The Efficacy and Safety of Direct-acting Antiviral Treatment for Chronic Hepatitis C Patients: A Single Center Study

Seong Jun Park; Ah Ran Kim; Won Hyeok Choe; Jeong Han Kim; Byung Chul Yoo; So Young Kwon

doi:10.4166/kjg.2018.72.4.197

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Park, Kim, Choe, Kim, Yoo, and Kwon: The Efficacy and Safety of Direct-acting Antiviral Treatment for Chronic Hepatitis C Patients: A Single Center Study

Original Article

Korean J Gastroenterol 2018;72(4):197-204.

Published online: 4 October 2018

DOI: https://doi.org/10.4166/kjg.2018.72.4.197

The Efficacy and Safety of Direct-acting Antiviral Treatment for Chronic Hepatitis C Patients: A Single Center Study

Seong Jun Park, Ah Ran Kim, Won Hyeok Choe, Jeong Han Kim, Byung Chul Yoo, So Young Kwon

Division of Gastroenterology, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Korea

Correspondence to: So Young Kwon, Division of Gastroenterology, Department of Internal Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea. Tel: +82-2-2030-7508, Fax: +82-2-2030-5029, E-mail: sykwonmd@hotmail.com, ORCID: https://orcid.org/0000-0003-4290-1950

Received 14 July 2018 Revised 3 September 2018 Accepted 19 September 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Direct-acting antiviral (DAA) therapy has been shown to achieve a high rate of sustained virologic response (SVR) and favorable outcomes in chronic hepatitis C (CHC) patients. We investigated the virologic response and its clinical impact in CHC patients.

Methods

CHC patients with compensated liver function treated with DAAs between 2016 and 2017 were included for retrospective analysis. We analyzed baseline characteristics and virologic and biochemical responses at on-treatment 4 weeks, end of treatment, and posttreatment 12 weeks. Fibrosis was measured as liver stiffness measurement by transient elastography (FibroScan). Adverse events were monitored during the treatment period.

Results

A total of 135 patients (61.5% with genotype [GT] 1b and 38.5% with GT 2a) were enrolled 47.4% were male, 79.3% were treatment naive, and 30.4% had cirrhosis. SVR 12 was observed in 97.6% (81/83) in the GT 1b and 98.1% (51/52) in the GT 2a; treatment with daclatasvir+asunaprevir was the most commonly used in GT 1b (55/83), and sofosbuvir+ribavirin was the most commonly used in GT 2a (49/52). The median change of liver stiffness measurement at two time points using the signed rank test was −3.2 kPa in patients who underwent transient elastography before treatment and at SVR 12 (n=25). The most common adverse events were anemia, dyspepsia, and insomnia. One GT 2a patient treated with sofosbuvir+ribavirin stopped the treatment at 8 weeks due to symptomatic bradyarrhythmia; however, he recovered spontaneously and achieved SVR 12.

Conclusions

DAA treatment of chronic hepatitis C genotype 1b and 2a resulted in a high rate of sustained virologic response and improvement of liver fibrosis score.

Keywords: Hepatitis C, chronic, Antiviral agents, Sustained virologic response

References

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Fig. 1.

Virological response. (A) SVR 12 according to DAAs in each genotype. The result of DAA treatment for 1b and 2a showed high SVR 12 results without any significant difference in the treatment regimens. (B) SVR 12 according to the presence of cirrhosis in each genotype. SVR 12 rate showed similar results in both genotypes regardless of LC and non-LC. SVR, sustained virologic response; DCV, daclatasvir; ASV, asunaprevir; EBR, elbasvir; GZR, grazoprevir; OBV, ombitasvir; PTV, paritaprevir; r, ritonavir; DSV, dasabuvir; SOF, sofosbuvir; LDV, ledipasvir; RBV, ribavirin; GT, genotype; LC, liver cirrhosis; DAAs, direct-acting antivirals.

Fig. 2.

FIB-4 scores pre- and posttreatment with DAA in all patients (n=135). The median FIB-4 scores decreased from 4.15±3.72 at baseline to 2.84±2.78 at SVR 12 (p<0.001). FIB-4, fibrosis-4; Pre-Tx, pretreatment; SVR, sustained virologic response; DAA, direct-acting antiviral.

Fig. 3.

LSM score (n=25). Significant improvement in the LSM score was observed after successful DAA treatment. LSM, liver stiffness measurement; kPa, kilopascal; Pre-Tx, pretreatment; SVR, sustained virologic response; DAA, direct-acting antiviral.

Table 1.

Baseline Clinical Characteristics of Patients

	Genotype 1b	Genotype 2a
	(n=83)	(n=52)
Age (years)	57.8±13.4	60.2±9.5
Male	44 (53.0)	20 (38.5)
BMI (kg/m²)	24.3±3.3	22.8±2.8
HCV viral load (log₁₀ IU/mL)	6.6±6.7	6.4±6.7
Prior HCV treatment
Treatment naive	63 (75.9)	44 (84.6)
Non-response	14 (16.9)	5 (9.6)
Relapse/breakthrough	6 (7.2)	3 (5.8)
Cirrhosis	25 (30.1)	17 (32.7)
Median ALT (ULN: 44 IU/L)	70±71	66±49
Median FIB-4 score	3.89±3.53	4.58±4.02
Median GFR (mL/min)	70.6±19.4	74.4±13.6
RASs	11 (13.3) ^a	−
Treatment regimen
Daclatasvir+asunaprevir	55 (66.3)	0 (0.0)
Elbasvir+grazoprevir	8 (9.6)	0 (0.0)
OPr+dasabuvir	7 (8.4)	0 (0.0)
Sofosbuvir+ledipasvir	9 (10.9)	0 (0.0)
Sofosbuvir+daclatasvir	1 (1.2)	1 (1.9)
Sofosbuvir+ribavirin	0 (0.0)	49 (94.2)
Sofosbuvir+ledipasvir+ribavirin	3 (3.6)	2 (3.9)

Values are presented as mean±standard deviation or n (%).

BMI, body mass index; HCV, hepatitis C virus; ALT, alanine transaminase; UNL, upper normal limit; FIB-4, fibrosis-4; GFR, glomerular filtration rate; RASs, resistance associated substitutions; OPr, ombitasvir/paritaprevir/ ritonavir; DCV, daclatasvir; ASV, asunaprevir.

^a RASs were not detected in all 55 patients who used DCV+ASV as the treatment. Of the 28 patients who selected other drugs, 12 patients did not undergo RASs test and among 5 patients, the RASs test was negative.

Table 2.

Treatment Response according to Genotype

	Genotype 1b (n=83)	Genotype 2a (n=52)
HCV RNA <15 IU/mL, n/n (%)
On treatment
4 week	82/83 (98.8)	50/52 (96.2)
12 week ^a	28/28 (100)	52/52 (100)
24 week	55/55 (100)	−
Post treatment
12 week (SVR)	81/83 (97.6)	51/52 (98.1)
Virological failure
On treatment	0	0
Relapse	2 ^b	1 ^c

HCV, hepatitis C virus; RNA, ribonucleic acid; SVR, sustained virologic response; LC, liver cirrhosis; SOF, sofosbuvir; DCV, daclatasvir; ASV, asunaprevir; LDV, ledipasvir; RASs, resistance associated substitutions; RBV, ribavirin.

^a One patient was LC-compensated treated with SOF+DCV for 16 weeks with non-responsive to previous DCV+ASV treatment

^b One relapse patient was treated with DCV+ASV and the other was seen in patient receiving a SOF+LDV. Resistance associated substitutions (RASs) (L31, Y93) were not detected in both patients

^c One patient was treated with SOF+RBV. The patient was treatment naive without cirrhosis.

Table 3.

Adverse Events

	Genotype 1b (n=83)	Genotype 2a (n=52)
Pts. with adverse events	17 (20.5)	34 (65.4)
Discontinuation of DAAs	0	0
Dyspepsia	6 (7.2)	−
Insomnia	3 (3.6)	1 (1.9)
Fatigue	3 (3.6)	−
Other minority ^a	5 (6.0)	−
Anemia ^b	−	31 (59.6)
Symptomatic bradycardia ^c	−	1 (1.9)
Cough	−	1 (1.9)

Values are presented as n (%).

Pts, patients; DAAs, direct-acting antivirals; Hb, hemoglobin; SOF, sofosbuvir; RBV, ribavirin; SVR, sustained virologic response.

^a Nausea (1), headache (1), skin rash (1), xeroderma (1), edema (1)

^b Defined as Hb <10 g/dL or decreased Hb >2 g/dL from baseline. Fourteen patients required dose reduction and 2 of them received

^c One patient treated with SOF+RBV stopped blood transfusion; treatment at 8 weeks due to symptomatic bradyarrhythmia. However, the patient recovered spontaneously and was found to have achieved SVR 12 during follow up.

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ORCID iDs: So Young Kwon
https://orcid.org/0000-0003-4290-1950
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