Clinical trial NCT02865369: Regression of Liver Fibrosis After Daclatasvir and Asunaprevir Treatment
Official title: Regression of Liver Fibrosis Assessed by Transient Elastography After Daclatasvir and Asunaprevir Combined Treatment in Advanced Fibrotic/Cirrhotic Patients With Chronic Hepatitis C Genotype 1b Infection
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis C
Keywords: chronic hepatitis C
Daclatasvir
Asunaprevir
fibrosis
transient elastography
Lead sponsor: Soonchunhyang University Hospital
Sponsor class: OTHER
Collaborators: name: Seoul National University Boramae Hospital
name: Severance Hospital
name: Inha University Hospital
name: Korea University
name: Gachon University Gil Medical Center
name: Hanyang University Seoul Hospital
name: Ewha Womans University Mokdong Hospital
name: Bristol-Myers Squibb
First posted: 2016-08-12
Enrollment: 103
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Genotype 1b, advanced fibrotic/cirrhotic Korean patients with chronic hepatitis C aged over 18, without baseline NS5A RAVs (Y93 and/or L31)

Brief summary: A study on regression of liver fibrosis assessed by transient elastography after Daclatasvir and Asunaprevir combined treatment in advanced fibrotic/cirrhotic patients with chronic hepatitis C genotype 1b Infection

Detailed description: The measurement of liver stiffness by transient elastography (TE) has been shown to correlate with the hepatic fibrosis stage and to have considerable accuracy for the diagnosis of cirrhosis in patients with chronic hepatitis C. Previous studied reported that liver stiffness is significantly reduced in SVR patients with pegylated interferon (IFN) and ribavirin treatment. Once a patient achieve sustained virological response (SVR), and resultingly lower liver stiffness score than baseline value, it is believed that he will have a better long-term outcome due to the improvement of liver fibrosis.

Daclatasvir(DCV) and Asunaprevir(ASV) combined treatment showed a greater SVR rate in CHC compared to IFN based therapy. The investigators hypothesize that DCV and ASV combined treatment may achieve the improvement of liver stiffness measured by TE and a more favorable clinical outcomes in patients with advanced liver fibrosis. The investigators will also compare the change of fibrosis stage assessed by TE between this study subjects and those treated with other DAA agents during same observational period.

Eligibility criteria: Inclusion Criteria:

* Chronically infected with Hepatitis C virus genotype 1b
* HCV RNA ≥ 10\^4 IU/mL (10,000 IU/mL)
* Chronic Hepatitis C with advanced fibrosis or cirrhosis (defined as ≥F3, ≥8 kilopascals)
* Treatment-naïve or those who previously failed to treatment with peg-interferon alfa and ribavirin
* Women of childbearing potential (WOCBP) and men, who use effective methods of birth control

Exclusion Criteria:

* Patients with baseline key NS5A RAVs (Y93 and/or L31)
* Estimated GFR \< 30mL/min without hemodialysis
* Alanine aminotransferase (ALT) \> 100 IU/L
* Coinfection with other hepatitis virus or human immunodeficiency virus
* A daily alcohol intake \>30 g
* Decompensated liver disease or hepatocellular carcinoma, liver or any other organ transplantation

Primary outcomes:
measure: The change of liver fibrosis stage at 48 weeks assessed by transient elastography in patients treated with Daclatasvir and Asunaprevir
timeFrame: baseline to 48weeks
Secondary outcomes:
measure: Proportion of patients who were treated with Daclatasvir and Asunaprevir achieved SVR12 assessed by HCV RNA
timeFrame: baseline to 36 weeks
measure: Proportion of patients who maintained sustained virologic response at SVR24, SVR72, SVR120, SVR168, and SVR216.
timeFrame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: The change of liver fibrosis stage assessed by transient elastography at 96weeks, 144weeks, 192weeks, 240weeks in patients treated with Daclatasvir and Asunaprevir
timeFrame: baseline to 96weeks, 144weeks, 192weeks, 240weeks
measure: The change of AST to Platelet Ratio Index
timeFrame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: The change of Fibrosis 4 (Fib-4) index
timeFrame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: Comparison of change of liver fibrosis stage assessed by transient elastography between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment
timeFrame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: Comparison of the incidence of hepatocellular carcinoma or liver cirrhosis complications between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment
timeFrame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: The change of Fibrometer score
timeFrame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Other outcomes:
Locations:
city: Cheonan
country: Korea, Republic of
facility: Soonchunhyang University Cheonan Hospital
state: Chungcheongnam-do
city: Bucheon
country: Korea, Republic of
facility: Soon Chun Hyang University Bucheon Hospital
state: Gyeonggi do
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
city: Jung-gu
country: Korea, Republic of
facility: Inha University Hospital
state: Incheon
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance hospital
city: Seoul
country: Korea, Republic of
facility: Soonchunhyang University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang university hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Wonju
country: Korea, Republic of
facility: Wonju severance christian hospital
Study officials:
affiliation: Soonchunhyang University Hospital
name: Sang Gyune Kim, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Ledinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005 Jan;41(1):48-54. doi: 10.1002/hep.20506.
citation: Hezode C, Castera L, Roudot-Thoraval F, Bouvier-Alias M, Rosa I, Roulot D, Leroy V, Mallat A, Pawlotsky JM. Liver stiffness diminishes with antiviral response in chronic hepatitis C. Aliment Pharmacol Ther. 2011 Sep;34(6):656-63. doi: 10.1111/j.1365-2036.2011.04765.x. Epub 2011 Jul 13.
citation: Arima Y, Kawabe N, Hashimoto S, Harata M, Nitta Y, Murao M, Nakano T, Shimazaki H, Kobayashi K, Ichino N, Osakabe K, Nishikawa T, Okumura A, Ishikawa T, Yoshioka K. Reduction of liver stiffness by interferon treatment in the patients with chronic hepatitis C. Hepatol Res. 2010 Apr;40(4):383-92. doi: 10.1111/j.1872-034X.2009.00618.x. Epub 2010 Mar 4.
citation: Wang JH, Changchien CS, Hung CH, Tung WC, Kee KM, Chen CH, Hu TH, Lee CM, Lu SN. Liver stiffness decrease after effective antiviral therapy in patients with chronic hepatitis C: Longitudinal study using FibroScan. J Gastroenterol Hepatol. 2010 May;25(5):964-9. doi: 10.1111/j.1440-1746.2009.06194.x.
citation: Crisan D, Radu C, Grigorescu MD, Lupsor M, Feier D, Grigorescu M. Prospective non-invasive follow-up of liver fibrosis in patients with chronic hepatitis C. J Gastrointestin Liver Dis. 2012 Dec;21(4):375-82.
citation: Bourliere, Marc, et al.
citation: Yoo HW, Park JY, Kim SG, Jung YK, Lee SH, Kim MY, Jun DW, Jang JY, Lee JW, Kwon OS. Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents. Sci Rep. 2022 Jan 7;12(1):193. doi: 10.1038/s41598-021-03272-1.