Regression of Liver Fibrosis After Daclatasvir and Asunaprevir Treatment

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Daclatasvir and Asunaprevir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Daclatasvir plus Asunaprevir treatment<br>Among patients taking Daclatasvir and Asunaprevir combined treatment and having advanced liver fibrosis assessed by transient elastography | Drug: Daclatasvir and Asunaprevir<br>* Daclatasvir and Asunaprevir combined treatment will not be assigned to the enrolled patients, but the patients who are treated with Daclatasvir and Asunaprevir will be included in this observational study.<br>* Other names: Daclatasvir and Asunaprevir combined treatment for 24 weeks;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of liver fibrosis stage at 48 weeks assessed by transient elastography in patients treated with Daclatasvir and Asunaprevir | To compare the change of liver fibrosis stage (defined as F3, ≥8; F4, ≥12) assessed by transient elastography between baseline and 48 weeks in advanced fibrotic/cirrhotic Chronic Hepatitis C patients who achieved sustained virological response with Daclatasvir and Asunaprevir combined treatment | baseline to 48weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who were treated with Daclatasvir and Asunaprevir achieved SVR12 assessed by HCV RNA |  | baseline to 36 weeks | 
| Proportion of patients who maintained sustained virologic response at SVR24, SVR72, SVR120, SVR168, and SVR216. |  | baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| The change of liver fibrosis stage assessed by transient elastography at 96weeks, 144weeks, 192weeks, 240weeks in patients treated with Daclatasvir and Asunaprevir |  | baseline to 96weeks, 144weeks, 192weeks, 240weeks | 
| The change of AST to Platelet Ratio Index | APRI = [(AST/upper limit of normal)/platelet count]x100 | baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| The change of Fibrosis 4 (Fib-4) index | FIB-4 = age (years) × AST [IU/L] / [platelet count × sqr(ALT [IU/L])] | baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| Comparison of change of liver fibrosis stage assessed by transient elastography between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment | Comparison of change of liver fibrosis stage assessed by transient elastography at 48weeks, 96weeks, 144weeks, 192weeks, 240weeks between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment during same observational period | baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| Comparison of the incidence of hepatocellular carcinoma or liver cirrhosis complications between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment | Compare the incidence of hepatocellular carcinoma or liver cirrhosis complications at 48weeks, 96weeks, 144weeks, 192weeks, 240weeks between Daclatasvir and Asunaprevir combined treatment versus other Direct antiviral agents during same observational period | baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| The change of Fibrometer score | alpha2 macroglobulin, GGT, AST, ALT, prothrombin index, urea, platelet count | baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic hepatitis C, Daclatasvir, Asunaprevir, fibrosis, transient elastography