Sex-related differences in patients with chronic hepatitis C infection treated with direct-acting antiviral drugs

Table 1 Baseline demographic and clinical characteristics of women and men depending on age, n (%)

Parameter	Women 15-44 years, n = 3118	Men 15-44 years, n = 4163	P value	Women 45-55 years, n = 1689	Men 45-55 years, n = 2185	P value	Women > 55 years, n = 4650	Men > 55 years, n = 3181	P value
BMI median (IQR), min-max	23.23 (20.94-26.35), 13.2-57.44	25.88 (23.51-28.39), 14.57-52.47	< 0.001	25.15 (22.51-28.34), 15.62-50.2	26.54 (24.22-29.33), 17.01-54.46	< 0.001	26.17 (23.44-29.32), 12.42-29.32	26.47 (24.22-29.07), 15.64-58.11	< 0.001
GT			< 0.001			< 0.001			< 0.001
1	69 (2.21)	69 (1.66)		32 (1.89)	34 (1.56)		115 (2.47)	62 (1.95)
1A	269 (8.63)	410 (9.85)		24 (1.42)	56 (2.56)		53 (1.14)	48 (1.51)
1B	2175 (69.76)	2616 (62.84)		1230 (72.82)	1404 (64.26)		3980 (85.59)	2600 (81.74)
2	8 (0.26)	8 (0.19)		12 (0.71)	3 (0.14)		16 (0.34)	6 (0.19)
3	358 (11.48)	643 (15.45)		268 (16.87)	437 (20)		320 (6.88)	319 (10.03)
4	175 (5.61)	312 (7.49)		84 (4.97)	178 (8.15)		87 (1.87)	84 (2.64)
5	0 (0)	0 (0)		0 (0)	1 (0.05)		0 (0)	0 (0)
6	1 (0.03)	1 (0.02)		1 (0.06)	2 (0.09)		0 (0)	1 (0.03)
Undetermined1	63 (2.02)	104 (2.5)		38 (2.25)	70 (3.20)		79 (1.7)	61 (1.92)
F4	212 (6.8)	649 (15.59)	< 0.001	319 (18.89)	713 (32.63)	< 0.001	1488 (32)	1240 (38.98)	< 0.001
Comorbidities
Any comorbidity	1172 (37.6)	1748 (41.99)	0.003	1012 (59.92)	1284 (58.76)	> 0.99	3767 (81.01)	2596 (81.61)	> 0.99
Hypertension	197 (6.32)	458 (11)	< 0.001	429 (25.4)	589 (26.96)	> 0.99	2591 (55.72)	1711 (53.79)	> 0.99
Diabetes	75 (2.41)	167 (4.01)	0.003	131 (7.76)	250 (11.44)	0.002	814 (17.5)	772 (24.27)	< 0.001
Renal disease	64 (2.1)	96 (2.31)	> 0.99	71 (4.2)	73 (3.34)	> 0.99	183 (3.94)	204 (6.41)	< 0.001
Autoimmune diseases	88 (2.82)	30 (0.72)	< 0.001	58 (3.43)	19 (0.87)	< 0.001	163 (3.5)	28 (0.88)	< 0.001
Non-HCC tumors	19 (0.61)	29 (0.7)	> 0.99	43 (2.55)	23 (1.1)	0.007	153 (3.29)	141 (4.43)	0.162
Depression	106 (3.4)	126 (3.03)	> 0.99	106 (6.28)	76 (3.48)	0.0003	230 (4.95)	101 (3.18)	0.0007
Other psychiatric disorders2	21 (0.67)	83 (1.99)	< 0.001	17 (1.01)	47 (2.15)	0.03	50 (1.08)	44 (1.38)	> 0.99
Concomitant medications	1074 (34.46)	1754 (42.13)	< 0.001	945 (55.95)	1300 (59.5)	0.081	3488 (75.01)	2365 (74.35)	> 0.99
Addiction to drugs	28 (0.9)	115 (2.76)	< 0.001	10 (0.59)	48 (2.2)	0.0005	3 (0.06)	16 (0.5)	0.001
Addiction to alcohol	27 (0.87)	141 (3.39)	< 0.001	17 (1.01)	94 (4.3)	< 0.001	18 (0.39)	61 (1.91)	< 0.001
HIV co-infection	161 (5.16)	530 (12.73)	< 0.001	95 (5.62)	282 (12.91)	< 0.001	16 (0.34)	52 (1.63)	< 0.001
HBV co-infection (anti-HBc+)	333 (10.68)	532 (12.78)	0.018	251 (14.86)	413 (18.9)	0.0027	625 (13.44)	501 (15.75)	0.012
HBs antigen+	34 (1.09)	65 (1.56)	0.09	15 (0.89)	39 (1.78)	0.02	17 (0.37)	19 (0.6)	0.14
History of HCC	3 (0.10)	18 (0.43)	0.024	6 (0.36)	44 (2.01)	0.00002	83 (1.78)	144 (4.53)	< 0.001
History of OLTx	7 (0.23)	16 (0.38)	0.687	11 (0.65)	27 (1.24)	0.201	33 (0.71)	52 (1.63)	0.0003

¹Pangenotypic hepatitis C virus drug regimens, including sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, can be used to treat individuals without identifying their hepatitis C virus genotype and subtype, simplifying therapy[18].

²Schizophrenia, bipolar affective disorder, psychotic disorders, dissociative disorders, personality disorders.

BMI: Body mass index; IQR: Interquartile range; GT: Genotype; F: Fibrosis; HCC: Hepatocellular carcinoma; HIV: Human immunodeficiency virus; HBV: Hepatitis B virus; HBc: Hepatitis B core; HBs: Hepatitis B surface; OLTx: Orthotopic liver transplantation.

Table 2 Comparison of treatment characteristics of women and men depending on age, n (%)

Parameter	Women 15-44 years, n = 3118	Men 15-44 years, n = 4163	P value	Women 45-55 years, n = 1689	Men 45-55 years, n = 2185	P value	Women > 55 years, n = 4650	Men > 55 years, n = 3181	P value
History of previous therapy			0.001			0.0006			0.06
Treatment-naïve	2748 (88.13)	3550 (85.28)		1399 (82.83)	1704 (77.99)		3572 (76.86)	2369 (74.5)
Treatment-experienced	370 (11.87)	613 (14.72)		290 (17.17)	481 (22.01)		1076 (23.14)	811 (25.5)
Current regimen			< 0.001			0.0004			0.02
Genotype-specific	1573 (50.45)	1817 (43.65)		823 (48.73)	930 (42.56)		2872 (61.76)	1869 (58.76)
Pangenotypic	1545 (49.55)	2346 (56.35)		866 (51.27)	1255 (57.44)		1778 (38.24)	1312 (41.24)

Table 3 Factors independently associated with virologic failure in multiple logistic regression

Parameter	Effect measure	Wald statistic	OR	95%CI	P value
Intercept		2198.843	0.009	0.007-0.011	< 0.001
Alcohol	Yes	5.181	1.725	1.079-2.759	0.023
Male sex	Yes	33.278	1.832	1.491-2.25	< 0.001
History of previous therapy	Yes	14.923	1.535	1.235-1.908	< 0.001
GT3 infection	Yes	115.101	3.154	2.557-3.891	< 0.001
F4	Yes	92.802	2.608	2.146-3.169	< 0.001

OR: Odds ratio; CI: Confidence interval; GT: Genotype; F: Fibrosis.

Table 4 Safety and characteristics of current therapy in women and men depending on age, n (%)

Parameter	Women 15-44 years, n = 3118	Men 15-44 years, n = 4163	P value	Women 45-55 years, n = 1689	Men 45-55 years, n = 2185	P value	Women > 55 years, n = 4650	Men > 55 years, n = 3181	P value
Treatment course			> 0.99			0.078			0.036
According to schedule	3076 (98.65)	4100 (98.49)		1657 (98.11)	2145 (98.17)		4484 (96.43)	3070 (96.51)
Therapy modification	17 (0.55)	33 (0.79)		23 (1.36)	16 (0.73)		102 (2.19)	48 (1.51)
Therapy discontinuation	25 (0.8)	30 (0.72)		9 (0.53)	24 (1.1)		64 (1.38)	63 (1.98)
Patients with at least one AE	457 (14.66)	491 (11.79)	0.001	319 (18.9)	332 (15.19)	0.007	918 (19.74)	544 (17.1)	0.009
Most common AEs (≥ 2%)
Weakness/fatigue	187 (6)	178 (4.28)	0.005	140 (8.29)	143 (6.54)	0.24	349 (7.51)	232 (7.29)	> 0.99
Headache	113 (3.63)	69 (1.66)	< 0.001	55 (3.26)	33 (1.51)	0.0018	118 (2.54)	47 (1.48)	0.0078
Severe AEs1	7 (0.22)	17 (0.41)	0.66	11 (0.65)	19 (0.87)	> 0.99	71 (1.53)	57 (1.79)	> 0.99
AEs of special interest (cirrhotics)
Ascites	8 (0.26)	12 (0.29)	> 0.99	7 (0.41)	19 (0.87)	> 0.99	35 (0.75)	48 (1.51)	0.009
Hepatic encephalopathy	2 (0.06)	9 (0.22)	> 0.99	6 (0.36)	12 (0.55)	> 0.99	17 (0.37)	34 (1.07)	0.001
Gastrointestinal bleeding	1 (0.03)	8 (0.19)	0.79	2 (0.12)	5 (0.23)	> 0.99	8 (0.17)	7 (0.22)	> 0.99
Death	1 (0.03)	10 (0.24)	0.09	6 (0.36)	11 (0.5)	> 0.99	31 (0.67)	54 (1.7)	0.00002

¹Serious adverse events include 5 patients who underwent liver transplantation during direct-acting antiviral treatment or in the 12-week follow-up period.

Two women, 67 years and 53 years and one man, 67 years, due to hepatocellular carcinoma diagnosed before treatment initiation. One man, 32 years, due to decompensation of liver cirrhosis (present before treatment). All four patients underwent the liver transplant in the 12-week follow-up period after the end of treatment. In one female, 38 years, liver transplantation was carried out during therapy after treatment discontinuation. Regardless, all patients achieved sustained virological response.

AE: Adverse event.