Biomedical subjects

G Moraleda

Publications and source records attributed to G Moraleda.

29 records · Page 2Linked to original sources

PubMed1993

Levamisole and interferon in children with chronic hepatitis B.

To evaluate the possible usefulness of simultaneous administration of levamisole and interferon, we randomly allocated 38 children with chronic hepatitis B to receive either 10 MU/m2 interferon-alpha-2a, three times a week for 6 mo (group 1, n = 20) or 90 mg/m2 of levamisole for 45 days, together with 10 MU/m2 of interferon-alpha-2a, three times a week for 6 mo (group 2, n = 18). At the end of the follow-up period (15 mo), no significant differences were observed between the groups with respect to loss of hepatitis B virus DNA and HBeAg from serum and normalization of serum ALT levels. During therapy, a significant increase in the serum levels of ALT and soluble interleukin-2 receptor was observed in both groups but was higher in patients from group 2. The combination of levamisole with interferon was associated with severe side effects. In summary, the combination of levamisole with interferon in children with chronic hepatitis B does not improve the results obtained with interferon alone.

Adolescent↗

PubMed1992

Persistence of hepatitis B virus DNA after reduction of viral replication in serum and liver.

Liver and serum samples from 67 children with hepatitis B chronic infection, whether or not treated with recombinant interferon, were analyzed for the presence of hepatitis B virus DNA. After follow-up, 44/67 (66%) still had serum and liver viral DNA; 23/67 (34%) were negative for serum hepatitis B virus DNA. Of the 23 children in the latter group, liver biopsy was available in 21 and viral DNA was not detected by Southern-blot in 20. In the remaining patient, viral DNA was in an episomal nonreplicative form. Polymerase chain reaction was performed in the 21 serum samples negative for viral DNA by conventional techniques and in the 21 liver samples (20 negative for hepatitis B virus DNA and 1 with episomal nonreplicative form). All liver samples resulted in a positive reaction to viral DNA by this technique. Serum viral DNA by polymerase chain reaction was detected in 15/21 (71%) of these patients. The mean of alanine aminotransferase values was similar in patients with or without hepatitis B virus DNA in serum by polymerase chain reaction. In summary, in the majority of the patients who respond to the therapy, there is a persistence of viral replication detected by polymerase chain reaction. This fact explains the persistence of serum HBsAg in these patients. However, more studies are necessary to determine the meaning of the presence of hepatitis B virus DNA that is only detectable by polymerase chain reaction.

Adolescent↗

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↗

PubMed1992

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

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

Adolescent↗

PubMed1991

Analysis of hepatitis B virus DNA, liver disease and influence of antibody to hepatitis C virus in anti-HBe chronic carriers.

Hepatitis B virus DNA (HBV-DNA) in serum was studied in 67 anti-HBe patients using dot-blot hybridization, a modified technique and polymerase chain reaction (PCR). All patients had abnormal aminotransferase (ALT) levels. Serum HBV-DNA was detected in 14/67 cases by dot-blot and in 39/67 (DNA probe) and 45/67 (RNA probe) using the modified technique. The RNA probe was more sensitive than the DNA probe when they were compared, using serial dilutions of HBV-DNA of known concentration (0.1 pg vs 1 pg, respectively). HBV-DNA was found by PCR in 57/67 patients. Ten patients were negative to serum HBV-DNA. The ALT level was significantly higher in patients with serum HBV-DNA by dot-blot as compared to those who had serum HBV-DNA by the modified technique and PCR. With respect to the presence of anti-HCV, 6/67 had anti-HCV confirmed by RIBA test. These 6 patients had serum HBV-DNA. The route of acquisition of HBV infection in anti-HCV positive patients was by parenteral exposure in 67% of the cases and 15% in HCV negative (p less than 0.05). All patients were negative to nonorganic specific autoantibodies. In summary, most of the anti-HBe patients (85%) had viral replication. HCV superinfection plays a minor role in the activity of liver disease.

Adult↗

PubMed1991

Detection of antibody to calmodulin in chronic viral hepatitis: lack of correlation with virus replication and hepatocellular damage.

We have analyzed the presence of IgG and IgM anti-calmodulin antibodies (anti-CaM) by ELISA in patients with chronic hepatitis due to B, delta and C viruses as well as in patients with other liver diseases. The specificity of the assay was demonstrated by preadsorption of positive serum with calmodulin (CaM) but not with myosin light chain. Among 164 patients with chronic viral hepatitis (B, delta and C) and 50 with non-viral hepatitis, 27 and 26%, respectively, had auto antibodies against CaM. There was a significantly increased frequency (37%) of these auto-antibodies in chronic delta infection as compared to that (21%) of patients with chronic B hepatitis (p less than 0.05). An intermediate incidence of anti-CaM, (24%) was found in chronic C infection. The frequency of anti-CaM was not related to the level of hepatitis B virus (HBV) or hepatitis delta virus (HDV) replication. A high occurrence of anti-CaM in the presence of liver membrane antibody (p less than 0.03) was observed. During follow-up of patients with chronic delta-hepatitis, the presence of anti-CaM was consistently observed, when the isotype was IgM, but transiently when it was IgG. The occurrence of anti-CaM correlated neither with ALT levels nor with histological diagnosis. Antibodies to CaM, are present in liver diseases especially in chronic delta-hepatitis, and do not play a pathogenic role on hepatocellular damage.

Adolescent↗

PubMed1991

Prospective, randomized controlled trial of interferon-alpha in children with chronic hepatitis B.

Thirty-six children with chronic hepatitis B were entered into a randomized controlled trial of recombinant human interferon-alpha. All patients had hepatitis B virus DNA and increased levels of aminotransferases in serum for at least 1 yr. Twelve children received 10 MU of interferon-alpha 2b/m2 body surface area three times a week (group I); 12 children received 5 MU/m2 under the same conditions (group II); and 12 children served as controls (group III). During 6 mo of therapy, 12 of 24 (50%) treated patients (7 from group I, 58%, and 5 from group II, 42%) and 2 of 12 (17%) controls lost hepatitis B virus DNA from serum and subsequently remained negative. Comparison of the rate of response in group I vs. controls showed a statistically significant difference (p less than 0.05). Eleven of 12 (92%) treated patients who cleared hepatitis B virus DNA from serum lost HBeAg, seroconverted to anti-HBe and had improvement in liver histological findings with loss of hepatitis B virus DNA from liver. In 10, serum ALT levels became normal. Interferon-alpha was well tolerated and all children finished therapy. These findings indicate that a 6-mo course of interferon-alpha is effective in inducing a serological, biochemical and histological remission of disease in approximately 50% of children with chronic hepatitis B.

Biopsy↗

PubMed1990

Influence of hepatitis delta virus replication in the presence of hepatitis B virus DNA in peripheral blood mononuclear cells.

The presence of hepatitis B virus DNA was studied in peripheral blood mononuclear cell samples from 259 HBsAg carriers (229 anti-hepatitis delta negative, 30 anti-hepatitis delta positive), 16 anti-HBc-positive HBsAg-negative patients and 30 patients without hepatitis B virus markers. Hepatitis B virus DNA sequences were detected in peripheral blood mononuclear cell from 115 (44.4%) of the chronic HBsAg carriers and from two (12%) of the anti-HBc-positive, HBsAg-negative patients. In anti-hepatitis delta-negative patients, viral DNA was positive in peripheral blood mononuclear cell from 74 (46%) and from 24 (35.5%) with and without serum HBV-DNA, respectively. With respect to anti-hepatitis delta-positive patients, viral DNA was found in peripheral blood mononuclear cell in 8 of 13 (61.5%) of the patients with circulating hepatitis delta virus RNA and in 9 of 17 (53%) of the hepatitis delta virus RNA-negative subjects. Regarding hepatitis B virus DNA in serum and peripheral blood mononuclear cell, 71% (5 of 7) of the patients with serum hepatitis B virus DNA had this marker in peripheral blood mononuclear cell, whereas 52% (12 of 23) of the patients without serum hepatitis B virus DNA had hepatitis B virus DNA in peripheral blood mononuclear cell. A Southern blot analysis was also carried out on peripheral blood mononuclear cell samples from 30 patients. Hepatitis B virus DNA was detected in 16 patients as free forms, in 12 patients as dimers and free forms and as free circular together with free linear forms in the remaining two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Hepatitis B virus DNA patterns in the liver of children with chronic hepatitis B.

The pattern of hepatitis B virus DNA (HBV-DNA) expression were studied in 2 sequential liver biopsies from 26 children (18 treated with interferon and 8 controls) with chronic hepatitis B. In the basal biopsy replicative forms of HBV-DNA were detected in all of the samples and integrated viral DNA was present in 1 case. At the end of the study, 8 children had lost serum HBV-DNA although 2 of the children were still HBeAg positive. (Six had been treated with interferon.) In all of the cases, HBV-DNA was not detectable in the final biopsy. For the rest of the patients, HBV-DNA was positive in serum and all of them had replicative forms of HBV-DNA in the second liver sample. None of the patients lost hepatitis B surface antigen (HBsAg). Peripheral blood mononuclear cells (PBMC) from these patients were studied. HBV-DNA was not found in the PBMC of the 8 children without serum HBV-DNA, and HBV-DNA was detected in the PBMC of 5/12 patients with serum HBV-DNA. In conclusion, HBV-DNA disappeared from the biopsies of children who lost circulating HBV-DNA, although some of the patients were still HBeAg positive. This result implies that the detection of HBV-DNA in liver is important in order to assess the efficacy of the antiviral therapy. On the other hand, HBsAG remained positive in all children at the end of the study although HBV-DNA was not detected in serum, liver, and PBMC by the conventional hybridization techniques.

Adolescent↗

PubMed1990

Hepatitis B virus DNA in liver and peripheral blood mononuclear cells during reduction in virus replication.

Changes in hepatitis B virus DNA in blood cells and liver were studied in 34 patients (12 controls, 22 under therapy). There were no basal differences in the presence of the viral genome in blood cells between treated and control patients. A significant decrease in the percentage of patients with viral genome in blood cells was observed in patients who lost this marker in serum. Replicative intermediates of the viral genome were observed in the basal liver samples from all patients. In patients who lost the viral DNA in serum, hepatitis B virus genome became undetectable in the second liver sample in all but two patients who had viral sequences integrated in the host genome. Replicative intermediates were found in all patients with serum viral DNA. The results of this study suggest that there may be a relation between the disappearance of hepatitis B virus DNA in liver and blood cells.

Biopsy↗

PubMed1990

Presence of HBV-DNA in peripheral blood mononuclear cells from anti-HIV symptomless carriers.

The presence of hepatitis B virus DNA (HBV-DNA) in the peripheral blood mononuclear cells (PBMC) of 29 anti-HIV symptomless carriers (eleven HBeAg positive, eleven anti-HBe positive and seven HBsAg negative) and of 40 anti-human immunodeficiency virus (HIV)-negative patients (15 HBeAg positive, 15 anti-HBe positive and ten HBsAg negative) has been studied by dot-blot and Southern blot hybridization. HBV-DNA has been found in similar proportions in both anti-HIV-positive and negative patients (36% and 46%, respectively, in the HBeAg positive group and 27% and 37% in the anti-HBe positive group). No HBV-DNA was detected in the PBMC of the HBsAg-negative patients. No relation has been observed between the presence of HBV-DNA in the PBMC of the anti-HIV-positive patients and the detection of HIV antigen (HIV Ag), number of CD4 cells or the CD4/CD8 ratio. In summary, the presence of HBV-DNA in the PBMC of anti-HIV symptomless carriers does not seem to imply that the patient's clinical state has worsened.

Alanine Transaminase↗