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DOI: 10.1055/s-2006-939751
Hepatitis B e Antigen-Negative Chronic Hepatitis B: Natural History and Treatment
Publication History
Publication Date:
03 May 2006 (online)
ABSTRACT
Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B evolves in the natural history of chronic hepatitis B virus (HBV) infection linked with selection of nonproducing HBeAg but replication-competent HBV mutants, and may have a potentially severe and progressive course. Effective suppression of HBV replication is the main therapeutic target. Sustained off-therapy responses are rare with treatment of finite duration, except perhaps for interferon-based therapies, which induce such responses in a sizeable, yet small proportion of patients. Eventually, the majority of patients will be treated with long-term oral antiviral therapy, which improves patients' outcome but is associated with progressively increasing rates of viral resistance. The long-term resistance profile of adefovir is significantly better than that of lamivudine (LMV), whereas data for entecavir currently are limited to 2 years, with resistance developing in LMV-resistant but not in treatment-naïve patients. Combination therapy with adefovir added to LMV in LMV-resistant patients is extremely effective; cases of adefovir-resistance have not been reported to date.
KEYWORDS
Chronic hepatitis B - interferon-alfa - lamivudine - adefovir - entecavir
REFERENCES
- 1 Hadziyannis S J, Lieberman H M, Karvountzis G G, Shafritz D A. Analysis of liver disease, nuclear HBcAg, viral replication and hepatitis B virus DNA in liver and serum of HBeAg vs anti-HBe positive carriers of hepatitis B virus. Hepatology. 1983; 3 656-662
- 2 Bonino F, Rosina F, Rizzetto M et al.. Chronic hepatitis in HBsAg carriers with serum HBV-DNA and anti-HBe. Gastroenterology. 1986; 90 1268-1273
- 3 Hadziyannis S J. Hepatitis B e antigen negative chronic hepatitis B: from clinical recognition to pathogenesis and treatment. Viral Hepatitis Reviews. 1995; 1 7-36
- 4 Hadziyannis S J, Vassilopoulos D. Hepatitis B e antigen-negative chronic hepatitis B. Hepatology. 2001; 34 617-624
- 5 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
- 6 Chan H L, Leung N W, Hussain M, Wong M L, Lok A S. Hepatitis B e antigen-negative chronic hepatitis B in Hong Kong. Hepatology. 2000; 31 763-768
- 7 Transmission of hepatitis B to patients from four infected surgeons without hepatitis B e antigen. The Incident Investigation Teams and others. N Engl J Med. 1997; 336 178-184
- 8 Carman W F, Fagan E A, Hadziyannis S et al.. Association of a precore genomic variant of hepatitis B virus with fulminant hepatitis. Hepatology. 1991; 14 219-222
- 9 Chen M, Sallberg M, Hughes J et al.. Immune tolerance split between hepatitis B virus precore and core proteins. J Virol. 2005; 79 3016-3027
- 10 Brunetto M R, Oliveri F, Rocca G et al.. Natural course and response to interferon of chronic hepatitis B accompanied by antibody to hepatitis B e antigen. Hepatology. 1989; 10 198-202
-
11 Hadziyannis S J, Bramou A, Alexopoulou A, Makris A.
Immunopathogenesis and natural course of anti-HBe-positive chronic hepatitis with replicating B virus . In: Hollinger FB, Lemon SM, Margolis HS Viral Hepatitis and Liver Disease. Baltimore; Williams and Wilkins 1991: 673-676 - 12 Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis. 2003; 23 47-58
- 13 McMahon B J. The natural history of chronic hepatitis B virus infection. Semin Liver Dis. 2004; 24(suppl 1) 17-21
- 14 Lok A S, Heathcote E J, Hoofnagle J H. Management of hepatitis B: 2000-summary of a workshop. Gastroenterology. 2001; 120 1828-1853
- 15 de Franchis R, Hadengue A, Lau G et al.. EASL International Consensus Conference on Hepatitis B. J Hepatol. 2003; 39(suppl 1) S3-S25
- 16 Lok A S, McMahon B J. Chronic hepatitis B: update of recommendations. Hepatology. 2004; 39 857-861
- 17 Hadziyannis S J, Papatheodoridis G V. Emerging treatments in chronic hepatitis B. Expert Opin Emerg Drugs. 2004; 9 207-221
- 18 Keeffe E B, Dieterich D T, Han S H et al.. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States. Clin Gastroenterol Hepatol. 2004; 2 87-106
- 19 Hoofnagle J H, Dusheiko G M, Seeff L B et al.. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med. 1981; 94 744-748
- 20 Fattovich G, Rugge M, Brollo L et al.. Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B. Hepatology. 1986; 6 167-172
- 21 Liaw Y F, Chu C M, Su I J et al.. Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology. 1983; 84 216-219
- 22 Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005; 5 215-229
- 23 Hadziyannis S, Gerber M A, Vissoulis C, Popper H. Cytoplasmic hepatitis B antigen in “ground-glass” hepatocytes of carriers. Arch Pathol. 1973; 96 327-330
- 24 Liaw Y-F, Sheen I-S, Chen T-J, Chu C-M, Pao C-C. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology. 1991; 13 627-631
- 25 de Franchis R, Meucci G, Vecchi M et al.. The natural history of asymptomatic hepatitis B surface antigen carriers. Ann Intern Med. 1993; 118 191-194
- 26 Villeneuve J-P, Descrochers M, Infante-Rivard C et al.. A long-term follow-up study of asymptomatic hepatitis B surface antigen-positive carriers in Montreal. Gastroenterology. 1994; 106 1000-1005
- 27 Fong T-L, Di Bisceglie A M, 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
- 28 Davis G L, Hoofnagle J H, Waggoner J G. Spontaneous reactivation of chronic hepatitis B virus infection. Gastroenterology. 1984; 86 230-235
- 29 Hsu Y S, Chien R N, Yeh C T et al.. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002; 35 1522-1527
- 30 Papatheodoridis G V, Hadziyannis S J. Diagnosis and management of pre-core mutant chronic hepatitis B. J Viral Hepat. 2001; 8 311-321
- 31 Fung S K, Lok A S. Hepatitis B virus genotypes: do they play a role in the outcome of HBV infection?. Hepatology. 2004; 40 790-792
- 32 Kramvis A, Kew M C. Relationship of genotypes of hepatitis B virus to mutations, disease progression and response to antiviral therapy. J Viral Hepat. 2005; 12 456-464
- 33 Jardi R, Rodriguez F, Buti M et al.. Mutations in the basic core promoter region of hepatitis B virus. Relationship with precore variants and HBV genotypes in a Spanish population of HBV carriers. J Hepatol. 2004; 40 507-514
- 34 Tanaka Y, Hasegawa I, Kato T et al.. A case-control study for differences among hepatitis B virus infections of genotypes A (subtypes Aa and Ae) and D. Hepatology. 2004; 40 747-755
- 35 Duong T N, Horiike N, Michitaka K et al.. Comparison of genotypes C and D of the hepatitis B virus in Japan: a clinical and molecular biological study. J Med Virol. 2004; 72 551-557
- 36 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
- 37 Orito E, Mizokami M, Sakugawa H et al.. A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Japan HBV Genotype Research Group. Hepatology. 2001; 33 218-223
- 38 Chu C J, Hussain M, Lok A S. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology. 2002; 122 1756-1762
- 39 Yuen M F, Fung S K, Tanaka Y et al.. Longitudinal study of hepatitis activity and viral replication before and after HBeAg seroconversion in chronic hepatitis B patients infected with genotypes B and C. J Clin Microbiol. 2004; 42 5036-5040
- 40 Sugauchi F, Kumada H, Sakugawa H et al.. Two subtypes of genotype B (Ba and Bj) of hepatitis B virus in Japan. Clin Infect Dis. 2004; 38 1222-1228
- 41 Norder H, Courouce A M, Coursaget P et al.. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 2004; 47 289-309
- 42 Carman W F, Jacyna M R, Hadziyannis S et al.. Mutation preventing formation of “hepatitis B e antigen” in patients with chronic hepatitis B infection. Lancet. 1989; 2 588-590
- 43 Okamoto H, Yotsumoto Y, Akahane T et al.. Hepatitis B viruses with precore defects prevail in persistently infected hosts along with seroconversion to anti-HBe. J Virol. 1990; 64 1298-1303
- 44 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
- 45 Brunetto M R, Giarin M, Oliveri F et al.. Wild type and e antigen-minus hepatitis B virus in course of chronic hepatitis. Proc Natl Acad Sci USA. 1991; 88 4186-4190
- 46 Brunetto M R, Giarin M, Saracco G et al.. Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B. Gastroenterology. 1993; 105 845-850
- 47 Loriot M A, Marcellin P, Talbodec N et al.. Low frequency of precore hepatitis B virus mutants in anti-hepatitis B e-positive reactivation after loss of hepatitis B e antigen in patients with chronic hepatitis B. Hepatology. 1995; 21 627-631
- 48 Talbodec N, Loriot M A, Gigou M et al.. Hepatitis B virus precore mutations and HBeAg negative reactivation of chronic hepatitis B after interferon therapy. Liver. 1995; 15 93-98
- 49 Okamoto H, Tsuda F, Akahane Y et al.. Hepatitis B virus with mutations in the core promoter for an e antigen-negative phenotype in carriers with antibody to e antigen. J Virol. 1994; 68 8102-8110
- 50 Lindh M, Horal P, Dhillon A P, Furuta Y, Norkrans G. Hepatitis B virus carriers without precore mutations in hepatitis B e antigen-negative stage show more severe liver damage. Hepatology. 1996; 24 494-501
- 51 Laras A, Koskinas J, Avgidis K, Hadziyannis S J. Incidence and clinical significance of hepatitis B virus precore gene translation initiation mutations in e antigen-negative patients. J Viral Hepat. 1998; 5 241-248
- 52 Hunt C M, McGill J M, Allen M L, Condreay L D. Clinical relevance of hepatitis B virus mutations. Hepatology. 2000; 31 1037-1044
- 53 Lok A S, Akarca U, Greene S. Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal. Proc Natl Acad Sci USA. 1994; 91 4077-4081
- 54 Chan H L, Hussain M, Lok A S. Different hepatitis B virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion. Hepatology. 1999; 29 976-984
- 55 Liaw Y F, Chu C M, Lin D Y et al.. Age-specific prevalence and significance of HBeAg/anti-HBe in chronic HBV infection in Taiwan: a comparison among asymptomatic carriers, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. J Med Virol. 1984; 13 385-391
- 56 Zarski J P, Marcellin P, Cohard M et al.. Comparison of anti-HBe positive and HBe-antigen-positive chronic hepatitis B in France. J Hepatol. 1994; 20 636-640
- 57 Hamasaki K, Nakata K, Nagayama Y et al.. Changes in the prevalence of HBeAg-negative mutant hepatitis B virus during the course of chronic hepatitis B. Hepatology. 1994; 20 8-14
- 58 Papatheodoridis G V, Dimou E, Dimakopoulos K et al.. Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine. Hepatology. 2005; 42 121-129
- 59 Liaw Y F, Tai D I, Chu C M, Pao C C, Chen T J. Acute exacerbation in chronic type B hepatitis: comparison between HBeAg and antibody-positive patients. Hepatology. 1987; 7 20-23
- 60 Tassopoulos N C, Papatheodoridis G V, Kalantzakis Y et al.. Differential diagnosis of acute HBsAg positive hepatitis using IgM anti-HBc by a rapid, fully automated microparticle enzyme immunoassay. J Hepatol. 1997; 26 14-19
- 61 Naoumov N V, Schneider R, Grotzinger T et al.. Precore mutant hepatitis B virus infection and liver disease. Gastroenterology. 1992; 102 538-543
- 62 Lai M E, Solinas A, Mazzoleni A P et al.. The role of pre-core hepatitis B virus mutants on the long-term outcome of chronic hepatitis B virus hepatitis. A longitudinal study. J Hepatol. 1994; 20 773-781
- 63 Di Marco V, Lo Iakono O, Camma C et al.. The long-term course of chronic hepatitis B. Hepatology. 1999; 30 257-264
- 64 Papatheodoridis G V, Manesis E, Hadziyannis S J. The long-term outcome of interferon-a treated and untreated patients with HBeAg-negative chronic hepatitis B. J Hepatol. 2001; 34 306-313
- 65 Brunetto M R, Oliveri F, Coco B et al.. 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
- 66 Fattovich G, Brollo L, Giustina G et al.. Natural-history and prognostic factors for chronic hepatitis type B. Gut. 1991; 32 294-298
- 67 Brunetto M R, Oliveri F, Colombatto P et al.. Treatment of chronic anti-HBe-positive hepatitis B with interferon-alpha. J Hepatol. 1995; 22 42-44
- 68 Chan H L, Tsang S W, Liew C T et al.. 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
- 69 Liaw Y F, Tsai S L, Sheen I S et al.. Clinical and virological course of chronic hepatitis B virus infection with hepatitis C and D virus markers. Am J Gastroenterol. 1998; 93 354-359
- 70 Yuan H J, Yuen M F, Ka-Ho W D, Sablon E, Lai C L. The relationship between HBV-DNA levels and cirrhosis-related complications in Chinese with chronic hepatitis B. J Viral Hepat. 2005; 12 373-379
- 71 Beasley R P. The major etiology of hepatocellular carcinoma. Cancer. 1988; 61 1942-1956
- 72 Fattovich G, Giustina G, Schalm S W et al.. 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
- 73 Realdi G, Fattovich G, Hadziyannis S et al.. Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. J Hepatol. 1994; 21 656-666
- 74 Manesis E, Papatheodoridis G V, Sevastianos V et al.. Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with HBeAg-negative chronic hepatitis B virus infection. Am J Gastroenterol. 2003; 98 2261-2267
- 75 Chu C-J, Hussain M, Lok A SF. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology. 2002; 36 1408-1415
- 76 Papatheodoridis G V, Hadziyannis S J. Current management of chronic hepatitis B. Aliment Pharmacol Ther. 2004; 19 25-37
- 77 Hadziyannis S J, Papatheodoridis G V, Vassilopoulos D. Treatment of HBeAg-negative chronic hepatitis B. Semin Liver Dis. 2003; 23 81-88
- 78 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
- 79 Lampertico P, Del Ninno E, Vigano M et al.. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatology. 2003; 37 756-763
- 80 Zhang X, Zoulim F, Habersetzer F, Xiong S, Trepo C. Analysis of hepatitis B virus genotypes and pre-core region variability during interferon treatment of HBe antigen negative chronic hepatitis B. J Med Virol. 1996; 48 8-16
- 81 Erhardt A, Reineke U, Blondin D et al.. Mutations in the core promoter and response to interferon treatment in chronic replicative hepatitis B. Hepatology. 2000; 31 716-725
- 82 Vinayek R, Shakil O. Adverse events associated with interferon-alfa therapy in patients with chronic viral hepatitis. Viral Hepatitis Reviews. 1997; 3 167-177
- 83 Wong J B, Koff R S, Tine F, Pauker S G. Cost-effectiveness of interferon-alpha 2b treatment for hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med. 1995; 122 664-675
- 84 National Institute of Health Consensus Development Conference Statement. Management of hepatitis C: 2002. June 10-12, 2002. Hepatology. 2002; 36(suppl 1) S3-S20
- 85 Marcellin P, Lau G K, Bonino F et al.. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004; 351 1206-1217
- 86 Marcellin P, Bonino F, Lau G K et al.. Factors associated with sustained virologic response 1 year after treatment with peginterferon alfa-2a (40KD) (Pegasys) monotherapy for HBeAg-negative chronic hepatitis B. Hepatology. 2005; 42(suppl 1) 580A
- 87 Tassopoulos N C, Volpes R, Pastore G et al.. Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Hepatology. 1999; 29 889-896
- 88 Papatheodoridis G V, Dimou E, Papadimitropoulos V. Nucleoside analogues for chronic hepatitis B: antiviral efficacy and viral resistance. Am J Gastroenterol. 2002; 97 1618-1628
- 89 Tassopoulos N C, Volpes R, Pastore G et al.. Post lamivudine treatment follow up of patients with HBeAg negative chronic hepatitis B. J Hepatol. 1999; 30(suppl 1) 117
- 90 Santantonio T, Mazzola M, Iacovazzi T et al.. Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine. J Hepatol. 2000; 32 300-306
- 91 Hadziyannis S J, Papatheodoridis G V, Dimou E, Laras A, Papaioannou C. Efficacy of long-term lamivudine monotherapy in patients with HBeAg negative chronic hepatitis B. Hepatology. 2000; 32 847-851
- 92 Papatheodoridis G V, Dimou E, Laras A, Papadimitropoulos V, Hadziyannis S J. Course of virologic breakthroughs under long-term lamivudine in HBeAg-negative precore mutant HBV liver disease. Hepatology. 2002; 36 219-226
- 93 Di Marco V, Marzano A, Lampertico P et al.. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine. Hepatology. 2004; 40 883-891
- 94 Gaia S, Marzano A, Smedile A et al.. Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B. Aliment Pharmacol Ther. 2004; 20 281-287
- 95 Fung S K, Wong F, Hussain M, Lok A SF. Sustained response after a 2-year course of lamivudine treatment of hepatitis B e antigen-negative chronic hepatitis B. J Viral Hepat. 2004; 11 432-438
- 96 Lampertico P, Vigano P, Manenti E et al.. Five years of sequential LAM to LAM+ADV therapy suppresses HBV replication in most HBeAg-negative cirrhotics, preventing decompensation but not hepatocellular carcinoma. Hepatology. 2005; 42(suppl 1) 582A
- 97 Hadziyannis S J, Papatheodoridis G V. Treatment of HBeAg negative chronic hepatitis B with new drugs (adefovir and others). J Hepatol. 2003; 39(suppl 1) S172-S176
- 98 Hadziyannis S J, Tassopoulos N C, Heathcote E J et al.. Adefovir dipivoxil for the treatment of hepatitis B antigen-negative chronic hepatitis B. N Engl J Med. 2003; 348 800-807
- 99 Hadziyannis S J, Papatheodoridis G V. Adefovir dipivoxil in the treatment of chronic hepatitis B virus infection. Expert Rev Anti Infect Ther. 2004; 2 475-483
- 100 Hadziyannis S J, Tassopoulos N C, Heathcote E J et al.. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005; 352 2673-2681
- 101 Hadziyannis S J, Tassopoulos N, Chang T T et al.. Three year study of adefovir dipivoxil (ADV) demonstrates sustained efficacy in presumed precore mutant chronic hepatitis B (CHB) patients in a long term safety and efficacy study (LTES). J Hepatol. 2004; 40(suppl 1) 17
- 102 Hadziyannis S, Tassopoulos N, Chang T-T et al.. Long-term adefovir dipivoxil treatment induces regression of liver fibrosis in patients with HBeAg-negative chronic hepatitis B: results after 5 years of therapy. Hepatology. 2005; 42(suppl 1) 754A
- 103 Locarnini S, Qi X, Arterburn S et al.. Incidence and predictors of emergence of adefovir resistant HBV during four years of adefovir dipivoxil (ADV) therapy for patients with chronic hepatitis B (CHB). J Hepatol. 2005; 42(suppl 2) 17
- 104 Angus P, Vaughan R, Xiong S et al.. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology. 2003; 125 292-297
- 105 Fung S K, Andreone P, Han S H et al.. Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. J Hepatol. 2005; 43 937-943
- 106 Qi X, Snow A, Thibault V et al.. Long-term incidence of adefovir dipivoxil (ADV) resistance in chronic hepatitis B (CHB) patients after 144 weeks of therapy. J Hepatol. 2004; 40(suppl 1) 20
- 107 Yang H, Qi X, Das K et al.. In vitro characterization and molecular modeling analysis of a novel adefovir resistance mutation RTN236T in the HBV polymerase. J Hepatol. 2004; 40(suppl 1) 114
- 108 Aloman C, Wands J R. Resistance of HBV to adefovir dipivoxil: a case for combination antiviral therapy?. Hepatology. 2003; 38 1584-1587
- 109 Peters M G, Hann H H, Martin P et al.. Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology. 2004; 126 91-101
- 110 Westland C E, Yang H, Namimi H et al.. Comparison of anti-HBV activity of adefovir against different lamivudine-resistant HBV strains in vitro and in liver transplant patients. Hepatology. 2001; 34 446A
- 111 Fung S K, Chae H B, Fontana R et al.. HBV genotype D and switch to adefovir (ADV) monotherapy are associated with increased risk of ADV resistance in chronic hepatitis B (CHB) patients. Hepatology. 2005; 42(suppl 1) 590A
- 112 Lee C K, Yeon J E, Hong S P et al.. More frequent and earlier emergence of adefovir (ADV) resistance mutations in lamivudine resistant patients treated with ADV compared to previously reported nucleoside-treatment naive patients. Hepatology. 2005; 42(suppl 1) 593A
- 113 Lampertico P, Marzano A, Battista G et al.. A multicenter Italian study of rescue adefovir dipivoxil therapy in lamivudine resistant patients: a 2-year analysis of 604 patients. Hepatology. 2005; 42(suppl 1) 591A
- 114 Manolakopoulos S, Bethanis S, Koutsounas S et al.. Adefovir alone or combination with lamivudine in patients with lamivudine-resistance chronic HBeAg-negative hepatitis B: a non randomized multicenter controlled study. Hepatology. 2005; 42(suppl 1) 592A
- 115 Shaw T, Locarnini S. Entecavir for the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther. 2004; 2 853-871
- 116 Shouval D, Lai C-L, Cheinquer H et al.. Entecavir demonstrates superior histologic and virologic efficacy over lamivudine in nucleoside-naive HBeAg(-) chronic hepatitis B: results of phase III trial ETV-027. Hepatology. 2004; 40(suppl 1) 728A
- 117 Chang T T, Gish R G, Hadziyannis S J et al.. A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients. Gastroenterology. 2005; 129 1198-1209
- 118 Colonno R, Rose R, Levine S et al.. Entecavir two year resistance update: no resistance observed in nucleoside naive patients and low frequency resistance emergence in lamivudine refractory patients. Hepatology. 2005; 42(suppl 1) 574A
- 119 Tenney D J, Levine S M, Rose R E et al.. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine. Antimicrob Agents Chemother. 2004; 48 3498-3507
- 120 Torresi J, Locarnini S. Antiviral chemotherapy for the treatment of hepatitis B virus infections. Gastroenterology. 2000; 118(suppl) S83-S103
- 121 Shaw T, Bowden S, Locarnini S. Rescue therapy for drug resistant hepatitis B: another argument for combination chemotherapy?. Gastroenterology. 2004; 126 343-347
- 122 Lai C-L, Gane E, Liaw Y-F et al.. Telbivudine (LdT) vs lamivudine for chronic hepatitis B: first-year results from the international phase III GLOBE trial. Hepatology. 2005; 42(suppl 1) 748A
Professor
Stephanos J HadziyannisM.D.
Department of Medicine and Hepatology, Henry Dunant Hospital
107 Messogion Avenue, 11526 Athens, Greece