Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C

Table 3 Main studies evaluating the effects of direct acting antivirals in patients with advanced cirrhosis and/or listed for liver transplantation

Ref.	HCV genotype	Fibrosis stage	Treatment	SVR rate	Observed improvement
Charlton et al[98], 2015	Cohort A	Child A: 1/108 (1%)	LDV/SOF + RBV 12 or 24 wk	Child B:	-
	G1a: 74/108 (68.5%)	Child B: 65/108 (60.2%)		-12 wk 26/30 (87%)
	G1b: 31/108 (28.7%)	Child C: 42/108 (38.9%)		-24 wk 24/27 (89%)
	G4: 3/108 (2.8%)
				Child C:
				-12 wk 19/22 (86%)
				-24 wk 20/23 (87%)
Belli et al[97], 2016	G1a: 20/103 (19.4%)	Child A: 0	SOF/RBV: 52/103 (50.4%)	SOF/RBV (24-48 wk): RVR 61%	MELD: - 3.4 points
	G1b: 40/103 (38.8%)	Child B: 46/103 (44.7%)	SOF/LDV ± RBV: 9/103 (8.7%)	EVR 98%
	G2: 3/103 (3%)	Child C: 57/103 (55.3%)	SOF/DCV ± RBV: 35/103 (33.9%)		Child: -2 points
	G3: 20/103 (19.4%)		SOF/SMV ± RBV: 7/103 (6.8%)	SOF + 2nd DAA (12-24 wk):
	G4: 20/103 (19.4%)			RVR 67%	Delisting: 20%
				EVR 98%
					Improvement in refractory ascites that became treatable with diuretics
Munoz et al[107], 2015	-	Only cirrhosis	SOF/LDV + RBV (12-24 wk): 230	SVR 84%	MELD: -2.9 + - 0.1
			DCV/SOF + RBV (12 wk): 56		Child B to Child A: 35%
			GRZ/ELB (12 wk): 27		Child C to Child B: 48%
			SOF/LDV/DCV ± RBV (12 wk): 220
Manns et al[101], 2016	G1a: 50/107 (46.7%)	Child A: 2/107 (2%)	LED/SOF + RBV 12 or 24 wk	genotype 1	MELD improvement in 72%
	G1b: 47/107 (43.9%)	Child B: 60/107 (56%)		Child B: 12 wk 20/23 (87%); 24 wk 22/23 (96%)	Child B to Child A: 28%
	G4: 10/107 (9.4%)	Child C: 45/107 (42%)		Child C: 12 wk 17/20 (85%); 24 wk 18/23 (78%), 1/2 (50%)	Child C to Child B: 68%
				Genotype 4
				Child B: 12 wk 2/3 (67%); 24 wk 100%
				Child C: 12 wk 0%
				24 wk
Poordad et al[100], 2016	G1a: 34/60 (56.7%)	Child A: 12/60 (20%)	DCV/SOF + RBV 12 or 24 wk	Child A: 11/12 (92%)	MELD improvement in 47% of pts
	G1b: 11/60 (18.3%)	Child B: 32/60 (53.3%)		Child B: 30/32 (94%)	Child improvement in 60% of pts
	G2: 5/60 (8.3%)	Child C: 16/60 (27.7%)		Child C: 9/16 (56%)
	G3: 6/60 (10%)
	G4: 4/60 (6.7%)
Jacobson et al[99], 2015	Part 1	Only Child B cirrhosis	GRZ/ELB 12 wk	SVR 27/30 (90%)	MELD improvement in 11/30 (36.7%) pts
	G1a: 27/30 (90%)
	G1b: 3/30 (10%)
Curry et al[26], 2015	G1a: 159/267 (59.6%)	Child A: 16/267 (6%)	SOF/VEL 12 or 24 wk	SOF/VEL 12 wk: 75/90 (83%)	MELD improvement in 51% of pts
	G1b: 48/267 (18%)	Child B: 240/267 (89.9%)	SOF/VEL + RBV 12 wk	SOF/VEL + RBV 12 wk: 82/87 (94%)	Child improvement in 47% of pts
	G2: 12/267 (4.5%)	Child C: 11/267 (4.1%)		SOF/VEL 24 wk: 77/90 (86%)
	G3: 39/267 (14.6%)
	G4: 8/267 (3%)
	G6: 1/267 (0.3%)
Gray et al[106], 2016	G1a: 29/101 (28.7%)	Child A: 15/101 (14.8%)	SOF/LDV ± RBV 12 wk	74.3%	No significant differences from baseline
	G1b: 19/101 (18.8%)	Child B: 67/101 (66.3%)			Mortality rate 7.9% (6% Child B, 21% Child C)
	G1 (no subtype): 27/101 (26.7%)	Child C: 19/101 (18.8%)
	G2: 0
	G3: 24/101 (23.8%)
	G4: 1/101 (1%)
	Mixed: 1/101 (1%)
Aquel et al[103], 2015	G1a: 82/119 (69%)	Child A: 84/119 (70%)	SMV/SOF ± RBV 12 wk	RVR: 82/119 (69%)	MELD improvement in 61/92 (66.4%) pts that achieved SVR 12
	G1b: 24/119 (20%)	Child B: 34/119 (29%)		SVR 12: 92/118 (78%; Child A: 83%, Child B: 68%) (1 pts died after achieving SVR4)
	G1 (no subtype): G13/119 (11%)	Child C: 1/119 (1%)
Saxena et al[104], 2015	1a: 98/160 (62%)	Child A: 101/160 (65%)	SMV/SOF ± RBV 12 wk	Child A (37% with RBV): 91%	No significant differences from baseline
	1b: 62/160 (38%)	Child B: 49/160 (31%)		Child B/C (35% with RBV): 73%
		Child C: 6/160 (4%)

Pts: Patients; LDV: Ledipasvir; SOF: Sofosbuvir; RBV: Ribavirin; DCV: Daclatasvir; SMV: Simeprevir; RVR: Rapid virological response (HCV-RNA < 15 UI after 4 wk of treatment); EVR: Early virological response (HCV-RNA < 15 UI after 12 wk of treatment); GRZ: Grazoprevir; ELB: Elbasvir; VEL: Velpatasvir; FCH: Fibrosing cholestatic hepatitis.