Natural History and Prognosis of Hepatitis B

Giovanna Fattovich

doi:10.1055/s-2003-37590

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2003; 23(1): 047-058
DOI: 10.1055/s-2003-37590

Natural History and Prognosis of Hepatitis B

Giovanna Fattovich

Professor of Medicine, Servizio Autonomo Clinicizzato di Gastroenterologia, University of Verona, Verona, Italy

Abstract

ABSTRACT

The natural history of hepatitis B virus (HBV) infection is complex and variable and is greatly influenced by the age at infection, the level of HBV replication, and host immune status. Chronic HBV infection generally consists of an early replicative phase with active liver disease (hepatitis B e antigen [HBeAg]-positive chronic hepatitis) and a late low or nonreplicative phase with HBeAg seroconversion and remission of liver disease (inactive carrier state). After HBeAg seroconversion, some patients may have active hepatitis due to HBV variants not expressing HBeAg (HBeAg-negative chronic hepatitis). Morbidity and mortality are linked to development of cirrhosis and hepatocellular carcinoma. Survival is reasonably good (about 85% probability at 5 years) in compensated cirrhosis but very poor in decompensated cirrhosis. Both cirrhotic and noncirrhotic patients with sustained reduction of HBV replication and normalization of aminotransferase after interferon alfa therapy have a reduced risk for liver-related complications.

KEYWORDS

Hepatitis B virus - chronic hepatitis B - interferon alfa

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Referenzen

REFERENCES

1 Maddrey W C. Hepatitis B: an important public health issue. J Med Virol . 2000; 61 362-366
2 Lee W M. Hepatitis B virus infection. N Engl J Med . 1997; 337 1733-1745
3 Lok A S, Heathcote E J, Hoofnagle J H. Management of hepatitis B: 2000-summary of a workshop. Gastroenterology . 2001; 120 1828-1853
4 Lok A SF, McMahon B J. Chronic hepatitis B. Hepatology . 2001; 34 1225-1241
5 Milich D R, Chen M K, Hughes J L, Jones J E. The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid: a mechanism for persistence. J Immunol . 1998; 160 2013-2021
6 Hadziyannis S J, Vassilopoulos D. Hepatitis B e antigen- negative chronic hepatitis B. Hepatology . 2001; 34 617-624
7 Chemin I, Zoulim F, Merle P. High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology. J Hepatol . 2001; 34 471-473
8 Kawatani T, Suou T, Tajima F. Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies. Eur J Haematol . 2001; 67 45-50
9 McMahon B J, Alward W LM, Hall D B. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis . 1985; 151 599-603
10 Smedile A, Farci P, Verme G. Influence of delta infection on severity of hepatitis B. Lancet . 1982; 2 945-947
11 Feray C, Gigou M, Samuel D. Hepatitis C virus RNA and hepatitis B virus DNA in serum and liver of patients with fulminant hepatitis. Gastroenterology . 1993; 104 549-555
12 Chang M H. Natural history of hepatitis B infection in children. J Gastroenterol Hepatol . 2000; 15(Suppl) E11-E19
13 Tassopoulos N C, Papaevangelou G J, Sjogren M H. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology . 1987; 92 1844-1850
14 Burk R D, Hwang L Y, Ho G YF, Shafritz D A, Beasley R P. Outcome of perinatal hepatitis B virus exposure is dependent on maternal virus load. J Infect Dis . 1994; 170 1418-1423
15 Cacciola I, Cerenzia G, Pollicino T. Genomic heterogeneity of hepatitis B virus (HBV) and outcome of perinatal HBV infection. J Hepatol . 2002; 36 426-432
16 Lok A SF, Lai C L, Wu P C, Leung E KY, Lam T S. Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection. Gastroenterology . 1987; 92 1839-1843
17 Realdi G, Alberti A, Rugge M. Seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection. Gastroenterology . 1980; 79 195-199
18 Hoofnagle J H, Dusheiko G M, Seef L B. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med . 1981; 94 744-748
19 Fattovich G, Rugge M, Brollo L. Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B. Hepatology . 1986; 6 167-172
20 Liaw Y F, Tai D I, Chu C M, Chen T J. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology . 1988; 8 493-496
21 Moreno-Otero R, Garcia-Monzòn C, Garcia-Sànchez A. Development of cirrhosis after chronic type B hepatitis: a clinicopathologic and follow-up study of 46 HBeAg-positive asymptomatic patients. Am J Gastroenterol . 1991; 86 560-564
22 Zarski J P, Marcellin P, Cohard M. Comparison of anti-HBe-positive and HBe-antigen-positive chronic hepatitis B in France. J Hepatol . 1994; 20 636-640
23 Di Marco V, Lo Iacono O, Cammà C. The long-term course of chronic hepatitis B. Hepatology . 1999; 30 257-264
24 Lin S M, Sheen I S, Chien R N, Chu C M, Liaw Y F. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology . 1999; 29 971-975
25 Yuen M F, Hui C K, Cheng C C. Long-term follow-up of interferon alfa treatment in Chinese patients with chronic hepatitis B infection: the effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complications. Hepatology . 2001; 34 139-145
26 Chang M H, Hsu H Y, Hsu H C. The significance of spontaneous hepatitis B e antigen seroconversion in childhood: with special emphasis on the clearance of hepatitis B e antigen before 3 years of age. Hepatology . 1995; 22 1387-1392
27 Bortolotti F, Jara P, Crivellaro C. Outcome of chronic hepatitis B in Caucasian children during a 20-year observation period. J Hepatol . 1998; 29 184-190
28 Hsu Y S, Chien R N, Yeh C T. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology . 2002; 35 1522-1527
29 Fong T L, Di Bisceglie M A, Gerber M A, Waggoner J G, Hoofnagle J H. Persistence of hepatitis B virus DNA in the liver after loss of HBsAg in chronic hepatitis B. Hepatology . 1993; 18 1313-1318
30 McMahon B J, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska natives chronically infected with hepatitis B virus. Ann Intern Med . 2001; 135 759-768
31 Bortolotti F, Cadrobbi P, Crivellaro C. Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood. Gastroenterology . 1990; 99 805-810
32 Wong D KH, Cheung A M, O'Rourke K. Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med . 1993; 119 312-323
33 Vajro P, Migliaro F, Fontanella A, Orso G. Interferon: a meta-analysis of published studies in pediatric chronic hepatitis B. Acta Gastroenterol Belg . 1998; 61 219-223
34 Chang M H, Sung J L, Lee C Y. Factors affecting clearance of hepatitis B e antigen in hepatitis B surface antigen carrier children. J Pediatr . 1989; 115 385-390
35 Alward W LM, McMahon B J, Hall D B. The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma. J Infect Dis . 1985; 151 604-609
36 Liaw Y F. Current trends in therapy for chronic viral hepatitis. J Gastroenterol Hepatol . 1997; 12 S346-S353
37 Perillo R P. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology . 2001; 120 1009-1022
38 Orito E, Mizokami M, Sakugawa H. A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotype B and C. Japan HBV Genotype Research Group. Hepatology . 2001; 33 218-223
39 Chu C J, Hussain M, Lok A SF. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared to hepatitis B virus genotype C. Gastroenterology . 2002; 122 1756-1762
40 Chan H LY, Leung N WY, Hussain M, Wong M L, Lok A SF. Hepatitis B e antigen-negative chronic hepatitis B in Hong Kong. Hepatology . 2000; 31 763-768
41 Funk M L, Rosenberg D M, Lok A SF. World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants. J Viral Hepat . 2002; 9 52-61
42 Rizzetto M, Volpes R, Smedile A. Response of pre-core mutant chronic hepatitis B infection to lamivudine. J Med Virol . 2000; 61 398-402
43 Fattovich G, Farci P, Rugge M. Randomized controlled trial of lymphoblastoid interferon alfa in patients with chronic hepatitis B who lacked hepatitis B e antigen. Hepatology . 1992; 15 584-589
44 Lampertico P, Del Ninno E, Manzin A. A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum. Hepatology . 1997; 26 1621-1625
45 Tassopoulos N C, Volpes R, Pastore G. Efficacy of lamivudine in patients with hepatitis B e antigen-negative/ hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Group. Hepatology . 1999; 29 889-896
46 Brunetto M R, Oliveri F, Coco B. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study. J Hepatol . 2002; 36 263-270
47 Papatheodoridis G V, Manesis E, Hadziyannis S J. The long-term outcome of interferon-α treated and untreated patients with HBeAg-negative chronic hepatitis B. J Hepatol . 2001; 34 306-313
48 De Franchis R, Meucci G, Vecchi M. The natural history of asymptomatic hepatitis B surface antigen carriers. Ann Intern Med . 1993; 118 191-194
49 Bellentani S, Dal Molin G, Miglioli L. Natural history of HBV infection: a 9 years follow-up of the Dionysos cohort. J Hepatol . 2002; 36(Suppl 1) 228
50 Fattovich G, Giustina G, Realdi G, Corrocher R, Schalm S W. Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa. Hepatology . 1997; 26 1338-1342
51 Fattovich G, Giustina G, Sanchez-Tapias J. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. Am J Gastroenterol . 1998; 93 896-900
52 McMahon B J, Alberts S R, Wainwright R B, Bulkow L, Lanier A P. Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska Native carriers. Arch Intern Med . 1990; 150 1051-1054
53 Huo T I, Wu J C, Lee P C. Sero-clearance of hepatitis B surface antigen in chronic carriers not necessarily implies a good prognosis. Hepatology . 1998; 28 231-236
54 Fattovich G, Brollo L, Giustina G. Natural history and prognostic factors of chronic hepatitis type B. Gut . 1991; 32 294-298
55 Ikeda K, Saitoh S, Suzuki Y. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation in 2215 patients. J Hepatol . 1998; 28 930-938
56 Mazzella G, Saracco G, Festi D. Long-term results with interferon therapy in chronic type B hepatitis: a prospective randomized trial. Am J Gastroenterol . 1999; 94 2246-2250
57 Fattovich G, Brollo L, Alberti A. Long term follow-up of anti-HBe positive chronic active hepatitis B. Hepatology . 1988; 8 1651-1654
58 Brunetto M R, Oliveri F, Rocca G. Natural course and response to interferon of chronic hepatitis B accompanied by antibody to hepatitis B e antigen. Hepatology . 1989; 10 198-202
59 Kao J H, Chen P J, Lai M Y, Chen D S. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology . 2000; 118 554-559
60 Chan H L, Tsang S W, Liew C T. Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection. Am J Gastroenterol . 2002; 97 406-412
61 Fattovich G, Tagger A, Brollo L. A Hepatitis C virus infection in chronic hepatitis B virus carriers. J Infect Dis . 1991; 163 400-402
62 Fong T L, Di Bisceglie M A, Waggoner J G, Banks S M, Hoofnagle J H. The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. Hepatology . 1991; 14 64-67
63 Sagnelli E, Coppola N, Scolastico C. Virologic and clinical expression of reciprocal inhibitory effect of hepatitis B, C and delta viruses in patients with chronic hepatitis. Hepatology . 2000; 32 1106-1110
64 Gaeta G B, Stroffolini T, Chiaramonte M. Chronic hepatitis D: a vanishing disease?. <~>An Italian multicenter study. Hepatology . 2000; 32 824-827
65 Fattovich G, Boscaro S, Noventa F. Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B. J Infect Dis . 1987; 155 931-935
66 Rosina F, Conoscitore P, Cuppone R. Changing pattern of chronic hepatitis D in Southern Europe. Gastroenterology . 1999; 117 161-166
67 Colin J F, Cazals-Hatem D, Loriot M A. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology . 1999; 29 1306-1310
68 Liaw Y F, Lin D Y, Chen T J, Chu C M. Natural course after the development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Liver . 1989; 9 235-241
69 Kato Y, Nakata K, Omagari K. Risk of hepatocellular carcinoma in patients with cirrhosis in Japan. Analysis of infectious hepatitis viruses. Cancer . 1994; 74 2234-2238
70 Mazzella G, Accogli E, Sottili S. Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis. J Hepatol . 1996; 24 141-147
71 Ikeda K, Saitoh S, Suzuki Y. Interferon decreases hepatocellular carcinogenesis in patients with cirrhosis caused by the hepatitis B virus. Cancer . 1998; 82 827-835
72 Fattovich G, Giustina G, Christensen E. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. Gut . 2000; 46 420-426
73 Realdi G, Fattovich G, Hadziyannis S. Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. J Hepatol . 1994; 21 656-666
74 Beasley R P. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer . 1988; 61 1942-1956
75 Yu M W, Hsu F C, Sheen I S. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am J Epidemiol . 1997; 145 1039-1047
76 McMahon B J, Bulkow L, Harpster A. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population based study. Hepatology . 2000; 32 842-846
77 Liaw Y F, Tai D I, Chu C M. Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study. Gastroenterology . 1985; 90 263-267
78 Oon C J. Long-term survival following treatment of hepatocellular carcinoma in Singapore: evaluation of Wellferon in the prophylaxis of high-risk pre-cancerous conditions. Cancer Chemother Pharmacol . 1992; 31(Suppl 1) S137-S142
79 Fattovich G, Pantalena M, Zagni I. Effect of hepatitis B and C virus infection on the natural history of compensated cirrhosis: a cohort study of 297 patients. Am J Gastroenterol . 2002; 97 2886-2895
80 Fattovich G, Giustina G, Schalm S W. Occurrence of hepatocellular carcinoma and decompensation in Western European patients with cirrhosis type B. Hepatology . 1995; 21 77-82
81 Benvegnù L, Fattovich G, Noventa F. Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. Cancer . 1994; 74 2442-2448
82 Chung H T, Lai C L, Lok A S. Pathogenic role of hepatitis B virus in hepatitis B surface antigen-negative decompensated cirrhosis. Hepatology . 1995; 22 25-29
83 De Jongh E F, Janssen H LA, De Man A R. M. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology . 1992; 103 1630-1635
84 Hui A Y, Chan H L, Leung N W. Survival and prognostic indicators in patients with hepatitis B virus-related cirrhosis after onset of hepatic decompensation. J Clin Gastroenterol . 2002; 34 569-572
85 Hoofnagle J H, Di Bisceglie M A. The treatment of chronic viral hepatitis. N Engl J Med . 1997; 336 347-356
86 Evans A A, Fine M, London W T. Spontaneous seroconversion in hepatitis B e antigen-positive chronic hepatitis B: implications for interferon therapy. J Infect Dis . 1997; 176 845-850
87 Manesis E K, Hadziyannis S J. Interferon alpha treatment and retreatment of hepatitis B e antigen-negative chronic hepatitis B. Gastroenterology . 2001; 121 101-109
88 Lampertico P, Viganò M, Iavarone M, Del Ninno E, Colombo M. Long-term outcome of patients with HBeAg-negative chronic hepatitis B treated with a 24-month course of interferon alfa. J Hepatol . 2001; 34(Suppl 1) 149
89 Niederau C, Heintges T, Lange S. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med . 1996; 334 1422-1427
90 EUROHEP: European Concerted Action on HBV-related Cirrhosis 2003. Updated analysis, data on file: Fattovich et al50
91 International Interferon-α Hepatocellular Carcinoma Study Group. Effect of interferon-α on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study. Lancet . 1998; 351 1535-1539
92 Lau D TY, Everhart J, Kleiner D E. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology . 1997; 113 1660-1667
93 Yao F Y, Terrault N A, Freise C, Maslow L, Bass N M. Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: a comparative study using a matched, untreated cohort. Hepatology . 2001; 34 411-416
94 Mutimer D. Beneficial effect of lamivudine for hepatitis B transplant recipients. Liver Transp . 2002; 8 440-442