Biomedical subjects
M Rizzetto
Publications and source records attributed to M Rizzetto.
Diagnostic value of different antiliver/kidney microsome antibodies.
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Type D hepatitis: the clinical significance of hepatitis D virus RNA in serum as detected by a hybridization-based assay.
Hepatitis D virus is a defective human pathogen that requires hepatitis B virus for its replication. A hybridization-based assay for the 1.75 kb RNA genome of hepatitis D virus was developed using as probe a radiolabeled transcript of a cloned cDNA fragment (pKD3 hepatitis D virus DNA). Sera from 120 chronic carriers of HBsAg with confirmed hepatitis D virus infection were analyzed for the presence of hepatitis D virus RNA. Serum hepatitis D virus RNA was detected in 43 of 74 (58%) patients with chronic liver disease; some patients were positive for hepatitis D virus RNA in multiple samples over a period of several years. Serum hepatitis D virus RNA was present in 17 of 28 (61%) patients during the acute phase of clinical hepatitis and was not detected after recovery from acute disease or in 18 asymptomatic chronic HBsAg carriers with antibody to hepatitis D virus. The presence of hepatitis D virus RNA correlated with other known markers of active hepatitis D virus replication; all chronic active liver disease patients with serum hepatitis D virus RNA were positive for antihepatitis D antigen IgM, and 34 of 37 (92%) had hepatitis D antigen in their liver biopsy specimens. The assay for hepatitis D virus RNA provides a direct and noninvasive method for the detection of hepatitis D virus in serum and will be useful in the study of the natural history of type D hepatitis, the identification of chronic hepatitis D virus carriers likely to transmit hepatitis D virus and the selection and monitoring of patients for potential antiviral therapy.
A histological study of hepatitis delta virus liver disease.
The histopathology of hepatitis delta virus disease was studied in carriers of HBsAg with chronic hepatitis delta antigen-positive hepatitis and in serial biopsies of patients with acute hepatitis delta virus hepatitis that progressed to chronicity. There was no histologic feature distinctive of hepatitis delta virus from other types of viral hepatitis. Biopsy specimens of patients with chronic disease exhibited portal and periportal inflammation with piecemeal necrosis, conforming to a picture of aggressive hepatitis often accompanied by cirrhosis. Characteristic was a marked intralobular infiltration by mononuclear cells and a degenerative eosinophilic change of the hepatocytic cytoplasms conducive to the formation of acidophilic bodies. Liver specimens from patients with hepatitis delta virus hepatitis exhibited aspects of focal, confluent and bridging necrosis. The disease progressed to chronicity irrespective of the original histological features. The expression of intrahepatic hepatitis delta antigen was reduced in the phase of the acute hepatitis but increased in parallel with the development of chronic active liver disease. In late-stage cirrhosis, expression of hepatitis delta antigen was usually low.
Serial passage of hepatitis delta virus in chronic hepatitis B virus carrier chimpanzees.
Five consecutive passages of hepatitis delta virus in hepatitis B virus carrier chimpanzees were performed in order to further characterize the infectious and pathogenic nature of this naturally occurring defective virus. Three animals received identical inocula at fourth passage in order to assess individual animal variation as a factor in the course of infection and disease. Acute hepatitis delta virus infection occurred in all hepatitis B virus carrier chimpanzees as demonstrated by coincident intrahepatic hepatitis delta antigen, serum hepatitis delta antigen and serum hepatitis delta virus RNA followed by seroconversion to antibody to hepatitis delta antigen. In all animals, acute hepatitis was temporally associated with hepatitis delta virus infection and was self-limited. The incubation period to hepatitis shortened with passage, whereas biochemical and histologic evidence of liver diseases increased. The marked increase in liver disease with passage was not associated with increasing markers of hepatitis delta virus replication or expression, thus indicating that adaptation to the chimpanzee by serial passage resulted in increased hepatitis delta virus virulence. The duration of hepatitis due to hepatitis delta virus infection in three chimpanzees which received the same inoculum varied from 1 to 8 months. The observations of passage adaptation and individual host variation in this experimental model of hepatitis delta virus disease parallel known pathogenic variations in human hepatitis delta virus infection.
Hepatitis delta virus (HDV) infection and disease.
The conformational and biologic properties of the hepatitis delta virus (HDV), a defective RNA hepatotropic pathogen dependent on obligatory helper functions provided by the hepatitis B virus (HBV), are different from the properties of conventional RNA animal viruses but resemble in many aspects the characteristics of the satellite RNAs and satellite viruses of higher plants. The HBsAg coat provided to HDV by HBV makes the defective virus transmissible via the vectors and modes of transmission of the ubiquitous helper; alike HBV, HDV is prevalent in tropical and subtropical areas and in the Mediterranean basin. In contrast to HBV, HDV is highly pathogenic and its infection aggravates the underlying HBV infection upon which it thrives. The defective pathogen has been recognized worldwide as a major cause of fulminant hepatitis and of severe chronic hepatitides leading to cirrhosis and liver failure. There is yet no established therapy for this ominous disease.
The immunological diagnosis of HBsAg liver disease by combined screening for the e system in the serum and the HB core and surface antigens in liver biopsy samples.
Serological screening for HBeAg and anti-HBe, combined with the immunohistochemical localization of the hepatitis B core and surface antigen in 110 HBsAg carriers, established different immunological profiles indicative of the liver status and prognostic of the future absence or progression of the disease. Intrahepatic HBcAg and serum HBeAg appeared the most sensitive indexes of chronic and progressive liver disease, anti-HBe and large amounts of cytoplasmic HBsAg suggest, instead, the asymptomatic carrier state without liver damage. Only the nuclear localization of HBcAg in immunohistochemical studies was a reliable prognostic indicator of transition to chronicity; absence or presence of serum HBeAg was of no help in predicitng the outcome of acute HBsAg hepatitis.
Interferon treatment of chronic hepatitis B surface antigen (HBsAg) carriers. A description of the activation profiles of natural killer cells obtained with different schedules of administration in three subsets of carriers.
By monitoring immunobiological parameters known to be influenced by interferon (IFN), the natural killer (NK) cell activity of 10 low replication (anti-HBe) virus B-DNA (HBV-DNA) hepatitis patients receiving rIFN alpha-A, of 5 anti-HBe/delta positive hepatitis patients treated with rIFN alpha-2, and of 6 high replication (HBeAg) HBV-DNA hepatitis patients on lymphoblastoid IFN was followed-up during therapy. Overall, strong and significant (p less than 0.01) shift to increase segregated with the low replication subset; the delta positive subset was non-significantly increased (0.30 greater than p greater than 0.2); the high replication subset was depressed in a nearly significant (0.10 greater than p greater than 0.05) manner. Kinetic studies showed the activation of the first subset to follow an early steep rise and a subsequent plateau as fitted with a quadratic curve (p = 0.02); an early rise and a depression at 2 months delineated a complex cubic model (p = 0.06) in the high replication subset. The profound NK depression was clinically witnessed by a sharp rise of the aminotransferases and following drop of viremia. The study shows that i. discrete patterns of NK response as amenable to mathematical models may associate to differential patterns of virus B replication in patients responding to IFN; ii. point(s) on the NK curve may acquire clinical meaning as they coincide with a consensual or opposite shift of a clinical index.
The e antigen and antibody in the serum of patients with HBsAg-positive liver disease and in asymptomatic carriers.
Serum samples from 103 HBsAg positive and 69 negative patients were examined in Ouchterlony double diffusion in agarose for the presence of e antigen and anti-e antibody. e antigen was found in 66% of the cases of active chronic hepatitis, 18% of those of active cirrhosis, and 12% of those of acute hepatitis. Anti-e antibody was found only in asymptomatic chronic carriers; it occurred in 56% of HBsAg-positive individuals with normal livers at biopsy. No e reactivity was found in 6 subjects with inactive disease and in 3 with chronic persistent hepatitis. The e system seems a valuable diagnostic tool utilizing the presence of the antigen to differentiate patients with chronic progressive disease from healthy carriers who, in contrast, often have circulating anti-e antibodies; its clinical value, however, is at present limited by the low sensitivity of the technique used for antigen detection. A significant association between e antigen and the intrahepatic expression of the core determinant of the HB virus was observed inthis study, suggesting they have a similar role in pathogenicity and infectivity; the association between anti-e antibody and HBsAg appeared uncertain, HBsAg being present in the liver irrespective of e reactivity.
Intrahepatic localization of the surface (HBsAg) and core (HBcAg) antigenic determinants associated with hepatitis B virus in biopsy samples from patients with liver disease.
109 biopsy samples from 35 HBAg serologically positive and 74 negative patients were examined by IFL for the presence of the surface and core antigenic determinants associated with the Dane particle. In no serologically negative case was specific IFL detected. Different patterns were observed in serologically positive patients: negative in acute hepatitis, strongly positive cytoplasmic HBs fluorescence in chronic HBAg carriers with normal liver, and discrete HBsAg parenchymal and mesenchymal staining and variable HBcAg staining in chronic liver disease, with HBsAg appearing more frequently in active and HBcAg in active disease. These results are compared with recent reports in this field and the clinical significance of the intrahepatic localization of HBAg is discussed.
Antibodies against the human pancreas in acute and chronic liver disease.
Different immunofluorescence reactions in the exocrine pancreas were observed with the sera of patients with acute and chronic liver disease. In the majority of cases the antibody, frequently associated with the antibody against the smooth muscle, reacted with diffuse organ-specific antigens in the cytoplasm; in one patient it reacted with fibrillar antigens in the cells, while in another case the fluorescence was due to antibodies against non-specific ribosomal antigens. The occurrence, nature and significance of these reactions are discussed.
Benign recurrent intrahepatic cholestasis. A clinico-pathologic study.
Authors report 6 cases of benign recurrent intrahepatic cholestasis (BRIC), a rare disease of unknown etiology first described 30 years ago by Summerskill and Walshe, and thought to represent a study model for human cholestasis. Clinical, biochemical and pathologic findings of BRIC are briefly summarized in this paper in order to emphasize some triggering factors of the cholestatic attack (e.g., flu-like episodes and pregnancy), the diagnostic problems and the importance to avoid a surgical procedure. Finally, the 'state of the art' of the pathogenesis of BRIC is briefly summarized.
Application of nucleic acid hybridization to the hepatitis delta virus research.
Cloning and sequencing of the genome of hepatitis delta virus (HDV) represented a remarkable progress in the knowledge of HDV infection and made available cDNA and RNA probes which can be successfully used to identify HDV-RNA in biological specimens. We review here the methods currently used for detecting HDV nucleic acids and report the most recent advances of the molecular biology of HDV. Finally, we examine the number of compelling reasons for the diagnostic laboratory to pursue this technology. Testing for HDV-RNA has become essential for the screening and the follow-up of both chronic HDV carriers, undergoing antiviral therapy and patients with terminal disease, eligible for liver transplant.
Viral hepatitis in the third millennium.
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Lymphocytic gastritis and protein-losing gastropathy.
Lymphocytic gastritis is a histopathological entity of unknown aetiology which is characterized by dense surface and foveolar epithelial T-cell infiltration. We report here an uncommon clinical presentation in a young female presenting with unexplained recurrent weight loss and peripheral oedema. Endoscopic and histological features before and after successful therapy with omeprazole are described.
Chronic Helicobacter pylori infection and migraine: a case-control study.
OBJECTIVE: To determine whether chronic Helicobacter pylori infection is a risk factor for migraine. BACKGROUND: Preliminary studies have shown a high prevalence of Helicobacter pylori infection in patients with primary headaches. METHODS: One hundred three consecutive patients with migraine were enrolled in the study and compared with a group of 103 matched controls. Helicobacter pylori infection was diagnosed by means of both (13)C-urea breath test and serology. RESULTS: Of patients with migraine, 30.1% were positive for Helicobacter pylori, compared with 31.1% of controls (P = NS). The odds ratio for migraine associated with chronic Helicobacter pylori infection was 0.96 (95% confidence interval, 0.51 to 1.80). Demographic, clinical, and psychological characteristics of Helicobacter pylori-positive migraineurs were compared with those of migrainous patients without infection. Helicobacter pylori-positive patients had a significantly (P<.05) lower incidence of food sensitivity than Helicobacter pylori-negative patients. No significant difference was found in any other feature examined. CONCLUSIONS: Our study suggests that chronic Helicobacter pylori infection is not more frequent in patients with migraine than in controls and that infection does not modify clinical features of the disease.
The long-term efficacy of interferon alfa in chronic hepatitis C patients: a critical review.
With current therapeutic regimens, sustained responses occur in no more than 25% of patients with chronic hepatitis C who are treated with interferon. Relapses occur usually within 6 months from therapy suspension, but clinical and virologic recurrencies can be observed as late as after 3 years of follow up. The rate of long-term responses seems to depend on the dosage and the period of administration of interferon, but the best therapeutic protocol remains unknown. As a direct marker of permanent recovery is not available, indirect signs of disease resolution are: (i) continuously normal alanine aminotransferase levels; (ii) clearance of HCV-RNA; (iii) disappearance of anti-C100/NS4; and (iv) significant histological improvements assessed at least 2 years after therapy withdrawal. Known baseline predictive features of long-term response are the absence of cirrhosis, low viraemic levels and infection with HCV of type III or IV genotype (Okamoto's classification). According to recent reports, the lower the heterogeneity of the hypervariable region of the envelope 2 gene of HCV, the higher the chance of a sustained remission. There is not yet any consensus on the efficacy of a second therapeutic course of interferon in inducing a permanent response, and controlled trials are needed to clarify this issue.
Pattern analysis of serum alpha-fetoprotein in the early diagnosis of hepatocellular carcinoma in liver cirrhosis.
In a surveillance program for hepatocellular carcinoma (HCC), serum alpha-fetoprotein (AFP) was determined every 4 months in 164 patients with liver cirrhosis. Ultrasonography (US) was performed yearly or as dictated by abnormal AFP levels. During a follow-up of 32.5 +/- 20.8 months HCC was identified by US in 16 patients. In 9 of them the AFP levels rose steadily over 4 months, increasing 7, 8 and 12 months in 3 cases before the lesion became detectable by US. In 4 patients tumors developed despite persistently normal AFP levels. Nine more patients showed abnormal fluctuations of AFP but HCC was not detected. AFP sensitivity was higher at a low cut-off point (40 ng/ml) while specificity of the test appeared higher at the 200 ng/ml cut-off point. An AFP value rising steeply over a few months appeared more reliable than a fixed preset threshold in indicating carcinomatous transformation. Screening for AFP can be expected to uncover about 3/4 of HCC developing in cirrhotics with few false-positive reactions. The test may have a unique role in identifying a subset of liver tumors whose early expression is AFP production.