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Biomedical subjects

G Fattovich

Publications and source records attributed to G Fattovich.

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

Human immunodeficiency virus infection and hepatitis C pathology.

To investigate the possible influence of human immunodeficiency virus (HIV) infection on hepatitis C virus-related liver disease, liver morphology was evaluated in 160 HBsAg-negative patients with chronic hepatitis C, including 68 HIV-positive and 92 HIV-negative cases. No differences were detected in the severity of necro-inflammatory hepatic lesions between HIV-negative and HIV-positive patients when the CD4+ lymphocytes count exceeded 400 cells/mm3. In contrast, HIV-positive patients with CD4+ lymphocytes below 400 cells/mm3 showed a significantly lower grade of portal inflammation and piecemeal necrosis. These results suggest that liver lesions in hepatitis C may largely depend on immunomediated mechanisms.

Adult↗
PubMed1993

Clinical and virological profiles in patients with multiple hepatitis virus infections.

BACKGROUND: The "in vivo" interplay between hepatitis B virus (HBV) and hepatitis C virus (HCV) both in terms of replication activity and cytopathic effect on liver cells is poorly understood. The aim of the study was to investigate their reciprocal influence in patients with HBV and HCV coinfection. METHODS: HBV and HCV genomic sequences in the serum and liver of 55 patients with chronic liver disease who were positive for anti-HCV and for markers of HBV were studied. RESULTS: Twenty-five hepatitis B surface antigen-positive patients, without markers of hepatitis D virus (HDV) infection, showed an inverse relation between seropositivity for HCV RNA and for HBV DNA (P < 0.001). HCV genomic sequences were detected in the liver of all patients positive for HBV DNA but negative for HCV RNA in serum. The biochemical activity and the histological severity of liver disease were lower in HCV RNA-positive/HBV DNA-negative patients, compared with HCV RNA (serum)-negative/HBV DNA-positive cases (P < 0.005). Nine of 10 patients with concurrent HDV infection were negative for serum and liver HCV RNA. None of 20 hepatitis B surface antigen-negative/HCV RNA-positive patients with antibodies to HBV had HBV DNA detectable in serum or liver. CONCLUSIONS: Our findings indicate a reciprocal inverse relation between HBV and HCV replication. Patients positive for antibody to HCV with antibodies to HBV usually have no evidence of HBV DNA persistence in the liver.

Base Sequence↗
PubMed1992

A randomized controlled trial of lymphoblastoid interferon-alpha in patients with chronic hepatitis B lacking HBeAg.

Ongoing hepatitis B virus replication in the presence of antibody to HBeAg can be observed in patients with active liver disease. These forms of chronic hepatitis B have been described as having a poor prognosis. We have conducted a randomized controlled trial to assess the efficacy of lymphoblastoid interferon-alpha in 60 patients with antibody to HBeAg and hepatitis B virus DNA-positive chronic hepatitis. Patients received 5 million U/m2 interferon three times a week for 6 mo, or no treatment. Final evaluation 18 mo after randomization showed hepatitis B virus DNA negativity and ALT normalization in 53% of treated patients and in 17% of controls (p less than 0.01). The probability of sustained hepatitis B virus DNA loss was significantly higher in treated patients than in controls (p less than 0.005). Blinded histological assessment revealed improvement in 50% of treated patients compared with 33% of controls. Pretreatment hepatitis B virus DNA and aminotransferase levels and histological appearance were not predictive of response. The results of this trial indicated that marked reduction of viral replication in serum and remission of liver damage can be obtained with lymphoblastoid interferon in about 50% of patients with HBeAg antibody- and HBV DNA-positive chronic hepatitis. This rate of response is higher than that reported previously.

Adult↗
PubMed1992

Induction of autoantibodies during alpha interferon treatment in chronic hepatitis B.

Thirty-two patients with chronic hepatitis B treated with alpha interferon were tested for 12 different antibodies. Only a minority (18%) of cases developed antinuclear antibodies and none developed clinical signs of autoimmune disease. These data suggest that, at the dose regimen used, interferon therapy of chronic hepatitis B is not associated with triggering of autoimmunity.

Adult↗
PubMed1992

Therapy for chronic hepatitis B with lymphoblastoid interferon-alpha and levamisole.

About one third of patients with chronic hepatitis B show a sustained response when treated with interferon-alpha. Combining interferon-alpha with immunomodulators might be a way to increase response rate. The aim of this study was to compare the efficacy of lymphoblastoid interferon-alpha given alone with its efficacy when combined with levamisole in chronic hepatitis B. Forty-five patients with HBeAg-positive chronic hepatitis were randomly selected (with stratification for ALT levels) to receive a 6-mo course of combination therapy with lymphoblastoid interferon-alpha (5 million units/m2 three times per week) and levamisole (150 mg three times per week) or lymphoblastoid interferon at the same dose regimen and a matching placebo. Final evaluation 18 mo after randomization revealed a loss of both HBeAg and hepatitis B virus DNA with ALT normalization in 38% of patients treated with interferon-alpha alone and in 10% of patients receiving combination therapy. The higher response rate observed in patients treated with interferon-alpha alone was maintained after stratification for basal ALT levels (i.e., higher [45% vs. 10%] or lower [31% vs. 9%] than three times the upper normal value). The length of time to sustained HBeAg clearance was significantly (p < 0.05) shorter in patients receiving monotherapy than in patients receiving combination therapy. Blinded histological assessment revealed improvement in 44% of patients treated with interferon-alpha alone compared with improvement in 6% of patients receiving combination therapy. These results indicate that levamisole has no additive effects when combined with interferon-alpha in the treatment of HBeAg-positive chronic hepatitis.

Adult↗
PubMed1991

Autoantibodies during alpha-interferon therapy for chronic hepatitis B.

The development of autoantibodies and autoimmune reactions has been reported during and after interferon (IFN) therapy. Thirteen different antibodies from the sera of 32 patients with chronic hepatitis B treated with alpha-interferon (alpha-IFN) were tested. Seventeen HBeAg-positive patients received 4.5 megaunits (MU) of recombinant IFN thrice weekly for 4 months, and 15 anti-HBe and HBV-DNA positive patients were treated with 5 MU/m2 of lymphoblastoid IFN thrice weekly for 6 months. Five patients (15%) had antinuclear antibodies (ANA) and one patient (3%) had smooth muscle antibodies before treatment. ANA appeared during IFN treatment in five (18%) of 28 previously negative patients. With discontinuation of treatment, the titer of ANA fell to undetectable levels in all patients. In contrast, none of the patients developed antibodies to endocrine organs, such as thyroid microsomal, thyroglobulin, parietal cells, pancreatic islet cell, and adrenal cortex antibodies or autoantibodies specifically associated with autoimmune liver disease such as liver kidney microsomal antibodies and antimitochondrial antibodies. There was no correlation between autoantibody positivity before therapy or autoantibody occurrence during treatment and response to IFN therapy. None of the patients developed clinical signs of autoimmune disease. These results indicate that these regimens of recombinant and lymphoblastoid IFN therapy of chronic hepatitis B are associated with a low risk of clinically significant autoimmunity.

Adult↗
PubMed1991

Hepatitis C virus infection in chronic hepatitis B virus carriers.

One hundred eighty-four patients with hepatitis B surface antigen-positive chronic hepatitis were evaluated for antibodies to hepatitis C virus (anti-HCV). Only 11 (8%) of 136 patients with hepatitis B virus (HBV) replication (HBV-DNA-positive in serum) while 7 (35%) of 20 positive for antibody to hepatitis B e antigen (anti-HBe) but HBV-DNA-negative were positive for anti-HCV. By contrast, anti-HCV was never found in 30 anti-HBe-positive "healthy" carriers. Anti-HCV was more frequent in hepatitis D virus (HDV)-positive than in HDV-negative cases (32% vs. 12%). During 1-11 years of follow-up, anti-HCV persisted in 90% of cases, who showed continuing alanine aminotransferase elevation. Liver histology deteriorated in 2 of 4 anti-HCV-positive, anti-HBe-positive, HBV-DNA-negative patients. These results demonstrate the existence of a subgroup of patients with anti-HBe-positive, HBV-DNA-negative, HDV-negative chronic hepatitis B, where HCV may play a leading role in causing liver disease.

Adult↗
PubMed1991

Natural history and prognostic factors for chronic hepatitis type B.

One hundred and five hepatitis B surface antigen (HBsAg) positive patients presenting with chronic persistent hepatitis (n = 46) or chronic active hepatitis without cirrhosis (n = 59) were followed longitudinally for one to 16 years (mean 5.5 years) and underwent follow up biopsy. During a mean histological follow up of 3.7 years, active cirrhosis developed in 21 (20%) patients one to 13 years after entry to the study with a calculated annual incidence of 5.9%. The probability of evolution to cirrhosis was significantly higher in patients with chronic active hepatitis and bridging hepatic necrosis than in those with moderate chronic active hepatitis or chronic persistent hepatitis (p less than 0.0001). Cox multiple regression analysis showed that the following three variables independently implied poor prognosis: older age, presence of bridging hepatic necrosis, and persistence of hepatitis B virus DNA in serum (p less than 0.0001). These findings indicate that patients with severe chronic active hepatitis and persistent hepatitis B virus replication are at very high risk of rapid progression to cirrhosis.

Adult↗
PubMed1990

Fine specificity of human antibody response to the PreS1 domain of hepatitis B virus.

The preS1 domain of hepatitis B virus envelope proteins contains a site of attachment to the hepatocyte membrane that has been shown to evoke virus-neutralizing antibodies. Using synthetic peptides, we have examined kinetics and specificity of the anti-body response to preS1 during acute and chronic HBV infection. Antibodies against two continuous B cell epitopes, p (21-32) and p (32-47), which overlap with the virus receptor for hepatocytes, were detected in 17 (28%) and 28 (47%) patients, respectively, of 60 patients who were tested during acute hepatitis B. Serial testing demonstrated these anti-preS1 specificities in more than 50% of patients who became virus free. By contrast, five patients with chronic evolution of hepatitis B and 61 of 66 patients with an established chronic HBV infection were negative, independent of serological profile and liver disease activity. Fifteen (22.7%) patients with chronic hepatitis B were positive for antibody to the C-terminus p (94-117) preS1 sequence that, unlike the acute-phase anti-(21-32) and anti-(32-47) reactivities, did not behave as a virus-precipitating antibody. Acute-phase sera were found to also contain virus-precipitating antibodies directed against conformational preS1 epitopes. These results indicate that the preS1 site, which contains the binding activity for the hepatocyte membrane, elicits an early antibody response during acute hepatitis B. A defect in such antibody repertoire may participate in the chronicity process as a result of continuing reinfection of hepatocytes by circulating virions.

Acute Disease↗
PubMed1990

Problems in the management of chronic hepatitis B with interferon: experience in a randomized, multicentre study.

In a multicentre trial, 82 patients known to be hepatitis B e antigen and hepatitis B virus DNA positive for at least 1 year, with elevated serum alanine aminotransferase levels and chronic liver lesions on biopsy, were randomized to receive either recombinant interferon alfa-2a at a dose of 4.5 million units thrice weekly for 4 months or no treatment. At the end of therapy, viral DNA clearance and aminotransferase normalization were significantly (p less than 0.05) more frequent in treated patients than in controls. After 16 months' follow up, the difference was still significant for hepatitis B e antigen clearance and transaminase normalization. Hepatitis B virus DNA reactivation was observed during follow up in 43% of treated patients and 50% of controls. Improvements in liver inflammation were observed in patients on interferon. High pre-treatment serum aminotransferase levels, female sex and a low score for fibrosis in the initial biopsy were predictive factors significantly (p less than 0.05) associated with termination of hepatitis B virus replication in treated cases. These results indicate that interferon is effective in inducing clearance of HBV from serum and improvement of biochemical and histological parameters of liver disease. However, a more prolonged regimen of therapy may be required to obtain stable suppression of hepatitis B virus replication.

Adult↗
PubMed1990

Chronic persistent hepatitis type B can be a progressive disease when associated with sustained virus replication.

In 44 hepatitis B virus (HBV) carriers with chronic persistent hepatitis (CPH), serial liver biopsies were available. At presentation 38 patients had HBV-DNA in their serum including 31 HBeAg positive and seven anti-HBe positive cases. The remaining six patients were anti-HBe positive and HBV-DNA negative. During a mean histologic follow-up of 4.2 years, 12 (32%) of the 38 HBV-DNA positive patients progressed to chronic active hepatitis (six cases) or to active cirrhosis (six cases), while 26 patients showed either unchanged features of CPH (21 cases), or histologic improvement to normal liver (five cases). Persistence of HBV-DNA in serum, independently of HBeAg/anti-HBe events, was significantly (p less than 0.01) associated with deterioration of liver disease, while termination of HBV replication correlated significantly (p less than 0.05) with spontaneous biochemical remission and with unchanged or improved histology. None of the six anti-HBe positive patients without serologic markers of hepatitis B virus replication showed histologic deterioration. These findings indicate that continuing HBV replication is a marker which predicts unfavourable evolution of chronic persistent hepatitis and frequent transition to chronic active hepatitis or cirrhosis.

Adolescent↗
PubMed1990

Spontaneous reactivation of hepatitis B virus infection in patients with chronic type B hepatitis.

Eighty-eight consecutive hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, heterosexual patients of Caucasian origin presenting with chronic hepatitis were followed for 1 to 15 years (mean, 5.4 years). During the study period, 45 (51%) patients cleared HBeAg and hepatitis B virus-deoxyribonucleic acid from serum and were followed for 53 +/- 29 months (mean +/- SD) after seroconversion to antibody to hepatitis B e antigen. All patients manifested biochemical improvement. During follow-up, 10 (22%) of the 45 patients experienced spontaneous reactivation of hepatitis B replication with reappearance of serum hepatitis B virus-deoxyribonucleic acid and, in 4 patients, of hepatitis B e antigen. All patients then showed biochemical exacerbation of disease. These serologic events were transient, lasting an average of 12 months, in 8 (80%) patients. All patients were asymptomatic or minimally symptomatic. Histologic findings of liver tissue from 7 patients showed progression from chronic active hepatitis to active cirrhosis in 2 (28%) patients, while in the remaining 6 cases histology remained unchanged or improved from chronic active to chronic persistent hepatitis. These data indicate that spontaneous reactivation of hepatitis B infection occurs in heterosexual patients with chronic hepatitis B and this event is usually transient and asymptomatic, although in some patients it may be the major cause of progressive hepatic damage.

Adult↗
PubMed1990

Antibodies to the RNase H domain of hepatitis B virus P protein are associated with ongoing viral replication.

Antibodies against the RNase H domain of human hepatitis B virus P protein(s) are frequent markers of acute and chronic virus infection (T. Weimer, K. Weimer, Z.-X. Tu, M.-C. Jung, G. R. Pape, and H. Will, J. Immunol. 143:3750-3756, 1989). In the present study, these antibodies were determined in serial serum samples of experimentally infected chimpanzees and naturally infected human patients with acute and chronic hepatitis B virus infection. Anti-P antibodies were found in the sera of both chimpanzees and humans early in infection shortly after the immunoglobulin M anti-HBc response; they persisted in chronic carriers with ongoing viral replication but declined and disappeared at the time of virus clearance from the sera. These data demonstrate that antibodies to the RNase H domain of the hepatitis B virus P protein are early markers of infection and a signal of ongoing virus replication. Falling titers indicate the decline or end of active virus production and may therefore be a prognostic sign of virus elimination in natural infection and after antiviral therapy.

Acute Disease↗
PubMed1989

Serum levels of soluble interleukin-2 receptors in acute and chronic viral hepatitis.

To analyze interleukin-2-dependent immunoregulatory function in hepatitis B virus infection and in other forms of viral hepatitis, levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked assay in sera from patients with acute and chronic viral hepatitis of different etiology. Increased sIL-2R levels were detected in the early phase of acute hepatitis type A and type B, but not during acute non-A, non-B hepatitis. Among 46 patients with chronic hepatitis B virus infection, levels of sIL-2R were significantly increased only in cases with chronic active hepatitis, while they were about normal in chronic persistent hepatitis or in healthy carriers of the infection. These differences were independent of virus replication, being maintained when patients were stratified according to HBeAg/anti-HBe status and to serum HBV-DNA. Nine patients with chronic active hepatitis type B and high sIL-2R levels at presentation were followed prospectively for two to eight years, and in HBeAg-positive patients, the behavior of receptor levels closely paralleled disease activity. These results, which may reflect increased shedding of IL-2R by activated T lymphocytes in patients with active destruction of HBV infected hepatocytes, indicate the usefulness and potential prognostic importance of serum sIL-2R determination in patients with chronic viral hepatitis. Patients with chronic non-A, non-B hepatitis had much lower sIL-2R levels, although their liver disease was similar to hepatitis B cases, suggesting that different pathogenetic mechanisms operate in these patients.

Acute Disease↗
PubMed1989

Hepatitis B virus DNA forms in the liver of chronically infected individuals. Relation to replication profile.

To analyze the profile of HBV-DNA forms in the liver in relation to different levels of virus replication, liver biopsies from 52 chronic HBsAg carriers were studied by Southern blot analysis. Quantitative evaluation of the major HBV-DNA molecules was carried out by densitometry in 27 patients with ongoing hepatitis B virus (HBV) replication in the liver. Significant variations in the intensity of the different bands were noted in individual cases, but statistical correlation between the amount of single stranded forms and levels of serum HBV-DNA was not observed. In contrast, the amount of linear 3.2 kb HBV-DNA appeared to have an inverse correlation with levels of circulating virions. Only the 3.2 kb form was detected in three patients negative for serum HBV-DNA. In these cases with 'inactive' state of episomic HBV genome seroconversion to anti-HBe occurred from 12 months before to 4 months after the time of liver biopsy testing. This 3.2 kb form can therefore be interpreted as a pattern of transition from the replicative to the non-replicative state of the virus.

Antigens, Viral↗
PubMed1989

Long-term effect of low dose recombinant interferon therapy in patients with chronic hepatitis B.

Thirty three heterosexual chronic hepatitis B virus (HBV) carriers were randomized, with stratification for disease activity, to receive intramuscular recombinant interferon alpha-2a (r-IFN) at doses of 4.5 megaunits thrice weekly for 4 months, or no treatment. During r-IFN treatment, serum HBV-DNA levels fell in all, but 2 patients. Final evaluation at 16 months after randomization revealed that the rate of complete response, i.e., loss of both HBV-DNA and HBeAg with ALT normalization was 22.2% (2 of 9 cases) in patients on interferon and 12.5% (1 of 8 cases) in untreated patients for the group with high serum alanine aminotransferase (ALT) and with piecemeal necrosis on liver biopsy on entry. The corresponding value was 25% (2 of 8 cases) in treated and 12.5% (1 of 8 cases) in untreated patients with low liver disease activity. Overall, a complete response was thus observed in 23.5% of treated patients and in 12.5% of controls. None of the patients on therapy became HBsAg negative. It is concluded that treatment of heterosexual patients with chronic hepatitis B with r-IFN in the dose regimen used here was not associated with a significant higher rate of serologic and clinical response compared to controls, independently of pretreatment biochemical and histologic activity of liver disease.

Adolescent↗
PubMed1989

Serum HBV-DNA in anti-HBe positive patients detected by filter and liquid phase hybridization assays.

Serum HBV-DNA is considered the best parameter for monitoring HBV replication in the liver. The filter hybridization assay (spot test) with 32P-labelled HBV-DNA has been the technique more frequently used to date. A simple solution hybridization assay, in which 125I HBV-DNA is used as labelled probe, has been recently standardized. We have compared the performances of these two assays for the detection of HBV-DNA. The results were similar with the two methods: an agreement was found in 39/44 (89%) samples. Three sera were positive only by the spot assay-and two only by the liquid phase assay. However, in these cases, HBV-DNA levels were near the sensitivity limits of the assay. Therefore, the filter and the liquid phase assays can be considered to be suitable methods to monitor HBV replication, a fundamental index for the clinical assessment and prognosis of patients with HBsAg positive chronic hepatitis.

Cloning, Molecular↗