Conventional Interferon Alpha Research Articles

Immunomodulatory and direct activities of ropeginterferon alfa-2b on cancer cells in mouse models of leukemia.

Although ropeginterferon alfa‐2b has recently been clinically applied to myeloproliferative neoplasms with promising results, its antitumor mechanism has not been thoroughly investigated. Using a leukemia model developed in immunocompetent mice, we evaluated the direct cytotoxic effects and indirect effects induced by ropeginterferon alfa‐2b in tumor cells. Ropeginterferon alfa‐2b therapy significantly prolonged the survival of mice bearing leukemia cells and led to long‐term remission in some mice. Alternatively, conventional interferon‐alpha treatment slightly extended the survival and all mice died. When ropeginterferon alfa‐2b was administered to interferon‐alpha receptor 1–knockout mice after the development of leukemia to verify the direct effect on the tumor, the survival of these mice was slightly prolonged; nevertheless, all of them died. In vivo CD4+ or CD8+ T‐cell depletion resulted in a significant loss of therapeutic efficacy in mice. These results indicate that the host adoptive immunostimulatory effect of ropeginterferon alfa‐2b is the dominant mechanism through which tumor cells are suppressed. Moreover, mice in long‐term remission did not develop leukemia, even after tumor rechallenge. Rejection of rechallenge tumors was canceled only when both CD4+ and CD8+ T cells were removed in vivo, which indicates that each T‐cell group functions independently in immunological memory. We show that ropeginterferon alfa‐2b induces excellent antitumor immunomodulation in hosts. Our finding serves in devising therapeutic strategies with ropeginterferon alfa‐2b.

Effect of interferon plus ribavirin therapy on hepatitis C virus genotype 3 patients from Pakistan: Treatment response, side effects and future prospective.

More than 10 million people are suffering from hepatitis C virus (HCV) in Pakistan. The available treatment option is a combination of interferon and ribavirin. Treatment response is linked with several factors and also induces a number of side effects. We searched in Pubmed, Pak Medi Net and Google Scholar for the articles presenting the effect of interferon plus ribavirin therapy on HCV patients from Pakistan, their side effects and future prospects. The major prevalent HCV genotype in Pakistan is 3. Conventional interferon alpha plus ribavirin showed sustained virological response of 54%-64% while pegylated interferon alpha plus ribavirin showed sustained virological response of 58%-75%. IL-28B CC genotype is linked with better sustained virological response. Studies on patients with HCV genotype 3 infections showed no correlation between treatment response and interferon sensitivity determining region mutations. Interferon therapy is linked with a number of side effects like thyroid dysfuncton, haematological disorders, weight loss, gastrointestinal tract side effects and neuropsychiatric side effects. Unusual side effects of clubbing of fingers and seizures were also observed in a couple of patients. Interferon alpha plus ribavirin therapy showed better response rate in HCV genotype 3 patients from Pakistan with number of side effects. A couple of interferon free therapies are light of hope for the patients living with HCV.

Efficacy and safety on tenofovire therapy in patients with hepatitis B viral infections resistent to lamivudin

Chronic viral hepatitis B (CHB) still represents a significant world health problem despite obligatory and worldwide immunization against infections of viral hepatitis B. In some patients with chronic viral hepatitis B infections, in the natural course of the disease, progression towards cirhossis and hepatocellular carcinoma is primarily targeted by antiviral CHB therapy stopping further progression of the disease. Today on the market there exist two classes of pharmnaceutical drugs for treatment of CHB: a) immunomodulatory therapy with conventional interferon alpha (INF) and PEGylated interferon alpha-2a, b) and oral antiviral therapy with nucleos( t)ide analogues. Lamivudine was for quite a period the only medicament available on our market for the treatment of HVB and in most of our patients led to the development of resistance. As of two years ago, a new oral analogue from the group of nucleotides is being registered in Serbia for market use: tenofovir disoproxil (TDF). In our work we have analysed 69 patients with chronic viral hepatitis B treated in the Clinic for Infectious and Tropical Diseases KCS Belgrade in the period between years 2012 and 2014. All patients involved in this reasearch were previously treated with LAM, and on subsequent development of resistance to LAM, TDF was used. TDF showed an excellent efficacy, a high resistance barrier and very few unwanted side effects over several years of treatment. Our experience with the use of this drug does not pertain to and acount for its long term use, in view of its brief availability on our market.

Efficacy and safety of interferon-based therapy in the treatment of adult thalassemic patients with chronic hepatitis C: a 12 years audit

Background. HCV infection and transfusional iron overload in Thalassemic patients may result in liver disease. HCV treatment in Thalassemia has raised safety concerns.Aim. Estimate effectiveness and tolerability of interferon-based therapy in HCV-infected Thalassemic patients.Material and methods. Over a 12-year period, consecutive patients with β Thalassemia major (TM) and chronic hepatitis C received treatment. Liver biopsy, HCV-RNA and genotyping were performed beforehand. Sustained virological response (SVR) was defined as negative HCV-RNA 6 months post-treatment. Forty eight patients (26 M-22 F, mean age 39.8) were enrolled. Twenty nine patients were treated with conventional interferon alpha (IFNa) for 48 weeks (group A). Nineteen patients (10 naïve-9 previously IFNa experienced) received pegylated interferon (PEG-IFN) (group B).Results. HCV-1 was found in 44%, HCV-2 in 14%, HCV-3 in 23% and HCV-4 in 19%. Group A: ten patients (38.5%) achieved SVR, 2 (7.5%) relapsed and 17 (54%) were non responders. Group B: five (28%) achieved SVR, 8 (44%) relapsed and 6 (28%) never responded. High HCV-RNA levels, genotype 1 and advanced liver fibrosis were independently associated with no response. Four patients (3 treated with IFNα, 1 with PEG-IFN) had to discontinue treatment due to complications.Conclusions. The response rate of IFN monotherapy in multi-transfused, HCV-infected Thalassemic patients is not inferior to that in non-multi-transfused patients. IFNa administration is well-tolerated and should be recommended as initial treatment schedule in this setting.

Long-term assessment of relapse and associated risk factors in chronic hepatitis C patients treated with interferon and ribavirin

To investigate viral relapse and the associated risk factors during a long-term follow-up study of chronic hepatitis C (CHC) patients who achieved end-of-treatment response (ETR) after interferon and ribavirin therapy. This retrospective study was conducted on 146 CHC patients treated with a combination of ribavirin and pegylated (PEG) interferon-alpha (IFNa) (n=126) or conventional IFNa (n=20) for 24 (hepatitis C virus (HCV) non-genotype 1b) or 48 (HCV genotype 1b) weeks. The main outcome measure was serum HCV RNA load. The risk factors analyzed included age, sex, HCV genotype, baseline HCV RNA load, and IFN type. The mean follow-up time for all patients was 33.45+/-16.41 months (range: 12-85 months). The cumulative relapse rate during follow-up was 14.80%. The relapse rate within six months (8.90%) was significantly higher than other periods during two years of follow-up, and no relapse occurred after 30 months. Of all relapsers (n=20), 65% occurred within six months, followed by 35% within 7-24 months after antiviral therapy. The relapse rates in patients with HCV genotype 1b and non-1b were not significantly different (20.37% vs. 12.12%, X2 =1.517, P=0.315). The mean baseline HCV RNA load was significantly higher in the relapsers than that in the non-relapsers (t=0.915, P=0.362). Relapse rates were similar in patients treated with PEG-IFNa-2b, PEG-IFNa-2a and IFNa (12.12% vs. 13.97% vs. 15.00%, respectively; X2=0.104, p=0.949). The mean age of relapsers was significantly higher than that of non-relapsers (P less than 0.005). The maximum probability of relapse for CHC patients exists within six months from when ETR is achieved by interferon and ribavirin therapy. A lower risk for relapse persists past this period. Thus, ETR CHC patients, especially older patients, should be carefully monitored during the two years after cessation of antiviral therapy. Standard antiviral therapy based on HCV genotype eliminates the influence of viral factors on treatment-response.

Predictors and scoring system for sustained complete response to conventional interferon-alpha therapy on chronic hepatitis B

To establish a predictive scoring system which may serve for the prediction of sustained response to conventional interferon-alpha (IFN-alpha) treatment on chronic hepatitis B. A total of 474 IFN-alpha treated hepatitis B virus e antigen (HBeAg)-positive patients were enrolled in the present study. The patients' baseline characteristics, such as age, gender, aminotransferases, activity grading (G) of intrahepatic inflammation, score (S) of liver fibrosis, hepatitis B virus (HBV) DNA and genotype were evaluated; therapy duration and response of each patient at the 24th wk after cessation of IFN-alpha treatment were also recorded. A predictive scoring system for a sustained complete response (CR) to IFN-alpha therapy was established based on genetic algorithm. About 10% of the patients were randomly drawn out as the test set. Responses to IFN-alpha therapy were divided into CR, partial response (PR) and non-response (NR). The mixed set of PR and NR was recorded as PR + NR. For the scoring system, the sensitivity and specificity were 78.8% and 80.6%, respectively. This SCR scoring system has satisfying prediction efficiency and is easily employed in clinical practice. With this scoring system, practitioners can propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.

Treatment of chronic hepatitis B: Evolution over two decades

There has been a recent paradigm shift in the indications and endpoints of treatment for chronic hepatitis B (CHB). Hepatitis B e antigen (HBeAg)-negative disease is being increasingly recognized. Antiviral treatment for both HBeAg-positive and HBeAg-negative patients should aim at long-term suppression of HBV DNA, with the ultimate ideal endpoint of hepatitis B surface antigen (HBsAg) seroconversion. Conventional interferon alpha (IFN-α), the only agent licensed in 1991, has been superseded by pegylated IFN-α. HBeAg seroconversion using pegylated IFN-α is 33%, with only 25% of HBeAg-positive patients achieving undetectable HBV DNA by polymerase chain reaction (PCR) assay. Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine, an L-nucleoside, is limited by the development of resistance in 76% of patients after 5 years of therapy. Telbivudine, another L-nucleoside, is more potent than lamivudine but resistance still develops in 25% of HBeAg-positive and 11% HBeAg-negative patients after 2 years. Adefovir, an acyclic phosphonate, is relatively weak, but is effective against lamivudine- and telbivudine- resistant mutations, for which it should be used in combination (add-on therapy) rather than substituted. Resistance to adefovir develops slowly, rising to 29% for HBeAg-negative patients by year 5, but more rapidly when used alone for lamivudine-resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir and tenofovir. Entecavir, a cyclopentane (D-nucleoside), is very potent, with 94% of patients having undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of treatment-naïve patients. Tenofovir, another acyclic nucleotide, is more potent with less renal toxicity compared to adefovir. It is effective against lamivudine-resistant mutations when used alone. No resistance to tenofovir has been described after its use for 3 years or longer, often for patients with human immunodeficiency virus/HBV co-infection. With these current, potent antiviral agents associated with very low rates of resistance, long-term HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved in a proportion of patients. In addition, long-term treatment with these antiviral agents is associated with a reduced risk of development of hepatocellular carcinoma.

Hemoglobin Level can be a Predictor of End Treatment Response in Chronic Hepatitis C?

Purpose: To study the correlation between hemoglobin level and end treatment response in chronic hepatitis C patients treated with conventional interferon and ribavirin. Methods: Chronic hepatitis C patients treated at Gastroenterology & Hepatology Division, Department of Medicine, Holy Family Hospital, Rawalpindi, Pakistan between January 2006 to August 2009. All patients were work-up with blood counts and ALT levels. Later, conventional interferon alpha 2b thrice a week + Ribavirin 800 mg daily for 6 months were prescribed. At treatment completion, end treatment response was determined. Data was collected on specially designed liver data file for each patient. Data was then transcribed into SPSS version 16 and analyzed. Results: Total of 422 patients were included in the study that dropped their hemoglobin levels with treatment with conventional interferon and ribavirin. 51% (n=215) were male and 49% (n=207) were female. Mean age of the patients was 35.79 + SD 8.408 years. Maximum patients 72.8% (n=307) were in the age range between 20-40 years. Youngest patient was of 15 years and oldest being of 58 years. Mean hemoglobin levels before and after the treatment were 14.04 +1.72 and 11.99+1.64 respectively. In the pretreatment period, maximum patients 39% (n=165) had hemoglobin range between 14-16 years while 40.8% (n=172) patients were having hemoglobin in the range of 10-12 mg/dl after treatment. Highest and lowest hemoglobin values in pre and post treatment patients were 18.50 mg/dl vs. 16.70 mg/dl and 10 mg/dl vs. 6.90 mg/dl respectively. Total of 422 patients who dropped their hemoglobin with conventional interferon and ribavirin treatment, 78.7% (n=332) dropped level between 0.1-3.0 mg/dl, 20.4% (n=86) between 3.1-6 and 0.9% (n=04) patients dropped hemoglobin more than 06 mg/dl. Considering the treatment response, 75.1% (n=317) achieved end treatment response while 24.9% (n=105) were non responder. Patient who dropped their hemoglobin from 0.1-3.0 mg/dl, 3.1-6.0 mg/dl, more than 6.1 mg/dl showed response rates 72.9%, 83.7% and 75% respectively while non responders frequencies were 27.1%, 16.3% and 25% respectively. P-value calculated using chi-square was 0.117 (95% Confidence Interval; Odd ratio 4.598) signifies that there is no positive correlation exists between the drop of hemoglobin levels and the end treatment response. Conclusion: There is no significant correlation between drop in hemoglobin level and treatment response in chronic hepatitis C patients treated with conventional interferon and ribavirin.

Does Histologic Activity Index (HAI) and ALT level Predict Response to Treatment For Hepatitis C with Conventional Interferon Alpha and Ribavarin?

Purpose: To determine whether Histologic Activity Index (HAI) and ALT level can be used to predict response to treatment of hepatitis C with conventional interferon alpha and ribavarin. Methods: A convenient sample of 296 patients was chosen for a retrospective study based on medical records of patients undergoing treatment for hepatitis C since August 2006 at the Liver Research Clinic Holy Family Hospital Rawalpindi Pakistan. Patients were treated with Interferon alpha 2b (3 million units thrice weekly subcutaneous) and ribavarin (400 mg twice every day orally) for a total period of six months. All patients underwent liver biopsy before initiation of treatment with conventional interferon and ribavarin. Knodell scoring (HAI) was performed by a team of pathologists. Data was entered and analyzed using SPSS version 13. Categorical variables were analyzed using chi-square test and continuous variables were analyzed using student t-test and one way ANOVA wherever applicable. Significance level was chosen at p<0.05. Results: Majority of patients had minimal 82(27.7%) to mild 181(61.1%) inflammation on liver biopsy. 54(65.9%) patients with minimal inflammation, 107(59.1%) with mild inflammation achieved End treatment response (ETR; HCV PCR negative at six months of treatment). 104 (61.9%) patients with stage 0 fibrosis were responders as compared to 62 (60.8%) patients with stage 1 fibrosis. A greater proportion of patients with minimal inflammation achieved Sustained Viral Response (SVR; HCV PCR negative at 12 months of treatment) as compared to patients with mild inflammation (52.4% vs. 45.9%). The initial ALT level increased proportionately with the degree of inflammation based on the Knodell score. Patients achieving end-treatment response had a lower mean ALT level at the beginning of treatment (83.6 vs. 85.3). The mean ALT level increased from 72.5 to 99.7 in patients progressing from stage 0 to stage 1 fibrosis (p<0.05). The mean ALT decreased progressively in responders from a value of 86.1 at initiation of treatment to 58.6 and 38.8 at 3 and 6 months respectively after initiation of treatment. Conclusion: A higher proportion of patients with minimal inflammation based on the HAI achieved ETR and SVR. Patients at a lower fibrosis stage were also more likely to achieve a positive ETR. Beginning treatment early in the course of chronic HCV is associated with better outcome. The ALT level before initiation of treatment was lower in patients who achieved ETR, increased progressively for patients with a higher Knodell score and was significantly higher in patients at a higher stage of fibrosis. The ALT level also decreased progressively over the course of treatment in patients achieving ETR.

A case of sudden-onset hearing loss in a patient treated with peginterferon α-2b and ribavirin for chronic hepatitis C

Combination therapy of pegylated interferon alpha and ribavirin has been associated with various adverse effects, but sudden-onset hearing loss is uncommon. We report a 60-year-old male patient who developed sudden-onset hearing loss during combination therapy with pegylated interferon alpha and ribavirin for chronic hepatitis C. This patient had been diagnosed with chronic hepatitis C (genotype Ib) and early-stage liver cirrhosis 3 years previously, and had been treated with conventional interferon-alpha and ribavirin for 12 months. However, 6 months from the end of the treatment course the patient relapsed and received combination retreatment with pegylated interferon alpha-2b and ribavirin. He developed sudden-onset right-side hearing loss and tinnitus 42 weeks after the start of this retreatment. Pure-tone audiometry revealed a right-side hearing loss of 60 approximately 90 dB. The patient consequently immediately discontinued the pegylated interferon therapy and was given prednisone 60 mg/day for 10 days, after which the hearing loss had almost completely recovered.

Durability of a sustained virologic response in combination therapy with interferon/peginterferon and ribavirin for chronic hepatitis C

The ultimate goal of antiviral therapy using interferon/pegylated interferon combined with ribavirin in chronic C-viral hepatitis is to achieve a sustained virologic response (SVR). Several studies have shown that the reappearance rate of hepatitis C virus (HCV) RNA in serum after the achievement of an SVR is less than 1%; the durability of an SVR in Korean patients is not known. The aim of this study was to determine the durability of the virologic response in chronic hepatitis C patients with an SVR to antiviral therapy. A total of 156 patients who were treated successfully with interferon/peginterferon and ribavirin were evaluated retrospectively. Patients received either subcutaneous conventional interferon alpha 3x10(6) units three times a week or subcutaneous pegylated interferon (alpha-2a: 180 microgram, alpha-2b: 80-100 microgram) once a week in combination with ribavirin at 600-1,200 mg daily (depending on body weight). Patients with HCV genotype 1 were treated for 48 weeks, whereas those with non-genotype 1 were treated for 24 weeks. Eighty-two patients underwent treatment with conventional interferon and ribavirin, whereas 74 patients were treated with pegylated interferon and ribavirin. An SVR was achieved in 73 patients (73/156, 46.8%). HCV RNA reappeared in eight patients (8/73, 11.0%; detected by qualitative PCR), including one patient with persistent viremia (1/73, 1.4%). Reappearance of HCV RNA after earlier achievement of an SVR might appear more frequently than previously reported. Close follow-up of these patients is recommended and the implication of temporary viremia should be determined in the future.

Interferon-alpha-associated presumed ocular sarcoidosis

Interferon alpha, used in the treatment of different viral, autoimmune and malignant diseases, is known to induce a variety of side effects. Recently, induction of sarcoidosis during interferon therapy has been reported. We analyzed patients for uveitis, possibly induced by interferon alpha. We report on three patients who had developed typical signs of ocular sarcoidosis under treatment with interferon alpha for chronic hepatitis C virus infection. In two patients, conventional interferon alpha was used and in another one, pegylated interferon alpha-2b. All patients additionally received ribavirin. In all three cases, panuveitis was diagnosed. The mean duration of interferon treatment before development of uveitis was 10 months. Clinically, all patients demonstrated granulomatous panuveitis with choroidal granulomas of various sizes. In one case, the uveitis developed together with renal failure, fever and malaise. In this patient, an elevated ACE level was detected. In another patient, the diagnosis of sarcoid induced uveitis was confirmed by positive chest CT scan. The intraocular inflammation was managed with a reduction of the interferon dosage. The therapy with ribavirin was not changed. All patients received topical steroids. Systemic steroids were applied only in the case with systemic disease manifestations. Uveitis can be a sign of sarcoidosis induced by interferon alpha. Further studies are required to support the observation that with early diagnosis the prognosis of uveitis seems to be good.

Natural history and clinical management of chronic hepatitis B virus infection in children

Hepatitis B virus (HBV) infection may cause acute, fulminant, or chronic hepatitis, leading to liver cirrhosis or hepatocellular carcinoma. Despite the availability of effective vaccine, HBV infection during infancy or early childhood is common in areas of high endemicity. In these regions, mother-to-infant transmission accounts for approximately 50% of chronic infections. Although the natural history of HBV infection in adults is well characterized, little information is available in the literature regarding the natural history of HBV infection in children. Similar to infection in adults, chronic HBV infection in children can be divided into distinct phases: immune tolerant, immune clearance, and inactive carrier state. However, acute exacerbation, with reactivation of HBV replication and re-elevation of alanine aminotransferase levels after hepatitis B e antigen seroconversion, is relatively rare in children, in comparison to adults. Although several potent antiviral agents are now available for the treatment of chronic hepatitis B, experience with these agents in the pediatric setting is limited. To date, conventional interferon alpha and lamivudine are the only two antiviral agents approved to treat chronic hepatitis B in children. The rapid emergence of resistant HBV associated with long-term lamivudine therapy, as well as poor tolerability associated with conventional interferon alpha, are factors that should be considered before initiating antiviral therapy. This article reviews current knowledge regarding the natural history and treatment of chronic hepatitis B in children. Factors that affect the natural history of HBV infection in children are also reviewed.

Retreatment of hepatitis C patients who previously experienced treatment failure

In its different formulations, interferon (IFN) alphacombined with ribavirin (RBV) is the best treatment alternativefor patients infected with the hepatitis C virus (HCV) [1]. Insuch patients, the objective is to achieve an end-of-treatmentvirological response – negative serum HCV ribonucleic acid(RNA) – followed by a sustained virological response (SVR),which is defined as HCV RNA negativity for six months afterthe suspension of treatment.The treatment regimens for HCV infection have evolvedfrom monotherapy with conventional IFN alpha to combinedtherapy with IFN and RBV and, more recently, to combinedtherapy with pegylated IFN (PEG-IFN alpha-2a or alpha-2b)and RBV [2,3]. It is known that approximately 60% of thepatients infected with HCV genotype 1 and nearly 40% ofthose infected with genotype 3 do not achieve an SVR whentreated with the conventional regimen of IFN and RBV [2-7].The availability of PEG-IFNs has reduced the percentage ofpatients experiencing treatment failure. In large internationaltrials involving treatment-naive patients, regimens that includethe combination of PEG-IFN and RBV have producedsignificantly higher rates of SVR than those observed withthe use of the conventional combination of IFN and RBV (54-56%

A phase II trial of pegylated interferon α‐2b therapy for polycythemia vera and essential thrombocythemia

Conventional interferon-alpha (IFN) is an effective treatment for patients with myeloproliferative disorders. However, many patients discontinue therapy because of side effects. In this 24-month, Phase II feasibility study of pegylated interferon alpha-2b (PEG-IFN) treatment, a starting dose of 0.5 microg/kg per week was received by 21 patients with polycythemia vera (PV) and 21 patients with essential thrombocythemia (ET). The treatment objective, a complete platelet response (CR), was a platelet count<400x10(9)/L in symptomatic patients and <600 in asymptomatic patients. Neutrophil polycythemia rubra vera-1 (PRV-1) messenger RNA expression was analyzed prior to and during therapy. Quality of life (QoL) was investigated by using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. At 6 months, 29 of 42 patients (69%) had achieved a CR after a median of 83 days. The CR rate was not related to diagnosis, gender, or previous therapy. Nineteen patients completed the planned 2-year treatment in CR. No thromboembolic or bleeding complications were observed. Phlebotomy requirements were reduced in the majority of patients with PV. Five of 14 patients (36%) who initially were positive for PRV-1 achieved normalized PRV-1 expression under PEG-IFN treatment. Side effects were the cause of therapy failure in 16 of 23 patients. However, only 8 of 19 patients reported any side effects at 2 years. The QLQ-C30 revealed clinically significant impairments in several aspects of QoL at 6 months; however, at 2 years, QoL measurements were not different from baseline. PEG-IFN effectively reduced platelet counts in 29 of 42 patients, but only 19 patients maintained a CR at 2 years. The reversal of PRV-1 positivity noted in a subset of patients suggested that PEG-IFN may have an effect on the malignant clone. PEG-IFN is a valuable therapeutic alternative for patients who tolerate its initial side effects.

Therapeutic modalities in hepatitis C: challenges and development

Our understanding of the pathogenicity of hepatitis C virus (HCV) is based on patients infected chronically for >20 years. The lack of a suitable animal model, the narrow host range of the virus, and the protracted onset of liver disease induced by HCV have hampered advances in treatment. In spite of these problems, we identified patient and viral characteristics that predict responses to current therapies, including HCV genotype, viral load, body weight, age, liver histology, co-infection with HIV and treatment adherence and tolerance. Interferon (IFN) alpha was the first therapy for chronic HCV infection. The combination of IFN plus ribavirin increases sustained virological response rates compared with IFN alone. Two pegylated IFNs have been developed and are widely approved for the treatment of chronic hepatitis C: peginterferon alpha-2a (40 KD), and pegylated IFN alpha-2b (12 KD). These products have reduced systemic clearance, prolonged half-lives and reduced antigenicity compared with conventional IFN. The reduced clearance results in sustained plasma levels of the drug and allows for once-weekly dosing. Pegylated IFN alpha-2b (12 KD) has a small, linear polyethylene glycol (PEG) moiety and has an intermediate duration of activity; peginterferon alpha-2a (40 KD) incorporates a large, branched-chain PEG moiety and has a longer half-life than both conventional IFN alpha and pegylated IFN alpha-2b (12 KD). The combination of a pegylated IFN plus ribavirin significantly increases sustained virological response rates compared with conventional IFN plus ribavirin in patients with chronic hepatitis C and is now recognized as the standard of care for these patients.

Acid-labile human interferon alpha production by peripheral blood mononuclear cells stimulated by HIV-infected cells.

We compared the properties of interferon (IFN) induced in peripheral blood mononuclear cells (PBMC) by free infectious HIV to that induced by HIV-infected cells fixed with glutaraldehyde. While the IFN induced by HIV was a conventional IFN alpha, the IFN induced by HIV-infected cells, although sharing with IFN alpha both antigenic properties and molecular weight, was strongly inactivated by treatment at pH lower than 4. The ability to induce acid-labile IFN alpha was exerted both by the chronically-infected cell line H9/HIV and by normal PBMC infected in vitro with HIV, while infection of inducers cells with viruses other than HIV made these cells capable of inducing only acid-stable IFN alpha. The cell involved in the production of this type of IFN seems to be B-lymphocyte. Because the presence of acid-labile IFN alpha in the serum of AIDS patients has been described, we suggest that this unusual IFN derives from interaction between circulating B-lymphocytes and the HIV-infected cells.