Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre– or post–liver transplant

Peters, Marion G.; Kottilil, Shyam; Terrault, Norah A.; Amara, Dominic; Husson, Jennifer; Huprikar, Shirish; Florman, Sander; Sulkowski, Mark S.; Durand, Christine M.; Luetkemeyer, Anne F; Rogers, Rodney; Grab, Joshua D.; Haydel, Brandy; Blumberg, Emily A.; Dove, Lorna; Emond, Jean C.; Olthoff, Kim M.; Smith, Coleman I.; Fishbein, Thomas M.; Masur, Henry; Stock, Peter G.

doi:10.1111/ajt.16427

Cited by 18 publications

(19 citation statements)

References 30 publications

(46 reference statements)

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“…However, it is important to recognize that despite many promising studies showing favorable response to DAAs both before and after LT, 19 there are recent data showing that in HIV/HCV coinfected patients, MELD did not improve in all patients achieved SVR, and 4-year transplant-free survival was 42.8%. 20 In addition, restrictions to DAAs remain for some PLWH, including HIV viral load suppression, CD4 thresholds or minimum fibrosis requirements. 21,22 Those restraints impact survival, 21 and HCV coinfection remains a significant cause of death among PLWH.…”

Section: Discussionmentioning

confidence: 99%

“…The steep reduction in 2018 might reflect a true decrease, similar to the HIV‐uninfected patients, but delayed. However, it is important to recognize that despite many promising studies showing favorable response to DAAs both before and after LT, 19 there are recent data showing that in HIV/HCV coinfected patients, MELD did not improve in all patients achieved SVR, and 4‐year transplant‐free survival was 42.8% 20 . In addition, restrictions to DAAs remain for some PLWH, including HIV viral load suppression, CD4 thresholds or minimum fibrosis requirements 21,22 .…”

Section: Discussionmentioning

confidence: 99%

“…HIV-infected patients also had lower MELD at the time of LT ( 23[IQR 17-32] compared with HIV-uninfected patients 25 [IQR [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], p = .049) (Table 1). These differences in recipient characteristics by HIV serostatus persisted after stratifying by viral and nonviral indications for LT.…”

Section: Ajtmentioning

confidence: 99%

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Nonviral liver disease is the leading indication for liver transplant in the United States in persons living with human immunodeficiency virus

Campos‐Varela

Dodge

Terrault

et al. 2021

American Journal of Transplantation

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We evaluated whether indications for liver transplantation (LT) have changed among people with/without human immunodeficiency virus (HIV) infection and compared LT outcomes and trends by HIV serostatus. LT recipients (2008LT recipients ( -2018 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network (UNOS/OPTN) were identifed. Among 62 195 LT recipients, 352 (0.6%)were HIV-infected. The proportion of HIV-infected patients increased over time (P trend = .001), as did the number of transplant centers performing LT for HIV-infected recipients; average annual percentage change of 9.2% (p < .001). Nonviral causes became the leading indication in 2015 for HIV-uninfected and in 2018 for HIV-infected (P trend < .001). Three-year cumulative patient survival rates were 77.5%, for HIVinfected and 84.6%, for HIV-uninfected (p = .15). Over time, graft and patient survival rates improved for both HIV-infected and uninfected (p < .001). Among HCV-infected LT recipients, 3-year patient survival rates were 72.5% for HIV-infected and 81.8% for HIV-uninfected (p = .02). However, in a subanalysis restricted to 2014-2018, differences in graft and patient survival by HIV serostatus were no longer observed (3-year patient survival rates were 81.2% for HIV-infected and 86.4% for HIV-uninfected, p = .34). In conclusion, in the United States, nonviral liver disease is now the leading indication for LT in HIV-infected patients, and posttransplant outcomes have improved over time.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Nonviral liver disease is the leading indication for liver transplant in the United States in persons living with human immunodeficiency virus

Campos‐Varela

Dodge

Terrault

et al. 2021

American Journal of Transplantation

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“…The real revolution came in 2013, with interferon-free DAAs, which have been well-tolerated with cure rates approaching 100%, including in liver transplant recipients with HIV. 3 Reflecting these advances, in this issue of the Journal, Campos-Varela and colleagues present a US registry analysis demonstrating major changes in the landscape and outcomes of liver transplantation in PWH. 4 First, they show HCV is no longer the primary indication for liver transplantation for PWH; in 2017, it was surpassed by nonviral causes, predominantly nonalcoholic steatohepatitis and alcoholic liver disease.…”

mentioning

confidence: 99%

“…In 2008, first‐generation DAA protease inhibitors (telaprevir and boceprevir) were introduced; however, these required interferon and ribavirin, which presented complex interactions in transplant recipients, particularly with HIV, and were poorly tolerated. The real revolution came in 2013, with interferon‐free DAAs, which have been well‐tolerated with cure rates approaching 100%, including in liver transplant recipients with HIV 3 …”

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confidence: 99%

Clearing the hepatitis hurdle: Obstacles and opportunities in liver transplantation for people with HIV

Werbel

Durand

2021

American Journal of Transplantation

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The early experience of liver transplantation for people with HIV (PWH) was plagued by three issues: hepatitis C virus (HCV), interactions with HIV antiretroviral therapy, and organ rejection. In the first multicenter trials in the United States and Spain, liver recipients with HIV-HCV coinfection had 3-year patient and graft survival around 60%, and acute rejection rates around 40%, significantly worse than in recipients with HCV mono-infection. 1,2 These findings generated concern. Without effective antivirals for HCV, some transplant programs stopped performing liver transplants in PWH. Thus, the hurdle of HCV coinfection was a major barrier to liver transplantation for PWH.

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Considerations for Use of Propensity Score Matching in Specific Patient Populations

Goei

Kurth

2022

JAMA Surg

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culated MEAF score on this subset of 70 patients is consistent with early allograft dysfunction analysis, indicating that preservation using OCS liver resulted in significantly lower MEAF scores within the overall subset (mean [SD], 3.45 [1.71] vs 4.90 [2.02]; P = .002) as well as for donation after circulatory death donors (mean [SD], 2.87 [1.96] vs 5.94 [1.40]; P = .009) when compared with the control group.That the OCS group contained a higher number of donation after circulatory death donors was the result of a higher number of organ declines in the control arm. We agree with Romero and Kalashnikov that this makes the findings of superiority when using the OCS liver all the more remarkable.Regarding concerns the authors raise about the potential for NMP to widen disparities, it is important to note that the costs of OCS liver are already fully reimbursed through the US Centers for Medicare & Medicaid Services under the organ acquisition cost report for all Medicare patients. In addition, following US Food and Drug Administration approval, a national program has been established to provide support services, consisting of surgical and perfusionist expertise, to any transplant program anywhere in the country wishing to use normothermic machine perfusion (NMP). This infrastructure diminishes workload barriers that might prevent a transplant center from using NMP to support and preserve a donor liver. The future impact of this NMP service on access and outcomes for liver transplant recipients in general, as well as specific populations, will require additional study.PROTECT results indicate that NMP is advantageous for the preservation of donor livers and offer the opportunity for organ assessment not afforded by oxygenated cold perfusion. 4 The widespread integration of NMP in donor procurement practices is ongoing and leading to a paradigm shift in our field with the potential to further enhance organ management during NMP to reap even greater benefits in the future.

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Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre– or post–liver transplant

Cited by 18 publications

References 30 publications

Nonviral liver disease is the leading indication for liver transplant in the United States in persons living with human immunodeficiency virus

Nonviral liver disease is the leading indication for liver transplant in the United States in persons living with human immunodeficiency virus

Clearing the hepatitis hurdle: Obstacles and opportunities in liver transplantation for people with HIV

Considerations for Use of Propensity Score Matching in Specific Patient Populations

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