Review of heart transplantation from hepatitis C-positive donors

Table 1 Heart transplantation from hepatitis C virus-positive donors in the pre-direct-acting antivirals era

Ref.	Study type	Study group	Outcome
Pereira et al[22], 1991	Retrospective, observational	6 HCV-negative recipients underwent HT from HCV Ab-positive donors	50% of recipients acquired HCV infection and higher incidence of liver disease was noted
Hayashi et al[23], 1994	Case Report	46-yr-old male with end- stage cardiomyopathy receiving HT from HCV Ab-positive donor	Fulminant liver failure and patient died in less than 2 yr
Lim et al[24], 1994	Case Report	51-yr-old male undergoing HT from HCV Ab-positive donor	Fulminant hepatitis, which was treated successfully with interferon-based therapy; Died due to pulmonary aspergillosis
Zein et al[25], 1995	Observational	1 HCV-negative recipient underwent HT from HCV Ab-positive donors	Cholestatic liver disease and liver failure-related mortality
Pfau et al[26], 2000	Retrospective	5 recipients without HCV infection underwent HT with HCV Ab-positive donors	1 out of 5 recipients became HCV Ab-positive; Elevated liver enzymes were noted and normalized by 12 mo
Marelli et al[27], 2002	Retrospective	20 recipients (10 were status I and 10 were status II) without HCV infection underwent HT from HCV NAT-positive donors	Overall survival was 90% in status I and 80% in status II group; Higher incidence of rejection and CAV were noted
File et al[5], 2003	Retrospective	10 recipients without HCV infection underwent HT from HCV-positive and NAT-positive	All recipients became HCV NAT-positive, 6 out of 9 recipients developed hepatitis and severe liver injury occurring in 2 patients; Inferior survival of 70% was noted
Gudmundsson et al[28], 2003	Retrospective	7 recipients without HCV infection underwent HT from HCV Ab-positive donors	Overall 5-yr survival was 71.4%; 3 developed chronic active hepatitis, 1 died from liver failure
Wang et al[29], 2004	Retrospective	4 recipients without HCV infection underwent HT with HCV Ab-positive donors	1 recipient became HCV Ab-positive without clinical hepatitis
Haji et al[30], 2004	Retrospective	34 recipients without HCV infection underwent HT from HCV Ab-positive donors and evaluated overall mortality and CAV	75% of recipients became HCV seropositive; Higher mortality by 2.8-fold and accelerated CAV by 3.0-fold was noted compared to the control group
Gasink et al[31], 2006	Retrospective, registry-based, cohort	261 recipients without HCV infection underwent HT with HCV Ab-positive donor	Overall inferior 1-yr, 5-yr, and 10-yr survival compared to control; Higher incidence of liver disease and CAV were noted

Ab: Antibodies; CAV: Cardiac allograft vasculopathy; HT: Heart transplant; HCV: Hepatitis C Virus; NAT: Nucleic acid test.

Table 2 Heart transplantation from hepatitis C virus-positive donors in the post-direct-acting antivirals era

Ref.	Study type	Study group	Outcome
Gottlieb et al[33], 2017	Case report	1 recipient without HCV infection underwent HT with HCV NAT-positive donor; treated with sofosbuvir/velpatasvir for 12 wk	A recipient acquired HCV infection on day 9, and it was cured at 12 wk
Jawad et al[39], 2018	Case report	1 recipient without HCV infection underwent HT with HCV-positive donor; in 2014, after approval of DAA, the patient was treated with sofosbuvir and daclatasvir for 8 mo	Patient acquired HCV infection in 2010 without any clinical sequelae and with treatment of DAA in 2014 it was eradicated; Progressive CAV was noted
Moayedi et al[40], 2018	Single center, single arm	2 recipients without HCV infection underwent HT with HCV NAT-positive donors	Low cost of HCV treatment compared to alternative treatment with mechanical cardiac support; Potential for 300-500 more HT annually noted
Moayedi et al[41], 2018	Retrospective, registry-based	From 2013 to 2017, 64 (5%) underwent HT from HCV-positive donors; Total of 1305 HCV-positive donors were recovered during this time period	Comparable survival was noted in recipients of HCV-positive donors to HCV-negative donors
Patel et al[10], 2018	Single center, single arm case series	14 HCV-negative recipients underwent HT in 2017 from HCV Ab-positive and NAT-negative donors	None developed HCV infection
Schlendorf et al[42], 2018	Single center, single arm prospective observational case series	13 HCV-negative (1 was treated) recipients underwent HT from HCV-positive donors and treated with DAA	69% of these recipients acquired HCV, and all of them achieved SVR following therapy with DAA except 1 who died due to pulmonary embolism
McLean et al[36], 2019	Single arm, single centered, prospective case series	10 HCV-negative recipients underwent HT with HCV NAT-positive donors, treated with elbasvir/grazoprevir after viral detection	Overall 9/10 recipients achieve SVR following DAA; 1 recipient died due to Ab cross-match leading to rejection, graft failure, and multiorgan failure
Woolley et al[43], 2019	Non-randomized, single center, prospective trial	8 HCV-negative recipients underwent HT from HCV NAT-positive donors; Treated with sofosbuvir-velpatasvir for 4 wk; Overall survival was compared to 12 recipients undergoing HT from HCV-negative donors	100% SVR was noted; Comparable survival rate at 12 mo in both groups
Frager et al[44], 2019	Single arm, single center, prospective trial	6 HCV-negative recipients underwent HT from HCV NAT-positive donors; multiple regimens of DAA were implemented	4 achieved SVR; 5 with 1R-2R rejection and 2 with stable chronic kidney disease; Decreased time on the waiting list noted
Schlendrof et al[11], 2019	Single arm, single center, prospective observational case series with a 1-year follow-up	80 HCV-negative recipients underwent HT from HCV Ab-positive and/or NAT-negative donors; Multiple DAA regimens utilized	95.7% of recipients acquired HCV infection from donors with HCV NAT-positive; DAA SVR was achieved in all recipients; No recipients acquired donor-derived HCV from NAT-negative recipients; Comparable 1-yr survival of 90.7% in both groups, and median wait time of 4 d was noted
Reyentovich et al[37], 2019	Non-randomized, single center, prospective observational case series	12 HCV-negative recipients underwent HT with HCV NAT-positive donors treated with glecaprevir/pibrentasvir for 8 wk compared to 13 controls undergoing HT from HCV-negative donors	Equivalent survival rate in both groups; Mean waiting period of 62 d noted
Aslam et al[45], 2019	Retrospective, single center, observational	21 HCV-negative recipients underwent HT with HCV Ab-positive and NAT-negative or positive donors	All recipients of NAT-positive donors acquired HCV infection; With DAA treatment 100% SVR was achieved; All recipients (2/2) were Ab-positive but NAT-negative and did not acquire HCV infection
Morris et al[46], 2019	Single center, retrospective	25 HCV-negative recipients underwent HT from HCV Ab-positive and NAT-positive (n = 23) or negative (n = 2) donors; DAA regimen was implemented, and outcomes were compared to 37 recipients undergoing HT from HCV- negative donors	22 of 23 recipients received hearts from HCV viremia acquired HCV infection; No difference in overall survival, rejection, hospitalization, and CAV between 2 groups; Delay in HCV treatment was due to insurance coverage
Lebeis et al[47], 2019	Single center, retrospective	23 HCV-negative recipients underwent HT with HCV-positive donors compared to control group receiving hearts from HCV donors	Recipients receiving preemptive treatment with DAA had preserved early allograft function receiving hearts from HCV-positive donors
Gaj et al[48], 2019	Single center, retrospective	Baseline characteristics were assessed in 111 HT; 23 of these organs came from HCV-positive donors	20% of recipients underwent HT from HCV-positive donors, and the donors were younger with a mean of 37 compared to 40 yr old; Short-term outcomes were similar in both groups
Kilic et al[21], 2020	Multicenter, retrospective, registry-based	Of 7889 HT, 343 HCV-negative recipients received hearts from HCV-positive donors	1-yr survival rate was indifferent between 2 groups; From 2016-2018, 28% of transplant centers utilized HCV-positive donors
Zhu et al[49], 2020	Single center, retrospective	10 HCV-negative recipients underwent HT from HCV-positive donors between 1997-2019	1-yr survival was 80%; 4 recipients acquired donor-derived HCV, and 3 of them demonstrated cure with DAA treatment
McMaster et al[50], 2020	Single center, retrospective	12 HCV-negative recipients underwent combined heart and kidney transplant from HCV Ab-positive and 10/12 were NAT-positive donors and were compared to 27 HCV-negative donors	A shorter median waitlist time for HCV-positive organs; Both groups had similar perioperative cardiac and renal function; Creatinine was higher in HCV-positive recipients at 3 mo compared to the control group, but at 1-yr it was similar in both groups; 80% of recipients acquired donor-derived HCV infection, and with DAA treatment 100% SVR was noted
Zalawadiya et al[51], 2020	Single center, retrospective	45 HCV-negative recipients underwent HT between 2016-2018 from HCV Ab-positive and NAT-positive donors; Renal function was assessed following transplantation	Data from 23 recipients were available at 12 wk and 18 recipients at 1 yr; No significant change in renal function up to 1-yr was noted
Reyentovich e et al[52], 2020	Single center prospective observational	22 HCV-negative recipients underwent HT between 2018-2019 from HCV NAT-positive donors; Data were compared to 28 HCV NAT-negative recipients	All recipients acquired donor-derived HCV; 20 recipients achieved 100% SVR following DAA therapy; Comparable outcomes with Ab-mediated rejection in both groups

Ab: Antibodies; CAV: Cardiac allograft vasculopathy; DAA: Direct acting antiretroviral; HT: Heart transplant; HCV: Hepatitis C Virus; NAT: Nucleic acid test; SVR: Systemic viral response.