Clinical efficacy of direct-acting antiviral therapy for recurrent hepatitis C virus infection after liver transplantation in patients with hepatocellular carcinoma

Table 1 Characteristics of the study population according to pre-transplantation hepatocellular carcinoma status

	Number (%)
Characteristic	Non-HCC (n = 38)	HCC (n = 68)	P value
Demographics
mean (± SD) age at treatment initiation, years	58.2 ± 11.1	62.2 ± 5.9	0.01
Median age at treatment initiation, yr (range)	62 (28-74)	62.5 (47.0-78.0)	0.2
Male	25 (66)	50 (74)	0.5
Female	13 (34)	18 (26)
White	19 (50)	37 (54)	0.4
Black	11 (29)	11 (16)
Hispanic	6 (16)	17 (25)
Asian	2 (5)	3 (4)
Epidemiologic characteristics
mean (± SD) baseline BMI	27.9 ± 5.5	28.5 ± 4.5	0.6
Median baseline BMI, (range)	27.0 (21.0-48.5)	28.5 (17.0-46.0)	0.3
Alcohol drinking	11 (29)	32 (47)	0.08
Cigarette smoking	18 (47)	51 (75)	0.01
Baseline co-morbidities
Diabetes Mellitus	20 (53)	53 (78)	0.01
CKD	20 (53)	23 (34)	0.06
eGFR < 30 mL/min/1.73 m2	7 (18)	2 (3)	0.01
Cirrhosis	5 (15)	4 (8)	0.5
HCV-positive allograft	0	4 (6)	0.3
Anti-HBc-positive allograft	1 (3)	10 (15)	0.09
Pre-transplant relapse to antiviral treatment	6 (16)	23 (34)	0.06
mean (± SD) time from LT to DAA initiation, mo	99.3 ± 79.7	39.4 ± 40.5	0.0001
Median time from LT to DAA initiation, months (range)	91.5 (2.0-331.0)	28 (1-171)	0.0001
Baseline laboratory values
mean (± SD) creatinine level, mg/dL	1.9 ± 1.9	1.2 ± 0.8	0.08
Median creatinine level, mg/dL (range)	1.2 (0.7-8.7)	1.0 (0.7-7.0)	0.01
mean (± SD) AFP level, ng/mL	10.2 ± 30.5	6.8 ± 12.8	0.5
Median AFP level, ng/mL (range)	3.2 (2.0-149.0)	3.1 (1.3-88.0)	0.5
mean (± SD) MELD-Na score	13 ± 5	10 ± 4	0.01
Median MELD-Na score (range)	13 (6-24)	9 (6-24)	0.01
Clinical outcomes
Relapse at follow-up week 12	1 (3)	5 (7)	0.4
SVR12	37 (97)	63 (93)	0.4
HCC recurrence after DAA treatment	0	6 (9)	0.08

HCC: Hepatocellular carcinoma; SD: Standard deviation; BMI: Body mass index; CKD: Chronic kidney disease; HCV: Hepatitis C virus; HBc: Hepatitis B core; LT: Liver transplant; DAA: Direct-acting antiviral; AFP: Alpha-fetoprotein; SVR: Sustained virologic response.

Table 2 Risk factors for post-liver transplant direct-acting antiviral therapy response (Logistic regression analysis)

Variable	Number of DAA therapy responses/failures (n = 100/6)	Univariate OR (95%CI)	P value	Multivariate OR (95%CI)	P value
Age > 60 yr	60/4	1.3 (0.2-15.4)	0.8
Male	70/5	2.1 (0.2-104.7)	0.9
Baseline BMI (≥ 25 kg/m2)	76/5	1.6 (0.2-77.7)	0.9
Alcohol drinking	39/4	3.1 (0.4-35.7)	0.4
Cigarette smoking	64/5	2.8 (0.3-136.6)	0.6
Diabetes Mellitus	70/3	0.4 (0.1-3.4)	0.5
CKD	42/1	0.30 (0.01-2.60)	0.4
Cirrhosis	9/0	-
Pre-LT relapse to DAA	25/4	5.9 (0.8-68.7)	0.09
Anti-HBc-positive allograft	9/2	4.9 (0.4-40.4)	0.2
HCV-positive allograft	2/2	22.0 (1.3-381.3)	0.02	3.2 (0.1-856.8)	0.8
HCV genotype 3a	15/4	10.9 (1.4-130.9)	0.03	1.40 (0.02-89.10)	0.9
Presence of HCC before LT	63/5	2.9 (0.3-142.6)	0.6
Rejection during/after DAA therapy	5/0	-	-
ALT level at treatment week 4 (> 35 IU/L)	16/4	1.02 (1.00-1.05)	0.001	1.04 (1.00-1.10)	0.04
Quantitative HCV PCR at treatment week 4 (> 15 IU/mL)	8/3	10.9 (1.3-96.4)	0.01	3.6 (0.1-172.3)	0.5

HCC: Hepatocellular carcinoma; BMI: Body mass index; CKD: Chronic kidney disease; DAA: Direct-acting antiviral; HCV: Hepatitis C virus; OR: Odds ratio; CI: Confidence interval; ALT: Alanine aminotransferase; LT: Liver transplant; HBc: Hepatitis B core; PCR: Polymerase chain reaction.

Table 3 mean (± SD) alanine aminotransferase levels in patients who had direct-acting antiviral therapy responses and failure (baseline, week 4, week 8, and week 12)

SVR12 Achievement	Baseline ALT,mean (± SD)	ALT at treatment week 4, mean (± SD)	ALT at treatment week 8, mean (± SD)	ALT at treatment week 12, mean (± SD)
Responders	80.67 (± 102.447)	25.21 (± 20.416)	19.78 (± 11.651)	20.21 (± 10.994)
Failures	133.00 (±103.057)	61.17 (± 71.337)	54.50 (± 63.385)	56.83 (± 43.938)
P values	0.2	0.001	0.0001	0.0001

ALT: Alanine aminotransferase.

Table 4 mean (± SD) platelet counts in patients who had direct-acting antiviral therapy responses and failure (baseline, week 4, week 8, and week 12)

SVR12 Achievement	Baseline PLT,mean (± SD)	PLT at treatment week 4, mean (± SD)	PLT at treatment week 8, mean (± SD)	PLT at treatment week 12, mean (± SD)
Responders	152.54 (± 55.880)	172.33 (± 72.156)	164.94 (± 53.580)	169.42 (± 59.499)
Failures	150.00 (± 35.157)	153.00 (± 58.258)	167.25 (± 57.058)	160.67 (± 60.902)
P values	0.9	0.5	0.9	0.7

PLT: Platelet.

Table 5 Risk factors for hepatocellular carcinoma recurrence post-liver transplant (Logistic regression analysis)

Variable	No HCC recurrence/HCC recurrence(n = 62/6)	Univariate OR(95%CI)	P value	Multivariate OR (95%CI)	P value
Age > 60 yr	39/3	0.6 (0.1-4.8)	0.8
Male	45/5	1.9 (0.2-94.5)	0.9
White	34/3	0.8 (0.1-6.7)	0.9
Baseline BMI(≥ 25 kg/m2)	50/4	0.5 (0.1-5.9)	0.7
EOT BMI (< 25 kg/m2)	11/4	8.8 (1.1-109.3)	0.03	12.3 (1.2-131.0)	0.03
Alcohol drinking	28/4	2.4 (0.3-28.3)	0.6
Cigarette smoking	48/3	0.3 (0.1-2.5)	0.3
Cirrhosis	4/0	-	-
Pre-LT relapse to DAA	18/5	11.7 (1.2-590.7)	0.006	14.9 (1.1-219.3)	0.04
Anti-HBc-positive allograft	8/2	3.3 (0.3-27.8)	0.4
HCV-positive allograft	4/0	-	-
HCV genotype 3a	12/3	4.1 (0.5-34.2)	0.2
Post-LT relapse to DAA	2/3	26.2 (2.2-432.9)	0.002	10.6 (1.0-121.6)	0.05

HCC: Hepatocellular carcinoma; BMI: Body mass index; DAA: Direct-acting antiviral; HCV: Hepatitis C virus; OR: Odds ratio; CI: Confidence interval; LT: Liver transplant; HBc: Hepatitis B core; EOT: End of treatment.

Table 6 Characteristics of the study population according to use of ribavirin

	Number (%)
Characteristic	RBV-containing DAA regimens (n = 68)	Non-RBV containing DAA regimens (n = 38)	P value
Age ≥ 60 yr	38 (58)	26 (70)	0.2
Male	51 (75)	24 (63)	0.3
Female	17 (25)	14 (37)
White	37 (54)	19 (50)	0.8
Black	15 (22)	7 (18)
Hispanic	13 (19)	10 (26)
Asian	3 (4)	2 (5)
Diabetes Mellitus	45 (66)	28 (74)	0.5
CKD	22 (32)	21 (55)	0.02
eGFR < 30 mL/min/1.73 m2	1 (2)	8 (21)	0.001
Cirrhosis	4 (8)	5 (16)	0.3
mean (± SD) creatinine level, mg/dL	1.2 ± 1.0	1.9 ± 1.8	0.02
mean (± SD) hemoglobin level, g/dL	14.0 ± 1.7	12.0 ± 2.0	0.0001
mean (± SD) MELD-Na score	11 ± 4	13 ± 6	0.01
SVR12	65 (95.5)	35 (92.1)	0.7

RBV: Ribavirin; CKD: Chronic kidney disease; DAA: Direct-acting antiviral; SVR: Sustained virologic response.