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I Castillo

Publications and source records attributed to I Castillo.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phylogenetic analysis of hepatitis GB virus type C/hepatitis G virus in Spanish patients with chronic hepatitis B or C virus infection.

The nucleotide sequence of hepatitis GB virus type C (HGBV-C)/hepatitis G virus (HGV) NS3/helicase and 5'-untranslated regions from 23 Spanish patients were analyzed to assign the HGV isolates one of the proposed HGBV-C/HGV genotypes. The analysis of the evolutionary distance frequency showed that the distances among all sequences in NS3/helicase region were distributed around a single peak of 0.20, suggesting that all included sequences belonged to the same HGBV-C/HGV genotype. By contrast, in the 5'-untranslated region, all the distances corresponding to our sequences and those of the HGBV-C/HGV types 2 and 3 were distributed around a major peak of 0.03. The remaining distances corresponding to the HGBV-C/HGV type 1 sequences were distributed around a minor peak of 0.11. The phylogenetic tree and pairwise comparison of evolutionary distances among the 5'-untranslated region of the infected patients and each HGBV-C/HGV genotype demonstrated that our HGBV-C/HGV isolates belonged to subtype 2a (17/23; 78%) and 2b (5/23; 22%). No relation was found between HGBV-C/HGV subtype and hepatitis B or C virus infection.

5' Untranslated Regions↗
PubMed1997

A pilot study of recombinant interleukin-2 for treatment of chronic hepatitis C.

The optimal and safer interleukin-2 (IL-2) dose for treatment of chronic hepatitis C virus (HCV) infection has been studied in 33 HCV-RNA positive patients with chronic hepatitis C. Patients were randomly allocated to receive 5 days per week during 12 weeks IL-2 doses of: 0.9 MIU (n = 10), 1.8 MIU (n = 10), or 3.6 MIU (n = 13). After 12 weeks, responder patients stopped treatment, whereas nonresponders received 12 additional weeks of IL-2 at the next higher dose: 1.8, 3.6, or 5.4 MIU. As a whole, after the first 12 weeks of IL-2 alanine aminotransferase (ALT) levels significantly decreased (P < .001) with respect to the baseline values (140 +/- 63 vs. 70 +/- 30 IU/L). At the end of treatment (24 weeks), the mean ALT level (80 +/- 50 IU/L) continued significantly lower (P < .001) than the baseline one, and 24% of patients normalized ALT levels; according to dosage, ALT normalization was: 0% for 0.9 MIU, 25% for 1.8 MIU, 5% for 3.6 MIU, and 18% for 5.4 MIU. HCV-RNA levels decreased during treatment, but in none of the patients became undetectable. All patients had a local reaction at the injection site with induration, erythema, and swelling, which was dose-related. The dose of 5.4 MIU was poorly tolerated and was reduced to 3.6 MIU in 4 of 11 patients. No changes in hematological parameters were observed. At the end of follow-up (6 months) four of eight responder patients continued with normal ALT. In conclusion, IL-2 treatment for chronic hepatitis C induced a biochemical response in 8 of 33 (24%) patients at the end of therapy while at the end of follow-up, 4 of 33 (8%) patients remained with normal ALT. The dose of 1.8 MIU is well tolerated and seems to be the most efficacious.

Adult↗
PubMed1997

Pilot interferon-beta trial in children with chronic hepatitis B who had previously not responded to interferon-alpha therapy.

BACKGROUND: Recombinant interferon alpha (IFN-alpha) treatment is useful in 40% of children with chronic hepatitis B. However, nonresponder children continue to have viral replication and a progressive disease. OBJECTIVE: To administer natural IFN-beta to hepatitis B virus chronic carrier children who had not responded to a previous IFN-alpha cycle. METHODS: Twenty-two children with chronic hepatitis B, nonresponders to a previous IFN-alpha cycle, were retreated with 5 MU/m2 of body surface of natural IFN-beta, administered intramuscularly, three times per week for 24 weeks. RESULTS: At the end of treatment, 9 (41%) of 22 children became hepatitis B virus DNA negative. Hepatitis B e antibodies (anti-HBe) developed in 5 of these children, and 6 had normal alanine aminotransferase values. At the end of the posttreatment follow-up (21 months from the beginning of the study), 10 (45%) of 22 children were viral DNA negative, 7 (32%) of 22 were anti-HBe positive (none of them had viral DNA in serum), and 11 (50%) of 22 had normal alanine aminotransferase levels (10 without detectable viral DNA and 7 anti-HBe positive). CONCLUSION: IFN-beta seems to be an effective retreatment therapy for children with chronic hepatitis B who are nonresponders to a first IFN-alpha cycle; however, a controlled study should be performed to confirm these results.

Adolescent↗
PubMed1996

Hepatitis E virus seroprevalence in acute viral hepatitis in a developed country confirmed by a supplemental assay.

Hepatitis E virus (HEV) infection is prevalent among cases of acute viral hepatitis in young adults in developing countries. HEV infection is not restricted to endemic areas, but would appear to be worldwide in distribution. In order to document the incidence of HEV infection in acute hepatitis cases in a developed country, IgG and IgM anti-HEV antibodies and HEV RNA were tested in 101 Caucasian patients with acute viral hepatitis; 92 of these cases had markers of acute viral hepatitis other than HEV. Forty-seven (46.5%) cases had IgG anti-HEV; IgM anti-HEV and HEV viremia were not detected. As the incidence of anti-HEV was higher than would be expected, the possibility of the occurrence of false positive results was subsequently investigated. Supplemental antibody testing, using a broadly reactive epitope region, reduced the frequency of anti-HEV to 17%. Therefore, supplemental antibody testing confirms the hepatitis E virus seroprevalence in a developed country. Since IgM anti-HEV and HEV viremia were not detected, persons with IgG anti-HEV may be "subclinical HEV cases," or have long-lived antibodies in their circulation.

Acute Disease↗
PubMed1996

Electro-oculographic recordings reveal reading deficiencies in learning disabled children.

This study was undertaken in order to learn the functional differences in reading tasks between two groups of children: those identified as learning disabled and a group of control children. During the earliest stages of learning to read, children adopt a logographic strategy, in which letter order is ignored and phonologic factors are secondary. The children later move into an alphabetic and then to an orthographic reading stage. Reading strategies can be studied by electro-oculographic (EOG) recordings during text reading. This investigation uses EOG to study text reading time, and number of saccadic and regressive movements, to test if learning disabled children show altered strategies on text reading. Nineteen learning disabled and thirteen control subjects were included in the study. Learning disabled children showed longer text reading time, and greater number of saccadic and regressive eye movements. Electro-oculographic recording is not a test customarily performed on learning disabled children. However, our results concerning the dynamic discriminative reading have shown that it can be a useful tool for the examination of learning disabled children.

Child↗
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

Hepatitis C virus genotypes in serum and liver of children with chronic hepatitis C.

Hepatitis C virus (HCV) 1a, 1b, 2a, and 2b subtypes have been studied in 30 serum samples and in 20 paired liver biopsies from children with chronic hepatitis C. One serum sample was negative to the four HCV subtypes studied. HCV 1b was detected alone in 53.3% (16/30) of the serum samples; HCV 1a alone in 23.3% (7/30) and a mixed infection in 20% (6/30). In liver samples, HCV mixed infection was detected in a significantly higher proportion (50%: p < 0.05) than in serum, whereas HCV 1b was detected alone in 35% (7/20) and HCV 1a alone in the remaining 15% (3/20) of liver samples. These results suggest that serum HCV genotyping may not reflect the viral population infecting the liver of a given patient. Additional studies should be performed concerning the pathobiology of hepatitis C virus with relation to the subtypes detected in liver.

Adolescent↗
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

Analysis of hepatitis B precore region in serum and liver of chronic hepatitis B virus carriers.

Using an oligonucleotide hybridization assay we studied the prevalence of wild-type and the predominant pre-core mutant hepatitis B virus in serum and liver of 49 antibody to hepatitis B e antigen carriers and three hepatitis B e antigen positive patients. Of the 45 serum samples from the anti-HBe carriers analyzed (no serum sample was available in four patients), 36 (80%) had hepatitis B virus DNA. In 26 of these 36 patients (72%) a mixed population was detected, wild-type genome alone was found in six patients (16%), the single mutant (nucleotide position 1896), in three cases (8%) and in one patient (2%) the viral DNA had the two nucleotide mutation (1896 and 1899). Of the liver biopsies from the 36 anti-HBe patients studied (no liver biopsy was available in 13 patients), 33 (92%) had hepatitis B virus DNA. A mixed viral population was detected in 23 patients (69%), only wild-type virus or a single mutation was found in eight (34%) and two patients (8%), respectively. In all cases, wild-type was the predominant genome. In serum and liver samples from the same patient, we found a concordance of the presence of wild-type HBV and the pre-core mutants studied in 23/26 (88%) of the patients. Alanine aminotransferase levels were higher (p < 0.01) and the duration of hepatitis B surface antigen carrier lower (p < 0.02) in patients with a predominance of precore mutant in comparison to wild-type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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 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

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↗