Efficacy and safety of the 12-week sofosbuvir-coblopasvir regimen in treatment of chronic hepatitis C

Wei ZHANG; Song ZHAI; Hong DU; Fuchun JING; Limei WANG; Ye ZHANG; Bibo KANG; Jiuping WANG; Shuangsuo DANG; Jianqi LIAN; Hong JIANG

doi:10.3969/j.issn.1001-5256.2023.03.009

Volume 39 Issue 3

Mar. 2023

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Efficacy and safety of the 12-week sofosbuvir-coblopasvir regimen in treatment of chronic hepatitis C

DOI: 10.3969/j.issn.1001-5256.2023.03.009

1.
Department of Infectious Diseases, The First Affiliated Hospital of Air Force Medical University, Xi'an 710032, China
2.
Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
3.
Department of Infectious Diseases, Baoji People's Hospital, Baoji, Shaanxi 721006, China
4.
Department of Infectious Diseases, The Second Affiliated Hospital of Air Force Medical University, Xi'an 710038, China
5.
Department of Microbiology and Pathogenic Biology, School of Basic Medical Sciences, Air Force Medical University, Xi'an 710032, China

Research funding:

National Natural Science Foundation of China (81671555)

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Corresponding author: JIANG Hong, jiangh518@126.com (ORCID: 0000-0003-2075-3272)
Received Date: 2022-08-27
Accepted Date: 2022-10-08
Published Date: 2023-03-20

Abstract

Abstract

Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of treatment, and the secondary endpoint was the effect of the 12-week treatment on liver biochemical parameters. The non-normally distributed continuous data were expressed as M(P₂₅-P₇₅), and the Mann-Whitney U test was used for comparison between groups. Results A total of 101 patients were included in the analysis, among whom there were 55 male patients (54.5%) and 46 female patients, and the median age was 53 years. Among these patients, 12.8% had liver cirrhosis, 1.0% had liver cancer, 3.0% were treatment-experienced patients, and 3.0% had type 2 diabetes. As for genotype distribution, 8% had CHC genotype 1, 60% had CHC genotype 2, 19% had CHC genotype 3, and 6% had CHC genotype 6, and genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 rate of 100%, with a significant reduction in the serum level of alanine aminotransferase (ALT) from baseline to week 12 of treatment (P < 0.05). Among these patients, 22.7% had concomitant medications such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.
- Hepatitis C, Chronic,
- Coblopasvir,
- Sofosbuvir,
- Treatment Outcome

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对乙酰氨基酚(APAP)过量仍然是急性肝功能衰竭的常见原因，在患者中通常伴随着血清胆汁酸(BA)水平的升高。然而，BA的病理生理作用仍不清楚。来自德国多特蒙德工业大学的Ghallab等研究了BA在APAP诱导的肝毒性中的作用。

研究者进行了活体显像，研究了BA在小鼠体内的转运，定量了APAP过量的小鼠和患者血清中内源性BA的浓度，并用MS和MALDI-MSI分析了肝组织和胆汁的BA浓度。通过紧密连接蛋白的免疫染色和荧光标记物的活体成像，评估血胆汁屏障的完整性和氧化应激的作用，确定BA的细胞毒性浓度，并进行干预以阻止BA从血液中摄取到肝细胞。在细胞死亡开始之前，APAP过量会在中心小叶周围区域引起大量的氧化应激，这与血胆汁屏障的破坏是一致的。结果，BA从胆小管渗漏到肝窦血液中，随后BA通过基底膜被肝细胞摄取，分泌到胆小管并重复循环。这就是所谓的BA的“无效循环”，导致细胞内BA浓度升高，高到足以导致肝细胞死亡。然而，重要的是，使用Myrcludex B和Oatp基因敲除的药物NTCP阻断BA的再摄取大大降低了APAP诱导的肝毒性。

综上所述，APAP过量会导致血胆汁屏障的破坏，引起无效的BA循环，从而导致肝细胞死亡。预防BA循环可能是APAP中毒后的一种治疗选择。

摘译自GHALLAB A, HASSAN R, HOFMANN U, et al. Interruption of bile acid uptake by hepatocytes after acetaminophen overdose ameliorates hepatotoxicity[J]. J Hepatol, 2022. DOI: 10.1016/j.jhep.2022.01.020. [Online ahead of print]

(吉林大学第一医院感染病与病原生物学中心肝胆胰内科刘雅丽高沿航报道)

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