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Biomedical subjects

G Realdi

Publications and source records attributed to G Realdi.

At least 73 records · Page 4Linked to original sources
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 antibodies to thymus epithelial cells in non-A, non-B and cryptogenic chronic liver disease.

Antibodies against thymus epithelial cells (anti-TEC) and the basal cell layer (BCLA) of squamous epithelia have been described in association with HDV-related chronic liver disease (CLD). Data are lacking on their presence during nAnB virus infection. Sera from 51 patients with nAnB post-transfusion hepatitis, including acute and chronic cases diagnosed during a prospective study on candidates for cardiac surgery, and 167 with various forms of CLD were tested for the presence of anti-TEC and BCLA using indirect immunofluorescence on human thymus and rat forestomach sections. Both antibodies mainly occurred in nAnB, HDV and cryptogenic CLD (anti-TEC: 51%, 47% and 42%; BCLA: 29%, 38% and 31%, respectively). The prevalence of anti-TEC in nAnB CLD turned out to be higher than that recorded in alcoholic, HBV-related, autoimmune, liver and kidney microsomal antibody positive CLD and primary biliary cirrhosis (p ranging from less than 0.03 to less than 0.0004). Two monoclonal antibodies (Mabs) to cytokeratins gave a pattern superimposable on that of spontaneous anti-TEC (both Mabs) and BCLA (only one). Antibodies against epithelial constituents, presumably targeting cytokeratin-associated antigens, occur not only in HDV CLD, as previously reported, but also in nAnB CLD, where they might represent a diagnostic aid, due to the unavailability of reliable serological markers of nAnB infection. The close similarity of anti-TEC and BCLA status between nAnB and cryptogenic CLD suggests a nAnB etiology of at least a proportion of chronic liver patients at present scored as cryptogenic.

Acute Disease↗
PubMed1989

Early detection of hepatocellular carcinoma in patients with cirrhosis by alphafetoprotein, ultrasound and fine-needle biopsy.

Hepatocellular carcinoma (HCC) may be detected at a relatively early stage in patients with liver cirrhosis regularly followed by screening programs using ultrasonography (US) and alpha-fetoprotein (AFP) measurement. Using both tests in 214 consecutive cirrhotic patients with no clinical signs of liver cancer, we detected HCC in 20 cases (9.4%). The sensitivity of US was greater (85%) than that of AFP (75%), and the combination of the two methods had a sensitivity of 100%. Only 50% of patients with focal liver lesions at US had a final diagnosis of HCC that was obtained in the majority of cases by US-guided fine needle biopsy.

Biopsy, Needle↗
PubMed1988

Blood-transmitted and clotting-factor-transmitted non-A, non-B hepatitis. Clinical differences and evolution.

In a prospective study of post-transfusion hepatitis (PTH) in open-heart surgery patients, non-A, non-B hepatitis was diagnosed by exclusion criteria in 100 patients (14.1%). The frequency of hepatitis was significantly higher (56.9%; p less than 0.001) in patients receiving blood units and clotting-factor concentrates of commercial origin, which were administered for the occurrence of bleeding complications during surgery, as compared to patients treated with blood units alone (10.3%). When clinical features of hepatitis at presentation were compared in the two groups of patients, a shorter incubation period (p less than 0.05) and a higher prevalence of jaundice (p less than 0.01) were found in patients receiving blood and clotting-factors. Persistence of abnormal alanine aminotransferase (ALT) levels after 12 months from onset were found in more than 70% of patients in both groups. Late biochemical remission, however, was observed in 21% of patients receiving blood units alone, but in none of those who received clotting factors. All these latter patients had histologic features of active liver disease during the chronic phase of the illness, as compared to only 46% of patients receiving blood units alone (p = 0.02). Our results show significant differences in the clinical course of non-A, non-B hepatitis transmitted by blood as compared to clotting factors, supporting the hypothesis of different etiological non-A, non-B agents.

Adult↗
PubMed1988

Cryptogenic chronic liver disease and serum or liver hepatitis B virus markers. Their possible correlations and etiologic significance.

In an attempt to evaluate a possible correlation between cryptogenic chronic liver disease and a present or past hepatitis B virus (HBV) infection, we studied 17 patients with hepatitis B surface antigen (HBsAg)-negative, nonalcoholic chronic liver disease; 9 of them were positive for serum HBsAg detected by a solid-phase enzyme immunoassay with monoclonal antibody (M-EIA) and 8 were negative for the same marker. Liver hepatitis B core antigen (HBcAg), studied by an indirect immunofluorescence technique, was present in 55.5% of the patients positive for serum HBsAg by M-EIA. In the same group of patients, liver HBV-DNA was found in 66.6% of the patients. On the other hand, only 1 patient without serum positivity for HBsAg by M-EIA was positive for liver HBcAg and HBV-DNA. None of our patients showed serum positivity for HBV-DNA sequences. We conclude that HBV infection may be a possible cause of cryptogenic chronic liver disease; this HBV-related, HBsAg-negative chronic liver disease seems to have no viral replication or undetectable levels of HBV-DNA in serum. HBsAg, detected by a monoclonal assay, seems to be a suitable marker to identify this subgroup of patients with HBsAg-negative chronic liver disease.

Antibodies, Monoclonal↗
PubMed1987

IgM antibody to hepatitis B core antigen in children with chronic type B hepatitis.

IgM antibody to hepatitis B core antigen (anti-HBc IgM) was investigated by an antibody-capture radioimmunoassay (serum dilution 1:4000) in serum samples from 31 untreated children with chronic hepatitis B who were followed prospectively for 1-7 years. At the start, all patients were positive for hepatitis B e antigen (HBeAg), and anti-HBc IgM was detected in 23 cases, including 15 out of 16 with chronic active hepatitis and 7 out of 14 with chronic persistent hepatitis. A significant positive correlation was found between anti-HBc IgM levels and severity of liver damage (P less than 0.05), while an inverse relationship was found between anti-HBc IgM levels and distribution of hepatitis B core (HBcAg) antigen in the liver as detected by immunofluorescence. In fact 75% of anti-HBc IgM positive patients showed a focal HBcAg pattern (less than 40% positive nuclei), whereas 87% of antibody negative cases exhibited a diffuse HBcAg expression (more than 60% stained nuclei). During follow-up, seroconversion from HBeAg to anti-HBe with subsequent remission of liver disease occurred in 82% of patients presenting with detectable levels of anti-HBc, including three out of seven cases with chronic persistent hepatitis, but in none of the cases that were initially negative (P less than 0.01). These results indicate that during the natural course of chronic hepatitis B in children, anti-HBc IgM levels in serum reflect the degree of host immune response to infected hepatocytes. The close correlation between anti-HBc IgM seropositivity and seroconversion from HBeAg to anti-HBe suggests that anti HBc IgM may have a prognostic value during the follow-up of children with chronic HBeAg positive hepatitis B.

Adolescent↗
PubMed1987

Cell-mediated immunity to HBcAg in chronic HBV infection.

The role of hepatitis B core antigen (HBcAg) as a possible target of cell-mediated immune response in chronic hepatitis B virus (HBV) infection has been recently emphasized. Peripheral blood leukocytes (PBLs) from 35 chronic carriers of hepatitis B surface antigen (HBsAg) were studied in vitro for their immune response to a purified preparation of HBcAg isolated from circulating Dane particles. PBLs from all the studied HBsAg-positive patients yielded a stimulation index above 3, with values ranging from 3.1 to 38.1. None of the healthy seronegative subjects, taken as control group, had a stimulation index above 2, with a mean value +/- SD of 1.28 +/- 0.35. Levels of PBL stimulation correlated with the histologic activity of liver disease, and the differences reached statistical significance. These results indicate that lymphocyte response to HBcAg may be relevant in determining liver cell damage.

Adult↗
PubMed1987

Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B.

Serological markers of hepatitis delta virus (HDV) infection were found in 18 (12%) of 146 consecutive patients with chronic hepatitis B, and the characteristics of patients who had antibody to HDV (anti-HDV-positive) were analyzed. During one to 15 years of follow-up, histological deterioration was documented in 77% of anti-HDV-positive patients; however, in hepatitis B surface antigen (HBsAg) carriers without HDV infection, histology deteriorated in 30% but improved or remained unchanged in the majority of patients (P less than .01). In seven (70%) of the 10 anti-HDV-positive patients who showed transition from chronic active hepatitis to cirrhosis, this event was observed within the first two years of follow-up. The probability of evolution to cirrhosis was significantly higher in anti-HDV-positive patients than in patients without antibody to HDV (P less than .001). These findings indicate that HDV infection in patients with chronic hepatitis B is associated with a more-rapid progression to cirrhosis compared with HBsAg carriers with chronic hepatitis and no evidence of HDV infection.

Adolescent↗
PubMed1987

HBV-DNA sequences are rarely detected in the liver of patients with HBsAg-negative chronic active liver disease and with hepatocellular carcinoma in Italy.

Hepatitis B virus sequences were studied by molecular hybridization in liver biopsies from patients with HBsAg-negative chronic liver disease or hepatocellular carcinoma, collected in Italy. Among the 42 patients with chronic liver disease who had no history of drug addiction, alcohol abuse nor evidence of metabolic and autoimmune disorders, only two (5%) had HBV-DNA sequences in the liver, although 23 of them (57%) were positive for antibodies to HBV in serum. HBV-DNA was also demonstrated in integrated form in the tumorous tissue of one out of eight cases with HBsAg-negative hepatocellular carcinoma. These incidences of HBV-DNA positivity in the liver are lower than those reported from other Mediterranean areas and similar to those of North Europe, United States and Japan, suggesting that etiologic factors other than HBV are responsible for the majority of HBsAg-negative chronic liver diseases in our region.

Base Sequence↗
PubMed1987

Prognosis of chronic hepatitis B transmitted from HBsAg positive mothers.

Nine children born to HBsAg positive mothers, who became chronic HBsAg carriers with associated liver disease, were followed for five to 10 years. Five children with active hepatitis or active cirrhosis at presentation achieved complete remission within six years, while three HBeAg positive patients with minimal histological lesions remained unchanged.

Female↗
PubMed1987

Definition of hepatitis B virus (HBV)-specific target antigens recognized by cytotoxic T cells in acute HBV infection.

We have investigated the specificity of cell-mediated cytotoxicity for autologous liver cells in 10 patients with acute hepatitis B in relation to the expression of hepatitis B virus (HBV) antigens and IgG on the surface of hepatocytes. Hepatitis B core antigen (HBcAg) was expressed on hepatocytes from six patients and hepatitis B surface antigen (HBcAG) from four, though always in association with HBcAg. Peripheral blood mononuclear cells (PBMC) were significantly cytotoxic in eight of the patients, and fractionation experiments revealed that the cytotoxic effect was equally mediated by T and non-T cells. Monoclonal antibody blocking experiments showed that HBcAg was the major target antigen recognized by T cells, although some inhibition of cytotoxicity was observed after pretreatment of target cells with monoclonal anti-HBs in patients with liver cell surface HBsAg. In contrast, non-T cells were not consistently inhibited by either monoclonal anti-HBc or anti-HBs. These findings further suggest that the HBV nucleoprotein serves as a target for recognition by cytotoxic T cells.

Acute Disease↗
PubMed1986

Levamisole therapy in chronic type B hepatitis. Results of a double-blind randomized trial.

A double-blind, randomized, controlled trial has been undertaken to evaluate treatment of chronic hepatitis type B with levamisole. Ten patients received levamisole (150 mg/day, 3 days/wk) and 10 received placebo until seroconversion to antibody to hepatitis B e antigen eventually occurred, or for a maximum of 18 mo. Final evaluation at 24 mo after starting treatment revealed that 60% of the patients in the levamisole group had become hepatitis B e antigen negative, 90% were hepatitis B virus-deoxyribonucleic acid negative in serum, and 8 of 9 (89%) patients had cleared hepatitis B core antigen from the liver. On the other hand, in the placebo group only 4 of the 10 subjects (40%) were hepatitis B e antigen and hepatitis B virus-deoxyribonucleic acid negative in serum and 3 of 8 (37.5%) of them became hepatitis B core antigen free in the liver. Moreover, in 8 patients of the treated group and in 4 of the control cases aminotransferase activities fell into the normal range. A liver biopsy specimen was obtained after treatment in 17 patients and 7 of 9 levamisole recipients showed marked improvement in hepatic histology, compared with 3 of 8 placebo recipients. These data show that patients treated with long-term levamisole therapy have a tendency toward normalization of aminotransferase activities and suppression of hepatitis B virus replication, suggesting that the drug may be of benefit in chronic hepatitis B e antigen-positive hepatitis.

Adolescent↗
PubMed1986

In vitro effect of lymphoblastoid alpha-interferon on subpopulations of effector cells mediating cytotoxicity for autologous hepatocytes in hepatitis B and non-A, non-B.

Controlled clinical trials are currently under way to assess the efficacy of interferon (IFN) in hepatitis B virus (HBV) infection. In the present study, T-enriched and non-T-enriched lymphocytes from six patients with acute and six patients with chronic HBV infection were cocultured with autologous liver cells with and without alpha-IFN (lymphoblastoid) at a concentration of 1000 U/ml of culture medium, in an 18 h cytotoxicity assay. IFN produced a significant enhancement of non-T-cell cytotoxicity in patients with acute and chronic HBV infection, from 34.3 +/- 19.6% to 60.0 +/- 11.2%, P less than 0.03, and from 41.2 +/- 17.2% to 65.5 +/- 9.8%, P less than 0.01, respectively. In contrast, no significant effect was observed on T cell-mediated cytotoxicity in either group of patients. The in vitro effect of alpha-IFN was also evaluated in four patients who developed chronic non-A, non-B hepatitis following blood transfusion, but no significant stimulatory effect was noted on either T- or non-T cell cytotoxicity. Similarly, no significant increase was observed in control subjects. The significant enhancement of non-T cell cytotoxicity, but not of T-cell cytotoxicity, for autologous hepatocytes in HBV infection suggests that alpha-IFN produces a selective stimulatory effect on non-T cells. The absence of a similar effect in patients with chronic non-A, non-B hepatitis and control subjects suggests that HBV infection alters the susceptibility of hepatocytes to IFN-stimulated non-T cell damage.

Adolescent↗