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Semin Liver Dis 2003; 23(1): 089-100
DOI: 10.1055/s-2003-37591
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Management of Patients with Decompensated HBV Cirrhosis

Robert J. Fontana
  • Assistant Professor of Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan
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Publication History

Publication Date:
03 March 2003 (online)

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ABSTRACT

Patients with decompensated hepatitis B virus (HBV) cirrhosis have a poor prognosis due to the development of progressive liver failure and hepatocellular carcinoma. Lamivudine appears to be a safe and effective antiviral agent, which may improve or stabilize liver disease in selected patients with advanced cirrhosis and active HBV replication. However, viral resistance can develop with prolonged treatment and some patients with advanced cirrhosis may not experience any discernible benefit. The use of hepatitis B immunoglobulin prophylaxis with or without lamivudine has resulted in excellent survival and a low rate of graft reinfection in patients who undergo liver transplantation for decompensated HBV cirrhosis. Adefovir and entecavir are newer antiviral agents that have activity against both wild-type and lamivudine-resistant HBV. Additional studies of individual or combination antiviral agents are urgently needed to improve further the prospects for the large number of patients worldwide with decompensated HBV cirrhosis.

KEYWORDS

Liver transplantation - lamivudine - hepatitis B - adefovir

REFERENCES

  • 1 Mast E E, Alter M J, Margolis H S. Strategies to prevent and control hepatitis B and C virus infections: a global perspective.  Vaccine . 1999;  17 1730-1733
    CrossrefPubMedGoogle Scholar
  • 2 McQuillan G M, Coleman P J, Kruszon-Moran D. Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition examination surveys, 1976 through 1994.  Am J Public Health . 1999;  89 14-18
    PubMedGoogle Scholar
  • 3 Margolis H S, Alter M J, Hadler S C. Hepatitis B: evolving epidemiology and implications for control.  Semin Liver Dis . 1991;  11 84-92
    PubMedGoogle Scholar
  • 4 Samuel D, Muller R, Alexander G. Liver transplantation in European patients with hepatitis B surface antigen.  N Engl J Med . 1993;  329 1842-1847
    CrossrefPubMedGoogle Scholar
  • 5 Weissberg J I, Andres L L, Smith C I. Survival in chronic hepatitis B. An analysis of 379 patients.  Ann Intern Med . 1984;  101 613-616
    PubMedGoogle Scholar
  • 6 De Jongh E F, Janssen H L, De Man A R. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver.  Gastroenterology . 1992;  103 1630-1635
    PubMedGoogle Scholar
  • 7 Fattovich G, Brollo L, Giustina G. Natural history and prognostic factors for chronic hepatitis B.  Gut . 1991;  32 294-298
    PubMedGoogle Scholar
  • 8 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
    PubMedGoogle Scholar
  • 9 Liaw Y F, Lin D Y, Chen T J. Natural course after the development of cirrhosis in patients with chronic type B hepatitis: a prospective study.  Liver . 1989;  9 235-241
    PubMedGoogle Scholar
  • 10 Donato F, Tagger A, Chiesa R. Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy.  Hepatology . 1997;  26 579-584
    CrossrefPubMedGoogle Scholar
  • 11 Nalpas B, Berthelot P, Thiers V. Hepatitis B virus multiplication in the absence of usual serological markers: a study of 146 chronic alcoholics.  J Hepatol . 1985;  1 89-97
    PubMedGoogle Scholar
  • 12 Krogsgaard K, Lindhardt B O, Nielsen J O. The influence of HTLV-III infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers.  Hepatology . 1987;  7 37-41
    PubMedGoogle Scholar
  • 13 Rustgi V K, Hoofnagle J H, Gerin J L. Hepatitis B virus infection in the acquired immunodeficiency syndrome.  Ann Intern Med . 1984;  101 795-797
    PubMedGoogle Scholar
  • 14 Liaw Y F. Role of hepatitis C virus in dual and triple hepatitis virus infection.  Hepatology . 1995;  22 1101-1108
    CrossrefPubMedGoogle Scholar
  • 15 Benvegnu L, Fattovich G, Noventa F. Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis: a prospective study.  Cancer . 1994;  74 2242-2248
    PubMedGoogle Scholar
  • 16 Fattovich G, Giustain G, Christensen E. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B.  Gut . 2000;  46 420-426
    CrossrefPubMedGoogle Scholar
  • 17 Sagnelli E, Piccinino F, Pasquale F. Delta agent infection: an unfavorable event in HBsAg positive chronic hepatitis.  Liver . 1984;  4 170-176
    PubMedGoogle Scholar
  • 18 Tur-Kaspa R, Shaul Y, Moore D D. The glucocorticoid receptor recognizes a specific nucleotide sequence in hepatitis B virus DNA causing increased activity of the HBV enhancer.  Virology . 1988;  167 630-633
    PubMedGoogle Scholar
  • 19 McMillan J S, Shaw T, Angus P W, Locarnini S A. Effect of immunosuppressive and antiviral agents on hepatitis B virus replication in vitro.  Hepatology . 1995;  22 36-43
    CrossrefPubMedGoogle Scholar
  • 20 Hoofnagle J H, Dusheiko G M, Schafer D F. Reactivation of chronic hepatitis B virus infection by cancer chemotherapy.  Ann Intern Med . 1982;  96 447-449
    PubMedGoogle Scholar
  • 21 Ahmed A, Keeffe E B. Lamivudine therapy for chemotherapy-induced reactivation of hepatitis B virus infection.  Am J Gastroenterol . 1999;  94 249-251
    CrossrefPubMedGoogle Scholar
  • 22 Lau G K, He M L, Fong D YT. Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation.  Hepatology . 2002;  36 702-709
    CrossrefPubMedGoogle Scholar
  • 23 Beasley R P. Hepatitis B virus. The major etiology of hepatocellular carcinoma.  Cancer . 1988;  61 1942-1956
    PubMedGoogle Scholar
  • 24 Yang H I, Lu S N, Liaw Y F. Hepatitis B e antigen and the risk of hepatocellular carcinoma N Engl J Med .  2002;  347 168-174
    PubMedGoogle Scholar
  • 25 Dragosics B, Ferenci P, Hitchman E, Denk H. Long-term follow-up study of asymptomatic HBsAg-positive voluntary blood donors in Austria: a clinical and histological evaluation in 242 cases.  Hepatology . 1987;  7 302-306
    PubMedGoogle Scholar
  • 26 Villeneuve J P, Desrochers M, Infante-Rivard C I. A long-term follow-up study of asymptomatic hepatitis B surface antigen positive carriers in Montreal.  Gastroenterology . 1994;  106 1000-1005
    PubMedGoogle Scholar
  • 27 Kamath P S, Wiesner R H, Malinchoc M. A model to predict survival in patients with end-stage liver disease.  Hepatology . 2001;  33 464-470
    CrossrefPubMedGoogle Scholar
  • 28 Keeffe E B. Liver transplantation: current status and novel approaches to liver replacement.  Gastroenterology . 2001;  120 749-762
    PubMedGoogle Scholar
  • 29 Seaberg E C, Belle S H, Beringer K C, Schivins J L, Detre K M. Liver transplantation in the United States from 1987-998: updated results from the PITT-UNOS liver transplant registry. In: Cecka JM, Terasaki PI, eds. Clinical Transplants 1998 Los Angeles: UCLA Tissue Typing Laboratory 1999: 17-37
    Google Scholar
  • 30 Fattovich G, Guistina G, Schalm S W. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B.  Hepatology . 1995;  21 77-82
    CrossrefPubMedGoogle Scholar
  • 31 Lok A SF, McMahon B J. Chronic hepatitis B.  Hepatology . 2001;  34 1225-1241
    CrossrefPubMedGoogle Scholar
  • 32 Keeffe E B. Is hepatitis A more severe in patients with chronic hepatitis B and other chronic liver diseases?.  Am J Gastroenterol . 1995;  90 201-205
    PubMedGoogle Scholar
  • 33 Centers for Disease Control and Prevention. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP).  MMWR Recomm Rep . 1996;  45 1-30
    PubMedGoogle Scholar
  • 34 Patel P, Voigt M D. Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States.  Am J Gastroenterol . 2002;  97 1198-1203
    CrossrefPubMedGoogle Scholar
  • 35 Teran J C, Imperiale T F, Mullen K D, Tavill A S, McCullough A J. Primary prophylaxis of variceal bleeding in cirrhotics: a cost effectiveness analysis.  Gastroenterology . 1997;  112 473-482
    PubMedGoogle Scholar
  • 36 Sharara A I, Rockey D C. Gastroesophageal variceal hemorrhage.  N Engl J Med . 2001;  345 669-680
    CrossrefPubMedGoogle Scholar
  • 37 Lucas A, D'Amico G, Galla R. TIPS for prevention of recurrent bleeding in patients with cirrhosis: meta-analysis of randomized controlled trials.  Radiology . 1999;  212 411-421
    CrossrefPubMedGoogle Scholar
  • 38 Rossle M, Ochs A, Gulberg V. A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.  N Engl J Med . 2000;  342 1701-1707
    CrossrefPubMedGoogle Scholar
  • 39 Lok A S, Heathcote E J, Hoofnagle J H. Management of hepatitis B: 2000-summary of a workshop.  Gastroenterology . 2001;  120 1828-1853
    PubMedGoogle Scholar
  • 40 Sherman M, Peltekian K M, Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population.  Hepatology . 1995;  22 432-437
    CrossrefPubMedGoogle Scholar
  • 41 Sallie R. Screening for hepatocellular carcinoma in patients with chronic viral hepatitis: can the results justify the effort?.  Viral Hepat Rev . 1995;  1 77-95
    PubMedGoogle Scholar
  • 42 Tsai S L, Huang G T, Yang P M. Plasma des-gamma-carboxyprothrombin in the early stage of hepatocellular carcinoma.  Hepatology . 1990;  11 481-488
    PubMedGoogle Scholar
  • 43 Perrillo R P, Schiff E R, Davis G L. A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B.  N Engl J Med . 1990;  323 295-301
    PubMedGoogle Scholar
  • 44 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;  119 312-333
    PubMedGoogle Scholar
  • 45 Niederau C, Heinteges 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
    CrossrefPubMedGoogle Scholar
  • 46 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
    CrossrefPubMedGoogle Scholar
  • 47 Hoofnagle J H, DiBisceglie A M, Waggoner J G, Park Y. Interferon alfa for patients with clinically apparent cirrhosis due to chronic hepatitis B.  Gastroenterology . 1993;  104 1116-1121
    PubMedGoogle Scholar
  • 48 Perrillo R, Tamburro C, Regenstein F. Low dose, titratable interferon alfa in decompensated liver disease caused by chronic infection with hepatitis B virus.  Gastroenterology . 1995;  109 908-916
    PubMedGoogle Scholar
  • 49 Lai C L, Yuen M F, Hui C K. Comparison of the efficacy of lamivudine and famciclovir in Asian patients with chronic hepatitis B: results of 24 weeks of therapy.  J Med Virol . 2002;  67 334-338
    CrossrefPubMedGoogle Scholar
  • 50 Aye T T, Bartholomeusz A, Shaw T. Hepatitis B virus polymerase mutations during antiviral therapy in a patient following liver transplantation.  J Hepatol . 1997;  26 1148-1153
    CrossrefPubMedGoogle Scholar
  • 51 Berenguer M, Prieto M, Rayon M. Famciclovir treatment in transplant recipients with HBV-related liver disease: disappointing results.  Am J Gastroenterol . 2001;  96 526-533
    CrossrefPubMedGoogle Scholar
  • 52 Singh N, Gayowski T, Wannstedt C F. Pretransplant famciclovir as prophylaxis for hepatitis B virus recurrence after liver transplantation.  Transplantation . 1997;  63 1415-1419
    PubMedGoogle Scholar
  • 53 Gish R G, Lau J Y, Brooks L. Ganciclovir treatment of hepatitis B virus infection in liver transplant recipients.  Hepatology . 1996;  21 1-7
    PubMedGoogle Scholar
  • 54 Dienstag J, Schiff E R, Wright T L. Lamivudine as initial treatment for chronic hepatitis B in the United States.  N Engl J Med . 1999;  341 1256-1263
    CrossrefPubMedGoogle Scholar
  • 55 Lai C, Chien R, Leung N WY. A one year trial of lamivudine for chronic hepatitis B.  N Engl J Med . 1998;  339 61-68
    CrossrefPubMedGoogle Scholar
  • 56 Villeneuve J, Condreay L D, Willems B. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B.  Hepatology . 2000;  31 207-210
    CrossrefPubMedGoogle Scholar
  • 57 Yao F Y, Bass N M. Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection.  J Hepatol . 2000;  33 301-307
    CrossrefPubMedGoogle Scholar
  • 58 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
    CrossrefPubMedGoogle Scholar
  • 59 Kapoor D, Guptan R C, Wakil S M. Beneficial effects of lamivudine in hepatitis B virus related decompensated cirrhosis.  J Hepatol . 2000;  33 308-312
    CrossrefPubMedGoogle Scholar
  • 60 Kitay-Cohen Y, Ben-ari Z, Tur-Kaspa R, Fainguelernt H, Lishner M. Extension of transplantation free time by lamivudine in patients with hepatitis B induced decompensated cirrhosis.  Transplantation . 2000;  69 2382-2383
    PubMedGoogle Scholar
  • 61 Fontana R J, Keeffe E B, Carey W. Effect of lamivudine treatment on survival of 309 North American patients awaiting liver transplantation for chronic hepatitis B.  Liver Transplant . 2002;  8 433-439
    CrossrefPubMedGoogle Scholar
  • 62 Perrillo R P, Wright T, Rakela J. A multi-center United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B.  Hepatology . 2001;  33 424-432
    CrossrefPubMedGoogle Scholar
  • 63 Fontana R J, Hann H L, Perrillo R P. Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy.  Gastroenterology . 2002;  123 719-727
    CrossrefPubMedGoogle Scholar
  • 64 Fontana R J, Lok A SF. Lamivudine treatment in patients with decompensated hepatitis B cirrhosis: for whom and when?.  [editorial] Hepatology . 2000;  33 329-332
    PubMedGoogle Scholar
  • 65 Leung N WY, Lai C L, Chang T T. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy.  Hepatology . 2001;  33 1527-1532
    CrossrefPubMedGoogle Scholar
  • 66 Allen M I, Deslauriers M, Andrews W. Identification and characterization of mutations in hepatitis B virus resistant to lamivudine.  Hepatology . 1998;  27 1670-1677
    CrossrefPubMedGoogle Scholar
  • 67 Melegari M, Scaglioni P P, Wands J R. Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective.  Hepatology . 1998;  27 628-633
    CrossrefPubMedGoogle Scholar
  • 68 Liaw Y, Chien R, Yeh C, Tsai S, Chu C. Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy.  Hepatology . 1999;  30 567-572
    CrossrefPubMedGoogle Scholar
  • 69 Yeh C T, Chien R N, Chu C M, Liaw Y F. Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy.  Hepatology . 2000;  31 1318-1326
    CrossrefPubMedGoogle Scholar
  • 70 Lok A S, Hussain M, Cursano C. Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen- negative patients receiving lamivudine therapy.  Hepatology . 2000;  32 1145-1153
    CrossrefPubMedGoogle Scholar
  • 71 Shouval D, Samuel D. Hepatitis B immune globulin to prevent hepatitis B virus graft reinfection following liver transplantation: a concise review.  Hepatology . 2000;  32 1189-1195
    CrossrefPubMedGoogle Scholar
  • 72 Mutimer D, Pillay D, Dragon E. High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft reinfection after liver transplantation.  J Hepatol . 1999;  30 715-721
    CrossrefPubMedGoogle Scholar
  • 73 Han S H, Ofman J, Holt C. An efficacy and cost-effectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy.  Liver Transplant . 2000;  6 741-748
    CrossrefPubMedGoogle Scholar
  • 74 Angus P W, McCaughan G W, Gane E J, Crawford D H, Harley H. Combination low-dose hepatitis B immune globulin and lamivudine therapy provides effective prophylaxis against posttransplantation hepatitis B.  Liver Transplant . 2000;  6 429-433
    CrossrefPubMedGoogle Scholar
  • 75 Yao F Y, Osorio R W, Roberts J P. Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation.  Liver Transplant Surg . 1999;  5 491-496
    CrossrefPubMedGoogle Scholar
  • 76 Locarnini S A. Hepatitis B virus surface antigen and polymerase gene variants: potential virological and clinical significance [editorial].  Hepatology . 1998;  27 294-297
    CrossrefPubMedGoogle Scholar
  • 77 Saab S, Kim M, Wright T L. Successful orthotopic liver transplantation for lamivudine-associated YMDD mutant hepatitis B virus.  Gastroenterology . 2000;  119 1382-1384
    PubMedGoogle Scholar
  • 78 Schiff E, Lai C L, Neuhaus P. Adefovir dipivoxil for the treatment of chronic hepatitis B in patients pre and post liver transplantation with lamivudine resistant hepatitis B virus patients (Abst).  Hepatology . 2002;  36 371A
    PubMedGoogle Scholar
  • 79 Rosenau J, Bahr M J, Tillmann H L. Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B reinfection after liver transplantation: possible role of mutations in the YMDD motif prior to transplantation as a risk factor for reinfection.  J Hepatol . 2001;  34 895-902
    CrossrefPubMedGoogle Scholar
  • 80 Marcellin P, Goodman Z, Chang T T. Histological improvement in HBeAg positive chronic hepatitis B patients treated with adefovir dipivoxil (Abst).  J Hepatol . 2002;  36(Suppl 1) 8
    PubMedGoogle Scholar
  • 81 Hadiziyannis S, Tassopolous N, Heathcote E. A double-blind, randomized placebo-controlled study of adefovir dipivoxil for presumed precore mutant chronic hepatitis B: 48 week results (Abst).  J Hepatol . 2002;  36(Suppl 1) 4
    PubMedGoogle Scholar
  • 82 Perrillo R, Schiff E, Yoshida E. Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants.  Hepatology . 2000;  32 129-134
    CrossrefPubMedGoogle Scholar
  • 83 Peters M, Schiff E, Benhamou Y. Adefovir dipivoxil demonstrates antiviral efficacy and clinical benefit in the treatment of lamivudine resistant chronic HBV: an analysis of four clinical trials (Abst).  Gastroenterology . 2002;  123(Suppl) 71
    PubMedGoogle Scholar
  • 84 Shakil A O, Lilly L, Angus P. Entecavir reduces viral load in liver transplant patients who failed prophylaxis or treatment for hepatitis B (Abst).  Hepatology . 2001;  34 619A
    PubMedGoogle Scholar
  • 85 DeMan R A, Wolters L MM, Nevens F. Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection.  Hepatology . 2001;  34 578-582
    CrossrefPubMedGoogle Scholar
  • 86 Levine S, Hernandez D, Yamanaka G. Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro.  Antimicrob Agents Chemother . 2002;  46 2525-2532
    CrossrefPubMedGoogle Scholar
  • 87 James J S. Tenofovir approved: broad indication.  AIDS Treat News . 2001;  26 2-3
    PubMedGoogle Scholar
  • 88 Van Bommel F, Wunsche T, Schurmann D, Berg T. Tenofovir treatment in patients with lamivudine-resistant hepatitis B mutants strongly affects viral replication.  Hepatology . 2002;  36 507-508
    CrossrefPubMedGoogle Scholar
  • 89 Chien R N, Liaw Y F, Atkins M. Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion and continued ALT normalization in Asian patients with chronic hepatitis B. Asian Hepatitis Lamivudine Trial Group.  Hepatology . 1999;  30 770-774
    CrossrefPubMedGoogle Scholar
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