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Treatment of Hepatitis B in Special Patient Groups: Hemodialysis, Heart and Renal Transplant, Fulminant Hepatitis, Reactivation under Immunosuppressive Therapy

Michael Peter Manns, Heiner Wedemeyer, Hans Ludger Tillmann
Departent of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Germany

Abstract

The treatment of hepatitis B virus infection is particular in certain patient groups such as patients prior to and after kidney transplantation and heart transplanted patients. For all these patient group interferon alpha is either of limited efficacy or even contraindicated. However, lamivudine is highly effective in these patients. If resistance emerges a newer nucleoside analogue, adefovir, has become available.

Furthermore the approach to treat and prevent HBV reactivation in immunosuppressed patients is crucial. Here, the prevention of reactivation is better than treating the reactivation. As the prevention of reactivation usually is only required for a limited time frame the risk of resistance development will be rare.

Finally, fulminant hepatitis is a severe course of acute hepatitis frequently progressing to fulminant hepatic failure. Once liver failure has developed a conservative approach is unlikely to prevent the need of liver transplantation. However, in the early phase of fulminant hepatitis, when severe impairment of liver function is already evident but encephalopathy still absent treatment with nucleosides, especially lamivudine, may be effective.

Introduction

An estimated 350 million worldwide are infected with the hepatitis B virus (HBV). More than 90% of immunocompetent adult patients clear the HBV after acute infection. In contrast, chronicity develops more frequently in immunocompromised patients, e.g. up to 60% in dialysis patients.[1] After organ transplantation, HBsAg clearance occurs only occasionally. Additionally, as the hepatitis B virus frequently persists even after clearance of HBsAg from the circulation, patients undergoing organ transplantation may suffer HBV reactivation. This is of special importance in patients receiving bone-marrow-transplantation (BMT). In addition organs from donors who are anti-HBc (+) but HBsAg (-) still can transmit HBV infection. While this has frequently been observed after liver transplantation it may also occur with other organ transplantations.[2]

The purpose of this review is to summarise the data on the relevance and treatment of HBV infection in hemodialysis patients and patients after kidney or heart transplantation. Additionally we discuss reactivation of hepatitis B and its treatment in organ transplant recipients and patients undergoing chemotherapy. Finally, we review the data on severe acute and fulminant hepatitis B and the available evidence for preventing liver failure in these patients by early treatment with antiviral agents.

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Hemodialysis patients

Due to the high infectivity of HBV and its infection route, many patients requiring dialysis have been infected with HBV in the past associated with blood transfusion and the dialysis procedure itself.[3], [4], [5] However, the introduction of vaccination against HBV has decreased the overall prevalence of HBV infection in this patient group from above 10% in the early 90-ties[6] to below 5% at the turn of the century in most European countries.[7], [8] Active HBV vaccination is recommended for all patients with end stage renal disease (ESRD). However, non-response or incomplete response to standard HBV vaccines are more frequent in these patients. Thus general precautions for the prevention of viral transmission are still mandatory.

A number of studies have shown that hepatitis C virus infection can be successfully eliminated with interferon-a in dialysis patients, but side effects are usually higher than in “normal patients”.[9], [10] If HCV has been eliminated during dialysis, reactivation after transplantation is rare. In contrast to HCV, neither interferon-a nor nucleoside analogues induce complete HBV elimination. Thus reactivation after transplantation can not be excluded in the case of HBV infection.

No controlled trials for the treatment of HBV with either lamivudine or interferon in dialysis patients are currently available. A single case series describes an HBeAg seroconversion in 3 of 9 dialysis patients treated with interferon-a,[11] thus being not significantly different from immunocompetent patients.

Indications for treatment intervention should thus be similar to immunocompetent patients. We would recommend to perform a liver biopsy if transaminases are elevated. Because of side effects, nucleosides appear to be superior to interferon in this patient population. The potential development of viral resistance to lamivudine should not result in withholding this treatment, as newer options with efficacy against lamivudine resistant HBV will be approved in the near future, and are available through an expanded access program..

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Kidney recipients

Since many patients have acquired HBV during the time on dialysis, chronic HBV infection can be found in a significant number of kidney recipients. While short term studies with a mean follow-up below 10 years after transplantation often failed to detect a negative effect of HBV infection in this patient population[12] studies including more than 10 year of follow-up usually show impaired survival of HBsAg positive kidney recipients.[13], [14], [15], [16] Liver failure becomes the leading cause of death in HBsAg positive patients 10 years post kidney transplantation.13 It is also important to note that the natural course of chronic hepatitis B is worse than that of hepatitis C after renal transplantation.[17].

Thus, treatment approaches against HBV are needed in this population. Interferon can lead to rejection precluding its use,[18], [19]. In some cases a remarkable response to interferon has been observed in single cases,[20], [21], [22]. However, a larger case series from Poland did showed disappointing results.[23] Fortunately, alternative options became available in the recent years, which are not associated with the induction of rejection. While famciclovir had been of limited efficacy[24] similar to its use in liver transplant recipients,[25] lamivudine leads to biochemical remission and reduction of viral load in up to 100% of treated patients.[26] Still resistance can emerge, and newer options are needed.[27]

There is a special severe form of hepatitis B occurring in immunosuppressed patients, so called fibrosing cholestatic hepatitis (FCH). This condition was originally described in patients after liver transplantation, but has also been reported in other immunocompromised patients. It is characterized clinically by cholestatic liver disease, and by severe periportal fibrosis, cholestasis, widespread balloon degeneration of hepatocytes, and only mild infiltration of inflammatory cells. Without treatment, FCH is universally fatal within a few months after diagnosis.[28] However, some cases of successful intervention with lamivudine have recently been reported. Interestingly, while the response to lamivudine was only limited for a few weeks in liver transplant recipients[29] a long term response was observed in kidney recipients.[30], [31], [32]

In summary, chronic hepatitis B leads to reduced survival in the second decade after renal transplantation and thus requires treatment. Due to the risk of rejection interferon-a is not recommended. Lamivudine is effective, in case of resistance adefovir should be considered.

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Heart transplant recipients

In the 1980-ties it has been recognized that HBV infection can be a cause for impaired liver function in heart transplanted patients.[33] This led to the recommendation that patients awaiting heart transplantation should be vaccinated against HBV. If immunity against HBV is achieved, either by previous infection or by vaccination, even HBsAg positive organs can be transplanted without the induction of HBV infection.[34] Here, it is important to note that patients undergoing heart transplantation should be vaccinated prior to transplantation due to the low response rates achieved after transplantation.[35]

Chronic hepatitis B after heart transplantation is surprisingly frequent. Outbreaks of HBV infection have been identified in several heart transplant centers. Patients frequently acquired HBV during the procedure of endomyocardial biopsies,[36], [37], [38] which they had to undergo for control of rejection.

In our centre survival was shown to be similar in HBsAg-positive and -negative patients during the first decade after transplantation in a large study including 74 HBsAg-positive heart transplant recipients. However and similar to the experience in kidney recipients, the survival of HBsAg-positive patients is impaired after more than 10 years after transplantation.[39], [40] Up to one third of the patients die from liver failure and hepatocellular carcinoma may develop.40 In accordance with our data, another recent study showed no impaired survival during the first 5 years after transplantation.37 However as outlined above, a five year follow-up is too short, as the impairment becomes evident in the second decade. Similar to the experience in other organ transplantations, the course of HBV infection is more severe than that of HCV infection after heart transplantation.[41]

Thus, treatment is highly warranted for these patients with long term survival. Different nucleosides have been used in heart transplant recipients. In 1996, Amand et al. were able to show a benefit of gancilovir, which led to a remarkable improvement of disease activity in a heart recipient who had developed decompensated liver disease due to HBV infection.[42]. In 1997, we initiated a controlled study for the use of famciclovir in HBsAg-positive heart transplant recipients. While virological and biochemical responses were weak using famciclovir, a remarkable improvement in histological grading and staging was observed after a median of 8 months of therapy (s. Figure 1).[43] Due to incomplete virological response or development of resistance, most patients were switched later on to lamivudine, which is nowadays widely used as a first line therapy in these patients. Similar to patients after kidney transplantation, adefovir, (expected to be approved within the year 2003 in many countries) can be used when lamivudine resistance develops.

In summary, as interferon can induce rejection, which might be fatal in heart transplantats, we regard this option as absolutely contraindicated. With direct antivirals, such as nucleoside analogues, not only a biochemical and virological response but also a reduction of liver inflammation and regression of fibrosis can be achieved leading to improved long-term survival. It should be emphasized that not all HBsAg-positive patients necessarily need therapeutic intervention. Thus, we recommend a liver biopsy prior to the start of an antiviral therapy.

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Hepatitis B Virus Reactivation

Reactivation of hepatitis B infection can frequently be observed during cancer chemotherapy in chronic HbsAg carriers especially, when immunosuppressive treatment is stopped, the return of immune competence can be followed by liver damage of varying degrees of severity, including fulminant hepatitis. Hepatitis B flares, during or shortly after chemotherapy, have been reported for more than 20 years.[44] It is a frequent problem, occurring in 21-53% of chronic HBsAg carriers.[45], [46], [47] Acute hepatitis caused by HBV reactivation may be severe, with jaundice occurring in 10-22% of cases and mortality rates from acute liver failure ranging from 4% to 41% of affected patients.47, [48], [49], [50] It is not possible to predict the occurrence and the clinical severity of HBV reactivation on an individual basis. The use of corticosteroids among the protocol drugs has to be considered a predisposing factor for treatment-induced HBV reactivation. [51], 45, [52], 52a The frequency of reactivation after chemotherapy cycles that did or did not include corticosteroids was 47% and 8%, respectively. Furthermore, it has been reported that the frequency as well as the severity of HBV flares were higher in HBeAg-negative patients.45, 47, 50 Furthermore, it is important to note that reactivation can also emerge in anti-HBc positive but HBsAg negative patients as HBV persists even after clearance of HBsAg.[53], [54] Thus PCR based detection of HBV-DNA prior to chemotherapy is recommended.[55], [56]

Viral hepatitis may cause delays and reductions in the application of cytostatic drugs, and may hinder the continuation of the treatment programme. With the more widespread use of chemotherapy and stem cell transplantation, the possibility of HBV reactivation is becoming a significant problem that may ultimately affect the outcome of cancer treatment.

Thus the prevention of such reactivation is highly desired. As chemotherapy usually only lasts for a few months, a suppression of HBV is only required for about half a year. Within this short time period the development of viral resistance to currently applied nucleosides is unlikely to occur.

Recombinant a-interferon has been widely administered, but its haemopoietic toxicity precludes its use as a prophylactic agent in association with aggressive chemotherapy. In addition, interferon-a is anticipated to be of low efficacy in immunocompromised patients. Nucleoside analogues, such as famciclovir and lamivudine, are active against HBV by interfering with viral DNA replication. Lamivudine has been used extensively and has been proven effective both in the treatment and as a prevention of chemotherapy-related HBV reactivation.46, [57], [58] However, treatment of HBV reactivation does not completely avoid the significant risk of fulminant hepatitis, particularly in HBeAg-negative patients.[59] Thus, primary prevention of HBV reactivation appears to be a more appropriate strategy. Famciclovir was effective in reducing the incidence of HBV reactivation after allogeneic bone marrow transplantation.[60] As shown previously, only about one third of the patients show a good response to famciclovir, while non response to lamivudine is rare.[61] The toxicity profile of lamivudine is particularly favourable because it does not overlap with that of cytostatic agents, making lamivudine particularly suitable for the simultaneous use with chemotherapies. Indeed, recent pilot studies confirmed the feasibility to prevent hepatitis B reactivation with lamivudine.[62], [63]

In summary, a prophylactic antiviral treatment with lamivudine appears to be indicated for HBsAg positive patients undergoing highly immunosuppressive therapy. A close monitoring of anti-HBc positive / HBsAg negative patients is recommended, and antiviral treatment should be started only if HBsAg turns positive or HBV-DNA levels increase.

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Fulminant hepatitis B

Fulminant hepatitic failure may develop in about 1% of patients suffering from acute hepatitis B.[64] In addition, as outlined above fulminant hepatitis can emerge in immunosuppressed patients. Without liver transplantation, death occurs in the majority of patients with acute fulminant hepatitic failure.[65], [66], [67], [68] However, in patients with underlying malignancies liver transplantation is contraindicated. No therapy is currently established for fulminant hepatitis B. Foscarnet has been reported useful in a patient with fulminant hepatitis B. The success to prevent death or transplantation has been related to the influence of therapy on the immune function rather than on the level of HBV replication..[69]

For the therapy of chronic hepatitis B, two approved treatment options are currently available: interferon-alpha or lamivudine. Interferon is immune-stimulating and thus may be dangerous in fulminant hepatitis B, where overwhelming immune reaction is believed to be involved in the pathogenesis.[70], [71] In contrast, the oral nucleoside analogue lamivudine inhibits hepatitis B viral replication with an immediate decline of serum HBV-DNA. Furthermore, lamivudine’s adverse event profile has been shown to be similar to placebo.[72], [73]

In the absence of alternatives lamivudine has been used in a few patients with fulminant hepatitis B due to reactivation following organ transplants[74] or anticancer therapy[75], [76], [77], [78].

However, no published data are available for fulminant hepatitis B. Thus, it is a matter of debate whether lamivudine therapy should be initiated in patients with fulminant hepatitis B, as there has been concerns that lamivudine treatment might be dangerous in fulminant hepatitis B or useless, since HBV-DNA is usually low in these patients. Based on the excellent safety profile of lamivudine, we started treating patients with fulminant hepatitis B with lamivudine immediately after the diagnosis of a fulminant course. Patients were treated with lamivudine 150mg daily (s. Figure 2). All except one of eight patients treated with lamivudine recovered quickly without adverse events. The only patients requiring transplantation despite lamivudine therapy had also ingested paracetamol, (Tillmann et al, unpublished data).

In Summary, lamivudine is safe in patients with fulminant hepatitis B, and might have the potential to prevent fatal liver failure or liver transplantation when administered early. Prospective controlled trails are necessary in order to establish a medical treatment for fulminant hepatitis B.

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References:

  1. Bruguera M, Vidal L, Sanchez-Tapias JM, Costa J, Revert L, Rodes J. Incidence and features of liver disease in patients on chronic hemodialysis. J Clin Gastroenterol 1990;12:298-302.
  2. Wachs ME, Amend WJ, Ascher NL, Bretan PN, Emond J, Lake JR, al. The risk of transmission of hepatitis B from HBsAg (-), HBcAb (+), HBIgM (-) organ donors. Transplantation 1995;59:230-234.
  3. Mioli VA, Balestra E, Bibiano L, Carletti P, Della Bella S, Fanciulli E, et al. Epidemiology of viral hepatitis in dialysis centers: a national survey. Nephron 1992;61:278-283
  4. Friedman EA, Thomson GE. Hepatitis complicating chronic hemodialysis. Lancet 1966;II, 675-678.
  5. Mazzoni A, Innocenti M, Consaga M. Retrospective study on the prevalence of B and non-A, non-B hepatitis in a dialysis unit: 17-year follow-up. Nephron 1992;61:316-317.
  6. Franco E, Olivadese A, Valeri M, Albertoni F, Petrosillo N. Control of hepatitis B virus infection in dialysis units in Latium, Italy. Nephron 1992;61:329-30
  7. Ambuhl PM, Binswanger U, Renner EL. Epidemiology of chronic hepatitis B and C among dialysis patients in Switzerland. Schweiz Med Wochenschr. 2000 ;130:341-348.
  8. Lopez-Alcorocho JM, Barril G, Ortiz-Movilla N, Traver JA, Bartolome J, Sanz P, et al. Prevalence of hepatitis B, hepatitis C, GB virus C/hepatitis G and TT viruses in predialysis and hemodialysis patients. J Med Virol 2001;63:103-107.
  9. Ellis ME, Alfurayh O, Halim MA, Sieck JO, Ali MA, Bernvil SS, et al. Chronic non-A, non-B hepatitis complicated by end-stage renal failure treated with recombinant interferon alpha. J Hepatol. 1993;18:210-216.
  10. Koenig P, Vogel W, Umlauft F, Weyrer K, Prommegger R, Lhotta K, et al. Interferon treatment for chronic hepatitis C virus infection in uremic patients. Kidney Int 1994;45,1507-1509.
  11. Zwolinska D, Inglot M, Makulska I, Gladysz A, Szprynger K, Szczepanska M, et al. Epidemiology of HBV infection and possibilities for therapeutic actions in children and adolescents with end-stage renal failure treated with dialysis. Pol Merkuriusz Lek 2001;10:267-270.
  12. Huo TI, Yang WC, Wu JC, King KL, Loong CC, Lin CY, et al, Kidney transplantation in patients with chronic hepatitis B virus infection: is the prognosis worse? Dig Dis Sci 2001,46:469-475.
  13. Kliem V, Ringe B, Holhorst K, Frei U. Kidney transplantation in hepatitis B surface antigen carriers. Clin-Investig. 1994; 72: 1000-1006.
  14. Rao KV; Kasiske BL; Anderson WR. Variability in the morphological spectrum and clinical outcome of chronic liver disease in hepatitis B-positive and B-negative renal transplant recipients. Transplantation 1992;51: 391-396.
  15. Aroldi A, Tarantino A, Montagnino G, Paparella M, Cesana B, Rumi MG, Ponticelli C. Renal transplant recipients and chronic liver disease: statistical evaluation of predisposing factors. Nephron 1992;61: 290-292.
  16. Fairley-CK; Mijch-A; Gust-ID; Nichilson-S; Dimitrakakis-M; Lucas-CR. The increased risk of fatal liver disease in renal transplant patients who are hepatitis Be antigen and/or HBV DNA positive. Transplantation 1991;52: 497-500
  17. Lee WC, Shu KH, Cheng CH, Wu MJ, Chen CH, Lian JC. Long term impact of hepatitis B, C virus infection on renal transplantation. Am J Nephrol 2001;21;300-306.
  18. Kramer P, ten Kate FW, Bijnen AB, Jeekel J, Weimar W. Recombinant leucocyte interferon A induces steroid-resistant acute vascular rejection episodes in renal transplant recipients. Lancet. 1984;1(8384):989-990.
  19. Kovarik J, Mayer G, Pohanka E, Schwarz M, Traindl O, Graf H, Smolen J. Adverse effect of low-dose prophylactic human recombinant leukocyte interferon-alpha treatment in renal transplant recipients. Cytomegalovirus infection prophylaxis leading to an increased incidence of irreversible rejections. Transplantation. 1988;45:402-405.
  20. Grotz W, Gondolf K, Rasenack J, Berthold H, Rump LC, Schollmeyer P. Imminent liver failure in a hepatitis-B-positive renal-allograft recipient: successful therapy with interferon-alpha. Nephrol Dial Transplant. 1995;10:1932-1934.
  21. Post AB, Hricik DE, Sterling RK, Bartucci MR, Jacobs GH, Schulak JA. Resolution of hepatitis B viremia in a renal transplant recipient treated with alpha-2b interferon. Nephron 1998;79:469-471.
  22. Rostaing L, Izopet J, Cisterne JM, Baron E, Rumeau JL, Chabannier MH, et al. Treatment of chronic hepatitis B and C with alpha interferon in a renal transplant patient. Scand J Urol Nephrol 1996;30:485-487.
  23. Durlik M, Gaciong Z, Rowinska D, Rancewicz Z, Lewandowska D, Kozlowska B, et al. Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients. Transpl Int 1998;11 Suppl 1:S135-139
  24. Tillmann HL, Kliem V, Eisenberger U, Petersen R, Koch KM, Pichlmayr R, et al. Famciclovir Therapie der chronischen Hepatitis B nach Nieren-Transplantation. Z Gastroenterol 1998; 36; 759.
  25. Krüger M, Tillmann HL, Trautwein C, Bode U, Oldhafer K, Maschek H, et al. Famciclovir treatment of hepatitis B virus recurrence after liver transplantation: a pilot study. Liver Transpl Surg 1996; 2:253-262.
  26. Rostaing L, Henry S, Cisterne JM, Duffaut M, Icart J, Durand D. Efficacy and safety of lamivudine on replication of recurrent hepatitis B after cadaveric renal transplantation. Transplantation 1997 Dec;64:1624-1627.
  27. Peters MG, Singer G, Howard T, Jacobsmeyer S, Xiong X, Gibbs CS, et al. Fulminant hepatic failure resulting from lamivudine resistant hepatitis B virus in a arenal transplant recipient. Transplantation 1999; 68: 1912-1914.
  28. Brind AM, Bennett MK, Bassendine MF. Nucleotide analogue therapy in fibrosing cholestatic hepatitis - a case report in an HBsAg positive renal transplant recipient. Liver 1998;18;134-9.
  29. Tillmann HL, Trautwein C, Bock CT, Glomb I, Krüger M, Böker KHW, et al. Lamivudine transiently reduces viral load and improves liver function in liver transplant recipients with fibrosing cholestatic hepatitis. Am J Gastroenterol 2002;97:777-778.
  30. Al Faraidy K, Yoshida EM, Davis JE, Vartanian RK, Anderson FH, Steinbrecher UP. Alteration of the dismal natural history of fibrosing cholestatic hepatitis secondary to hepatitis B virus with the use of lamivudine. Transplantation 1997;64:926-928.
  31. Chan TM, Wu PC, Li FK, Cheng IK, Lai KN. Treatment of fibrosing cholestatic hepatitis with lamivudine. Gastroenterology 1998;115:177-181.
  32. Jung S, Lee HC, Han JM, Lee YJ, Chung YH, Lee YS, et al, Four cases of hepatitis B virus-related fibrosing cholestatic hepatitis treated with lamivudine. J Gastroenterol Hepatol 2002;17:345-350.
  33. Cadranel JF, Grippon P, Mattei MF, Lunel F, Pauwels A, Rossant P, et al. Prevalence and causes of long-lasting hepatic dysfunction after heart transplantation: a series of 80 patients. Artif Organs 1988, 12, 234-238
  34. Ko WJ, Chou NK, Hsu RB, Chen YS, Wang SS, Chu SH, Lai MY. Hepatitis B virus infection in heart transplant recipients in a hepatitis B endemic area. J Heart Lung Transplant 2001;20:865-875.
  35. Wagner D, Wagenbreth I, Stachan-Kunstyr R, Thoma HA, Hemmerling AE, Flik J. Hepatitis B vaccination of immunosuppressed heart transplant recipients with the vaccine Hepa Gene 3 containing pre-S1, pre-S2, and S gene products.Clin Investig 1994;72:350-352
  36. Drescher J, Wagner D, Haverich A, Flik J, Stachan-Kunstyr R, Verhagen W, Wagenbreth I. Nosocomial hepatitis B virus infections in cardiac transplant recipients transmitted during transvenous endomyocardial biopsy. J Hosp Infect 1994;26:81-92.
  37. Lunel F, Cadranel JF, Rosenheim M, Dorent R, Di-Martino V, Payan C, et al. Hepatitis virus infections in heart transplant recipients: epidemiology, natural history, characteristics, and impact on survival. Gastroenterology 2001;119:1064-1074.
  38. Osterhaus AD, Vos MC, Balk AH, de Man RA, Mouton JW, Rothbarth PH, et al. Transmission of hepatitis B virus among heart transplant recipients during endomyocardial biopsy procedures. J Heart Lung Transplant 1998;17:158-166.
  39. Wedemeyer H, Pethig K, Wagner D, Flemming P, Oppelt P, Petzold DR, et al. Long-term outcome of chronic hepatitis B in heart transplant recipients. Transplantation 1998; 66: 1347-1353.
  40. Wedemeyer H, Pethig K, Manns MP, Böker KHW. Hepatitis B in heart transplant recipients. Gastroenterology 2001;120:1311-1313.
  41. Fagiuoli S, Minniti F, Pevere S, Farinati F, Burra P, Livi U, et al. HBV and HCV infections in heart transplant recipients. J Heart Lung Transplant 2001;20:718-24
  42. Anand BS, Yoffe B, Young JB.. Ganciclovir treatment of active hepatitis B virus infection in a heart transplant patient. J Clin Gastroenterol 1996; 22:144-146
  43. Wedemeyer H, Boker KH, Pethig K, Petzold DR, Flemming P, Tillmann HL, et al. Famciclovir treatment of chronic hepatitis B in heart transplant recipients: a prospective trial. Transplantation 1999; 68:1503-1511.
  44. Hoofnagle JH, Dusheiko GM, Schafer DF, Jones EA, Micetich KC, Young RC, Costa J. Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann Intern Med 1982;96:447-449.
  45. Nakamura Y, Motokura T, Fujita A, Yamashita T, Ogata E. Severe hepatitis related to chemotherapy in hepatitis B virus carrier with hematologic malignancies. Survey in Japan. 1987-91.Cancer 1996 78:2210-2215
  46. Yeo W, Chan PKS, Zhong S, Ho WM, Steimberg JL, Tam JS, et al. Frequency of hepatitis B virus reactivation in cancer patient undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol 2000;62, 299-307.
  47. Kumagai K, Takagi T, Nakamura S, Sawada U, Kura Y, Kodama F, et al. Hepatitis B virus carriers in the treatment of malignant lymphoma : an epidemiological study in Japan. Ann Oncology 1997:8:107-109.
  48. Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D. Rectivation of B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology 1991;100:182-188.
  49. Liang,R, Lau GK, Kwong YL. Chemotherapy and bone marrow transplantation for cancer patients who are also chronic hepatitis B carriers: a review of the problem. J Clin Oncol 1999;17:394-8
  50. Markovic S, Drozina G, Vovk M, Fidler-Jenko M. Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosoppressive therapy. A prospective study in 305 patients. Hepatogastroenterol 1999;46:2925-2930
  51. Ohtsu T, Sai T, Oka M, Sugai Y, Tobinai K. Activation of hepatitis B virus infection by chemotherapy containing glucocorticoid in hepatitis B virus carriers with hematologic malignancies. Jpn J Clin Onco 1991 21:360-365.
  52. Cheng AL. Steroid-free chemoteraphy decreases the risk of hepatitis flare-up in hepatitis B virus carriers with non-Hodgkins lymphoma. Blood 1996;87:1202.
    52a Caselitz M, Link H, Hein R, Maschek H, Boker K, Poliwoda H, Manns MP. Hepatitis B associated liver failure following bone marrow transplantation. J Hepatol 1997;27:572-577.
  53. Marusawa H, Imoto S, Udea Y, Chiba T. Reactivation of latently infected hepatitis B virus in a leukemia patients with antibodies to hepatitis core antigen. J Gastroenterol 2001;36:633-6.
  54. Iwai K, Tashima M, Itoh M, Okazaki T, Yamamoto K, Ohno H, et al. Fulminant hepatitis B following bone marrow transplantation in an HbsAg-negative, HbsAB positive recipient; reactivation of dormant virus during the immunosuppressive period. Bone Marrow Transplant 2000;25:105-108.
  55. Kawatani T, Suou T, Tajima F, Ishiga K, Omura H, Endo A, et al. Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies. Eur J Haematol 2001;67:45-50
  56. Ishiga K, Kawatani T, Suou T, Tajima F, Omura H, Idobe Y, Kawasaki H. Fulminant hepatitis type B after chemotherapy in a serologically negative hepatitis B virus carrier with acute myelogenous leukemia. Int J Hematol 2001;73:115-118
  57. Wong WWS, Ma MM, Bain WG. Treatment of immunosuppression-related HBV exacerbation with lamivudine. Hepatology 1998; 28 , Part 2, 725.
  58. Silvestri F, Ermacora A, Sperotto A, Patriarca F, Zaja F, Damiani D, et al. Lamivudine allows completion of chemotherapy in lymphoma patients with hepatitis B reactivation. British Journal of Haematology 2000;108,394-396.
  59. Kosaka Y, Takase K, Kojima M, Shmizu M, Inoue K, Yoshiba M, et al. Fulminant hepatitis B: induction by hepatitis B virus mutants defective in the precore region and incapable of encoding e antigen. Gastroenterology 1991;100:1087-1094.
  60. Lau GK, Liang R, Wu PC, Lee CK, Lim WL, Au WY. Use of famciclovir to prevent HBV reactivation in HBsAg positive recipients after allogeneic bone marrow transplantation. J Hepatol 1998;28:359-368.
  61. Tillmann HL, Trautwein C, Bock T, Böker KHW, Jäckel E, Glowienka M, et al. Mutational pattern of hepatitis B virus on sequential therapy with Famciclovir and Lamivudine in patients with hepatitis B virus reinfection occurring under HBIg immunoglobulin after liver transplantation. Hepatology 1999; 30: 244-256.
  62. Rossi G, Pelizzari A, Motta M, Puoti M. Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy. Br J Haematol 2001;115:58-62
  63. Endo T, Sakai T, Fujimoto K, Yamamoto S, Takashima H, Haseyama Y, et al. A possible role for lamivudine as prophylaxis against hepatitis B reactivation in carriers of hepatitis B who undergo chemotherapy and autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Bone Marrow Transplant 2001;27:433-436
  64. Lettau LA, McCarthy JG, Smith MH, Halder SC, Morse LJ, Ukena T, et al. Outbreak of severe hepatitis due to delta and hepatitis B viruses in parenteral drug abusers and their contacts. N Engl J Med 1987;317:1256-1262.
  65. O’Grady JG, Gimson AES, O’Brien CJ, Pucknell A, Hughes RD, Williams R. Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology 1988;94:1192-1198.
  66. Bernuau J, Goudeau A, Poynard T, Dubois F, Lesage G, Yvonnet B, et al. Mulitivariate an analysis of prognostic factors in fulminant hepatitis B. Hepatology 1986;6:648-651.
  67. Acharya SK, Dasarathy S, Kumer TL, Sushma S, Prasanna KS, Tandon A, et al. Fulminant hepatitis in a Tropical population: Clinical course, cause, and early predictors of outcome. Hepatology 1996;23:1448-1455.
  68. Takahashi Y, Shimizu M. Aetiology and prognosis of fulminant viral hepatitis: a multicentre study. The Study of Fulminant Hepatitis. J Gastroenterol Hepatol 1991;6:159-164.
  69. Hansson BG, Riesbeck K, Nordenfelt E, Weiland O. Successful treatment of fulminant hepatitis B and fulminant hepatitis B and D coinfection explained by inhibitory effect on the immune response? Prog Clin Biol Res 1991;364:421-427
  70. Kimura K, Ando K, Tomita E, Ohnishi H, Ishikawa T, Kakumu S, et al. Elevated intracellular IFN-gamma levels in circulating CD8+ lymphocytes in patients with fulminant hepatitis. J Hepatol 1999;31:579-583
  71. Mundt B, Kühnel F, Bortlik S, Waltemathes M, Zender L, Tillmann H, et al. Involvement of TRAIL-Ligand and receptors in virus mediated acute liver failure. J Hepatol 2001; 34: 86.
  72. Lai CL, Chien RN, Leung NWY, Chang TT, Guan R, Tai DI, et al. A one year trial of lamivudine for chronic hepatitis B. N Engl. J Med 1999;329:61-68
  73. Jarvis B, Faulds D. Lamivudine: A review of its therapeutic potential in chronic hepatitis B. Drugs 1999;58:101-141.
  74. Lee WC, Wu MJ, Cheng CH, Chen CH, Shu KH, Lian JD. Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients. Am J Kidney Dis 2001;38:1074-1081
  75. ter Borg F, Smorenburg S, de Man RA, Rietbroek RC, Chamuleau RA, Jones EA. Recovery from life-threatening, corticosteroid-unresponsive, chemotherapy-related reactivation of hepatitis B associated with lamivudine therapy. Dig Dis Sci 1998:43:2267-2270.
  76. Clark FL, Drummond MW, Chambers S, Chapman BA, Patton WN. Successful treatment with lamivudine for fulminant reactivated hepatitis B infection following intensive therapy for high-grade non-Hodgkin’s lymphoma. Ann Oncol 1998;9:385-387.
  77. Santantonio T, Mazzola M, Pastore G. Lamivudine is safe and effective in fulminant viral hepatitis. J Hepatol 1999;30:551.
  78. Kawai Y, Ikegaya S, Hata M, Kawahito M, Imamura S, Yoshida A, Tsutani H, Ueda T. Successful lamivudine therapy for post-chemotherapeutic fulminant hepatitis B in a hepatitis B virus carrier with non-Hodgkin's lymphoma: case report and review of the literature. Ann Hematol 2001;80:482-484.

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