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Biomedical subjects

M Rizzetto

Publications and source records attributed to M Rizzetto.

At least 199 records · Page 11Linked to original sources
PubMed1994

Interferon in chronic hepatitis B.

In patients with typical chronic hepatitis B (HBsAg, HBeAg, HBV-DNA-positive), treatment with interferon-alpha must be carried out for 4-6 months on an alternate-day basis and dosage should be not less than 5 million units/square meter of body surface. The therapeutic response (i.e., clearance of replicative markers, transaminases normalization, histologic improvement) is achieved in about 40% of treated patients and the long-term beneficial effect is maintained in about 90% of them. Oriental HBV carriers, children, immunodeficient and highly viraemic patients are less likely to respond. Patients given combinations therapy (with steroids, antivirals, stimulators of the immune system) do not appear to gain more benefit from the association in comparison with treatment with interferon alone. Side-effects are usually minor (flu-like symptoms), but in a minority major adverse events have also been reported. In conclusion, interferon-alpha is effective in inhibiting viral replication but new therapeutic regimens and a better selection of patients are needed in order to induce persistent remissions and to reduce the cost benefit ratio.

Chronic Disease↗
PubMed1994

Ribavirin treatment for chronic hepatitis D: a pilot study.

To assess whether therapy with Ribavirin may affect the course of chronic delta hepatitis, nine Italian patients with this disease received the drug orally at a dosage of 15 mg/kg daily for 16 weeks. At the end of the therapy period, all patients were followed for 12 additional months. Seven patients completed the trial. Two patients were withdrawn: one developed hemolytic anemia, and the other intractable itching. At the end of treatment HD viremia was reduced in one patient, had cleared in another, and was unchanged in the remaining five patients. None of the patients decreased their alanine transferase (ALT) levels by more than 50%. At the doses given in this study. Ribavirin did not show significant antiviral effects in chronic hepatitis D, and was not effective in reducing the biochemical markers of liver inflammation and necrosis.

Adult↗
PubMed1994

Expression of the c-myc protooncogene product in cells infected with the hepatitis delta virus.

The intrahepatic accumulation of the c-myc protooncogene product was observed on immunofluorescence in each of six patients with chronic hepatitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that contained the hepatitis D antigen. C-myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was detected in only 1 of 32 viral and nonviral liver disorders unrelated to hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with a plasmid containing a hepatitis delta virus cDNA trimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-transfected PLC/PRF/5 or HepG2 cells, strong c-myc nuclear fluorescence was observed when these same cells were transfected with the hepatitis D antigen expression vector. Similar results were obtained after infection of HeLa cells with a recombinant vaccinia virus expressing the hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not due to increased amounts of its mRNA. The c-myc protein accumulates selectively in the livers of patients with chronic hepatitis delta virus infection and in the same nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis D antigen-containing cells does not require the presence of hepatitis B virus infection.

Amino Acid Sequence↗
PubMed1994

Advances in hepatitis D virus biology and disease.

Studies over the last decade have defined the natural history and diagnostic features of hepatitis D. Whereas hepatitis D encompasses a wide spectrum of clinical manifestations, patients usually have severe and progressive liver disease. In areas of high endemicity such as Italy, hepatitis D accounts for a significant proportion of requests for liver transplantation. Research interest is now focused on the underlying mechanisms of HDV pathogenesis and identification of the specific interactions of HDV/HBV/host that influence the clinical outcome. Much has been learned about the virology of HDV and its interactions with its helper, HBV. However, little is known about the host response to HDV infection and whether certain immune responses to HDV gene products can modulate the disease course, although there has been some evidence in an animal model that this might be the case. The unique characteristics of HDV replication, eg, autocatalytic self-cleavage and editing of the viral RNA, may influence the disease course and the heterogeneity of HDV genome sequence found in various geographic settings may in part account for the spectrum of disease outcomes by influencing the efficiency of any number of complex interactions. Fortunately, in vitro and in vivo experimental systems are available to address many of these issues and, indeed, further research may identify specific and novel targets for therapeutic intervention. Current medical therapy for hepatitis D is unsatisfactory. The only drug of proven benefit, recombinant interferon, brings relief to only a small proportion of hepatitis D patients. Other antiviral drugs have failed in clinical trials, although studies with some drugs are currently in progress. Fortunately, liver transplantation provides a valid option, because HDV reinfection of the graft occurs much less frequently than does HBV reinfection of HBV transplants and can be adequately prevented by the administration of anti-HBs immunoglobulin. Because of the critical contribution of HBV to the life cycle of HDV, universal immunization against HBV infection represents the ultimate solution for the eradication of hepatitis D. Mass vaccination for HBV and other public health measures for the control of blood-borne pathogens have already resulted in a dramatic decrease in hepatitis D in Italy.

Antigens, Viral↗
PubMed1994

Monoethylglicinexylidide test: a prognostic indicator of survival in cirrhosis.

The aim of this study was to assess the value of the monoethylglicinexylidide assay, a dynamic liver function test based on the determination of the serum concentration of lidocaine major metabolite, as a predictor of survival in cirrhosis. For this purpose, the predictive value of monoethylglicinexylidide was evaluated in comparison with the Pugh score, ascites, encephalopathy and a number of different biochemical parameters as collected from the prospective follow-up of 118 patients with cirrhosis. A stepwise regression analysis was performed on the variables of prognostic value according to the Cox model and with respect to 1-yr survival; because Pugh score and monoethylglicinexylidide were the sole variables selected, they were proved to supply independent prognostic information. The most reliable cutoff values for discrimination between death and survival were 25 ng/ml or less for monoethylglicinexylidide and less than 9 for the Pugh score. In 74 patients without overt signs of liver failure (i.e., Pugh < or = 9), monoethylglicinexylidide provided a wide range of results (i.e., 4 to 77 ng/ml), namely values ranging from very low to elevated. Of the 38 patients with satisfactory Pugh scores (< or = 9) but poor monoethylglicinexylidide values (< or = 25), 11 died during follow-up and 3 underwent liver transplantation, despite having shown no clinical signs of liver failure at entry. On the bases of discriminant levels, the monoethylglicinexylidide test is suitable for adoption as a reliable and sensitive indicator of survival in patients with cirrhosis because it supplies more accurate prognostic information compared with the Pugh score.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Accumulation of a cellular protein bearing c-myc-like antigenicity in hepatic and non-hepatic delta antigen expressing cells.

Patients with chronic but not acute hepatitis delta virus infection undergo a strong accumulation of a protein of cellular origin which specifically reacts with a panel of anti-c-myc antibodies and which is expressed in the same nuclei that express the delta antigen. In this paper we report on the in vitro characterization of this phenomenon. The delta antigen induced c-myc antigen accumulation can occur in vitro upon transfection of HBsAg positive and negative cell lines with HDAg expression vectors. Using recombinant vaccinia viruses expressing only p24 or p27 we demonstrate that structures common to the two isoforms of HDAg are responsible for the phenomenon, which is not restricted to cells of hepatic origin.

Antigens, Viral↗
PubMed1993

Clinical types of HBsAg-positive hepatitis.

Hepatitis B is a parenterally and sexually transmitted disease of global importance. It associates with hepatitis D in a consistent proportion of cases. The disease most frequently runs a subclinical and anicteric course, with a significant number of cases that become chronic. Chronic hepatitis may progress to cirrhosis or cancer. The strategies by which hepatitis B and hepatitis D can be diminished and eventually eliminated are: immunization, measures to prevent exposure to infective blood or blood derivatives and education (in particular awareness that hepatitis B is a sexually transmitted disease).

Adult↗
PubMed1993

Long-term evolution of chronic delta hepatitis in children.

Twenty-three children, aged 3 to 15 years, with chronic delta hepatitis have been followed for 5 to 12 years to evaluate long-term outcome. Although 83% of patients had chronic active hepatitis when first seen, with cirrhosis in 26%, the clinical and biochemical features of the disease remained reasonably stable during observation; liver histologic findings, obtained in 14 patients, worsened in only two.

Adolescent↗
PubMed1993

Pathobiology of hepatitis delta virus.

Early observations in humans and infectivity studies in the chimpanzee suggested a direct cytotoxic effect as the major pathogenetic factor in delta hepatitis. Data acquired in liver transplant patients, as well as additional experimental and clinical evidence, have modified this view and indicate instead that liver damage depends on several factors. To explain the array of different clinical presentations, the replication strategy of hepatitis delta virus, the helper function and genetic heterogeneity of the co-infecting Hepadnavirus, and the response of the host immune system should all be taken into consideration.

Animals↗
PubMed1993

Role of screening in prevention and treatment.

Since viral hepatitis may be the most common form of chronic viral disease in the world, strenuous attempts are being made to reduce the incidence. To achieve this, strategies are being developed by various national and international bodies involving both the immunisation and screening of certain groups of the population. These strategies are by no means universal, and the value of screening specific groups is the subject of much debate. This paper will address a number of the issues related specifically to the question of screening for hepatitis B virus and hepatitis C virus (HBV and HCV, respectively) namely (a) what is screening?; (b) why should we consider screening?; (c) who should we consider screening?; (d) what are the benefits and liabilities of screening?; (e) what constitutes an acceptable screening test?; (f) should we be screening for HBV or HCV?

Blood Donors↗
PubMed1993

Pulmonary embolism due to compression of the inferior vena cava by a hepatic hemangioma.

We describe a 35-year-old man who had a pulmonary embolism with thrombosis of the inferior vena cava, apparently resulting from compression by a hepatic hemangioma. The diagnosis of pulmonary embolism was confirmed by pulmonary angiography; however, the hemangioma was detected only incidentally, as a hyperechoic mass, during an echocardiogram for intracardiac thrombosis. Abdominal sonography, computed tomography, celiac angiography, technetium 99m-labeled red blood cell scintigraphy, and ultrasound-guided liver biopsy all assisted in the diagnosis of hepatic hemangioma and its compression of the inferior vena cava. Because of the multisegmental and perihilar involvement of the tumor, surgery was not performed. For dissolution of the clots, the patient was given thrombolytic therapy followed by heparin administration. He was then placed on long-term warfarin therapy and is well after 5 years; the size of the hemangioma is unchanged. Cases of pulmonary embolism due to diseases of the upper abdominal organs are rare and probably underestimated. This case stresses the need for a systematic investigation of the abdomen when a pulmonary embolism is present without evidence of deep vein thrombosis.

Adult↗