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Biomedical subjects

J A Quiroga

Publications and source records attributed to J A Quiroga.

At least 55 records · Page 3Linked to original sources
PubMed1994

Serum levels of soluble immune factors and pathogenesis of chronic hepatitis C, and their relation to therapeutic response to interferon-alpha.

To test the role of immune reactivity in the pathogenesis of hepatitis C, serum soluble immune factors were measured in a cohort of 57 patients with chronic hepatitis C, and in 20 healthy subjects. Levels of interleukin-1 beta, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-6 were detected in some, but not all, HCV patients and were in general undetectable in healthy subjects. Patients had significantly higher concentrations of neopterin (P = 0.0026), beta 2-microglobulin (P = 0.046), soluble interleukin-2 receptor (P = 0.021), and soluble CD8 (P < 0.039), than healthy controls; conversely, interferon-gamma levels were significantly lower (P = 0.023). Significant correlations were observed between beta 2-microglobulin concentration and Knodell's index (r = 0.638, P = 0.00045), the score of piecemeal necrosis (r = 0.572, P = 0.0023), and the degree of fibrosis (r = 0.527, P = 0.0056). Interleukin-2 levels correlated significantly with Knodell's index (r = 0.412, P = 0.037), and the degree of lobular cytolysis (r = 0.389, P = 0.048). According to therapeutic outcome, pretreatment levels of soluble CD8 were only significantly elevated (P = 0.042) in patients with a sustained biochemical response. On interferon-alpha treatment, the levels of beta 2-microglobulin, neopterin, and soluble interleukin-2 receptor increased significantly (P < 0.05), irrespective of therapy outcome. In summary, HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-gamma.

Adult↗
PubMed1994

Long-term follow-up study of serum IgM antibody to hepatitis C virus (HCV), HCV replication, and liver disease outcome in chronic hepatitis C.

IgM anti-hepatitis C virus (HCV) and HCV RNA were longitudinally tested for 4.0-8.7 years in 40 patients with chronic HCV infection. Patients in disease remission usually lost IgM anti-HCV and HCV RNA, but most patients experiencing disease reactivation had increased levels of the IgM antibody or it reappeared before the biochemical relapse, even when HCV RNA was undetectable. IgM anti-HCV was detectable in most patients with ongoing viral replication and persistent liver disease. Despite long-term disease remission, IgM anti-HCV may persist and be detectable with or without evidence of serum HCV RNA; this indicates a possible disease reactivation, which could occur after several years of sustained transaminase normalization. Detection of IgM anti-HCV in chronic hepatitis C indicates an active immune response to persistent viral infection and should, therefore, be considered as a sensitive marker of active HCV replication and HCV-associated liver disease.

Adult↗
PubMed1994

Evidence of subtype-specific antibodies to antigenic epitopes in the NS5 region of hepatitis C virus in the circulation of patients with chronic hepatitis C.

The antigenicity of the NS5 region of type 1 hepatitis C virus (HCV) was investigated by epitope mapping of the region spanning amino acids 2530 to 2723 of the HCV polyprotein. Six antigenic regions were recognized by anti-HCV positive sera from individuals with chronic hepatitis C in a modified enzyme-linked immunosorbent assay with synthetic oligopeptides. Five of these regions demonstrated intra-type 1 sequence variations defining subtype 1a and 1b HCV sequences. The region between amino acids 2623 and 2634 allowed testing of subtype-specific anti-NS5 antibodies; serological reactivity to subtypes 1a and 1b was observed in 27 and 61%, respectively, of 150 cases with chronic hepatitis C. Simultaneous reactivity to subtypes 1a and 1b was found in 23% of the patients. Detection of subtype-specific anti-NS5 antibody correlated in more than 80% of the cases with the HCV genotype (subtypes 1a and 1b) analyzed by PCR amplification of the NS5 sequence. These data provide evidence of the existence of a subtype-specific anti-NS5 response in the circulation of patients with chronic hepatitis C.

Adolescent↗
PubMed1994

Changes in cytokine production during therapy with granulocyte-macrophage colony-stimulating factor in patients with chronic hepatitis B.

Recombinant human granulocyte-macrophage colony-stimulating factor therapy significantly reduces serum hepatitis B virus DNA levels, associated with increased 2',5'-oligoadenylate synthetase activity in cultured mononuclear cells of patients with chronic hepatitis B. To assess changes in immune function during therapy of chronic hepatitis B patients, spontaneous and mitogen-induced production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha and interferon-gamma were measured-along with serum levels of soluble CD4, soluble CD8, soluble interleukin-2 receptor and beta 2-microglobulin-before, during and after a 6-wk course of granulocyte-macrophage colony-stimulating factor in nine patients with chronic hepatitis B. Treatment statistically enhanced spontaneous production of tumor necrosis factor-alpha (p < 0.05) and interleukin-1 beta (p < 0.02). Furthermore, spontaneous interleukin-6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin-1 beta production correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.0005). In addition, statistically significant increases were found during therapy in serum levels of soluble interleukin-2 receptor (p < 0.01), soluble CD4 (p < 0.01) and beta 2-microglobulin (p < 0.05). Levels of soluble interleukin-2 receptor and soluble CD4 correlated negatively with levels of hepatitis B virus DNA (p < 0.05), and levels of soluble interleukin-2 receptor and beta 2-microglobulin correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.003 and p < 0.02, respectively). Thus recombinant human granulocyte-macrophage colony-stimulating factor administration may induce reductions in hepatitis B virus DNA levels, perhaps by altering the immune status and increasing cytokine production.

CD4 Antigens↗
PubMed1993

Pilot study of recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of chronic hepatitis B.

Recombinant human granulocyte-macrophage colony-stimulating factor is being used to improve the immunological function of patients with various diseases and to ameliorate hematological disorders. We investigated the tolerance and possible antiviral effect of the administration of daily doses of recombinant human granulocyte-macrophage colony-stimulating factor (3, 1 or 0.5 micrograms/kg body wt) to nine patients with chronic hepatitis B, alone or in combination with 5 MU interferon-alpha 2b. Recombinant human GM-CSF reduced significantly (p < 0.02) hepatitis B virus DNA levels. The three doses used were equally effective. Of the eight patients who completed the study, four became negative for HBV DNA and HBeAg; two of them seroconverted to HBe antibody. These four patients showed improvement in the histological activity of their liver disease. Ultimately, two patients regained normal ALT values. 2',5'-Oligoadenylate synthetase activity increased significantly (p < 0.01) in cell lysates of mononuclear cells cultured in vitro, coinciding with the reductions in hepatitis B virus DNA levels. Recombinant human granulocyte-macrophage colony-stimulating factor was well tolerated but produced a dose-dependent increase in white blood cell counts. It became intolerable at doses of 3 micrograms (and was reduced to 1.5 microgram); this effect was reversible after cessation of recombinant human granulocyte-macrophage colony-stimulating factor treatment. No remarkable variations occurred in other parameters. In conclusion, recombinant human granulocyte-macrophage colony-stimulating factor administration is safe and tolerable at doses of 0.5 to 1 microgram/kg body wt and may exert an antiviral effect in chronic hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Treatment with recombinant alpha-interferon of chronic hepatitis C in anti-HIV-positive patients.

A pilot study of chronic hepatitis C treatment was conducted in 14 patients (13 had chronic active hepatitis and 1 had liver cirrhosis). All patients were asymptomatic for the human immunodeficiency virus (HIV) type 1 (mean CD4 count of 584 +/- 283 cells/mm3). Patients received 9 MU rIFN-alpha 2A per day for three months. After this, patients received 9 MU three times weekly for three months, 6 MU for another three months on the same protocol, and finally 3 MU again three times weekly for the last three months. After the first month of ALT treatment in 9 patients (64%) returned to normal; a significant decrease in ALT levels was observed with respect to the pretreatment values (mean of 42 IU/l, range 15-75 vs 152 IU/l, range 69-355; P < 0.01). Of the 9 patients who completed the treatment period, 5 had a complete response, and 4 of these 5 continued with normal ALT values during follow-up (sustained response) while the other patient relapsed within one month after cessation of therapy. The remaining 4 patients were non-responders (including one case with a break-through of the response). HCV-RNA was not detectable in 3 of the 5 responders at the end of therapy while during follow-up viral RNA became undetectable in the other 2 patients. 2/4 non-responder patients had detectable HCV-RNA during follow-up. Liver histology improved in all the patients. No changes were observed in the immunological status or HIV infection.

Adult↗
PubMed1993

An escalating dose regime of recombinant interferon-alpha 2A in the treatment of chronic hepatitis C.

Interferon-alpha (IFN-alpha) has proven useful in the treatment of chronic hepatitis C, but a relapse in response is frequently observed. The possible benefit of daily administration of recombinant IFN-alpha 2A at an escalating (from 1.5 to 9 MU) regime depending on the evolution of serum aminotransferase (ALT) levels was evaluated in 31 adult patients with chronic hepatitis C. At the end of the first month with 1.5 MU of rIFN-alpha 2A, 9/31 (29%) had normal ALT values. Then, 22 patients were given 3 MU daily and at the second month 4 patients (18%) normalized ALT values. The 18 non-responders received 6 MU and 4 of them (22%) normalized ALT values (1 patient dropped out). Finally, the remaining 13 non-responders were given 9 MU and in 4 (30%) ALT fell to normal ranges. Three non-responders to 1.5 MU normalized ALT values when the dose of rIFN-alpha 2A was increased (n = 2, 3 MU; n = 1, 9 MU). The overall response achieved was 68%. Within 3 months after cessation of treatment, 12/20 (60%) responder patients had a relapse in ALT levels. Therefore, although daily administration of rIFN-alpha 2A does not improve the results obtained with a thrice-weekly schedule, a proportion of non-responders could benefit from an escalating dose to a high amount (63 MU/week) of rIFN-alpha 2A.

Adult↗
PubMed1993

Detection of hepatitis C virus RNA in serum and peripheral blood mononuclear cells.

Hepatitis C virus (HCV) RNA is the most reliable marker of HCV infection. However, because of HCV genome heterogeneity and the procedures used to isolate the viral genome and to perform the amplification steps, results do not accurately reflect the actual rate of HCV infection. In this study, several isolation procedures and sets of primers to perform PCR were compared for the detection of HCV-RNA in serum and peripheral blood mononuclear cells (PBMC) of patients with HCV infection. It was found that the extraction with guanidinium isothiocyanate prior to cDNA synthesis followed by PCR amplification of the 5'-UTR region gave the best results in serum and PBMC. The presence of the viral genome in PBMC is a frequent event during HCV infection and this has important consequences for the understanding of the viral pathogenesis.

Base Sequence↗
PubMed1993

Other approaches to the treatment of chronic viral hepatitis.

Interferon (IFN) therapy of chronic hepatitis C has proved useful in recent years. A major goal in the treatment of hepatitis C is the prevention of the high relapse rate after cessation of therapy and the improvement of the response rate in non-responders. Several approaches can be tried. The administration of higher doses of IFN results in an increase in the response rate, but does not prevent ultimate relapse. Similarly, prolongation of the treatment period gives better results, but one third of cases still relapse. In these cases, re-treatment results in ALT normalization once again, but does not prevent subsequent relapse; in non-responders to IFN, re-treatment will not lead to improvement of the response rate. Analysis of the viral genome reveals its presence in serum in spite of the normalization of ALT values. The role of HCV genome heterogeneity in the response to IFN needs to be assessed and it is necessary to find other antiviral agents that are able to clear HCV from all relevant hosts (serum, liver tissue and mononuclear cells).

Chronic Disease↗
PubMed1992

Treatment of chronic hepatitis C by continuous subcutaneous infusion of interferon-alpha.

The effectiveness of a daily continuous infusion of interferon-alpha was evaluated in 12 patients (10 males, 2 females; mean age of 33 years, range 19-62) with biopsy-proven chronic active hepatitis C. Nine million units (MU) of recombinant interferon-alpha 2A (rIFN-alpha 2A) were administered by continuous subcutaneous infusion with a portable syringe pump, Graseby model MS 16A, for 24 h over 28 days. A significant decrease (P less than 0.01) in median serum alanine aminotransferase (ALT) levels was observed after the first week of treatment (96 IU/L, range 58-263) with respect to the pre-treatment values (188 IU/L, range 119-670). ALT became normal in four patients only by the fourth week. When IFN was interrupted, an increase in ALT was observed in all patients (1.5 to 5 times the pre-treatment values). The maximum decrease in ALT coincided with a significant increase in serum levels of the enzyme 2',5'-oligoadenylate (2-5A) synthetase (two to fourteen times the pretreatment values) and these parameters were inverse-correlated (r = -0.598, P less than 0.05). 2-5A synthetase levels returned to pre-treatment values after discontinuing IFN administration. Hepatitis C virus (HCV) RNA (as detected by the polymerase chain reaction using oligonucleotide primers of the NS5 region) was positive in all cases, remaining so during the treatment period. IgM antibody to HCV (as tested by ELISA) was present in 10/12 cases at baseline without changes throughout the study. No irreversible side effects were noted during therapy, which needed to modify the schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Immunoglobulin M antibody to hepatitis C virus during interferon therapy for chronic hepatitis C.

Testing for immunoglobulin (Ig) M antibody to hepatitis C virus (anti-HCV) as a predictive factor of therapeutic response to recombinant interferon alfa (rIFN-alpha) in chronic hepatitis C was evaluated in 122 patients with IgG anti-HCV. IgM anti-HCV was present in the pretreatment sample of 88% of patients who responded to treatment, including 20 of 21 (95%) long-term responders and 24 of 29 (83%) responders who had relapses after cessation of therapy. In contrast, IgM anti-HCV was present in only 23 of 39 (59%) nonresponders and 22 of 33 (66%) untreated controls (P less than 0.05). The number of cases with detectable IgM anti-HCV tended to decrease in responder patients, which was more evident for complete responders (42%) than for responders who relapsed (72%). During follow-up, the antibody became undetectable in the majority of long-term responders (28% were still IgM anti-HCV positive) but remained detectable in 69% of responders who relapsed (P less than 0.05). No special changes were noted in nonresponder or control patients. Thus, testing for IgM anti-HCV may help to identify a subset of patients who will benefit from rIFN-alpha therapy in chronic hepatitis C.

Adult↗
PubMed1992

Comparison of several PCR procedures for detection of serum HCV-RNA using different regions of the HCV genome.

Different methods for the isolation of hepatitis C virus RNA and several sets of primers from the 5' untranslated, core, NS3, NS3/NS4 and NS5 regions of the hepatitis C virus genome were used for the detection of the viral genome by the polymerase chain reaction. Serum samples from 10 patients with chronic hepatitis C and 10 healthy controls were studied. The best method for the RNA extraction was with cold guanidinium isothiocyanate followed by a denaturation step prior to the polymerase chain reaction. Using this method, the percentage of positivity to hepatitis C virus sequences in serum depending on the region amplified were: 5' untranslated, 90%; Core, 20%; NS3, 80%; NS3/NS4, 60% and NS5, 60%.

Base Sequence↗
PubMed1992

Protein composition of the hepatitis B virus e antigen in the natural course of disease and following interferon therapy.

The protein composition of hepatitis B virus (HBV) e antigen (HBeAg) in serum was analyzed for 63 viremic patients with chronic HBV and found to consist of polypeptides with molecular masses of 16, 18, and 20 kDa (P16e, P18e, and P20e, respectively). Several experiments demonstrated their viral nature and HBeAg specificity and that P16e occurs either in free soluble form or as aggregates or immunocomplexes, while P18e and P20e occur essentially as immunocomplexes. Of 63 patients, 45 (71%) had P16e, P18e, and P20e, and the remaining 18 (29%) had only P16e. During the natural history of the disease, spontaneous clearance of HBV DNA and HBeAg took place only in six of nine (67%) patients with the three HBe polypeptides but in none of the five patients having P16e alone (P less than 0.05). Similarly, 22 of 23 (96%) patients responding to interferon therapy had P16e, P18e, and P20e, but these polypeptides occurred in only 14 of 26 (54%) nonresponder patients (P less than 0.001). Following the loss of HBV DNA and HBeAg, before the development of anti-HBe, the only HBe species detected were P18e and P20e, but these became no longer detectable after complete normalization of liver function tests. Therefore, persistence of P16e represents a failure to recover from HBV, and the appearance of HBe polypeptides P18e and P20e is associated with virus clearance and a favorable outcome of the disease.

Adolescent↗
PubMed1991

IgM antibody to hepatitis C virus in acute and chronic hepatitis C.

To assess possible role of testing for IgM-specific antibody in the diagnosis and monitoring of patients with hepatitis C, we tested sera from 14 patients with acute and 97 patients with chronic non-A, non-B hepatitis for IgG and IgM antibody to hepatitis C virus. IgG antibody to hepatitis C virus was detected in 93% of acute cases and 91% of chronic cases. Of the 101 patients with IgG antibody to hepatitis C virus, 57% had IgM antibody to hepatitis C virus. None of the 20 healthy subjects or 40 patients with acute or chronic hepatitis A or hepatitis B had IgM antibody to hepatitis C virus. At the onset of clinical symptoms in acute hepatitis C, IgG antibody to hepatitis C virus was detected in 8 (57%) and IgM antibody to hepatitis C virus in 9 of 14 patients (64%). Eventually, both IgG and IgM antibody to hepatitis C virus became detectable in 13 of 14 patients with acute hepatitis C. Seven patients with antibody to hepatitis C virus resolved the acute infection within 6 mo and all seven cleared IgM antibody to hepatitis C virus, whereas two cleared IgG antibody to hepatitis C virus. Six patients had a chronic outcome of the acute infection and IgM antibody to hepatitis C virus persisted in detectable amounts for more than 6 mo in all (mean = 15.5 mo). Among 88 patients with chronic non-A, non-B hepatitis with IgG antibody to hepatitis C virus, IgM antibody to hepatitis C virus was detected in 45 (51%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗