Hepatitis C virus reinfection after liver transplantation: Is there a role for direct antiviral agents?

Table 1 Current stage of development of direct antiviral agents

Inhibitors of the NS3/4A serine protease
First-generation
Boceprevir	Approved
Telaprevir	Approved
Faldaprevir	Active clinical development
Sovaprevir	Active clinical development
Asunaprevir	Active clinical development
Simeprevir	Active clinical development
Danoprevir	Active clinical development
Vaniprevir	Active clinical development
Second-generation
MK-5172	Active clinical development
NS5A inhibitors
Daclatasvir	Advanced clinical development
GS-5885	Active clinical development
ABT-267	Active clinical development
PPI-461	Active clinical development
MK-8762	Active clinical development
NS5B polymerase inhibitors
Nucleos(t)ide inhibitors
Sofosbuvir	Advanced clinical development
Mericitabine	Active clinical development
ALS-2200	Active clinical development
Non-nucleos(t)ide inhibitors
Setrobuvir	Active clinical development
ABT-333	Active clinical development
GSK625433	Active clinical development

Table 2 Available data from the studies in extenso on the use of direct-acting antiviral agents in the post-liver transplantation setting

	Pungpapong et al[44]	Coilly et al[45]	Werner et al[46]	Werner et al[48]
Patients (n)	60	37	9	14
Baseline characteristics
Regimen (n)
TLV	35	19	9	14
BCV	25	18	0	0
Four-week lead-in phase	100%	100%	0%	0%
IS therapy (n)
TAC	3	15	4	6
CSA	65	22	4	6
SIR	1	0	1	2
Fibrosis stage (n)
FO-F2	31	20	6	7
F3-F4	38	17	3	7
Cholestatic hepatitis (n)	NA	6	1	NA
Results
HCV-RNA negative
Week 4	NA	51% (19/37)	44% (4/9)	43% (6/14)
Week 8	NA	NA	NA	NA
Week 12	91% (55/60)	73% (27/37)	89% (8/9)	71% (10/14)
Week 24	56% (24/43)	NA	NA	57% (8/14)
Week 48	NA	61% (17/28)	NA	50% (7/14)
Adverse events
Hematological AEs
Anemia	93%	92%	66%	71%
Leukopenia	77%	40%	22%	36%
Thrombocytopenia	12%	32%	44%	64%
Infectious complication	12%	27%	11%	14%
Renal insufficiency	38%	13%	11%	7%
Acute rejection	5%	NA	0%	7%
Dermatological toxicity	10%	5%	33%	NA
Hepatic decompensation	12%	NA	0%	7%
Death	3%	8%	0%	7%

BCV: Boceprevir; TLV: Telaprevir; HCV: Hepatitis C virus; IS: Immunosuppressive; TAC: Tacrolimus; CSA: Cyclosporine; SIR: Sirolimus; NA: Not available.

Table 3 Preliminary data on virological response during triple therapy in post-liver transplantation

	Verna et al[49]	Aqel et al[50]	McCashland et al[51]	Burton et al[52]	Kwo et al[53]	de Oliviera et al[54]
Patients (n)	101	23	10	12	7	6
Regimen
BCV	10	23	0	0	0	0
TVL	91	0	10	12	7	6
Four-week lead-in phase	96%	100%	NA	100%	100%	NA
Fibrosis
F0–F2	58	NA	7	8	5	NA
F3–F4	43	NA	3	4	2	NA
Cholestatic hepatitis (n)	10	NA	NA	NA	7	NA
IS therapy
TAC	23	0	0	0	2	6
CSA	67	23	10	12	5	0
HCV genotype	1	1	1	1	1	1
HCV-RNA negative
Week 4	70% (64/92)	43% (10/23)	22% (2/9)	92% (11/12)	29% (2/7)	NA
Week 8	78% (61/78)	NA	NA	NA	71% (5/7)	NA
Week 12	79% (68/86)	NA	100% (3/3)	NA	NA	33% (1/3)
Week 24	NA	17% (4/23)	100% (1/1)	NA	NA	NA

BCV: Boceprevir; TLV: Telaprevir; HCV: Hepatitis C virus; IS: Immunosuppressive; TAC: Tacrolimus; CSA: Cyclosporine; SIR: Sirolimus; NA: Not available.