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Biomedical subjects

M Rizzetto

Publications and source records attributed to M Rizzetto.

At least 163 records · Page 9Linked to original sources
PubMed1998

Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope.

Patients receiving orthotopic liver transplantation (OLT) because of type D hepatitis frequently exhibit what appears to be an autonomous, or "isolated," hepatitis D virus (HDV) infection following the transplantation, with no evidence of hepatitis B virus (HBV) in the graft or in the serum. These observations have led to the hypothesis that HBV might not always be required for HDV infection, or that HDV could exist as a latent infection until rescued by HBV. Alternatively, an apparently autonomous HDV infection could be explained by coinfection of a small number of hepatocytes with both viruses following transplantation, with a very low level of HBV expression that supports low-level HDV propagation. Our results are consistent with the latter hypothesis. Sensitive polymerase chain reaction (PCR)-based analysis of HBV and HDV viremia in transplantation patients with HDV infection previously characterized as isolated showed that HDV viremia was not independent of HBV viremia. Additional analyses, including PCR amplification, buoyant density analysis in a CsCl gradient, and immunoprecipitation with monoclonal hepatitis B surface antigen antibodies (anti-HBs), indicated that the posttransplant HDV particle is typical: it contains full-length HDV RNA and an envelope of hepatitis B surface antigen (HBsAg) and is not different from that found during the acute and chronic stages of HDV superinfection or coinfection. Moreover, an experimental test of the first hypothesis in chimpanzees did not support the idea that HDV can persist for several weeks as an isolated, latent infection that can be rescued subsequently by HBV. The data indicate, therefore, that latent HDV infection is not a factor in OLT recipients. We conclude that the HDV virion in the posttransplantation setting is typical, and that HDV viremia following OLT requires the helper function of HBV infection.

Adult↗
PubMed1998

Sequential versus concomitant administration of ribavirin and interferon alfa-n3 in patients with chronic hepatitis C not responding to interferon alone: results of a randomized, controlled trial.

We conducted a three-arm, randomized trial in 96 patients with chronic hepatitis C who did not respond to interferon alfa to compare treatments. Group 1 (33 patients) received ribavirin alone (1,000 mg/daily for 6 months) followed by interferon alfa n-3 alone (3 MU thrice weekly for 6 months); group 2 (33 patients) received ribavirin plus interferon alfa n-3 for 6 months at the above doses; and group 3 (30 patients) received interferon alfa n-3 alone (3 MU thrice weekly for 6 months). At the end of treatment, 3 patients (10%) in group 1, 13 (41%) in group 2, and 5 (17%) in group 3 had normal alanine transaminase (ALT) levels (group 2 vs. groups 1 and 3, P = .008). After 6 months of follow-up, only 4 patients (12.5%) in group 2 still had normal ALT values (P = .03). At the end of therapy, hepatitis C virus (HCV) RNA was no longer detectable by polymerase chain reaction in 4 (13%), 9 (27%), and 2 (7%) patients, respectively, in groups 1, 2, and 3 (P = NS). Six months posttherapy, only 5 (15%) patients in group 2 were still HCV RNA negative (P = .02). At the time of follow-up liver biopsy, performed 6 months after the end of treatment, a significant improvement of the necroinflammatory scores was observed among group 2 patients (P = .01) but not in the other two groups. Side effects reflected the profile of each drug as monotherapy; mild hemolytic anemia was the most frequent side effect caused by ribavirin. In conclusion, concomitant administration of ribavirin and interferon alfa n-3 was significantly superior to the sequential schedule or interferon alfa n-3 monotherapy in inducing a sustained response in patients with chronic hepatitis C who had not responded to interferon alone. However, combination therapy at the dose and duration adopted in this study is capable of modifying the natural course of the disease in only a minority of these patients.

Adolescent↗
PubMed1998

Efficacy and efficiency of oral microemulsion cyclosporin versus intravenous and soft gelatin capsule cyclosporin in the treatment of severe steroid-refractory ulcerative colitis: an open-label retrospective trial.

We have used cyclosporin to treat patients with acute steroid-resistant ulcerative colitis since the beginning of 1991. Of the 55 patients so far elected for treatment, 40 received the drug intravenously at 2 mg/kg/day for 14 days, with the responders being maintained on traditional soft-gelatin-capsule cyclosporin at a dose of 6-8 mg/kg/day for 6 months; the remaining 15 received oral microemulsion cyclosporin, 5 mg/kg/day, for 3 months. The doses were titrated to ensure whole-blood drug concentrations of 60-240 ng/ml, with levels of approximately 200 ng/ml being attained by both regimens. One-hundred percent of the patients receiving oral microemulsion cyclosporin and 65% of those receiving the intravenous regimen achieved a short-term response (p = 0.011). Both the responder subsets received additional azathioprine and relapsed on treatment with the same frequency of 40%. However, 17% of the patients who received intravenous cyclosporin developed major toxicity (including one fatality), whereas no major toxicity was observed in the oral microemulsion cyclosporin group. The microemulsion formulation was therefore more effective than intravenous cyclosporin in achieving the short-term remission of steroid-unresponsive ulcerative colitis. As the maintenance drug, it led to the same frequency of disease relapse as traditional oral cyclosporin. However, because it did not involve invasive in-hospital procedures or cause major toxicity, it was more efficient than the combination of the intravenous and traditional oral drug.

Administration, Oral↗
PubMed1998

[Cyclosporin for steroid refractory ulcerative colitis. Results of a study conducted at Turin General Hospital between 1990 and 1997].

BACKGROUND: Four every ten patients receiving high-dose parenteral steroids for severe ulcerative colitis fail and may have their colon removed. Intravenous followed by oral cyclosporin has been shown to initially rescue approx. 70% of these non-responder patients, but dosages and long term-efficacy are still debated. We reviewed the clinical outcomes of patients treated with cyclosporin for refractory ulcerative colitis at our Center in the last 7 years. METHODS: Fifty-four patients destined to colectomy because of refractory ulcerative colitis (previous failure to respond to 7 days of 1 mg/kg/day steroids) were enrolled to initially receive a two-week continuous infusion of 2 mg/kg/day cyclosporin. Responders (showing at least a 50% reduction of activity) were meant to be treated with oral drug at 6-8 mg/kg/day for 6 months with the maintenance of remission and the spare of steroids being the end-points. RESULTS: Data are available for 47 patients followed-up for a minimum of 6 months up to 6 years. Of these 47, 14 did not respond to the intravenous drug and were submitted to surgery; of the remaining 33 responders (70%) entering the oral 6-month phase, 17 relapsed before end or on leaving the drug and were considered as failures. The remaining 16 (34% of the 47) left cyclosporin in remission and in need of less than 20 mg steroids daily. Of them, 12 avoided colectomy in a follow-up of 6 months-6 years. CONCLUSIONS: Intravenous cyclosporin may be rapidly effective in 7 every 10 patients whose acute ulcerative colitis fails a full-dose steroid course. However, only 3 of the initial 10 may maintain remission over a 6-month oral course. Further efforts should concentrate on improving the long term efficacy of cyclosporin.

English Abstract↗
PubMed1998

[Lipohyperplasia or intestinal lipomatosis].

Lipohyperplasia or intestinal lipomatosis is an infrequent disease characterised by anomalous infiltration of adipose tissue in the intestinal submucosa. Localised forms are generally asymptomatic, whereas diffuse forms may lead to intestinal subocclusion, digestive hemorrhage or diarrhoea. Although benign, the differential diagnosis of intestinal lipomatosis with malignant pathologies of the colon or appendix often prompts the need for surgical exploration and the histological analysis of biopsy material. Surgical exeresis of the lesion is generally associated with the normalisation of clinical symptoms. The authors report the onset and clinical evolution of two cases of intestinal lipomatosis referred to their attention.

English Abstract↗
PubMed1998

Recurrence of hepatitis B in liver transplants treated with antiviral therapy.

BACKGROUND AND AIMS: In patients with terminal Hepatitis B Virus-related liver diseases, liver transplantation carries a consistent risk of Hepatitis B Virus recrudescence in the graft. In the attempt to reduce the reinfection rate with antiviral therapy, we studied a total of 16 viraemic patients. PATIENTS AND METHODS: Twelve patients received Ganciclovir, starting 4-67 days (mean 25 days) before transplantation and prolonged for 10 days after transplantation; four patients were treated with Lactosaminated Arabinoside-Monophosphate 6 hours before surgery and prolonged for 28 days after surgery. All received hepatitis B immunoglobulins. RESULTS: At transplantation, HBV-DNA had decreased to about 10(4) virus/ml (as assessed by the polymerase chain reaction assay) in 10 of the 12 patients treated with Ganciclovir. Of these patients, 4 died perioperatively from causes unrelated to Hepatitis B Virus reinfection. Of the eight survivors, only the patient who maintained a titre of 10(6) virus/ml at the time of transplantation developed viral recurrence 4 months after surgery. Before transplantation, 2 of the patients treated with Lactosaminated Arabinoside-Monophosphate had a viraemic load of 10(6) and 2 of 10(4) virus/ml. In all cases, viraemia became undetectable at the end of therapy. None died and Hepatitis B Virus recurred 2 months after transplantation in one. The overall rate of Hepatitis B Virus recurrence was 16.6%. The recurrence rate decreased to 9% in patients in whom the viraemic load decreased to around 10(4) virus/ml following treatment, compared to an overall recurrence rate of 50% in our historical series of patients transplanted for Hepatitis B Virus-related cirrhosis. CONCLUSION: Antiviral therapy was effective in decreasing the risk of Hepatitis B Virus reinfection of the liver graft by decreasing the viral load before surgery.

Adult↗
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

Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis.

Primary biliary cirrhosis is an autoimmune disease characterized by high titer autoantibodies predominantly against mitochondrial antigens PDC-E2, BCOADC-E2 and OGDC-E2. Currently orthotopic liver transplant (OLT) is the major form of treatment for end-stage primary biliary cirrhosis (PBC), but it is still unclear whether the autoimmune response continues post-transplantation. In this study we took advantage of a well-defined collection of sera collected serially before and after liver transplantation. We assayed these sera for quantitative and isotype-specific titers of antibodies against a set of recombinant mitochondrial autoantigens. We also studied reactivity to gp210. Serum samples were taken before transplantation and at intervals of 6 months, 1, 2, and 3 years after OLT. Before OLT 24/35 patients were AMA-positive, including seven out of the 35 to PDC-E2 alone, eight to both PDC-E2 and OGDC-E2, six to both PDC-E2 and BCOADC-E2, two to BCOADC-E2 alone and one to OGDC-E2. Following OLT, the frequency of sera that responded to PDC-E2 alone increased from seven to 12/35. Similarly, reactivity to BCOADC-E2 slightly increased from two to four out of 35. However, there was an overall decrease in sera that responded to more than one antigen. Neither Ig isotype nor subclass of the autoimmune response changed following OLT. Findings with gp210 were similar, in that reactivity to gp210 was found in nine out of 35 patients pre-OLT; following OLT the frequency decreased to seven out of 35 patients. Overall, the titers of AMAs decline slightly during the first year post-OLT, but are equivalent to pre-OLT values by 6 months. Moreover, the antibody subclass/ isotype remained unchanged. These data suggest that the removal of a diseased PBC liver has little, if any, impact on the serological characteristics of PBC. Moreover, it provides information regarding the natural history of PBC, particularly on the long latency time for disease development.

Antibodies, Monoclonal↗
PubMed1997

Prolonged treatment (2 years) with different doses (3 versus 6 MU) of interferon alpha-2b for chronic hepatitis type C. Results of a multicenter randomized trial.

BACKGROUND/AIMS: To examine the effect of prolonged treatment with different doses of interferon alpha-2b on the relapse rate in patients with chronic hepatitis C. METHODS: One hundred and seventy-one patients with non-cirrhotic chronic hepatitis C were enrolled in an Italian multicenter trial. All patients were treated for 3 months with 3,000,000 Units (3 MU) of interferon alpha-2b given subcutaneously three times a week (t.i.w.). Patients with abnormal alanine aminotransferase (ALT) values were given 6 MU of interferon for an additional 3 months. If ALT remained persistently abnormal, therapy was then suspended. If ALT levels were normal, therapy was continued (6 MU t.i.w.) for an additional 18 months (total=2 years). Patients with normal ALT were randomly assigned to two groups, one receiving 3 MU and the other receiving 6 MU t.i.w. for an additional 21 months (total=2 years). Follow-up continued for 2 years after therapy withdrawal. RESULTS: Seven patients stopped treatment during the first 3 months. Of the remaining 164 patients, 76 (46%) showed abnormal ALT levels after 3 months of therapy: 11 of these (14%) normalized ALT values when given 6 MU and a sustained response was maintained in eight during the follow-up. Overall, 54 and 34 patients were allocated respectively to the groups receiving the 3 MU and 6 MU long-term treatment. At the end of therapy, 35/54 patients of the group 3 MU and 21/34 patients of the group 6 MU showed normal ALT levels (65% vs 62%, p=N.S.). After 2 years of follow-up, 24/35 (69%) patients of the group 3 MU and 16/21 (76%) of the group 6 MU were still in remission (p=N.S.). In an intention-to-treat analysis, 48/171 (28%) patients showed a long-term response (normal ALT values, HCV-RNA negative). About 65% of the sustained responders showed low baseline viremia compared with 33% of non-responders (p=0.005) while genotype 1b was more frequently found among non-responders than in long-term responders (84% vs 25%, p=0.0001). CONCLUSIONS: About 14% of patients who do not respond to a 3-month course of 3 MU of interferon normalize ALT levels when given 6 MU. In prolonged treatment, there is no significant difference between 3 and 6 MU in inducing a sustained response. Patients with low baseline viremia and genotype 2a respond significantly better to prolonged interferon therapy than highly viremic patients with genotype 1b.

Antiviral Agents↗
PubMed1997

HCV genotypes in patients with liver disease of different stages and severity.

UNLABELLED: AIMS/MATERIAL: Hepatitis C virus (HCV) genotyping was performed in 213 anti-HCV-positive patients with chronic liver disease ranging from minimal histological changes to hepatocellular carcinoma. One hundred and twenty-two patients had non-cirrhotic chronic active or persistent hepatitis (including 29 who were asymptomatic with persistently normal ALT levels) (chronic liver disease group). The other 91 had hepatocellular carcinoma and, in all but three cases, cirrhosis (hepatocellular carcinoma group). RESULTS: The overall prevalence of HCV variants was: 54.9% type 1b, 37.8% type 2, 2.5% type 1a, 2.0% type 3a, 2.0% type 4a. The genotype distribution showed no relation to the stage (chronic liver disease vs. hepatocellular carcinoma) or severity (chronic active vs. chronic persistent hepatitis) of the liver disease, or to the duration of the disease (<10 years vs. >10 years). Within the hepatocellular carcinoma group, the duration of type-1b disease was similar to that of type-2 infections. Ages at the time of infection and genotype were both independently associated with progression to cirrhosis and hepatocellular carcinoma, but multivariate analysis revealed that the effect of age was much stronger than that of genotype 1b. CONCLUSIONS: The predominance of HCV type 1b in this study reflects the higher frequency of this variant in our area. Our findings indicate that infections caused by each HCV genotype are capable of progressing to hepatocellular carcinoma.

Adolescent↗
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↗
PubMed1997

[Chronic diarrhea: a difficult diagnosis. A rare cause: lymphocytic colitis].

Lymphocytic colitis is a clinicopathological entity, characterized by chronic watery diarrhea, not bloody. Previously termed microscopic, it is now named lymphocytic for histological features, the most important seems to be the diffuse infiltration of intraepithelial lymphocytes, that must be investigated in multiple biopsies during colonoscopy. This review evidences that during endoscopy the mucosa is normal, but this does not exclude a biopsy, only way for take a diagnosis. Ethiologies are unknown too although a correlation with autoimmune diseases as possible. Lymphocytic colitis is a definition histological entity, while the term ''microscopic'' includes different histological entities under the same ''umbrella'', in relation to the concept of no macroscopic changes and multiple different histological specimens. The treatment is based for the first time on mesalazine or sulphasalazine and then in case of non responders, on corticosteroids.

Editorial↗
PubMed1997

[LKM (Liver-Kidney-Microsome) antibodies and hepatitis C virus. Description of a clinical case].

BACKGROUND: Diagnostic and therapeutic issues related to hepatitis C virus infection and autoimmune hepatitis are discussed. The authors report a 56 year old female patient with chronic hepatitis and both HCV-RNA positivity and a high titer of LKM-1 antibody on blood samples. METHODS: In the absence of clinical signs of autoimmunity the patient was started on interferon treatment. After four months she experienced a flare-up with a sharp increase of transaminases and a concomitant rise in LKM-1 titer. Viremia was persistently detected by PCR. As interferon therapy was discontinued transaminases and autoantibody titer fell to baseline values. A few months later she received immunosuppressive therapy, that resulted in a decrease in LKM1 titer and complete normalization of liver enzymes. Anti LKM-1 antibody was detected by indirect immunofluorescence, serum immunoblot assay (Western Blot), and enzyme immunoassay (ELISA). RESULTS AND CONCLUSIONS: Therapy of patients with HCV/LKM positive chronic hepatitis should be settled on an individual basis. Patients eligible for interferon treatment should be carefully selected and closely monitored because of the risk of adverse reaction.

English Abstract↗
PubMed1997

[Recurring duodenal ulcer. Evaluation of previous complications as a predictive factor of ulcer recurrence after eradication of Helicobacter pylori].

Duodenal ulcer is a chronic disease, punctuated by acute relapses. The pathogenic mechanism in 90-100% of cases is infection by Helicobacter pylori. Two major strains exist of this bacterium: I strain, which secretes a vacuolating cytotoxin (Vac-A), and another protein named cytotoxin-associated (Cag-A) and type II strain, unable to produce both proteins and unable to produce duodenal pathology. We sought to identify the natural history of relapsing duodenal ulcer after cure of the bacterial infection. In particular, we followed the outcome of patients who repeatedly had bled from their recurrent ulcer disease, after success in eliminating the microorganism from the stomach. None of 12 repeated bleeders had an ulcer recurrence after the cure of Helicobacter pylori infection. Only 3 (5%) of 60 frequent relapser had a new episode of duodenal ulcer during a follow-up reinfection by Helicobacter pylori. We demonstrated that the cure of bacterial infection is also the cure of duodenal ulcer recurrence, but for a few cases, in the latter, event one could hypothesize a defect in the production of growth factors (Epidermal Growth Factor, Fibroblast Growth Factor) or of cellular polyamines synthesis. It is important to improve the diagnosis of reinfection by implementing the urea breath test.

English Abstract↗