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:

1. To access liver fibrosis progression/regression in CHC patients after sofosbuvir-based treatment.
2. To investigate the long-term outcomes of extrahepatic manifestations of the sofosbuvir-based treated cohort as compared to their pretreatment status.

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:

1. To evaluate hepatic fibrosis progression or regression in CHC patients after sofosbuvir-based therapy.
2. To evaluate the durability of sustained viral response (SVR) in patients achieving SVR after sofosbuvir-based therapy.
3. 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.
4. 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:

1. Main hepatic complications as liver fibrosis, hepatic malignancy, liver decompensation with ascites, hepatic encephalopathy and variceal bleeding, and liver-related mortality.
2. Life quality, extrahepatic symptoms as cryoglobulinemia, diabetes mellitus, insulin resistance, lipid profiles, renal insufficiency and other non-liver morbidities and malignancy.

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

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, Written informed consent will be obtained after full explanation to the patients who had ever participated in parent studies, GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643) and had received at least one dose of sofosbuvir-based therapy in the parent studies.