PubMed HealthSearch

Biomedical subjects

M Pernice

Publications and source records attributed to M Pernice.

11 recordsLinked to original sources

Severe outcome of hepatitis B virus (HBV) infection and lack of HBV e antigen-defective virus emergence in patients homozygous for HLA class I alleles.

In the Mediterranean region almost all patients with hepatitis B virus (HBV)-related cirrhosis are anti-HBV e antigen (anti-HBeAg)-positive and carriers of HBeAg-negative virus mutants. The six members of a family who acquired HBV infection were recently studied: two siblings developed cirrhosis with persistence of HBeAg positivity, whereas their parents and two more siblings cleared the virus. The two cirrhotic patients showed homozygosity for HLA class I by phenotype, which is a rare occurrence in the general population, while the other family members were heterozygous for HLA class I. The sequencing analyses of the entire viral DNAs isolated from both cirrhotic patients showed that the two viral genomes were almost identical and no mutation preventing HbeAg synthesis or viral gene expression was present. These findings might suggest that homozygosity for HLA class I molecules might be responsible for an insufficient response to the virus, favouring chronic outcome of the infection and the long-lasting persistence of HBV populations that produce HBeAg.

Adult

Chronic hepatitis in patients with active hepatitis B virus and hepatitis C virus combined infections: a histological study.

OBJECTIVES: To evaluate whether peculiar histological changes are present in liver tissue of patients with chronic hepatitis by hepatitis B and hepatitis C (HBV and HCV) virus combined infections. METHODS: We studied liver biopsy specimens from 14 HB surface antigen/anti-HCV-positive patients consecutively admitted to hospital because of chronic liver disease from 1987 to 1992. Alcohol abusers, drug addicts, hepatitis delta virus- and HIV-infected subjects were excluded from the study. All of them were positive for serum HBV-DNA and/or intrahepatic HB core antigen and for serum HCV-RNA. Histological examination showed mild or moderate chronic hepatitis in nine cases and severe chronic hepatitis with cirrhosis in five cases. Two additional sets of liver biopsy specimens were also included in the study, consisting of liver samples from 14 patients with chronic liver disease due to active HBV infection alone (group B) and from 14 patients with active HCV infection alone (group C). Cases from group B and C matched for age, sex, and histological diagnosis with those from group B + C. Histological patterns of all the liver specimens of the three groups were re-examined by two authors who scored the found features using a scale from 0 to 3. RESULTS: No peculiar histological pattern was revealed in group B + C, and most of the detected microscopic features were similarly present in all three groups. Bile duct lesions and well defined lymphoid follicles were found only in liver samples of patients from groups C and B + C. Ground-glass hepatocytes were observed only in cases from the groups B and B + C. CONCLUSIONS: Histological examination of liver tissue from patients with chronic HBV and HCV combined infection does not show either typical patterns or evidence that this subgroup of chronic viral hepatitis is a more severe form of liver disease than that caused by a single virus infection. The observation in liver samples of peculiar lesions by HBV or HCV infection does not exclude a combined infection by both viruses.

Adult

Persistence of "wild-type" and "e-minus" hepatitis B virus infection in chronic healthy HBsAg/anti-HBe positive carriers.

We examined nine chronic healthy hepatitis B surface antigen/antibody to hepatitis Be carriers with consistently normal liver chemistries and negative serum hepatitis B virus-DNA. Liver biopsy, performed twice, 10-11 years apart in all patients, showed normal histology and negative hepatitis B core antigen. DNA extracted from the second liver biopsy specimen, from 1 ml of serum from each patient and from an additional serum sample of 6 ml from two patients, was tested for pre-C/C and pre-S regions of hepatitis B virus-DNA by polymerase chain reaction amplification. Viral sequences were found in six of nine liver DNA extracts. In four cases both pre-C/C and pre-S regions were amplified, while the pre-C/C alone and the pre-S alone were detected in one case each. Direct sequencing of the amplified DNAs revealed no significant genomic changes in the pre-S and Core regions, while analysis of the pre-Core demonstrated the presence of a double viral population (wild-type and "e-defective") in four cases, and only "e-defective" hepatitis B virus in one case. No hepatitis B virus genomes were revealed in the serum sample when DNA was extracted from 1 ml of serum, while viral sequences were detected in both extracts of 6 ml of serum, indicating the presence of very low levels of viremia. These data suggest that episomal hepatitis B virus-DNA may persist for years in the liver of chronic healthy carriers in a latent state which may involve both wild-type and HBeAg-defective hepatitis B virus.

Carrier State

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

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

Haemodynamic effects of coffee and purified caffeine in normal volunteers: a placebo-controlled clinical study.

In order to evaluate the effects of 'espresso' Italian coffee on resting flow, blood pressure, and peripheral resistance, 15 non-coffee drinking healthy volunteers received 2 cups of regular coffee, 200 mg purified caffeine or placebo in a latin square double-blind crossover protocol. Before and 30, 60, 90 and 120 min after ingestion, segmental resting flow and BP were measured and peripheral resistance was calculated. An echocardiogram was also performed before and 60 and 120 min after caffeine intake. Both regular coffee and caffeine produced a significant decrease in resting flow and a significant increase in resistance; both systolic and diastolic BP also increased, although not significantly. No variation was observed in heart rate and in cardiac contractility. Placebo (highly decaffeinated coffee for regular coffee and china bitter extract for caffeine) did not produce any haemodynamic effect. In five other healthy volunteers used to drinking more than 5 cups of coffee a day, coffee administration had no effect. These data demonstrate that the caffeine contained in espresso Italian coffee is a vasoconstrictor agent whose effects however are completely blunted in usual coffee drinkers as a consequence of adaptation.

Adult

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

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

[Atrial fibrillation in a cohort of the elderly: etiopathogenic role of occult hyperthyroidism and diagnostic and therapeutic considerations. Results of the CASTEL (CArdiovascular STudy in the ELderly)].

This work was performed in order to evaluate the weight of hyperthyroidism on the genesis of atrial fibrillation in elderly subjects. The data are from the CASTEL (CArdiovascular STudy in the ELderly), an epidemiologic study performed in a town of northern Italy (Castelfranco Veneto), whose 3088 elderly subjects were called and 2254 enrolled for a 7-year intervention trial. From 2224 elderly persons examined in the present study, 90 had atrial fibrillation (AF) as determined by the presence of Minnesota Code 8-3; the other 2134 were used as control population. In the 90 with AF and in the randomly chosen controls, the thyroid function was studied by means of the TRH-test. Taking into consideration an increase of TSH greater than 0.5 or greater than or greater than 1 muUI/ml over the basal value after TRH administration, 5.5% of subjects with atrial fibrillation had a suppressed response (i.e. hyperthyroidism); taking into consideration a peak value of TSH greater than or equal to 2.3 muUI/ml irrespective to the basal value, the prevalence of hyperthyroidism was higher (17.8%), but not different than in control subjects. In conclusion, hyperthyroidism is frequent in elderly subjects but it does not play a role in the pathophysiology of AF. On the contrary, AF may be explained in the majority of cases by concomitant cardiovascular disease, i.e. left atrial enlargement, arterial hypertension, myocardial ischemia, and heart failure.

Aged

Polyphasic type A hepatitis: histological features.

The histology of polyphasic type A hepatitis was analyzed in liver biopsy specimens of two patients. The microscopic examination showed, together with changes of acute viral hepatitis, portal plasma cell infiltration, limiting plate erosion and porto-portal bridging necrosis. These features, although sometimes described in classical HAV hepatitis, appear to be similar to those commonly observed in severe and evolving forms of acute hepatitis due to other hepatotropic viruses. Only careful serological analyses can lead to a correct diagnosis and prognosis in case of polyphasic type A hepatitis.

Adult