História natural da hepatite crónica pelo vírus da hepatite B

Autores

  • J. Areias Professor Auxiliar de Medicina Interna do Instituto de Ci­ências Biomédicas de Abel Salazar da Universidade do Por­to; Assistente estrangeiro de Hepatologia dos Hospitais de Paris; Assistente Hospitalar Graduado de Gastrenterologia do Hospital Geral de Santo António

Palavras-chave:

vírus da hepatite B, hepatite cró­nica B, história natural

Resumo

As lesões hepáticas de hepatite crónica podem ser da responsabilidade do vírus da hepatite B (VHB).

A prevalência da infecção pelo VHB varia larga­ mente através do mundo, desde áreas altamente en­démicas na maior parte dos países em vias de de­ senvolvimento, até áreas de baixa endemicidade nos países desenvolvidos. A nível mundia calculam-se em mais de 300 milhões as pessoas cronicamente infec­tadas com o VHB. A hepatite crónica pelo VHB conti­tui causa importante de morte, quer por cirrose, quer por carcinoma hepatocelular.

O objectivo deste trabalho consistiu na revisão da epidemiologia, história natural e prognósti­co da hepatite crónica pelo VHB.

Downloads

Não há dados estatísticos.

Referências

Hoofnagle JH. Alter HJ. Chronic viral hepatitis. ln: Vyas GN. Diienstag JL. Hoofnagle JH. eds. Viral hepatitis and Liver disease. New York: Grune & Straton 198 : 97-113.

Mavnard JE. Kane MA. Hadler SC. Global control of hepatitis 1 through vaccination: role of hepatitis B vaccine in the Expan­ded Programme on lmmunization. Rev lnfect Dis 1989:11( Su­ppl. 3): 574-578.

Tandon BN, Acharva SK. Viral diseases involving the liver. Bailliére's Clinical Gastroenterology 1987: 1 :211-230.

Rizzetto M. Hepatitis Delta: the virus and the disease. J Hepatol 1990:11: S145-S148.

Margolis HS. Alter MJ. Hadler SC. Hepatitis B: evolving epidemiolo­gy and implications for control. Sem Liver Dis 1991: 11: 84-92.

Lecour H. Hepatite vírica. Epidemiologia e diagnóstico. Disserta­ção de Doutoramento. Faculdade de Medicina da Universi­dade do Porto. 1983.

Blumherg B. Alter H. Visnich S. A new antigen in leukemia sera. JAMA. 1965: 191: 541-546.

Elfassi E. füoad specificiry of the heparitis B enhancer function. Virology 1987: 160. 259-262

Miller RH. Comparative molecular biology of the hepatitis viru­ses. Sem Liv Dis 1991: 11: 113-120.

Robinson WS. Marion P. Feitelson M. et al. The hepadnavirus group: hepatitis B and relatted virus. ln: Szmuness W, Alter Hj, Maynard JF. eds. Viral hepatitis 1981 ( lnt Symp. ). Philadelphia: Franklin Institute Press. 1982. 57-68

Zarski JP. Thelu MA. Rachail M et al. Biologie Moleculaire du virus de l'hepatite B: Premiére partie: sctruture, organisation génétique, replication, transcruption. Gastroenterol Clin Biol. 1991: 15: 489-496

Freiman JS. Jilbert AR. Dixon RJ. et al. Experimental Duck hepatitis B infection: pathology and evolution of hepatic and extra hepatic infection. Hepatology. 1988: 8: 507-513

Korba B. Cole PJ. Gerin JL. Mitogen-induced replication of wodehuck ­hepatitis virus in cultured peripheral blood lvmphocytes: Science 1988. 241: 1213-1216

lmazeki F. Yagmuma K. Omata M. et al. integrated structures of duck hepatitis B virus DNA in hepatocelular carcinoma. J Virol. 1988. 62. 861-862

Korba B. Wells F. Tennent BC. et al. Hepadnavirus infection of periferal blood lymphocites in vivo: woodchuck and chimpanzee models of viral hepatitis. J Virol 1986: 58: 1-8

Chang MH. Chen PJ. Chen JY. et al. Hepatitis B Virus integration in hepatitis B virus - related hepatocellular carcinoma in chil­dhood. Hepatology 1991: 13: 316-320

Hsu HC. Wu MZ. Chang MH. et al. Childhood hepatocellular carcinoma develops exclusively in hepatitis B surface anti­gen carriers in 3 decades in Taiwan - report of 51 cases stron­gly associated with rapid development of liver cirrhosis. J Hepatol. 1987: 5: 260-267

Kaklamanie E. Trichopoulos D. Tzonou A. et al: Hepatitis B and C viruses and their interaction in the origin of hepatocellular carcinoma. JAMA 1991: 265. 1974-1976.

Kalayci C. Johnson PJ. Da Viesse. et al. Hepatitis B virus related hepatocellular carcinoma in the non-cirrotic liver. J Hepatol 1991;12: 54-59.

Kew MC. Macerollo P. Effect of age on the etiologic role of the hepatitis B virus in hepatocellular carcinoma in blacks. Gastroenterology 1988: 94: 439-442.

Lai MY. Chen PJ. Yang PM, et al. ldentification and characteriza­tion of intrahepatic hepatitis B virus DNA in HBsAg-sero-ne­gative patients with chronic liver disease and hepatocellular carcinoma in Taiwan. Hepatology. 1990:12: 575-581

Lok ASF, Ma OCK. Hepatitis B virus replication in chinese pati­ents with hepatocellular carcinoma. Hepatolog.y 1990: 12: 582-588.

Marcellin P, Thiers V. Degott C. et al. Hepatocelular carcinoma with normal adjacent liver. Hepatitis B virus DNA status. J Hepatol 1989: 8: 249-253

Oka H, Kurioka N. Kim K, et al. Prospective study of early detection of hepatocellular carcinoma in patients with cirrhosis. Hepatology 1990: 12: 680-687.

Popper H. Viral versus chemical hepatocarcinogenesis. J Hepatol 1988: 6: 229-238.

Summers J. O´'connell A. Millman I. Genome of hepatitis B virus: restriction enzyme cleavage and structure of DNA extracted from Dane particles. Proc Nati Sci USA. 1975: 72: 4597-4601

Charmay P. Pourcel C. Louise A. et al. Cloning in Escherichia coli and physical structures of Hepatitis B viron DNA. Proc Nati Sci USA. 1975: 72: 4597-4601

Miller RH. Kaneko S. Chung CT. et al. Compatct organization of the Hepatitis B virus genome. Hepatology 1989: 9: 322-327

Courouce-Pauty AM. Pancon A. Soulier JP. Distribution of hbsag subtype in the world. Vox Sang 1983. 44: 197: 211

Thomas HC. The hepatitis B virus and the host response. J Hepatol 1990: 11 (Suppl 1): S83-S89.

Thung SN. Gerber MA. Poly albumin receptors: their role in the attatchment of hepatitis B virus to hepatocities. Semin liver dis. 1984: 4

:69-75

Thung SN. Gerber MA. Albumin hbinding sites sites on human hepatocytes. Liver 1983: 3: 290-294 .

Gerber MA. Thung SN. The pre-s2 region of Hepatitis B virus: more questions than answers. Hepatologv. 1989: 9: 328-330

Brahm J. Alexander GJM. Fagan FA. et al. Clearance of pre-s2 antigen: a marker of successful interferon therapy in Hepatitis B vírus infection. J Med Virol. 1988: 24: 453-460

Benhamou JP. Erlinger S. ln Maladies du Foie et des voues biliaires. 1986. Flammarion. Paris.

lnternational Working Party. Terminology of chronic hepatitis hepatic allograft rejection. and nodular lesions of the liver: summary of rccommendations developed by an lnternational Working Partv. supported bv the World Congress of Gastro­enterology. Los Angeles. 1994. Am J Gastroenterol. 1994: 89: S177-S181.

Scheuer PJ The nomenclature of chronic hepatitis: time for a change.J Hepatol 1995: 22:112-114.

Bomino F. Hoyer B. Nelson J et al. Hepatitis B virus DNA in the sera of HBs Ag carriers marker of active hepatitis B vírus replication in the liver. Hepatology 1981:1: 386-391.

Hsu H-C. Su IJ. Lai MY. et al. Biologic and prognostic signifi­cance of hepatocyte hepatitis B core antigen expressions in the natural course of chronic hepatitis B virus infection. J Hepatol 1987: 5: 45-50

Bodsworth NJ. Cooper DA. Donovan B. The influence of human immunodeficiency virus type 1 infection on the develo­pment of the hepatitis B virus carrier state. J lnfect Dis 1991: 163: 1138-1140

McQuillan GM. Thousand TR. Fields HA et al. Seroepidemiolo­gy of hepatitis B virus infection in the United States 1976 to 1980. Am J Med 1989: 87: Suppl 3A: 5S-IOs

Bomino F. Rosina F. Rizzetto M et al. Chronic hepatitis in HBs Ag carriers with serum HBV DNA and anti-HBe. Gastroenterology 1986: 90:1268-1273

Hadziyannis S, Bramou T. Makris A et al. lnterferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B. J Hepatol .1990:11 (Suppl. 1): S133- SU6.

Liaw YF. Sheen IS. Chen TJ et al. lncidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology l991: 13: 627-631

Moestrup T, Hansson BG. Widell A et al. Long-terme follow-up of chronic hepatitis B virus infection in intravenous drug abu­sers and homosexual men. BMJ 1986: 292: 854-857.

Chu CM. Shyu WC. Kuo RW et al. HLA class I antigen display on hepatocyte membrane in chronic hepatitis B virus infection: its role in the pathogenesis of chronic type B hepatitis. Hepa­tology 1987: 7: 1131-1136.

Ferns R. Tedder RS. Human and monoclonal antibodies to he­patitis B core antigen recognize a single immunodominant epitope. J Med Virol 1986;19:193-196.

Kojima T. Bloemen J, Desmet VJ. lmmune electron microscopic demonstration of hepatitis B core antigen (H13cAg) in liver cell plasma membranes. Liver 1987; 7:191-200.

Moller B, Hopf C. Stemcrowicz R et al. HBcAg expressed on the surface of circulating Dane particles in patients with hepatitis B virus infection without evidence of anti-HBc formation. Hepatology 1989:10: l 79-185.

Ramalho F. Rrunetto MR. Rocca G et al. Scrum markers of hepa­titis B vírus replication. liver histology and intrahepatic ex­pression of hepatitis B core antigen. J Hepatol 1988: 7:14-20.

Bortolotti F. Cadrobhi P. Crivellaro C et al. Long-terme out come of chronic type B hepatitis in patients who acquire hepatits B virus infection in childhood. Gastroenterology 1990; 99: 805-810.

Chu CM. Karayiannis P, Fowler MJF et al. Natural history of chro­nic hepatitis B virus infection in Taiwan: studies of hepatitis B virus DNA in serum. Hepatology 1985; 5: 431-434.

Davis GL. Hoofnagle JH. Reactivation of chronic type B hepatitis presenting as acute viral hepatitis. Ann lnt Med 1985;102: 762-765.

Dragosics B, Ferenci P, Hitchma E et al. Long-terme follow-up study of asymptomatic HBsAg- positive voluntary blood do­nors in Austria: a clinical and histologic evaluation of 242 ca­ses. Hepatology 1987; 7: 302-306.

Krogsgaard K. Aldershvile J. Kryger P et al. Reactivation of viral replication in anti-HBe positive chronic HBsAg carriers. Liver 1990:10: 54-58.

Krogsgaard K, Aldershvile J et al. Hepatitis B virus DNA. HIJe Ag and Delta infection during the course from acute to chronic hepatitis B virus infection. Hepatology 1985: 5: 778-782.

Lindh G. Weiland O, Glaumann H. The application of a numeri­cal scoring system for evaluating the histological outcome in patients with chronic hepatitis B followed in long term. He­patology 1988: 8:98-103

Viola LA. Barrinson IG, Coleman JC et al. Natural history of liver disease in chronic hepatitis B surface antigen carriers. Lancet 1981: 1: 1156-1159

Degos F. Marcellin P, Benhamou JP. Traitement de l'hépatite chro­nique active due à l'infection parle virus de l'hépatite B. Gas­troenterol Clin Biol 1988:12: 845-854.

Van Ditzhuijsent JM. Yap SH. Clinical aspects of hepatitis B Virus DNA detection. Scand J Gastroenterol 1989:24 (Suppll 71 ): '67-68.

Areias J. Prevenção da infecção vírica B e B-D do enxerto pela terapêutica com inteferão recombinante alfa antes da trans­plantação hepática. Dissertação de Doutoramento. lnstituto de Ciências Biomédicas Abel Salazar. Universidade do Porto. Porto, 1993

Knodell RG, lshak KG, Black WC et al. Formulation anel applica­tion of a numerical score system for assessing histological ac­tivity in asymptomatic chronic active hepatitis. Hepatolo­gy 1981;1: 431-435

Bartolomé J. Moraleda G. Molina J et al. Hepatitis B vírus DNA in liver and peripheral blood mononuclear cells during reducti­on in virus replication. Gastroenterology 1990: 99: 1745-1750

Fattovich G, Brollo L Alherti A et al. Long-term follow-up of anti-HBe positive chronic active hepatitis B. Hepatology 1988: 8:1651-1654.

Velosa J, Marinho R, Gouveia A et al. Factores de risco para o carcinoma hepatocelular em doentes com cirrose hepática. GE - Jornal Português de Gastrenterologia 1994;1: 1-10

Areias J, Marcellin P, Benhamou JP. Reactivaçào de hepatite B num doente anti-HBs positivo no decurso ele uma infecção pelo HIV. Arquivos ele Medicina 1991: 5(2):133-134.

Bianchi L, Gudat F. Chronic Hepatitis. ln: MacSween RMM. An­thony PP, Sheuer PJ. Portman B, Burt AD, eds. Pathology of the Liver, 3rd edit. Edimburgh: Churchill Livingstone. 1995

Levy P, Marcellin P. Maltino T, Peignoux M et al. Clinical course of spontaneous reactivation of hepatitis B virus infection in patients with chronic hepatitis B. Hepatology 1990: 12: 570-574.

Tong MJ, Sampliner RE. Govindarajan S et al. Spontaneous reac­tivation of hepatitis B in chinese patients with Hl3sAg-positi­ve chronic active hepatitis. Hepatology 1987; 7: 713-718.

Castillo 1, Bartolomé J, Quiroga JA et al. Detection of HBeAg; anti-Hl3e immune complexes in the reactivation of hepatitis B virus replication among anti-HBe chronic carriers. Liver 1990;10: 79-84.

Hess G, Gerken G, Weber C et al. Reactivation of chronic type B hepatitis: the effect on expression of serum HBV-DNA and pre-S encocled proteins.. J Med Virol 1988; 25:197-204.

Marcellin P. Cirrhoses post-hépatitiques virales 13, 13D et C. Rev Prat (Paris) 1991; 41(13):1149-1155.

13as C, Bartolomé J, LA 13anda F et ai. Assessment of hepatitis B virus DNA levels in chronic HBsAg carriers with or without

hepatitis delta virus superinfection. J Hepatol 1988: 6: 208-21).

Monjardino J. Velosa J. Thomas HC et ai. Scrum HBV DNA detec­ted by PCR in dot blot negative HBV chronic carriers with active liver disease. Hepatol 1991: 13: -14-48.

Scotto J Hadchouel M. Hery C et al. Detection of hepatitis B virus DNA in serum by a single spot hybridization technique: comparison with results for other viral markers. Hepatology 1983: 3: 279-284.

Akahane Y, Yamanaka T Suzuki H et al. Chronic active hepatitis with hepatitis B virus DNA and antibody against e antigen in the serum. Disturhed synthesis and secretion of e antigen from hepatocytes duo to a point mutation in the precore region. Gastroenterology 1990: 99: 1113-1119.

Kulms MC. .Monitoring hepatitis B virus replication. J Hepatol 1990: 11 ( Suppl. 1) S90-S94

Liehcrman HM. La Brecque DR. Kew MC et al. Detection of he­patitis B virus DNA directly in human serum by a simplifi­ed molecular hybridization test: comparison to HBe Ag/anti­ HBc status in HBs Ag carriers. Hepatology l983: 3 285-291.

Matsuyama Y. Omata M. Yokosuka O et al. Discordance of hepa­titis B e antigen. antibody and hepatitis B virus deoxyribonu­cleic acid in serum. Gastroentcrology 1985: 89: 110-1.

Walter F. Blum HE. Offensberger WB et al. Spot-blot hybridizati­on assay for the detection of hepatitis B virus DNA in scrum: factors determining its sensibility and specificity. Hepatology 1987: 7: 557-562

Chu C-M. Liaw Y-F. Intrahepatic expressiun of HBcAg in chro­nic HBV hepatitis: lessons from molecular biology. Hepato­logy 1990:12:1443-1445

Govindarajan S. Fong TL. Valinluck B et al. Markers of viral repli­cition in patients with chronic hepatitis B infection. Am J Clin Pathol 1988: 89: 233-237.

Hsu H-C. Lai MY. Su IJ et al. Correlation of hepatocyte HBsAg expression with vírus replication and liver pathology. Hepa­tology 1988: 8: 749-754.

Hsu HC. Lin YH. Chang MH et al. Pathology of chronic hepatitis B virus infection in children: with special reference to the in­tra-hepatic expression of hepatitis B vírus antigens . Hepato­logy 1988: 8: 378-382

Weller I. Fowler M. Monjardino J et al. The detection of HBV DNA in serum by molecular hybridization: a more sensitive method for the detection of complete HRV particles. .J Med Virol 1982: 9: 273-280.

Paz MOA. Brennes F. Karayiannis P.et al. Chronic hepatitis B vírus infection. Viral replication and patterns of inflammatory activity: serological. clinical and histological correlation. J Hepatol 1986: 3: 371-377.

Karayiannis P. Fowler MJF. Lok SF et al. Detection of serum HBV­ DNA by molecular hybridization. Correlation with HB e Ag/ anti-HBe status. racial origin. liver histology and hepatocellu­lar carcinoma. J Hepatol 1985:1: 99-106.

Krogsgaard K. Wantzin P, Aldershville J. Kryger P et al. Hepatitis B DNA in hepatitis B surface antigen positive blood donors. Relation to hepatitis B r system and outcome in recipients. J lnfect Dis 1986; 153: 298-303.

Bonino F. Rizetto M. Will H. Hepatitis B virus unable to secrete e antigen. Gastroenterology 1991:100:1158-1141.

Fattovich G. Farei P, Brollo L et al. Anti-HBe and HBV DNA posi­tive chronic hepatitis B. Response to interferem therapy. J Hepatol 1989: 9: 529 (Abstr. ).

Takeda K. Akahane Y. Suzuki H et al. Defects in the precore region of the HBV genome in patients with chronic hepatitis B after sustained seroconversion from HBeAg to anti-HBe in­duced spontaneously or with interferon therapy. Hepatology 1990: 12:1284-1289

Negro F. Chiaherge E. Oliviero S. Hepatitis B vírus DNA ( HBV DNA) in anti-HBe positive sera. Liver 1984: 4: 177-183.

Brunetto MR. Stemler M. Bonino F et al. A new hepatitis B vírus stram in patients with severe anti-HBe positive chronic hepa­titis B. J Hepatol 1990:10 258-260

Carman WF. Hadziyannis S. .McGaney MJ et al. Mutation pre­venting formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet 1989: 2: 588-591

Tanaka Y. Esumi M. Shikata T. Persistence of hepatitis B Virus DNA after serological clearance of hepatitis B virus. Liver 1990: 10: 6-10.

Brechot C. Degos F. Lugassy C et al. Hepatitis B virus DNA in patients with chronic discase and negative tests for hepatitis B surface antigen. N Engl J Med 1985: 3: 270-276.

Brechot C, Hadchouel M, Scotto J et al. Detection of hepatitis B vírus DNA in liver and scrum: a direct appraisal of the chro­nic carrier state. Lancet 1981:1: 765-768.

Hoofnagle JH. Alpha interferon therapy of chronic hepatitis B. Current status and recommendations. J Hepatol 1990: 11 ( Suppl. 1): S100-S107.

Hoofnagle JH. Dusheiko GM. Schafer DF et al. Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann lnt Med 1982: 96 : 447-449

Naginton J. Cossart YE, Cohen BJ. Reactivation of hepatitis B after transplantation operations. Lancet. 1977:1 : 558-560

Davis GL, Hoofnagle JH. Waggoner JG. Spontaneous reactiva­tion of chronic hepatitis B virus infection. Gastroenterology. 1984: 86: 230-235.

Kaneko S, Miller RH, Di Bisceglie AM et al. Detection of hepatitis B virus DNA in serum by polymerase chain reaction. Ap­plication for clinical diagnosis. Gastroenterology 1990: 99: 799-804.

Hadler SC, Francis DP, Maynard JE et al. Long-term immunoge­nicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med 1986; 215: 209-214.

Ferrari C, Penna A, Degliantonni A et al. Cellular immune response to hepatitis B virus antigens. An overview. J Hepatol 1988: 7: 21-33.

Verter D, Doffoel M et al. Aspects immunologiques de la physi­opathologie des hépatites virales B. Gastroenterol Clin Biol 1989; 916-921 e 928-933

O'Brien CJ. Eddleston ALWF. Immunology of autoimmune and vira! chronic active hepatitis. Bailliére's Clinical Gastroente­rol 1987;1: 647-674.

Doherty PC, Zinkernagel RM. A biological role for the major histocompatibility antigen. Lancet 1975: i : 1405-1409.

Eddleston WLF, Mondelli M, Mieli-Vergani G et al. Lym­phocyte cytotoxicity to autologous hepatocytes in chro­nic hepatitis B vírus infection. Hepatology 1982: 2: 122S- 127S

Pignatelli NI, Waters J, Lever AML et al. Cytotoxic T-cell respon­ses to the nucleocapsid proteins of HBV in chronic hepatitis. J Hepatol 1987; 4:15-21.

Wilson B, Wands J Recent advances in the biology and immu­nology of hepatitis B. Bailliére's Clinical Gastroenterology 1987;1: 623-645.

Zarski JP. Seigneurin JM. La variabilité génétique du virus de l'hepatite B: relation eventuelle avec la pathogénicité. Gastroenterol Clin Biol 1991:11: 217-219.

Thomas HC. Shipton U. Montano L. The HLA system: its relevance to the pathogenesis of liver disease. ln: Progress in liver disease. Vol 16. New York. Grune & Straton 1982: 517-57

Attali P. Prod'homme S et al. Carcinome hépatocéllulaire un France. Aspects cliniques. biologiques et virologiques chez 197 malades. Gastroenterol Clin Biol 1985: 9: 396-402.

Parkin DM. Muire S. . Estimates of the world wide frequency of twelve major cancers. Bull World Health Organ 1984: 62: 162-182.

Davison FD'. Fagan EA. Portmann B et al. HBV DNA sequences in tumor tissue in a patient with the fibrolamelar variance of hepatocellular carcinoma. Hepatology 1990:12: 676-679

Giacchino R,. Pontisso P. Navone CJ et al. Hepatitis B virus HBV DNA positive hepatocellular carcinoma following hepatitis B virus infection in a child. J Med Virol 1987: 23: 151-156

Shih C. Burke K. Chou MJ et al. Tight clustering of human hepatitis B virus integration sites in hepatomas near a triple-stran­ded region. J Virol 1987: 61: 3491-3498

Zuckerman AJ. Harrison TJ. Hepatitis B virus chronic liver disease and hepatocellular carcinoma. Postgrad Med J 1987: 63; 13-20.

Beasley RP. Hwang LY. Hepatocellular carcinoma and hepatitis B virus. Sem Liver Dis 1984: 4: 113-121

Beasley RP. Kiu CC. Hwang LY et al. Hepatocelular carcinoma and hepatitis B virus. A prospective study of 22707 Man in Taiwan. Lancet. 1981. 2: 1129-1133

Velosa J. lnfecção crónica pelo vírus da hepatite B. História natural e influência da terapêutica com interferão. Disserta­ção de Doutoramento. Faculdade de Medicina. Universidade de Lisboa. 1992

Chen JY. Harrison TJ. Lee CS et al. Detection of hepatitis B virus DNA in hepatocellular carcinoma: analisis by hybridization with subgenomic DNA fragments. Hepatology. 1988: 8: 518-523

Bonino F. Brunetto MR. Negro F et al. Hepatitis Delta virus. a model of liver cell pathology.. J Hepatol 1991: 13: 260-266.

Ficheiros Adicionais

Publicado

30-06-1995

Como Citar

1.
Areias J. História natural da hepatite crónica pelo vírus da hepatite B. RPMI [Internet]. 30 de Junho de 1995 [citado 25 de Junho de 2024];2(2):86-9. Disponível em: https://revista.spmi.pt/index.php/rpmi/article/view/2372

Edição

Secção

Artigos de Revisão