Search PubMed⌕ Search

Biomedical subjects

G Raimondo

Publications and source records attributed to G Raimondo.

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

Inapparent "wild-type" and "e-minus variant" HBV infection in patients with HCV-related chronic hepatitis.

We analysed DNA extracted from liver biopsy specimens and serum samples from 42 HCV-RNA-positive/HBsAg-negative subjects with chronic hepatitis. Twenty-eight of them were anti-HBs/anti-HBc-positive (group A), while 14 were negative for all HBV markers (group B). HBV sequences were found in hepatic DNA of 12 cases (11 of group A, one of group B), but in the serum of only two cases of group A. Sequencing analysis of pre-core region of HBV-DNA showed the presence of wild-type HBV in three cases, HBeAg-defective HBV in three cases, and the coexistence of both viral populations in six cases. These results indicate that HBV and HCV infection may coexist in HBsAg-negative chronic hepatitis, particularly in anti-HBs/anti-HBc-positive patients. However, HBV replication appears suppressed in these cases, and this state of latency may involve both wild and HBeAg-defective HBV types.

Adult↗
PubMed1993

Is the course of perinatal hepatitis B virus infection influenced by genetic heterogeneity of the virus?

We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to anti-hepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3-4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G+A), indicating a mixture of wild-type and "e minus" variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity.

Base Sequence↗
PubMed1992

Histological behaviour of chronic hepatitis in patients treated with alpha interferon.

To evaluate the histological effects of alpha Interferon (IFN) therapy, serial liver biopsy specimens from 30 patients with chronic hepatitis were studied. The biopsies were examined using a scoring system. After 12 mths of IFN therapy responders were 8 out of 11 HBV infected patients, 10 out of 12 HCV infected patients and only 1 out of 7 patients with cryptogenetic hepatitis. As spontaneous improvement of hepatic changes is infrequent, our data indicate that in terms of histological patterns interferon therapy is effective in chronic viral hepatitis.

Hepatitis B↗
PubMed1991

Hepatitis B virus variant, with a deletion in the preS2 and two translational stop codons in the precore regions, in a patient with hepatocellular carcinoma.

We analyzed hepatitis B virus (HBV) genomes obtained from serum samples and liver biopsy specimen of a chronic HBsAg/anti-HBe carrier with hepatocellular carcinoma (HCC). Before the liver biopsy, performed at the time of HCC diagnosis, the patient had been followed for 2 years; the serum samples collected in that period resulted negative for HBV-DNA dot blot hybridization. The hepatic DNA was at first examined by Southern blot, but no HBV sequence was detected. Polymerase chain reaction (PCR) amplification revealed the presence of HBV genomes in DNA extracted from the liver tissue and from two serum samples collected, respectively, 1 and 2 years before the biopsy. Direct sequence of the amplified preC/C and preS regions showed that the viral populations present in serum and liver were identical and that they had a 34 nucleotide deletion in the preS2 region, while the preC region presented two mutations each introducing a translational stop codon, one at the carboxy terminal end and the other at the second codon of the region, both able to prevent HBeAg expression. These results identify a new HBV variant which was selected during a chronic infection, and had very low levels of replication as shown by its detection only after PCR amplification.

Base Sequence↗
PubMed1991

HBe antibody unrelated to 'e minus' hepatitis B virus variant infection in patients with chronic type D hepatitis.

The presence of HBV-DNA sequences was evaluated in DNA extracted from serum samples, peripheral blood lymphocytes and liver biopsy specimens of five HBsAg/anti-HBe-positive carriers with chronic HDV infection. DNAs were tested by polymerase chain reaction (PCR) amplification technique using two pairs of oligonucleotide primers specific for the preC/C and S regions of the HBV; viral sequences were found exclusively in liver extracts and only in three out of the five cases. The direct sequencing of the amplified preC/C regions showed wild-type sequences in two cases, while in the third case a combination of 'wild' and 'e minus variant' viral populations was observed. Moreover, liver DNA of one positive case was electrophoresed through a low melting agarose gel and the following amplification, performed on DNA re-extracted from three different fragments of the gel, showed the presence of free HBV genomes but the absence of replicative intermediate forms. These results show that anti-HBe positivity is not constantly related to precore mutant HBV infection and suggest that HDV inhibits HBeAg production. Moreover, as it was observed in 'e minus' HBV variants, also during a chronic HBV wild-type infection, the viral replication might be suppressed to undetectable levels.

Base Sequence↗
PubMed1991

Abnormal alanine aminotransferase activity reflects exposure to hepatitis C virus in haemodialysis patients.

Prospective studies have shown that the annual incidence of non-A, non-B (NANB) hepatitis may be high in haemodialysis patients. To assess whether hepatitis C virus (HCV), the major causative agent of post-transfusion and community-acquired NANB hepatitis, has a role in the pathogenesis of liver disease in dialysed patients, we have studied the prevalence and significance of antibodies to HCV in a cohort of patients with end-stage renal disease on chronic haemodialysis treatment. Seventy-four (30%) had circulating antibodies to HCV. Statistically significant associations with the anti-HCV carrier status were duration of haemodialysis treatment, blood transfusions, and the finding of abnormally elevated ALT on retrospective analysis. In contrast, only one of 103 dialysis staff members showed transient positivity for anti-HCV, suggesting a low risk of professional exposure to HCV. These findings suggests that HCV infection is relatively frequent in haemodialysis patients and may be responsible for a significant proportion of liver disease in this clinical setting.

Adolescent↗
PubMed1991

Histological features in liver biopsy specimens of patients with acute reactivation of chronic type B hepatitis.

The histological features in liver biopsy specimens from seven patients with acute exacerbation of chronic type B hepatitis were analysed. In all the cases typical changes of acute hepatitis were superimposed on signs of chronicity, namely peripheral piecemeal necrosis, plasma cell infiltration and porto-portal bridges, which in three cases contained elastic fibres. Reactivation of silent hepatitis B virus chronic infection should be considered as a possible diagnosis in any patient with histological findings of acute and chronic hepatitis.

Biopsy↗
PubMed1990

A new hepatitis B virus variant in a chronic carrier with multiple episodes of viral reactivation and acute hepatitis.

To examine whether there are HBV variants not yet described which cannot express HBe due to a mutation in the pre-C region, and, if they exist, whether they cause a particular course of infection and disease, we analyzed the HBV genomes of a HBs/anti-HBe positive chronic carrier who had several episodes of acute reexacerbations of chronic hepatitis with at least two viremic phases. Direct sequencing of the precore/core and the pre-S regions of the HBV sequences of both viremic phases amplified by the polymerase chain reaction revealed that they were very similar to each other but substantially divergent from published HBV genomes. Both virus populations contained a mutation in the first nucleotide of the pre-C translation initiation codon (AUG/CUG) which prevents HBeAg expression. These data demonstrate the existence of a new HBV variant which can enter a latent phase from which it can be reactivated with acute reexacerbation of liver inflammation.

Adult↗
PubMed1990

Hepatitis B virus (HBV) markers and HBV-DNA in serum and liver tissue of patients with acute exacerbation of chronic type B hepatitis.

We analysed the serum samples and the liver biopsies of six consecutive chronic HBsAg/anti-HBe carriers admitted to hospital because of an episode of acute hepatitis. The six patients became positive for IgM anti-HBc and negative for HBeAg, hepatitis Delta virus (HDV) markers, IgM anti-hepatitis A virus (HAV), anti-cytomegalovirus (CMV) and anti-Epstein-Barr virus (EBV). Two patients showed positivity for hepatitis B virus (HBV)-DNA in serum obtained on admission, with no positivity in the subsequent weeks; the results of the other four patients were always negative for seric HBV-DNA. The Southern-blot analysis of the DNA extracted from the liver tissue of four subjects showed the presence of HBV-DNA in the form of replicative intermediates; focal positivity of HBcAg was detected in the liver of only one. The liver biopsies of the last two patients were negative for HBV-DNA and for HBcAg. The analysis of HBV-DNA in the liver extracts and the demonstration of an increase of the IgM anti-HBc titre at the time of the abrupt elevation of the aminotransferase levels seem to be the most useful tools in revealing HBV activation as a cause of acute hepatitis in chronic HBsAg carriers, overall when the phase of viremia is transient.

Antigens, Viral↗
PubMed1990

Latency and reactivation of a precore mutant hepatitis B virus in a chronically infected patient.

In human patients infected with hepatitis B virus (HBV) seroconversion from HBe to anti-HBe often signals virus elimination. Occasionally, a second viremic phase is observed which may be due to superinfection with a variant or reactivation of a latent virus. To differentiate between these two possibilities we investigated the nucleotide sequences of virus populations from sera of a chronically infected patient who had two distinct viremic phases, one e-antigen positive and one anti-HBe antibody positive. By direct sequencing of amplified HBV C- and pre-S gene sequences we found that the viruses in the two populations differed by only two point mutations, one of which prevents expression of precore derived e-antigen. In the nonviremic phase viral DNA and antigen were found in the liver but nucleocapsid protein expression appeared drastically downregulated. These data demonstrate that HBV can enter a latent phase with low expression of core protein and selection for HBV variants which cannot synthesize e-antigen. This suggests that e-antigen expression can be a critical target for virus elimination and that loss of its expression can prolong chronicity and provoke latency of HBV infection.

Antigens, Viral↗
PubMed1989

Hepatitis B-DNA replication and histological patterns in liver biopsy specimens of chronic HBsAg positive patients with and without hepatitis delta virus superinfection.

The role of active hepatitis B virus (HBV) infection in chronic HBsAg positive hepatitis with and without hepatitis delta virus (HDV) superinfection was analysed in percutaneous liver biopsy specimens from 50 patients. Each specimen was divided into two--one part for histological evaluation and for the detection of HBcAg and delta antigen; the other part was tested for HBV-DNA using Southern blotting. Ten cases were of chronic lobular hepatitis, 10 of chronic persistent hepatitis, and 30 of chronic active hepatitis. Ten cases were delta antigen positive and showed high grade lobular activity but no evidence of HBV-DNA episomal forms or HBcAg reactivity. Twenty one cases showed HBV-DNA replicative intermediate forms; 19 had high grade lobular activity, which occurred in five cases without evidence of free viral DNA. Of the 21 biopsy specimens with HBV-DNA episomal forms, 14 were positive for HBcAg; only one of the 19 cases without detectable viral DNA was positive for such antigen. These data indicate that the presence of HBV or HDV active infection correlates with the histological finding of prominent lobular necrosis. Moreover, intrahepatic HBV-DNA seems to be a more sensitive marker than the presence of viral antigens for indicating HBV replication.

Carrier State↗
PubMed1988

Interrupted replication of hepatitis B virus in liver tissue of HBsAg carriers with hepatocellular carcinoma.

To search for events underlying reduction of peripheral viremia and integration of hepatitis B virus (HBV) DNA into the liver cell genome in long-term virus carriers with hepatocellular carcinoma, paired samples of liver and tumor tissue were analyzed by molecular hybridization and immunological methods. Most tumor tissues contained integrated viral DNA; in none was extrachromosomal HBV DNA detected. Integrated HBV DNS was also found in peritumor liver tissue in the majority of patients. However, liver of patients either with or without peripheral viremia also contained free HBV DNA and replicative intermediates. In three nonviremic patients with replicative HBV DNA in liver, viral core antigen expression was markedly reduced or absent, whereas viral envelope protein (surface antigen) expression was normal. In one case, replicative intermediates in liver were sensitive to DNase I digestion, indicating that viral DNA was not encapsidated in normal viral core particles. These results suggest that decreased or defective core antigen production can lead to reduced viremia associated with blocked virus assembly/secretion and accumulation of unencapsidated HBV DNA replicative intermediates in the liver cell. Accumulation of such HBV DNA molecular forms in the liver may lead to an increased propensity for HBV DNA to integrate into the host genome, which has been found with high frequency in hepatic neoplasms from patients infected with hepatitis B virus.

Carcinoma, Hepatocellular↗
PubMed1987

Expression of pre-S gene-encoded proteins in liver and serum during chronic hepatitis B virus infection in comparison to other markers of active virus replication.

Pre-S gene-encoded proteins of the hepatitis B virus (HBV) were studied in the liver by immunofluorescence and in serum by radioimmunoassay in 30 patients with chronic HBV infection. The results were compared with molecular hybridization analysis of HBV-DNA in liver and serum, with serum hepatitis B e antigen/antibody (HBeAg/anti-HBe) status and with underlying liver histology. Pre-S peptides were detected in the serum of 11 patients, 10 of whom were positive for serum HBV-DNA and/or liver hepatitis B core antigen. Only 4 of these patients were HBeAg positive. The prevalence of serum pre-S among HBV replicating carriers was 59% (10/17) compared to only 8% (1/13) among those with non-replicating virus (P less than 0.01). All patients with circulating pre-S peptides had active liver disease. Anti-pre-S was detected in the serum of only 4 patients, 3 with integrated HBV-DNA. In contrast to serum findings, pre-S peptides were detected in the liver of all patients with histochemically demonstrable hepatitis B surface antigen (HBsAg), regardless of HBV replicative status. HBsAg carriers with integrated HBV-DNA had abundant cytoplasmic pre-S1 and pre-S2 localized in numerous ground-glass hepatocytes. It is concluded that pre-S peptides are usually displayed in the liver simultaneously with histochemically detectable HBsAg; they are secreted in the serum in association with high HBV replication and release of HBV particles, but in the absence of episomal HBV replication, pre-S peptides seem to be largely retained within hepatocytic membranes.

Adult↗
PubMed1985

Polyalbumin receptors, hepatitis B surface antigen (HBsAg), and HBsAg/IgM complexes in HBsAg positive patients with and without delta superinfection.

Receptors for polymerized human albumin are found at high titres during high-level hepatitis B virus (HBV) replication and in small amounts in chronic low-level infection. Complexes between hepatitis B surface antigen (HBsAg) and IgM without specificity for HbsAg are expressed in a pattern similar to that of receptors. Anti-albumin antibodies could be involved in their formation. Delta infection depresses the synthesis of gene products of HBV. To assess whether delta modifies the expression of receptors on HBsAg and the level of HBsAg/IgM complexes, and if anti-albumin antibodies are actually part of the complex, we tested sera from 86 subjects with acute and chronic HBV infection. Our findings show that the amounts of circulating receptors and HBsAg/IgM are proportional to the concentration of HBsAg and thus probably to the degree of viral replication. We did not find any correlation between circulating anti-albumin antibodies of the IgM class and HBsAg/IgM complexes. Delta infection depresses HBsAg synthesis and causes a related decrease in receptors and HBsAg/IgM titres if superimposed on the more active stage of HBV infection. When HBsAg, receptors, and HBsAg/IgM are at low levels, no further depression is caused by delta infection. HBsAg/IgM titre is not enhanced by presence of anti-delta antibodies, thus excluding a role of the latter in forming these complexes.

Acute Disease↗
PubMed1985

Familiar clustering and spreading of hepatitis delta virus infection.

The prevalence of hepatitis delta virus (HDV) infection was significantly higher among the relatives of 79 carriers of HBsAg with antibody to HDV (index cases) than among relatives of 111 carriers without serological evidence of HDV infection (controls). Antibody to HDV was found in 45 of the 80 (56%) carriers of HBsAg in families of index cases but only in 2 of 59 (3%) carriers in families of controls (P less than 0.0001). During follow-up new HDV infection developed in 31% of 13 susceptible carriers in families of index cases, but only in 1.2% of 162 susceptible carriers in families of controls (P less than 0.001). None of the family members previously unexposed to the hepatitis B virus had HDV markers in serum or developed this infection during the follow-up. Familial clustering shows that HDV is transmitted by personal contacts, presumably through the inapparent permucosal or percutaneous passage of virus during close or intimate contact. The family model indicates that endemic HDV is maintained and spread through the network of carriers in the community, and that HBsAg carriers in contact with HBsAg/HDV carriers are at high risk of contracting HDV.

Adult↗
PubMed1984

Delta agent infection in acute hepatitis and chronic HBsAg carriers with and without liver disease.

Hepatitis B virus (HBV) is a major cause of chronic liver disease in southern Italy. In the same area superinfection with the delta agent is endemic. To assess the prevalence of delta infection in a large population of patients with acute and chronic HBV related liver disease and to look for differential features among delta infected and uninfected subjects sera from 592 consecutive HBsAg positive patients were tested for the delta/anti-delta system by RIA. In no case was delta Ag found in serum. The prevalence of anti-delta was low in acute hepatitis (6.6%) and in asymptomatic carriers (6.4%) but raised in chronic active hepatitis with or without cirrhosis (52.3%). A decrease in frequency of anti-delta was seen in inactive cirrhosis (38.8%) and in hepatocellular carcinoma (11.9%). A younger mean age of delta-infected subjects was observed in each type of chronic liver disease. Our data confirm that delta agent superinfection is definitely associated with severe chronic active liver disease. The difference in age between anti-delta positive and negative patients suggests that delta infection accelerates the natural history of HBV related liver disease.

Acute Disease↗