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©The Author(s) 2022.
World J Gastroenterol. Dec 7, 2022; 28(45): 6380-6396
Published online Dec 7, 2022. doi: 10.3748/wjg.v28.i45.6380
Published online Dec 7, 2022. doi: 10.3748/wjg.v28.i45.6380
Table 1 Baseline characteristics of 11385 genotype 1b-infected patients treated with interferon-free regimens
Parameter | GT1b patients, n = 11385 |
Sex, female/male, n (%) | 6085 (53.4)/5300 (46.6) |
Age in yr, mean ± SD; min-max | 53 ± 14.8; 17-97 |
Females | 54.8 ± 15.1; 18-92 |
Males | 51 ± 14.3; 17-97 |
BMI, kg/m2 mean ± SD; min-max | 26.3 ± 4.5; 13.2-57.4 |
Comorbidities, n (%) | |
Any comorbidity | 7280 (63.9) |
Hypertension | 4013 (35.2) |
Diabetes | 1447 (12.7) |
Renal disease | 470 (4.1) |
Autoimmune diseases | 251 (2.2) |
Non-HCC tumors | 237 (2.1) |
Other | 5330 (46.8) |
Concomitant medications, n (%) | 6842 (60.1) |
Liver fibrosis n(%) | |
F0 | 237 (2.1) |
F1 | 4440 (39) |
F2 | 2135 (18.8) |
F3 | 1587 (13.9) |
F4 | 2768 (24.3) |
No data | 218 (1.9) |
HCC history, n (%) | 175 (1.5) |
OLTx history, n (%) | 122 (1.1) |
HBV coinfection (HBsAg+), n (%) | 106 (0.9) |
HIV coinfection, n (%) | 359 (3.1) |
ALT IU/L, mean ± SD | 75.8 ± 65.5 |
Bilirubin mg/dL, mean ± SD | 0.8 ± 0.9 |
Albumin g/dL, mean ± SD | 4.3 ± 3.2 |
Creatinine mg/dL, mean ± SD | 0.9 ± 1.8 |
Hemoglobin g/dL, mean ± SD | 14.4 ± 1.8 |
Platelets × 1000/μL, mean ± SD | 195.3 ± 77.8 |
HCV RNA × 106 IU/mL, mean ± SD | 2.1 ± 4.7 |
Table 2 Genotype 1b-infected patients with liver cirrhosis treated with direct-acting antivirals
Parameter | GT1b patients, n = 2768 |
History of hepatic decompensation, n (%) | |
Ascites | 322 (11.6) |
Encephalopathy | 87 (3.1) |
Documented esophageal varices, n (%) | 860 (31) |
Hepatic decompensation at baseline, n (%) | |
Ascites - moderate responded to diuretics and tense | 164 (5.9) |
Encephalopathy | 72 (0.3) |
Child-Pugh, n (%) | |
B | 362 (13.1) |
C | 20 (0.1) |
No data | 223 (8.1) |
Table 3 Treatment characteristics of genotype 1b-infected patients treated with direct-acting antiviral
Parameter | GT1b patients, n = 11385 |
History of previous therapy | |
Treatment-naïve | 8497 (74.6) |
Non-responder | 949 (8.3) |
Relapser | 831 (7.3) |
Discontinuation due to safety reason | 338 (3) |
Unknown type of response | 728 (6.4) |
No data | 42 (0.4) |
Previous treatment regimen in treatment-experienced, n = 2846 | |
IFN ± RBV | 149 (5.2) |
PegIFN ± RBV | 2080 (73.1) |
IFN + RBV + DAA | 438 (15.4) |
DAA | 155 (5.4) |
No data | 24 (0.9) |
Genotype-specific treatment regimens | |
ASV + DCV | 135 (1.2) |
LDV/SOF ± RBV | 2652 (23.3) |
OBV/PTV/r + DSV ± RBV | 3685 (32.4) |
GZR/EBR ± RBV | 2270 (19.9) |
Other (SOF ± SMV ± DCV ± RBV, SMV ± DCV ± RBV) | 16 (0.1) |
Pangenotypic regimens | |
GLE/PIB | 1684 (14.8) |
GLE/PIB + SOF + RBV | 3 (< 0.1) |
SOF/VEL ± RBV | 931 (8.2) |
VOX/VEL/SOF | 9 (0.1) |
Table 4 The overall treatment effectiveness and according to treatment regimens in relation to different risk factors among the studied patients (per protocol analysis)
Parameter | Whole population | Females | Males | F4 | T-ex | History of hepatic decompensation | ≥ 70-year-old | eGFR ≤ 60 mL/min | Obese1 | HIV+ |
All regimens | 10903/11112 (98.1) | 5891/5969 (98.7) | 5012/5143 (97.5) | 2590/2678 (96.7) | 2726/2795 (97.5) | 319/336 (94.9) | 1490/1509 (98.7) | 281/284 (98.9) | 1880/1923 (97.8) | 327/341 (95.9) |
ASV + DCV | 119/132 (90.2) | 72/79 (91.1) | 47/53 (88.7) | 47/55 (85.5) | 40/47 (85.1) | 0/1 (0) | 22/24 (91.7) | 5/5 (100) | 26/28 (92.9) | 1/1 (100) |
LDV/SOF ± RBV | 2534/2582 (98.1) | 1381/1398 (98.8) | 1153/1184 (97.4) | 679/707 (96) | 680/696 (97.7) | 173/181 (95.6) | 386/389 (99.2) | 67/67 (100) | 446/459 (97.2) | 103/107 (96.3) |
OBV/PTV/r + DSV ± RBV | 3563/3627 (98.2) | 1949/1973 (98.8) | 1614/1654 (97.6) | 969/992 (97.7) | 1490/1516 (98.3) | 72/74 (97.3) | 397/403 (98.5) | 80/82 (97.6) | 602/611 (98.5) | 26/28 (92.9) |
GZR/EBR ± RBV | 2179/2216 (98.3) | 1201/1215 (98.8) | 978/1001 (97.7) | 362/372 (97.3) | 291/297 (98) | 19/20 (95) | 397/401 (99) | 87/88 (98.9) | 380/389 (97.7) | 48/48 (100) |
GLE/PIB | 1625/1643 (98.9) | 869/874 (99.4) | 756/769 (98.3) | 264/268 (98.5) | 112/114 (98.2) | 12/12 (100) | 147/150 (98) | 24/24 (100) | 267/267 (100) | 72/76 (94.7) |
GLE/PIB + SOF + RBV | 3/3 (100) | 1/1 (100) | 2/2 (100) | 1/1 (100) | 3/3 (100) | - | - | - | 1/1 (100) | - |
SOF/VEL ± RBV | 857/884 (96.9) | 409/419 (97.6) | 448/465 (96.3) | 260/275 (94.5) | 91/101 (90.1) | 40/44 (90.9) | 138/139 (99.3) | 16/16 (100) | 158/167 (94.6) | 74/78 (94.9) |
VOX/VEL/SOF | 9/9 (100) | 2/2 (100) | 7/7 (100) | 3/3 (100) | 7/7 (100) | - | 3/3 (100) | - | - | 3/3 (100) |
Table 5 The comparison of virological responders and non-responders to direct-acting antiviral therapy
Parameter | Responders, n = 10903 | Non-responders, n = 209 | P value |
Sex, females/males, n (%) | 5891 (54)/5012 (46) | 78 (37.3)/131 (62.7) | < 0.001 |
Age in yr, mean ± SD; min-max | 52.9 ± 14.8; 17-97 | 53.4 ± 13; 25-84 | 0.69 |
BMI, kg/m2 mean ± SD; min-max | 26.3 ± 4.5; 13.2-57.4 | 27 ± 4.6; 15.4-48 | 0.005 |
Genotype-specific treatment regimens, n (%) | |||
ASV + DCV | 119 (1.1) | 13 (6.2) | < 0.001 |
LDV/SOF ± RBV | 2534 (23.2) | 48 (22.9) | 0.99 |
OBV/PTV/r + DSV ± RBV | 3563 (32.6) | 64 (30.7) | 0.58 |
GZR/EBR ± RBV | 2179 (20) | 37 (17.7) | 0.46 |
Other (SOF ± SMV ± DCV ± RBV, SMV ± DCV ± RBV) | 14 (0.1) | 2 (1) | 0.03 |
Pangenotypic regimens, n (%) | |||
GLE/PIB | 1625 (14.9) | 18 (8.6) | 0.01 |
GLE/PIB + SOF + RBV | 3 (< 0.1) | 0 | 0.06 |
SOF/VEL ± RBV | 857 (7.8) | 27 (12.9) | 0.01 |
VOX/VEL/SOF | 9 (0.2) | 0 | 0.42 |
Regimen, n (%) | 0.65 | ||
Genotype-specific | 8409 (77.1) | 164 (80.5) | |
Pangenotypic | 2494 (22.9) | 45 (21.5) | |
Comorbidities, n (%) | |||
Any comorbidity | 6958 (63.8) | 138 (65.7) | 0.55 |
Hypertension | 3842 (35.2) | 75 (35.7) | 0.90 |
Diabetes | 1369 (12.6) | 24 (11.4) | 0.72 |
Renal disease | 446 (4.1) | 7 (3.3) | 0.71 |
Autoimmune diseases | 240 (2.2) | 4 (1.9) | 0.96 |
Non-HCC tumors | 214 (2) | 6 (2.9) | 0.49 |
Other | 5085 (46.6) | 106 (50.5) | 0.27 |
Concomitant medications, n (%) | 6517 (59.8) | 141 (67.5) | 0.03 |
Liver fibrosis, n (%) | |||
F0 | 229 (2.1) | 2 (1) | 0.37 |
F1 | 4308 (39.5) | 50 (23.9) | < 0.001 |
F2 | 2054 (18.8) | 38 (18.2) | 0.88 |
F3 | 1522 (14) | 25 (12) | 0.47 |
F4 | 2590 (23.8) | 88 (42.1) | < 0.001 |
No data | 200 (1.8) | 6 (2.9) | 0.40 |
History of previous therapy, n (%) | |||
Treatment-naïve | 8138 (74.6) | 140 (67) | 0.01 |
Non-responder | 908 (8.3) | 24 (11.5) | 0.13 |
Relapser | 803 (7.4) | 21 (10) | 0.18 |
Discontinuation due to safety reason | 320 (2.9) | 9 (4.3) | 0.34 |
Unknown type of response | 695 (6.4) | 15 (7.2) | 0.74 |
No data | 39 (0.4) | 0 | 0.78 |
Previous DAA treatment | 120 (1.2) | 18 (9) | < 0.001 |
History of hepatic decompensation, n (%) | |||
Ascites | 286 (2.6) | 14 (6.7) | < 0.001 |
Encephalopathy | 75 (0.7) | 7 (3.3) | < 0.001 |
Documented esophageal varices, n (%) | 778 (7.1) | 38 (18.2) | < 0.001 |
Hepatic decompensation at baseline, n (%) | |||
Ascites | 136 (1.3) | 10 (4.8) | < 0.001 |
Encephalopathy | 58 (0.5) | 6 (2.9) | < 0.001 |
HCC history, n (%) | 150 (1.4) | 8 (3.8) | 0.01 |
OLTx history, n (%) | 117 (1.1) | 2 (0.9) | 0.86 |
Child-Pugh, n (%) | |||
B | 306 (2.8) | 23 (11) | < 0.001 |
C | 15 (0.1) | 0 | 0.67 |
HBV coinfection (HBsAg+), n (%) | 102 (0.9) | 2 (0.9) | 0.74 |
HIV coinfection, n (%) | 327 (3) | 14 (6.7) | 0.004 |
ALT IU/L, mean ± SD | 75.6 ± 65.3 | 85.5 ± 71.1 | 0.005 |
Bilirubin mg/dL, mean ± SD | 0.8 ± 0.8 | 1 ± 0.7 | < 0.001 |
Albumin g/dL, mean ± SD | 4.3 ± 3.3 | 4.1 ± 2.8 | < 0.001 |
Creatinine mg/dL, mean ± SD | 0.9 ± 1.9 | 0.8 ± 0.2 | 0.93 |
Hemoglobin g/dL, mean ± SD | 14.4 ± 1.8 | 14.3 ± 1.9 | 0.71 |
Platelets, × 1000/μL, mean ± SD | 196.5 ± 77.4 | 160.6 ± 73.3 | < 0.001 |
HCV RNA × 106 IU/mL, mean ± SD | 2.1 ± 4.8 | 2.2 ± 2.8 | 0.02 |
Table 6 Factors associated with virologic response in logistic regression model in studied hepatitis C virus-genotype 1b population
Effect | Effect measure | Wald stat | OR | -95%CI of OR | +95%CI of OR | Pvalue |
Intercept | 10.742 | 24.208 | 3.600 | 162.775 | 0.001 | |
Sex | Female | 10.075 | 1.668 | 1.216 | 2.289 | 0.002 |
HIV-coinfection | Yes | 9.278 | 0.393 | 0.216 | 0.717 | 0.002 |
Platelets × 1000/μL | Per 1 U increase | 7.619 | 1.004 | 1.001 | 1.006 | 0.006 |
Decompensation at baseline | No | 4.359 | 2.423 | 1.056 | 5.559 | 0.037 |
HCC | Yes | 3.733 | 0.459 | 0.208 | 1.011 | 0.053 |
BMI kg/m2 | Per 1 U increase | 3.154 | 0.971 | 0.940 | 1.003 | 0.076 |
Treatment-experience | No | 0.972 | 1.180 | 0.849 | 1.639 | 0.324 |
Albumins g/dL | Per 1 U increase | 0.822 | 1.027 | 0.970 | 1.088 | 0.365 |
Bilirubin mg/dL | Per 1 U increase | 0.294 | 0.963 | 0.839 | 1.104 | 0.588 |
Fibrosis | 1 | 0.020 | 0.902 | 0.217 | 3.749 | 0.888 |
Fibrosis | 2 | 0.255 | 0.690 | 0.164 | 2.911 | 0.614 |
Fibrosis | 3 | 0.054 | 0.840 | 0.194 | 3.639 | 0.816 |
Fibrosis | 4 | 0.547 | 0.580 | 0.137 | 2.460 | 0.460 |
ALT IU/mL | Per 1 U increase | 0.053 | 1.000 | 0.998 | 1.002 | 0.818 |
History of decompensation | No | 0.010 | 1.039 | 0.500 | 2.160 | 0.918 |
Table 7 Safety of antiviral therapy in genotype 1b-infected patients according to treatment regimens
Parameter | GT1b patients, n = 11385 | ASV + DCV, n = 135 | LDV/SOF ± RBV, n = 2652 | OBV/PTV/r + DSV ± RBV, n = 3685 | GZR/EBR ± RBV, n = 2270 | GLE/PIB, n = 1684 | GLE/PIB + SOF + RBV, n = 3 | SOF/VEL ± RBV, n = 931 | VOX/VEL/SOF, n = 9 |
Therapy course, n (%) | |||||||||
According to schedule | 11031 (96.9) | 130 (96.3) | 2549 (96.1) | 3513 (95.3) | 2245 (98.9) | 1666 (98.9) | 3 (100) | 900 (96.7) | 9 (100) |
Discontinuation | 134 (1.2) | 5 (3.7) | 27 (1) | 60 (1.6) | 18 (0.8) | 8 (0.5) | 0 | 16 (1.7) | 0 |
Modification | 151 (1.3) | 0 | 62 (2.4) | 76 (2.1) | 1 (< 0.1) | 3 (0.2) | 0 | 9 (1) | 0 |
No data | 69 (0.6) | 0 | 14 (0.5) | 36 (1) | 6 (0.3) | 7 (0.4) | 0 | 6 (0.6) | 0 |
Patients with at least one AE, n (%) | 2167 (19) | 49 (36.3) | 518 (19.5) | 911 (24.7) | 362 (15.9) | 184 (10.9) | 1 (33.3) | 133 (14.3) | 0 |
Serious adverse events, n (%) | 123 (1.1) | 7 (5.2) | 27 (1) | 59 (1.6) | 11 (0.5) | 5 (0.3) | 0 | 14 (1.5) | 0 |
AEs leading to treatment discontinuation, n (%) | 82 (0.7) | 2 (1.5) | 20 (0.8) | 47 (1.3) | 7 (0.3) | 4 (0.2) | 0 | 2 (0.2) | 0 |
Most common AEs (≥ 1%), n (%) | |||||||||
Weakness/fatigue | 1073 (9.4) | 20 (14.8) | 409 (15.4) | 395 (10.7) | 141 (6.2) | 57 (3.4) | 0 | 46 (4.9) | 0 |
Anemia | 142 (1.2) | 1 (0.7) | 65 (2.5) | 55 (1.5) | 9 (0.4) | 1 (0.1) | 1 (33.3) | 5 (0.5) | 0 |
Sleep disorders | 214 (1.9) | 4 (3) | 49 (1.8) | 95 (2.6) | 29 (1.3) | 25 (1.5) | 0 | 12 (1.3) | 0 |
Skin lesions | 106 (0.9) | 6 (4.4) | 24 (0.9) | 41 (1.1) | 10 (0.4) | 13 (0.8) | 0 | 12 (1.3) | 0 |
Itchy skin | 205 (1.8) | 0 | 31 (1.2) | 135 (3.7) | 6 (0.3) | 27 (1.6) | 0 | 5 (0.5) | 0 |
Diarrhea | 83 (0.7) | 4 (3) | 20 (0.8) | 32 (0.9) | 17 (0.7) | 4 (0.2) | 0 | 6 (0.6) | 0 |
Nausea | 136 (1.2) | 4 (3) | 29 (1.1) | 50 (1.4) | 25 (1.1) | 20 (1.2) | 0 | 8 (0.9) | 0 |
Headaches | 306 (2.7) | 5 (3.7) | 87 (3.3) | 95 (2.6) | 60 (2.6) | 45 (2.7) | 0 | 13 (1.4) | 0 |
Myalgia/arthralgia | 166 (1.5) | 5 (3.7) | 27 (1) | 65 (1.8) | 45 (2) | 13 (0.8) | 0 | 11 (1.2) | 0 |
Abdominal pain | 159 (1.4) | 10 (7.4) | 27 (1) | 45 (1.2) | 41 (1.8) | 22 (1.3) | 0 | 14 (1.5) | 0 |
Loss of appetite | 52 (0.5) | 3 (2.2) | 6 (0.2) | 24 (0.7) | 9 (0.4) | 4 (0.2) | 0 | 6 (0.6) | 0 |
AEs of particular interest (cirrhotics), n (%) | n = 2768 | n = 55 | n = 737 | n = 1019 | n = 380 | n = 278 | n = 1 | n = 290 | n = 3 |
Ascites | 60 (2.2) | 0 | 31 (4.2) | 21 (2.1) | 2 (0.5) | 0 | 0 | 6 (2.1) | 0 |
Encephalopathy | 44 (1.6) | 0 | 22 (3) | 16 (1.6) | 1 (0.3) | 2 (0.7) | 0 | 3 (1) | 0 |
Gastrointestinal bleeding | 16 (0.6) | 0 | 10 (1.4) | 4 (0.4) | 0 | 0 | 0 | 2 (0.7) | 0 |
Death, n (%) | 64 (0.6) | 0 | 19 (0.7) | 18 (0.5) | 9 (0.4) | 5 (0.3) | 0 | 13 (1.4) | 0 |
- Citation: Zarębska-Michaluk D, Brzdęk M, Jaroszewicz J, Tudrujek-Zdunek M, Lorenc B, Klapaczyński J, Mazur W, Kazek A, Sitko M, Berak H, Janocha-Litwin J, Dybowska D, Supronowicz Ł, Krygier R, Citko J, Piekarska A, Flisiak R. Best therapy for the easiest to treat hepatitis C virus genotype 1b-infected patients. World J Gastroenterol 2022; 28(45): 6380-6396
- URL: https://www.wjgnet.com/1007-9327/full/v28/i45/6380.htm
- DOI: https://dx.doi.org/10.3748/wjg.v28.i45.6380