atitis,and thyroid disease is the most common side-effect in endocrine aspects. Thus, clinicians are drawing much attention to the interferon induced thyroiditis (IIT). Though the etiology is not clear,some factors may contribute to the susceptibility to IIT, such as genetic predisposition, gender,and hepatitis C virus (HCV) in-fection. The pathogenesis may be secondary to immune modulation by IFNα and/or by its direct effects on the thyroid. Autoimmune IIT may manifest as Graves' disease, Hashimoto's thyroiditis and the development of thyroid antibodies without clinical symptoms. Non-autoimmune IIT can manifest as destructive thyroiditis or hypothyroidism with negative thyroid antibodies. Screening for autoantibodies and serum thyroid-stimulating hormone(TSH)is recommended before, during and after IFNα treatment. Early detection and therapy of these conditions is important.     

Thyroid diseases associated with interferon α treatment for viral hepatitis

There are many complications during the interferon alpha (IFNα) treatment for viral hep-atitis,and thyroid disease is the most common side-effect in endocrine aspects. Thus, clinicians are drawing much attention to the interferon induced thyroiditis (IIT). Though the etiology is not clear,some factors may contribute to the susceptibility to IIT, such as genetic predisposition, gender,and hepatitis C virus (HCV) in-fection. The pathogenesis may be secondary to immune modulation by IFNα and/or by its direct effects on the thyroid. Autoimmune IIT may manifest as Graves' disease, Hashimoto's thyroiditis and the development of thyroid antibodies without clinical symptoms. Non-autoimmune IIT can manifest as destructive thyroiditis or hypothyroidism with negative thyroid antibodies. Screening for autoantibodies and serum thyroid-stimulating hormone(TSH)is recommended before, during and after IFNα treatment. Early detection and therapy of these conditions is important.     

Thyroid diseases associated with interferon α treatment for viral hepatitis

There are many complications during the interferon alpha (IFNα) treatment for viral hep-atitis,and thyroid disease is the most common side-effect in endocrine aspects. Thus, clinicians are drawing much attention to the interferon induced thyroiditis (IIT). Though the etiology is not clear,some factors may contribute to the susceptibility to IIT, such as genetic predisposition, gender,and hepatitis C virus (HCV) in-fection. The pathogenesis may be secondary to immune modulation by IFNα and/or by its direct effects on the thyroid. Autoimmune IIT may manifest as Graves' disease, Hashimoto's thyroiditis and the development of thyroid antibodies without clinical symptoms. Non-autoimmune IIT can manifest as destructive thyroiditis or hypothyroidism with negative thyroid antibodies. Screening for autoantibodies and serum thyroid-stimulating hormone(TSH)is recommended before, during and after IFNα treatment. Early detection and therapy of these conditions is important.     

Safety of interferon β treatment for chronic HCV hepatitis

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicat einfection and prevent progression of the disease. The treatment has evolved from the use of m-interferon (IFNα) alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjectsare not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety ofIFNβ treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported.A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-lb HCV hepatitis unresponsive to IFNα treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNβ and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.     

Hepatitis C infection in hemodialysis patients: A review

Hepatitis C virus(HCV)-related liver disease is a significant cause of morbidity and mortality in patients with end-stage renal disease(ESRD) who is treated with dialysis or kidney transplantation(KT). The survival rate for HCV-infected renal transplant recipients is better than that for HCV-infected hemodialysis patients on transplant waiting lists. Early diagnosis and treatment HCV infection prior to KT prevents complications posttransplantation and reduces mortality. In addition to screening for anti-HCV antibodies and detecting HCV RNA, percutaneous liver biopsy is particularly valuable for assessing the stage of liver damage in HCV-infected patients, because the stage of fibrosis is importantdetermining optimal treatment for HCV. Studies have been demonstrated that with conventional interferon(IFN) monotherapy or pegylated IFN monotherapy are similar efficacy and safety in HCV-infected hemodialysis patients. Sustained viral responses(SVRs) with these monotherapies have ranged approximately 30% to 40%. Limited reports support the use of IFN and ribavirin combination therapy as antiviral treatment for ESRD patients or patients on hemodialysis. Ribavirin can be started at low dose and careful monitoring for side effects. Patients that show SVR after treatment are strong candidates for KT. It is also generally accepted that ESRD patients with decompensated cirrhosis and portal hypertension should be referred to the liver transplant team for consideration of combined liver-KT.     

Effects of antiviral therapy on preventing liver tumorigenesis and hepatocellular carcinoma recurrence

Chronic hepatitis B virus(HBV)infection is the key driving force of liver disease progression,resulting in the development of hepatic dysfunction,cirrhosis and hepatocellular carcinoma(HCC).The primary aim of therapy is to suppress or eliminate HBV replication to reduce the activity of hepatitis,thus reducing the risk of,or slowing the progression of,liver disease.Nucleos(t)ide analogues(Nucs)may result in rapid suppression of HBV replication with normalization of serum transaminases and restore liver function,thus increasing survival in patients with hepatic decompensation.Long-term Nuc therapy may result in histological improvement or reversal of advanced fibrosis and reduction in disease progression,including the development of HCC.The long-term benefits of a finite course of interferon(IFN)-αtherapy also include a sustained and cumulative response,as well as hepatitis B surface antigen seroclearance and reduction in the development of cirrhosis and/or HCC.Pegylated IFN and newer Nucs may achieve better long-term outcomes because of improved efficacy and a low risk of drug resistance.However,treatment outcomes are still far from satisfactory.Understanding the effects of anti-HBV treatment against HCC incidence and recurrence after hepatectomy or liver transplantation is required for further improvement of outcome.     

Hepatocellular carcinoma occurrence in DAA-treated hepatitis C virus patients: Correlated or incidental? A brief review

Hepatitis C virus(HCV) chronic infection induces liver fibrosis and cirrhosis but is also responsible for a significant portion of hepatocellular carcinoma(HCC) occurrence. Since it was recognized as a causative factor of chronic hepatitis,there have been multiple efforts towards viral eradication,leading to the first-generation HCV treatment that was based on interferon(IFN)-α and its analogs,mainly PEGylated interferon-α(PEG IFNα). Sustained virological response(SVR),defined as the absence of detectable RNA of HCV in blood serum for at least 24 wk after discontinuing the treatment,was accepted as a marker of viral clearance and was achieved in approximately one-half of patients treated with PEG IFNα regimens. Further research on the molecular biology of HCV gave rise to a new generation of drugs,the so-called direct antiviral agents(DAAs). DAA regimens,as implied by their name,interfere with the HCV genome or its products and have high SVR rates,over 90%,after just 12 wk of per os treatment. Although there are no questions about their efficacy or their universality,as they lack the contraindication for advanced liver disease that marks PEG IFNα,some reports of undesired oncologic outcomes after DAA treatment raised suspicions about possible interference of this treatment in HCC development. The purpose of the present review is to investigate the validity of these concerns based on recent clinical studies,summarize the mechanisms of action of DAAs and survey the updated data on HCV-induced liver carcinogenesis.     

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults

Inflammatory bowel diseases(IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease(CD) and ulcerative colitis(UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria(microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroidfree long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered(oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease(CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems(Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8~+ T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.     

Systemic lupus erythematosus following virological response to peginterferon alfa-2b in a transplanted patient with chronic hepatitis C recurrence

Autoimmune manifestations are common both in patients chronically infected by hepatitis C virus, and in patients transplanted for non-autoimmune diseases. A correlation between interferon based treatment and autoimmune diseases or the development of autoantibodies is well established in non-transplanted patients, but few data are available about transplanted patients. It is unclear whether interferon may increase the incidence of acute cellular rejection and there are few reports on the development of atypical autoimmune manifestations during post-liver transplantation interferon or pegylated interferon treatment. We describe a case of systemic lupus erythematosus following treatment with pegylated interferon alfa-2b in a transplanted patient with recurrence of chronic hepatitis C. Our experience suggest that pegylated interferon may induce autoimmune diseases in the immunosuppressed host, different from acute cellular rejection and call for a great attention to possible autoimmune disorders development during interferon based treatments in liver transplanted patients.     

Safety of interferon β treatment for chronic HCV hepatitis

Hepatitis C is a major cause of liver-related morbidity andmortality worldwide.In fact,chronic hepatitis C is consideredas one of the primary causes of chronic liver disease,drrhosisand hepatocellular carcinoma,and is the most commonreason for liver transplantation.The primary objectives forthe treatment of HCV-related chronic hepatitis is to eradicateinfection and prevent progression of the disease.Thetreatment has evolved from the use of α-interferon (IFNα)alone to the combination of IFNα plus ribavirin,with asignificant improvement in the overall efficacy,and to thenewer PEG-IFNs which have further increased the virologicalresponse,used either alone or in combination with dbavirin.Despite these positive results,in terms of efficacy,concernsare related to the safety and adverse events.Many patientsmust reduce the dose of PEG-IFN or ribavirin,others muststop the treatment and a variable percentage of subjectsare not suitable owing to intolerance toward drugs.IFNβrepresents a potential therapeutic alternative for thetreatment of chronic viral hepatitis and in some countries itplays an important role in therapeutic protocols.Aim of thepresent paper was to review available data on the safety ofIFNβ treatment in HCV-related chronic hepatitis.The rates of treatment discontinuation and/or dosemodification due to the appearance of severe side effectsduring IFNβ are generally low and in several clinical studiesno requirements for treatment discontinuation and/or dosemodifications have been reported.The most frequent sideeffects experienced during IFNβ treatment are flu-likesyndromes,fever,fatigue and injection-site reactions.Nodifferences in terms of side-effect frequency and severitybetween responders and non-responders have been reported.A more recent study,performed to compare IFNβ alone or incombination with ribavirin,confirmed the good safety profileof both treatments.Similar trends of adverse event frequencyhave been observed in subpopulations such as patients withgenotype-1b HCV hepatitis unresponsive to IFNα treatmentor with HCV-related cirrhosis and patients with acute viralhepatitis.If further studies will confirm the efficacy of combinedIFNβ and ribavirin treatment,this regimen could represent asafe and alternative therapeutic option in selected patients.     

Cardiovascular involvement in inflammatory bowel disease: dangerous liaisons

Increasing evidence of a link between inflammatory bowel disease(IBD) and adverse cardiovascular events has emerged during the last decade.In 2014,an important number of meta-analyses and cohort studies clarified the subtle dangerous liaisons between gut inflammation and cardiovascular pathology.The evidence suggests that patients with IBD have a significantly increased risk of myocardial infarction,stroke,and cardiovascular mortality,especially during periods of IBD activity.Some populations(e.g.,women,young patients) may have an even greater risk.Current effective treatment of IBD is aimed at disease remission and seems to reduce cardiovascular risk in these patients.A beneficial effect was demonstrated for salicylates,but not for steroids or azathioprine.tumor necrosis factor-α antagonists,which are highly effective in the reduction of inflammation and in the restoration of the digestive mucosa,lead to conflicting cardiovascular effects,as they seem to reduce the risk for ischemic heart disease but increase the rate of cerebrovascular events.Future supplemental treatment strategies that may reduce the atherothrombotic risk during periods of IBD activity should be explored.     

Clinical impact of immunomonitoring in the treatment of inflammatory bowel disease

Despite improvement in outcomes, loss of response(LOR) to tumor necrosis factor-alpha (TNFα) therapies is a big concern in the management of inflammatory bowel disease. LOR is associated with flares of disease, increased hospitalisation rates, need for surgical interventions, and decline in quality of life. LOR may be multifactorial, but immunogenicity makes a significant contribution. Traditionally doses of anti-TNFα have been adjusted based on clinical response, using a standard approach. Immunomonitoring involves the measurement of anti-TNFα trough and antibody levels. It takes into account the underlying pharmacokinetics of anti-TNFα therapies. Expanding on this a treat to target approach may be used, where doses are intensified, or tailored to the individual based on the measurement of anti-TNFα trough and antibody levels. This review looks at the history, evolution, and clinical impact that immunomonitoring is having in the treatment of inflammatory bowel disease. It will focus on the role of immunomonitoring in helping to achieve long lasting deep remission and mucosal healing. It will explore the different options in terms of best measuring trough and antibody levels, explore possible advantages of immunomonitoring, and discuss its role in best optimising response, at induction, during the maintenance phase of treatment, as well as a role in withdrawing or switching therapy.     

New serological markers in pediatric patients with inflammatory bowel disease

The spectrum of serological markers associated with inflammatory bowel disease(IBD)is rapidly growing.Due to frequently delayed or missed diagnoses,the application of non-invasive diagnostic tests for IBD,as well as differentiation between ulcerative colitis(UC)and Crohn’s disease(CD),would be useful in the pediatric population.In addition,the combination of pancreatic autoantibodies and antibodies against Saccharomyces cerevisiae antibodies/perinuclear cytoplasmic antibody(pANCA)improved the sensitivity of serological markers in pediatric patients with CD and UC.Some studies suggested that age-associated differences in the patterns of antibodies may be present,particularly in the youngest children.In CD,most patients develop stricturing or perforating complications,and a significant numberof patients undergo surgery during the disease course.Based on recent knowledge,serum antibodies are qualitatively and quantitatively associated with complicated CD behavior and CD-related surgery.Pediatric UC is characterized by extensive colitis and a high rate of colectomy.In patients with UC,high levels of antiCBir1 and pANCA are associated with the development of pouchitis after ileal pouch-anal anastomosis.Thus,serologic markers for IBD can be applied to stratify IBD patients into more homogeneous subgroups with respect to disease progression.In conclusion,identification of patients at an increased risk of rapid disease progression is of great interest,as the application of early and more aggressive pharmaceutical intervention could have the potential to alter the natural history of IBD,and reduce complications and hospitalizations.     

Hepatitis C in hemodialysis patients

Despite reduction of hepatitis C prevalence after recognition of the virus and testing of blood products, hemodialysis(HD) patients still comprise a high risk group. The natural history of hepatitis C virus(HCV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted bymilder histological features on liver biopsy. Furthermore, the "silent" clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the "beneficial" impact of uremia and hemodialysis on chronic HCV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of "hepatoprotective" cytokines such as interferon(IFN)-α and hepatocyte growth factor. However, chronic hepatitis C is associated with a higher liver disease related cardiovascular and allcause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HCV infected HD patients, though data are still lacking.     

Treatment strategy for gastric non-invasive intraepithelial neoplasia diagnosed by endoscopic biopsy

Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment.Based on the histological findings of the biopsy specimen,it is difficult to differentiate between reactive or regenerative changes,inflammation and neoplastic changes,intraepithelial and invasive tumors.Therefore,gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and highfrequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection(ESD),a therapeutic option for gastric intraepithelial neoplasia,including low-grade neoplasms.Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.