Utility of the low-accelerating-dose regimen in 182 liver recipients with recurrent hepatitis C virus

Table 1 Baseline characteristics of the study patients n (%)

Recipient characteristics	n
Median age (yr)	182	52 ± 8.2
Male gender	182	145 (80)
Ethnicity	182
Caucasian		91 (50)
Black		18 (10)
Hispanic		52 (29)
Asian		14 (8)
Arabic		6 (3)
Others		1 (1)
IL28B	122
CC		40 (33)
CT		51 (42)
TT		31 (25)
HCC (pre-LT)	182	75 (41)
Diabetes mellitus	182	71 (39)
CMV positivity	181	126 (70)
Duration from LT to anti-viral therapy (mo)	182	20.5 ± 43.5
Median peak PEG dose (mcg/wk)	181	180 ± 31.6
Median peak RBV daily dose (mg)	181	800 ± 294
Median treatment duration (wk)	182	48 ± 21.5
HCV genotype	182
1		141 (77)
1a		80/141 (57)
1b		51/141 (36)
Subtype not available		10/141 (7)
2		15 (8)
3		14 (8)
4		12 (7)
Median baseline lab values
ALT (IU)	181	84 ± 128.3
AST (IU)	181	80 ± 112.5
ALP (IU)	180	131 ± 144.3
Total bilirubin (mg)	181	0.9 ± 3.1
HCV RNA (IU/mL)	181	3870000 ± 23602918
Hemoglobin (g/dL)	180	13 ± 1.7
White cell count	180	4.3 ± 1.9
Platelets	181	123 ± 73
Creatinine	181	1.2 ± 1.3
Immunosuppression at start of LADR1	182
Tacrolimus		146 (80)1
Cyclosporine		25 (14)
Sirolimus		4 (2)
Mycophenolate mofetil		66 (36)
Prednisone		9 (5)
Donor characteristics
Male gender	175	99 (57)
Median age	177	48 ± 18
CMV positivity	178	117 (66)
Ethnicity	182
White		118 (65)
Black		26 (14)
Hispanic		12 (7)
Asian		6 (3)
American indian/alaskan native		3 (2)
Other/unknown		17 (9)
Donor IL28B	122
CC		66 (54)
CT		35 (29)
TT		21 (17)

¹Percentages add to > 1 due to combination therapy. HCC: Hepatocellular carcinoma; LT: Liver transplant; CMV: Cytomegalovirus; HCV: Hepatitis C virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; LADR: Low-accelerating-dose regimen.

Table 2 Viral kinetics and SVR

	Percentage	Percentage who went on to achieve SVR	P value
RVR			0.0003
Yes	14	31
No	86	69
Week 8 negativity			< 0.0001
Yes	29	72
No	71	20
EVR			< 0.0001
Yes	41	72
No	59	11

Table 3 Univariate analysis

Factors associated with SVR	SVR (%)	P value
HCV genotype 1 vs non-1	29 vs 71	< 0.0001
HCV viral load < 1 million vs≥ 1 million IU/mL	54 vs 33	0.009
Recipient IL28B-CC vs non-CC	55 vs 34	0.03
Paired IL28b recipient CC and donor non-CC vs other recipient and donor combinations	72 vs 36	0.007
Pre-treatment total bilirubin < 1.5 mg vs≥ 1.5 mg	44 vs 25	0.02
Pre-treatment ALP < 150 vs≥ 150	44 vs 29	0.04
Treatment duration ≥ 48 wk vs < 48 wk	45 vs 27	0.02
Peak RBV dose ≥ 800 mg vs < 800 mg	44 vs 25	0.02
Administration of MMF vs No MMF	30 vs 43	0.09
RVR vs no RVR	34 vs 66	0.0006
EVR vs no EVR	85 vs 15	< 0.0001
Week 8 HCV RNA undetectable vs detectable	72 vs 20	< 0.0001
Donor age ≤ 40 vs > 40	58 vs 29	0.0002
Matched recipient and donor ethnicity vs unmatched	46 vs 33	0.09
Mismatched CMV status (D+/R-) vs other combinations	54 vs 35	0.04
Pre-treatment fibrosis stage 0-2 vs 3-4	43 vs 26	0.08
Factors associated with patient survival	10-year survival (%)
Week 8 HCV RNA undetectable vs detectable	71 vs 44	0.003
Week 12 HCV RNA undetectable vs detectable	73 vs 44	< 0.001
Pre-treatment fibrosis stage 0-2 vs 3-4	70 vs 31	0.004
Pre-treatment ALP < 150 vs≥ 150	67 vs 42	< 0.001
Pre-treatment total bilirubin < 1.5 mg vs≥ 1.5 mg	62 vs 46	< 0.001
Pre-treatment creatinine < 2 vs≥ 2	61 vs 0	< 0.001

HCV: Hepatitis C virus; ALP: Alkaline phosphatase; RBV: Ribavirin.

Table 4 Multivariate analysis

Factors associated with SVR	Comparison	Adjusted OR for SVR	95%CI		P value
			Lower	Upper
HCV genotype	2 vs 1	11.40	2.8	47.3	< 0.0001
	3 vs 1	43.10	6.5	286.3
	4 vs 1	10.70	2.4	48.8
Pre-treatment total bilirubin	≥ 1.5 vs < 1.5	0.21	0.08	0.57	0.002
Donor age	Each 10 yr	0.69	0.54	0.88	0.003
CMV mismatch	Donor +/recipient -	4.80	1.8	12.6	0.001
	vs all others
HCV viral load (baseline)	Each 1 million	0.97	0.94	0.999	0.040
		Adjusted HR
Pre-treatment ALP	≥ 150 vs < 150	2.01	1.18	3.43	0.010
Pre-treatment total bilirubin	≥ 1.5 vs < 1.5	2.49	1.47	4.21	0.001
Pre-treatment creatinine	≥ 2 vs < 2	5.88	2.68	12.92	< 0.001

CMV: Cytomegalovirus; HCV: Hepatitis C virus; ALP: Alkaline phosphatase.

Table 5 Histological characteristics (76 patients) n (%)

	Pre-anti viral treatment	Post-anti viral treatment	P value
Fibrosis stage (n = 76)(based on the Scheuer scheme)
Stage 0-2	65 (86)	41 (54)	< 0.001
Stage 3-4	11 (14)	35 (46)
Grade (n = 76)
Grade 0-2	51 (67)	46 (61)	0.33
Grade 3-4	25 (33)	30 (39)
Degree of steatosis (brunt classification) (n = 78)
Score 0-1	69 (88)	73 (94)	0.29
Score 2-3	9 (12)	5 (6)
Steatohepatitis grade (n = 75)
Grade 0	69 (92)	71 (95)	0.73
Grade 1-2	6 (8)	4 (5)
Steatohepatitis stage (n = 75)
Stage 0-1	72 (96)	73 (97)	1.00
Stage 2-4	3 (4)	2 (3)

Table 6 Change in fibrosis stage after anti-viral treatment (76 cases) n (%)

Fibrosis		SVR (n =32) P = 0.08	Survived (n =60) P = 0.03
Progressed
one stage	32 (42)	17 (53)	27 (45)
two stages	10 (13)	5 (16)	9 (15)
≥ three stages	5 (7)	1 (3)	2 (4)
Unchanged	23 (30)	5 (16)	17 (28)
Improved	6 (8)	4 (12)	5 (8)

Table 7 Frequency of rejection, plasma cell hepatitis and fibrosing cholestatic hepatitis n (%)

	Pre-anti viral treatmentn = 153	On-anti viral treatmentn =90	Post-anti viral treatmentn = 89
Rejection	39 (25)	12 (13)1	8 (9)
ACR	39 (25)	10 (11)	7 (8)
CDR	0	5 (6)	1 (1)
Plasma cell hepatitis	7 (5)	11 (12)	12 (13)
Fibrosing cholestatic hepatitis	7 (5)	5 (6)	1 (1)