PubMed Health⌕ Search

Biomedical subjects

V Carreño

Publications and source records attributed to V Carreño.

At least 19 recordsLinked to original sources
PubMed1995

Hepatitis B and D genomes in hepatitis B surface antigen negative patients with chronic hepatitis C.

Hepatitis B and hepatitis D viral genomes were tested by nested polymerase chain reaction in the serum and liver of 69 hepatitis B surface antigen (HBsAg) negative, anti-hepatitis C virus (HCV) positive patients (47 with HCV RNA and 22 without HCV RNA). Serum hepatitis B virus (HBV) DNA-was detected in 49% of the patients with HCV-RNA and in 64% of those without HCV-RNA. Furthermore, intrahepatic HBV-DNA was found in four of five (80%) of the biopsies analysed. Delta genome was found in 72% and 73%, respectively, of the anti-HCV positive patients with or without HCV-RNA. In addition, intrahepatic delta virus genome was detected in another four liver biopsies studied. In the group of patients with HCV-RNA, the simultaneous presence of hepatitis B and D genomes was statistically higher in transfused patients than in drug addicts, or in those with an unknown infection route (P < 0.001). These results show a high percentage of B and D genomes in HBsAg negative patients with anti-HCV, irrespective of the presence or absence of the HCV genome. However, the clinical implications of this finding should be examined in future studies.

DNA Primers↗
PubMed1995

Treatment of chronic hepatitis C with cirrhosis with recombinant human granulocyte colony-stimulating factor plus recombinant interferon-alpha.

Interferon therapy in cirrhotic patients with hepatitis C virus infection is not efficient. In an attempt to improve the response rate, a pilot study using recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone, and in combination with recombinant interferon-alpha (rIFN), was carried out. Fifteen cirrhotic patients with hepatitis C virus infection were randomly allocated into 3 groups to receive treatment: 0.5, 1, or 1.5 micrograms/kg of rhG-CSF daily for 4 weeks, followed by a 4 week resting period, and by the same dose of rhG-CSF daily, plus 6 MU of rIFN 3 times weekly for 4 weeks. They then continued to receive 6 MU of rIFN alone for 4 weeks, followed by 3 MU of rIFN for 16 weeks. After the 4 weeks of treatment with rhG-CSF alone, no changes in alanine aminotransferase (ALT) levels were observed. No changes occurred during the resting period. Three of 10 patients who ended the rhG-CSF plus rIFN treatment period had normal ALT values. During the treatment with rIFN alone, two responders suffered a relapse. The other responder had normal ALT until the first month of follow-up. In summary, the combination of rhG-CSF and rIFN seems promising for the treatment of patients with chronic hepatitis C and liver cirrhosis.

Adult↗
PubMed1995

Factors predictive of response to interferon therapy in children with chronic hepatitis B.

BACKGROUND/AIMS: The efficacy of interferon therapy in Caucasian children with chronic hepatitis B is similar to that in adults. However, little information is available about factors predicting response to this therapy in children. We have performed a univariate analysis to assess the strength of association between basal variables and response, and a multivariate analysis to determine the combination of basal variables which give the best prediction of response in terms of sensitivity and specificity. METHODS: The basal parameters were studied in 50 children included in three different trials of interferon alpha therapy (360-700 MU/square meter of body surface, 2 or 3 times weekly for 12 to 24 weeks). RESULTS: Of these, 18 (36%) were responders. In the univariate analysis, a higher histological activity (p < 0.05), a lower percentage of HBcAg-stained hepatocytes (p < 0.001), aspartate amino transferase and alanine aminotransferase levels (p < 0.05) and alanine aminotransferase peak prior to serum HBV-DNA clearance (p < 0.05), were associated to the response. In the multivariate analysis, the combinations of the percentage of HBcAg stained cells with alanine aminotransferase levels and with the histological activity index were the best variables for predicting response (sensitivity: 100% and specificity: 89% and 86%, respectively). CONCLUSIONS: Factors predictive of response in children with chronic hepatitis B are similar to those found in adults, and may help in identifying those children with a better chance of responding.

Child↗
PubMed1995

Sequence of non-structural regions 3 and 5 of hepatitis C virus genomes from Spanish patients: existence of a predominant variant related to type 1b.

Several hepatitis C viruses (HCV) have been described. In this study, the prevalence of HCV subtypes 1a, 1b, 2a and 2b has been studied by means of specific PCR in 93 serum samples of Spanish patients. Among these, the HCV-1b subtype was the most frequently detected (62%). Complementary DNA fragments from non-structural region 3 (NS3) and 5 (NS5), obtained from serum samples of three Spanish patients, were amplified by PCR and the products were cloned and sequenced. Comparison of the sequence obtained with those previously published shows the highest homology (91.7% in NS3 and 91.8% in NS5) with the HCV-1b subtype. The incidence of the local variant was analysed among the HCV-1b-infected patients. In order to distinguish between the local and HCV-1b prototype subtype, a new specific PCR assay was designed using primers from NS5. In the majority of the 76 HCV-1b-infected patients, the local variant was the only subtype detected (53%). These findings support the existence of a local variant, belonging to the HCV-1b subtype.

Amino Acid Sequence↗
PubMed1995

Immunoglobulin M antibody to hepatitis C virus core antigen: correlations with viral replication, histological activity, and liver disease outcome.

Immunoglobulin M (IgM) antibody to hepatitis C core antigen (anti-HCV-core) was tested by enzyme immunoassay against a synthetic peptide representing amino acids 1 to 62 of the core protein. Of 214 patients with different categories of histological activity, 193 (90%) showed positive results for IgM anti-HCV-core, and 207 (97%) had HCV RNA; most cases (186, 87%) had both markers detectable simultaneously. No differences in the frequency of IgM anti-HCV-core were observed with respect to epidemiological, biochemical, or histological parameters. In 175 interferon alfa (IFN-alpha) recipients, and in 39 untreated controls, pretreatment IgM anti-HCV-core frequencies were similar: 28 of 32 (88%) in sustained responders; 55 of 61 (90%) in responders with relapse; 72 of 82 (88%) in nonresponders; and 38 of 39 (97%) in untreated controls. After IFN-alpha therapy, IgM anti-HCV-core levels became undetectable with significantly greater frequency in sustained responders (P = .014); a similar trend was observed for HCV RNA (P < .0001). IgM anti-HCV-core levels decreased after therapy in responders (P < .001) but increased in nonresponders. Fifty-one cases were longitudinally tested in relation to long-term disease outcome. Both markers remained detectable in most nonresponders with persistent liver disease, in most responders before relapse, and in all but one case at the time of biochemical relapse. IgM anti-HCV-core and HCV RNA became undetectable in most sustained responders, but reappeared despite a long-lasting transaminase normalization, behaving as asymptomatic HCV carriers; the possibility that disease reactivation may take place years afterwards cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Biologic response modifiers in chronic hepatitis C.

Biologic response modifiers include various colony-stimulating factors and interleukins such as granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-2. Their use as therapy has proven to be beneficial in the treatment of various diseases, and in preventing hematologic disorders. Their biologic effects and the rationale for their use in chronic viral hepatitis, alone or in combination with interferon-alpha, are reviewed with respect to the treatment of chronic hepatitis C.

Chronic Disease↗
PubMed1995

Semiquantification by Amplicor assay of hepatitis C virus genome during therapy.

In this study, 42 hepatitis C virus (HCV)-infected patients included in different treatment protocols were assessed by semiquantitative Amplicor assay to evaluate the changes in HCV-RNA titer during antiviral therapy. Amplicor detected change to negative HCV-RNA at the end of treatment in four biochemically responding patients; a decrease in HCV-RNA titer from base line was observed in 2/6 complete responder patients, in 7/11 responders with relapse, and in 6/21 nonresponder patients. Furthermore, Amplicor also detected an increase in HCV-RNA titer from the end of treatment to the follow-up samples in 3/6 complete responder patients, in 7/11 responders with relapse, and in 3/6 nonresponder patients in whom HCV-RNA titer at the end of treatment was lower than in the basal sample. None of the nonresponder patients showed a change to negative HCV-RNA either at the end of treatment or at follow-up. When comparing the detection of HCV-RNA by this semiquantitative method and by nested-PCR, we found a concordance in 113/118 polymerase chain reaction (PCR) results (96%), including three negative results by both methods. With respect to the noncorrelated results, negative PCR samples were found to be positive by Amplicor assay in three cases (correspondent to final samples of treatment); by contrast, two positive PCR samples were found to be negative by Amplicor assay (correspondent to final and follow-up samples of different patients).

Case-Control Studies↗
PubMed1995

Porphyria cutanea tarda and hepatitis C and B viruses infection: a retrospective study.

Based on the knowledge that patients with porphyria cutanea tarda (PCT) usually have chronic liver disease, several authors studied a possible relationship to hepatotropic virus infections. However, the prevalence of hepatitis B virus (HBV)-DNA by polymerase chain reaction (PCR) in serum of these patients, as well as the presence of hepatitis C virus (HCV)-RNA in paired liver, peripheral blood mononuclear cells (PBMCs), and serum samples in these patients has not been reported. We have studied 34 patients with sporadic PCT. Antibodies against HBV were detected in 91% of the patients, but in only 41% of the patients against HBV (P < .01). Viral genomes of HCV and HBV were detected in 65% and 40% of our patients, respectively (P < .05). Genomic and antigenomic HCV strands were found in liver biopsy specimens (100% and 54%), mononuclear cells (100% and 54%), and serum (45% and 0%) from 11 patients. Twelve patients were retrospectively studied, and no correlation was observed between the appearance or disappearance of viral genomes and the simultaneous presence of both genomes with the course of porphyria. In our patients with PCT, detection of viral genomes did not correlate with phlebotomy or length of time since PCT was diagnosed. Our findings demonstrate that HCV infection may be underestimated when detection is performed only in serum of PCT patients, and that HBV infection might also be increased in PCT.

Adult↗
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

Positive and negative hepatitis C virus RNA strands in serum, liver and peripheral blood mononuclear cells in anti-HCV patients: relation with the liver lesion.

To investigate the replicative hepatitis C virus status and its relation to liver damage, serum, peripheral blood mononuclear cells and liver-paired samples from 45 untreated hepatitis C virus infected patients (38 with chronic hepatitis, three with minimal changes, and four with normal liver) were studied by nested polymerase chain reaction, using primers from the 5' untranslated region. Positive HCV-RNA strand was detected in serum (69%), peripheral blood mononuclear cells (100%) and liver samples (100%). The presence of negative HCV-RNA strand was confirmed using specificity controls assays and was only detected in liver and peripheral blood mononuclear cells samples, (95% and 82%, respectively). No correlation between the presence of negative HCV-RNA strand in peripheral blood mononuclear cells and positive HCV-RNA strand in serum was found, whereas serum HCV-RNA was not detected in patients without negative HCV-RNA strand in the liver. Both positive and negative HCV-RNA strands were found in liver and peripheral blood mononuclear cells of four patients with normal liver histology, and three with minimal changes. Furthermore, the presence of HCV-RNA in serum did not correlate with the alanine aminotransferase values and the histological activity index. These data confirm the existence of replicative intermediates in the liver, not only from patients with histologically proven chronic hepatitis, but also from those with normal liver, suggesting the existence of hepatitis C virus in true healthy carriers.

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 against transmission of hepatitis C virus through hemodialysis ultrafiltrate and peritoneal fluid.

Hepatitis C virus (HCV) infection is highly prevalent in the chronic renal failure population treated in dialysis units. Transmission of HCV via blood transfusions is becoming an increasing problem, but, nevertheless, the routes by which this transmission occurs are incompletely known. We have searched for the presence of HCV RNA by the polymerase chain reaction (PCR) in serum and dialysis ultrafiltrate in 12 hemodialysis and 5 continuous ambulatory peritoneal dialysis (CAPD) patients, all of whom were HCV-antibody-positive. Serum PCR were positive for HCV RNA in all the cases, whereas PCR performed on samples of hemodialysis ultrafiltrate or peritoneal effluent were always negative for HCV RNA. In addition, 13 patients tested positive for HCV antibodies and 19 out of 32 patients sharing the dialysis monitors with 17 PCR-positive individuals remained negative. From these findings, we conclude that the dialysis ultrafiltrate or peritoneal fluid seems to be an improbable source of HCV dissemination in the dialysis setting. Moreover, a significant group of patients remained HCV-antibody-negative although they shared the same dialysis machine with positive patients. Therefore, the importance of other sources of HCV transmission, namely blood-contaminated material, should be emphasized.

Ascitic Fluid↗
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↗
PubMed1994

Treatment of chronic hepatitis D virus infection with low and high doses of interferon-alpha 2a: utility of polymerase chain reaction in monitoring antiviral response.

We examined the efficacy of decreasing high doses (beginning at 18 MU/day) of interferon-alpha 2a vs. that of daily low doses (3 MU) in the treatment of chronic hepatitis delta virus infection. Patients treated with 18 MU had a somewhat higher frequency of normalization of serum ALT levels than patients treated with low doses (31% and 12%, respectively, on an intention-to-treat basis). A decrease in the percentage of hepatitis D virus RNA positivity was observed in both groups at the end of treatment. Thus, whereas in baseline samples 10 (62%) of the patients in each group were positive for hepatitis D virus RNA in serum on slot-blot hybridization, these numbers decreased to 5 (31%) and 4 (25%) patients in groups 1 and 2, respectively, at the end of therapy. However, hepatitis D virus RNA, detected by means of nested polymerase chain reaction, remained in all but two (one in each group) patients who completed the treatment. Finally, during posttreatment follow-up, hepatitis D virus RNA levels returned to baseline values, and only one patient remained negative for this marker. The beneficial effect of interferon-alpha was only transient. Only two patients (one from each treatment group) had persistently normal serum ALT levels after 18 mo of follow-up. Finally, the presence of serum hepatitis D virus RNA at the end of therapy, detected with nested polymerase chain reaction, might be a good marker for the prediction of viral replication relapse.

Adult↗