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

Abstract

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.

Antiviral treatment for chronic hepatitis B in renal transplant patients

“…None of the HBsAg positive patients receiving prophylactic or pre-emptive therapy developed reactivation, while 50% of the patients not been treated suffered reactivation [51,52] . These results were confirmed by others, but there is some controversy about the clinical impact of prophylactic/preemptive therapy vs salvage therapy [51][52][53][54][55] . One study showed that there was no differences in survival between HBsAg positive RT patients treated preemptively with LAM and HBsAg negative controls.…”

“…One study showed that there was no differences in survival between HBsAg positive RT patients treated preemptively with LAM and HBsAg negative controls. HBsAg positive patients transplanted without preemptive therapy had in increased mortality rate [relative risk of death, 9.7 (P < 0.001); relative risk of liver-related mortality, 68.0 (P < 0.0001) [53] . Twenty five RT candidates received pre-transplantation prophylactic/preemptive NUC therapy, 22 (88%) were treated with LAM and 3 (12%) with ETV [54] .…”

Analysis of baseline hepatitis B virus DNA levels in chronic hepatitis B patients with non-hematological malignancies prior to the initiation of cancer chemotherapy

“…Based on previous report, the incidence of lamivudine resistance was ~14-32% after 1 year and ~60-70% after 5 years of therapy for patients with CHB (20). Despite its prophylactic use, drug-resistant mutations and hepatitis flares have been reported in patients treated with lamivudine during immunosuppressive therapy (18,30). Recently, a newer generation of oral antivirals with higher antiviral potency, such as entecavir and tenofovir, have become available.…”

“…For patients with positive HBsAg, a higher HBV DNA level prior to therapy (>2,000 IU̸ml) has been demonstrated to be an important risk factor for HBV reactivation compared with those having lower HBV DNA levels (11,12 HBV DNA levels; however, the risk of HBV reactivation remains higher for the minority with detectable HBV DNA at baseline (13,14). To prevent HBV reactivation during cancer chemotherapy, clinical studies, including randomized controlled trials, demonstrated that prophylactic use of an oral antiviral agent, mainly lamivudine, may reduce the rate of HBV reactivation and the severity of associated hepatitis flares and mortality (15)(16)(17)(18)(19). According to the 2009 American Association for the Study of Liver Diseases (AASLD) CHB practice guideline update (20), patients with a high baseline HBV DNA (>2,000 IU̸ml) level must continue treatment until they reach treatment endpoints as in immunocompetent patients.…”

Infectious Complications in Kidney Transplantation

“…The primary goals of management are maximal suppression of viral replication, while minimizing development of resistance and prevention of hepatic fibrosis. Cessation of antiviral therapy in the immunocompromised host is associated with an increased risk of flare of liver disease and rarely decompensated liver disease in transplant recipients (Chan et al, 2002;Liaw et al, 1999). Indefinite therapy carries its own risks, including that of antiviral toxicity (rare) and of drug resistance.…”