Effect on the improvement of liver fibrosis through anti-hepatitis C virus treatment by direct acting antivirals

doi:10.3877/cma.j.issn.1674-1358.2019.05.012

Abstract

Abstract:

Objective

To investigate the improvement of liver fibrosis in patients with chronic hepatitis C (CHC) after removal of hepatitis B virus (HCV) by directly acting antivirals (DAAs).

Methods

Total of 111 CHC patients with sustained virological response (SVR) after treatment with DAAs were enrolled. White blood cell (WBC), red blood cell (RBC), platelets (PLT), and alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil), blood urea nitrogen (BUN), creatinine (Cr), liver stiffness measurement (LSM), aspartate transferase/platelets ratio index (APRI) and Fib-4 scores (Fib-4) of patients, before and after treatment respectively. Patients were divided into groups according to the diagnosis before treatment with DAAs, including 77 patients as chronic hepatitis group, 13 patients as compensated cirrhosis group, and 21 patients as decompensated cirrhosis group. LSM, APRI and Fib-4 before and after treatment with DAAs in each group were compared, respectively. Logistic binary regression analysis of the effects of baseline values of gender, genotype, body mass index (BMI), WBC, PLT, ALT, AST, TBil, APRI and Fib-4 scores on LSM changes were analyzed by Logistic binary regression.

Results

Compared with pretherapy, the counts of WBC and PLT were significantly elevated, ALT, AST and TBil were significantly reduced in 111 patients (Z =-3.842, P < 0.001; Z =-3.854, P < 0.001; Z =-8.919, P < 0.001; Z =-8.882, P < 0.001; Z =-4.487, P < 0.001). There were no significant differences in serum Cr and BUN before and after treatment of the 111 patients (Z =-0.287, P = 0.774; Z =-0.424, P = 0.671). The three noninvasive liver fibrosis markers LSM, APRI and Fib-4 of 111 patients were significantly different from those before treatment (Z =-6.955, P < 0.001; Z =-8.836, P < 0.001; Z =-6.838, P < 0.001).The three noninvasive liver fibrosis markers were statistically significant of patients in chronic hepatitis group compared with those of compensated liver cirrhosis group and decompensated cirrhosis group (LSM: χ² = 13.52, P < 0.001; χ² = 34.00, P < 0.001. APRI: χ² = 10.84, P < 0.001; χ² = 28.38, P < 0.001. Fib-4: χ² = 16.83, P < 0.001; χ² = 29.36, P < 0.001). But there was no significant difference in the three noninvasive liver fibrosis markers between patients in compensated cirrhosis group and decompensated cirrhosis group (LSM: χ² = 1.08, P = 0.58; Fib-4: χ² = 0.84, P = 0.66; APRI: χ² = 0.09, P = 0.96). Patients with higher ALT [P = 0.045, OR (95%CI) = 0.918 (0.844-0.998)], AST [P = 0.013, OR (95%CI) = 0.862 (0.767-0.969)], APRI [P = 0.032, OR (95%CI) = 0.001 (0.000-0.555)] baseline levels or lower WBC [P = 0.019, OR (95%CI) = 2.508 (1.161-5.421)] baseline level had a significant improvement on LSM after SVR, all with significant differences.

Conclusions

The degree of liver fibrosis was significantly reduced in patients with CHC whose HCV were successfully removed, and the changes are more significantly in LC patients. Antiviral therapy should be initiated as soon as possible for patients with CHC. Early realization of SVR could block liver inflammation and liver fibrosis for patients with CHC, thus reducing the occurrence and development of cirrhosis decompensation complications.

Key words: Chronic hepatitis C, Directly acting antivirals, Liver fibrosis, Liver stiffness measurement, Aspartate aminotransferase to platelet ratio index, Fib-4 score

Yujie Sun, Yintang Jia. Effect on the improvement of liver fibrosis through anti-hepatitis C virus treatment by direct acting antivirals[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2019, 13(05): 414-420.

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References 25

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指标	检测例数	治疗前	获得SVR后	Z值	P值
WBC（× 10⁹/L）	111	4.62（4.05，6.59）	5.02（4.30，6.54）	－3.842	< 0.001
PLT（× 10⁹/L）	111	157.00（115.00，240.00）	182.00（132.00，219.00）	－3.854	< 0.001
ALT（U/L）	111	39.00（27.00，75.00）	15.00（11.00，21.00）	－8.919	< 0.001
AST（U/L）	111	40.00（25.00，66.00）	20.00（15，00，24.00）	－8.882	< 0.001
TBil（μmol/L）	85	17.70（13.65，21.55）	14.30（12.40，18.80）	－4.487	< 0.001
Cr（μmol/L）	67	61.60（51.70，70.10）	63.70（54.15，71.55）	－0.287	0.774
BUN（mmol/L）	73	4.44（3.49，5.17）	4.31（3.71，5.15）	－0.424	0.671
LSM（kPa）	68	9.15（5.53，13.35）	5.30（3.50，8.90）	－6.955	< 0.001
APRI	111	0.58（0.36，1.49）	0.29（0.21，0.43）	－8.836	< 0.001
Fib-4	111	1.83（0.80，3.88）	1.35（0.70，2.28）	－6.838	< 0.001

指标	检测例数	治疗前	获得SVR后	Z值	P值
WBC（× 10⁹/L）	111	4.62（4.05，6.59）	5.02（4.30，6.54）	－3.842	< 0.001
PLT（× 10⁹/L）	111	157.00（115.00，240.00）	182.00（132.00，219.00）	－3.854	< 0.001
ALT（U/L）	111	39.00（27.00，75.00）	15.00（11.00，21.00）	－8.919	< 0.001
AST（U/L）	111	40.00（25.00，66.00）	20.00（15，00，24.00）	－8.882	< 0.001
TBil（μmol/L）	85	17.70（13.65，21.55）	14.30（12.40，18.80）	－4.487	< 0.001
Cr（μmol/L）	67	61.60（51.70，70.10）	63.70（54.15，71.55）	－0.287	0.774
BUN（mmol/L）	73	4.44（3.49，5.17）	4.31（3.71，5.15）	－0.424	0.671
LSM（kPa）	68	9.15（5.53，13.35）	5.30（3.50，8.90）	－6.955	< 0.001
APRI	111	0.58（0.36，1.49）	0.29（0.21，0.43）	－8.836	< 0.001
Fib-4	111	1.83（0.80，3.88）	1.35（0.70，2.28）	－6.838	< 0.001

纤维化指标		慢性肝炎组		代偿期肝硬化组		失代偿期肝硬化组		χ ²值	P值
纤维化指标		例数	指标值	例数	指标值	例数	指标值	χ ²值	P值
LSM（kPa）		?	?	?	?	?	?	?	?
?	治疗前	42	6.00（4.55，8.33）	10	13.00（11.58，14.18）	16	22.75（14.92，29.48）	45.861	< 0.001
?	SVR后	42	3.80（3.10，5.00）	10	8.10（6.80，10.83）	16	14.20（10.15，19.43）	44.582	< 0.001
?	变化值	42	－2.40（－3.85，－0.83）	10	－5.05（－5.33，－3.75）	16	－7.25（－12.40，4.50）	26.539	< 0.001
APRI		?	?	?	?	?	?	?	?
?	治疗前	77	0.43（0.32，0.65）	13	1.25（0.77，2.86）	21	2.66（1.23，3.36）	43.429	< 0.001
?	SVR后	77	0.25（0.18，0.31）	13	0.39（0.26，0.99）	21	0.56（0.35，0.86）	34.087	< 0.001
?	变化值	77	－0.19（－0.36，－0.12）	13	－1.08（－2.10，－0.41）	21	－2.20（－2.69，－0.59）	36.939	< 0.001
Fib-4		?	?	?	?	?	?	?	?
?	治疗前	77	1.19（0.66，2.19）	13	3.81（2.78，5.22）	21	6.50（4.44，8.08）	50.046	< 0.001
?	SVR后	77	1.07（0.57，1.77）	13	2.58（1.17，3.62）	21	2.80（1.90，4.28）	35.283	< 0.001
?	变化值	77	－0.21（－0.58，0.10）	13	－1.16（－1.74，－0.68）	21	－3.87（－5.11，－1.78）	39.566	< 0.001

纤维化指标		慢性肝炎组		代偿期肝硬化组		失代偿期肝硬化组		χ ²值	P值
纤维化指标		例数	指标值	例数	指标值	例数	指标值	χ ²值	P值
LSM（kPa）		?	?	?	?	?	?	?	?
?	治疗前	42	6.00（4.55，8.33）	10	13.00（11.58，14.18）	16	22.75（14.92，29.48）	45.861	< 0.001
?	SVR后	42	3.80（3.10，5.00）	10	8.10（6.80，10.83）	16	14.20（10.15，19.43）	44.582	< 0.001
?	变化值	42	－2.40（－3.85，－0.83）	10	－5.05（－5.33，－3.75）	16	－7.25（－12.40，4.50）	26.539	< 0.001
APRI		?	?	?	?	?	?	?	?
?	治疗前	77	0.43（0.32，0.65）	13	1.25（0.77，2.86）	21	2.66（1.23，3.36）	43.429	< 0.001
?	SVR后	77	0.25（0.18，0.31）	13	0.39（0.26，0.99）	21	0.56（0.35，0.86）	34.087	< 0.001
?	变化值	77	－0.19（－0.36，－0.12）	13	－1.08（－2.10，－0.41）	21	－2.20（－2.69，－0.59）	36.939	< 0.001
Fib-4		?	?	?	?	?	?	?	?
?	治疗前	77	1.19（0.66，2.19）	13	3.81（2.78，5.22）	21	6.50（4.44，8.08）	50.046	< 0.001
?	SVR后	77	1.07（0.57，1.77）	13	2.58（1.17，3.62）	21	2.80（1.90，4.28）	35.283	< 0.001
?	变化值	77	－0.21（－0.58，0.10）	13	－1.16（－1.74，－0.68）	21	－3.87（－5.11，－1.78）	39.566	< 0.001

指标	单因素分析（68例）		多因素分析（68例）
指标	OR值（95%CI）	P值	OR值（95%CI）	P值
性别	0.438（0.158～1.209）	0.111	—	—
基因型	1.683（0.165～17.126）	0.660	—	—
BMI（kg/m²）	1.065（0.890～1.274）	0.493	—	—
WBC（× 10⁹/L）	1.407（1.00～1.980）	0.050	2.508（1.161～5.421）	0.019
PLT（× 10⁹/L）	1.003（0.997～1.010）	0.289	—	—
ALT（U/L）	0.979（0.961～0.998）	0.032	0.918（0.844～0.998）	0.045
AST（U/L）	0.973（0.950～0.996）	0.020	0.862（0.767～0.969）	0.013
TBil（μmol/L）	0.990（0.955～1.027）	0.598	—	—
APRI	0.577（0.340～0.980）	0.040	0.001（0.000～0.555）	0.032
Fib-4	0.889（0.745～1.062）	0.195	—	—

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