Antiviral therapies for chronic hepatitis C virus infection with cirrhosis

Table 1 Sustained virological response rates for cirrhotic patients who were treated with direct-acting antiviral agents against hepatitis C virus including peginterferon and ribavirin

Ref. (name of trial)	Regimen; genotype; No. of patients (n)	Tx history	SVR rates	SVR rates for P + R
			Cirrhosis vs Non-cirrhosis
Jacobson et al[10] (ADVANCE)	TVR + P + R; G1; n = 363: P + R; n = 361	-	62% vs 78%1	33% vs 47%
Sherman et al[11] (ILLUMINATE)	TVR + P + R; G1; n = 540	-	63% vs 75%1
Zeuzem et al[12] (REALIZE)	TVR + P + R; G1; n = 530: P + R; n = 132	+	Relapse; 84%-85% vs 83%-90%1	12% vs 38%
			PR; 40%-44% vs 70%-75%	10% vs 18%
			Null; 22%-28% vs 31%-50%	5% vs 6%
Poordad et al[13] (SPRINT-2)	BOC + P + R; G1; n = 734: P + R; n = 363	-	41%-52% vs 67%1	38% vs 38%
Bacon et al[14] (RESPOND-2)	BOC + P + R; G1; n = 299: P + R; n = 76	+; relapse or PR	35%-77% vs 64%-66%	0% vs 24%
Jacobson et al[17]	SMV + P + R; G1; n = 521: P + R; n = 264	-	60% vs 84%23	34% vs 55%
Manns et al[18] (QUEST1/2)
Forns et al[19] (PROMISE)	SMV + P + R; G1; n = 260: P + R; n = 133	+; relapse	74% vs 82%23	26% vs 41%
Zeuzem et al[20] (ASPIRE)	SMV + P + R; G1; n = 199: P + R; n = 66	+	Relapse; 73% vs 95%	0% vs 56%2
			PR; 82% vs 79%	0% vs 8%
			Null; 31% vs 66%	0% vs 23%
Lawitz et al[25] (NEUTRINO)	SOF + P + R; G1, 4-6; n = 327	-	80% vs 92%3

¹Comparison between cirrhosis/bridging fibrosis vs others, or between F3, 4 vs F0-2 (METAVIR score);

²Comparison between F4 vs F0-2 (METAVIR score);

³Data for SVR12. BOC: Boceprevir; G: Genotype; P: Peginterferon; PR: Partial response; R: Ribavirin; SMV: Simeprevir; SVR: Sustained virological response; TVR: Telaprevir; Tx; Treatment; SOF: Sofosbuvir.

Table 2 Safety data of antiviral treatments for cirrhotic patients infected with hepatitis C virus

Ref. (name of trial)	Regimen; genotypes; No. of patients (n)	Patient characteristics	AE (serious AE) rate;
			cirrhosis vs non-cirrhosis
Kumada et al[27] (AI447026)	ASV + DCV; G1; n = 222	IFN-intolerant/IFN-ineligible or IFN-non-responders	(9% vs 6%)
Forns et al[19] (PROMISE)	SMV + P/RBV; G1; n = 260	Treatment experienced; relapse	100% vs 92%-93% (1% vs 1%)1
Jacobson et al[30] (POSITRON, FUSION)	SOF + RBV; G2-3; n = 408	IFN-ineligible/IFN-intolerant (POSITRON); IFN-failure (FUSION)	97% vs 88% (7% vs 5%)
		12-wk regimen	86% vs 91% (11% vs 2%)
		16-wk regimen	88% vs 88% (6% vs 2%)
Lawitz et al[35] (COSMOS)	SMV + SOF ± RBV	F0-2; non-responders	87% vs 88% (5% vs 0%)
	for 12 or 24 wk; G1; n = 167	F3-4; non-responders or naïve

¹Comparison between F3-4 and F0-2 (METAVIR score) during the first 12 wk of therapy. AE: Adverse event; ASV: Asunaprevir; DCV: Daclatasvir; G: Genotype; IFN: Interferon; P: Peginterferon; RBV: Ribavirin; SMV: Simeprevir; SOF: Sofosbuvir.

Table 3 Sustained virological response rates for cirrhotic patients who were treated with interferon-free regimens

Ref. (name of trial)	Regimen; genotypes; No. of patients (n)	Patient characteristics	SVR rates: cirrhosis
			vs non-cirrhosis
Kumada et al[27] (AI447026)	ASV + DCV; G1; n = 222	IFN-intolerant/IFN-ineligible	91% vs 87%
		IFN-non-response1	91% vs 79%
Manns et al[28] (HALLMARK-DUAL)	ASV + DCV; G1; n = 645	Treatment naïve	91% vs 89%3
		IFN-non-response1	87% vs 80%
		IFN-intolerant/IFN-ineligible	79% vs 84%
Lawitz et al[32] (LONESTAR)	SOF + LDV ± RBV; G1; n = 40	Treatment experienced2	91% vs 100%34
			100% vs 100%5
Osinusi et al[29]	SOF + RBV; G1; n = 50	Treatment naïve	38% vs 65%6
Lawitz et al[26] (FISSION)	SOF + RBV; G2-3; n = 256	Treatment naïve; 12-wk regimen	G2; 83% vs 97%3
			G3; 34% vs 61%3
Jacobson et al[30] (POSITRON, FUSION)	SOF + RBV; G2-3; n = 408	IFN-ineligible/IFN-intolerant	G2; 94% vs 92%3
		(POSITRON); 12-wk regimen	G3; 21% vs 68%3
		IFN-failure7 (FUSION)
		12-wk regimen	G2; 60% vs 96% (90%)
			G3; 19% vs 37%
		16-wk regimen	G2; 78% vs 100% (92%)
			G3; 61% vs 63%
Zeuzem et al[31] (VALENCE)	SOF + RBV; G2-3; n = 323	Treatment-naïve
		12-wk regimen	G2; 100% vs 97%3
		24-wk regimen	G3; 92% vs 93%3
		Treatment-experienced
		12-wk regimen	G2; 88% vs 91%
		24-wk regimen	G3; 60% vs 85%
Lawitz et al[35] (COSMOS)	SMV + SOF ± RBV for 12 or 24 wk; G1; n = 167	F0-2; non-responders	F0-2; 90%3
		F3-4; non-responders or naive	F3-4; 94%
Poordad et al[36] (TURQUOISE-II)	Paritaprevir, ritonavir, ombitasvir	Treatment-naïve	94%38
	+ dasabuvir + RBV 12 or 24 wk; G1; n = 380	Treatment-experienced
		Relapse	98%
		Partial response	96%
		Null response	91%

¹Null or partial response during previous treatment;

²Patients experienced triple therapy including telaprevir or boceprevir;

³Data for SVR12;

⁴SVR rates for ribavirin-containing regimens;

⁵SVR rates for regimens without ribavirin;

⁶Comparison between F3-4 and F0-1 (Knodell score);

⁷Relapse, null or partial response to previous treatment;

⁸All patients included in the study had cirrhosis. ASV: Asunaprevir; DCV: Daclatasvir; G: Genotype; IFN: Interferon; LDV: Ledipasvir; RBV: Ribavirin; SOF: Sofosbuvir; SVR: Sustained virological response; SMV: Simeprevir.