Biomedical subjects

J C Porres

Publications and source records attributed to J C Porres.

At least 37 records · Page 2Linked to original sources

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

[Reactivation of hepatitis B virus in chronic carriers with anti-HBe].

Thirty-eight hepatitis B virus (HBV) carriers, AgHBs and anti-HBe positive, with histologic diagnosis of chronic hepatitis have been periodically revised for three years. Three of them were homosexuals. Fourteen patients presented reactivation of viral replication characterized by the appearance in serum of HBV-DNA and an increase in transaminase levels. Only 7/27 (26%) presented spontaneous reactivation in contrast with 7/11 (64%) patients who had been treated with immunosuppression (p less than 0.05). Furthermore, in 3 cases free AgHBe was temporarily detected during reactivation. Histologic diagnosis and Knodell index were basically similar in reactivated patients and the rest. However, those who presented spontaneous reactivation presented a higher number of AgHB positive cells in liver tissue, both in nucleus and cytoplasm, than patients without reactivation, although, there were no significant differences in relation to the type of reactivation. In summary, this study suggests that immunosuppressants should not be given to HBV carriers with anti-HBe, since this would facilitate the reactivation of viral replication.

Adult↗

PubMed1991

[A controlled study of treatment with recombinant interferon alpha of chronic hepatitis due to the B virus in childhood].

The natural history of chronic hepatitis B virus (HBV) infection in children may lead to hepatic cirrhosis and hepatoma. Since the antiviral effect of recombinant interferon alpha (rIFN-alpha) in the treatment of chronic hepatitis in adults has been proven, a controlled study of therapy using rIFN-alpha in children chronic hepatitis due to HBV has been carried out. Twenty-four children (4-14 years old) HBsAg, HBeAg and HBV-DNA positive were randomly allocated to one of three groups: 1) n = 8, control; II) n = 8, who received 10 MU/m2 of rIFN-alpha (Boehringer Ingelheim)/m2 body surface, I.M., twice a week for six months and III) n = 8, treated with 7.5 MU/m2 under the same conditions. No basal differences between the three groups were observed. No intolerable toxicity was observed and all children completed the treatment period. At the end of the therapy, 5 patients in groups I (1 case), II (2 cases) and III (2 cases), had lost circulating HBV-DNA. With respect to HBeAg, 3 patients (one from each group) were negative by the sixth month, developing anti-HBe. Decreases in ALT levels among rIFN-alpha responder patients were observed, while no changes occurred in the rest. A significant decrease in the percentage of HBcAg positive hepatocytes was detected only among treated patients, when comparing the basal and final liver biopsies. In summary, rIFN-alpha therapy in children is well tolerated. In addition, these results suggest that rIFN-alpha has an antiviral effect.

Adolescent↗

PubMed1990

Recombinant gamma-interferon as adjuvant to hepatitis B vaccine in hemodialysis patients.

Patients undergoing long-term hemodialysis are at high risk of acquiring hepatitis B yet tend to have poor rates of response to hepatitis B vaccine. The effect of recombinant human gamma-interferon (2 million units/m2) on the response to a recombinant hepatitis B vaccine was evaluated in a prospective, randomized controlled trial in 81 hemodialysis patients. A similar proportion of both groups of vaccinees ultimately developed antibody to HBsAg including 81% of the 41 recipients of vaccine alone (group I) and 89% of the 40 recipients of vaccine with gamma-interferon (group II). However, the antibody to HBsAg response occurred earlier in recipients of vaccine with gamma-interferon, so that at 4 mo 63% of group I and 88% of group II had antibody to HBsAg (p less than 0.025). Furthermore, titers of antibody to HBsAg tended to be higher in the vaccinees given interferon; the final geometric mean titers were 232 IU/L in group I and 330 IU/L in group II (p = not significant). Retrospective testing for antibody to hepatitis C virus revealed that 21 (26%) hemodialysis patients were seropositive at entry into this trial, but the presence of antibody to hepatitis C virus did not appear to affect the response rate to the hepatitis B vaccine. These results suggest that the effects of gamma-interferon as an adjuvant in increasing the response rate to hepatitis B vaccination deserve further evaluation perhaps most appropriately in persons who have not responded to an initial course of vaccine.

Adult↗

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↗

PubMed1990

Prolonged treatment (18 months) of chronic hepatitis C with recombinant alpha-interferon in comparison with a control group.

The effectiveness of recombinant alpha-interferon was evaluated in chronic non-A, non-B hepatitis of parenteral transmission. Thirty patients were randomly allocated two groups: control group (without treatment) and treatment group (alpha-interferon 5 mega units thrice weekly for 2 months, and then 1.5 mega units until the eighteenth month). Retrospectively, 26 patients had anti-hepatitis C antibodies. After the first month, 40% of the treated patients had normal serum alanine aminotransferase levels, and no one in the control group (p less than 0.05). After 18 months of treatment, 40% (6/15) of treated patients and 7% (1/14) of controls had normal serum transaminases (p less than 0.05). Interferon was well tolerated. A decrease in the Knodell Index score on final biopsy was found in treated patients (p less than 0.05), with no variations in the control group. Relapse within 7 months after the end of treatment occurred in two out of six complete responders. Thus, recombinant alpha-interferon therapy given for 18 months normalizes serum transaminases and improves histological lesions in chronic hepatitis C of parenteral epidemiology. This long-term interferon schedule is well tolerated.

Adult↗

PubMed1990

Detection of HDV-RNA by PCR in serum of patients with chronic HDV infection.

In this paper, we studied the usefulness of polymerase chain reaction (PCR) in HDV-RNA detection. Using serial dilutions of serum samples of known concentrations of HDV-RNA, PCR was 10,000-times more sensitive than slot-blot hybridization. PCR was used for the detection of HDV-RNA in 33 serum samples negative to HDV-RNA by conventional slot-blot hybridization. HDV-RNA was detected in 18/33 (54%) of the samples included in this study using PCR. When positivity to a viral genome was related to other viral replication markers, it was found that among the 18 patients positive to the viral genome, 13 (72%) had hepatitis delta antigen in the liver, and five (28%) were negative. In conclusion, HDV-RNA detection by gene amplification is 10,000-times more sensitive than slot-blot hybridization, and allows the detection of viral replication in patients without other viral replication markers.

Alanine Transaminase↗

PubMed1990

Changes in anti-idiotype antibodies against anti-HBs during recombinant interferon treatment of chronic hepatitis B.

To determine the possible changes in the presence and level of anti-idiotype (anti-Id) antibodies against anti-HBs induced by recombinant interferon (rIFN) therapy in chronic hepatitis B virus (HBV) infection, a study of patients under rIFN treatment has been carried out. A total of 62 (38 treated and 24 controls), HBeAg and HBV-DNA positive HBsAg carriers were tested serially for the presence of IgG and IgM anti-Id antibodies. According to serological evolution, treated patients were divided in responders (HBeAg and HBV-DNA became negative) (n = 18) and nonresponders (n = 20). Control patients were also classified as having spontaneous seroconversion (n = 11) and without changes (n = 13). Basally all patients had IgG and IgM anti-Id. At the end of the follow-up period (15th month), a significant decrease was observed in the percentage of cases positive to anti-Id among rIFN-responders (IgG, 67%, p less than 0.01; IgM, 44%, p less than 0.001). In contrast, only one nonresponder lost IgM anti-Id during the study. Among controls, only one with spontaneous loss of HBV-DNA and HBeAg clearance became negative to both IgG and IgM anti-Id. In addition, in the basal sample, the rIFN-responders had significantly lower anti-Id levels than the nonresponders (p less than 0.05). Similar results were obtained when comparing the controls with or without spontaneous response (p less than 0.05). Furthermore, a significant decrease in the anti-Id levels among the rIFN responders at the 9th month was detected (p less than 0.01). In summary, the anti-Id antibodies decreased significantly in patients who became HBV-DNA negative following rIFN administration. This result confirms the close relationship between HBV replication and the anti-idiotype against anti-HBs.

Adolescent↗

PubMed1990

Detection of HBeAg/anti-HBe immune complexes in the reactivation of hepatitis B virus replication among anti-HBe chronic carriers.

Sixty-four chronic hepatitis B surface antigen (HBsAg) carriers with hepatitis B e antibody (anti-HBe) were followed in order to detect reactivations of hepatitis B virus (HBV) infection and to assess the incidence and specificity of hepatitis B e antigen/hepatitis B e antibody (HBeAg/anti-HBe) immune complexes (ICs). In 18 out of 19 patients who suffered an increase in alanine transaminase (ALT) values, serum HBV-DNA reappeared co-occurring with the peak(s) of transaminases. HBeAg/Anti-HBe immune complexes were detected in 17/18 (94.4%) patients positive for HBV-DNA. In nine of them, the appearance of immune complexes co-occurred with prednisone therapy, in two following seroconversion after recombinant interferon alpha-2A treatment, and spontaneously in the remaining seven patients. When ALT levels dropped to normal values, immune complexes as well as HBV-DNA became undetectable. In conclusion, the detection of HBeAg/anti-HBe immune complexes seems to be a specific method to detect HBV replication among anti-HBe positive patients.

Antigen-Antibody Complex↗

PubMed1990

A controlled trial of recombinant interferon-alpha in Caucasian children with chronic hepatitis B.

Twenty-four children with chronic active hepatitis due to hepatitis B virus (HBV) infection, who were positive for HBeAg and had increased levels of transaminases, were included in a controlled study of treatment using recombinant interferon-alpha (rIFN-alpha), 10 MU/m2 body surface, intramuscularly, 3 times a week over a period of 3 months. During therapy, a significant decrease in HBV-DNAp was observed in the 12 patients treated. By the end of therapy, the HBV-DNA had disappeared in 3 children, the same occurring in 1 child (33% overall) during the course of the 4th month. By this time, all the controls remained with HBV replication markers (p less than 0.05). The 4 treated patients who responded became HBeAg-negative, developing anti-HBe during the first 12 months after therapy. In the control group, the HBV-DNA disappeared in 3 children in the 7th month of follow-up. All of the children remained HBsAg-positive. The therapy with rIFN-alpha was well tolerated, secondary effects consisting of a flu-like syndrome and a slight decrease in leukocytes and platelets. At the second biopsy, 15 months after the beginning of therapy, a significant decrease in Knodell's index of histological activity was observed in the responders. In the light of these results and since treated children lost viral replication markers in a shorter period of time than the controls, who seroconverted spontaneously, we consider that rIFN-alpha may be useful in the treatment of chronic hepatitis B in childhood.

Child↗

PubMed1989

A dynamic study of the intrafamilial spread of hepatitis B virus infection: relation with the viral replication.

A total of 848 household contacts of 285 hepatitis B surface antigen (HBsAg) chronic carriers were included in a prospective study. Of the total number of contacts negative for hepatitis B virus (HBV) markers at baseline, 330 relatives of 145 HBsAg carriers were observed over a mean period of 20.1 months. Among all household contacts, 284 (33.5%) were found positive for at least one HBV marker. The prevalence of HBV markers was significantly higher among the contacts of more than one HBsAg carrier (75.9%) than among those with only one (26.0%) (P less than .001). The presence of hepatitis B e antigen (HBeAg), specific HBV-DNA polymerase (HBV-DNAp), HBV-DNA, and polymerized human serum albumin (pHSA-R) in the index case was associated with a significantly higher incidence of HBV markers among household contacts. During the follow-up, the number of household contacts initially negative for HBV markers who became infected was found to be in direct relation to the presence of HBeAg, HBV-DNAp, HBV-DNA and pHSA-R in the index case.

Adolescent↗

PubMed1989

Interferon antibodies in patients with chronic HBV infection treated with recombinant interferon.

In different trials, a total of 46 adults and 12 children suffering from chronic hepatitis B virus (HBV) and who were HBV-DNA- and HBeAg-positive were treated with recombinant interferon-alpha (rIFN alpha)-2A. The interferon was administered intramuscularly in different doses ranging from 1.5 MU to 20 MU/m2 of body surface, two or three times weekly during 4-6 months. Specific detection of anti-IFN antibodies by enzymoimmunoassay (EIA), radioimmunoassay (RIA) and biological assays during treatment and follow-up periods were performed. None of the children developed anti-IFN antibodies. During therapy, 12 adult patients (26%) were found to have anti-IFN antibodies. A total of five patients became HBV-DNA-negative during therapy, but in three cases a reactivation of viral replication occurred subsequently. In these three patients, the appearance of anti-IFN antibodies occurred prior to or at the same time as HBV-DNA loss. The other seven patients did not respond to therapy. In conclusion, the development of anti-IFN antibodies during rIFN alpha treatment of chronic hepatitis B may modify the response to therapy, especially if they appear before HBV-DNA negativization.

Adolescent↗

PubMed1989

Treatment of chronic delta infection with recombinant human interferon alpha 2c at high doses.

Superinfection by hepatitis delta virus (HDV) in hepatitis B virus chronic carriers is normally associated with a progressive liver injury. For this reason, the aim of the present study was to determine the efficacy of recombinant interferon alpha (rIFN-alpha) treatment of chronic delta hepatitis, by giving high doses of rIFN-alpha 2c during a prolonged period. A total of 20 HBsAg, anti-HD carriers with a chronic active hepatitis were randomly allocated in two groups: (I) n = 10, control and (II) n = 10, treated with 10 MU/m2 body surface of rIFN-alpha, twice weekly, intramuscularly (im) during 6 months. Basally, all patients presented HDAg in the liver and serum IgM anti-HD. Serum HDV-RNA was positive in 8 and 7 patients from groups I and II, respectively. The interferon therapy was well tolerated and all patients finished the treatment period. During the first 6 months, a decrease in ALT levels among treated patients (255 +/- 98 vs. 193 +/- 117) was observed. In addition, a transient drop in HDV-RNA levels was also observed. No changes in anti-HD titer, IgM anti-HD and HBsAg concentration were detected. At the end of the follow-up period (15 months) two treated patients had lost IgM anti-HD. In addition, another two patients were HDV-RNA negative. In conclusion, no permanent antiviral effects of rIFN-alpha 2c in chronic delta hepatitis, using this schedule, was achieved.

Adult↗

PubMed1989

Detection of proteins encoded by the pre-S region of hepatitis B virus in the sera of HBsAg carriers: relation to viral replication.

In order to determine the relationship between the presence of pre-S1 and pre-S2 proteins and the level of hepatitis B virus (HBV) replication, a study of 94 HBsAg chronic carriers, 15 anti-HBe positive patients who suffered a viral reactivation and 12 HBeAg, HBV-DNA positive cases under antiviral therapy, has been carried out. Pre-S1 and pre-S2 antigens were detected by RIA using polystyrene beads coated with anti-preS1 or anti-preS2 (Dr W. Gerlich, Göttingen) and 125I-anti-HBs as tracer. The presence of pre-S1 and pre-S2 antigens was detected in 74 (79%) and 85 (90%), respectively, out of the 94 HBsAg chronic carriers included. The level of these antigens was significantly higher in HBeAg, HBV-DNA positive patients than in the other patients (p less than 0.05). Among anti-HBe positive patients suffering a reactivation, a significant increase of pre-S1 and pre-S2 levels was observed, concurring with ALT exacerbation and HBV-DNA positivity. After reactivation, the level of pre-S antigens returned to the basal values. A significant decrease in pre-S antigen levels (p less than 0.05) among patients who respond to recombinant interferon therapy was observed, while no changes were detected among non-responder cases. The detection of pre-S1 and pre-S2 antigens in serum is more frequent in those patients with high viral replication. Furthermore, among anti-HBe carriers with a viral reactivation, synthesis of pre-S antigens takes place again.

Adult↗

PubMed1989

Serological and histological follow up of chronic hepatitis B infection.

In order to study the clinical, serological, and morphological evolution of chronic hepatitis B virus infection in childhood, a prospective study has been carried out. A total of 90 children with a chronic infection were followed up for a mean (SD) of 3 (1.8) years. At the beginning of the study, 61 children were asymptomatic and 77 were household contacts of chronic carriers. Serologically 77 were hepatitis B e antigen (HBeAg) positive and 71 of them were positive to hepatitis B virus DNA. The mean alanine aminotransferase activities were higher among HBeAg positive patients than in antihepatitis B e (anti-HBe) positive ones. The most severe histological damage was also found among HBeAg positive patients. The annual seroconversion rate was 14%. A significant increase in the alanine aminotransferase activity was observed 13 (5.6) months before appearance of anti-HBe in the 85% of cases. Among anti-HBe positive patients, the alanine aminotransferase activities were normal in all except three (19%), two of whom had intrahepatic delta antigen. An increase in the histological activity was observed among patients who maintained HBeAg presence while an amelioration of liver damage was observed in anti-HBe carriers.

Adolescent↗