Forms Of Interferon Research Articles

Pharmacokinetics and Pharmacodynamics of Ropeginterferon Alfa-2b in Healthy Japanese and Caucasian Subjects After Single Subcutaneous Administration

Ropeginterferon alfa-2b is a novel monopegylated recombinant interferon alfa-2b for the treatment of patients with polycythemia vera. The objectives of this study were to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of ropeginterferon alfa-2b in healthy Japanese subjects compared with Caucasian subjects. In this multicenter, parallel-group phase I study, a cohort consisting of six Japanese and six Caucasian subjects was designated to receive a single subcutaneous dose of ropeginterferon alfa-2b (100, 200, 300, and 450 µg). Pharmacokinetic and pharmacodynamic parameters, and immunogenicity were evaluated. Safety was assessed throughout the study. Cohort 4 (450-µg dose) was not initiated because the primary objective of this study was achieved based on the three completed cohorts. A total of 36 enrolled subjects (18 Japanese and 18 Caucasian) in three cohorts were included in the safety, pharmacokinetic, and pharmacodynamic analysis sets. Ropeginterferon alfa-2b exposure in terms of the area under the serum concentration-time curve (AUC) from time zero extrapolated to infinity and the AUC from time zero to the time of the last quantifiable concentration was approximately 1.7-fold and two-fold higher in Japanese subjects than in Caucasian subjects, respectively. Across the same dose range, the maximum serum concentration was approximately 1.25-fold higher in Japanese subjects than in Caucasian subjects. The time to reach the median maximum serum concentration was similar between ethnicities (approximately 96-111 h). The terminal half-life was 48-57 h in Japanese subjects and 31-75 h in Caucasian subjects. The slope of the relationship between dose and drug exposure was greater than 1 in both ethnicities. The dose-dependent induction of beta-2 microglobulin and neopterin expression was observed in both ethnicities, and the two groups showed similar pharmacodynamic parameters. At the end of the study, 22.2% of Japanese subjects and 11.1% of Caucasian subjects developed anti-ropeginterferon alfa-2b-binding antibodies. The neutralizing capacity of these antibodies was not tested. Ropeginterferon alfa-2b up to 300 µg was safe and well tolerated, with no unexpected safety findings based on previous experiences with ropeginterferon alfa-2b and other forms of interferon. Ropeginterferon alfa-2b exposure was higher in Japanese subjects than in Caucasian subjects. The increase in ropeginterferon alfa-2b exposure was greater than the dose proportion in the dose range of 100-300 µg. Ropeginterferon alfa-2b was safe and well tolerated. ClinicalTrials.gov identifier NCT03546465, registered on 6 June, 2018.

A real-world single-center retrospective study on efficacy and safety of pegylated interferon alpha-2a in patients with myeloproliferative neoplasm.

e19536 Background: Pegylated forms of interferon (PEG-IFN) have a better pharmacologic profile than short-acting interferons, resulting in a more convenient less-frequent schedule of injections, less immunogenicity and possibly less toxicity. Several clinical studies of PEG-IFN-α-2a have reported promising results in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Herein, we present the outcomes of MPN patients treated with PEG-IFN-α-2a seen outside of a clinical trial setting at a single center. Methods: Thirty-five MPN Patients treated with PEG-IFN-α-2a between January 2014 and October 2019 were included this retrospective analyses. Therapeutic responses for ET and PV were calculated by the revised ELN/IWG-MRT criteria. Responses in myelofibrosis (MF) were calculated by both EUMNET and ELN/IWG-MRT criteria. Best responses over all cycles of treatment were assessed. Molecular data was limited to JAK V617F. Results: Twenty patients with ET, 13 with PV and two with MF were enrolled in this study. The median age at diagnosis was 47 years (range; 21-83 years). JAK2 V617F mutation was detected in 16 patients (45.7%). Overall, the majority of patients (62.9%) had received at least one prior cytoreductive therapy for underlying disease. Median starting dose of PEG-IFN-α-2a was 90 mcg/week via self injection (range: 45-135 mcg/w). Treatment duration was pursued for a median duration of 21.4 months (range: 1.2-109.8). In the PV/ET group 33 patients were evaluated and overall best response rate was 87.8% (CR in 15 pts and PR in 14 pts). In the MF group (n = 2); a PR was seen in one patient and CR in one patient. No vascular events occurred within the cohort while on therapy. Of the eight patients receiving at least phelebotomy per month, all patients became phelobotomy independent with therapy. Of the 20 ET patients, 12 patients (60%) had platelet normalization (< 450 x 109/L). Among all patients, fatigue (31.4%), muscle pain (20%) and depression (8.6%) were the most common adverse events (AEs). Any grade of hematological AEs was not seen with PEG-IFN-α-2a. Eleven patients discontinued therapy secondary to: treatment associated severe AEs in 8 patients, lack of response in two patients and pregnancy in one patient. No death was reported during the analyses period. Conclusions: Our results suggest that PEG-IFN-α-2a remains a viable treatment option especially for younger patients who want to avoid prolonged cytotoxic therapy.

真性红细胞增多症患者干扰素治疗中合并亚急性甲状腺炎一例报告并文献复习

目的：报道真性红细胞增多症(PV)患者干扰素α(IFNα)治疗中合并亚急性甲状腺炎1例，初步探讨该类干扰素诱导的甲状腺炎(IIT)的临床特征，加深对IFNα不良反应的认识。方法：对本例患者的临床资料进行分析，并复习相关文献。结果：本例IIT的临床特征：1) 年轻女性，治疗前甲状腺自身抗体阴性，属于非自身免疫性IIT；2) 第一次亚甲炎发生于IFNα治疗2月时，第二次发生于IFNα治疗4月时；3) IIT的发生似乎与干扰素的剂型无关；4) IIT症状有轻有重，但是可控的，多数可以完成疗程；5) 中断后重新应用IFNα治疗时可再次发生甲状腺炎。结论：IFNα治疗中可出现甲状腺炎或甲状腺功能异常的不良反应。在血液系统疾病应用IFNα治疗时应严密监测甲状腺功能和甲状腺自身抗体。根据临床症状轻重决定是否停用IFNα，多数可继续使用，若停用后再次开始治疗时一定要严密监测甲状腺功能。 Object: A case of subacute thyroiditis associated with interferon therapy of polycythemia vera is reported. To explore the clinical features of interferon induced thyroiditis and to deepen the understanding of IFNα’s side effects. Methods: The clinical data of this patient were analyzed and related literatures were reviewed. Results: 1) The patient is a young woman.IIT manifested as non-autoimmune thyroiditis without TAb’s. 2) The first course of subacute thyroiditis was diagnosed in treatment 2 months and the second course was diagnosed in treatment 4 months. 3) It seems that there’s no association between different forms of interferon and IIT. 4) The symptoms of IIT were mild or severe, but they could be controlled. Most of them can complete the course of treatment. 5) Patients frequently developed recurrent thyroiditis when re-treating with IFNα. Conclusions: One of the side-effects of IFNα therapy is thyroiditis or thyroid dysfunction. IFNα therapy of hematological diseases should undergo routine thyroid screening. IFNα therapy should be treated based on the clinical presentation. IFNα therapy can be continued in most cases. Thyroid functions should be carefully monitored if treatment is resumed.

Manufacturing Pharmaceutical-Grade Interferons Using Silkworm- Baculovirus System

To develop feline and canine interferons as medicine for companion animal, silkworm-baculovirus expression system was established as a manufacturing technology. Thus produced interferons were successfully cleared for a sale in commercial market. For expression of feline interferon in the silkworm, recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) was constructed carrying feline interferon cDNA. When the recombinant BmNPV was injected to silkworm larvae, as much as 1.2 × 10 8 unit/mL of feline interferon was produced in their hemolymph. This productivity is 100–fold higher than those of E. coli, yeast and mammalian cell expression system. Similarly, canine interferon-γ was produced in the largest amount in silkworm. Two or more forms of interferons were produced due to various processing in silkworm. For feline interferon, two forms of protein molecule resulting from two different cleavage sites in signal peptide sequence was solved by reconstitution of a single amino acid in signal sequence. In the case of canine interferon- γ, several variations were produced due to glycosylation pattern and C-terminal degradation, but removal of glycosylation sites and elimination of C-terminal 16 amino acids sequence from native sequence lead to uniformity of the expressed protein. Drug formulated two recombinant animal interferons were approved as a treatment of viral diseases and atopic dermatitis by regulatory authorities. Especially, feline interferon is now sold in 20 countries including Japan and Europe.

New approaches to optimize treatment responses in chronic hepatitis B

Substantial advances have been made in the treatment of chronic hepatitis B in the past decade. Currently, there are seven approved agents including two forms of interferon (conventional and pegylated), and five oral nucleoside/nucleotide analogues (lamivudine, adefovir, entecavir, telbivudine and tenofovir disoproxil fumarate). The availability of these multiple treatment options has led to expansion of treatment indications. However, the need for a long duration of treatment with some therapies, the high costs of HBV medications, the side effects associated with some treatments and the risks of drug resistance during long-term use of oral antiviral medications necessitate the careful assessment of the risk-benefit ratio prior to initiating treatment, and the evaluation of better strategies to optimize response once treatment is initiated. In this article, we review the current approaches to optimize treatment response to nucleoside/nucleotide analogue- and interferon-based therapies for chronic hepatitis B.

Investigational drugs for hepatitis C

Importance of the field: Hepatitis C virus (HCV) infection affects 180 million people worldwide. Standard anti-HCV therapy combines effect of pegylated IFN-alpha on immune response and antiviral activity of ribavirin. Sustained virological response rate achieved with this standard of care medication is around 50% for HCV genotype 1, the most prevalent worldwide genotype. So there is an obvious need to enhance efficacy of treatment.Areas covered in this review: We describe novel treatment options studied within the recent few years, which are focused on inhibitors of HCV-specific enzymes such as NS3/4 protease and NS5B polymerase or influence host-virus interactions.What the reader will gain: According to the most recent data, triple therapies consisted of pegylated interferons, ribavirin and protease inhibitors demonstrate significant improvement of treatment efficacy in comparison to current standard of care medication. Moreover, new forms of interferons and ribavirin, more effective, less toxic, and more convenient, become probably a fundamental component of anti-HCV therapy in the near future.Take home message: In coming years, we can expect that triple therapy becomes a standard medication, and treatment without interferon and/or ribavirin becomes a new studied therapeutic scenario.

Interferon (IFN) for malignant melanoma unmasking an autoimmune hepatitis

Autoimmune hepatitis is a disease of unknown etiology which, if left untreated, leads to progressive destruction and, eventually, liver cirrhosis and liver failure. Eighty percent of patients with autoimmune hepatitis are female. Autoimmune hepatitis may be associated with other autoimmune diseases, such as autoimmune thyroiditis, vasculitis, or rheumatoid arthritis. Typical changes in laboratory values are the elevation of total serum protein and gamma-globulin. In addition, different kinds of auto-antibodies may be detectable. Most patients with type 1 autoimmune hepatitis present with antinuclear antibodies (ANA), smooth muscle cell antibodies (SMA), and anti-neutrophil cytoplasmic antibodies with perinuclear fluorescence (p-ANCA), respectively. Type 2 autoimmune hepatitis is characterized by liver–kidney microsomal (LKM) antibodies [1]. Overlap syndromes with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and chronic hepatitis C have been described [2]. Interferon (IFN) is a cytokine produced by different cells of the immune system. IFN-α is released by monocytes. Commonly used for therapy are IFN-α 2b, consensus interferon, and pegylated forms of IFN (PEG-IFN-α 2a or 2b). IFN-β is produced by fibroblasts, while IFN-γ is released by T lymphocytes. IFN exerts immunomodulating effects by activating natural killer cells, macrophages, and cytotoxic T

C 型 肝炎ウイルスの抗ウイルス療法

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and liver cancer. Previously, the consensus strategy against HCV infection was interferon mono-therapy. Now, pegylated interferon (PEG-IFN) with ribavirin combination therapy for 24-48 weeks is used against chronic hepatitis C and can achieve a sustained viral response (SVR) in about 50% of patients with genotype 1b and high viral loads. The number of elderly Japanese patients with chronic hepatitis C has increased compared to that in western countries. The efficacy of IFN therapy for elderly patients with genotype 1 and high viral titers is lower than in young patients, because the side effects of combination therapy with PEG-IFN and ribavirin are pronounced with a reduction in blood count. To avoid discontinuation of therapy and overcome the low SVR in elderly patients, ribavirin dosing, based on the total clearance of ribavirin (CL/F), may be considered to be increasingly valuable. Approximately 25% of HCV carriers have normal ranges of serum alanine amino transferase (ALT). The rate of SVR in patients with persistently normal serum ALT (PNALT) is almost as same as that in HCV carriers, in terms of IFN therapy. This evidence suggests that patients with PNALT should be considered for IFN therapy. Novel treatment options currently in development are focused on inhibition of HCV-specific enzymes, NS3 protease and NS5B polymerase, and several drugs have entered clinical trials. Now, patients with HCV and liver cirrhosis can be given IFN therapy, except in the case of genotype 1b and high viral loads. This therapy should contribute to an improvement in the prognosis. It would appears that interferon will remain an element of anti-HCV therapy for the immediate future, although new regimens will be necessary for advanced combination therapy. It is hoped that new forms of interferon that are more effective, less toxic, and more convenient can be developed.

Viral kinetics in the treatment of chronic hepatitis C

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis, and chronic infection can frequently progress to cirrhosis, end-stage liver disease and hepatocellular carcinoma. Treatment with pegylated interferons (INFs) plus ribavirin has been shown to be more effective than pegylated INFs alone or standard INFs with or without ribavirin. The early response of HCV to treatment with peg-INF has been used to predict treatment outcomes in infected patients, emphasizing the importance of viral kinetics and genotyping in their treatment. Mathematic modelling of viral dynamics has shown the importance of optimal doses of drug, with early virologic response at week 12 predictive of sustained virologic response. Maintaining INF concentration above a therapeutically effective level is necessary to prevent viral rebound and subsequent treatment failure. Once-weekly dosing with peg-INF-alpha2a, which has a longer half-life than other forms of INF, plus daily dosing with ribavirin, has been shown to be effective in reducing viral load.

Treatment of hepatitis C virus genotype 4 with peginterferon alfa-2a: Impact of bilharziasis and fibrosis stage

To evaluate pegylated interferon alpha2a (PegIFN-alpha2a) in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. A total of 73 naive patients (61 with history of bilharziasis) with compensated chronic HCV genotype 4 were enrolled into: group A (38 patients) who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B (35 patients) received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. Significant improvement in both end of treatment response (ETR) (P < 0.002) and sustained response (SR) (P < 0.05) was noted with pegylated interferon, where ETR was achieved in 29 (76.3%) and 14 patients (40%) in both groups respectively, and 25 patients in group A (65.8%) and 9 (25.7%) in group B could retain negative viraemia by the end of follow up period. Sustained virological response (SVR) showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR (P < 0.001), but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis (grade 3 and 4) with PegIFN-alpha2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect; both drugs were comparable. PegIFN-alpha2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.

Pegylated interferon‐alpha 2b–ribavirin combination in Egyptian patients with genotype 4 chronic hepatitis

Egypt has a high prevalence rate of hepatitis C (HCV) infection and as much as 90% is genotype 4. Response to interferon (IFN) varies with viral genotype and degree of fibrosis. Genotype 4 is poorly sensitive to standard IFN and IFN-ribavirin combination. We evaluated pegylated interferon (PEG-IFN)-alpha2b in our patients. Sixty-one patients with compensated chronic HCV genotype 4 were enrolled in two groups: group A (31 patients) received IFN-alpha2b 3 MU three times per week and group B (30 patients) received 1.5 mug/kg PEG-IFN-alpha2b once weekly. Ribavirin was added to each regimen in a dose of 800-1200 mg based on body weight. Patients were followed up for 24 weeks to assess the sustained response (SR). End-of-treatment response (ETR) was achieved in 11 of 31 patients (35.48%) in group A, and 13 of 30 patients (43.33%) in group B (P < 0.05). Only eight patients in group A and 10 in group (B) achieved a sustained virological response (25.8 and 33.3%, respectively) (P < 0.05). By computing ETR, SR or relapse and pretreatment baseline data (pretreatment, viral load, alanine transaminases, necroinflammatory and hepatic fibrosis), both inter- and intragroup, no significant correlations could be detected. In terms of safety and tolerability, PEG-IFN-alpha2b and IFN-alpha2b were comparable. In spite of mild insignificant increase in ETR and SR with the pegylated form, the poor response of genotype 4 in Egypt (genotype 4a) to different forms of IFNs may be related to an intrinsic resistance to the direct antiviral effect of IFN.

Management of newly diagnosed hepatitis C virus infection.

All patients with chronic hepatitis C virus infection are potential candidates for antiviral therapy. Careful patient selection can optimize the response to therapy and enhance safety. Pegylated forms of interferon, when combined with ribavirin, can "cure" the majority of patients undergoing therapy, and these agents have become the new standard of care for chronic hepatitis C. Careful and timely management of side effects, which are experienced by all patients, can improve adherence to antiviral therapy and further improve response rates.

Therapies for Hepatitis C Infection: Targeting the Non-Structural Proteins of HCV

The hepatitis C virus infects an estimated 1-3% of the world population. A large proportion of individuals afflicted by this rapidly spreading epidemic eventually progress to chronic liver disorders. Liver failures associated with chronic hepatitis C infections are the leading cause for liver transplantations in the US. Currently, the backbone of anti-HCV therapy, consisting of various forms of interferon in combination with broad-spectrum antivirals such as ribavirin, has only met with limited success. This review will provide coverage of recent efforts towards the development of novel antiviral strategies that target inhibition of essential enzymatic functions encoded by the non-structural region of the HCV genome. These include principally, inhibition of the NS3 protease and helicase, and of the NS5B RNA-dependent RNA polymerase.

Comparative assessment of immunomodulating therapies for relapsing-remitting multiple sclerosis.

The past decade has seen unprecedented advances in the development of disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS), a disease that has a worldwide prevalence of two million patients. Four agents with the ability to modulate the immune system are now being widely used for RRMS. Of these, three are forms of interferon (IFN)-beta [IFNbeta-1b and two preparations of IFNbeta-1a (Avonex and Rebif], and one is a polypeptide of four amino acids (glatiramer acetate) with a unique mechanism of action. The administration regimens for the IFNbeta-1a products differ, with Avonex being given as 30 microg intramuscularly once a week and Rebif being given as 22 or 44 microg subcutaneously three times a week. It appears safe to predict that both forms of IFNbeta and glatiramer acetate will remain standard treatments for MS for years to come. However, with four therapeutic options available for RRMS, selecting a single therapy is often difficult and necessitates comparisons of the agents, which can be contentious. All four agents have shown superiority over placebo in pivotal phase III trials. Three recent prospective comparative studies have indicated that IFNbeta-1b, Rebif and glatiramer acetate may be more optimal choices than Avonex for patients with RRMS. In a pharmaceutical environment with an estimated worldwide market of $US2.5 billion annually for RRMS, comparative studies are understandably provocative, but at the same time provide meaningful information to clinicians and patients.

Changes in serum lipoprotein profile during interferon therapy in chronic hepatitis C.

Therapy with a interferon is associated with a rise in serum triglyceride levels, although this effect has not been well studied with newer forms of interferon or interferon in combination with ribavirin. Review of combined data obtained from several prospective, randomized controlled clinical trials conducted in the clinical studies unit of a tertiary care referral center among patients with chronic hepatitis C undergoing treatment with various forms of a interferon, with or without the addition of ribavirin. Serum levels of triglycerides and cholesterol were measured before and during therapy. Changes in these levels were correlated with baseline characteristics. At baseline, the mean serum triglyceride level among 152 patients studied was 130 mg/dL (range 32-620) and was elevated above normal in three patients (2%). During therapy, triglyceride levels rose significantly early on and began to decline spontaneously after 12 wk, returning to baseline after stopping treatment. Triglyceride levels rose above 500 mg/dL in 18 patients (12%) and above 1000 mg/dL in two patients (1.3%) although none experienced acute complications or clinical symptoms. Serum cholesterol levels did not change significantly during therapy (mean at baseline 172 vs 168 mg/dL at 24 wk). Factors correlated with the rise in triglycerides included baseline triglyceride levels, HCV genotype, and the type of interferon used. Serum triglyceride levels increase consistently in patients with chronic hepatitis C treated with all forms of a interferon, often to very high levels. These changes do not seem to be associated with clinical signs or complications and triglyceride levels decline while patients are still on therapy and return to normal after stopping.

Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities.

For the past 40 years, various forms of interferon (IFN) have been evaluated as therapy in a number of malignant and non-malignant diseases. With the advent of gene cloning, large quantities of pure IFN became available for clinical study. This paper reviews the biology, pharmacology, and clinical applications of IFN formulations most commonly used in oncology. It then reviews the most common side effects seen in patients treated with IFN, and makes recommendations for the management of IFN-induced toxicity. The major oncological indications for IFN include melanoma, renal cell carcinoma, AIDS-related Kaposi's sarcoma, follicular lymphoma, hairy cell leukemia, and chronic myelogenous leukemia. Unfortunately, IFN therapy is associated with significant toxicity, which can be divided into constitutional, neuropsychiatric, hematologic, and hepatic effects. These toxicities have a major impact on the patient's quality of life, and on the physician's ability to optimally treat the patient. Careful attention to all aspects of patient care can result in improved tolerability of this difficult but promising therapy. a better understanding of IFN biology, indications, side effect profiles, and toxicity management will aid in optimizing its use in the treatment of patients with cancer.

All-trans-retinoic acid and polyriboinosinoic:polyribocytidylic acid cooperate to elevate anti-tetanus immunoglobulin G and immunoglobulin M responses in vitamin A-deficient lewis rats and Balb/c mice.

Vitamin A (VA) deficiency compromises antibody responses to T-cell-dependent antigens such as tetanus toxoid, but this effect can be reversed through administration of retinol or retinoic acid (RA). To test whether RA and polyriboinosinioc : polyribocytidylic acid (PIC), a known inducer of several forms of interferon (IFN), can cooperate to increase specific immunoglobulin (Ig)G and IgM production during VA deficiency, rats and mice were made VA-deficient, immunized with TT and treated with all-trans-RA, PIC or their combination. VA-deficient rats produced low primary and secondary anti-tetanus IgG responses (VA-deficient controls v. VA-sufficient controls P < 0.001), although total IgG was slightly elevated when compared with VA-sufficient control rats. Although RA administered alone elevated antibody production during VA deficiency to control levels, RA combined with PIC synergistically enhanced these responses (RA and PIC group v. all other groups P < 0.0001). In contrast, Balb/c mice maintained on a VA-deficient diet and immunized in a similar fashion showed no impairment in antigen-specific IgG levels, but treatment with a combination of RA and PIC still evoked an additive enhancement in antigen-specific antibody production. Additionally, RA and PIC administration to VA-sufficient mice resulted in elevated antibody responses, suggesting that this combination should be evaluated further for its immuno-stimulatory effects.

Hepatitis C virus infection: immune responsiveness and interferon-alpha treatment.

Hepatitis C virus (HCV) is responsible for most cases of posttransfusion hepatitis and sporadic or community-acquired non-A, non-B hepatitis. Different generations of enzyme-linked immunosorbent assay have been generated for detecting antibodies to HCV epitopes. HCV-RNA quantitative analysis has been developed by means of polymerase chain reaction technique. This approach is the only reliable method for HCV-RNA tissue localization, being helpful in early diagnosis. HCV infected liver is characterized by an inflammatory infiltrate including CD4+, CD8+, and B lymphocytes. Evidence has been provided that in HCV patients CD8+ cell response is associated with low level of viraemia and higher level of disease activity. CD4+ T cells exhibit specificity for the core antigen, also correlating with disease activity and viraemia. Costimulatory molecules, cytokines, oxygen radicals, the complex Fas/Fas-ligand and soluble class I HLA structures are discussed as putative cofactors involved in disease evolution. Various forms of interferon (IFN)-alpha have been evaluated for the treatment of patients with HCV infection. Initial enthusiasm has been attenuated by the evidence of a low sustained virological response rate and the constant side effects of IFN-alpha therapy in patients with chronic HCV disease. Among possible markers for predicting therapeutic outcome in HCV-positive individuals, anti-core antibodies correlate positively with response to IFN-alpha administration, as well as reduction of interleukin-2 serum levels has been detected in patients with a good therapeutic response. Association between HCV infection and autoimmune phenomena, also in relation to IFN-alpha therapy has been reported. Finally, results of the combined treatment with IFN-alpha/ribavirin are illustrated.

Pathophysiology and Treatment of Hepatitis C Infection

The pathophysiology and treatment of hepatitis C infection, formerly known as non-A, non-B hepatitis, are discussed. The worldwide prevalence is approximately 1%. The majority of patients infected with hepatitis C virus will develop chronic infection, leading to cirrhosis in a significant percentage. Transmission of hepatitis C is primarily through parenteral routes. Those who use intravenous drugs or received blood transfusions prior to 1992 comprise the major risk groups for the infection. The progression of chronic hepatitis C infection is insidious with possible progression to an inflammatory hepatitis developing within 5–10 years, cirrhosis in 10–20 years, and hepatocellular carcinoma in 20–30 years. Combination therapy with interferon alpha-2b and ribavirin is currently the treatment of choice. Therapy for hepatitis C continues to evolve with newer forms of interferon and HCV antivirals under development.

De novo development of psoriatic plaques in patients receiving interferon alfa for treatment of erythrodermic cutaneous T-cell lymphoma

Presumably because of its potent immunomodulatory activity, the use of interferon has led to the development of autoimmune disease in susceptible individuals. Because psoriasis is considered to be, in part, an autoimmune phenomenon, it is plausible that interferon may influence disease activity. We describe the development of psoriatic plaques in two patients without a history of this disease while they were receiving interferon alfa and extracorporeal photochemotherapy for erythrodermic cutaneous T-cell lymphoma. Paradoxically, in both patients the erythroderma resolved with subsequent de novo onset of psoriasis. This clinical sequence provides support for disparate immune mechanisms in the pathogenesis of these disorders, both of which are typified by lymphoid infiltrates. A review of the literature reveals that all forms of interferons have been associated with the exacerbation of psoriatic plaques, but that only interferon alfa has induced de novo development of psoriasis.