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Biomedical subjects

F Bonino

Publications and source records attributed to F Bonino.

At least 163 records · Page 9Linked to original sources
PubMed1990

A new hepatitis B virus strain in patients with severe anti-HBe positive chronic hepatitis B.

In hepatitis B virus carriers who are anti-HBe positive despite ongoing viral replication (HBcAg in liver and HBV-DNA in serum) the natural course of hepatitis is severe and the response to interferon is low. We investigated whether a new hepatitis B virus (HBV) strain could be involved. A translational termination codon at the carboxyterminal end of the pre-C region responsible for the lack of HBeAg secretion was found in 18 of 19 HBV clones isolated from seven pedigreed patients with this clinical syndrome. The same findings were confirmed by direct sequencing. One of these patients underwent a liver transplant and HBV infection of the new liver resulted in high titered viremia and intrahepatic expression of HBcAg, without detectable HBeAg in serum. Another patient was superinfected by hepatitis delta virus (HDV) and developed high titres of total and IgM anti-HD. In spite of this, chronic hepatitis remained unchanged during 7 years of follow-up. These data strongly suggest that a viable precore minus mutant of hepatitis B virus is responsible for the lack of HBeAg in the serum of these patients. The HBV variant may explain the peculiar geographic distribution of anti-HBe positive hepatitis. The variations in the virus genome sequence may cause the more severe form of liver disease and modify the pathogenicity in the case of HDV superinfection.

Adult↗
PubMed1990

Immunohistochemical research of HDV infection in Chinese patients with chronic liver disease.

The prevalence of HDAg in the liver of Chinese patients with chronic hepatitis and hepatocellular carcinoma was determined using direct immunofluorescence and immunoperoxidase. Overall, 6 patients (6.31%) out of 95 HBsAg carriers with inflammatory liver disease and neoplasia were found to be HDAg positive. HDAg was detected in the livers of 6 (7.59%) out of 79 chronic hepatitis patients. The relative frequency of HDAg in cirrhosis-B, CAH-B and CPH-B was 14.3%, 7.1%, and 5.89%, respectively. These results suggest that a sizeable number of HBsAg carriers are also carriers of HDV. In view of the large number of HBV carriers in China, the relatively minor but distinct presence of HDV represents an important health problem.

Carcinoma, Hepatocellular↗
PubMed1989

Natural course and response to interferon of chronic hepatitis B accompanied by antibody to hepatitis B e antigen.

The course of chronic hepatitis B was studied in 30 patients who had antibody to hepatitis e antigen and hepatitis B virus DNA in the serum and hepatitis B core antigen in the liver. Over a 2-year period, no patient experienced a sustained spontaneous remission of disease, and follow-up liver histology revealed worsening of the disease in four patients. After 2 years of observation, 24 patients were allocated randomly to one of two groups: 12 patients served as untreated controls and 12 received recombinant human alpha-interferon-2a in a dose of 9 million units intramuscularly three times weekly for 16 weeks. Patients who remained viremic after 16 weeks received 3 million units three times weekly for an additional 8 weeks. Abnormal amino-transferases and serum hepatitis B virus DNA persisted without appreciable changes in all untreated patients. Hepatitis B virus DNA rapidly became undetectable and serum aminotransferases fell to normal in eight treated patients. After the end of treatment, hepatitis B virus DNA became detectable once again in seven patients, in six of whom a peak of aminotransferases (range: 256 to 850 units per liter) ensued; subsequently, hepatitis B virus DNA disappeared, and serum aminotransferases again fell to normal in two of the seven. Overall, hepatitis B virus DNA was no longer detectable in serum and liver histology improved in three treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Intrahepatic markers of hepatitis delta virus infection: a study by in situ hybridization.

The intrahepatic distribution of hepatitis delta virus RNA was studied by in situ hybridization in 33 formalin-fixed, paraffin-embedded biopsies from 17 chronic hepatitis B virus carriers superinfected with hepatitis delta virus. The findings were correlated with the expression of the hepatitis delta antigen, the duration of the hepatitis delta virus infection and the eosinophilic degeneration of the hepatocytes. Intranuclear hepatitis delta virus RNA and antigen were found in 28 specimens, whereas the remaining five were negative for both markers. Hepatitis delta virus RNA and antigen were mostly found within the same cell. In 20 specimens, however, a variable number of hepatocytes showed the presence of hepatitis delta virus RNA alone. The percentage of these over the total number of infected cells was higher in the specimens taken within 1 year from the acute delta hepatitis, whereas their absence was invariably associated with a long-established hepatitis delta virus infection. Interestingly, the vast majority of hepatocytes undergoing eosinophilic degeneration, a change significantly associated with hepatitis delta virus infection, did not show the presence of either hepatitis delta virus RNA or the viral antigen, suggesting a lack of association, at the cellular level, between viral replication and cytopathological change. The specificity of the detection of hepatitis delta virus RNA was confirmed by negative findings in nine specimens from seven chronic hepatitis B virus carriers without evidence of past or current hepatitis delta virus infection. The loss in sensitivity due to the formalin fixation was estimated to be 50% of that obtained in frozen biopsies, as determined by counting autoradiographic grains over infected cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Immunohistochemical research on HDV infection in Chinese patients with chronic liver disease.

The prevalence of HDAg in the liver of Chinese patients with chronic hepatitis and hepatocellular carcinoma was determined by using direct immunofluorescence and immunoperoxidase. Six patients (6.3%) out of 95 HBsAg carriers with inflammatory liver disease and neoplasia were found to be HDAg positive. HDAg was shown in the liver of 6 patients (7.6%) among 79 patients with chronic hepatitis. The relative frequency of HDAg in cirrhosis-B, chronic active hepatitis B and chronic persistent hepatitis B was 14.3%, 7.1% and 5.9% respectively. These results suggest that a sizeable number of HBsAg carriers are superinfected with HDV. In view of the large amount of HBV carriers in China, the relative minor but distinct presence of HDV poses an important community health problem.

Carcinoma, Hepatocellular↗
PubMed1989

Relationship between the intrahepatic expression of 'e' and 'c' epitopes of the nucleocapsid protein of hepatitis B virus and viraemia.

The relationship between hepatitis B viraemia and intrahepatic HBV nucleocapsid proteins (HBcAg and HBeAg) was studied in 18 patients with chronic hepatitis B. Monoclonal antibodies (MoABs) were obtained in BALB/c mice primed with recombinant HBV nucleocapsid proteins. Four MoABs reacting with recombinant proteins gave positive results in competitive assays. Two reacted as anti-HBc and two as anti-HBe. One of them showed a strong affinity for the cytoplasmic, membrane-bound antigen (P23e) of infected hepatocytes while the latter showed a higher specificity for serum HBeAg than for the intrahepatic antigen. Anti-HBc MoABs had a staining capacity for liver cell nuclei comparable with that of polyclonal antibodies. Overall the anti-HBc MoABs stained the liver cell nuclei in 86% of cases, while anti-HBe MoABs stained in 58% of cases. The hepatocyte cytoplasm was stained by anti-HBc MoABs and anti-HBe MoABs in 64% and 72% of cases respectively. Not one of 12 control liver biopsies was stained. Viraemia (HBV-DNA) was measured by dot blot hybridization and was correlated with the number of hepatocytes containing the nucleocapsid antigen. The highest levels of HBV-DNA (greater than 10(8) genomes/ml) were detected in patients with prevalent nuclear staining while the lowest ones were observed in those with prevalent cytoplasmic expression of this antigen. The application of anti-HBV-nucleocapsid MoABs in diagnostics requires careful scrutiny since some are specific for the circulating antigen while others show a higher affinity for the intrahepatic antigen.

Antibodies, Monoclonal↗
PubMed1988

Inhibition of hepatitis B virus replication by vidarabine monophosphate conjugated with lactosaminated serum albumin.

Vidarabine (ara A) produces severe dose-dependent side-effects. To examine whether its monophosphate ester (ara-AMP) can be effective in the treatment of chronic hepatitis B when given in reduced dosage as a conjugate with lactosaminated human serum albumin (L-HSA), which selectively enters hepatocytes, five patients with chronic type B hepatitis (HBsAg/HBV-DNA positive for at least 2 years) were treated with the conjugate. The daily dose of conjugate given (35 mg/kg) contains 1.5 mg ara-AMP, whereas the usual daily dose of free ara-AMP is 5-10 mg/kg. In three patients HBV-DNA fell to undetectable levels and remained negative in two; in one of them anti-HBe developed. In the other two patients HBV-DNA decreased but was detectable during treatment--one received three cycles of therapy, and became HBV-DNA negative and anti-HBe positive 45 days after the end of treatment; the other remained HBeAg/HBV-DNA positive. No adverse effects were observed, and biochemical variables (including aminotransferases) remained unchanged or decreased with viraemia. No antibodies (IgM and IgG classes) that bound the conjugate were detected. Thus L-HSA-ara-AMP inhibits HBV replication as well as free ara-AMP but at a third to a sixth of the dose.

Adult↗
PubMed1988

Delta and non-A, non-B hepatitis viruses.

A review is given on the current knowledge of the hepatitis delta virus (HDV), the only hepatotropic non-A and non-B (NANB) virus characterized, although the infection it causes requires infection with hepatitis B virus (HBV). Studies in chimpanzees have provided the most data now available on the putative NANB agents. Histologic and electron microscopic changes occurring in HDV and NANB hepatitis have been shown to be comparable, and some biologic, epidemiologic and clinical features are similar. However, the lack of cross-protection between NANB and HDV hepatitis in cross-challenge transmission experiments and the lack of hybridization between HDV-RNA and nucleic acids from NANB material indicate that HDV and the putative NANB agents are minimally, if at all, related.

Animals↗
PubMed1988

Chronic HDV (hepatitis delta virus) hepatitis. Intrahepatic expression of delta antigen, histologic activity and outcome of liver disease.

The expression of intrahepatic delta antigen (HDAg) was studied in relation to the morphologic features of HDV hepatitis and the outcome of liver disease. The study was performed in 101 patients followed up for an average of 12 years; one or more liver biopsies were available from each patient, giving a total of 167 specimens. The histologic features were assessed using numerical scores. A significant positive relation was observed between the number of HDAg-positive cells and the extent of portal inflammation (Spearman's rank coefficient 0.75). The highest degree of inflammation and intrahepatic expression of HDAg was found before the elimination of the virus, while the outcome of HDV disease was unrelated to the severity of the initial morphologic lesion. These results suggest that the individual immune response may play an important role in the pathogenesis of HDV hepatitis.

Adolescent↗
PubMed1988

Serum markers of hepatitis B virus replication, liver histology and intrahepatic expression of hepatitis B core antigen.

The presence and distribution of hepatitis B core antigen (HBcAg) was studied in the liver of 227 chronic carriers of hepatitis B surface antigen (HBsAg) to investigate its relationship with serum HBV-DNA, the status of hepatitis B 'e' antigen/antibody (HBeAg/anti-HBe) and the underlying liver disease. HBcAg was detected in 144 of the 227 (63%) liver specimens and HBV-DNA in 132 (58%) of the corresponding sera. Serum HBV-DNA showed a constant link with intrahepatic HBcAg. Out of 96 HBeAg-positive patients, 91 (95%) had HBcAg in the liver and 85 (89%) had HBV-DNA in serum. Overall there was a significant link between HBeAg and HBV-DNA in serum, but there was no correlation in 58 out of 227 (26%) cases. In HBeAg/HBV-DNA-positive carriers, HBcAg expression was predominantly nuclear. It was nuclear and cytoplasmic in patients with the highest levels of viremia. Eleven out of 13 (85%) HBV-DNA-positive patients who had only cytoplasmic HBcAg were HBcAg-negative and had low levels of HBV-DNA. Nine of 13 (69%) patients with exclusively cytoplasmic HBcAg had severe chronic liver disease. Neither the presence of HBV-DNA and HBeAg in serum nor the nuclear localization of HBcAg were associated with the severity of liver damage. In the group of HBV-DNA-positive patients (132), the presence of liver disease was significantly connected with the absence of HBeAg in serum (P less than 0.05; C.L. 3-35).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

[Evaluation of the usefulness of ultrasonics in the diagnosis of cancerous cirrhosis. Comparison with CT].

Cirrhotic liver hepatocellular carcinoma (HCC) was evaluated with both US and CT. In a group of 600 cirrhotic patients 64 had HCC, which was confirmed at histology in 24 cases, and by disease evolution in the other 40; single focal degeneration was proven in 40 patients, multiple (2, 3 focal lesions), or diffuse degeneration (more than 3 focal lesions) in the remaining 24. Sixteen patients had associated portal thrombosis. US recognized 38/40 single HCC, 22/24 multiple or diffuse lesions, and 11/16 portal vein thromboses. Degeneration was most frequently hypo/isoechoic in small tumors, hyperechoic and mixed in large lesions. When small lesions are hyperechoic their differentiation from both hemangiomas and regeneration noduli is extremely difficult. In such cases CT is mandatory. US diagnostic accuracy is by far superior to that of CT: 95% vs 85% in single lesions and 91.6% vs 87.5% in diffuse forms. Overall accuracy is 93.7% for US and 85.9% for CT. The authors believe that US should be performed every 6 months on cirrhotic patients, so as to allow HCC to be detected in time for radical surgery, while CT should be performed only when doubts persist.

Adult↗
PubMed1988

Delta virus infection in Jerusalem.

The role of hepatitis delta virus (HDV) infection was analyzed retrospectively in a highly selected population of 76 patients who were hospitalized in Jerusalem for hepatitis B surface antigen positive for chronic active hepatitis and cirrhosis. Of 25 patients in whom serum and liver tissue were available, 5 patients (20%) showed evidence for HDV infection using a serum anti-HDV IgG radioimmunoassay; in one of them, HDV was also detected in nuclei of infected hepatocytes by immunofluorescence (IF). When only serum was tested, 12 of 45 patients (27%) were anti-HDV IgG positive. The use of IF alone had a very low yield of HDV detection. All HDV-positive patients with available serum had superinfection with the delta agent as confirmed by a negative anti-HBc IgM assay. The majority of HDV-positive patients were immigrants from Rumanian or Middle Eastern and Mediterranean origin. The mean age of delta-positive patients was 10 years lower at clinical presentation as compared with HDV-negative patients. HDV-positive patients had a higher mortality as compared with the HDV-negative group. In conclusion, HDV infection is prevalent among Israeli patients with chronic liver disease and persistent hepatitis B virus infection and leads to a significant morbidity and mortality.

Adolescent↗
PubMed1987

Rapidly progressive HBsAg-positive hepatitis in Italy. The role of hepatitis delta virus infection.

Serum or liver markers of hepatitis delta virus (HDV) infection were found in 20 of 22 (90%) Italian patients presenting with an ostensible type B hepatitis that ran an accelerated course to cirrhosis. The features of the illness conformed to a syndrome of HDV infection in young males carrying the hepatitis B surface antigen (HBsAg); a latent HBsAg state was documented in many patients by a history of prior exposure to the hepatitis B virus (HBV) or by the absence of IgM antibodies to the HB core antigen. Characteristic of the disease were the clinical overture as a severe hepatitis, the lobular involvement by an extensive necroinflammatory reaction, the exuberant expression of intrahepatic hepatitis delta antigen and an atypical HBV profile of inactive infection or accelerated seroconversion from HBeAg to anti-HBe. Superimposed upon HBV infection, HDV may create a rapidly progressive course which resembles very aggressive hepatitis B but is infrequently observed in hepatitis B alone.

Adolescent↗