Long-term Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Treatment

Study Overview
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Brief Summary
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Primary Objective: To evaluate the long-term outcomes including liver related morbidity, mortality and hepatocellular carcinoma (HCC) development as compared to those of historical control with interferon(IFN)-based treatment. Secondary Objective: To access liver fibrosis progression/regression in CHC patients after sofosbuvir-based treatment. To investigate the long-term outcomes of extrahepatic manifestations of the sofosbuvir-based treated cohort as compared to their pretreatment status.

Detailed Description
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Primary Endpoint: To evaluate the long-term event-free effect after sofosbuvir-based therapy, in terms of free of major liver events (including HCC, decompensation with ascites, variceal bleeding, hepatic encephalopathy, and liver-related mortality) in CHC patients. Secondary Endpoints: To evaluate hepatic fibrosis progression or regression in CHC patients after sofosbuvir-based therapy. To evaluate the durability of sustained viral response (SVR) in patients achieving SVR after sofosbuvir-based therapy. To evaluate long-term effect of sofosbuvir-based therapy on the extra-hepatic manifestations of the cohort. The items include mixed cryoglobulinemia, chronic kidney diseases, insulin resistance, diabetic status, cardiovascular events and dyslipidemia. To evaluate long-term effect of sofosbuvir-based therapy on quality of life on the cohort. Study Design Prospective, longitudinal observational study Study procedure A total of 200 patients receiving sofosbuvir based direct antiviral agents (DAAs) in the parent studies will be included for following up to 5 years. Their serological, image study and disease status description will be prospectively documented to present the long term effects of sofosbuvir-based therapy. The presentation of illness will be specified as: Main hepatic complications as liver fibrosis, hepatic malignancy, liver decompensation with ascites, hepatic encephalopathy and variceal bleeding, and liver-related mortality. Life quality, extrahepatic symptoms as cryoglobulinemia, diabetes mellitus, insulin resistance, lipid profiles, renal insufficiency and other non-liver morbidities and malignancy.

Official Title
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Long-term Hepatic and Extra-hepatic Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Interferon-free Treatment (LONGHEAD Study)

Conditions
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Liver Fibroses, HepatoCellular Carcinoma, Cryoglobulinemia, Metabolic Disease, Diabetes Mellitus

Intervention / Treatment
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* Other: Observation only


Participation Criteria
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Eligibility Criteria
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Main inclusion criteria: For Sofosbuvir-based therapy observational group: Patients ≥ 20 of years who had ever participated in parent studies, GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643) Patients who had received at least one dose of sofosbuvir-based therapy in the parent studies. Who IFN-based therapy historical controls, matched with sex, age, level of liver fibrosis and virological response: Patients ≥ 20 of years who had received pegylated interferon plus ribavirin therapy with match of sex, age, level of liver fibrosis and virological response Patients who have ever participated study will be collected as historical control. Main exclusion criteria: Patients not qualified by the main inclusion criteria were excluded. For Sofosbuvir-based therapy observational group: Patients < 20 of years Patients who are unwilling to participate the current study Patients who had never participated in parent studies, GS-US-337-0131 (NCT02021656) nor GS-US-334-0115 (NCT02021643) Patients who had never received at least one dose of sofosbuvir-based therapy in the parent studies. Who IFN-based therapy historical controls: Patients < 20 of years Patients who are unwilling to participate the current study Patients who had never received pegylated interferon plus ribavirin therapy Patients who did not participate study

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| IFN-based therapy historical controls<br>Patients who had ever participated the parent studies, GS-US-334-0115 or GS-US-337-0131, will be invited to participate the current study in outpatient clinic. For the patients who have participated study will be invited to participate the current study as matched historical control n our outpatient clinic, | Other: Observation only<br> <br> |
| Sofosbuvir-based therapy observational group<br>Patients ≥ 20 of years who had ever participated in parent studies, GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643) Patients who had received at least one dose of sofosbuvir-based therapy in the parent studies. Who IFN-based therapy historical controls, matched with sex, age, level of liver fibrosis and virological response: Patients ≥ 20 of years who had received peginterferon plus ribavirin therapy with match of sex, age, level of liver fibrosis and virological response Patients who have ever participated study will be collected as historical control. | Other: Observation only<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with liver-related morbidity development during 5-year follow-up period after sofosbuvir-based treatment | Number of participants with liver-related morbidity during 5-year follow-up period after sofosbuvir-based treatment, including liver fibrosis progression and decompensation | 6 years | 
| Number of participants with liver-related mortality development during 5-year follow-up period after sofosbuvir-based treatment | Number of participants with liver-related mortality assessed by death due to HCC and/or liver decompensation | 6 years | 
| Number of participants with hepatocellular carcinoma (HCC) development during 5-year follow-up period after sofosbuvir-based treatment | Number of participants with HCC assessed by histocytology or positive dynamic image plus alpha fetoprotein (AFP) > 400 ng/ml | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Life quality | The change of short form(SF)-36 from baseline | 6 years | 
| Cryoglobulinemia | Change of proportion of participants with cryoglobulinemia from baseline cryoglobulinemia from baseline) | 6 years | 
| Diabetes mellitus (DM) | Number of participants without DM develop DM assessed by Ac sugar > 126 g/ml | 6 years | 
| Insulin resistance | Change of homeostatic model assessment (HOMA-IR), assessed by Glucose x insulin/22.5 from baseline | 6 years | 
| Lipid profiles | Change of the serum profile of lipids including triglyceride(TG), cholesterol(Chol), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) from baseline | 6 years | 
| Renal disease | the change of the estimated glomerular filtration rate (eGFR) from baseline | 6 years |