Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders

Table 1 Baseline characteristics of chronic hepatitis C patients with (group A) and without (group B) psychiatric disorders, %, n

Parameter	All patients (n = 14272)		Group A (n = 942)	Group B (n = 13330)	P value
Age, mean (min-max yr)	51.2 (18-92)		50.8 (19-90)	51.2 (18-92)	0.599 (U = 6216478)
Men/women	49.3/50.7 (7035/7237)		54.9/45.1, 507/435	49.0/51.0, 6528/6802	0.004 (χ2 = 8.3)
BMI, mean (SD)	26.2 (4.5)		26.9 (5.1)	26.1 (4.5)	0.0001 (U = 5811710)
BMI ≥ 30	17.4 (2486)		23.9 (225)	17.0 (2261)	< 0.0001 (χ2 = 29.4)
Comorbidities
Hypertension	32.0 (4567)		34.4 (324)	31.8 (4243)	0.103 (χ2 = 2.6)
Diabetes	11.3 (1614)		13.0 (122)	11.2 (1492)	0.100 (χ2 = 0.5)
Renal disease	3.8 (543)		3.4 (32)	3.8 (511)	0.498 (χ2 = 0.5)
Autoimmune disease	2.1 (304)		2.0 (19)	2.1 (285)	0.803 (χ2 = 0.06)
Non-HCC tumor	2.0 (279)		2.1 (20)	1.9 (259)	0.700 (χ2 = 0.15)
ALT (IU/L), median (IQR)	58.0 (37.0-97.0)		59.0 (36.0-96.0)	58.0 (37.0-97.0)	0.581 (U = 6204221)
Albumin (g/dL), median (IQR)	4.1 (3.8-4.4)		4.1 (3.8-4.4)	4.1 (3.8-4.4)	0.633 (U = 6222478)
Bilirubin (mg/dL), median (IQR)	0.6 (0.5-0.9)		0.6 (0.5-0.9)	0.6 (0.5-0.9)	0.060 (U = 6050856)
Hemoglobin (g/dL), median (IQR)	14.5 (13.4-15.5)		14.4 (13.4-15.4)	14.5 (13.4-15.6)	0.307 (U = 6120464)
Platelets (× 1000/μL), median (IQR)	197.0 (146.0-244.0)		190.0 (136.0-240.0)	197.0 (146.0-244.0)	0.01 (U = 597757)
Creatinine (mg/dL), median (IQR)	0.8 (0.7-0.9)		0.8 (0.7-0.9)	0.8 (0.7-0.9)	0.798 (U = 6101372)
HCV RNA, × 106 IU/mL, median (IQR)	0.97 (0.32-2.53)		1.17 (0.38-3.0)	0.96 (0.31-2.48)	0.0005 (U = 5856849)

The reported P value relates to Pearson’s chi-square test (or Fisher’s exact test if the number of observations in a category was less than 10) or the Mann-Whitney U test. BMI: Body mass index; ALT: Alanine transaminase; HCC: Hepatocellular carcinoma; IQR: Interquartile range; HCV: Hepatitis C virus; RNA: Ribonucleic acid.

Table 2 Characteristics of liver disease in patients with chronic hepatitis C with (group A) and without (group B) psychiatric disorders, %, n

Parameters	All patients (n = 14272)	Group A (n = 942)	Group B (n = 13330)	P value
Genotype
1a	4.4 (633)	4.1 (39)	4.5 (594)	0.649 (χ2 = 0.2)
1b	77.3 (11029)	67.8 (639)	77.9 (10390)	< 0.0001 (χ2 = 51.2)
1	2.1 (303)	2.4 (23)	2.1 (280)	0.483 (χ2 = 0.5)
2	0.2 (29)	0.2 (2)	0.2 (27)	> 0.948 (χ2 = 0.004)
3	11.1 (1580)	17.5 (165)	10.6 (1415)	< 0.0001 (χ2 = 42.6)
4	4.9 (695)	8.0 (74)	4.7 (621)	< 0.0001 (χ2 = 19.4)
5	0.007 (1)	0.0 (0)	0.007 (1)	1.0
6	0.01 (2)	(0.0) 0	0.01 (2)	1.012
Liver fibrosis
F0	2.5 (361)	1.4 (13)	2.6 (348)	0.02 (χ2 = 5.4)
F1	40.8 (5831)	34.8 (328)	41.3 (5503)	< 0.0001 (χ2 = 15.2)
F2	19.2 (2743)	21.0 (198)	19.1 (2545)	0.147 (χ2 = 2.1)
F3	13.5 (1925)	13.2 (124)	13.5 (1801)	0.763 (χ2 = 0.09)
F4	23.9 (3412)	29.6 (279)	23.5 (3133)	< 0.0001 (χ2 = 18.1)
Child-Pugh
Child-Pugh-B	2.8 (398)	4.4 (41)	2.7 (357)	0.003 (χ2 = 9.1)
Child-Pugh-C	0.2 (23)	0.4 (4)	0.1 (19)	0.061
HCC history	1.3 (191)	1.2 (11)	1.3 (180)	0.637 (χ2 = 0.2)
Coinfection
HIV	5.9 (848)	9.1 (86)	5.7 (762)	< 0.0001 (χ2 = 18.4)
HBV	13.5 (1933)	17.5 (165)	13.3 (1768)	0.0002 (χ2 = 13.6)
HIV/HBV	1.6 (225)	3.4 (32)	1.4 (193)	< 0.0001 (χ2 = 21.6)

The reported P value relates to Pearson’s chi-square test or Fisher’s exact test if the number of observations in the category was less than 10. HCC: Hepatocellular carcinoma; HIV: Human immunodeficiency virus; HBV: Hepatitis B virus.

Table 3 Treatment characteristics in chronic hepatitis C patients with (group A) and without (group B) psychiatric disorders, %, n

Parameter	All patients (n = 14272)	Group A (n = 942)	Group B (n = 13330)	P value
History of antiviral treatment
Treatment-naïve	78.7 (11238)	80.6 (760)	78.6 (10478)	0.132 (χ2 = 2.2)
Nonresponder to IFN-based regimens	19.6 (2791)	16.7 (157)	19.8 (2634)	0.02 (χ2 = 5.3)
Nonresponder to IFN-free regimens	1.7 (247)	2.7 (25)	1.6 (222)	0.02 (χ2 = 5.1)
Current treatment regimen
Pangenotypic regimens	35.2 (5028)	43.0 (405)	34.7 (4619)	< 0.0001 (χ2 = 26.0)
Genotype-specific regimens	64.8 (9248)	57.0 (537)	65.3 (8711)
Current-RBV-containing regimens	16.2 (2308)	16.5 (155)	16.1 (2153)	0.807 (χ2 = 0.05)
Genotype-specific treatment regimens
ASV + DCV	0.8 (118)	1.3 (12)	0.8 (106)	0.117 (χ2 = 2.5)
SOF/LDV ± RBV	19.6 (2795)	21.8 (205)	19.4 (2590)	0.081 (χ2 = 3.1)
OBV/PTV/r ± DSV ± RBV	25.4 (3626)	14.1 (133)	26.2 (3493)	< 0.0001 (χ2 = 67.8)
GZR/EBR ± RBV	16.8 (2400)	16.3 (154)	16.8 (2246)	0.691 (χ2 = 0.1)
Other SOF ± SMV ± DCV ± RBV, SMV ± DCV ± RBV	2.2 (305)	3.2 (33)	2.1 (272)	0.02 (χ2 = 5.7)
Pangenotypic regimens
GLE/PIB	20.6 (2940)	20.6 (194)	20.6 (2746)	0.997 (χ2 = 0.0)
GLE/PIB + SOF + RBV	0.05 (6)	0.0 (0)	0.05 (6)	1.0
SOF/VEL ± RBV	14.4 (2058)	22.2 (209)	13.9 (1849)	< 0.0001 (χ2 = 49.3)
SOF/VEL/VOX	0.2 (24)	0.2 (2)	0.2 (22)	0.670

The reported P value relates to Pearson’s chi-square test or Fisher’s exact test if the number of observations in the category was less than 10. CHC: Chronic hepatitis C; IFN: Interferon; RBV: Ribavirin; ASV: Asunaprevir; DCV: Daclatasvir; LDV: Ledipasvir; SOF: Sofosbuvir; OBV: Ombitasvir; PTV: Paritaprevir; r: Ritonavir; DSV: Dasabuvir; GZR: Grazoprevir; EB: Elbasvir; SMV: Simeprevir; GLE: Glecaprevir; PIB: Pibrentasvir; VEL: Velpatasvir; VOX: Voxilaprevir.

Table 4 Logistic multiple regression results on the association between lack of sustained viral response, bipolar disorder (for which lower frequency of sustained viral response was observed in the present study), and known risk factors of non-response to antiviral treatment in the studied cohort (n = 14272)

Parameter	OR	95%CI	P value
Bipolar disorder	3.52	0.76-16.34	0.109
Male sex	1.93	1.51-2.45	< 0.0001
Obesity (BMI > 30 kg/m2)	1.08	0.82-1.43	0.579
GT3	3.26	2.50-4.27	< 0.0001
Cirrhosis	2.55	2.01-3.22	< 0.0001
HIV-coinfection	1.37	0.88-2.13	0.165
HBV-coinfection	0.85	0.61-1.18	0.323
History of HCV-treatment failure	1.46	1.14-1.87	0.003
ASV+DCV	4.97	2.60-9.55	< 0.0001
SOF/VEL	0.86	0.61-1.20	0.371
SOF/VEL+RBV	2.37	1.34-4.17	0.003

BMI: Body mass index; GT: Genotype; HIV: Human immunodeficiency virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; ASV: Asunaprevir; DCV: Daclatasvir; SOF: Sofosbuvir; VEL: Velpatasvir; RBV: Ribavirin; OR: Odds ratio; CI: Confidence interval.

Table 5 Safety of direct-acting antiviral treatment in chronic hepatitis C patients with (group A) and without (group B) psychiatric disorders, %, n

Parameter	All patients (n = 14272)	Group A (n = 942)	Group B (n = 13330)	P value
Treatment course
According to schedule	97.5 (13848)	96.8 (907)	97.6 (12941)	0.164 (χ2 = 1.9)
Therapy discontinuation	1.1 (157)	1.4 (13)	1.1 (144)	0.394 (χ2 = 0.7)
Therapy modification	1.4 (194)	1.8 (17)	1.3 (177)	0.222 (χ2 = 1.5)
No data	0.5 (73)	0.5 (5)	0.5 (68)	0.813
Death	0.5 (71)	0.4 (4)	0.5 (67)	1.0
SAE	1.0 (145)	1.6 (15)	0.97 (130)	0.068 (χ2 = 3.3)
Psychiatric complications
New incidence of depression	0.1 (8)	0.2 (2)	0.05 (6)	0.093
New incidence of schizophrenia	0.0 (1)	0.0 (0)	0.0 (1)	1.0
New incidence of sleep disorders	1.8 (262)	3.3 (31)	1.7 (231)	0.001 (χ2 = 10.4)
New incidence of anxiety	0.0 (1)	0.1 (1)	0.0 (0)	1.0
Drinking binge	0.0 (1)	0.1 (1)	0.0 (0)	1.0
Exacerbation of psychiatric disease		0.6 (6)
Depression		0.5 (5)
Schizophrenia		0.1 (1)

The reported P value relates to Pearson’s chi-square test or Fisher’s exact test if the number of observations in the category was less than 10. SAEs: Serious adverse events.