Management of hepatitis C infection before and after liver transplantation

Table 1 Summary of clinical studies of triple therapy for recurrent hepatitis C virus infection before and after liver transplantation

Study	n	Design	Treatment	Duration	Genotype	Immunosuppressant	Efficacy	Tolerability	Other
Before liver transplantation
Curry et al[56]	61	OL study	SOF (400 mg)/RBV	48 wk	1 (n = 45) 2 (n = 8) 3 (n = 11) 4 (n = 1)	PRED TAC MMF	pTVR12: 70%	2 pts discontinued due to AE (pneumonitis, sepsis/acute renal failure) 11 (18%) pts had SAEs	1 treatment-related death (sepsis) and 4 non-treatment related deaths (pneumonitis, liver graft failure, cariogenic shock, sepsis)
After liver transplantation
Coilly et al[37]	37	Cohort study	BOC/PEG-IFN/RBV (n = 18) TVR/PEG-IFN/RBV (n = 19)	12 wk	1	CyA (n = 22) TAC (n = 15)	Complete virological response: BOC 89% and TVR 58% (P = 0.06) SVR: BOC 71% and TVR 20%	Therapy discontinuation in 16 (lack of efficacy 11, AEs 5). Infections in 27%, 3 (8%) fatal Most common AE anemia (92%), treated with EPO and/or a RBV dose reduction; 35% required red blood cell transfusions	CyA and TAC dose reductions required
Werner et al[38]	9	Pilot study	TVR/PEG-IFN/RBV	12 wk	1	CyA (n = 4) TAC (n = 4) SIR (n = 1)	4/9 pts HCV RNA negative at wk 4	Hematological AEs requiring RBV dose reductions, EPO or transfusions in 2/3rds of pts	Dose reductions in all patients (CyA, 2.5-fold; SIR, 7-fold; and TAC, 22-fold)
Werner et al[70]	9	Long-term follow-up	TVR/PEG-IFN/RBV	48 wk (= 24 wk follow-up after EOT)	1	CyA (n = 4) TAC (n = 4) SIR (n = 1)	SVR at wk 24 after EOT in 5/9	2 pts discontinued due to AEs	5/9 completed 48 wk’ therapy
Rogers et al[44]	2	Case report	TVR/PEG-IFN/RBV	NS	NS	TAC	HCV RNA undetectable at 10 wk in 1 pt (NS in pt 2)	NS	TAC dose adjustment required
Burton and Everson[39]	12	Retrospective	TVR/PEG-IFN/RBV	12 wk	NS	CyA	Wk 4: 11/12 pts had HCV RNA < 43 IU/mL	Anemia; 5 pts required transfusion	2 pts developed TVR resistance
Pungpapong et al[42]	7	OL study	TVR/PEG-IFN/RBV	12 wk	1	CyA	83% HCV RNA < 1000 IU/mL at wk 4	TVR discontinued due to severe anemia in 12 pt; 5 pts required EPO and 2 filgrastim	Graft rejection in 1 pt CyA dose adjustment required
de Oliveira Pereira et al[40]	6	OL study	TVR/PEG-IFN/RBV	5 wk	1	CyA	2 pts achieved SVR at 5 wk (one was persistent at 12 wk)	Tolerated in 5/6 pts; 1 pt discontinued due to rash and headache	NR
Reddy and Everson[46]	1	Case report	BOC/PEG-IFN/RBV	32 wk	1	TAC	HCV RNA undetectable at wk 12 of TT	AEs: fatigue, anemia, and syncope, requiring hospital admission. Anemia managed with RBV dose reduction, EPO and transfusion	TAC dose reduction
Sam et al[47]	3	Case report	BOC (800 mg q8h)/PEG-IFN/RBV	19 d	NS	CyA	NS	NS	Minor increased CyA concentrations, requiring dose adjustments
Schilsky et al[48]	3	Case report	BOC (800 mg q8h)/PEG-IFN/RBV	19 d	NS	CyA	1 pt achieved undetectable HCV-RNA and one achieved > 2log decrease by day 19; significant improvement in liver tests Histological improvement only in pt 3	Fatigue (did not require discontinuation)	-
Forns et al[54]	87	NS	SOF (400 mg)/RBV ± PEG-INF	48 wk	1 (n = 72) 2 (n = 2) 3 (n = 6) 4 (n = 3) Mixed (n = 4)	NS	SVR at 12 wk: SOF/RBV 54% and SOF/RBV/PEG-INF 44%	SAEs reported by 33% of pts (none attributable to study drug)	13 pts (17%) dead, all due to progression of liver disease or associated complications
Samuel et al[1]	40	OL study	SOF (400 mg)/RBV	24 wk	1 (n = 22) 2 (n = 11) 3 (n = 6) 4 (n = 1)	NS	HCV RNA undetectable at wk 4 in all pts 27 pts out of 35 achieved SVR at 4 wk	2 pts discontinued due to pneumonia and HCV progression AEs: fatigue, headache, arthralgia, diarrhea

AE: Adverse event; BOC: Boceprevir; CHC: Chronic hepatitis C; CyA: Cyclosporine; EOT: End of therapy; EPO: Erythropoietin; HCV: Hepatitis C virus; LT: Liver transplantation; MMF: Mycophenolate mofetil; NA: Not applicable; NS: Not stated; pbo: Placebo; PEG-IFN: Pegylated interferon; PRED: Prednisone; pts: Patients; pTVR12: Post-transplant virologic response 12 wk after transplant; RBV: Ribavirin; SAEs: Serious adverse events; SIR: Sirolimus; SOF: Sofosbuvir; SVR: Sustained virological response; TAC: Tacrolimus; TT: Triple therapy; TVR: Telaprevir.