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Biomedical subjects

G Fattovich

Publications and source records attributed to G Fattovich.

At least 73 records · Page 4Linked to original sources

Expression of preS1 and preS2 in the liver of chronic hepatitis B virus carriers.

Using monoclonal antibodies we have studied the expression and distribution pattern of preS1 and preS2 proteins in the liver of 25 patients with chronic hepatitis B virus infection. Both preS1 and preS2 were detected in the liver of most cases, independently of viral replication and of the state of the viral genome in the liver. In fact, preS1 and preS2 were present in the liver of 14 out of 15 patients with HBV-DNA in the serum as well as of 7 out of 10 cases with no evidence of viral replication, including 2 with integrated HBV-DNA sequences in the liver and 5 patients with no evidence of liver damage. The pattern of distribution of preS proteins was identical to that of hepatitis B surface antigen, with exclusive cytoplasmic staining in cases without viral replication and cytoplasmic and membranous positivity in those with viral replication. These results clearly indicate that translation of preS proteins is independent of viral replication and is not necessarily associated with liver damage.

Antibodies, Monoclonal↗

Interferon treatment of anti-HBe positive and HBV DNA positive chronic hepatitis B.

The efficacy of human lymphoblastoid interferon (Wellferon) was studied in 25 patients with anti-HBe positive, HBV DNA positive chronic hepatitis B. The patients were randomized to receive 5 MU/m2, three times weekly or no treatment for 6 months. The study is ongoing and to date 19 patients have been followed up for more than 3 months and 14 for more than 6 months. At 9 months, serum HBV DNA had become negative and ALT levels normalized in 57% of interferon-treated patients. This compared with 33% becoming serum HBV DNA negative and 16% with ALT normalization in the untreated group. Clearance of HBV DNA in interferon treated patients was not consistently associated with the appearance of transaminase peaks during therapy, in contrast with those seen in HBeAg positive patients. The preliminary results of this trial suggest that interferon reduces HBV replication in anti HBe/HBV DNA positive patients with chronic hepatitis B.

Alanine Transaminase↗

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↗

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↗

Changes in serum hepatitis B virus (HBV) DNA positivity in chronic HBV infection: results of a long-term follow-up study of 138 patients.

In an assessment of the clinical relevance of serum hepatitis B virus (HBV) DNA testing in chronic HBV infection, changes in the presence of this marker were investigated by spot hybridization in 138 hepatitis B surface antigen (HBsAg)-positive patients with chronic liver disease who were followed up for one to eight years. Forty-one patients were treated with steroids, often with evidence of potentiation of viral replication, whereas 92 patients remained untreated and had no evidence of sigma agent infection during follow-up. Data analysis in these patients allowed us to determine the significance of testing for hepatitis B e antigen and for HBV DNA in the natural history of the infection. The findings indicate that sequential testing for serum HBV DNA may be of great importance in HBsAg chronic carriers with liver disease for adequate evaluation of HBV replication and for the contribution of HBV DNA to the clinical assessment of chronic hepatitis.

DNA, Viral↗

Hepatitis B core antigen (HBcAg) in serum of patients with chronic hepatitis B detected by a modified radioimmunoassay.

Serum hepatitis B core antigen (HBcAg) was investigated in 85 patients with chronic hepatitis B virus (HBV) infection using a modified radioimmunoassay technique, based on high molarity treatment of samples to avoid masking of the antigen by the excess homologous antibody. Eighty-eight percent of HBeAg-positive cases and 19% of anti-HBe-positive cases were HBcAg positive in serum, with a positive correlation with the presence of HBcAg in the liver. Although the sensitivity of the method for the presence of complete virions was not absolute, as shown by the comparison with serum HBV-DNA testing, this technique may be helpful for assessing virus synthesis in patients with HBV infection.

Carrier State↗

Relationship between HBcAg in serum and liver and HBV replication in patients with HBsAg-positive chronic liver disease.

The expression of hepatitis B core antigen (HBcAg) in serum and in hepatocytes was evaluated in relation to HBV replication. Fifty chronic HBsAg carriers with histological evidence of liver disease were studied, including 24 HBeAg-positive patients, 2 HBeAg/anti-HBe-negative patients, and 24 anti-HBe-positive cases, two of them with evidence of delta agent infection. Serum HBV-DNA was evaluated in all patients and related to HBcAg examined at the same time in frozen liver biopsies by immunofluorescence and to HBcAg detected in the corresponding serum by a recently developed radioimmunoassay. HBV-DNA was present in serum in 20 (83%) HBeAg-positive patients, all positive for serum HBeAg, whereas liver core antigen was detected in 14 (73%) of 19 cases. Among HBeAg-negative patients, 50% showed the presence of circulating DNA viral sequences, and HBcAg was identified in five of 26 (19%) cases in serum and in six of 24 (25%) in the liver respectively. In 15 patients, liver fragments permitted examination in parallel by immunofluorescence for HBcAg and molecular hybridization for viral DNA in liver cells. A DNA pattern characteristic of viral replication was found in cases with evidence of active virion production, independently from HBeAg and anti-HBe, and in these patients HBcAg was present both in serum and in hepatocytes. In two cases with free HBV-DNA, without evidence of replicative activity, core antigen was not detected in the liver, but in one patient HBcAg was found in the serum. A similar finding was also noted in another patient, in whom the hybridization pattern was consistent with integration of viral genome into high-molecular-weight cellular DNA. Whether serum HBcAg detected in these patients without HBV-DNA in serum reflects the presence of defective viral particles or of core antigen released as a viral protein remains to be determined.

Chronic Disease↗

Virus replication and liver disease in chronic hepatitis B virus infection.

Recent studies on the natural history of chronic hepatitis B virus infection have provided evidence for a close temporal relationship between the phase of active virus replication and development of liver lesions. To assess the role that virus replication plays in this phase in determining the severity of the liver disease, we studied serum levels of virus-specific DNA-polymerase activity and hepatitis Be antigen/antibody status in 48 chronic carriers of the hepatitis B surface antigen found positive for the hepatitis B core antigen in the liver. There was a remarkably evident inverse correlation between virus replication activity and liver disease activity, patients with minimal histological changes having the highest DNA-polymerase levels (mean +/- SD: 3879 +/- 2557 cpm) and those with severe chronic active hepatitis the lowest enzyme levels (419 +/- 246 cpm), while cases of chronic persistent hepatitis and of mild chronic active hepatitis had intermediate levels. Serum hepatitis Be antigen was detected in 31/32 patients with milder liver lesions and in 11/16 with severe liver lesions; the remaining five cases were anti-HBe-positive despite the presence of the core antigen in the liver. Serum levels of virus replication markers closely correlated with the distribution pattern of the core antigen in the liver. These findings indicate that in chronic hepatitis B the severity of liver disease is not directly related to levels of virus replication, thus suggesting a predominant role of host immune mechanisms.

Carrier State↗

Cellular immunity to the hepatitis B virion in acute hepatitis type B.

Ten patients were studied serially during acute hepatitis type B for lymphocyte sensitization to the hepatitis B surface antigen (HBsAg) and to the complete hepatitis B virion (Dane particle). Using the lymphocyte transformation test, sensitization to purified HBsAg was not observed during the first 10 days of illness but became detectable later, being particularly evident during convalescence, while sensitization to antigens of the complete virion, other than HBsAg, was demonstrable as soon as at the onset of symptoms, often at the time of maximum liver cell damage. These results indicate that in the course of acute hepatitis type B, lymphocyte sensitization to other antigens of the complete virion precedes that to HBsAg and may be of greater pathogenetic importance.

Acute Disease↗

Virological changes in chronic hepatitis type B treated with levamisole.

8 children, known to have been hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive for more than 6 months and with chronic active hepatitis on biopsy, received 2.5 mg levamisole/kg/day, 2 days a week for 6-18 months. In 6 of the 8 children transaminases normalized within 4-18 months of therapy, with seroconversion to antibody to HBeAg (anti-HBe) and disappearance of HBV-DNA polymerase from serum and of hepatitis B core antigen (HBcAg) from liver. In these cases liver biopsies taken after treatment showed histological regression to chronic persistent hepatitis. Two distinct patterns of response to levamisole were noted: patients having higher pretreatment transaminase levels and lower expression of HBcAg in the liver showed an early transaminase normalization and anti-HBe seroconversion with therapy, while in patients with less active disease and more diffuse HBcAg positivity in pretreatment liver biopsies, longer treatment periods were necessary to achieve these effects. Our results suggest that long-term levamisole therapy may be beneficial in HBeAg-positive chronic hepatitis type B.

Adolescent↗

Effect of exogenous gastrointestinal peptides containing the C-terminal tetrapeptide of gastrin on calcium, calcitonin and parathormone serum levels in man.

Gastrointestinal hormones containing the C-terminal tetrapeptide of gastrin are involved in calcium homeostasis. The aim of this study was to investigate: 1) the effect of a standard meal (schedule a) and of a duodenal infusion of 5% aminoacid solution (schedule b) on calcium, CT and PTH serum levels in man; 2) the behaviour of these parameters during I.V. infusions of pentagastrin (mcg 1.5/Kg-hour), sincalide (mcg 0.04/Kg-hour) and caerulein (ng 75/Kg-hour) (schedule c). In order to avoid any possible interference by endogenous secretin release, schedule c was performed in 5 patients previously submitted to total gastrectomy. Schedule a and b were studied in 5 healthy volunteers. After a standard meal a slight increase of CT and PTH was measured. Duodenal infusion of aminoacid was followed by hypocalcaemia and slight but constant rise of CT levels, without significant variations of circulating PTH. Pentagastrin, sincalide and caerulein induced a slight but significant hypocalcaemia and a rise of serum CT levels, together with a significant increase of serum PTH. These findings suggest that peptides containing the C-terminal tetrapeptide of gastrin directly affect calcium homeostasis in the absence of secretin release.

Amino Acids↗

[Relationships between clinico-therapeutic parameters and immunological status in patients with lung cancer].

150 patients with lung cancer have been studied from the immunological point of view: the two years that elapsed between the study and processing of the data permitted an evaluation of the prognosis in terms of immunology also. This study has been carried out in vivo by means of skin tests (BCG, PPD, Candida, Varidase, CCB, Mumps, BNCB) and in vitro with lymphocyte blastization in the presence of PHA and dependent antibody cytotoxicity. Serum factors which can interfere with lymphocyte cytotoxicity have also been studied. Peri- and intra-tumour lymphocyte infiltration and the lymph node activation stage have been analyzed in patients who underwent surgery. A real depression of the cell mediated immunity observed in the negative response to skin tests has been found. The study of in vitro parameters showed a deficient blast response in 86% of the cases examined, decreased cytotoxicity in 62% and the presence of inhibiting serum factors in 53%. No correlation was observed between positivity to skin tests, normal response to PHA, normal concentration of inhibiting serum factors on the one hand and survival on the other. The only finding which seems to be correlated with survival is lymphocyte infiltration; its peri- and intrastromal presence on the neoplasia may be associated with a significantly better prognosis.

Antigens↗

Suppressor cell activity in viral and non-viral chronic active hepatitis.

Suppressor cell function was studied in twenty-nine patients with chronic active hepatitis (CAH) in relation to possible aetiological causes and activity of liver disease. All fifteen patients with evidence of viral aetiology (ten HBsAg-positive CAH and five non-A, non-B CAH) showed normal suppressor cell function independently of severity of liver damage. In contrast, fourteen patients with HBsAg-negative CAH, including four cases with circulating antibodies to the hepatitis B virus, demonstrated a significant reduction in supprpessor cell activity compared to control subjects. No significant difference was found in this group between cases with and without circulating autoantibodies. In four out of five HBsAg-negative patients tested serially suppressor cell defect correlated with disease activity suggesting an abnormality in the regulation rather than a depletion of suppressor cells. These results suggest that different mechanisms are responsible for autoimmunity to the liver in virus and non-virus-related CAH.

Adolescent↗