A Clinical, Epidemiological, Laboratorial, Histological And Ultrasonographical Evaluation Of Anti-hcv Eia-2 Positive Blood Donors

Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3) detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6% were repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history, with only 2% mentioning previous jaundice. In 47% of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8%). Blood transfusion was the second factor for HCV transmission (27.2%). Hepatomegaly was detected in 54% of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65% of the subjects, being the steatosis the most frequent (50%). In 83.5% of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89%) with mild or moderate grade in most of the cases (99.5%). The histopathological exam of the liver was normal in 1.5% of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82% of the RIBA-2 positive subjects, in 37.5% of the indeterminate RIBA-2 donors and in 9% of the negative RIBA-2 donors. Chronic hepatitis has also been observed in 50% of the histopathologieal exams of the anti-HCV EIA-2 reagent donors which were, indeterminate RIBA-2. Among 18 blood donors with minimal changes histopathological exam 11 (61%) were HCV-RNA positive. Our blood donors anti-HCV reagent generally had clinical, laboratorial and histopathological features observed in patients with chronic HCV hepatitis and a high proportion could be identified in interviews and medical evaluation realized in blood blanks. Generally, these HCV infected donors are identified and discharged only by the serological tests results.423147152Alter, H.J., To C or not to C: These are the questions (1995) Blood, 85, pp. 1631-1695Alter, H.J., Conry-Cantilena, C., Melpolder, J., Hepatitis C in asymptomatic blood donors (1997) Hepatology, 26 (1 SUPPL.), pp. 29S-33SAlter, H.J., Purcell, R.H., Shih, J.W., Detection of antibodies to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis (1989) New Engl. J. Med., 321, pp. 1494-1500Alter, H.J., Tegtmeier, G., Jett, B., The use of a recombinant immunoblot assay in the interpretation of anti-hepatitis C virus reactivity among prospectively followed patients, implicated donors, and random donors (1991) Transfusion, 31, pp. 771-776Alter, M.J., Epidemiology of hepatitis C in the West (1995) Semin. 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Med., 323, pp. 1107-1112Garcia-Samaniego, J., Enriquez, A., Soriano, V., Third-generation recombinant immunoblot assay to confirm hepatitis C virus-indeterminate serological samples (1993) Vox Sang., 64, pp. 191-192. , BaselHoofnagle, J.H., Hepatitis C: The clinical spectrum of disease (1997) Hepatology, 26 (1 SUPPL.), pp. 15S-20SKleinman, S., Alter, H., Busch, M., Increased detection of hepatitis C virus (HCV)-infected blood donors by a multiple-antigen HCV enzyme immunoassay (1992) Transfusion, 32, pp. 805-813Kuo, G., Choo, Q.L., Alter, H.J., An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis (1989) Science, 244, pp. 362-364Lok, A.S.F., Gunaratnam, N.T., Diagnosis of hepatitis C (1997) Hepatology, 26 (1 SUPPL.), pp. 48S-56SPrati, D., Capelli, C., Zanella, A., Influence of different hepatitis C virus genotypes on the course of asymptomatic hepatitis C virus infection (1996) Gastroenterology, 100, pp. 178-183Prieto, M., Olaso, V., Verdu, C., Does the healthy hepatitis C virus carrier state really exist? 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Comparative Study Of Patients With Chronic Hepatitis C Virus Infection Due To Genotypes 1 And 3 Referred For Treatment In Southeast Brazil

Background: The progression of liver disease in patients with chronic hepatitis C virus (HCV) infection is influenced by host and viral factors. Distinct clinical outcomes in patients infected with different HCV genotypes have been described in the literatute. However, the association between specific HCV genotype and clinical outcome remains unclear. We set out to study the natural history of HCV genotype 1 and 3 infections in Campinas, São Paulo state, Brazil, focusing on epidemiological, clinical, biochemical, and histological characteristics. Methods: Patients with HCV infection referred for treatment between January 2003 and December 2006 were included in this study. We collected epidemiological, clinical, and laboratorial data using standard forms. Results: A total of 283 patients were included; genotype 1 was idenfied in 163 (57.6%) patients, genotype 3 in 112 (39.6%), genotype 2 in 7 (2.5%), and genotype 4 in 1 (0.35%). Patients with genotype 2 and 4 were excluded from analysis. Multivariate analysis showed that intravenous energetic drug, positive cryoglobulin, and cirrhosis were independently and significantly associated with HCV genotype 3 (p < 0.05). Conclusion: Genotype 3 currently seems to be associated with intravenous energetic drug, high frequency of cryoglobulinemia, and advanced liver disease in our region. Understanding the distribution of the different HCV genotypes can elucidate transmission of HCV and support optimal prevention strategies. © 2008 Vigani et al; licensee BioMed Central Ltd.8Armstrong, G.L., Alter, M.J., McQuillan, G.M., The past incidence of hepatitis C virus infection: Implications for the future burden of chronic liver disease in the United States (2000) Hepatology, 31, pp. 777-782. , 10.1002/hep.510310332 10706572Consensus Statement (1999) J Hepatol, 30, pp. 956-961. , EASL International Consensus Conference on Hepatitis C 10.1016/ S0168-8278(99)80154-8 10365827Treatment of hepatitis C. Guidelines (2002) Gastroenterol Clin Biol, 26, pp. B312-B320. , Consensus ConferenceCodes, L., Freitas, L.A.R., Santos-Jesus, R., Comparative study of Hepatitis C virus genotypes 1 and 3 in Salvador, Bahia (2003) Braz J Infect Dis, 7, pp. 409-417. , 10.1590/S1413-86702003000600009 14636481Silva, G.F., Nishimura, N.F., Coelho, K.I.R., Soares, E.C., Grading and staging chronic hepatitis C and its relation to genotypes and epidemiological factors in Brazilian blood donors (2005) Braz J Infect Dis, 9, pp. 142-149. , 16127590Alberti, A., Chemello, L., Bevebnú, L., Natural history of hepatitis C (1999) J Hepatol, 31, pp. 17-24. , 10.1016/S0168-8278(99)80369-9 10622555Poynard, T., Bedossa, P., Opolon, P., Natural history of liver fibrosis progression in patients with chronic hepatitis C (1997) The Lancet, 349, pp. 825-832. , 10.1016/S0140-6736(96)07642-8Simmonds, P., Viral heterogeneity of the hepatitis C virus (1999) J Hepatol, 31 (SUPPL. 1), pp. 54-60. , 10.1016/S0168-8278(99)80375-4 10622561Zein, N.N., Rakela, J., Krawitt, E.L., Hepatitis C virus genotypes in the United States: Epidemiology, pathogenicity, and response to interferon therapy (1996) Ann Intern Med, 125, pp. 634-639. , 8849147McOmish, F., Yap, P.L., Dow, B.C., Geographical distribution of hepatitis C virus genotypes in blood donors: An international collaborative survey (1994) J Clin Microbiol, 32, pp. 884-892. , 263157 7913097Zein, N.N., Clinical significance of hepatitis C genotypes (2000) Clin Microbiol Rev, 13, pp. 223-235. , 100152 10755999 10.1128/CMR.13.2.223-235.2000Bedossa, P., Poynard, T., An algorithm for the grading of activity in chronic hepatitis C (1996) Hepatology, 24, pp. 289-293. , The METAVIR cooperative study group 10.1002/hep.510240201 8690394Simmonds, P., Genetic diversity and evolution of hepatitis C virus - 15 years on (2004) J Gen Virol, 85, pp. 3173-3188. , 10.1099/vir.0.80401-0 15483230Campiotto, S., Pinho, J.R.R., Carrilho, F.L., Geographic distribution of hepatitis C virus genotypes in Brazil (2005) Braz J Med Biol Res, 38, pp. 41-49. , 10.1590/S0100-879X2005000100007 15665987Pawlotsky, J.M., Tsakiris, L., Roudot-Thoraval, E., Relationship between hepatitis C virus genotypes and sources of infection in patients with chronic hepatitis C (1995) J Infect Dis, 171, pp. 1607-1610. , 7769300Liakina, V., Speiciene, D., Irnius, A., Prevalence of cryoglobulinemia in patients with chronic HCV infection (2002) Med Sci Monit, 8 (1), pp. CR31-CR36. , 11782678Frangeul, L., Musset, L., Cresta, P., Hepatitis C virus genotypes and subtypes in patients with hepatitis C, with and without cryoglobulinemia (1996) J Hepatol, 25, pp. 427-432. , 10.1016/S0168-8278(96)80200-5 8912140Willems, M., Sheng, L., Roskams, T., Hepatitis C virus and its genotypes in patients suffering from chronic hepatitis C with or without a cryoglobulinemia-related syndrome (1994) J Med Virol, 44, pp. 266-271. , 10.1002/jmv.1890440310 7531756Zehender, G., De Maddalena, C., Bernini, F., Compartmentalization of hepatitis C virus quasispecies in blood mononuclear cells of patients with mixed cryoglobulinemic syndrome (2005) J Virol, 79, pp. 9145-9156. , 1168762 15994809 10.1128/JVI.79.14.9145-9156.2005Parise, E.R., de Oliveira, A.C., Ferraz, M.L., Cryoglobulinemia in chronic hepatitis C: Clinical aspects and response to treatment with interferon alpha and ribavirin (2007) Rev Inst Med Trop S Paulo, 49, pp. 67-72. , 10.1590/S0036-46652007000200001 17505661Silini, E., Bottelli, R., Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: A case control study (1996) Gastroenterology, 111 (1), pp. 1999-2005. , 10.1053/gast.1996.v111.pm8698200Zeuzem, S., Franke, A., Lee, J.H., Phylogenetic analysis of hepatitis C virus isolates and their correlation to viremia, liver function tests, and histology (1996) Hepatology, 24, pp. 1003-1009. , 10.1002/hep.510240505 8903367Manns, M.P., McHutchison, J.G., Gordon, S.C., Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial (2001) Lancet, 358, pp. 958-965. , 10.1016/S0140-6736(01)06102-5 11583749Fried, M.W., Shiffman, M.L., Reddy, K.R., Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection (2002) N Engl J Med, 26 (347), pp. 975-982. , 10.1056/NEJMoa02004

Elevated Alanine Aminotransferase (alt) In Blood Donors : An Assessment Of The Main Associated Conditions And Its Relationship To The Development Of Hepatitis C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/ 101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.404219224Aach, R.D., Szmuness, W., Mosley, J.W., Serum alanine aminotransferase of donors in relation to the risk of non-A, non-B hepatitis in recipients (1981) New Engl. J. Med., 304, pp. 989-994Alter, H.J., Purcell, R.H., Holland, P.V., Alling, D.W., Koziol, D.E., Donors transaminase and recipient hepatitis. Impact on blood transfusion services (1981) J. Amer. Med. Ass., 246, pp. 630-634Alter, H.J., The cloning and clinical implications of HGV and HGBV-C (1996) New Engl. J. Med., 334, pp. 1536-1537Alter, H.J., Transfusion transmitted hepatitis C and non-A, non-B, non-C (1994) Vox Sang. 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(Wash.), 92, pp. 3401-3405Vanderborght, B.O., Reis, A.M., Rouzere, C.D., Prevalence of anti-hepatitis C virus in the blood donor population of Rio de Janeiro (1993) Vox Sang. (Basel), 65, pp. 122-12

Kinetics Of Hepatitis C Virus Load And Hemodialysis: Is There Any Influence Of The Reuse Of Dialysis Membrane On Hcv Viremia?

Background: Patients with chronic kidney disease (CKD) on regular hemodialysis are at increased risk of acquiring hepatitis C virus (HCV). Although controversial, a distinct dynamic of the HCV load has been reported in this group a lower HCV viremia compared to non-uremic patients. The reasons for this remain unclear, but the host immune response related to the hemodialysis procedure and the reuse of dialysis membranes are the most investigated factors. Methods: We analyzed the kinetics of HCV RNA viremia in 21 hemodialysis patients infected with genotype 1, through a highly sensitive quantitative method (real-time polymerase chain reaction), immediately before and at the end of the first use and the last reuse of the cellulose diacetate dialysis membrane. Results: Initial HCV load did not correlate with demographic or biochemical parameters, but higher HCV viremia was associated with a longer time on hemodialysis (r = 0.44, p = 0.04). Although not significant, HCV RNA decreased in 11/21 (52.3%) patients after the first dialysis session (median 279,000 vs 176,000 IU/ml, p = 0.91). However, a significant increase in HCV RNA viremia was observed in 17/21 (80.9%) patients after the tenth session (median 187,000 vs 342,000 IU/ml, p = 0.009). Conclusions: Except for the first session of hemodialysis, we did not confirm a decrease in HCV viremia related to the time on hemodialysis or with the reuse of the dialysis membrane. 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