HEPATITIS C VIRUS INFECTION MAY ALWAYS TERMINATE WITH CHRONIC MANIFESTATIONS OF IT IF LIFE SPAN OF THE HUMAN BEING WOULD BE ENOUGH

Yıl 2005, Sayı: 009, 187 - 194, 15.12.2005

M. Helvacı , H. Dayıoğlu M.C. Algın E. Coşar E. Soyücen

Öz

Background: It seems that hepatitis C virus (HCV) infection is more common in elderlies. Its outcome is probably influenced by status of immune system. We have tried to understand whether or not there is an increase in prevalence of HCV infection by aging and if so could it be explained by a time period, at least in some of infecteds, required for virus until onset of clinical manifestations.Patients and methods: Patients with anti-HCV positivity, never treated with interferon (INF), have been taken, randomly and prospectively. Additionally anti-HBs, HBsAg, routine hematologic and biochemical tests, alpha-fetoprotein, urinalysis, and abdominal ultrasonography have been performed in all cases. In anti-HCV positives, HCVRNA via polymerase chain reaction and in HBsAg positives, HBVDNA via molecular hybridization have been studied. Tissue samples and additional radiographic films, including computed tomography, have been obtained in required cases.Results: We have taken anti- HCV positive and never INF therapy taken 92 cases into study. Sixtysix of 92 patients have been positive for HCVRNA. Rates of HCVRNA positivity have been 14.28 % under the age of 40 years, 68.88 % between the ages of 40 and 59 years, and 85.00 % at and above the age of 60 years. Additionally, 19 cases of cirrhosis, four HBsAg positivity in the absence of HBVDNA positivity, five hepatocellular carcinoma, two membranoproliferative glomerulonephritis, one of which is together with rheumatoid arthritis and cirrhosis, two lichen planus, three asthma, one prolymphocytic leukemia together with cirrhosis, one idiopathic thrombocytopenic purpura, one bronchiectasis, one fibromyalgia, one monoclonalgammopathy of unknown significance (MGUS), and two cases of non-Hodgkin’s lymphoma have been detected in 92 cases with anti-HCV positivity. As a big difference, except two cases of asthma, one case of fibromyalgia, and one case of MGUS, all of the others have been detected in HCVRNA positive cases. Conclusion: As a result, prevalence of HCVRNA positivity increases by age and anti-HCV positive individuals should be followed-up during their life span for high risk of even delayed-onset hepatic and multisystemic manifestations.

Anahtar Kelimeler

Hepatitis C virus infection

HEPATITIS C VIRUS INFECTION MAY ALWAYS TERMINATE WITH CHRONIC MANIFESTATIONS OF IT IF LIFE SPAN OF THE HUMAN BEING WOULD BE ENOUGH

Öz

Hepatit C virüs (HCV) enfeksiyonu yaşlılarda daha sık gibi görünmektedir. Enfeksiyon sonucu muhtemelen immün sistem tarafından belirlenmektedir. Biz HCV enfeksiyonu prevalansının yaşla birlikte artış gösterip göstermediğini ve eğer gösteriyor ise bu sürenin, enfeksiyonun klinik bulgularının ortaya çıkması için gerekli bir sürenin varlığı ile izah edilip edilemeyeceğini anlamaya çalıştık. Çalışmaya gastroenteroloji polikliniğine herhangibir şikayetle başvuran, daha önce interferon (INF) tedavisi almamış, HCV antikor (anti-HCV) pozitif hastalar rastgele ve prospektif olarak alındı. Anti-HCV yanında tüm hastalardan hepatit B virüs yüzey antijeni ve antikoru (sırasıyla HBs Ag ve anti-HBs), alfa-fetoprotein, rutin hematolojik ve biyokimyasal testler ve idrar analizi istendi. Anti-HCV pozitif vakalarda polimeraz zincir reaksiyonu ile HCV RNA ve HBs Ag pozitif vakalarda moleküler hibridizasyon ile HBV DNA çalışıldı. Gereken vakalarda doku biyopsileri alındı ve bilgisayarlı tomografiyi de içeren ilave radiyografik görüntülemeler yapıldı. Toplam 92 anti- HCV pozitif, INF tedavisi almamış hasta çalışmaya alındı. Hastaların toplam 66’sında HCV RNA pozitifliği tespit edildi. HCV RNA pozitifliği oranı 40 yaş altında %14.28, 40-59 yaşları arasında %68.88 ve 60 yaş ve üzerinde %85 olarak tespit edildi. Ek olarak, toplam 19 siroz, beş hepatosellüler karsinom, dört HBs Ag taşıyıcılığı, birisi romatoid artrit ile birlikte sirozlu olmak üzere iki membranoproliferatif glomerulonefrit, iki liken planus, üç astım, bir siroz ile birlikte prolenfositik lösemi, bir idiyopatik trombositopenik purpura, bir bronşektazi, bir fibromyalji, bir önemi bilinmeyen monoklonal gammopati ve iki non-Hodgkin lenfoma vakası, toplam 92 anti-HCV pozitif birey arasında tespit edildi. Büyük bir fark olarak, iki astım, bir fibromyalji ve bir önemi bilinmeyen monoklonal gammopati vakası haricindeki tüm vakalar HCV RNA pozitif bireyler arasında tespit edildi. Sonuç olarak, HCV RNA pozitifliği yaşla birlikte artış göstermektedir ve anti-HCV pozitif bireyler, hayatları boyunca geç ortaya çıkabilen karaciğer ve multisistemik tutulum riski nedeniyle takip edilmelidirler.

Anahtar Kelimeler

Hepatit C virüs enfeksiyonu

Kaynakça

• [1] Gumber, S.C. and Chopra, S. (1995) Hepatitis C: a multifacted disease. Annals of Internal Medicine;123:615-620.
• [2] Agnello V. Mixed cryoglobulinemia and other extrahepatic manifestations of HCV infection. In: Liang TJ, Hoofnagle JH,editors.Hepatitis C. New York:Academic Press; 2000:295-315.
• [3] Anonymous - Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47:1-39.
• [4] Villano SA, Vlahov D, Nelson KE, et al. Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology 1999;29:908- 914.
• [5] Knodell, R.G.; Ishak, K.G.; Black, W.C. et al. - Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1: 431-435.
• [6] Fornasiere A, D’Amico G. Type II mixed cryoglobulinemia, hepatitis C infection, and glomerulonephritis. Nephrol Dial Transplant 1996;11:25-30.
• [7] Agnello V. Mixed cryoglobulinemia and other extrahepatic manifestations of HCV infection. In: Liang TJ, Hoofnagle JH,editors.Hepatitis C. New York:Academic Press;2000:295-315.
• [8] Cordonnier D, martin H, Groslambert P, Micouin C, Chenais F, Stoebner P. Mixed IgGIgM cryoglobulinemia with glomerulonephritis. Immunochemical, florescent, and ultrastructural study of kidney and in vitro cryoprecipitate. Am J Med 1975;59:867-872.
• [9] Stoebner P, Renversez JC, Groulde J, Vialtel P, Cordonnier D. Ultrastructural study of human IgG and IgG-IgM crystalcryoglobulins. Am J Clin Pathol 1979;71:404- 405.
• [10] Pucillo LP, Agnello V. Membranoproliferative glomerulonephritis associated with hepatitis B and C viral infections: from virus like particles in the cryoprecipitate to viral localization in paramesangial deposits, problematic investigations prone to artifacts. Curr Opin Nephrol Hypertens 1994;3:465- 470.
• [11] Arase Y, Ikeda K, Murashima N, Chayama K, Tsubota A, Koida I, et al. Glomerulonephritis in autopsy cases with hepatitis C virus infection. Intern Med 1998;37:836-840.
• [12] Agnello V. Mixed cryoglobulinaemia after hepatitis C virus: more and less ambiguity. Ann Rheum Dis 1998;57:701-702.
• [13] Lunel F, Musset L. Mixed cryoglobulinemia and hepatitis C virus infection. Minerva Med 2001;92:35-42.
• [14] Kayali Z, Buckwold VE, Zimmerman B, Schmidt WN. Hepatitis C, cryoglobulinemia, and cirrhosis: a meta-analysis. Hepatology 2002;36:978- 985.
• [15] Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, et al. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology 1994;106:1291-1300.
• [16] Gorevic PD, Frangione B. Mixed cryoglobulinemia cross-reactive idiotypes: implications for the relationship of MC to rheumatic and lymphoproliferative diseases. Semin Hematol 1991;28:79-94.
• [17] Invernizzi F, Galli M, Serino G, Monti G, Meroni LP, Granatieri C. Secondary and essential cryoglobulinemias. Frequency, nosological classification, and long-term follow-up. Acta Haematol 1983;70:73-82.
• [18] Silvestri F, Pipan C, Barillari G, Zaja F, Fanin R, Infanti L, et al. Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders. Blood 1996;87:4296-4301.
• [19] Kuniyoshi M, Nakamuta M, Sakai H, Enjoji M, Kinukawa N, Kotoh K, et al. Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin’s lymphoma. J Gastroenterol Hepatol 2001;16:215-219.
• [20] Zuckerman E, Zuckerman T, Levine AM, Douer D, Gutekunst K, Mizokami M, et al. Hepatitis C virus infection in patients with B-cell non-Hodgkin’s lymphoma. Ann Intern Med 1997;127:423-428.
• [21] Luppi M, Longo G, Ferrari MG, Barozzi P, Marasca R, Morselli M, et al. Clinicopathological characterization of hepatitis C virus-related B-cell non- Hodgkin’s lymphomas without symptomatic cryoglobulinemia. Ann Oncol 1998;9:495-498
• [22] Ohsawa M, Shingu N, Miwa H, Yoshihara H, Kubo M, Tsukama H, et al. Risk of non-Hodgkin’s lymphoma in patients with hepatitis C virus infection. Int J Cancer 1999;80:237-239.
• [23] Brind AM, Watson JP, Burt A, Kestevan P, Wallis J, Proctor SJ, et al. Non- Hodgkin’s lymphoma and hepatitis C virus infection. Leuk Lymphoma 1996;21:127-130.
• [24] Ray RB, Lagging LM, Meyer K, Ray R. Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype. J Virol 1996;70:4438-4443.
• [25] Machida K, Shimodaira S, Sung VM, Cheng K, Lindsay KL, Levine AM, et al. Hepatitis C virus is a potent mutator: enhanced hypermutation of immunoglobulin and oncogenes in HCV-infection (abstr). 9th International Meeting on HCV and Related Viruses. San Diego, CA. July 2002;p 196.
• [26] Hermine O, Lefrere F, Bronowicki JP, Mariette X, Jondeau K, Eclache- Saudreau V, et al. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002;347:89-94.
• [27] Pilli M, Penna A, Zerbini A, Vescovi P, Manfredi M, Negro F, et al. Oral lichen planus pathogenesis: a role for the HCV-specific cellular immune response. Hepatology 2002;36:1446-1452.
• [28] Bonkovsky HL, Poh-Fitzpatrick M, Pimstone N, Obando J, DiBisceglie A, Tattrie C, et al. Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America. Hepatology 1998;27:1661-1669.
• [29] Moran MJ, Fontanellas A, Brudieux E, Hombrados I, De Ledinghen V, Couzigou P, et al. Hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients: the influence of virus C infection. Hepatology 1998;27:584-589.
• [30] Mateescu RB, Rimbas M, Voiosu R. The immunopathogenesis of viral hepatitis. Rom J Intern Med. 2004;42(1):59-67.
• [31] Steel CM, Ludlam CA, Beatson D, et al. HLA haplotype A1 B8 DR3 as a risk factor for HIV-related disease. Lancet 1988;1:1185-1188.
• [32] Abbas AK, Lichtman AH, Poker JS. Cellular and molecular immunology. 3. ed. Philadelphia, W.B. Saunders, 1997.
• [33] Ahn SH, Han KH, Park JY, et al. Association between hepatitis B virus infection and HLA-DR type in Korea. Hepatology 2000;31:1371–1373.
• [34] Aikawa, T, Kojima M, Onishi H, et al. HLA DRB1 and DQB1 alleles and haplotypes influencing the progression of hepatitis C. J Med Virol 1996;49: 274-278.
• [35] Almarri A, Batchelor JR. HLA and hepatitis B infection. Lancet 1994;344:1194-1195.
• [36] Alric L, Fort M, Izopet J, et al. Genes of the major histocompatibility complex II influence the outcome of hepatitis C virus infection. Gastroenterology 1997;113:1675- 1681.