2.1 Baseline characteristics
A total of 285 patients with GT 3 HCV infection with liver cirrhosis were selected (Figure 1). There were no statistical differences in age, gender, and HCV RNA among patients. The RBC, TBIL, ALB, ALP, and CHE indexes of patients in the decompensated stage were higher than those in the compensated stage of cirrhosis, and the differences were statistically significant (P<0.05)(see Table 1,2).
Tab.1 Baseline clinical characteristics of enrolled patients[x̄±s/n(%)/ M(P25,P75)]
*P<0.05
Abbreviations: GT, genotype; CC, compensated cirrhotic ;DCC, decompensated cirrhosis ;RBC, Red Blood Cell; TBIL, total bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALB, albumin; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; CHE, Cholinesterase; CR, creatinine;UA, Uric Acid.
Tab.2 Baseline clinical characteristics of enrolled patients[x̄±s/n(%)/ M(P25,P75)]
*P<0.05
Abbreviations: GT, genotype; CC, compensated cirrhotic ;DCC, decompensated cirrhosis ;RBC, Red Blood Cell; TBIL, total bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALB, albumin; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; CHE, Cholinesterase; CR, creatinine;UA, Uric Acid.
2.2 Virological response after treatment in three groups of patients
After 4 weeks of antiviral treatment, the total sustained virologic response (SVR 4) rate was 94.38% (269/285), the total SVR 4 rate in patients with compensated cirrhosis was 93.98% (125/133) (all patients achieved SVR 4 except 3 cases of HCV alone, and 5 patients with HCV/HIV co-infection), and the total SVR 4 rate in patients with cirrhotic decompensation was 94.74/% (144/152 ) (all patients achieved SVR 4 except 3 patients with HCV alone, 4 patients with HCV/HIV co-infection, and 1 patient with HCV/HBV co-infection), with no statistical difference (P=0.783). And the total sustained virological response (SVR 12) rate was 98.94% (282/285) at the end of 12 weeks of antiviral treatment discontinuation, and only one patient with cirrhotic liver cancer in GT3a cirrhosis relapsed after discontinuation, without statistical difference (P=0.642) see Figure 2. in this study No statistical difference was observed in the virological response negative rates [SVR 4 , SVR12] in cirrhotic compensated and cirrhotic decompensated stages (as shown in Table 3).
Tab.3 Comparison of Sustained Virologic Response in Patients with Therapeutic Genotype 3 Hepatitis C [n(%)]
group
|
SVR4
|
X2
|
P
|
SVR12
|
X2
|
P
|
CC
|
DCC
|
CC
|
DCC
|
GT3
|
125(93.98)
|
144(94.74)
|
0.076
|
0.783
|
132(99.25)
|
150(98.68)
|
0.217
|
0.642
|
3a
|
25(89.29)
|
14(87.50)
|
0.032
|
0.858
|
28(100.00)
|
15(93.75)
|
1.791
|
0.181
|
3b
|
100(95.24)
|
130(95.59)
|
0.017
|
0.897
|
104(99.05)
|
135(99.26)
|
0.034
|
0.854
|
Abbreviations: RVR , rapid virological response; EVR , early virological response ; SVR, sustained virological response.
3.3 Cirrhosis and liver fibrosis scores in the three groups after treatment
In this study, the mean APRI at baseline in the compensated phase of cirrhosis was 5.27, with a total of 115 (86.47%) patients with APRI>2. The mean APRI after 12 weeks of treatment was 1.98, with a total of 27 (20.30%) patients with APRI>2. The difference was statistically significant (P=0.001). The mean APRI value at baseline in the cirrhosis decompensated stage was 5.35 and the total number of patients with APRI>2 was 128 (84.21%), the mean APRI value after 12 weeks of treatment was 2.59, and the total number of patients with APRI>2 was 73 (48.03%), the difference was statistically significant (P=0.001). After 12 weeks of treatment, the mean APRI score decreased by 3.29 (P=0.001) from 5.27 to 1.98 in the group with compensated cirrhosis and by 2.76 (P=0.021) from 5.35 to 2.59 in the group with decompensated cirrhosis. Although no statistical significance was observed numerically in both groups, the proportion of patients with APRI >2 in the cirrhotic compensated stage was lower than in the cirrhotic decompensated stage group at 12 weeks after treatment (P=0.001), as shown in Tables 4, 5 and Figure 3.
In this study, the mean FIB-4 value at baseline in the compensated stage of cirrhosis was 7.07, and the total number of patients with FIB-4>3.25 was 111(83.46%). The mean APRI value after 12 weeks of treatment was 4.05, with a statistically significant difference from baseline (P=0.001), and the total number of patients with FIB-4>3.25 was 41 (30.83), with a statistically significant difference from baseline (P=0.045). The mean FIB-4 value at baseline in cirrhotic decompensation was 8.39, and the total number of patients with FIB-4>3.25 was 141 (92.76%) . The mean FIB-4 value after 12 weeks of treatment was 6.87, with a statistically significant difference from baseline (P=0.004), and the total number of patients with FIB-4>3.25 was 117 (76.97%), with a statistically significant difference (P=0.001). The proportion of patients with FIB-4>3.25 in the compensated phase of cirrhosis from baseline to 12 weeks post-treatment was lower than that in the decompensated phase of the cirrhosis group (P baseline=0.014, P 12 weeks post-treatment=0.001), and numerically there was also a statistically significant difference between both compensated and decompensated phases of cirrhosis from baseline to post-treatment FIB-4 scores (P baseline=0.045, P 12 weeks post-treatment= 0.003), (as shown in Tables 5 and 6 and Figure 3).
Tab 4. APRI for GT3 CHC patients Before and After Treatment [n(%)]
APRI
|
GT3 HCV with CC
|
GT3 HCV with DCC
|
P
|
APRI>2
|
APRI≤2
|
APRI>2
|
APRI≤2
|
Before treatment
|
115(86.47)
|
18(13.53)
|
128(84.21)
|
24(15.79)
|
0.592
|
After treatment
|
27(20.30)
|
106(79.70)
|
73(48.03)
|
79(51.97)
|
0.001*
|
P
|
0.001*
|
0.001*
|
|
*P<0.05
Tab 5. FIB-4 for GT3 CHC patients Before and After Treatment [n(%)]
FIB-4
|
GT3 HCV with CC
|
GT3 HCV with DCC
|
P
|
FIB-4>3.25
|
FIB-4≤3.25
|
FIB-4>3.25
|
APRI≤3.25
|
Before treatment
|
111(83.46)
|
22(14.47)
|
141(92.76)
|
11(7.24)
|
0.014*
|
After treatment
|
41(30.83)
|
92(69.17)
|
117(76.97)
|
35(23.03)
|
0.001*
|
P
|
0.001*
|
0.001*
|
|
*P<0.05
Tab 6. APRI and FIB-4 for GT3 CHC patients Before and After Treatment [x̄±s]
|
APRI
|
FIB-4
|
CC
|
DCC
|
P
|
CC
|
DCC
|
P
|
Before treatment
|
5.27±3.22
|
5.35±7.02
|
0.470
|
7.07±8.61
|
8.39±6.85
|
0.045*
|
After treatment
|
1.98±1.80
|
2.59±2.50
|
0.199
|
4.05±3.44
|
6.87±5.14
|
0.003*
|
P
|
0.001*
|
0.021*
|
|
0.001*
|
0.004*
|
|
*P<0.05
2.4 Biochemical response in the three groups of patients after treatment
Patients' pre- and post-treatment ALT recurrence rate and AST indexes improved significantly after 4 weeks of treatment (P=0.002), and TBIL indexes improved significantly after 12 weeks of treatment (P=0.002). After stratification by genotype, GT3a and GT3b obtained similar results as overall, with improvement in ALT normality and AST indexes at week 4 of treatment and TBIL indexes at week 12 of treatment. However, after stratification by cirrhosis, patients with cirrhotic decompensation showed significant improvement in AST index after 12 weeks of treatment (P=0.008), compared to the overall improvement after 4 weeks of treatment, patients with cirrhotic decompensation showed improvement in AST index later, and it can be observed in Figure 4 that patients with cirrhotic decompensation showed an increase in AST level after 12 weeks of drug administration but the difference was not statistically significant (P= 0.347), and the time to appearance of improvement in overall AST was consistent in cirrhotic compensated stage, as shown in Table 7.
Among the patients, the ALT recurrence rate increased from 12.98% at baseline to 80.00%, with statistically significant differences (P<0.05), and all showed a statistically significant difference from the previous observation node with sustained improvement during the observation period. No statistical difference was observed between GT 3a and GT 3b after stratification by genotype. After stratification by cirrhosis stage, there was no statistical difference between the two groups at baseline, but a statistical difference began to appear after the fourth week of treatment in patients with cirrhotic decompensation compared to patients with cirrhotic compensation, and the difference persisted. The ALT recurrence rate was 69.17% in cirrhotic compensated patients at the fourth week of treatment and 48.03% in patients in the decompensated group, with a statistically significant difference (P=0.003). The ALT normalization rate in compensated cirrhosis at week 12 of treatment was 75.94%, and the ALT normalization rate in patients in the decompensated group was 64.47%, with a statistically significant difference (P=0.035). The ALT normalization rate in compensated cirrhosis at the 12th week of discontinuation was 96.24%, and the ALT normalization rate in patients in the decompensated group was 72.37%, with a statistically significant difference (P=0.001), as shown in Table 7 and Figure 4.
Tab 7. Comparison of serum biochemical indexes in patients with hepatitis C virus genotype 3(GT3)[M(P25,P75)]
*P<0.05
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin;
Tab 8 . Changes of ALT normalization rate in patients with hepatitis C virus genotype 3(GT3) before and after treatment[n(%)]
Time
|
Delamination
|
P
|
Delamination
|
P
|
3a
|
3b
|
CC
|
DCC
|
Baseline
|
5(11.36)
|
32(13.28)
|
0.728
|
17(12.78)
|
20(13.16)
|
0.925
|
4 weeks of treatment
|
28(63.64)
|
137(56.85)
|
0.402
|
92(69.17)
|
73(48.03)
|
0.003*
|
12weeks of treatment
|
32(72.73)
|
167(69.29)
|
0.648
|
101(75.94)
|
98(64.47)
|
0.035*
|
12 weeks off medication
|
39(88.64)
|
189(78.42)
|
0.119
|
128(96.24)
|
110(72.37)
|
0.001*
|
*P<0.05
2.5 safety evaluation
A total of 284 patients (133 with CC and 151 with DCC) completed full treatment, and 1 case was discontinued from RBV due to drug interactions. adverse reactions are shown in Table 8. the incidence of adverse reactions was 43.61% in patients with CC and 71.71% in patients with DCC. The most frequent adverse effects were anemia, elevated bilirubin, and malaise. There were no serious adverse reactions, deaths, or discontinuation of treatment due to adverse events in the study observations, as shown in Table 9.
Tab 9 . Adverse reaction in patients with hepatitis C virus genotype 3(GT3) [n(%)]
Adverse effects
|
CC(n=133)
|
DCC(n=152)
|
Any adverse effects
|
58(43.61)
|
109(71.71)
|
Severe adverse effects
|
0
|
0
|
Adverse reactions leading to discontinuation of the drug
|
0
|
0
|
anaemia
|
Mild
|
16(12.03)
|
47(30.92)
|
Moderate
|
5(3.75)
|
17(11.18)
|
Severe
|
1(0.75)
|
11(7.24)
|
Bilirubin is elevated
|
43(32.33)
|
84(55.26)
|
fatigue
|
25(18.80)
|
27(17.76)
|
headache
|
9(6.77)
|
18(11.84)
|
dizzy
|
13(9.77)
|
21(7.89)
|
rash
|
11(8.27)
|
25(16.45)
|