Systematic Review

Hepatitis C Viraemic Allografts to Hepatitis C-negative Recipients in Solid Organ Transplantation

Taaj Raasikh; Taher Jamali; Avegail Flores; Ronald T. Cotton; Venkat Ramanathan; Henkie P. Tan; Ruben Hernaez

Aliment Pharmacol Ther. 2021;54(5):571-582.

Conclusion

Our study of 852 solid organ transplantations from HCV NAT-positive allografts into HCV seronegative recipients showed minimal impact on graft survival, rejection and adverse events. Furthermore, no patient deaths were related to the transmission of HCV, and a high rate of SVR12 was attained due to treatment with DAAs. These results suggest that transplanting organs from HCV viraemic allografts to seronegative recipients could become standard practice for patients who do not have contraindications to DAAs, as this can potentially help to alleviate organ donor shortage.

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Funding information
This material is based on work supported by the Center for Innovations in Quality, Effectiveness and Safety (CIN 13–413), Michael E. DeBakey VA Medical Center, Houston, TX. The supporting body played no part in the literature search, determination of study eligibility, interpretation of findings, or preparation of the manuscript for publication. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government.

Acknowledgement
Authorship
Guarantor of the article
Ruben Hernaez.

Data Availability Statement
Data available in article supplementary material.

Table 1. Summary table of HCV viraemic allografts to HCV-negative recipients in solid organ transplantation: prophylactic/pre-emptive studies
Author, year	Design	Recipients of HCV viraemic (NAT+)organ (n)	Recipients that were not eligible for SVR12 (reason, n)	Follow up median (months)	Transplant to DAA, median (days)	Total recipients that achieved SVR12 (n)	HCV relapse? (n)	Side effects from DAAs (n)	Complications from HCV infection	Death (n), Cause of death	Patient death related to HCV?
Kidney
Durand, 2018¹³	OLNRCT	10	0	6	Pre-op	10	No	No	NR	0	N/A
Gupta, 2019¹⁷	OLNRCT	50	A (1)	8	Pre-op	5	Yes (2)	No	NR	(1), Pneumonia	No
Franco, 2019²⁰	Prosp	4	0	6.5	Pre-op	4	No	No	NR	0	N/A
Durand, 2021³⁶	OLNRCT	10	0	12	Pre-op	10	No	NR	NR	0	N/A
Duerr, 2020³⁵	Prosp	3	0	28	Pre-op	3	No	NR	NR	(1), Sepsis	No
Sise, 2020³⁸	Prosp	30	0	9	3	30	No	Dizziness (7), HTN(7), hypotension (5), hyperglycaemia(5)Hyperkalaemia (5), vomiting(5)	No	(1), bacteraemia	No
Heart
Bethea, 2019²³	OLNRCT	20	0	10.7	Pre-op	20	No	No	NR	0	N/A
Woolley, 2019²⁷	OLNRCT	8	B (1)	9.4	Post-op day 0	7	No	No	NR	Bacteraemia (1)	No
Liver
Bethea, 2019²⁹	OLNRCT	9	0	11.5	1.7	9	No	No	NR	0	N/A
Lung
Woolley, 2019²⁷	OLNRCT	36	A (8)	9.4	Post-op day 0	28	No	No	NR	0	N/A
Smith, 2020³⁹	Prosp	16	0	9.2	1	16	No	No	No	PE (1)	No

Of note: not all patients who received an HCV viraemic organ developed HCV infection, and thus were not included in the total SVR12 count.
Abbreviations: ABMR, acute antibody-mediated rejection; ACR, acute cellular rejection; CS, compartmental syndrome; FCH, fibrosing cholestatic hepatitis; FSG, focal segmental glomerulosclerosis; HTN, hypertension; MOF, multi-organ failure; OLNRCT, open-label; non-randomized control trial; NR, not reported; PE, pulmonary embolism; PGF, primary graft failure; Prosp, Prospective; Retros, retrospective; SVR12, sustained virological response at 12 weeks.
A: Unspecified/Incomplete follow-up B: Completed DAA and awaiting (or not eligible for) SVR12 testing E: Patient death prior to SVR12.

Table 2. Summary table of HCV viraemic allografts to HCV-negative recipients in solid organ transplantation: reactive studies
Author, year	Design	Recipients of HCV viraemic (NAT+) organ (n)	Recipients that developed HCV viraemia post-transplant (n)	Recipients that developed HCV viraemia post-transplant but were not eligible for SVR12 (reason, n)	Follow up median (months)	Transplant to DAA, median (d	Total recipients that achieved SVR12 (n)	HCV relapse? (n)	Side effects from DAAs (n)	Complications from HCV infection	Death (n), Cause of death	Patient death related to HCV?
Kidney
Goldberg, 2017⁴⁷	OLNRCT	10	10	0	12	3	10	No	No	FSG (1)	0	N/A
Reese, 2018¹⁴	OLNRCT	10	10	0	6	3	10	No	No	Proteinuria (1)	0	N/A
Crismale, 2019¹⁵	Retros	13	11	C (2), D (2)	8	40	7	No	Pruritus (1)	NR	0	N/A
Friebus-Kardash, 2019¹⁶	Prosp	7	7	0	12	7	7	No	HTN (3)	NR	0	N/A
Kapila, 2019¹⁸	Retros	64	61	B (3), C (7), D (10)	12	72	41	No	No	FCH (2)	(1), Unknown	Unknown
Molnar, 2019¹⁹	Retros	66	66	NR (13)	10	76	53	No	No	FCH (1)	0	N/A
Graham, 2020²¹	Prosp	30	30	0	10	9	30	No	No	NR	0	N/A
Terrault 2021⁴⁴	OLNRCT	11	10	0	NR (at least 12 weeks)	16.5	10	NR	NR	Abnormal serum liver tests (2)	0	N/A
Jandovitz, 2020³⁷	Retros	25	25	0	NR (at least 12 week)	13	25	Yes, (1)	No	No	0	N/A
Heart
Aslam, 2019²²	OLNRCT	19	19	E(1)	12	31	18	No	No	CS(1)	Heart Failure (1)	No
McLean, 2019²⁴	OLNRCT	10	10	E(1)	12	3	9	No	No	NR	ABMR, MOF(1)	No
Morris, 2019²⁵	Retros	23	22	NA	7.3	74	NR	Yes (1)	No	NR	0	N/A
Schlendorf, 2019²⁶	Prosp	70	67	B (12), C (5), D (13)	9.1	5	37	No	No	NR	PGF(5), PE (1)	No
Kapila, 2019¹⁸	Retros	7	7	C (1)	12	103	6	No	No	NR	0	N/A
Gernhofer, 2019³²	Retros	19	19	C (4), E (1)	0.3–12	22	14	No	No	CS(1)	Multifactorial (1)	Unknown
McMaster, 2020⁴⁵	Retros	10	8	C (2), E(1)	12	NR	6	No	NR	NR	Graft dysfunction (1)	Yes
Reyentovich, 2020⁴⁶	Prosp	22	22	0	12	7	22	No	Hyperbilirubinaemia(1)	NR	Necrotizing pancreatitis (1)	No
Smith, 2020³⁹	Prosp	22	22	0	9.2	7.5	22	No	No	No	Necrotizing pancreatitis (1)	No
Zhu, 2020⁴⁰	Retros	3	3	0	12	16.3	3	No	No	NR	0	N/A
Liver
Kwong, 2018²⁸	Retros	10	10	0	12.6	43	10	No	NR	NR	0	N/A
Crismale, 2019¹⁵	Retros	13	13	E (1)	16.4	42	12	No	NR	NR	Respiratory failure (1)	No
Kapila, 2019¹⁸	Retros	6	6	C (2), D (1)	12	51	3	No	NR	NR	0	N/A
Ting, 2019³⁰	Retros	20	20	B(1),C (5),D(3)	8	37	11	No	NR	NR	Ischemic bowel, ACR (1)	No
Aqel, 2020³³	OLNRCT	20	20	0	6	27.5	20	No	No	Acute membranous nephropathy (1)	septic shock (1)	No
Bohorquez, 2020³⁴	Retros	61	60	B(1), C(5),E(3)	NR (at least 12 months)	66.9	51	Yes (1)	No	No	sepsis and multi-organ failure (3), recurrent cholangiocarcinoma (1)	No
Nair, 2021⁴¹	Retros	23	23	0	NR (at least 12 months)	118	23	No	No	No	recurrent Primary sclerosis cholangitits/severe Ulcerative colitis (1)	No
Said, 2020⁴²	Prosp	8	8	E(1)	NR (at least 12 months)	13.5	7	No	Fatigue (2), headache (3), leucopenia (6)	No	chronic ischemic encephalopathy (1)	No
Sobotka, 2021⁴³	Retros	21	20	A(5)	NR	37	15	No	No	No	post-surgical complications and sepsis (1)	No
Terrault, 2021⁴⁴	OLNRCT	13	13	0	NR (at least 12 months)	7	13	No	Idiopathic Cardiomyopathy (1)	Intrahepatic biliary sclerosis (1)	Graft vs host disease (1)	No
Lung
Cypel, 2019³¹	OLNRCT	20	20	0	6	21	20	Yes (2)	No	FCH (1)	Sepsis (1)	No

Of note: not all patients who received an HCV viraemic organ developed HCV infection, and thus were not included in the total SVR12 count.
Abbreviations: ABMR, acute antibody-mediated rejection; ACR, acute cellular rejection; CS, compartmental syndrome; FCH, fibrosing cholestatic hepatitis; FSG, focal segmental glomerulosclerosis; HTN, hypertension; MOF, multi-organ failure; OLNRCT, open-label, non-randomized control trial; PE, pulmonary embolism; PGF, primary graft failure; Prosp, Prospective; Retros, retrospective; SVR12, sustained virological response at 12 weeks, NR, not reported.
A: Unspecified/Incomplete follow-up; B: Did not receive DAA therapy (due to insurance approval or other reason); C: Started but did not complete DAA therapy; D: Completed DAA and awaiting (or not eligible for) SVR12 testing; E: Patient death prior to SVR12.