SEARCH · PubMed Health

Results for “INTERFERON”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 73 records · Page 4Linked to original sources

PubMed1983

Human interferon-gamma enhances the expression of class I and class II major histocompatibility complex products in neoplastic cells more effectively than interferon-alpha and interferon-beta.

Human interferon-gamma was more effective than interferon-beta or -alpha in stimulating production of immunoassociated antigens; HLA-A, -B, and -C; and beta(2)-microglobulin in human M14 and Namalva cells. The comparison was made on the basis of antiviral units, and the stimulation could be abolished by treatment of the interferon-gamma preparation with pH 2 or anti-interferon-gamma serum.

Animals↗

PubMed1990

Modulation of interferon receptor expression during combination beta ser-interferon and gamma-interferon treatment of human colon carcinoma cells.

Combination treatment of SKCO1 human colon carcinoma cells with beta ser-interferon (IFN-beta ser) and gamma-interferon (IFN-gamma) results in a synergistic antiproliferative effect. The role of IFN-beta ser and IFN-gamma receptor modulation was investigated as a possible mechanism for this response. IFN-gamma (0.05-50 ng/ml) pretreatment of SKCO1 cells for 24 h decreased specific binding of 125I-IFN-beta ser by 35-60%. Scatchard analysis of binding data obtained following 24-h treatment with 5 ng/ml IFN-gamma showed that this reduction in binding was due to a decreased receptor affinity (control cells, Kd = 46 +/- 1.6 pM; IFN-gamma-treated cells, Kd = 106 +/- 6 pM, n = 2) rather than a significant change in receptor number (receptor number/control cell = 1214 +/- 471, receptor number/IFN-gamma treated cell = 1118 +/- 153, n = 2). In contrast, pretreatment of SKCO1 cells with IFN-beta ser (5 ng/ml) resulted in slight (10-35%) increases in 125I-IFN-gamma-specific binding. Scatchard analysis of binding data obtained following 24-h treatment with 5 ng/ml IFN-beta ser showed a decrease in binding affinity (control cells, Kd = 28 +/- 7 pM; IFN-beta ser-treated cells, Kd = 38 +/- 7 pM, n = 2) and a 32% increase in IFN-gamma receptor sites (receptor number/control cell = 4257 +/- 464, receptor number/IFN-beta ser-treated cell = 5570 +/- 730; n = 2). 125I-IFN-gamma internalization studies performed at 37 degrees C confirmed the cell surface binding assays; IFN-beta ser-treated cells internalized 30-50% more labeled IFN-gamma than untreated cells. However, it is unlikely that differences in binding and internalization of this magnitude play a primary role in the synergistic antiproliferative effect of IFN-gamma with IFN-beta ser in SKCO1 cells. Biochemical modulation at sites distal to the ligand receptor interaction should be investigated.

Cell Division↗

PubMed1984

Potentiating effect of murine interferon-gamma-containing lymphokine preparations on the antiviral and antiproliferative effects of murine interferon-alpha/beta: identification of the potentiation factor as murine interferon-gamma itself.

Mixed preparations of murine interferon-gamma (MuIFN-gamma) and murine interferon-alpha/beta (MuIFN-alpha/beta) have been shown to induce more than additive levels of antiviral protection, when compared to those induced by these interferons given separately. MuIFN-gamma preparations contain many lymphokines and several of these as well as MuIFN-gamma itself may participate in this potentiation. In the present study, natural as well as three recombinant DNA-derived MuIFN-gamma's, in combination with antibody to MuIFN-gamma have been employed to examine the precise role of MuIFN-gamma. The antiviral effect was examined with a single cycle virus yield reduction assay and the antiproliferative effect with a colony formation inhibition assay. Recombinant DNA-derived MuIFN-gamma was as effective as natural MuIFN-gamma at participating in the potentiation of both the antiviral and antiproliferative activities. Antibody to MuIFN-gamma effectively blocked the potentiation of both the antiviral and the antiproliferative activities of natural and recombinant DNA-derived MuIFN-gamma's. Since the recombinant DNA-derived preparations from E. colie can be assumed not to contain mammalian proteins other than MuIFN-gamma, the data conclusively demonstrate that the potentiation factor in MuIFN-gamma preparations is MuIFN-gamma itself.

Animals↗

PubMed1983

A new mass-spectrometric C-terminal sequencing technique finds a similarity between gamma-interferon and alpha 2-interferon and identifies a proteolytically clipped gamma-interferon that retains full antiviral activity.

A novel mass-spectrometric technique is described that permits the identification of the C-terminal peptide of a protein. The technique involves the incorporation of 18O into all alpha-carboxy groups liberated during enzyme-catalysed partial hydrolysis of the protein, followed by mass spectrometry to identify as the C-terminal peptide the only peptide that did not incorporate any 18O. The technique has been used to identify the true C-terminal tryptic peptide of a bacterially produced gamma-interferon and to distinguish it from a peptide produced by anomalous tryptic cleavage. It was found that a closely similar sequence segment of bacterially produced alpha 2-interferon undergoes an analogous cleavage. The technique was also used to identify the C-terminus of a clipped gamma-interferon that retains full antiviral activity.

Amino Acid Sequence↗

PubMed2001

Measurement of intracellular cytokines in MS patients treated with beta-interferon and association of a beta-interferon induced exacerbation with increased expression of gamma-interferon by monocytes.

The effects that immunomodulatory agents such as beta-Interferon (IFN-beta) exert upon cytokine production in autoimmune disease such as multiple sclerosis remain incompletely understood. The recent development of techniques to directly assess cytokine production within peripheral blood leucocytes promises to advance this field. beta-Interferon treatment occasionally causes short-lived exacerbations of neurological dysfunction, often associated with systemic flu-like symptoms. Whereas these side effects usually occur and remit within the first few months of therapy, we have identified several patients who have developed symptoms many months after the onset of treatment. To begin to investigate the cause of these late onset exacerbations, we assessed the intracellular cytokine profiles of two patients, one stable on IFN-beta treatment and another experiencing side effects. The latter patient exhibited an increase in the percentage of monocytes that expressed g-Interferon after IFN-beta administration, whereas no such modulation was seen in the patient without side effects.

Adjuvants, Immunologic↗

PubMed1993

Role of the nitric oxide synthase pathway in inhibition of growth of interferon-sensitive and interferon-resistant Rickettsia prowazekii strains in L929 cells treated with tumor necrosis factor alpha and gamma interferon.

The ability of tumor necrosis factor alpha (TNF-alpha) alone and in combination with gamma interferon (IFN-gamma) to inhibit the growth of interferon-sensitive and -resistant Rickettsia prowazekii strains in mouse L929 cells was examined, and the possible role of the nitric oxide synthase pathway in the suppression of rickettsial growth induced by TNF-alpha, IFN-gamma, or both cytokines was evaluated. TNF-alpha inhibited the growth of strains Madrid E (IFN-gamma sensitive and alpha/beta interferon [IFN-alpha/beta] sensitive) and Breinl (IFN-gamma sensitive and IFN-alpha/beta resistant), but not that of strain 83-2P (IFN-gamma resistant and IFN-alpha/beta resistant), in L929 cells. Inhibition of the growth of the Madrid E strain in L929 cells treated with TNF-alpha and IFN-gamma in combination was greater than that observed with either TNF-alpha or IFN-gamma alone. Similarly, inhibition of the growth of the Breinl strain in L929 cells treated with both cytokines was greater than that observed with TNF-alpha alone; however, it did not differ significantly from the inhibition observed with IFN-gamma alone. Although strain 83-2P was resistant to TNF-alpha or IFN-gamma alone, its growth was inhibited in L929 cells treated with TNF-alpha and IFN-gamma in combination. Nitrite production was measured in mock-infected and infected L929 cell cultures, and the nitric oxide synthase inhibitors NG-methyl-L-arginine (NGMA) and aminoguanidine were used to evaluate the role of the nitric oxide synthase pathway in cytokine-induced inhibition of rickettsial growth. Nitrite production was induced in mock-infected or R. prowazekii-infected L929 cell cultures treated with IFN-gamma plus TNF-alpha, but not in mock-infected cultures that were untreated or treated with IFN-gamma or TNF-alpha alone. Nitrite production was also not induced in untreated, R. prowazekii-infected cultures; however, in some instances, it was induced in infected cultures treated with IFN-gamma or TNF-alpha alone. Nitrite production was blocked by NGMA or aminoguanidine, and these compounds markedly relieved the synergistic inhibitory effect of IFN-gamma plus TNF-alpha on the growth of strain 83-2P in L929 cells. In contrast, NGMA did not alleviate the inhibition of the growth of the Madrid E strain in L929 cells treated with IFN-gamma or TNF-alpha alone; however, it slightly and variably relieved the inhibition of the growth of the Madrid E strain in L929 cells treated with IFN-gamma and TNF-alpha in combination.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Oxidoreductases↗

PubMed2006

Genetic polymorphism of interferon-gamma, interferon-gamma receptor, and interferon regulatory factor-1 genes in patients with hepatitis B virus infection.

The natural history of hepatitis B virus (HBV) infection is probably related to host immune factors. Interferon-gamma (IFN-gamma) plays significant roles in immune defense. This study was undertaken to investigate the association between HBV infection and single nucleotide polymorphisms (SNPs) of IFN-gamma, IFN-gamma receptor (IFNGR)-1 and 2, and interferon regulatory factor (IRF)-1 genes. Between March 2002 and December 2002, 614 Korean patients were enrolled in two different groups: an HBV clearance group (n = 201), who were hepatitis B surface antigen (HBsAg) negative with antibodies to HBsAg and hepatitis B core antigen, and an HBV persistence group (n = 413), who were repeatedly HBsAg positive. We assessed polymorphisms in the IFN-gamma gene at position +874, in the IFNGR-1 gene at positions -56 and +95, in the IFNGR-2 gene at the second position of codon 64 (Gln64Arg), and in the IRF-1 gene promoter (-410, -388), and the genotype distributions of the HBV clearance and persistence groups were compared. On the basis of unconditional logistic regression analysis with adjustment for age and sex, no statistically significant association with susceptibility to persistent HBV infection was observed with the IFN-gamma, IFNGR-1 and 2, and IRF-1 gene polymorphisms under the codominant, dominant, and recessive models.

Adolescent↗

PubMed1993

Induction of type I interferon genes and interferon-inducible genes in embryonal stem cells devoid of interferon regulatory factor 1.

Overexpression of interferon regulatory factor 1 (IRF-1) can induce expression of the interferon (IFN) beta gene, at least in certain cells. A role of IRF-1 in the activation of IFN-alpha genes has also been claimed. We have generated embryonal stem cells in which both IRF-1 alleles were disrupted. In undifferentiated embryonal stem cells, virus-induced levels of IFN-alpha RNA were similar for wild-type and IRF-1%, and there was little induction of IFN-beta RNA in either cell type. In 8-day differentiated cells, the levels of virus-induced IFN-beta RNA, but not of IFN-alpha RNA, were about 10-fold higher than in undifferentiated cells and only slightly higher in wild-type than in IRF-1% cells. Thus, although IRF-1 at high levels may elicit or augment induction of IFN genes under certain circumstances, it is not essential for IFN gene induction by virus. Lack of IRF-1 had no effect on the IFN-induced expression levels of the IFN-inducible genes tested; however, there was little or no constitutive expression of (2'-5')oligoadenylate synthetase in IRF-1% embryonal stem cells, in contrast to wild-type cells.

Animals↗

PubMed1999

The proximal tyrosines of the cytoplasmic domain of the beta chain of the type I interferon receptor are essential for signal transducer and activator of transcription (Stat) 2 activation. Evidence that two Stat2 sites are required to reach a threshold of interferon alpha-induced Stat2 tyrosine phosphorylation that allows normal formation of interferon-stimulated gene factor 3.

The precise role of the different subunits (alpha/IFNAR1 and betaL/IFNAR2) of the type I interferon receptor (IFN-R) in the activation of signal transducer and activator of transcription (Stat) 1, Stat2, and Stat3 has not yet been established. In this report we demonstrate that there are functionally redundant phosphotyrosine-dependent and -independent binding sites for Stat2 in the alpha and beta subunits of the type I IFN-R. Expression of a type I IFN-R containing only the constitutive Stat2 site or the proximal tyrosines of betaL, but not the docking site on the alpha chain (Tyr466 and Tyr481), supported low levels of Stat2 activation. However, the presence of only one intact Stat2 site did not lead to induction of interferon-stimulated gene factor 3 (ISGF3) or an antiviral state. Normal levels of Stat2 tyrosine phosphorylation, induction of ISGF3, and an antiviral effect always required the proximal tyrosines of betaL and at least one of the other Stat2 sites (Tyralpha466, 481 or betaL404-462). These data suggest that a threshold of Stat2 tyrosine phosphorylation is required for complete activation of ISGF3. Interestingly, a receptor in which all tyrosines were mutated to phenylalanine shows normal Stat3 phosphorylation and low levels of activation of Stat1.

Animals↗

PubMed1999

Interferon consensus sequence binding protein and interferon regulatory factor-4/Pip form a complex that represses the expression of the interferon-stimulated gene-15 in macrophages.

Interferon consensus sequence binding protein (ICSBP), a transcription factor of the interferon (IFN) regulatory factor (IRF) family, binds to the IFN-stimulated response element (ISRE) in the regulatory region of IFNs and IFN-stimulated genes (ISG). To identify target genes, which are deregulated by an ICSBP null-mutation in mice (ICSBP-/-), we have analyzed transcription of an ISRE-bearing gene, ISG15. We have found that although ISG15 expression is unchanged in B cells, it is upregulated in macrophages from ICSBP-/- mice. Three factors, ICSBP, IRF-2, and IRF-4/Pip interact with the ISRE in B cells, however only ICSBP and IRF-4/Pip were found to bind this sequence in macrophages of wild-type mice. Although IRF-4 was considered to be a lymphoid-specific factor, we provide evidence for its role in macrophage gene regulation. Our results suggest that the formation of cell-type-specific heteromeric complexes between individual IRFs plays a crucial role in regulating IFN responses.

Animals↗

PubMed2002

Interferon-gamma, interleukin-18, monokine induced by interferon-gamma and interferon-gamma-inducible protein-10 in histiocytic necrotizing lymphadenitis.

Apoptosis of histiocytes is a characteristic feature of necrotizing lymphadenitis (HNL). Recent studies have indicated that Fas and perforin-based pathways are involved in the apoptotic process of HNL. Elevated levels of serum interferon (IFN)-gamma are reported in HNL. The CXC chemokine interferon-gamma-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) cause tissue necrosis, and interleukin (IL)-18 induces the expression of IFN-gamma and Fas ligand (FasL) by T and natural killer (NK) cells. This study was designed to determine the expression of IFN-gamma, IL-18, MIG and IP-10 in HNL. Ten cases of HNL were analyzed by using immunohistochemical staining and/or reverse transcriptase-polymerase chain reaction (RT-PCR). As a control, we included four cases of non-specific lymphadenitis. MIG and IP-10 proteins, which enhance the release of granzyme, showed a similar distribution pattern in viable tissues surrounding dead tissue, mostly within histiocytes, and lymphocytes in HNL. IL-18 was located within histiocytes, especially phagocytic histiocytes, but not within lymphocytes. In addition, IFN-gamma-positive lymphocytes were frequently detected in the surrounding dead tissue, and the lymphocytes in the same area were frequently positive for CXCR3, a specific receptor of MIG and IP-10. In non-specific lymphadenitis, MIG, IP-10 and IL-18 positive cells were detected, but their numbers were relatively small compared with HNL, while IFN-gamma positive cells were rarely encountered. Our findings suggest that the cytokine and chemokine pathways of IFN-gamma, IL-18, MIG and IP-10 play an important role in the pathogenesis of apoptosis associated with HNL.

Adolescent↗

PubMed1999

Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon. The Consensus Interferon Study Group.

Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a "breakthrough" while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-alpha2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18%) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19%) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs (P =.102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in those without breakthroughs (P =.014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.

Alanine Transaminase↗

PubMed1994

The human interferon alpha-receptor protein confers differential responses to human interferon-beta versus interferon-alpha subtypes in mouse and hamster cell transfectants.

The human interferon alpha-receptor (IFNAR gene product or IFN alpha R protein) was expressed in hamster CHO cells and in mouse A9 cells. The response of the IFN alpha R cDNA transfectants to human IFNs was studied by measuring induction of (2'-5') A synthetase (2'-5' AS). In the murine cells, the IFN alpha R protein conferred response to the human IFN-alpha-8 (alpha-B) subtype, but not to huIFN-alpha-2 (alpha-A) or to huIFN-beta. In murine huIFN alpha R cDNA transfectants, containing a hygromycin B resistance gene placed under the control of the 2'-5' AS gene Interferon Response Sequence (IRS), survival and growth of the cells in the presence of hygromycin B was induced by huIFN-alpha-8 but not by huIFN-alpha-2, indicating that the effect of huIFN alpha R is transcriptional. In hamster CHO cells, the huIFN alpha R protein conferred a completely different pattern of response to human IFN subtypes. Thus, the CHO-IFN alpha R transfectants responded to huIFN-beta by 2'-5' AS induction as well as by activation of the ISGF3 and IRF-1 transcription factors. In contrast, the CHO-IFN alpha R cells showed no response to huIFN-alpha-8. The differential response conferred by the huIFN alpha R protein in the two types of rodent cells, indicates that IFN subtype recognition is influenced by another component contributed by the rodent host cell. The ability of human cells, and of human-mouse hybrid cells containing human chromosome 21, to respond to all IFN subtypes is likely to depend also on interactions of the IFN alpha R protein with additional receptor components.

2',5'-Oligoadenylate Synthetase↗

PubMed1990

A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma.

This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously.

Adolescent↗

PubMed2006

Dynamics of interferon-specific gene expression in peripheral blood of interferon alfa-naïve patients with genotype 1 chronic hepatitis C infection treated with albumin-interferon alfa.

Albumin-interferon alfa (alb-IFN) is a novel recombinant protein derived from IFNalpha-2b genetically fused to human albumin, which combines in a single polypeptide the antiviral properties of IFNalpha with the long serum half-life of albumin. Interferon alfa (IFNalpha) mediated biological responses stem from the engagement of IFNalpha with its target receptor and subsequent modulation of interferon-specific gene (ISG) expression. The dynamics of ISG expression were evaluated in a Phase 2a study conducted in IFNalpha naïve patients with genotype 1 chronic hepatitis C (CHC) treated with alb-IFN. Whole blood was obtained pre-dose and on days 7 and 28 from 47 patients enrolled to receive two subcutaneous injections of alb-IFN 14 days apart in five dose cohorts ranging from 200 to1200mug. Gene expression of nine candidate genes including four ISGs was determined by a TaqMan Real-time PCR assay. There was sustained >5-fold median induction on days 7 and 28 of the ISG's- OAS1, IRF7, IFI44 and IFI27. While all subjects showed a molecular response to alb-IFN, individual variability in pre-treatment gene expression levels and fold of modulation during treatment was observed. At days 7 and 28, induction of OAS1, IFI44 and IRF7 showed significant pair-wise correlation in individual patients (r>0.7 and P<0.001). There was no correlation of baseline expression or induction of gene expression with antiviral response. In conclusion, alb-IFN demonstrated robust induction of ISG that was consistent with the molecular response associated with an IFNalpha.

Journal Article↗

PubMed2001

Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) alphabeta+ CD8+ single-positive T cells, TCRgammadelta+ T cells, and natural killer-type cells in human thymus.

Strong reactivity for interferon-inducible protein 10 (IP-10), monokine induced by interferon gamma (Mig), and interferon-inducible T-cell alpha chemoattractant (I-TAC) was found in epithelial cells mainly localized to the medulla of postnatal human thymus. The CXC chemokine receptor common to the 3 chemokines (CXCR3) was also preferentially expressed in medullary areas of the same thymuses and appeared to be a property of 4 distinct populations: CD3+ T-cell receptor (TCR) alphabeta+ CD8+ single-positive (SP) T cells, TCRgammadelta+ T cells, natural killer (NK)-type cells, and a small subset of CD3+(low) CD4+ CD8+ TCRalphabeta+ double-positive (DP) T cells. IP-10, Mig, and I-TAC showed chemoattractant activity for TCRalphabeta+ CD8+ SP T cells, TCRgammadelta+ T cells, and NK-type cells, suggesting their role in the migration of different subsets of mature thymocytes during human thymus lymphopoiesis.

CD8-Positive T-Lymphocytes↗

PubMed1992

The Japanese Interferon Study Group (JISG) has established the efficacy of human interferon-beta for serious CMV pneumonitis in kidney recipients. Japanese Interferon Study Group.

The Japanese Interferon Study Group (JISG) is a research organization formed by 30 special hospitals for organ transplantation. A joint multi-centre, double-blind trial was conducted in order to investigate the efficacy of human interferon-beta (HuIFN-beta) against serious cytomegalovirus pneumonitis in kidney recipients.

Acute Disease↗

PubMed2003

A randomized trial to assess the efficacy of interferon alpha in combination with ribavirin in the treatment of interferon alpha nonresponders with chronic hepatitis C: superior efficacy of high daily dosage of interferon alpha in genotype 1.

A randomized trial was conducted to assess the efficacy of daily (QD) or thrice weekly (TIW) administration of interferon-alpha (IFN) in high doses in combination with ribavirin (1.0-1.2 g/day) in patients with chronic hepatitis C (CHC) who were nonresponders to previous IFN monotherapy. Interferon was administered as 10 MU IFN (QD or TIW) for 4 weeks, followed by 5 MU IFN (QD or TIW) for 20 weeks, and then by 3 MU IFN (QD or TIW) for 24 weeks. Sustained virological response (SVR) was evaluated in 142 patients who received at least one dose of medication. One-fourth of the patients achieved SVR, 26% of those treated with IFN QD and 25% of those treated with IFN TIW (P = 0.85). For genotype 1 patients, SVR rates were 32.4 and 15.8% for IFN QD and IFN TIW, respectively, whereas for genotype non-1 patients the corresponding SVR rates were 20.6 and 36.4%, respectively (test of homogeneity: P = 0.031). This finding was further confirmed by multivariate logistic regression analysis where a statistically significant interaction (P = 0.012) was found between treatment and HCV genotype indicating that the IFN QD regimen was superior to IFN TIW among genotype 1 patients whereas, among genotype non-1 patients, the two treatments were similar (odds ratio of SVR in IFN QD vs IFN TIW: 3.33 among genotype 1 patients, 95% CI: 1.00-11.14). In conclusion, re-treatment of patients not responding to previous IFN monotherapy with a combination of high daily dose of IFN with ribavirin may be beneficial for genotype 1 infected patients.

Adolescent↗