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Biomedical subjects

M Rizzetto

Publications and source records attributed to M Rizzetto.

At least 145 records · Page 8Linked to original sources

Intrafamilial transmission of hepatitis delta virus: molecular evidence.

BACKGROUND/AIMS: Epidemiologic studies have suggested that transmission of hepatitis delta virus (HDV) occurs by intrafamilial routes in some populations in southern Italy, where HDV infection is endemic. To further evaluate intrafamilial transmission of HDV, we obtained the partial sequence of the viral genome from HDV-RNA positive members of families in which two or more immediate family members were positive for HDV-RNA. METHODS: The region analyzed was the semi-conserved region from nucleotides 908 to 1265. Sequences obtained from family members were compared with those obtained from a control group of 20 unrelated patients. RESULTS: The mean genetic divergence among HDV isolates was 2.8 +/- 1.7% within the 9 families analyzed, and 7.6 +/- 2.2% among the control group of unrelated individuals (p < 0.0001). A Receiver Operating Characteristic curve and Youden Index were used to define a cut-off value of 3.5% to discriminate sequence variations calculated within families and in the control group. CONCLUSIONS: The data indicate that in most family units, HDV-infected members harbored nearly identical strains of HDV, and provide molecular support that HDV infection can be transmitted within the family. Such spreading among family members highlights the role of inapparent transmission through personal contacts.

Carcinoma, Hepatocellular↗

Treatment of recurrent hepatitis C virus infection after liver transplantation.

Therapeutic strategies were designed based on experience from the treatment options of the last 10 years in the ordinary clinical setting. Interferon was the first treatment used. This monotherapy was discontinued with the arrival of ribavirin. Ribavirin monotherapy has also been shown to have a limited effect and in recent years the combination of interferon and ribavirin has become the first line therapy.

Antiviral Agents↗

Endosonography in decision making and management of gastrointestinal endocrine tumors.

OBJECTIVE: gastroenteropancreatic (GEP) neuroendocrine tumors, suspected on clinical basis, are often difficult to localize. We report our experience with endoscopic ultrasonography (EUS) in the preoperative localization of pancreatic endocrine tumors (PETs), compared to other imaging modalities, and in staging and following up carcinoid tumors (CTs) of the gastrointestinal (GI) wall. METHODS: 50 patients (20 males; mean age 54 years), 39 with suspected PETs and 11 with GI CTs underwent EUS (Olympus GF-UM2 or GF-UM3). EUS data could be compared with resected specimens in 25 out of the 39 PETs and five out of the 11 CTs. RESULTS: in the PETs group 42 tumors (35<20 mm) were removed: 23 in the pancreas, eight in the duodenum, and 11 in the lymph nodes. EUS correctly localized 20 out of the 23 (87%) pancreatic tumors, included 11 out of the 12 (91.6%) insulinomas, three out of the eight (37.5%) duodenal gastrinomas, and ten out of the 11 (90.9%) metastatic lymph nodes. Furthermore EUS accurately evaluated the depth of parietal invasion of CTs in three out of four patients (75%) (two after and one prior to endoscopic resection). In three patients EUS was confirmed as normal on resected specimens (two pancreas and one stomach). In the PETs group, a correct localization was obtained by ultrasonography (US) only in 17.4% of cases, by computed tomography (CT) in 30.4%, by magnetic resonance imaging (MRI) in 25%, by angiography in 26.6%, and by somatostatin receptor scintigraphy in 15.4%. CONCLUSION: EUS must be considered the first-intention method in localizing PETs and is helpful in decision making and management of GEP endocrine tumors.

Endosonography↗

Evaluation of hepatic function in liver cirrhosis: clinical utility of galactose elimination capacity, hepatic clearance of D-sorbitol, and laboratory investigations.

Assessment of hepatic function is based on both liver blood tests and functional tests, the extensive application of which is still controversial. The aim of this study was to evaluate the clinical utility of a few selected tests as discriminatory and prognostic indexes: serum albumin, pseudocholinesterase, prothrombin time, as well as galactose elimination capacity and hepatic sorbitol clearance. Two separate studies were performed: Study I to investigate how well these tests assessed severity, and Study II to evaluate their prognostic value. A total of 128 consecutive cirrhotic patients classified according to the Child-Pugh score were included in Study I; Study II was carried out on 47 of these 128 during a two-year follow-up period. Pairwise correlations between all tests and Child-Pugh score yielded higher significant values for liver blood tests than for the functional ones. In Study I functional tests such as galactose elimination capacity and hepatic sorbitol clearance did not appear to be better than conventional biochemical tests in discriminating clinical severity of cirrhotic patients, as defined by Child-Pugh classification. Results of Study II confirmed that in severe liver cirrhosis Child-Pugh score remains the best method for medium- and long-term prognosis and for planning liver transplantation. Functional tests should be reserved for defining the residual functioning liver mass or for studies about functional liver plasma flow.

Adolescent↗

Mixed cryoglobulinaemia associated with hepatitis C virus infection: a predictor factor for treatment with interferon?

BACKGROUND AND AIMS: Mixed cryoglobulinaemia (MC) is a frequent finding among patients infected with hepatitis C virus (HCV). The response to treatment with alpha-interferon (alpha-IFN) in these patients is linked to predictive factors. The aim of this study was to ascertain whether the presence of MC was a predictive factor of response in patients treated with alpha-IFN for chronic hepatitis due to HCV. METHODS: Thirty-two patients with MC and HCV infection (24 with chronic hepatitis and eight with cirrhosis) were compared with 30 patients with HCV infection without MC (23 chronic hepatitis, seven cirrhosis) of a similar mean age. All were treated with lymphoblastoid alpha-IFN, at 3 MU, t.i.w., for 6-12 months and then followed up. RESULTS: No statistical difference was observed between the two groups in terms of sustained response (P = 0.83), relapse (P = 0.88) and non-response (P = 0.92). The mean follow up was 24.3 months (range 17-28) for patients with sustained response and for the patients with MC and 22.6 months (range 15-26) for patients without MC. CONCLUSIONS: The presence of cryoglobulinaemia does not influence the response to alpha-IFN in patients with chronic HCV infection.

Adult↗

Oral microemulsion cyclosporin to reduce steroids rapidly in chronic active ulcerative colitis.

OBJECTIVE: The list of the therapeutic tools for chronic active ulcerative colitis lacks a potent and reliably absorbed immune modifier to help wean patients from steroids. We investigated whether oral microemulsion cyclosporin (Neoral) can achieve this goal. DESIGN: Retrospective analysis. SETTING: Tertiary care referral centre. PARTICIPANTS: Nine consecutive patients facing colectomy because of steroid-dependent chronic active ulcerative colitis were studied: the disease was left-sided in six of them and had lasted a median of 10 years. Two patients depended on prednisone 12.5 mg/day, six on 25 mg, and one on 35 mg. The median cumulative steroid dose in the month preceding the trial had been 750 mg. INTERVENTIONS: Neoral was started at a dose of 5 mg/kg/day, which was then titrated to reach a whole-blood therapeutic range of 60-240 ng/ml. During the three-month trial, previous drugs were continued but steroids were tapered according to the patient's clinical condition. PRIMARY OUTCOME MEASURES: The number of patients leaving the trial with quiescent disease and a significantly decreased need for steroids. RESULTS: Eight of the nine patients (89%) showed an initial response and commenced tapering steroids. Remission to the end of the 3rd month was observed in five cases treated with < or = 15 mg steroids daily (median cumulative dose 150 mg). Of the remaining four cases, two were partial responders and two failures, with the failure being linked to poor drug absorption in at least one patient. CONCLUSION: Neoral may help wean patients with chronic active ulcerative colitis from steroids, but this novel indication of cyclosporin must be tested in a specifically designed study.

Adult↗

Long-term results with interferon therapy in chronic type B hepatitis: a prospective randomized trial.

OBJECTIVES: The aims of this long-term, prospective randomized study were to evaluate the clinical usefulness of alpha-interferon in treating chronic HBV infection and to establish whether clearance of viral replication markers and normalization of liver function tests induced by alpha-interferon were sustained. METHODS: Sixty-four patients with chronic wild type (HBeAg-positive) hepatitis B, enrolled between 1983 and 1987, were randomized into two groups. Thirty-three patients received alpha-interferon (5 MU/m2 three times weekly for 6 months; treated group), and 31 were not treated (controls). Treated and control patients were prospectively followed for a mean of 86.4 +/- 6.96 and 79.7 +/- 6.8 (p = NS) months, respectively. RESULTS: Clearance of the following viral markers was found in treated and control patients as follows: HBV-DNA, 26 (78.9%) and 18 (58.1%) (p = 0.106); HBeAg, 30 (90.9%) and 19 (61.2%) (p < 0.007); and HBsAg, 12 (36.4%) and three (9.8%) (p < 0.017). Persistent abnormal ALT levels were found in 11 (33.3%) treated and in 22 (70.9%) control patients (p < 0.025). Four control and three treated patients developed portal hypertension whereas two control and one treated patient developed hepatocellular carcinoma. Seven patients (five treated and two controls) were retrospectively found to have hepatitis C virus (HCV) coinfection before enrollment. To date, all coinfected patients remain positive for HCV-RNA. Also, all HCV coinfected patients, except one in the treated group, had persistent increased serum ALT levels. One of the coinfected patients developed portal hypertension. CONCLUSIONS: Chronic HBV hepatitis patients responding to interferon treatment had a faster, more complete, and sustained clearance of viral markers than controls; HCV coinfection does not seem to negatively affect the clearance of HBV replicative markers. However when coinfection occurs, hepatic disease persists despite HBV marker clearance.

Adolescent↗

Anticardiolipin antibodies in patients with liver disease.

OBJECTIVE: Our aim was to test the hypothesis that anticardiolipin antibodies (aCL) may cause an antiphospholipid syndrome and thrombotic events in patients with liver disease. METHODS: aCL were measured in 116 healthy controls and 372 patients with liver disease of different stage and etiology: 136 cases secondary to hepatitis C virus (HCV) infection, 139 due to hepatitis B virus (HBV) infection, 69 with alcoholic liver damage, and 28 cryptogenic in origin. Prior thrombotic events were recorded. The results were related to age, gender, stage, severity, and etiology of the liver disease, as well as to the occurrence of organ- and nonorgan-specific autoantibodies. RESULTS: aCL were positive in 4.4% of controls and in 18.8% of patients (p < 0.0002). Patients with aCL were more frequently men with an advanced cirrhosis and simultaneous occurrence of anti-smooth-muscle antibodies (ASMA) in serum (p < 0.0006); their liver damage was often secondary to HBV (37.3%) or alcohol abuse (18.5%). At conditional logistic regression analysis, only the presence of ASMA (odds ratio [OR] = 3.02, 95% confidence interval [CI] 1.7-5.5, p = 0.0003), HBV (OR = 3.4, 95% CI 1.6-7.2, p = 0.0013), or alcoholic liver disease (OR = 5.3, 95% CI 2.3-12.2, p = 0.0001) were independently associated with aCL. Thrombosis was encountered in 24 patients (6.4%). At conditional logistic regression analysis, thrombosis was significantly associated with advanced age (OR = 1.07, 95% CI 1.0-1.1, p = 0.0094), development of hepatocellular carcinoma (OR = 17.8, 95% CI 1.6-196.0, p = 0.01), HBV etiology (OR = 6.3, 95% CI, 1.6-24.6, p = 0.0076), or cryptogenic liver disease (OR = 54.8, 95% CI 5-599.9, p = 0.001). Of the five patients with newly documented portal thrombosis during the follow-up, only one tested positive for aCL. CONCLUSIONS: In patients with nonautoimmune liver disease, aCL production is an epiphenomenon of the liver damage and is not associated with thrombotic complications. These data do not support the hypothesis that HCV is a cause of the antiphospholipid syndrome.

Antibodies, Anticardiolipin↗

Hypercalcaemia secondary to hepatocellular carcinoma.

Many syndromes reflecting impaired metabolism have been described in association with primary neoplastic diseases. Hypercalcaemia secondary to malignancy without bone metastases and with normal parathyroid glands has been described as "pseudohyperparathyroidism". Differentiation from primary hyperparathyroidism is difficult and care should be taken to exclude an occult malignancy prior to surgical exploration for a parathyroid adenoma. Hypercalcaemia associated with hepatocellular carcinoma is not uncommon. Nevertheless, we describe a rare case of coma with persistent hypercalcaemia in a cirrhotic patient not previously known to have hepatocellular carcinoma.

Adult↗

Patients with acute myocardial infarction in northern Italy are often infected by Helicobacter pylori.

BACKGROUND: The classical risk factors for acute myocardial infarction (AMI) fail to explain all the epidemiological variations of the disease. Among the new risk factors recently reported, several infectious agents appear to increase the risk of AMI. In particular, acute and chronic respiratory diseases due to Chlamydia pneumoniae, and Helicobacter pylori (H. pylori) infection seem to be strongly involved. The aim of this work is to determine the prevalence of H. pylori infection in a group of male patients with AMI, in a case-control study, where a group of blood donors matched for sex and age served as control. We searched for the classical risk factors in all patients. METHODS: We studied 212 consecutive male patients, aged 40-65 years, admitted for AMI at the Coronary Care Units at Hospitals in three towns of Northern Italy. H. pylori infection was assessed by the highly specific and sensitive 13C-urea breath test and by presence of antibodies (IgG) against H. pylori in circulation. Volunteer blood donors attending our Hospital Blood Bank served as controls. Among the patients we investigated the presence of hypertension, cholesterol and glucose levels in serum, fibrinogen in plasma and the smoking habit. RESULTS: H. pylori infection was present in 187/212 (88%) of the patients and in 183/310 (59%) of the control population (p < 0.0001). Classical risk factors for AMI did not differ among patients with and without H. pylori infection. CONCLUSION: Patients admitted to the Coronary Care Unit for acute myocardial infarction had a notably higher prevalence of H. pylori infection than the general population. The classical risk factors for coronary disease were equally present in all patients with AMI irrespective of H. pylori status.

Adult↗

Therapy of chronic viral hepatitis: a critical view.

Many oral nucleoside analogues that are potent inhibitors of hepatitis B virus have recently been developed for the treatment of hepatitis B. The problems with these drugs are bioavailability, toxicity and the time-dependent emergence of resistant hepatitis B virus mutants. Lamivudine appears to be the most useful in terms of clinical benefit, safety and tolerance. It is active on wild type hepatitis B virus as well as on HBeAg-minus variants of the virus. However, although hepatitis B virus is consistently repressed while on therapy, only a minority of patients are cured or remain in remission after Lamivudine withdrawal. Maintenance therapy would appear to be in order, but the long-term use of Lamivudine is precluded by the emergence of polymerase gene-mutants which may rekindle disease. Combination with other antivirals (Adefovir?) active also against Lamivudine escape mutants opens promising new prospects. There is, as yet, no valid therapy for chronic hepatitis D virus hepatitis. Attempts to improve the results of alpha-interferon therapy in chronic hepatitis C with new interferons, or the manipulation of interferon monotherapy so as to obtain the maximum results compatible with tolerance, have not produced significantly better results than the classic protocols of alpha-interferon monotherapy. A more concrete improvement has been achieved by the combination of interferon with Ribavirin, with the overall rate of response increasing three times compared to interferon monotherapy. Anaemia, however, is a common additional side-effect induced by Ribavirin. Combination therapy has become the treatment of choice for interferon naive patients as well as for interferon relapses; it is not efficacious in patients who have not responded to interferon.

Antiviral Agents↗

Management of duodenal ulcer disease in the era of H. pylori.

BACKGROUND: Today it is expected that the great majority of patients with duodenal ulcer (DU) respond to H. pylori eradication treatment without DU recurrence. The aim of the research is to identify patients who need a different therapeutic approach and the best management of their disease. METHODS: We examined retrospectively the medical history of 474 patients (326 males, mean age 61 years), followed up in 5 years in the outpatients department of a third level GI Center. From our research, 5 subgroups of patients emerged: 1) 63.5% carrying H. pylori infection, with successful eradication treatment and without DU recurrence; 2) 4% failing 3 courses of H.pylori eradication treatment; 3) 11% with DU lacking evidence of H. pylori infection or relapsing after verified eradication; 4) 8% being treated with NSAIDs; 5) 13% with DU complicated by hemorrhage or perforation. RESULTS: 23% of patients with DU need long-term therapy after H. pylori eradication treatment. Concerning this, the percentage of ulcerous recurrences in patients receiving anti-H2 therapy is 18.5%, but decreases considerably to 2% when PPI were used. CONCLUSIONS: Although representing the mainstay of DU therapy, H. pylori eradication treatment may not abolish all issue in DU management. Actually, of DU patients referred to a third level GI Center, 23% need a different therapeutic approach, which results from a thorough analysis of the medical history of the patient.

Journal Article↗

Hepatitis B vaccination: current status.

BACKGROUND: Hepatitis B remains a crucial Public Health problem worldwide, with a numerical impact of infected persons and long term sequences higher than other infectious diseases preventable by vaccines. Around 75% of the world population is living in areas where HBV is endemic (Africa, most of south America, eastern Europe, eastern Mediterranean basin, south-eastern Asia, China and Pacific islands except Australia, new Zealand and Japan); 5-15% of these populations are affected by chronic HBV infection. Rates of chronicity depend on the age of exposure to HBV. Newly infected adults generally clear the infection and only about 5% become chronic carriers of the virus. Infected children rarely develop clinical disease but 25-90% become chronic carriers. Over two billions of persons worldwide have been infected in their life and 350 millions are chronic carriers of HBV. About 25% of the chronic carriers will die of cirrhosis or hepatocellular carcinoma. In recent years control of the spread of HBV has been achieved by the large-scale availability of safe and effective vaccines. This review summarizes the current perspective and use of hepatitis B vaccination, with particular attention to implementation needs and results in Italy, the first country that has introduced universal vaccination against hepatitis B.

Journal Article↗

Role of coinfection by transfusion-transmitted virus (TTV) in patients with chronic HCV hepatitis.

A novel DNA virus, associated with non A-G post-transfusion hepatitis, has been recently discovered. TTV is detectable in acute and chronic liver diseases with a variable incidence. The clinical significance of TTV coinfection in patients with chronic HCV hepatitis has not yet been defined. In this review we report the data regarding the possible pathogenetic role of TTV infection in chronic HCV hepatitis.

Journal Article↗

Efficacy of lamivudine re-treatment in a patient with hepatitis B virus (HBV) recurrence after liver transplantation and HBV-DNA breakthrough during the first treatment.

BACKGROUND: Transplantation for terminal hepatitis B virus (HBV) disease is aggravated by a high rate of reinfection and disease recurrence. Lamivudine, a new nucleoside analog, is a potent inhibitor of HBV synthesis, but its use may lead to the emergence of HBV-DNA polymerase mutants resistant to the drug. METHODS AND RESULTS: We describe the case of a patient who developed an HBV recurrence after liver transplantation and was treated with lamivudine. An HBV-DNA breakthrough occurred 7 months after the start of therapy, and the drug was stopped after 9 months. The molecular state of HBV-DNA was analyzed, and a mutation in the YMDD (tyrosine, methionine, aspartate, aspartate) locus of HBV-DNA polymerase was identified. Nine months after the suspension of lamivudine the patient experienced a new hepatic attack accompanied by high HBV-DNA levels. Lamivudine was given again. Serum HBV-DNA levels normalized after 45 days of re-treatment, but lamivudine-resistant mutants were again the prevalent viral population after 3 months. CONCLUSIONS: The case described suggests that retherapy with lamivudine after a first emergence of YMDD mutants is temporarily effective in recontrolling HBV synthesis but ultimately induces the accelerated reemergence of a prevalently mutant population of HBV. This emphasizes the need for combined antiviral therapy.

Antiviral Agents↗

Characterization of antimitochondrial antibodies in health adults.

The detection of antimitochondrial antibodies (AMAs) is an important criterion for the diagnosis of primary biliary cirrhosis (PBC). During the last decade, the mitochondrial autoantigens have been cloned, sequenced, and identified as members of the 2-oxo-acid dehydrogenase pathway, including the E2 subunits of pyruvate dehydrogenase (PDC-E2), branched-chain 2-oxo-acid dehydrogenase (BCOADC-E2), and 2-oxo-glutarate dehydrogenase (OGDC-E2). We have developed a rapid and sensitive diagnostic test for use in PBC based on a triple hybrid recombinant molecule (r-MIT3) that contains the autoepitopes of PDC-E2, BCOADC-E2, and OGDC-E2. To help understand the frequency and antigen specificity of AMAs in an asymptomatic population and to identify patients with early disease, we investigated the prevalence of AMA, by enzyme-linked immunosorbent assay (ELISA), in a cohort of 1,530 people from northern Italy. Positive sera were further analyzed for immunoglobulin (Ig) isotypes, subclasses, and epitopes of AMA by a combination of ELISA and immunoblotting. In this cohort of 1,530 people, 9 (0.5%) reacted to r-MIT3 by ELISA. Of the 9 reactive sera, 2 recognized PDC-E2, 2 of 9 recognized BCOADC-E2, 1 of 9 recognized OGDC-E2, 2 of 9 recognized both PDC-E2 and BCOADC-E2, and 1 of 9 recognized PDC-E2 and OGDC-E2. AMA reactivity was primarily IgM and IgA. Epitope mapping revealed an AMA pattern of reactivity to PDC-E2 that differed from that found in patients with histologically proven PBC in most of the sera. However, 1 sera of a 72-year-old female with a normal alkaline phosphatase had an AMA profile identical to typical PBC. After a variable follow-up period (8-14 months), sera from 8 of 9 of these people were re-obtained for AMA and relative epitope mapping. Interestingly, the reactivity had a wider AMA pattern than before.

Adult↗

Serum immunoglobulin M antibody to hepatitis D as a surrogate marker of hepatitis D in interferon-treated patients and in patients who underwent liver transplantation.

The kinetics of the immunoglobulin (Ig) M type antibody to the hepatitis D virus (IgM anti-HD) were investigated in hepatitis B surface antigen (HBsAg) carriers with chronic hepatitis D treated with interferon (IFN) and in patients with terminal hepatitis delta virus (HDV) cirrhosis who underwent liver transplantation. The IgM antibody disappeared in each of 8 patients who responded to IFN therapy with the persistent normalization of aminotransferases and with the clearance of serum HBsAg and HDV-RNA. The IgM reactivity did not decline in the 45 treated patients who did not respond to the cytokine or who experienced a relapse after responding while on therapy. The antibody rapidly disappeared from serum post-transplantation in each of 10 examined patients with HDV who underwent transplantation. In 5 patients who underwent transplantation and who became reinfected with HDV, the antibody remained undetectable during the early reinfection phase, as marked by HDV replication and by the absence of liver damage; however, it rapidly raised to pre-transplantation levels with the recurrence of hepatitis D (HD) in the liver graft. Monomeric 7S IgM anti-HD predominated over pentameric 19S antibody in each of the two patients examined for IgM anti-HD molecular species. The IgM antibody to HDV raises in response to HDV-induced damage and represents a valid surrogate marker of liver damage which is immunopathologically related to HDV infection. Besides providing diagnostic information, it provides the best predictor of impending resolution of chronic HDV disease, whether spontaneous or IFN-induced.

Adult↗