First results from a prospective randomized trial comparing steroid-free induction therapy with tacrolimus and MMF versus tacrolimus and steroids in patients after liver transplantation for HCV

Langrehr, Jan M.; Neumann, Ulf; Lang, M; Müller, A.R; Jonas, Sven; Settmacher, Utz; Steinmüller, Th.

doi:10.1016/s0041-1345(02)03024-5

Cited by 30 publications

(26 citation statements)

References 2 publications

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“…Five studies were based in the USA [26, 32, 35, 36, 38], three in Germany [25, 28, 31], three in Italy [17, 29, 34], and one each in Spain [27], China [9], UK [30], France [33], Belgium [37], and Poland [18]. The 17 prospective randomized controlled studies enrolled patients with distinct primary diseases eligible for OLT such as hepatitis B virus (HBV) [18, 27, 31–33], HCV infection [18, 25–27, 30–33, 35, 36, 38], HCC [9, 17, 26, 27, 30, 31, 33, 37], primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC) [17, 18, 31, 32], alcoholic cirrhosis [17, 18, 26, 27, 31], and autoimmune hepatitis (AIH) [28, 32]. A proportion of selected studies (6/17) described concomitant diseases such as diabetes [27, 29–31, 33], hypertension [27, 31], cytomegalovirus (CMV) infection [33, 34], Epstein-Barr virus (EBV) infection [33, 34], and metabolic disease [31, 33, 34, 37].…”

Section: Resultsmentioning

confidence: 99%

“…of patients ( n )Patient survival ( n )Graft survival ( n )Acute rejection ( n )Chronic rejection ( n )1 year2 year3 year5 year1 year2 year3 year5 yearComparison of Tac-based regimen with steroid or not (Sect. I) Langrehr [25]425 days100Tac + steroid1514147Tac + MMF1514144 Pelletier [26]412 days100Tac + MMF + steroid3632325Tac + MMF3630299 Margarit al. [27]100Tac + steroid32272523241919100Tac28…”

Section: Resultsmentioning

confidence: 99%

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Role of steroid minimization in the tacrolimus-based immunosuppressive regimen for liver transplant recipients: a systematic review and meta-analysis of prospective randomized controlled trials

Lü

et al. 2014

Hepatol Int

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To evaluate the efficacy and safety of early steroid withdrawal or steroid avoidance in the tacrolimus (Tac)-based immunosuppressive regimen for liver transplant recipients. According to the requirements of the Cochrane systematic review, a thorough literature search was performed in the PubMed/MEDLINE and Cochrane electronic databases between 1995 and 2011 using the key words “liver transplantation,” “Tac,” and “steroid free” or “steroid withdrawal,” restricting articles to the English language. Data were processed for a meta-analysis by Stata 12 software. Altogether 17 prospective randomized controlled trials containing 1,980 transplanted patients were included in this study. The overall pooled RR estimates of 1-, 2-, 3-, and 5-year patient and graft survival rates were 0.985, 0.998, 0.995, and 1.100 (95 % CI 0.925–1.048, 0.934–1.067, 0.894–1.107, and 0.968–1.250, respectively), as well as 0.998, 0.993, 0.945, and 1.053, respectively (95 % CI 0.928–1.072, 0.902–1.092, 0.833–1.072, and 0.849–1.307, respectively). The other pooled RR estimates of acute rejection and chronic rejection rates for all enrolled studies were 1.077 and 0.311 (95 % CI 0.864–1.343 and 0.003–37.207). As for secondary predictors, the pooled RR estimates such as HCV recurrence, HCC recurrence, diabetes, hypertension, kidney dysfunction, bacterial infection, and CMV were 1.101, 1.403, 1.836, 1.607, 0.842, 1.096, and 2.280, respectively (95 % CI 0.964–1.257, 0.422–4.688, 1.294–2.606, 0.926–1.228, 0.693–1.022, 0.783–1.533, and 1.500–3.465, respectively). There were no differences between the steroid group and steroid-free group for all clinical observational indices except for the incidence of diabetes (p = 0.001) and CMV infection (p < 0.001). In summary, our study indicate that rapid discontinuation of steroid in the Tac-based immunosuppressive regimen may not lead to an increased risk of morbidity and rejection rate.Electronic supplementary materialThe online version of this article (doi:10.1007/s12072-014-9523-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Role of steroid minimization in the tacrolimus-based immunosuppressive regimen for liver transplant recipients: a systematic review and meta-analysis of prospective randomized controlled trials

Lü

et al. 2014

Hepatol Int

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“…Publications eligible for analysis included 18 articles12, 15, 18–33 and 12 abstracts,34–45 with 19 uniquestudies12, 15, 18, 20, 24–31, 33, 35, 36, 40, 41, 43, 44 and 11 reported updates of those studies19, 21–23, 32, 34, 37–39, 42, 45 (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Steroid avoidance in liver transplantation: Meta-analysis and meta-regression of randomized trials

et al. 2008

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Steroid use after liver transplantation (LT) has been associated with diabetes, hypertension, hyperlipidemia, obesity, and hepatitis C (HCV) recurrence. We performed meta-analysis and meta-regression of 30 publications representing 19 randomized trials that compared steroid-free with steroid-based immunosuppression (IS). There were no differences in death, graft loss, and infection. Steroid-free recipients demonstrated a trend toward reduced hypertension [relative risk (RR) 0.84, P ϭ 0.08], and statistically significant decreases in cholesterol (standard mean difference Ϫ0.41, P Ͻ 0.001) and cytomegalovirus (RR 0.52, P ϭ 0.001). In studies where steroids were replaced by another IS agent, the risks of diabetes (RR 0.29, P Ͻ 0.001), rejection (RR 0.68, P ϭ 0.03), and severe rejection (RR 0.37, P ϭ 0.001) were markedly lower in steroid-free arms. In studies in which steroids were not replaced, rejection rates were higher in steroid-free arms (RR 1.31, P ϭ 0.02) and reduction of diabetes was attenuated (RR 0.74, P ϭ 0.2). HCV recurrence was lower with steroid avoidance and, although no individual trial reached statistical significance, meta-analysis demonstrated this important effect (RR 0.90, P ϭ 0.03). However, we emphasize the heterogeneity of trials performed to date and, as such, do not recommend basing clinical guidelines on our conclusions. We believe that a large, multicenter trial will better define the role of steroid-free regimens in LT. Liver Transpl 14:512-525, 2008. © 2008 AASLD. The use of corticosteroids has historically been the mainstay of decreasing rejection risk following liver transplantation (LT). Steroids, however, are associated with a multitude of side effects, including diabetes, hypertension, altered lipid metabolism, decreased wound healing, decreased immune defense against infection, osteoporosis, fractures, and obesity.Another potential side effect of steroid use in LT is recurrence of hepatitis C virus (HCV). In the past decade, there has been a dramatic shift in the indications for LT, and HCV has emerged as the single most important cause of end-stage liver disease leading to LT. Although only 16% of transplants were performed for HCV-related cirrhosis in 1991, this increased to over 50% by 2001. 1 Immunosuppression (IS) in HCV patients is a fine balance between adequate IS to prevent rejection and avoidance of over-IS to prevent severe HCV recurrence. 2,3 There is also circumstantial evidence to suggest that steroid boluses result in active viral replication and more aggressive recurrence including fibrosing cholestatic hepatitis. Furthermore, the development of diabetes and hyperlipidemia associated with steroids may increase the risk of steatosis, which has been implicated in worsening the outcome with HCV. 4,5 With significantly improved short-term outcomes over the last 2 decades, 6 the current challenges in LT

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“…In fact, we found a beneficial interaction between mycophenolate and patients who received DHCVϩ kidneys after adjustment for comorbid conditions. Recent trials have yet to show a benefit of mycophenolate in either renal or liver transplantation for recipients with HCV infection, albeit with very short follow-up and lack of a direct comparison with azathioprine (27)(28)(29)(30)(31)(32). However, Fasola et al (33) showed that manifestations of hepatitis C disease recurrence after steroidresistant allograft rejection following orthotopic liver transplantation seems to be less severe in patients who use mycophenolate.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C and Renal Transplantation in the Era of Modern Immunosuppression

Abbott¹,

Bucci²,

Matsumoto³

et al. 2003

Journal of the American Society of Nephrology

102

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Abstract. Kidneys from donors who are positive for hepatitis C virus (DHCVϩ) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001 followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCVϩ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P Ͻ 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCVϩ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCVϩ, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCVϩ was independently associated with mortality in each subgroup. It is concluded that DHCVϩ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCVϩ organs should be considered at high risk for excessive immunosuppression.The expected clinical course of hepatitis C infection as it affects organ transplant recipients, as well as the use and effect of kidneys from donors who are positive for hepatitis C, remain controversial topics in renal transplantation. Recently published data confirmed that kidneys from donors who were hepatitis C positive (HCVϩ) were associated with an independently increased risk of death in renal transplant recipients regardless of recipient HCV status (1). However, donor hepatitis C seropositivity (DHCVϩ) was not independently associated with mortality when limited to patients with valid information (Centers for Medicare and Medicaid Studies [CMS] Form 2728) on comorbid conditions at the time of dialysis initiation. This may have been because of the relatively small numbers of transplant recipients for whom complete data were available during the study period or because cardiovascular comorbidity was actually lower in patients who received DHCVϩ kidneys, yet the mortality risk for recipients of DHCVϩ kidneys was still greater than for patients who received DHCVϪ kidneys. Possibly, recipients of DHCVϩ kidneys were sicker to start with and thus had a higher risk of death unrelated to receiving a DHCVϩ kidney. Since that study, there have been substantial changes in maintenance immunosuppression practices in the United States. In particular, recent reports have confirmed tha...

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First results from a prospective randomized trial comparing steroid-free induction therapy with tacrolimus and MMF versus tacrolimus and steroids in patients after liver transplantation for HCV

Cited by 30 publications

References 2 publications

Role of steroid minimization in the tacrolimus-based immunosuppressive regimen for liver transplant recipients: a systematic review and meta-analysis of prospective randomized controlled trials

Role of steroid minimization in the tacrolimus-based immunosuppressive regimen for liver transplant recipients: a systematic review and meta-analysis of prospective randomized controlled trials

Steroid avoidance in liver transplantation: Meta-analysis and meta-regression of randomized trials

Hepatitis C and Renal Transplantation in the Era of Modern Immunosuppression

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