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Biomedical subjects

M R Brunetto

Publications and source records attributed to M R Brunetto.

At least 91 records · Page 5Linked to original sources
PubMed1993

Is high AgNOR quantity in hepatocytes associated with increased risk of hepatocellular carcinoma in chronic liver disease?

AIMS: To evaluate whether high numbers of silver staining nucleolar organiser regions (AgNORs) in hepatocytes are associated with increased risk of hepatocellular carcinoma in chronic liver disease. METHODS: The quantitative distribution of AgNORs was studied in the liver biopsy specimens of 33 patients with chronic liver disease, 11 of whom developed hepatocellular carcinoma. The interval between liver biopsy and diagnosis of hepatocellular carcinoma was 26 months (range one to 61 months); the mean follow up of patients without hepatocellular carcinoma was 45 months (range 24-59 months). Quantitative evaluation of AgNORs was carried out on silver stained routine sections by morphometric analysis, using a computer assisted image analysis system. RESULTS: High interphase AgNOR values (> 3 microns2) were found in hepatocytes of nine out of the 11 (82%) patients in whom neoplastic transformation occurred. Of the remaining 22 patients, only seven (31%) had AgNOR values higher than > 3 microns2 (chi 2 4.83; p = 0.036). CONCLUSIONS: These results indicate that high numbers of interphase AgNORs are associated with increased risk of hepatocellular carcinoma in patients with chronic liver disease.

Adult↗
PubMed1992

Variants of hepatitis B virus.

Variations in the course of disease caused by hepatitis B virus may often be attributed to genomic variants of the virus. It must be kept in mind, however, that other factors, i.e. immunocompetence of the host and new methods of detection such as PCR, may also result in apparently aberrant phenotypic expression. Examples of both situations are presented here and the need is stressed for combined virological, biochemical and clinical studies.

DNA, Viral↗
PubMed1992

Observation on a human intentional poisoning case by the organophosphorus insecticide fenthion.

A case of acute poisoning by oral ingestion of fenthion is reported. Plasma cholinesterase activity and fenthion whole blood concentration were thoroughly evaluated during the therapeutic intervention that consisted in administration of atropine, toxogonine and fresh plasma. Correlation studies between clinical signs, cholinesterase activity and fenthion levels revealed that pChE activity was not as helpful as the patient's clinical status in determining when the atropine infusion could be stopped. Moreover pChE was also useless in signaling sudden relapses. It is concluded, based on this case, that supportive care combined with antidotal therapy remains the cornerstone of treatment specially in severe acute poisoning cases.

Adult↗
PubMed1992

Treating chronic liver disease: lessons from a day hospital.

The relationship between the professional background of the physician requesting the biopsy procedure (whether non-specialist or specialist in hepatology/gastroenterology) and the subsequent decision of treatment of the patients was analyzed. Treatment was divided into two categories named arbitrarily "no therapy" (general supportive measures) or "therapy" (causal treatment based on active drugs or measures aimed at affecting the cause of the disease). Of the 204 cases of outpatient needle biopsies available for study, 157 were made by specialist request and 47 were made by a non-specialist request. Sixty-eight (43%) of the former, but only 3 (2%) of the latter had "therapy" (p = 0.0001). Also, patients in which histology showed chronic active liver disease had "therapy" more frequently (49 of 109, 44.9%) than those without chronic active liver disease (22 of 95, 23%) with p less than 0.01. However, patients with histological active chronic disease were not more frequent among specialist requests (56.6%) than among the non-specialist requests (42.5%). But among patients attended by the specialist, there were more patients (31.8%) with positive serum markers of Hepatitis B virus infection than among those sent by others (12.7%) with p less than 0.01. We conclude that at least in the premises in which this study was carried out, blind liver biopsies will lead to active treatment more often in patients treated by a specialized physician, because these patients are more likely to have a virus identified as the cause of their liver disease and consequently will receive antiviral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis.

Using an oligonucleotide hybridization assay, we studied the clinical implication of wild-type hepatitis B virus (HBV) and a HBV mutant that is unable to secrete hepatitis B e antigen (HBeAg) because of a translational defect due to a stop codon in the pre-C region in 106 hepatitis B surface antigen-positive patients with chronic hepatitis B. Wild-type HBV was detected in 31 of 42 (73.8%) HBeAg-positive patients, whereas a mixed viral population was present in 10 (23.8%). Significant differences in the severity and outcome of liver disease were not observed in the two groups of patients. However, the emergence of HBeAg-minus HBV in wild-type HBV carriers was associated with an exacerbation of liver disease and was followed by the presence of antibodies against HBeAg (anti-HBe) in serum in 50% of the cases. In 61 of 64 (95.3%) anti-HBe-positive patients, HBeAg-minus HBV was the predominant virus: HBeAg-minus HBV was detected in 42 patients (65.6%), whereas both wild-type and HBeAg-minus HBV were present in 19 (29.7%). HBeAg-minus HBV was associated with a course of hepatitis characterized by flare-ups of liver cell necrosis interspersed with periods of asymptomatic HBV carriage (P less than 0.01). These data support the hypothesis that genetic heterogeneity of HBV significantly influences the course and outcome of chronic hepatitis B. Wild-type HBV secreting HBeAg induces immunologic tolerance and causes chronic infection. HBeAg-minus HBV might be unable to induce chronic infection without the helper function of wild-type HBV, but it appears to be more pathogenic. Once chronic infection is established, HBeAg-minus HBV variants may prevail and displace wild-type virus.

Adolescent↗
PubMed1991

Role of hepatitis delta virus infection in hepatocellular carcinoma.

Hepatitis B virus (HBV) DNA integrates into the host DNA and shows a series of potentially oncogenetic properties, but HBV is not an acutely transforming virus, because HCC develops decades after infection. Other factors, namely cirrhosis, inflammation, alcohol intake, and viral superinfections, could promote the oncogenetic process induced by HBV-DNA integration. We studied the impact of HDV infection in the pathogenesis of HCC in 62 consecutive patients. Their mean age was 59 years (range 25-75 years), 54 were male and eight female; 58 had cirrhosis. The findings suggest that HBsAg-positive patients with HDV superinfection developed cirrhosis and HCC at an earlier age than HBsAg carriers without HDV infection. HDV appears to represent a "promotion" factor for HCC in subjects with an oncogenic risk induced by HBV. A long-lasting necroinflammatory lesion of the liver substained by productive HBV and HDV infections may be a major pathogenetic mechanism.

Carcinoma, Hepatocellular↗
PubMed1991

'e' antigen defective hepatitis B virus and course of chronic infection.

We studied the relations between HBV heterogeneity and different phases of HBV infection and disease in 145 HBsAg-positive carriers followed-up for 28 months (range 24-60 months). Viraemia was characterized for the relative prevalence of wild-type and HBeAg minus HBVs after HBV-DNA amplification by PCR using an oligonucleotide hybridization assay. HBeAg minus HBV was detected in 27% of immunotolerant HBV carriers, in 67% of patients with chronic hepatitis B (immunoelimination phase) and in 17% of HBsAg carriers with latent infection. Serum HBV-DNA and IgM anti-HBc became undetectable and ALT levels normalized, either spontaneously or after interferon therapy in 12 (36.3%) of 33 patients with an exclusive wild-type viraemia, but only in two (5.7%) of 35 patients with homogeneous HBeAg minus HBV (p = 0.005). An HBeAg minus viraemia higher than 20% was associated, in both HBeAg- and anti-HBe-positive patients, with HBV-induced liver disease and an unfavourable outcome of hepatitis. These findings suggest that surgence of HBeAg defective HBV is a virus strategy to survive under peculiar conditions dictated by the interplay between HBV and the host's immune system. The HBeAg/anti-HBe serological status is determined not only by the extent of virus replication and integration of HBV-DNA into cellular DNA but also by heterogeneity of HBV. The study of HBV heterogeneity in baseline sera of patients undergoing antiviral therapy appears to have a predictive value of the outcome of HBV infection in the single patient.

Adult↗
PubMed1991

Serological diagnosis of hepatitis B and delta virus (HBV/HDV) coinfection.

Diagnosis of acute hepatitis B virus/hepatitis delta virus (HBV/HDV) coinfection is currently based on detection of anti-HD, however this antibody may be undetectable during the acute phase of hepatitis. To evaluate the entity of misdiagnosis of HBV/HDV coinfection in acute HBsAg-anti-HBc IgM positive hepatitis we examined sera from 245 consecutive patients obtained at admission and day 30, 60, 120, 210 and 400 of their follow-up. Anti-HD was detected in the serum of 26 out of 245 patients (10.6%). In 15% of cases it was present at admission, while in 92% it was found after 30 days. The combined detection of HDV-RNA, HDAg and IgM anti-HD in acute phase sera allowed a correct etiologic diagnosis in 69% of the cases. These findings suggest that the prevalence of HBV/HDV coinfection is underestimated when anti-HD is the only marker to be detected during the acute phase of disease. A correct etiologic diagnosis can only be made by testing acute phase sera for all the available markers of HDV. However, the best cost-effective procedure is to test any patient with HBV markers at presentation for anti-HD, 30-40 days after the onset of symptoms.

Adult↗
PubMed1991

Treatment with interferon of chronic hepatitis B associated with antibody to hepatitis B e antigen.

Persistence of HBV replication (serum HBV-DNA and intrahepatic HBcAg) and markers of HBV-induced (IgM anti-HBc positive) liver disease in anti-HBe-positive patients characterize a peculiar form of chronic hepatitis B. This form of hepatitis B prevails in the Mediterranean Basin, Middle and Far East and is associated with the infection of an HBV variant that lacks the capacity to produce HBeAg. We analysed the results of interferon treatment of 90 patients with chronic anti-HBe-positive hepatitis included in four randomized controlled trials. Interferon inhibited viral replication to undetectable levels and ALT normalized in about 70% of patients. However, the effect was transient in the majority of cases and hepatitis B relapsed in 41 to 90% of patients. A discrepancy in the rate of relapses could be explained by a significant difference in patients populations with a higher prevalence of cirrhotic patients in studies with poorer response. Therefore, in advanced anti-HBe-positive chronic hepatitis B, interferon shows a lower efficacy than in HBeAg-positive patients. The earlier treatment starts, the more efficacious is the response to interferon. Future clinical trials should focus on higher doses for longer periods, repeated courses or on combination therapy with nucleoside analogs or immuno-stimulant drugs.

Chronic Disease↗
PubMed1991

Pathobiology of chronic hepatitis virus infection and hepatocellular carcinoma (HCC).

Hepatitis viruses may cause liver cancer (HCC) through an indirect mechanism inducing inflammation and cirrhosis. Only hepatitis B virus (HBV) was shown to have a direct oncogenetic potential. Hepatitis D virus (HDV) infection, superimposed on the oncogenetic background provided by chronic HBV infection, appears to provide an additional risk for HCC. Patients with florid infections from both HBV and HDV and active liver inflammation develop HCC at a significantly younger age than those infected by HBV alone or infected by hepatitis C virus (about 10 years earlier). In patients positive for serum HBV-DNA/HDV-RNA and/or IgM anti-HBc/IgM anti-HD it is mandatory to program a more frequent (thrice a year) schedule of screenings (ultrasound scan, alpha-1-phetoprotein, etc.) for prophylaxis of HCC.

Animals↗
PubMed1991

Diagnostic advances in viral hepatitis: the discovery of hepatitis C virus and genetic heterogeneity of hepatitis B virus.

The discovery of hepatitis C virus (HCV) and its serological markers represents a new milestone in the history of viral hepatitis and allows a specific diagnosis of viral hepatitis in more than 90 percent of cases. In addition, testing for anti-HCV plays a crucial role in prevention of post-transfusion non-A, non-B hepatitis. The multifaceted spectrum of liver disease associated with hepatitis B virus (HBV) infection, spanning from a healthy carrier state to severe forms of chronic hepatitis, was traditionally attributed to variability of host's antiviral immune response. The finding that a peculiar natural course and response to interferon of chronic hepatitis B is associated with the infection of a defective HBV unable to secrete the "e" antigen (HBeAg-minus) emphasizes the clinical implications of the genetic heterogeneity of hepatitis viruses.

Biomarkers↗