Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “INTERFERON”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1995

Recombinant interferon-alpha and ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic hepatitis C: a randomized clinical trial with long-term follow-up.

OBJECTIVES: The purpose of this study was to compare, within a randomized controlled trial, the efficacy of recombinant interferon-alpha in combination with ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic HCV hepatitis. METHODS: Forty anti-HCV positive chronic hepatitis patients with ALT levels persistently greater than 3 times the upper normal level were randomized to receive either interferon-alpha (6 million units three times/wk for 6 months) plus ursodeoxycholic acid (10 mg/kg/day for 9 months) (n = 20) or interferon-alpha (6 million units three times/wk for 6 months) alone (n = 20). Disease activity was monitored monthly by ALT measurement until 18 months after interferon-alpha cessation. Serum HCV-RNA was measured at baseline and after 6, 9, and 24 months. Liver biopsies (basal and at the 9th month) were evaluated blindly and scored by Knodell's criteria. RESULTS: The probability of full or partial response during interferon-alpha treatment was similar in the two groups. The probability of biochemical relapse (i.e, any persistent return of ALT above normal) after 18-month of posttreatment follow-up was 75% in both the combination and the monotherapy group. Relapse, however, occurred significantly later in the combination than in the monotherapy group (6.6 +/- 5.4 [SD] months and 1.8 +/- 1.6 months after IFN-alpha cessation, respectively, p < 0.02). Severe biochemical relapse (i.e., a persistent ALT elevation greater than 3 times normal) occurred more frequently and earlier (p = 0.05) in patients treated with interferon-alpha (58.3%) than in those receiving the combination therapy (27.3%). The cumulative duration of normalized ALT periods during and after treatment was significantly greater (p = 0.005, chi 2) in patients treated with IFN-alpha + UDCA than with monotherapy (189/354 months vs 136/323 months. Lobular necrosis improved in both groups (p = 0.056 and p = 0.001, respectively), whereas portal inflammation improved (p = 0.009) only in the combination therapy group. Among the 30 patients who were viremic at entry, plasma HCV-RNA was no longer detectable after 6 months in four from the combination group and in five from the monotherapy group, yet all patients but one returned HCV-RNA positive 3 months after interferon-alpha cessation and were still viremic after 18 months. Cox's multiple regression identified the histological degree of posttreatment portal inflammation as the sole positive indicator of relapse. CONCLUSIONS: The combination of interferon-alpha and ursodeoxycholic acid prolongs the efficacy of interferon-alpha alone in chronic hepatitic C by delaying the probability of biochemical relapse and/or by reducing its severity, without affecting HCV viremia.

Adult↗
PubMed1998

Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS.

BACKGROUND: The beneficial effects of interferon beta have only been shown for patients in the relapsing-remitting phase of multiple sclerosis (MS). The role of interferon beta in the treatment of patients who are in the secondary progressive phase of the disease (SP-MS), and for whom no effective drug treatment is available, has not been assessed. METHODS: In this multicentre, double-masked, randomised, placebo-controlled trial, outpatients with SP-MS having scores of 3.0-6.5 on the Expanded Disability Status Scale (EDSS) received either 8 million IU interferon beta-1b every other day subcutaneously, or placebo, for up to 3 years. The primary outcome was the time to confirmed progression in disability as measured by a 1.0 point increase on the EDSS, sustained for at least 3 months, or a 0.5 point increase if the baseline EDSS was 6.0 or 6.5. A prospectively planned interim analysis of safety and efficacy of the intention-to-treat population was done after all patients had been in the study for at least 2 years. FINDINGS: 358 patients with SP-MS were allocated placebo and 360 were allocated interferon beta-1b; 57 patients (31 placebo, 26 interferon beta-1b) were lost to follow-up. There was a highly significant difference in time to confirmed progression of disability in favour of interferon beta-1b (p=0.0008). Interferon beta-1b delayed progression for 9-12 months in a study period of 2-3 years. The odds ratio for confirmed progression was 0.65 (95% CI 0.52-0.83). This beneficial effect was seen in patients with superimposed relapses and in patients who had only progressive deterioration without relapses. Positive results were also obtained regarding time to becoming wheelchair-bound, relapse rate and severity, number of steroid treatments and hospital admissions, as well as on magnetic resonance imaging variables. The drug was safe and side effects were in line with previous experience with interferon beta-1b. The study was stopped after the interim results gave clear evidence of efficacy. INTERPRETATION: Treatment with interferon beta-1b delays sustained neurological deterioration in patients with SP-MS. Interferon beta-1b is the first treatment to show a therapeutic effect in patients with SP-MS.

Adult↗
PubMed1998

Expression of interferon receptor genes (IFNAR1 and IFNAR2 mRNA) in the liver may predict outcome after interferon therapy in patients with chronic genotype 2a or 2b hepatitis C virus infection.

Hepatitis C virus (HCV) genotype 2a or 2b is associated with a favorable outcome after interferon therapy. However, 19% to 33% of patients do not respond to therapy. We investigated whether interferon receptor gene (IFNAR1 and IFNAR2 mRNA) expression in the liver before interferon therapy predicts long-term response to therapy in patients with genotype 2a or 2b HCV infection. Twenty-seven patients who subsequently received interferon-alpha therapy underwent liver biopsies before interferon therapy. Hepatic IFNAR1 and IFNAR2 mRNA were determined using a reverse transcription-polymerase chain reaction assay. Twenty (74%) patients responded to interferon therapy, while the remaining seven (26%) patients were nonresponders. The expression rates of IFNAR1 and IFNAR2 mRNA in the liver were significantly higher in responders than nonresponders (p < 0.01, by chi-square test). The presence of either IFNAR1 or IFNAR2 mRNA predicted complete response to interferon treatment, with a positive predictive value of 100%. Multiple logistic regression analysis showed that IFNAR1 and/or IFNAR2 mRNA expression was the only significant predictor of the effectiveness of IFN therapy (p = 0.0002). We conclude that expression of interferon receptor genes in the liver is a useful index for predicting the long-term efficacy of interferon therapy in patients with chronic genotype 2a or 2b HCV infection.

Adult↗
PubMed1995

Cultured human myocardial fibroblasts of pediatric origin: natural human interferon-alpha is more effective than recombinant interferon-alpha 2a in carrier-state coxsackievirus B3 replication.

Cultured human myocardial fibroblasts of pediatric origin seem to be a useful species-specific model for studying various heart diseases which involve the myocardial interstitium, for example enterovirus heart disease. Cells were propagated from small samples of human ventricular tissues (0.2 g) obtained from standard surgical procedure for the correction of Fallot-tetralogy. Cultured cells exhibited typical fibroblastoid morphology over a period of 4 months and were uniformly immunoreactive with a monoclonal antibody directed against prolyl-4-hydroxylase, a marker enzyme of fibroblasts. Infection of cell cultures with coxsackievirus B3, a cardiotropic enterovirus, resulted in a typical carrier-state type of virus persistence. Average virus titers of 2.3 x 10(5) plaque-forming units/ml (SD = 9.9 x 10(4)) were maintained over a period of up to 10 weeks by productive infection of about 8-10% of the cell population. Coxsackievirus B3 carrier cultures of human myocardial fibroblasts were used to evaluate in vitro the long-term antiviral effects of recombinant interferon alpha-2a and natural human interferon-alpha. Recombinant interferon-alpha reduced virus yields by 90% with a concentration of 423 IU/ml, whereas with natural interferon-alpha a 90% reduction of virus yields was achieved with concentrations as low as 21 IU/ml. Antiviral effects of both recombinant and natural interferon-alpha were highly specific and not related to inhibition of cell-proliferation (< 50% with interferon-alpha concentrations as high as 6250 IU/ml). Since effective concentrations of interferon-alpha can be easily attained in vivo with subcutaneous application, interferon-alpha (in particular: natural interferon-alpha) may become useful in the treatment of patients with enterovirus myocarditis and enterovirus induced dilated cardiomyopathy.

Antiviral Agents↗
PubMed1993

Alpha- and gamma-interferon versus alpha-interferon alone in chronic hepatitis B. A randomized controlled study.

Thirty-two patients with chronic hepatitis B were randomly assigned to two groups. Sixteen patients received 10 million units of alpha-interferon per square meter of body surface (MU/m2), three times weekly for 4 months. Sixteen patients were treated simultaneously with gamma-interferon at a dose of 2 MU/m2, and 10 MU/m2 of alpha-interferon. At the end of the study (13th month), hepatitis B virus DNA was negative in 50% of the patients treated with alpha-interferon and in only 25% of those treated with alpha- and gamma-interferon. A similar trend was observed with respect to the hepatitis B e antigen negativization (31% and 19% of HBeAg negativization in patients treated with alpha- and gamma-interferon, respectively). In summary, these data demonstrate that, at the doses used in this study, the combination of alpha- and gamma-interferon does not give better results than the administration of alpha-interferon alone. The tolerance to simultaneous alpha- and gamma-interferons is poor and may decompensate the liver disease.

Adult↗
PubMed2003

Induction interferon and ribavirin for re-treatment of chronic hepatitis C patients unresponsive to interferon alone.

BACKGROUND: The optimal treatment for hepatitis C patients unresponsive to interferon is unclear. High-dose induction interferon may enhance early viral clearance, whilst ribavirin reduces relapse; in combination, they may improve sustained virological response rates. AIM: To compare the efficacy and safety of re-treatment with interferon induction, with or without ribavirin, in interferon non-responders. METHODS: We randomized 218 biochemical interferon non-responders to 10 MU interferon alpha 2b daily for 4 weeks, followed by 5 MU thrice weekly for 48 weeks plus ribavirin (II + R), or to the same interferon regimen plus placebo (II + P). All patients were viraemic at entry. RESULTS: The sustained virological response in the II + R group was 39%[95% confidence interval (CI), 30-48%], compared with 16% (95% CI, 9-23%) in the II + P group (P < 0.002). The study drug was discontinued for intolerable symptoms during induction in 9% of the II + R group and in 5% of the II + P group. By logistic regression, a sustained virological response was more likely following II + R treatment (odds ratio, 4.4; 95% CI, 2.1-9.7) and less likely in patients with genotype 1 or 4 (odds ratio, 0.16; 95% CI, 0.07-0.36). CONCLUSION: High-dose induction interferon plus ribavirin is well tolerated and effective for patients unresponsive to interferon alone.

Adolescent↗
PubMed1980

Interferon induction by viruses. VI. Reovirus: virion genome dsRNA as the interferon inducer in aged chick embryo cells.

The interferon-inducing particle (IFP) activity of avian and human reoviruses in aged chick embryo cells was determined by analyzing dose (multiplicity)-response (interferon yield) curves. These curves fit best a model in which each cell infected with greater than or equal to 1 IFP produces a quantum yield of interferon. Avian reovirus stocks contained as many as 60 times more IFP than plaque-forming particles (PFP). Upon UV-irradiation the ratio of IFP:PFP became 197, suggesting that virtually every physical particle of avian reovirus could function as an interferon-inducing particle. Thus, about one-third of the non-infectious particles were intrinsically IFP and the other two-thirds could be converted to IFP status at an optimal dose of UV radiation, the equivalent of 9.4 lethal hits, i.e., 8000 ergs/mm2. UV-irradiated avian reovirus induced about twice the usual yield of interferon on a per cell basis. Wildtype human reovirus (type 3) and mutants ts201(A,RNA+) and ts447(C,RNA-) were excellent inducers of interferon, but only about 1 in 3 infectious particles functioned as an interferon-inducing particle, meaning that virtually all physical particles failed to function as IFP, UV-irradiation of human reoviruses resulted in a slight loss of IFP activity. Our data support the hypothesis that virion genome dsRNA constitutes the interferon inducer moiety of avian reoviruses and that in its permissive host cell the processing of genome dsRNA from most particles to a putative recognition site in the cytoplasm occurs naturally with a high probability. For human reovirus this is a much rarer event which may be intrinsic only to infectious virus, and may require limited transcription for expression. The sensitivity of the avian reovirus-aged chick embryo cell system recommends it for further study on the mechanism of interferon induction by virions containing pre-existing dsRNA.

Animals↗
PubMed1979

Interferon induction by viruses. II. Sindbis virus: interferon induction requires one-quarter of the genome--genes G and A.

We have measured the amounts of interferon formed by chick cells 'aged' in vitro in response to different amounts of infectious wild-type Sindbis virus. Our results suggest that one plaque-forming unit is enough to induce maximum interferon formation. With higher m.o.i. the yield of interferon is less. To inactivate the interferon-inducing activity of Sindbis virus, four times more u.v.-radiation was needed than to inactivate the infectivity of the virus. This suggests that only 25% of the virus genome need be intact in order to induce interferon. Temperature-sensitive Sindbis virus mutants from the three RNA+ complementation groups, C. D and E, gave rise to interferon in chick cells incubated at a non-permissive temperature, Similarly, mutants from two of the RNA- groups, B and F, gave rise to interferon, but not mutants from groups G and A. We conclude that no pre-formed inducer of interferon is present in Sindbis virus. It appears, however, that genes G and A represent a special one-quarter of the genome which must be functional in order to synthesize an interferon-inducing moiety. We suggest that this moiety is a double-stranded RNA molecule formed after synthesis of a segment of RNA complementary to the genome.

Animals↗
PubMed1988

Interferon induction by viruses. XVI. 2-Aminopurine blocks selectively and reversibly an early stage in interferon induction.

A purine analogue, 2-aminopurine, reported to act as an inhibitor of protein kinase, selectively, reversibly and in a dose-dependent manner blocked a very early stage in interferon induction. With chick embryo cells and mouse L cells as hosts, and different viral inducers of interferon, maximal effects of 2-aminopurine were observed during the first 4 h of induction. At 10 mM-2-aminopurine there was a 20-fold reduction in the yield of interferon from both cell types. 2-Aminopurine and actinomycin D both prevented interferon induction with the same time course, indicating a transcriptional block to induction; however, only the action of the former was reversed upon removal of the drug. Addition of 2-aminopurine to an agarose overlay resulted in high efficiency plaque formation by vesicular stomatitis virus New Jersey (Hazelhurst) under conditions where endogenous induction of interferon and its feedback action on aged chick embryo cells normally prevented plaque formation. Two other inducible systems, representing genes involved in interferon action (both its development and activation), and those of heat shock, were not affected by 2-aminopurine. A model is presented implicating the interferon-inducible dsRNA-dependent protein kinase as an interferon induction receptor which, on interaction with dsRNA, generates an amplified signal via phosphorylation that ultimately derepresses the interferon gene(s).

2-Aminopurine↗
PubMed2003

Twenty-four vs. forty-eight weeks of re-therapy with interferon alpha 2b and ribavirin in interferon alpha monotherapy relapsers with chronic hepatitis C.

BACKGROUND/AIM: Roughly 50% of patients with chronic hepatitis C, who relapsed after a previous monotherapy with interferon alpha, will respond in a sustained fashion to 24 weeks of re-therapy with the combination of interferon alpha plus ribavirin. Whether prolonging treatment duration to 48 weeks will further increase sustained response rates remains ill defined. In this randomised controlled pilot trial we compared the efficacy and tolerability of a 24 week with that of a 48 week course of combination therapy with interferon alpha and ribavirin in interferon monotherapy relapsers with chronic hepatitis C. METHODS: Interferon alpha monotherapy relapsers with chronic hepatitis C were randomised to receive interferon alpha 2b (3 x 3 MIU sc weekly) and oral ribavirin (1000/1200 mg po daily) for either 24 weeks or 48 weeks. Virological response was evaluated by HCV RNA PCR at week 10 (initial response), at the end of treatment (end of- treatment response) and at the end of 24 weeks follow-up (sustained response). Only patients with negative HCV RNA at week 10 continued treatment. Adverse events were recorded at regular intervals. RESULTS: Thirty-seven patients were enrolled, 19 (6 females, median age 43) in the 24 week and 18 (5 females, median age 40) in the 48 week treatment arm. Baseline characteristics were similar in both groups. At treatment week 10, 12/19 (63%) in the 24 week group and 14/18 (78%) patients in the 48 week group had lost HCV RNA in serum (p = 0.33). All initial responders remained HCV RNA negative throughout the treatment period. Sustained response rates were 10/19 (53%) in the 24 week group and 13/18 (72%) in the 48 week group (p = 0.31). Three patients discontinued treatment early (two due to moderate adverse events, one due to non-compliance). Dose modifications were necessary in 9 patients, 4 in the 24 week and 5 in the 48 week group for anaemia, neutropenia, nausea and depression, respectively. CONCLUSION: Prolonging interferon / ribavirin combination therapy in interferon alpha monotherapy relapsers with chronic hepatitis C from 24 to 48 weeks may increase sustained response rates. Larger controlled trials using pegylated interferon alpha and ribavirin in relapsers with chronic hepatitis C seem warranted.

Adult↗
PubMed2002

Triple antiviral re-therapy for chronic hepatitis C with interferon-alpha, ribavirin and amantadine in nonresponders to interferon-alpha and ribavirin.

BACKGROUND: Therapy options for patients with chronic hepatitis C who failed prior treatment are needed. In recent studies triple antiviral therapy with Interferon-alpha, ribavirin, and amantadine seemed to increase sustained virological response rates in this group. METHOD: To evaluate efficacy, side effects and safety of a triple re-therapy in an open labeled prospective study, we compared 23 nonresponders to interferon monotherapy (9 nonresponders, 3 relapsers, 11 with breakthrough) with 23 nonresponders to standard combination therapy (interferon plus ribavirin) (16 nonresponders, 7 breakthroughs). All outpatients enrolled for re-therapy received interferon-alpha 2a (6 mega units [MU] three times in week), ribavirin (1000-1200 mg daily in divided doses) and amantadine (200 mg daily) for six months. In case of virological re-therapy response (negative qualitative HCV RNA) study medication was continued with interferon monotherapy for another six months. RESULTS: Sustained virological response was achieved in 16 (35%) out of 46 prior therapy nonresponders. Response rates were dependent on pretreatment outcome. In the standard combination therapy group only 1 (6%) primary nonresponder achieved sustained response, but none of the 9 monotherapy nonresponders did. After primary breakthrough sustained response was seen in 8 of 11 (73%) patients in the interferon monotherapy and in 5 of 7 (71%) in the combination therapy group. Of 3 monotherapy relapsers 2 (66%) did also clear the virus sustained. Safety profile under triple therapy was similar to the previous therapy. Compliance was higher and side effects lower in those patients already experienced in combination therapy. CONCLUSION: In patients with a breakthrough or relapse after interferon monotherapy or standard combination therapy with interferon and ribavirin a re-therapy with a triple combination of interferon, ribavirin, and amantadine results in a high rate of sustained virological response.

Adult↗
PubMed1992

Treatment with interferon gamma versus interferons alfa and gamma in children with chronic hepatitis B.

Thirty-five children with chronic hepatitis B were randomly assigned to three groups: group 1 (n = 12), untreated; group 2 (n = 11), treated with 1 million units of interferon gamma per square meter of body surface (MU/m2), three times a week for 24 weeks; and group 3 (n = 12), treated with interferon alfa at a dose of 5 MU/m2, three times a week for 12 weeks followed by 1 MU/m2 of interferon gamma with the same schedule. At the end of the treatment (6th month), hepatitis B virus DNA was negative in 16.5% of the control group, in 9% of the children treated with interferon gamma, and in 16.5% of those treated with interferons alfa and gamma. No child had lost the hepatitis B e antigen by this time. No basal differences in the serum hepatitis B virus DNA concentration among the groups were observed. At follow-up (15th month), viral genome was negative in 25% of the untreated children, in 36% of the group treated with interferon gamma, and in 41.5% of the children who had received interferons alfa and gamma. Hepatitis B e antigen was negative in 25% of the children who belonged to groups 1 and 3 and in 27% of the children treated with interferon gamma only. These data suggest that interferon gamma does not have a powerful antiviral effect on chronic hepatitis B in children. However, it is well tolerated.

Adolescent↗
PubMed1991

Gamma interferon-like immunoreactive material in rat neurons: evidence against a close relationship to gamma interferon.

Gamma interferon is a potent immunoregulatory peptide produced by activated lymphocytes. Recently, a gamma interferon-like immunoreactive molecule has been demonstrated immunohistochemically in subpopulations of rat neurons. We have now further characterized this molecule. Western blot analysis of spinal ganglia homogenates revealed a single 60,000 mol. wt band that was immunoreactive with monoclonal antibody DB1 directed against rat gamma interferon. A polyclonal antiserum and the monoclonal antibodies DB10 and DB12 failed to detect this band although all antibodies were able to label the major 18,000 mol. wt band of recombinant gamma interferon on the same blots. The 60,000 mol. wt band was selectively present in homogenates from primary sensory and sympathetic ganglia but was absent from the central nervous system and other peripheral organs, corresponding to the reported immunocytochemical distribution of gamma interferon-like immunoreactivity. The 60,000 mol. wt protein does not appear to be glycosylated. It could not be solubilized by detergents such as Triton X-100 and it co-purified with cytoskeleton-enriched preparations. At the nucleic acid level, Northern blot analysis using probes specific for rat gamma interferon mRNA failed to detect specific mRNA in rat spinal ganglia, whereas a strong 1.2 kb signal was detected in activated spleen cells. Functionally, gamma interferon-like immunoreactive material is strongly induced in superior cervical ganglion neurons after preganglionic axotomy of the sympathetic chain, but remains constant or slightly decreases in L5 spinal ganglion neurons after sciatic nerve transection. In contrast, major histocompatibility complex antigens are strongly induced on non-neuronal cells in both systems. We conclude that the neuronal gamma interferon-like immunoreactive material is clearly distinct from lymphocyte-derived gamma interferon and might not be involved in the control of major histocompatibility complex expression on glial cells.

Animals↗
PubMed1987

Quantitation of ozone-induced lung lesion density after treatment with an interferon inducer or an anti-interferon antibody.

Inhalation of ozone by experimental animals produces activation of lymphocytes in the mediastinal lymph node complex. Both the number and functional reactivity are affected, with evidence of blastic transformation in T cell but not B cell areas of the nodes. In the present work we determine the extent that modulation of a possible product of immune system activation, interferon, is capable of influencing the way that experimental animals respond to zone. Outbred CD-1 mice were treated with an interferon inducer, poly I:C, or with an anti-interferon antibody while being exposed to ozone at a concentration of 0.7 or 0.9 ppm for 20 h per day for 4 days. Interferon induction produced a significant reduction in lesion volumes in both exposure groups, while anti-interferon produced the opposite effect. Less alveolar damage was observed in interferon-induced, ozone-exposed animals than in animals exposed to ozone alone. In contrast, anti-interferon-treated, ozone-exposed animals showed larger lesions which extended to more peripheral structures and were more extensively infiltrated with neutrophilic leukocytes. These results show that interferon induction protects against zone-mediated lung damage. They also suggest that cells are activated during ozone inhalation which mitigate the effects of ozone on the lung by secretion of interferon.

Animals↗
PubMed1983

A comparison of vertebrate interferon gene families detected by hybridization with human interferon DNA.

Cloned human interferon complementary DNAs were used as hybridization probes to detect interferon alpha and beta gene families in restriction endonuclease digests of total genomic DNA isolated from a wide range of vertebrates and invertebrates. A complex interferon-alpha multigene family was detected in all mammals examined, whereas there was little or no cross-hybridization of human interferon-alpha complementary DNA to non-mammalian vertebrates or invertebrates. In contrast, human interferon-beta complementary DNA detected one or two interferon-beta genes in all mammals tested, with the exception of the cow and the blackbuck, both of which possessed a complex interferon-beta multigene family which has presumably arisen by a recent series of gene duplications. Interferon-beta sequences could also be detected in non-mammalian vertebrates ranging from birds to bony fish. Detailed restriction endonuclease mapping of DNA sequences neighbouring the interferon-beta gene in a variety of primates indicated a strong evolutionary conservation of flanking sequences, particularly on the 3' side of the gene.

Animals↗
PubMed1999

Interferon-alpha plus ribavirin in chronic hepatitis C resistant to previous interferon-alpha course: results of a randomized multicenter trial.

BACKGROUND/AIMS: Interferon-alpha plus ribavirin seem to be more efficacious than interferon monotherapy in chronic hepatitis C. In a multicenter randomized trial, we evaluated the efficacy of this association for interferon-alpha resistant chronic hepatitis C. METHODS: Fifty patients who were non-responders to recombinant or lymphoblastoid interferon-alpha were randomized to receive either ribavirin (800 mg/day) plus leucocytic interferon-alpha (3 mega units thrice weekly) or the same dose of interferon-alpha alone, for 6 months. Effects of therapy were evaluated by serum aminotransferase and hepatitis C virus RNA levels and control liver biopsies. RESULTS: At the end of treatment, aminotransferase levels become normal in 9/26 patients receiving combination therapy (35% [confidence interval, 16% to 53%]) and in 2/24 receiving interferon-alpha alone (8% [confidence interval, -3% to 19%]) (p = 0.03). Aminotransferase normalization was never associated with hepatitis C virus RNA clearance. All patients with normal aminotransferase relapsed after discontinuation of therapy. At the end of treatment, mean hepatitis C virus RNA levels significantly decreased only in the group receiving combination therapy, but returned to pretreatment values 6 months thereafter. No histological improvement was observed in either group. CONCLUSIONS: There is no indication for treatment with interferon-alpha at the dose of 3 mega units thrice weekly plus 800 mg/day of ribavirin for 6 months in chronic hepatitis C resistant to interferon-alpha.

Antiviral Agents↗
PubMed2001

Combination therapy with ribavirin and alpha interferon for the treatment of chronic hepatitis C refractory to interferon.

BACKGROUND: Up to 80% of hepatitis C patients are refractory to treatment with interferon-alpha. These patients are not likely to benefit from higher dosages or longer duration of interferon alone. The addition of ribavirin has been shown to improve the response rate in patients resistant to a previous course of interferon-alpha alone. AIM: To evaluate whether a sustained hepatitis C virus (HCV) RNA response could be obtained with combination therapy of interferon-alpha and ribavirin in patients who did not respond to or relapsed after a standard interferon-alpha treatment. METHODS: A total of 73 patients, 59 non-responders and 14 relapsers after interferon-alpha alone, were treated with a combination of ribavirin (1000-1200 mg/day) and interferon-alpha (3 MU three times a week) for 24 weeks. Alanine aminotransferase levels and HCV RNA were checked for 24 weeks after completion of therapy. RESULTS: At the end of the combination therapy, 36 patients (49%) showed alanine aminotransferase normalization and in 20 patients (27%), HCV RNA was undetectable in serum. At the end of the 24 weeks follow-up period, only 12 patients (16%) had a sustained response with serum negativity of HCV RNA. This response was significantly higher in relapsers than in non-responders: five (36%) vs. seven (12%) patients (P=0.03), respectively. Adverse effects were restricted to flu-like symptoms and moderate haemolytic anaemia. CONCLUSIONS: Combination of interferon-alpha and ribavirin is quite limited, both in scope and efficacy, in HCV patients who had a non-response to monotherapy with interferon. Better results may be expected in relapsers, but larger studies are necessary.

Adult↗
PubMed2002

Modulation in vitro of keratinocyte integrins by interferon-alpha and interferon-gamma.

BACKGROUND: Interferon-alpha and -gamma are glycoproteins with antiviral and immunoregulatory properties. In vitro studies have shown a role for these cytokines in the regulation of epidermal keratinocyte growth and differentiation. In the same way, integrins are adhesion molecules which regulate keratinocyte proliferation and differentiation. AIM: To determine whether the regulatory activity of interferons on keratinocyte proliferation and differentiation is related to a modulation of keratinocyte integrins. METHODS: Two different methods were used: monolayers and reconstituted skin, incubated either with 1,200 U/mL interferon-alpha or 500 U/mL interferon-gamma or control medium for 48 h. The integrin expression was assessed by flow cytometry and immunohistochemistry. RESULTS: In monolayers, only the alpha3 subunit was significantly inhibited by interferon-gamma. In reconstituted skin, where keratinocytes are differentiated, both interferons had an inductive effect on beta1 expression and interferon-alpha had an inhibitory effect on alpha6 expression. CONCLUSION: Interferon-alpha and -gamma induce a modulatory effect on alpha3, alpha6 and beta1 which appears to be related to the state of differentiation. Moreover, the decreased expression of alpha6 and alpha3 could be one of the mechanisms involved in the formation of bullous lesions during long-term interferon therapy.

Antigenic Modulation↗