The Impact of Renal Transplantation on the Course of Hepatitis B Liver Disease

Parfrey, Patrick S.; Forbes, R. D. C.; Hutchinson, Tom; Kenick, Scott; Farge, Dominique; Dauphinee, W. Dale; Seely, John F.; Rd, Guttmann

doi:10.1097/00007890-198506000-00007

Cited by 131 publications

(43 citation statements)

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“…[1][2][3]8,9,[24][25][26][27][28][29][30][31] The detrimental effects of HBV infection have become more evident with the improving overall survival of kidney transplant recipients, consequent to advances in the management of other complications. 5 There is increasing agreement that liver-related complications are common in HBsAg-positive kidney transplant recipients and may account for 37% to 57% of mortality.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5] The number of chronic HBV carriers exceeds 300 million worldwide, and up to 14% of renal allograft recipients in endemic areas are hepatitis B surface antigen (HBsAg) positive. 6,7 Progressive liver disease affects more than 80% of HBsAg-positive renal transplant recipients 8,9 and accounts for 37% to 57% of mortality. 3,4,9 Life-threatening exacerbation of liver disease can develop in previously healthy HBV carriers.…”

Section: See Editorial On Page 1041 H Epatitis B Virus (Hbv) Infectiomentioning

confidence: 99%

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Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients

et al. 2002

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Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and the feasibility of discontinuing treatment have not been determined. This study examined these issues with a novel management protocol. Serum hepatitis B virus (HBV) DNA levels were measured serially in HBsAg-positive kidney transplant recipients, and lamivudine was administered preemptively to patients with increasing HBV DNA levels with or without elevation of aminotransferase levels. Outcomes of patients who underwent transplantation before or after institution of this preemptive management strategy (in January 1996) were compared. H epatitis B virus (HBV) infection is an importantcause of morbidity and mortality after kidney transplantation. [1][2][3][4][5] The number of chronic HBV carriers exceeds 300 million worldwide, and up to 14% of renal allograft recipients in endemic areas are hepatitis B surface antigen (HBsAg) positive. 6,7 Progressive liver disease affects more than 80% of HBsAg-positive renal transplant recipients 8,9 and accounts for 37% to 57% of mortality. 3,4,9 Life-threatening exacerbation of liver disease can develop in previously healthy HBV carriers. An optimal monitoring and treatment regimen for HBsAg-positive renal allograft recipients has not been defined.Lamivudine is a nucleoside analogue with proven efficacy in suppressing HBV DNA levels and ameliorating aminotransferase and histologic abnormalities in nonimmunosuppressed patients with chronic hepatitis B. 10,11 Short-term studies have shown virologic and biochemical efficacy in small series of renal transplant recipients. [12][13][14][15][16] We and others have reported favorable results with lamivudine in the treatment of fibrosing cholestatic hepatitis B, which hitherto has been associated with nearly uniform mortality. 17,18 However, many critical issues remain unresolved. It is not known whether patient survival can be Abbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; ALT, alanine aminotransferase; HBeAg, hepatitis B e antigen.

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Section: Discussionmentioning

confidence: 99%

Section: See Editorial On Page 1041 H Epatitis B Virus (Hbv) Infectiomentioning

confidence: 99%

Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients

et al. 2002

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“…The HBeAg concentrations that were detected rapidly progress to cirrhosis. [12][13][14][15][16] Direct cytotoxic effects of an HBV-related virus in ducks with mutations in the envelope in the serum are presumably also produced by these wildtype HBV genomes as one of the e-antigen epitopes fully or gene were reported. 33 Experiments in transgenic mice and cell culture provided evidence for direct cytopathic effects of partially deleted in most of the C-gene deletion mutants (Fig.…”

Section: Discussionmentioning

confidence: 99%

Accumulation and persistence of hepatitis B virus core gene deletion mutants in renal transplant patients are associated with end-stage liver disease

Günther¹

1996

Hepatology

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Evidence is accumulating that HBV variants may influence In renal transplant recipients, chronic hepatitis B vithe clinical course of hepatitis B. For instance, HBV with rus (HBV) infection often leads to cirrhosis and liver a point mutation in the preC-region (preC-variant), which failure. In this study, we investigated whether or not prevents the expression of the hepatitis B e antigen (HBeAg), in these patients viral variants would emerge despite can be associated with severe liver disease and, in some geoimmunosuppression, and whether they are associated graphic areas, with acute fulminant hepatitis. 1 Recently, it with a specific course of liver disease. In a population was proposed that preC-variants may also be predisposed to of 552 renal transplant recipients hepatitis B 24 surface early graft loss following liver transplantation. 2 In some, but antigen (HBsAg)-positive patients were available for a not all, studies, variants with clustered point mutations or 2-year follow-up. By polymerase chain reaction (PCR) variable long overlapping deletions in the middle of the core and DNA sequencing, HBV genomes with deletions in gene (C-gene) were found in patients with chronic active hepthe middle of the core gene (C-gene) were found in 9 out atitis, but not in patients with mild liver lesions. 3-5 of the 24 patients. Seven of the 9 patients (group I)Some of these and other variants are probably selected by showed either persistent or increasing amounts of these immune-mediated mechanisms, because they were shown to variants; all patients had cirrhosis, and 5 died of endemerge spontaneously in chronic carriers during seroconverstage liver disease. The viral variants emerged at least sion from HBeAg to antibody to HBe (anti-HBe) 6 during in-1 year before liver failure. In 2 out of the 9 patients, terferon therapy 7 and after vaccination. 8 However, other varithe core deletion variants disappeared, and no further ants with deletions or insertions in the C-gene promoter deterioration of the liver function was observed thereafregion seem to have a selective disadvantage when the imter. In the remaining 15 patients (group II) without delemune system is activated. 9 Thus, an effective immune retion mutants detected at any time, only 3 had cirrhosis sponse can trigger both the emergence and the disappearance (P õ .001, group I vs. II), and none died (P õ .001). Beof HBV variants. tween both groups, there were no statistically signifiIt is generally believed that the recognition of a wild-type cant differences in the other relevant variables that or variant HBV by the immune system will result in hepatiwere examined. These results indicate that HBV C-gene tis. The recognition of virtually all viral proteins by the hudeletion mutants can accumulate in long-term immunomoral and cellular immune system 10-11 supports this view, suppressed patients, and that their persistence is associand suggests that an effective immune response is a prerequiated with progressive liver disease. The accumulation site for liver injury. Howe...

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“…immunosuppressed patients such as renal transplant recipients with chronic HBV infection, [1][2][3][4] which is not fully compatible with immunopathogenesis. In past years, there was increasing evidence that HBV mutants may be involved in hepatopathogenesis in immunosuppressed patients.…”

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confidence: 99%

Complex HBV populations with mutations in core promoter, C gene, and pre-S region are associated with development of cirrhosis in long-term renal transplant recipients

et al. 2002

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Long-term immunosuppressed renal transplant recipients with chronic hepatitis B virus (HBV) infection often develop liver cirrhosis (LC) and end-stage liver disease (ESLD).This study investigated accumulation and persistence of specific HBV mutants in relation to the clinical course in these patients (n ‫؍‬ 38; mean follow-up, 3.5 years). HBV was analyzed longitudinally via length polymorphism of polymerase chain reaction (PCR) fragments (median, 6.5 serum samples per patient) as well as by cloning and partial sequencing of 346 full-length HBV genomes. Fourteen patients (group 1) developed LC or died from ESLD, whereas 24 patients (group 2) showed no evidence of LC during follow-up. Development of LC and ESLD was associated with persistence of HBV mutant populations characterized by deletions/insertions in core promoter plus deletions in the C gene and/or deletions in the pre-S region (86% of group 1 vs. 17% of group 2; P < .0001). HBV without these mutations or with core promoter mutations alone were predominantly found in group 2 (14% of group 1 vs. 75% of group 2). In patients infected with core promoter mutants, the additional appearance and persistence of deletions in the C gene and/or the pre-S region were accompanied or followed by development of LC and ESLD. The mutations were distributed on individual genomes in various combinations, leading to a high complexity of the virus population. In conclusion, these data suggest that accumulation and persistence of specific HBV populations characterized by mutations in 3 subgenomic regions play a role in pathogenesis of LC and ESLD in long-term renal transplant recipients. (HEPATOLOGY 2002;35: 466-477.)H epatitis B virus (HBV) infection is associated with various courses of liver disease ranging from asymptomatic carrier state to fulminant hepatitis. It is generally accepted that liver injury is immune mediated. However, severe liver disease and liver cirrhosis (LC) are also observed in long-term immunosuppressed patients such as renal transplant recipients with chronic HBV infection, 1-4 which is not fully compatible with immunopathogenesis. In past years, there was increasing evidence that HBV mutants may be involved in hepatopathogenesis in immunosuppressed patients. Mutations in the core promoter/enhancer II (Cp/EnII) that create a novel hepatocyte nuclear factor (HNF) 1 binding site and deletions in the pre-S region were found in a heart transplant recipient who died from fulminant HBV infection under immunosuppression. 5 A liver transplant recipient died from fibrosing cholestatic hepatitis following the accumulation of HBV with deletions in the pre-S1/2 region. 6 In a previous study, we showed that HBV with deletions in the C gene is significantly associated with development of HBV-related end-stage liver disease (ESLD) and death in renal transplant recipients. 7 Whereas the former studies reported just single cases without a control group, the latter was focused on 1 subgenomic region of HBV. Therefore, on the HBV genome level, it is still unclear wh...

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The Impact of Renal Transplantation on the Course of Hepatitis B Liver Disease

Cited by 131 publications

References 0 publications

Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients

Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients

Accumulation and persistence of hepatitis B virus core gene deletion mutants in renal transplant patients are associated with end-stage liver disease

Complex HBV populations with mutations in core promoter, C gene, and pre-S region are associated with development of cirrhosis in long-term renal transplant recipients

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