Hepatitis C in non-hepatic solid organ transplant candidates and recipients: A new horizon

Table 1 Outcomes of interferon-based therapy in hemodialysis patients

Author	Number of studies included	Patients (n)	Regimen	SVR	Treatment discontinued for adverse effects	Predictors of SVR
Alavian et al[60]	21	491	IFN α 2a or 2b	39.1%	29.7%	Age < 40
	12	279	PegIFN α 2a or 2b	39.3%	22.6%
Gordon et al[59]	20	459	IFN	41%	26%	Lower HCV RNA non-cirrhotic elevated ALT genotype 1
	3	38	PegIFN	37%	28%
	2	49	PegIFN/RBV	43%-97%
Fabrizi et al[58]	13	539	IFN	1OR of no SVR	1OR dropout	N/A
			(10 studies)	0.081	0.389
			IFN + RBV	(0.029-0.230)	(0.155-0.957)
			(3 studies)

¹This analysis only reported the OR, rather than %SVR and dropout; data support relative benefit of IFN-based therapy on SVR, but do not provide absolute benefit. IFN: Interferon; PegIFN: Pegylated interferon; RBV: Ribavirin; OR: Odds ratio; SVR: Sustained virologic response.

Table 2 Summary of recommendation for interferon-free hepatitis C virus therapy in naïve patients without (a) and with (b) cirrhosis[65,66,90,91,94,115-126]

	SOF + RBV[65,66]	SOF + LDV[65,66]	PTV/r + OMB + DSV[65,66]	PTV/r + OMB[65,66]	SOF + SMV[65,66]	SOF + DCV[66]
	(SVR)	(SVR)	(SVR)	(SVR)	(SVR)	(SVR)
Without cirrhosis
Genotype 1a		8-12 wk	12 wk with RBV		12 wk without RBV	12 wk without RBV
		(93%-99%)	(95%-97%)		(93%-100%)	(95%-100%)
Genotype 1b		8-12 wk	12 wk without RBV		12 wk without RBV (93%-100%)	12 wk without RBV
		(93%-99%)	(98%-99%)			(95%-100%)
Genotype 2	12 wk
	(97%)
Genotype 3	24 wk					12 wk without RBV
	(94%)					(89-97%)
Genotype 4		12 wk		12 wk with RBV	12 wk without RBV	12 wk without RBV
		(95%)				(89%-97%)
Genotype 5 or 6		12 wk				12 wk without RBV
						(89%-97%)
With cirrhosis
Genotype 1a		12 wk without RBV (95%)	24 wk with RBV		12 wk without RBV	12 wk with or 24 wk without RBV
			(92%)		(93%)
Genotype 1b		12 wk without RBV	12 wk with RBV
			(96%)
Genotype 2	16-20 wk					12 wk without RBV
	(78%-83%)
Genotype 3	24 wk					24 wk with RBV
	(92%)
Genotype 4		12 wk with RBV or 24 wk without RBV		24 wk with RBV	12 wk without RBV	12 wk with RBV or 24 wk without RBV
Genotype 5 or 6		12 wk with RBV or 24 wk without RBV				12 wk with RBV or 24 wk without RBV

HCV: Hepatitis C virus; Peg: Pegylated interferon; RBV: Ribavirin; SOF: Sofosbuvir; SMV: Simeprevir; LDV: Ledipasvir; PTV: Paritaprevir; r: Ritonavir; OMB: Ombitasvir; DSV: Dasabuvir; DCV: Daclatasvir.

Table 3 Drug interactions with immunosuppressants and other common post-transplant medications

	SOF	SMV	LDV	PTV/r + OMB + DSV	DCV
Cyclosporine	*	***	**	**	*
Tacrolimus	*	**	**	**	*
Sirolimus	*	**	**	**	*
MMF	*	*	*	**	*
Azathioprine	*	*	*	*	*
Prednisone	*	**	*	**	*
Fluconazole	*	***	*	*	*
Voriconazole	*	***	*	***	**
Posaconazole	*	***	*	***	**
PPI	*	*	**	**	*

SOF: Sofosbuvir; SMV: Simeprevir; LDV: Ledipasvir; PTV: Paritaprevir; r: Ritonavir; OMB: Ombitasvir; DSV: Dasabuvir; DCV: Daclatasvir; PPI: Proton pump inhibitor. ***Contraindicated, do not co-administer; **Potential for interaction, use with caution; may require altered dosing; *No clinically significant interaction.

Table 4 Considerations with direct acting antivirals in renal dysfunction

DAA agent or combination	Issues in renal dysfunction
Sofosbuvir	Contraindication in GFR < 30 mL/min due to insufficient safety data[127]
Simeprevir	No dose adjustment[75]
Ledipasvir	Limited data; no theoretical concerns[127]
PTV/r + OMB + DSV	Safe and effective and no dose adjustment in ESRD[100]
Daclatasvir	No dose adjustment[78]
Elbasvir/Grazoprevir	Safe and effective and no dose adjustment in ESRD[101]

DAA: Direct acting antiviral; ESRD: End stage renal disease; GFR: Glomerular filtration rate; PTV: Paritaprevir; r: Ritonavir; OMB: Ombitasvir; DSV: Dasabuvir.