Hepatitis: Prati D

Puoti C, Guido M, Mangia A, Persico M, Prati D, Anonymous00025. · Department of Gastroenterology and Internal Medicine, E. De Santis Hospital, Via A. Grandi 43, 00045 Genzano, Rome, Italy. · Dig Liver Dis. · Pubmed #12846410 No free full text.

Abstract: An ad hoc committee appointed by the Italian Association for the Study of the Liver (AISF) proposed these Practice Guidelines for the management of HCV carriers with persistently normal aminotransferase levels. Only stringent ALT determinations will make it possible to distinguish these subjects from those in temporary biochemical remission. The overall prevalence in Italy has been estimated between 1.5 and 10.6%. HCV RNA quantitation and genotype determination are not predictors of the presence and severity of liver damage nor correlate with the outcome of the disease, and should not be used in clinical practice for the management and surveillance of HCV carriers with normal ALT. Only a minority of HCV carriers with normal ALT levels show a normal morphological picture (true 'healthy carriers'). Disease activity is mild in most cases; fibrosis is generally mild and cirrhosis is very rare. Histological activity, as monitored by sequential liver biopsies, seems to have very slow evolution. HCV carriers should not undergo liver biopsy on a routine basis. Liver biopsy can be reasonably proposed only in selected cases. Until the results of studies with PEG interferon plus ribavirin are available, HCV carriers should not receive antiviral treatment outside controlled experimental studies.

Zeuzem S, Alberti A, Rosenberg W, Marcellin P, Diago M, Negro F, Prati D, Puoti C, Roberts SK, Shiffman ML. · Department of Internal Medicine, , Saarland University Hospital, 66421 Homburg/Saar, Germany. · Aliment Pharmacol Ther. · Pubmed #17014573 No free full text.

Abstract: BACKGROUND: Hepatitis C virus infection, a major cause of chronic liver disease, occurs with normal serum alanine aminotransferase activity in approximately 25% of patients. These patients have historically remained untreated but substantial evidence indicates liver damage, progression of disease and impaired quality of life in some individuals. AIM: To review the current management of patients with chronic hepatitis C and normal alanine aminotransferase activity. METHODS: This review represents the summary of discussions at a Clinical Workshop with a comprehensive literature searching of available databases (PubMed and Embase). RESULTS: Current limits defining normal serum alanine aminotransferase activity are not representative of a "healthy" status. Most patients with hepatitis C and normal alanine aminotransferase levels have histologically proven liver damage that, although generally mild, may be significant (> or =F2) in up to 20% of patients and progresses at approximately 50% of the rate in patients with elevated alanine aminotransferase levels. Some patients have persistently normal alanine aminotransferase activity and may have a more benign outcome, but a significant proportion (> or =20%) experience periods of increased serum alanine aminotransferase activity which may be associated with enhanced disease progression. CONCLUSIONS: A treatment approach that considers host and virus-related variables and optimizes patient and cost benefits may therefore provide more effective management of patients with chronic hepatitis C and normal alanine aminotransferase activity.

Prati D. · Department of Transfusion Medicine and Hematology, Ospedale Alessandro Manzoni, Lecco, Italy Postgraduate School of Gastroenterology, University of Milan, Italy. <> · J Hepatol. · Pubmed #16901579 No free full text.

Abstract: Hepatitis C virus (HCV) is a leading cause of chronic blood-borne infection and chronic liver disease. The global epidemic of HCV infection emerged in the second half of the 20th century, and several lines of evidence indicate that it was primarily triggered and fed iatrogenically by the increasing use of parenteral therapies and blood transfusion. In developed countries, the rapid improvement of healthcare conditions and the introduction of anti-HCV screening for blood donors have led to a sharp decrease in the incidence of iatrogenic hepatitis C, but the epidemic continues to spread in developing countries, where the virus is still transmitted through unscreened blood transfusions and non-sterile injections. This article reviews the published literature concerning HCV transmission through blood transfusions and other unsafe medical procedures. Given the substantial difference in current disease transmission patterns between the northern and southern hemispheres, the situation in developed and developing countries is separately analysed.

Prati D. · Blood Transfusion and Transplantation Immunology Centre, Postgraduate School of Gastroenetrology, IRCCS Ospedale Maggiore, University of Milan, Italy. · Dig Liver Dis. · Pubmed #12546518 No free full text.

Abstract: For more than 40 years in the history of transfusion medicine, transmission of viral hepatitis from infected donors to recipients has been a frequent and serious adverse effect of the administration of blood components and plasma derivatives. This epidemic is now over, at least in developed and resource-rich countries. Hence, the attention of clinicians and investigators now focuses mainly on the measures to reduce the residual risk, on the possible emergence of novel or undiscovered agents causing post-transfusion hepatitis, and on the long-term outcome of patients who became infected more than ten years ago. The present article reviews these issues.

Conte D, Colucci A, Minola E, Fraquelli M, Prati D. · Chair of Gastroenterology, IRCCS Maggiore Hospital, Milan, Italy. · Dig Liver Dis. · Pubmed #11432518 No free full text.

Abstract: As far as concerns chronic hepatitis C virus infection in pregnant women, different points remain to be elucidated, such as the clinical course, the rate of mother-to-child hepatitis C virus transmission and, in particular, its route and the possible risk factors. This review aimed to analyse current data on the prevalence of chronic hepatitis C virus infection in pregnant women and its relationship with risk factors, the rate of mother-to-child hepatitis C virus transmission and the factors possibly involved, particularly the maternal hepatitis C virus viral load and the human immunodeficiency virus coinfection, and the type of delivery and feeding. Finally, the appropriate timing for HCV-RNA testing in newborns has been reviewed.

Prati D. · Centro Trasfusionale e di Immunologia dei Trapianti, IRCCS Ospedale Maggiore di Milano, Italia. · Vox Sang. · Pubmed #11111230 No free full text.

Abstract: Early and regular blood transfusion therapy in patients with homozygous beta-thalassaemia decreases the complications of severe anaemia and prolongs survival. In the long term, however, the beneficial effects of transfusions are limited by the organ damage resulting from iron overload, a consequence of the body's limited capacity to excrete iron, and by the complications of infection with blood-borne agents. Transfusion regimens for beta-thalassaemia have changed substantially during the past four decades. In current protocols, pre-transfusion haemoglobin concentration should not exceed 95 g/l. This allows adequate control of anaemia, with a relatively low rate of iron accumulation. Although iron chelation therapy has successfully improved survival free from cardiac disease, thalassaemic patients continuously present new clinical challenges. In fact, the vast majority of them suffer from post-transfusion chronic hepatitis C, which is expected to significantly contribute to morbidity in the forthcoming years. Furthermore, recent studies demonstrated that thalassaemics are at high risk of acquiring several blood-borne viruses. The potential role of these multiple infections in inducing clinical disease is still uncertain, and needs to be thoroughly clarified in future surveys.

Prati D, Shiffman ML, Diago M, Gane E, Rajender Reddy K, Pockros P, Farci P, O'Brien CB, Lardelli P, Blotner S, Zeuzem S. · Ospedale A. Manzoni, Lecco and IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milan, Italy. · J Hepatol. · Pubmed #16487620 No free full text.

Abstract: BACKGROUND/AIMS: In chronic hepatitis C, disease progression and clinical manifestations are heterogenous. To clarify the role and interactions of viral and host factors in inducing liver cell injury, we examined the associations of several virological and metabolic variables with serum alanine aminotransferase levels. METHODS: Patients with chronic hepatitis C enrolled in three phase III clinical trials of peginterferon alfa-2a (40KD) plus ribavirin (two studies analysing 'elevated' and one persistently 'normal' alanine aminotransferase) were included. RESULTS: Multivariate analyses of 2,881 patients before treatment and of 1,403 patients with a sustained virological response indicated that gender, viral factors (genotype, HCV RNA titer) and indicators of metabolic syndrome (body mass index, blood pressure, blood glucose, cholesterol and triglyceride concentration) were associated with alanine aminotransferase levels. In addition, hepatitis C virus infection influenced serum lipids concentration according to a genotype-specific effect. CONCLUSIONS: Heterogeneity in alanine aminotransferase levels in patients with chronic hepatitis C partially depends on the degree of derangement of fat and carbohydrate metabolism. As this is the result of an interaction of chronic hepatitis C infection with the patient's individual characteristics, treatment decisions should not be based on alanine aminotransferase level alone but rather on global evaluation of the patient.

Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, Shiffman M, Farci P, Gitlin N, O'Brien CB, Lamour F, Lardelli P, Anonymous00311. · Saarland University Hospital, Homburg/Saar, Germany. · Gastroenterology. · Pubmed #15578510 No free full text.

Abstract: BACKGROUND & AIMS: Patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels have been routinely excluded from large randomized treatment trials; consequently, the efficacy and safety of antiviral therapy in this population are unknown. METHODS: Patients with at least 3 normal ALT values over an 18-month period were randomized (3:3:1) to treatment with peginterferon alfa-2a 180 mug/wk plus ribavirin 800 mg/day for 24 weeks (212 patients), the same combination for 48 weeks (210 patients), or no treatment (69 patients) in a multinational study. All patients were monitored for 72 weeks. The primary measure of efficacy was sustained virologic response (SVR), defined as undetectable serum hepatitis C virus (HCV) RNA by qualitative polymerase chain reaction at the end of 24 weeks of untreated follow-up. RESULTS: No patient cleared HCV RNA in the untreated control group. SVR rates of 30% and 52% were obtained in the 24- and 48-week treatment groups, respectively. In patients infected with HCV genotype 1, SVR rates of 13% and 40% were obtained with 24 and 48 weeks of treatment, respectively (P < .0001). In patients infected with genotypes 2 or 3, SVR rates were 72% and 78% with 24 and 48 weeks of treatment, respectively (P = .452). Treatment-related flares in ALT activity were not observed. CONCLUSIONS: The efficacy and safety of peginterferon alfa-2a and ribavirin combination therapy in patients with chronic hepatitis C and persistently normal ALT levels are similar to that in patients with elevated ALT levels. The indication for treatment of hepatitis C can be evaluated independently from baseline ALT activity.

Prati D, Zanella A, Zanuso F, Vianello L, Della Torre E, Mozzi F, Carriero PL, Zahm F, Donato MF, Colombo M, Sirchia G. · Centro Trasfusionale e di Immunologia dei Trapianti, IRCCS Ospedale Maggiore di Milano, Milano, Italy; Divisione di Ematologia, IRCCS Ospedale Maggiore di Milano, Italy; Roche Italy, Milano, Italy; Hoffman-LaRoche Ltd, Basel, Switzerland; Istit. · J Viral Hepat. · Pubmed #10971823 No free full text.

Abstract: Subjects with minimal-to-mild chronic hepatitis C may suffer long-term consequences of hepatitis C virus (HCV) infection. Nonetheless, they are not candidates for antiviral treatment, mainly because little data are available concerning the efficacy and safety of therapy. Thirty-two HCV RNA positive individuals aged 18-45 years, who had a histological activity index score < or = 8 and alanine aminotransferase (ALT) levels < or = 1.5 times lower than the normal limit for at least 1 year, were prospectively enrolled among a cohort of 35358 candidate blood donors, and treated with 4.5 mega units (MU) of recombinant interferon-alpha2a (IFN-alpha2a) thrice weekly for 6 months, and for an additional 6 months if a virological response was observed. Twelve months after the completion of treatment, 13 of 31 evaluable patients were HCV RNA negative, accounting for a sustained response rate of 42%. Patients without fibrosis had a lower response rate than those with mild fibrosis (two of 14 vs 11 of 17; P=0.012). In responders, median aminotransferase levels were significantly lower after therapy than before (11.04 +/- 3.98 vs 27.3 +/- 12.32 U l-1, respectively; P < 0. 005). When the analysis was limited to the six responders whose pretreatment aminotransferase levels were consistently normal, this difference was still significant (9.33 +/- 4.12 vs 20.58 +/- 6.73 U l-1; P=0.002). In conclusion, a durable suppression of viraemia can be obtained by IFN monotherapy in a relatively high proportion of young subjects with minimal-to-mild chronic hepatitis C, especially when portal fibrosis is found on liver biopsy. The disappearance of viraemia always leads to a reduction in the degree of hepatocellular necrosis.

Ronchetti A, Prati D, Pezzotta MG, Tavian D, Colombo R, Callea F, Colli A. · Department of Internal Medicine, Ospedale Alessandro Manzoni, Lecco, Italy. · J Hepatol. · Pubmed #18644654 No free full text.

Abstract: Fatty liver disease is mainly caused by alcohol consumption, excessive body weight, dyslipidemia and impaired glucose tolerance, but inherited disorders can sometimes be involved. We report the case of a 40-year-old woman with steatohepatitis and severe portal hypertension, associated with ichthyosis, cataract and hypoacusia. The clinical, pathological and genetic findings were consistent with a diagnosis of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive inherited neutral lipid storage disorder, and genetic analysis showed that a novel ABHD5 mutation is responsible.

Mangia A, Antonucci F, Brunetto M, Capobianchi M, Fagiuoli S, Guido M, Farci P, Lampertico P, Marzano A, Niro G, Pisani G, Prati D, Puoti M, Raimondo G, Santantonio T, Smedile A, Lauria F, Anonymous00030. · Liver Unit, IRCCS, Ospedale "Casa Sollievo della Sofferenza" San Giovanni Rotondo, Italy. · Dig Liver Dis. · Pubmed #18321798 No free full text.

Abstract: Molecular assays are instrumental in the clinical management of viral hepatitis. During the past years, a wide variety of molecular assays have been developed and implemented. This considerably improved the understanding of the natural history and pathogenesis of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Hepatitis delta virus (HDV) hepatitis, but also caused uncertainties in the selection of the most appropriate assays for clinical requirements. Indeed, a rational choice and application of these assays requires adequate knowledge of the performance of the single test. Moreover, the choice of the most accurate assay for patients' needs and physicians' objectives, needs to be oriented to specific contexts, such as diagnosis, management or treatment. In the past, a hurdle in the routine use of assays for hepatitis viruses nucleic acid quantification was represented by the availability of only "home brew" methods which lacked standardization. Major improvement in addressing the use of molecular assays for viral hepatitis has been derived from recent standardization procedures that allowed a comparison between different tests after results were given as International Units. In addition, it should be reminded that, before getting into the market, molecular assays should be approved by European regulation authorities and validated using internationally recognized standards. A subsequent clinical validation should address the diagnostic accuracy of the assay. These proceedings have the aim of identifying which molecular tests, among those currently available, meet clinical requirements for each specific application.

Hornberger J, Farci P, Prati D, Zeuzem S, Green J, Patel KK. · Acumen LLC/The SPHERE Institute, Burlingame, CA 94010, USA. · J Viral Hepat. · Pubmed #16842440 No free full text.

Abstract: Peginterferon alpha-2a (40 kDa) plus ribavirin is effective at achieving sustained viral response compared with no treatment in patients with chronic hepatitis C (CHC) and persistently normal aminotransferase levels (PNALT). The cost-effectiveness of treating CHC in the setting of PNALT has not been assessed. Disease progression in patients with PNALT was simulated in a Markov model. The rate of fibrosis progression, quality of life and costs for each health state were based on literature estimates. The perspective of the Italian National Health Service was adopted and costs (euro 2003) and benefits were discounted at 3%. Sensitivity analyses were performed on important parameters. The primary analysis compared combination therapy with peginterferon alpha-2a (40 kDa) plus ribavirin to no treatment in a cohort of patients with mean age 45 years, and was based on findings from a multinational, randomized trial in patients with PNALT. In genotype 1 patients, the risk of cirrhosis at 30 years is forecast to fall from 32% with no treatment to 19% with combination therapy, increasing quality-adjusted life years (QALYs) by 0.74 years at an incremental cost per QALY gained of euro 16,831. The 30-year risk of cirrhosis in genotype 2 or 3 is projected to fall to 9% with combination therapy, an increase in QALYs of 1.34 years, at an incremental cost per QALY gained of euro 3,000. Thus treatment of PNALT with peginterferon alpha-2a (40 kDa) plus ribavirin is projected to reduce the incidence of cirrhosis, increase life expectancy and have an acceptable cost-effectiveness ratio from a societal perspective.

Shiffman ML, Diago M, Tran A, Pockros P, Reindollar R, Prati D, Rodríguez-Torres M, Lardelli P, Blotner S, Zeuzem S. · Virginia Commonwealth University Medical Center, Richmond, Virginia 23298, USA, and Hospital General de Valencia, Spain. · Clin Gastroenterol Hepatol. · Pubmed #16630770 No free full text.

Abstract: BACKGROUND & AIMS: Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa). METHODS: The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks. RESULTS: More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable. CONCLUSIONS: Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.

Prati D, Maggioni M, Milani S, Cerino M, Cianciulli P, Coggi G, Forni GL, Magnano C, Meo A, Gramignoli R, Rebulla P, Fiorelli G, Cappellini MD, Anonymous00363. · Dept. of Blood Transfusion and Transplantation Immunology, IRCCS Ospedale Maggiore, Milan, Italy. <> · Haematologica. · Pubmed #15477201 links to  free full text

Abstract: BACKGROUND AND OBJECTIVES: Updated information on liver disease in transfusion-dependent beta-thalassemia is lacking. We conducted a multicenter study within the Cooleycare Group to describe the clinical and histopathological features of liver disease in currently treated thalassemics. DESIGN AND METHODS: Two-hundred and three thalassemics with laboratory signs of liver disease were eligible. Liver biopsy was performed in the 129 (63.5%) who consented (age 26+/-7 years). Biological samples were sent to the central laboratory. RESULTS: Anti-hepatitis C virus (HCV) antibodies were found in 118 patients (91%), 85 (72%) of whom were viremic. Ninety-one patients (70%) had abnormal aminotransferase concentrations. In the 117 liver biopsies that met the criteria for evaluation (88%), the median Ishak's necroinflammatory and fibrosis scores were 4 (range, 0-9) and 2 (range, 0-6), respectively. Significant fibrosis (score >or=3) was found in 53 (45%); 9 (8%) had cirrhosis. At multivariate analysis, necroinflammation was related to HCV viremia, and fibrosis to increased serum aminotransferases, higher iron stores (including serum ferritin, Deugnier's total iron score, and liver iron content) and male gender (p<0.05). In HCV-RNA negative subjects, the median total iron score was 27 (range, 0-52). Iron accumulated in both mesenchymal cells and hepatocytes, and the presence of a lobular gradient was interpreted to indicate intestinal hyperabsorption. INTERPRETATION AND CONCLUSIONS: Transfusion-dependent thalassemics have mild liver necroinflammation, mainly attributable to HCV infection. Significant fibrosis is frequent, and its progression is mostly influenced by iron overload which, with current therapy regimens, may be attributable to both erythrocyte catabolism and iron hyperabsorption.

Fraquelli M, Conte D, Cammà C, Casazza G, Di Bona D, Rebulla P, Prati D. · Postgraduate School of Gastroenterology, Pad. Granelli 3rd floor, IRCCS Maggiore Hospital, Via F Sforza 35, 20122 Milan, Italy. · Dig Liver Dis. · Pubmed #15334774 No free full text.

Abstract: BACKGROUND: The amount of hepatology-related information available on the Internet has substantially increased, but little is known about the characteristics and quality of the websites. AIM: The aim of this study was to describe analytically and evaluate critically the information concerning three diseases of hepatological interest: chronic hepatitis, hemochromatosis and Caroli's disease. METHODS: In accordance with a validated method, the three search terms were entered into four English language search engines and the first five links of each were considered (a total of 60 sites). The characteristics of the websites were described and their quality was evaluated by three independent reviewers who assigned scores of 1-5 for accuracy, reliability and depth. The relationships between the site characteristics and quality scores were analysed by means of multiple logistic regression. RESULTS: The overall rating score was sufficient (>3) in 51% (95% confidence interval: 38-65%) of cases. The majority of the sites (73%) were aimed at patients rather than at physicians. Commercial sponsorship was significantly more frequent among the chronic hepatitis sites (45%) than among the hemochromatosis (15%) or Caroli's disease sites (0%) (P = 0.002); 61% of the commercial sites did not include a financial disclosure. The only variable that independently related to poor quality was the presence of commercial sponsorship (odds ratio 18.1; 95% confidence interval: 1.7-192.5). CONCLUSIONS: Hepatological websites are characterised by poor quality and are mainly aimed at patients. Quality is negatively affected by commercial interests, which are often undeclared. Guidelines for the certification and surveillance of websites relating to liver diseases are highly advisable.

Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G. · Centro Trasfusionale e di Immunologia dei Trapianti, Laboratorio di Epidemiologia, Divisione di Ematologia, Istituto di Statistica Medica e Biometria, Cattedra di Gastroenterologia, Milan, Italy. · Ann Intern Med. · Pubmed #12093239 links to  free full text

Abstract: BACKGROUND: Serum alanine aminotransferase (ALT) activity, the variable most commonly measured to assess hepatic disease, fails to identify many patients with hepatic injury. Current standards for "normal" ALT level were defined by using populations that included persons with subclinical liver disease. OBJECTIVE: To update definitions of healthy ranges for serum ALT level. DESIGN: Retrospective cohort study. SETTING: A university hospital in Milan, Italy. PARTICIPANTS: 6835 persons who were first-time blood donors from 1995 through 1999, were negative for anti-hepatitis C virus (HCV), and had no contraindications to donation and 209 persons who attempted to donate blood from 1990 through 1999 but were found to have anti-HCV antibodies. Of the latter group, 131 had HCV viremia. MEASUREMENTS: Univariate and multivariate analyses examined associations between clinical and laboratory factors and ALT levels. Healthy ranges for ALT were computed from the population at lowest risk for liver disease. Sensitivity and specificity of healthy ALT ranges were evaluated in the donors with HCV antibodies, of whom 133 had liver biopsy. RESULTS: Serum ALT activity was independently related to body mass index and to laboratory indicators of abnormal lipid or carbohydrate metabolism. Updated upper limits (for men, 500 nkat/L [30 U/L]; for women, 317 nkat/L [19 U/L]) were lower than current limits (for men, 667 nkat/L [40 U/L]; for women, 500 nkat/L [30 U/L]) and, during 6-month follow-up, showed superior sensitivity in identifying participants with HCV viremia (sensitivity, 76.3% [95 % CI, 69.1% to 83.6%] vs. 55% [CI, 46.4% to 63.5%]). The related tradeoff in specificity was acceptable (88.5% [CI, 79.2% to 94.6%] vs. 97.4% [91% to 99.7%]). The increased sensitivity targeted patients with minimal to mild histologic lesions. CONCLUSION: In patients with chronic HCV infection or nonalcoholic fatty liver disease, revision of normal limits for ALT level is advisable.

Minola E, Prati D, Suter F, Maggiolo F, Caprioli F, Sonzogni A, Fraquelli M, Paggi S, Conte D. · Infectious Diseases Unit, Ospedali Riuniti, Bergamo, Italy. · Blood. · Pubmed #12036892 links to  free full text

Abstract: Before the introduction of hepatitis C virus (HCV) screening for blood donors, the risk of acquiring HCV infection as a result of a transfusion was about 10%. The aim of this study was to assess the frequency and rate of progression to cirrhosis in patients with transfusion-associated chronic HCV infection and identify possibly negative prognostic factors. Of 2477 consecutive patients with clinical or laboratory evidence of liver disease, 392 (16%) were anti-HCV- and HCV-RNA-positive, had anamnestic evidence of a single and precisely dated transfusion event, and showed no other causes of chronic liver disease; 268 (68%) underwent ultrasound-guided liver biopsy and were enrolled in the study. After a mean interval of 18.4 years, 54 patients (20.1%) had cirrhosis, which multivariate analysis showed to be independently associated with the duration of follow-up, age at infection and at the time of liver biopsy, and serum alanine aminotransferase levels at biopsy. The time necessary to have a 50% probability of developing cirrhosis in patients aged 21-30, 31-40, and more than 40 years was 33, 23, and 16 years, respectively. In comparison with those aged 20 years or less at infection, the risk ratio of developing cirrhosis over a period of 30 years for patients aged 21-30 and at least 31 years at infection was, respectively, 4.51 (95% confidence interval, 1.03-19.76) and 12.29 (95% confidence interval, 3.06-49.40). In patients with transfusion-associated chronic hepatitis C, the risk of cirrhosis is related to age at infection and disease activity. Our findings suggest that an aggressive therapeutic approach should be adopted in patients infected by HCV at an older age to prevent the progression to end-stage liver disease.

Donato MF, Arosio E, Monti V, Fasani P, Prati D, Sangiovanni A, Ronchi G, Colombo M. · A.M. & A. Migliavacca Liver Center & Italian Foundation for Research on Cancer, Unit of Liver Cancer, IRCCS Maggiore Hospital, University of Milan, Italy. · Dig Liver Dis. · Pubmed #11990392 No free full text.

Abstract: BACKGROUND: Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. AIM: To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. MATERIALS: Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. METHODS: Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). RESULTS: Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender; higher transaminase levels, hepatitis C virus, higher histological gradIng and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. CONCLUSIONS: Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity

Tosti ME, Solinas S, Prati D, Salvaneschi L, Manca M, Francesconi M, Ciuffreda M, Girelli G, Mele A. · Reparto di Epidemiologia Clinica, Istituto Superiore di Sanità, Servizio Trasfusionale e Immunoematologia, Università La Sapienza, Rome, Italy. · Br J Haematol. · Pubmed #11918558 No free full text.

Abstract: We conducted a retrospective cohort study to estimate the incidence of major blood-borne agents among Italian blood donors and calculated the risk of infection among blood recipients using the 'incidence/window period model'. The study was conducted among 46 180 blood donors enrolled in six blood centres between 1994 and 1999. During follow-up, seven new infections were confirmed: three donors seroconverted for anti-human immunodeficiency virus (HIV); two for anti-hepatitis C virus (HCV); and two showed hepatitis B surface antigen (HBsAg) reactivity; no cases of syphilis were observed. The incidence rates per 100 000 person/years were: 4.06 (95% CI: 0.82-11.85) for HIV; 2.41 (95% CI: 0.29-8.70) for HCV; and 2.70 (95% CI: 0.32-9.77) for HBsAg; the incidence for total hepatitis B virus (HBV) infection was 9.77 per 100 000 person/years (95% CI: 1.16-35.36). The estimated risk of an infectious blood unit not being detected was: 2.45 (95% CI: 0.13-12.33) per 1 million units for HIV; 4.35 (95% CI: 0.30-22.39) for HCV; and 15.78 (95% CI: 1.16-84.23) for HBV. Overall, an estimated 22.58 per 1 million units are infected. In Italy, the risk of transfusion-transmitted infections is low and is similar to that in other western countries. The introduction of new more sensitive screening tests could reduce the residual risk of transfusion-transmitted infection by 40-80%.

Mele A, Ippolito G, Craxì A, Coppola RC, Petrosillo N, Piazza M, Puro V, Rizzetto M, Sagliocca L, Taliani G, Zanetti A, Barni M, Bianco E, Bollero E, Cargnel A, Cattaneo M, Chiaramonte M, Conti E, D'Amelio R, De Stefano DM, Di Giulio S, Franco E, Gallo G, Levrero M, Mannella E, Erli SM, Milazzo F, Moiraghi A, Polillo R, Prati D, Ragni P, Sagnelli E, Scognamiglio P, Sommella L, Stroffolini T, Terrana T, Tosolini G, Vitiello E, Zanesco L, Ziparo V, Maffei C, Moro ML, Satolli R, Traversa G. · Institute of Health, L. Spallanzani Hospital, Italian Association for the Study of the Liver, Rome, Italy. · Dig Liver Dis. · Pubmed #11838616 No free full text.

Abstract: Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.

Silvani C, Vianello L, Rebulla P, Prati D, Mozzi F, Taioli E, Sirchia G. · Centro Trasfusionale e di Immunologia dei Trapianti, IRCSS Ospedale Maggiore, via F. Sforza, 35, 20122 Milan, Italy. · Haematologica. · Pubmed #11025597 links to  free full text

Abstract: BACKGROUND AND OBJECTIVES: We conducted a longitudinal prospective study to assess the eligibility to blood donation of donors with 'minor' risk factors (i.e. minor surgery, professional exposure, cohabitation with 'high risk' people, occasional use of light drugs) or 'medium' risk factors for human immuno-deficiency virus (HIV) infection (i.e. casual sexual relationship, multiple heterosexual exposure, sexual partnership with subjects at risk, regular use of light drugs). DESIGN AND METHODS: During a 4-year period we administered a psychosocial questionnaire to all donors attending our Center. In addition we determined anti-HIV, anti-hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) and syphilis serology (TPHA) at entry to the study and at 6-month intervals. RESULTS: Of 25,367 donors, 1,535 (6%) reported medium and 8,761 (34%) minor risk. At enrollment into the study, 4 medium risk donors were anti-HIV positive and there was a significantly higher rate of positivity for TPHA (0.33% vs 0.07%) and anti-HCV (1.17% vs 0.63%) in this group than in donors reporting no risk. No anti-HIV positivity was observed in minor or no risk donors. During a median follow-up of 18 months, none of 24,404 donors undergoing 106,503 visits seroconverted to HIV. The incidences of novel HCV and syphilis infections were almost one log greater in donors at medium risk (3 and 1x10-4/yr, respectively) than in no risk donors (0.4 and 0.1x10-4/yr, respectively). Medium risk donors were more frequently males (Odds Ratio=3.2, 95% confidence interval= 2.8-3.7), aged 26-35 yrs (1.52; 1.3-1.78), single (1.4; 1.2-1.6), divorced (2; 1.4-2.8), freelance workers (1.43; 1.1-1.9) and first-time donors (1.8; 1.6-2.1) than no risk donors. INTERPRETATION AND CONCLUSIONS: The only 4 HIV positive subjects of the cohort were medium risk donors picked up at enrollment. No HIV seroconversion was observed during the study. On the basis of this study we will continue to defer 'medium' risk donors.

Conte D, Fraquelli M, Prati D, Colucci A, Minola E. · Cattedra di Gastroenterologia, IRCCS Ospedale Maggiore, Milan, Italy. · Hepatology. · Pubmed #10706568 No free full text.

Abstract: The prevalence and natural course of chronic hepatitis C virus (HCV) infection was evaluated in 15,250 consecutive pregnant women. The rate of HCV vertical and perinatal transmission was also assessed. The presence of anti-HCV was tested by means of EIA III and confirmed by recombinant immunoblot assay III. Alanine transaminase (ALT), anti-human immunodeficiency virus (HIV), and HCV-RNA were tested during the first month and third trimester of pregnancy, and 6 months after delivery; the same tests were made in all of the newborns of anti-HCV-positive mothers at birth (on cord blood samples) and then at 4-month intervals. Anti-HCV positivity was found in 370 cases (2.4%), 72% of whom were also HCV-RNA-positive. The proportion of women with hypertransaminases decreased from 56.4% at the first examination during the first month of pregnancy to 7.4% in the last trimester, and then increased again after delivery (54. 5%), without any concomitant changes in the proportion of those with viremia. The proportion of anti-HCV- and HCV-RNA-positive newborns was 5.1% after 1 year (8 of 155), all of whom had the same genotype as their mother. The rate of HCV transmission was not affected by the type of delivery or feeding, or the HIV status of the mother. The results of this large-scale study confirm previous data in smaller series concerning the prevalence of HCV infection in pregnant women, and strongly support the hypothesis of a favorable (possibly immunomediated) effect of pregnancy on liver cell necrosis in anti-HCV-positive women.

Chen BP, Rumi MG, Colombo M, Lin YH, Ramaswamy L, Luna J, Liu JK, Prati D, Mannucci PM. · Sentinel BioSciences, Inc, Palo Alto, CA, USA. · Blood. · Pubmed #10590078 links to  free full text

Abstract: The prevalence of the blood-borne TT virus (TTV) in Italian hemophiliacs treated with different preparations of factor VIII was determined. Of the 178 hemophilic patients (mean age, 29 years), TTV-DNA was found in 123 (69%), in comparison to 22 of 100 (22%) blood donors (P <.0001). Of the 123 patients who tested positive for TTV, significant numbers were also infected with human hepatitis viruses and/or human immunodeficiency virus (HIV): 31% had TTV and hepatitis C virus (HCV), 22% had TTV, and at least 2 of the 4 known human blood-borne viruses tested, whereas 15% had TTV alone. The risk of acquiring TTV alone was only slightly higher in recipients of unmodified plasma factor concentrates (78%, odds ratio, 1.24; 95% confidence interval [CI], 0.27 to 5.79) than in patients treated with virus inactivated concentrates (67%), whereas the risk was significantly lower in recipients of recombinant factors (11%, odds ratio, 0.09; 95% CI, 0.01 to 0.52). Serum alanine aminotransferase (ALT) levels were elevated in 2 of 27 patients (7%) with TTV alone compared with 43 of 56 patients (77%) coinfected with TTV and HCV and compared with 16 of 21 patients (76%) with HCV alone. Taken together, these results indicate that TTV frequently infects Italian hemophiliacs treated with plasma-derived factor VIII concentrates, both unmodified and virus-inactivated. Our results do not suggest a causal effect of TTV on chronic liver disease in these patients.

Prati D, Poli F, Farma E, Picone A, Porta E, De Mattei C, Zanella A, Scalamogna M, Gamba A, Gronda E, Faggian G, Livi U, Puricelli C, Viganò M, Sirchia G. · Centro Trasfusionale e di Immunologia dei Trapianti, IRCCS Ospedale Maggiore, Milano, Italy. · J Med Virol. · Pubmed #10335857 No free full text.

Abstract: Preliminary epidemiological and histological studies from Japan suggested that hepatitis C virus (HCV) infection has a role in the development of dilated cardiomyopathy (DCM). This multicenter study was conducted to verify this hypothesis on a large cohort of Italian patients with end-stage heart failure. Antibodies to HCV were determined in the 752 consecutive patients (608 males and 144 females; age, 53 +/- 13 years) who entered the waiting list for cardiac transplantation from 1995 to 1997 at the six cardiac surgery centers participating in the North Italy Transplant program. Three hundred and nine patients (41%) had dilated, 9 (1%) restrictive, and 4 (0.5%) hypertrophic cardiomyopathy; 284 patients (38%) had ischemic, 65 (9%) valvular, and 22 (3%) congenital heart disease; 5 patients (0.5%) had primary pulmonary hypertension; 54 patients (7%) had other or nonspecified heart disease. Overall, 41 of 752 patients (5.4%) resulted anti-HCV-reactive. Serological evidence of HCV infection was found in 12 of 309 patients with DCM (3.9%; 95% CI, 1.7-6.0), and in 29 of 443 without DCM (6.5%; 95% CI, 4.2-8.8), without statistical difference (difference of prevalence rate: 2.6%; 95% CI, -4.9 to 5.8). In conclusion, HCV does not seem to have a primary role in the pathogenesis of DCM. However, since our findings are in disagreement with those obtained in smaller series of patients of other ethnicity, large studies from different countries should be conducted.

Prati D, Lin YH, De Mattei C, Liu JK, Farma E, Ramaswamy L, Zanella A, Lee H, Rebulla P, Allain JP, Sirchia G, Chen B. · Centro Trasfusionale e di Immunologia dei Trapianti, Divisione di Ematologia, IRCCS Ospedale Maggiore, Milano, Italy. · Blood. · Pubmed #10029577 links to  free full text

Abstract: A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine-aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare-ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread.