Search PubMed⌕ Search

Biomedical subjects

M Rizzetto

Publications and source records attributed to M Rizzetto.

At least 19 recordsLinked to original sources
PubMed1997

The predominance of hepatitis delta virus genotype I among chronically infected Italian patients.

The sera of 46 Italian patients with chronic hepatitis delta virus (HDV) infection were analyzed for HDV RNA by polymerase chain reaction (PCR) amplification. Genetic analysis of sequences amplified from two regions of the HDV genome indicated that all HDV RNA-positive patients (98%) were infected with HDV genotype I. In Italy, infection with this genotype appeared to be associated with a broad spectrum of chronic disease. No subtypes of HDV genotype I were identified, nor were genetic variations clearly associated with different disease patterns; however, clustering of some sequences suggested correlations with geography and transmission route. Italian HDV genotype I sequences were more diverse than those from east Asia and North America, suggesting that HDV genotype I was likely introduced to Italy earlier and/or from multiple sources as compared to those areas. All sequences analyzed were predicted to fold into the unbranched rod structure typical of HDV RNA. Within this structure, three conserved features were identified, including sequences around the RNA editing site and the polyadenylation signal site. We conclude that in Italy, where HDV infection has been endemic, the overwhelmingly predominant genotype of HDV is genotype I.

Adult↗
PubMed1997

Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non-neoplastic liver tissues.

We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.

Carcinoma, Hepatocellular↗
PubMed1997

A practical guide to the use of interferons in the management of hepatitis virus infections.

The recommended interferon dosage for patients with chronic hepatitis and typical hepatitis B virus (HBV) infection is 10 MU 3 times weekly for 4 to 6 months; with such a regimen sustained alanine aminotransferase (ALT) normalisation, liver histology improvement, clearance of HBV DNA and seroconversion from hepatitis B e antigen (HBeAg) to anti-HBe are obtained in about 40% of treated patients. Patients with elevated disease activity (high ALT values, active chronic hepatitis, low HBV DNA levels) tend to respond better to therapy; Oriental patients and immunocompromised patients are not ideal candidates for interferon. Patients with chronic hepatitis B and the HBeAg-negative variant should be given intermediate dosages (6 to 9 MU thrice weekly) of interferon for prolonged periods (12 months); however, even with this approach, the relapse rate is high (> 60%) during the follow-up. In chronic hepatitis D virus (HDV) infection, therapy with 9 to 10 MU of interferon 3 times weekly for 12 months induces a transient remission in disease (ALT normalisation, HDV RNA clearance) in more than 50% of treated patients, but a sustained response is found in less than 20% of patients. In such disease, baseline predictive factors of long term response are still unknown. In chronic hepatitis C, treatment with 3 to 5 MU of interferon given 3 times weekly for 6 to 12 months induces a sustained remission in no more than 30% of treated patients. Probable predictive factors of long term response are: low viraemia, genotype other than 1, absence of cirrhosis, low intrahepatic iron content, low nucleotide diversity of the envelope 2 gene of the hepatitis C virus. Prolonged (> 12 months) therapeutic courses seem to enhance the sustained response rate; in nonresponders/relapsers, combined therapy (interferon plus indomethacin, interferon plus ketoprofen, interferon plus ribavirin) is promising but randomised controlled trials are needed in order to establish the real efficacy and safety of such therapeutic regimens.

Hepatitis B↗
PubMed1996

Reperfusion damage to the bile canaliculi in transplanted human liver.

In 19 patients who have undergone orthotopic liver transplantation (OLT), the trend and degree of cholestasis was statistically monitored in terms of plasma levels of L-gamma-glutamyl transferase (GGT) and total bilirubin. In addition, the ultrastructure of the bile canaliculus was examined during the entire OLT procedure, i.e., during explantation, cold ischemia, and after 60 to 90 minutes of organ reperfusion. Cholestasis was evident from the second day after surgery, with a peak after approximately 10 to 16 days. Defined, small changes in the functional state of actin filaments were noted in the bile canalicular area after prolonged ischemia. But the morphological status of the bile canaliculi changed dramatically after reperfusion. In fact, the mean area and perimeter of the canaliculi had increased significantly, and there was a marked loss in the number of bile microvilli per unit of canalicular area. The bile canaliculus appears to be one of the liver structures most susceptible to ischemia-reperfusion damage. A series of biochemical changes occurring during ischemia and after reoxygenation of the transplanted liver, especially, would provide a reason for the observed early morphological damage of the bile canaliculus, which, in turn, would explain the cholestasis of these patients in the first posttransplantation period.

Adenosine Triphosphate↗
PubMed1996

Predictors of response to interferon therapy.

An optimal treatment schedule is the first factor that influences sustained responses to interferon (IFN) therapy. There is growing evidence that prolonged IFN therapy (at least 12 months or longer) increases the sustained response rate. A low viremia at baseline favorably affects the long-term response to IFN. High viral replication does not preclude response, but highly viremic patients tend not to sustain their response. Patients with genotypes 2 and 3 (Simmonds classification) have an improved likelihood of responding compared to patients with genotype 1; unfortunately, genotype 1 predominates in Western countries. The "quasispecies" diversity of hepatitis C virus (HCV) may play a role in determining response to IFN, which is more likely in patients with lesser degrees of HCV diversity. However, studying the nucleotide diversity of the hypervariable region 1 of HCV is a very complex and expensive process that cannot be applied to a large number of patients. The sustained response rate is higher in patients with mild disease than in cirrhotic patients. Cirrhotics should be treated with caution, since IFN therapy could induce serious side effects and decompensation. Baseline predictive factors of response are useful to improve the cost-benefit ratio of IFN therapy but cannot be considered inclusion/exclusion criteria. The decision on how to treat should be based upon the individual characteristics of each patient.

Chronic Disease↗
PubMed1996

Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis.

BACKGROUND & AIMS: Approximately 13% of patients with chronic hepatitis D virus (HDV) infection have liver-kidney microsomal antibodies type 3 (LKM-3) directed against family 1 uridine 5'-diphosphate-glucuronosyl-transferases (UGT-1). The aim of this study was to characterize the prevalence and specificity of LKM-3 by recombinant antigen testing systems. METHODS: Enzyme-linked immunosorbent assay (ELISA) and Western blot were performed using baculovirus-generated human UGT-1.1 and -1.6 and rabbit UGT-1.6. Sera from patients with HDV (n = 50), autoimmune hepatitis (AIH) type 2 (n = 50), hepatitis B virus (n = 26), hepatitis C virus (HCV) (n = 25), and LKM-1 autoantibody-positive HCV (n = 14) and sera from normal controls (n = 50) and italian patients with HDV and known LKM-3 autoantibodies were studied. RESULTS: Six percent of patients with HDV from Germany and 8% of patients with type 2 AIH had LKM-3. Sera from italian patients with HDV and patients with AIH type 2 recognized all three recombinant UGT-1. HDV sera from Germany selectively recognized human UGT-1. LKM-3 titers were lower in HDV than in AIH. One patient with AIH had LKM-3 as the only marker of AIH. CONCLUSIONS: This study indicates a molecular target and titer difference of LKM-3 autoantibodies in German subjects with HDV and AIH. It also suggests a geographic target and titer difference of LKM-3 in HDV. LKM-3 are identified as a rare and previously undescribed independent marker of AIH.

Adult↗
PubMed1996

Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study.

We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis B e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-alpha treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.

Adolescent↗
PubMed1996

Hepatitis C virus infection and monoclonal gammopathies not associated with cryoglobulinemia.

A pathogenetic role of HCV has been recently postulated in some lymphoproliferative disorders and in particular in essential mixed cryoglobulinemia. To assess the relevance of HCV infection in multiple myeloma, Waldenström's macroglobulinemia and monoclonal gammopathy of undetermined significance in the absence of cryoglobulinemia (cryo-ve MG), 102 patients were evaluated for antiHCV, HCVRNA and HCV genotypes. A control group of 466 patients referring for acute trauma to the Orthopedic Division of our hospital was also studied. The overall prevalence of HCV was 15.6% in MG patients and 5.4% in the control group (P= < 0.001). Since only patients with MG older than 50 years had HCV infection, we compared the prevalence rate of infection in patients aged 50 and older: in cryo-ve MG HCV prevalence was 17.9%, while in patients with an acute trauma it was 10%; the difference was not statistically significant. In addition, occurrence of cryo-ve MG was investigated in 614 antiHCV+ patients with chronic liver disease and was found in 1.9%. Comparing all the 28 cryo-ve MG patients HCV+ with an appropriately matched control group of HCV+ patients without MG, no difference in severity of liver disease and genotype distribution was detected. These findings show that: (1) among cryo-ve MG, HCV infection is frequent as shown in the appropriately matched control population; (2) prevalence of cryo-ve MG in antiHCV patients with chronic liver disease is similar to the rate found in the general population; and (3) HCV infection and disease do not differ in patients with and without cryo-ve MG.

Adult↗
PubMed1996

Epithelioid haemangioendothelioma of the liver: report of a case submitted to orthotopic liver transplantation.

A case of hepatic epithelioid haemangio-endothelioma is described in a 42-year-old female who presented with abdominal pain and hepatomegaly. The radiographic finding showed multiple hepatic lesions in both lobes. Diagnosis was based on the liver biopsy. The tumour cells were immunoreactive with factor VIII related antigen and vimentine. A liver transplantation was performed. Although at the time of diagnosis there was no clinical evidence of metastasis, the intra-operatorive examination revealed multiple mesenteric and pulmonary neoplastic nodules. The patient is alive and well seven months after liver transplantation.

Adult↗
PubMed1996

Effect of patient characteristics on hospital costs for cirrhosis: implications for the disease-related group (DRG) reimbursement system.

The Prospective Payment System uses Diagnosis-Related Groups (DRG) as a reimbursement system. DRG 202 is a disease-related group including liver cirrhosis as a whole. Patients referring to the inpatient unit complain of variable severity and complications of cirrhosis, possibly implying different expenditure of resources. Aim of the investigation was to identify factors affecting cost variability in patients with cirrhosis. A total of 73 consecutive, DRG 202-assigned, cirrhotic patients classified according to demographic and clinical variables were evaluated for length and costs of hospitalization calculated on a full-cost basis. Mean length of hospitalization was 10.2 +/- 7 days. Mean cost of hospitalization was Lit. 4.348.000 +/- 2.718.000. Medical, nursing, diagnostic, drug and general charges accounted for 13%, 29%, 37%, 5% and 16% of the cost, respectively. Child-Pugh score significantly correlated with drug consumption (p < 0.005), length (p < 0.01) and costs (p < 0.001) of hospitalization, but not with cost per day. Age, sex, admission status, referral reason, associated diseases and liver transplant susceptibility did not correlate with duration and costs of hospitalization. Disease severity significantly modifies costs of hospital admission in cirrhotic patients mostly on account of longer hospital stay. Surrogate indexes of disease severity, derived from ISTAT/DRG records, cannot identify patients consuming larger resources. In liver cirrhosis, the DRG system could be improved by introducing parameters, such as Child-Pugh score, directly taking into account disease severity.

Adolescent↗
PubMed1995

Detection of hepatitis D virus RNA in serum by a reverse transcription, polymerase chain reaction-based assay.

We designed a reverse transcription, polymerase chain reaction-based assay for serum hepatitis D virus RNA. Amplified hepatitis D virus cDNA was revealed by ethidium bromide staining, followed by blotting onto a nylon membrane and hybridization with a 32phosphorus-labelled oligonucleotide, or by a DNA enzyme immunoassay (DEIA) using a double stranded DNA-specific monoclonal antibody. The absolute sensitivity was expressed as number of hepatitis D virus RNA molecules, using a serum of known viral RNA concentration. Three sets of primers were used, encompassing the base positions 66-686 (variable rod-stabilizing region), 701-962 (conserved, viroid-like domain) and 886-1,333 (portion of the open reading frame 5 encoding for the carboxyterminus of the hepatitis D antigen) of the viral genome. The lower detection limits, after amplification of the three RNA portions, as assessed by ethidium bromide staining, were 7.5 x 10(6), 7.5 x 10(4) and 7.5 x 10(2) molecules of hepatitis D virus RNA per assay, respectively. The region encompassing bases 886-1,333 was chosen for blotting and hybridization to a radiolabelled oligonucleotide probe or for a capture-based DNA enzyme immunoassay, where the microplate was coated with this same probe. The two procedures showed comparable sensitivity, i.e., about 10 molecules of viral RNA per assay. The specificity of the assay was further on a panel of both anti-hepatitis D-positive and -negative sera. Amplification of serum hepatitis D virus RNA by reverse transcription/polymerase chain reaction followed by detection of the amplified cDNA by DNA enzyme immunoassay is a promising and feasible routine assay for detecting low amounts of circulating virions.

Animals↗
PubMed1995

Heterogeneity of liver-kidney microsomal autoantibodies in chronic hepatitis C and D virus infection.

BACKGROUND/AIMS: Anti-liver-kidney microsomal (LKM) autoantibodies occur in a proportion of patients with chronic hepatitis C and D infections. Because of different immunofluorescence patterns, antibodies in hepatitis C and D were termed LKM-1 and LKM-3, respectively. The aim of the present study was to evaluate the different specificities of LKM-1 and LKM-3 antibodies. METHODS: Forty-nine samples of LKM-1 sera and 16 samples of LKM-3 sera were studied for reactivity against rat and human liver microsomal proteins by immunofluorescence, enzyme-linked immunosorbent assay, and Western blot. RESULTS: Thirty-four percent of the LKM-1 sera reacted with 50-kilodalton cytochrome P4502D6 in Western blot. In addition, a proportion of the sera recognized either a 59- or 70-kilodalton antigen, and 45% of the sera did not react in Western blot. Recently, the major LKM-3 antigen was identified as an autoepitope expressed on uridine diphosphate-glucuronosyltransferases (UGT). Seven LKM-3-positive sera reacted with recombinant rabbit family one UGT. None of the anti-LKM-1-positive hepatitis C sera reacted with UGT. Antibody reactivity against liver microsomal proteins in enzyme-linked immunosorbent assay ended when antigens were pretreated with sodium dodecyl sulfate, confirming that antibodies recognize conformational epitopes. CONCLUSIONS: LKM-1 antibodies in hepatitis C are more heterogeneous and react with different antigens compared with LKM-3 antibodies in hepatitis D.

Animals↗
PubMed1995

Recent results in the treatment of chronic B virus hepatitis.

Of the drugs evaluated to date for the therapy of chronic hepatitis B, only alpha-interferons have gained wide acceptance as single-agent therapy. In HBeAg-positive carriers, treatment must be carried out for 4-6 months on an alternate-day basis and dosage should be not less than 5 million U/m2 of body surface. Oriental patients, children, immunodeficient and highly viremic patients are less likely to respond. Patients given combination therapy (with steroids, antivirals, stimulators of the immune system) do not appear to benefit from the association in comparison with treatment with interferon alone. In most patients (60-80%) with atypical chronic type B infections (anti-HBe-positive, HBV-DNA-positive, intrahepatic HBcAg), HBV-DNA becomes negative and transaminases normalize during interferon treatment; however, many (80%) experience a relapse of viremia and disease during follow-up. Side effects are usually minor (flu-like symptoms), but in a minority of patients, major adverse events have also been reported. alpha-Interferon is effective in inhibiting viral replication in a significant number of patients with chronic type B hepatitis, but new therapeutic regimens and a better selection of patients are needed in order to induce persistent remissions and reduce the cost/benefit ratio.

Hepatitis B↗
PubMed1995

Efficacy and safety of interferon alfa therapy in chronic hepatitis C with autoantibodies to liver-kidney microsomes.

Interferon alfa (IFN) therapy is efficacious in chronic viral hepatitides. It may, however, cause adverse immunologic reactions in patients with concomitant autoimmune phenomena. A minority of patients with chronic type C hepatitis have antibodies against liver and kidney microsomes (anti-LKM) in serum. We therefore carried out this study to find out whether IFN is safe and efficacious also in this subgroup. We treated 92 consecutive cases of chronic hepatitis C with IFN. Twelve patients had anti-LKM< and the remaining 80 tested negative to the anti-LKM. The hepatitis C virus (HCV) infection was diagnosed on the basis of positive anti-HCV and HCV-RNA tests. We compared the clinical and virological virological results of the therapy and the side effects found in the two groups. We found that the response to therapy and the outcome after 1 year of follow-up were similar. Treatment was discontinued in one anti-LKM-positive patient because of a drastic increase in ALT levels at the fourth month of therapy. No untoward effect was observed in the other cases. Hepatitis C patients with anti-LKM may be exposed to an increased risk of an adverse hepatitic reaction while being treated with IFN. However, we found that the extent of the risk was minimal compared with the expected benefits of the therapy. IFN is therefore recommended as the first therapy to choose in these patients. They must, however, be monitored more closely for possible liver dysfunction than the ordinary hepatitis C patient.

Adult↗
PubMed1995

Diagnosis of hepatitis delta virus infection.

The hepatitis delta virus (HDV) is a cause of severe liver disease in man. Several assays are available to detect both the HDV genome and its only encoded antigen, HDAg, as well as specific antibodies against HDAg (anti-HD), of both the IgG and IgM class. Different serologic patterns enable the clinician to formulate a correct diagnosis, crucial for effective treatment.

Animals↗