O vírus da hepatite B na doença hepática alcoólica: avaliação clínica e bioquímica

Lacet, Celina M.C.; Strauss, Edna

doi:10.1590/S0037-86821993000400001

Resumos

Foram estudados prospectiva e seqüencialmente 107 pacientes com doença hepática alcoólica (DHA) crônica, sendo 83 casos de cirrose e 24de hepatite alcoólica. Além do etilismo, ingestão mínima de 70 gramas de etanol puro ao dia por período superior a sete anos, todos apresentaram disfunção hepatocelular. De acordo com o perfil sorológico para o VHB os pacientes foram alocados em quatro grupos a saber: grupo I infectados: AgHBs e anti-HBc positivos; grupo II imunes: anti-HBs e anti-HBc positivos; grupo III sem marcadores do VHB: AgHBs, anti-HBc e anti-HBs negativos; grupo IV anti-HBc positivo isoladamente. A prevalência de infecção pelo VHB na DHA foi alta: 42,06% apesar dos índices pouco elevados de imunidade: 26,17% sugerindo que na DHA ocorre maior exposição ao VHB com resposta imunológica deficiente. A análise dos parâmetros clínico-bioquímicos, quando considerados isoladamente, não mostrou diferenças estatisticamente significantes entre os grupos I, II, e III, entretanto a classificação de Child/Campbell, discriminou o grupo infectado, onde houve predomínio da classe C, de pior prognóstico.

Doença hepática alcoólica; Vírus da hepatite B; AgHBs; Avaliação clínico-bioquímica

The aim of our work was to study the prevalence of HBV markers in Alcoholic Liver Disease (ALD) by evaluating clinical and biochemical parameters that couldfurther characterize the association. A prospective and sequential study of 107 patients with ALD was performed, including 83 cases of cirrhosis and 24 cases of alcoholic hepatitis. Daily ingestionofpure ethanolwas of at least 70gm for seven years or more and always associated with hepatocelullar disfunction. According to the serological profilefor HBVmarkers the patients were allocated to one of four groups: group I infected (positivity ofHBsAg and anti-HBc); group II immunized (positivity of anti-HBs and anti-HBc); group 111 without HBV markers (negativity of HBsAg, anti-HBc and anti- HBs); group IV isolated anti-HBc. The prevalence of HBsAg positivity in ALD was high: 15.89% whereas immunity was low: 26.17% suggesting a great exposure to the virus and a deficient immunological response. No significant statistical differences were found among the three groups when clinical and biochemicalparameters were individually considered. Nevertheless, when a Chitd/Campbell classification was applied, patients with ALD associated with HBV (group 1) showed a significant difference, presenting a predominance of child C, with a bad prognosis.

Alcoholic liver disease (ALD); Hepatitis B virus; AgHBs; Clinical-biochemical evaluation

ARTIGOS

O vírus da hepatite B na doença hepática alcoólica: avaliação clínica e bioquímica

Celina M.C. Lacet; Edna Strauss

^{Endereço para correspondência} Endereço para correspondência: Prof a Edna Strauss. R. Nebraska 251/13 04560-010 São Paulo SP, Brasil.

RESUMO

Foram estudados prospectiva e seqüencialmente 107 pacientes com doença hepática alcoólica (DHA) crônica, sendo 83 casos de cirrose e 24de hepatite alcoólica. Além do etilismo, ingestão mínima de 70 gramas de etanol puro ao dia por período superior a sete anos, todos apresentaram disfunção hepatocelular. De acordo com o perfil sorológico para o VHB os pacientes foram alocados em quatro grupos a saber: grupo I infectados: AgHBs e anti-HBc positivos; grupo II imunes: anti-HBs e anti-HBc positivos; grupo III sem marcadores do VHB: AgHBs, anti-HBc e anti-HBs negativos; grupo IV anti-HBc positivo isoladamente. A prevalência de infecção pelo VHB na DHA foi alta: 42,06% apesar dos índices pouco elevados de imunidade: 26,17% sugerindo que na DHA ocorre maior exposição ao VHB com resposta imunológica deficiente. A análise dos parâmetros clínico-bioquímicos, quando considerados isoladamente, não mostrou diferenças estatisticamente significantes entre os grupos I, II, e III, entretanto a classificação de Child/Campbell, discriminou o grupo infectado, onde houve predomínio da classe C, de pior prognóstico.

Palavras-chave: Doença hepática alcoólica. Vírus da hepatite B. AgHBs. Avaliação clínico-bioquímica.

ABSTRACT

The aim of our work was to study the prevalence of HBV markers in Alcoholic Liver Disease (ALD) by evaluating clinical and biochemical parameters that couldfurther characterize the association. A prospective and sequential study of 107 patients with ALD was performed, including 83 cases of cirrhosis and 24 cases of alcoholic hepatitis. Daily ingestionofpure ethanolwas of at least 70gm for seven years or more and always associated with hepatocelullar disfunction. According to the serological profilefor HBVmarkers the patients were allocated to one of four groups: group I infected (positivity ofHBsAg and anti-HBc); group II immunized (positivity of anti-HBs and anti-HBc); group 111 without HBV markers (negativity of HBsAg, anti-HBc and anti- HBs); group IV isolated anti-HBc. The prevalence of HBsAg positivity in ALD was high: 15.89% whereas immunity was low: 26.17% suggesting a great exposure to the virus and a deficient immunological response. No significant statistical differences were found among the three groups when clinical and biochemicalparameters were individually considered. Nevertheless, when a Chitd/Campbell classification was applied, patients with ALD associated with HBV (group 1) showed a significant difference, presenting a predominance of child C, with a bad prognosis.

Keywords: Alcoholic liver disease (ALD). Hepatitis B virus. AgHBs. Clinical-biochemical evaluation.

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Recebido para publicação em 04/06/93.

Trabalho da Clínica de Gastroenterologia do Hospital Heliópolis, SP.

1. Anderson TW. An introduction to multivariate statistical analysis. John Wiley & Sons, New York 1952.
2. Antonácio F. Antígeno austrália em doadores de Sangue. Tese de doutorado Universidade de São Paulo, São Paulo, 1971.
3. Attali P, Thibaut N, Buffet C, Briantais MJ, Papoz L, Chaput JC, Etienne JP. Leus marqueurs du virus B chez les alcooliques chroniques. Gastroenterologie clinique et biologique 5:1095-1102, 1981.
4. Basile A, Vitale G, Macor C, Scudeller G. Hepatitis B virus infection in alcoholic cirrhosis. British Medical Journal 282:1705, 1981.
5. Bianchini E, Frosi A, Bertoli G, Bianchi G. Relationships betweenalcoholism, HBsAg inserum, liver histology and serum enzymes (CGT, GOT, GPT) in chronic liver diseases: a study of 328 patients. Italian Journal of Gaslroenterology 17:14- 17, 1985.
6. Bishop YMM, Fienberg SE, Holland PW. Discrete multivariate analysis: theory and practice. Cambrigde, the MIT press, 1975.
7. Brechot C, Nalpas B, Corouce AM, Duhamel G, Callard P, Camot F, Tiollais P, Berthelot P. Evidence that hepatitis B virus has a role in liver-cell carcinoma in alcoholic liver disease. New England Journal of Medicine 306:1384-1387, 1982.
8. Bruguera M. T ransmisión de la hepatitis B. Medicina Clinica (Barcelona) 84:312-314, 1985.
9. Campbell DP, Parker DE, Anagnostopoulos CE. survival prediction in portocaval shunts. A computerized statistical analysis. American Journal of Surgery 126:748-751, 1973.
10. Carrilho FJ, Baldy JLS, Takata PK, Adum S, Zeitune JMR. Prevalenceand study ofassymptomatic carrier of hepatitis B surface antigen in blood donnors in Londrina, South of Brazil. Gastroenterologia Endoscopia digestiva 3:13.-20, 1984.
11. Chalmers DM, Brillen AW, Levi AJ. Evidence for previous hepatitis B virus infection in alcoholic cirrhosis. British Medical Journal 282:819, 1981.
12. Chevillotte G, Durbec JP, Gerolami A, Berthezene P, Bidart JM, Camatte R. Interaction between hepatitis B virus and alcohol comsuption in liver cirrhosis. An epidemiologic study. Gastroenterology 85:141-145, 1983.
13. ChiaramonteM, Heathcote J, Cress M, Sherlook S. Detection by three techniques of hepatitis B surface antigen (HBsAg) and determination ofHBsAg and anti-H Bs titres in patients with chronic liver disease. Gut 18:1-6, 1977.
14. Coste T, Gié A, Fischer D, Karsenti P, Paraf A. Fréquence des marqueurs du virus B chez les alcooliques chroniques avec ou sans cirrhoses. Gastroenterologie clinique biologique 6:515-516, 1982.
15. Degos F, Brechot C, Nalpas B, Duhamel G, Courouce AM, Tron F, Berthelot P. Hepatitis B vaccination and alcoholic cirrhosis. Lancet 2:1496, 1983.
16. Fleiss JL. Statistical methods for rates and proportions. John Wiley & Sons, New York, 1973.
17. Garcia-Tsao G, Groszmann RJ, Fischer RL, Conn HO, Atterbury CE, Glickman M. Portal pressure presence of gastroesophageal varices and variceal bleeding. Hepatology 5:419-424, 1985.
18. Gayotto LCC, Quarentei AA, Cabral GL. Soro- epidemiologia das hepatitis A e B nas regiões dos rios Biá e Alto Juruá, Amazônia Ocidental. Gastroenterologia Endoscopia digestiva 3:106-112, 1984.
19. Gluud C, Gluud B, Aldershvile J, Jacobsen A, Dietrichson O. Prevalence of hepatitis B infection in out-patient alcoholics Infection 12:72-74, 1984.
20. Guimarães RX. Frequência do antígeno australiano em indivíduos normais, índios do Parque Nacional do Xingu e portadores de esquistossomose mansônica. São Paulo, 1973 Tese de doutorado - Escola Paulista de Medicina.
21. Hadengue A, N'dri N, Benhamou JP. Relative risk of hepatocellular carcinoma in HBsAg positive vs alcoholic cirrhosis. A cross-sectional study. Liver 10:147-151, 1990.
22. HislopWS, FollettEAC, BouchierlAD, Macsween RNM. Serological markers of hepatitis B in patients with alcoholic liver disease: a multi-centre survey. Journal of Clinical Pathology 34:1017-1019, 1981.
23. Inoue KL, Kojima T, Koyata H, Matsui S, Aoyama K, Konda T, Ishida T, Sasaki H. Hepatitis B virus antigen and antibodies in alcoholic. Etiological role ofHBV in liver diseases of alcoholic patients. Liver 5:247-252, 1985.
24. Kobayashi K, Unoura M, Tanaka N, Hattori N. A comparison between hepatocellular carcinoma developing and non-carcinoma-developing patients with cirrhosis overa long follow-up period. Hepato- gastroenterology 33:445-448, 1990.
25. Lybecker LA, Mendenhall CL, Marshall LE, Weesner RE, Myre RE. Response to hepatitis B vaccine (HBVac) in the alcoholic. Hepatology 3:807, 1983.
26. Mcmahon BJ, Wainright K, Bulkow L, Parkinson AJ, Lindenbaum M, Wainright R, Helminiak C. Response to hepatitis B vaccine in Alaska natives with chronic alcoholism compared with non-alcoholic control subjects. American Jounal of Medicine 88:460-464, 1990.
27. Mendes TF, Kutz H, Mexas PPF, Herbert BA. Infection by the hepatitis B virus in patients of a General Hospital. Arquivos de Gastroenterologia 16:73-80, 1979.
28. Mills PR, Follet EA, Urguhart GED, Clements G, Macsween RNM, Watkinson G. Evidence for previous hepatitis B virus infection in alcoholic cirrhosis. British Medical Journal 282:437-438, 1981.
29. Mills PR. Pennington TH, Kay P, Macsween RNM, Watkinson H. Hepatitis Bs antobody in alcoholic cirrhosis. Journal Clinical Pathology 32:778-782, 1979.
30. Mineis M, Guimarães RX, Farinazzo Neto J, Novo NF, Chechter L. Marcadores imunológicos do virus B da hepatite em alcoolatras e indivíduos normais. Revista Paulista de Medicina 102:205-213, 1984.
31. Nalpas B. Alcool et virus de l'hepatite B: une association insolite aux consequences imprevisibles. Gastroenterologie Clinique biologique 9:385-388, 1985.
32. Nalpas B, Driss F, Pol S, Hamelin B, Hosset C, Brechot C, Berthelot P. Association between HCV and HBV infection in hepatocellular carcinoma and alcoholic liver disease. Journal ofHepatology 12:70- 74, 1991.
33. Omata M, Yokosuka O, Imazeki F, Ito Y, Mori J, Ichiumi K, Okuda K. Correlation ofhepatitis B virus DNA and antigens in the liver - a study in chronic liver disease. Gastroenterology 92:192-196, 1987.
34. Pettigrew NM, Goudie RB, Russel RJ, Chaudhurt AKR. Evidence for a role of hepatitis B virus in chronic alcoholic liver disease. Lancet 2:724-725, 1972.
35. Saunders JB, Wodak AD, Morgan-Capner P, White YS, Portmann B, Davis M, Willians R. Importance of markers of hepatitis B virus in alcoholic liver disease. British Medical Journal 286:1851-1853, 1983.
36. Stigendal L, Hermodsson S, Olsson R. Prevalence of markers of hepatotropic viruses in alcoholic with symptomatic liver cirrhosis or pancreatitis. Scandinavian Journal of Gastroenterology 19:588- 590, 1984.
37. Strauss E, Maffei Jr RA, Sá MFG, Dutra AP, Takeda AK. Incidência de HBsAg e anti-HBs. Frequência do antígeno de superfície da hepatite B e de seus anticorpos detectados por radioimunoensaio, em pessoal hospitalar. Revista do Instituto de Medicina Tropical de São Paulo 25:246-253, 1983.
38. Tamburro CH, Lee HM. Primary hepatic cancer in alcoholic. Clinical Gastroenterology 10:457-477, 1981.
39. Trichopoulos D, Gerety RJ, Sparros L, Tabor E, Xirouchaki E, Munez N, Linsell CA. Hepatitis B and primary hepatocellular carcinoma in a european population. Lancet 2:1217-1219, 1978.
40. VetterD, Doffoel M, Gut JP, Doffoel S, North ML, Charrault A, Ventre G, Mayer S, Bockel R. Virus de l'hepatite B, marqueurs serologiques d'infections virales et immunité humorale au cours de la cirrhose alcoolique. Gastroenterologie clinique et biologique 9:389-395, 1985.
41. Villa E, Baldini G, Distalibe S, Pasquinelli C, Antonioli A, Plessi M, Braghiroli D, Barchi T, Monzani A, Manenti F. Alcohol and hepatitis B virus infection. Acta medica scandinavica 703(suppl):97-101, 1985.
42. Villa E, Barchi T, Grisendoi A, Bellentani S, Rubbiani L, Ferreti I, De Palma M, Mamenti F. Susceptibility of chronic symptomless HBsAg carriers to ethanol-induced hepatic damage. Lancet 2:1243-1244, 1982.
43. Zuckerman AJ. Controversies in immunization against hepatitis B. Hepatology 5:1227-1230,1985.

Endereço para correspondência:

Prof

^a Edna Strauss.

R. Nebraska 251/13

04560-010

São Paulo SP, Brasil.

Datas de Publicação

Publicação nesta coleção
11 Abr 2013
Data do Fascículo
Dez 1993

Histórico

Aceito
04 Jun 1993
Recebido
04 Jun 1993

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Anderson TW. An introduction to multivariate statistical analysis. John Wiley & Sons, New York 1952.

[2] 2. Antonácio F. Antígeno austrália em doadores de Sangue. Tese de doutorado Universidade de São Paulo, São Paulo, 1971.

[3] 3. Attali P, Thibaut N, Buffet C, Briantais MJ, Papoz L, Chaput JC, Etienne JP. Leus marqueurs du virus B chez les alcooliques chroniques. Gastroenterologie clinique et biologique 5:1095-1102, 1981.

[4] 4. Basile A, Vitale G, Macor C, Scudeller G. Hepatitis B virus infection in alcoholic cirrhosis. British Medical Journal 282:1705, 1981.

[5] 5. Bianchini E, Frosi A, Bertoli G, Bianchi G. Relationships betweenalcoholism, HBsAg inserum, liver histology and serum enzymes (CGT, GOT, GPT) in chronic liver diseases: a study of 328 patients. Italian Journal of Gaslroenterology 17:14- 17, 1985.

[6] 6. Bishop YMM, Fienberg SE, Holland PW. Discrete multivariate analysis: theory and practice. Cambrigde, the MIT press, 1975.

[7] 7. Brechot C, Nalpas B, Corouce AM, Duhamel G, Callard P, Camot F, Tiollais P, Berthelot P. Evidence that hepatitis B virus has a role in liver-cell carcinoma in alcoholic liver disease. New England Journal of Medicine 306:1384-1387, 1982.

[8] 8. Bruguera M. T ransmisión de la hepatitis B. Medicina Clinica (Barcelona) 84:312-314, 1985.

[9] 9. Campbell DP, Parker DE, Anagnostopoulos CE. survival prediction in portocaval shunts. A computerized statistical analysis. American Journal of Surgery 126:748-751, 1973.

[10] 10. Carrilho FJ, Baldy JLS, Takata PK, Adum S, Zeitune JMR. Prevalenceand study ofassymptomatic carrier of hepatitis B surface antigen in blood donnors in Londrina, South of Brazil. Gastroenterologia Endoscopia digestiva 3:13.-20, 1984.

[11] 11. Chalmers DM, Brillen AW, Levi AJ. Evidence for previous hepatitis B virus infection in alcoholic cirrhosis. British Medical Journal 282:819, 1981.

[12] 12. Chevillotte G, Durbec JP, Gerolami A, Berthezene P, Bidart JM, Camatte R. Interaction between hepatitis B virus and alcohol comsuption in liver cirrhosis. An epidemiologic study. Gastroenterology 85:141-145, 1983.

[13] 13. ChiaramonteM, Heathcote J, Cress M, Sherlook S. Detection by three techniques of hepatitis B surface antigen (HBsAg) and determination ofHBsAg and anti-H Bs titres in patients with chronic liver disease. Gut 18:1-6, 1977.

[14] 14. Coste T, Gié A, Fischer D, Karsenti P, Paraf A. Fréquence des marqueurs du virus B chez les alcooliques chroniques avec ou sans cirrhoses. Gastroenterologie clinique biologique 6:515-516, 1982.

[15] 15. Degos F, Brechot C, Nalpas B, Duhamel G, Courouce AM, Tron F, Berthelot P. Hepatitis B vaccination and alcoholic cirrhosis. Lancet 2:1496, 1983.

[16] 16. Fleiss JL. Statistical methods for rates and proportions. John Wiley & Sons, New York, 1973.

[17] 17. Garcia-Tsao G, Groszmann RJ, Fischer RL, Conn HO, Atterbury CE, Glickman M. Portal pressure presence of gastroesophageal varices and variceal bleeding. Hepatology 5:419-424, 1985.

[18] 18. Gayotto LCC, Quarentei AA, Cabral GL. Soro- epidemiologia das hepatitis A e B nas regiões dos rios Biá e Alto Juruá, Amazônia Ocidental. Gastroenterologia Endoscopia digestiva 3:106-112, 1984.

[19] 19. Gluud C, Gluud B, Aldershvile J, Jacobsen A, Dietrichson O. Prevalence of hepatitis B infection in out-patient alcoholics Infection 12:72-74, 1984.

[20] 20. Guimarães RX. Frequência do antígeno australiano em indivíduos normais, índios do Parque Nacional do Xingu e portadores de esquistossomose mansônica. São Paulo, 1973 Tese de doutorado - Escola Paulista de Medicina.

[21] 21. Hadengue A, N'dri N, Benhamou JP. Relative risk of hepatocellular carcinoma in HBsAg positive vs alcoholic cirrhosis. A cross-sectional study. Liver 10:147-151, 1990.

[22] 22. HislopWS, FollettEAC, BouchierlAD, Macsween RNM. Serological markers of hepatitis B in patients with alcoholic liver disease: a multi-centre survey. Journal of Clinical Pathology 34:1017-1019, 1981.

[23] 23. Inoue KL, Kojima T, Koyata H, Matsui S, Aoyama K, Konda T, Ishida T, Sasaki H. Hepatitis B virus antigen and antibodies in alcoholic. Etiological role ofHBV in liver diseases of alcoholic patients. Liver 5:247-252, 1985.

[24] 24. Kobayashi K, Unoura M, Tanaka N, Hattori N. A comparison between hepatocellular carcinoma developing and non-carcinoma-developing patients with cirrhosis overa long follow-up period. Hepato- gastroenterology 33:445-448, 1990.

[25] 25. Lybecker LA, Mendenhall CL, Marshall LE, Weesner RE, Myre RE. Response to hepatitis B vaccine (HBVac) in the alcoholic. Hepatology 3:807, 1983.

[26] 26. Mcmahon BJ, Wainright K, Bulkow L, Parkinson AJ, Lindenbaum M, Wainright R, Helminiak C. Response to hepatitis B vaccine in Alaska natives with chronic alcoholism compared with non-alcoholic control subjects. American Jounal of Medicine 88:460-464, 1990.

[27] 27. Mendes TF, Kutz H, Mexas PPF, Herbert BA. Infection by the hepatitis B virus in patients of a General Hospital. Arquivos de Gastroenterologia 16:73-80, 1979.

[28] 28. Mills PR, Follet EA, Urguhart GED, Clements G, Macsween RNM, Watkinson G. Evidence for previous hepatitis B virus infection in alcoholic cirrhosis. British Medical Journal 282:437-438, 1981.

[29] 29. Mills PR. Pennington TH, Kay P, Macsween RNM, Watkinson H. Hepatitis Bs antobody in alcoholic cirrhosis. Journal Clinical Pathology 32:778-782, 1979.

[30] 30. Mineis M, Guimarães RX, Farinazzo Neto J, Novo NF, Chechter L. Marcadores imunológicos do virus B da hepatite em alcoolatras e indivíduos normais. Revista Paulista de Medicina 102:205-213, 1984.

[31] 31. Nalpas B. Alcool et virus de l'hepatite B: une association insolite aux consequences imprevisibles. Gastroenterologie Clinique biologique 9:385-388, 1985.

[32] 32. Nalpas B, Driss F, Pol S, Hamelin B, Hosset C, Brechot C, Berthelot P. Association between HCV and HBV infection in hepatocellular carcinoma and alcoholic liver disease. Journal ofHepatology 12:70- 74, 1991.

[33] 33. Omata M, Yokosuka O, Imazeki F, Ito Y, Mori J, Ichiumi K, Okuda K. Correlation ofhepatitis B virus DNA and antigens in the liver - a study in chronic liver disease. Gastroenterology 92:192-196, 1987.

[34] 34. Pettigrew NM, Goudie RB, Russel RJ, Chaudhurt AKR. Evidence for a role of hepatitis B virus in chronic alcoholic liver disease. Lancet 2:724-725, 1972.

[35] 35. Saunders JB, Wodak AD, Morgan-Capner P, White YS, Portmann B, Davis M, Willians R. Importance of markers of hepatitis B virus in alcoholic liver disease. British Medical Journal 286:1851-1853, 1983.

[36] 36. Stigendal L, Hermodsson S, Olsson R. Prevalence of markers of hepatotropic viruses in alcoholic with symptomatic liver cirrhosis or pancreatitis. Scandinavian Journal of Gastroenterology 19:588- 590, 1984.

[37] 37. Strauss E, Maffei Jr RA, Sá MFG, Dutra AP, Takeda AK. Incidência de HBsAg e anti-HBs. Frequência do antígeno de superfície da hepatite B e de seus anticorpos detectados por radioimunoensaio, em pessoal hospitalar. Revista do Instituto de Medicina Tropical de São Paulo 25:246-253, 1983.

[38] 38. Tamburro CH, Lee HM. Primary hepatic cancer in alcoholic. Clinical Gastroenterology 10:457-477, 1981.

[39] 39. Trichopoulos D, Gerety RJ, Sparros L, Tabor E, Xirouchaki E, Munez N, Linsell CA. Hepatitis B and primary hepatocellular carcinoma in a european population. Lancet 2:1217-1219, 1978.

[40] 40. VetterD, Doffoel M, Gut JP, Doffoel S, North ML, Charrault A, Ventre G, Mayer S, Bockel R. Virus de l'hepatite B, marqueurs serologiques d'infections virales et immunité humorale au cours de la cirrhose alcoolique. Gastroenterologie clinique et biologique 9:389-395, 1985.

[41] 41. Villa E, Baldini G, Distalibe S, Pasquinelli C, Antonioli A, Plessi M, Braghiroli D, Barchi T, Monzani A, Manenti F. Alcohol and hepatitis B virus infection. Acta medica scandinavica 703(suppl):97-101, 1985.

[42] 42. Villa E, Barchi T, Grisendoi A, Bellentani S, Rubbiani L, Ferreti I, De Palma M, Mamenti F. Susceptibility of chronic symptomless HBsAg carriers to ethanol-induced hepatic damage. Lancet 2:1243-1244, 1982.

[43] 43. Zuckerman AJ. Controversies in immunization against hepatitis B. Hepatology 5:1227-1230,1985.