Cryoglobulinemia

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,

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.

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.

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.

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

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

Number of participants with liver-related morbidity during 5-year follow-up period after sofosbuvir-based treatment, including liver fibrosis progression and decompensation

Number of participants with liver-related mortality assessed by death due to HCC and/or liver decompensation

Number of participants with HCC assessed by histocytology or positive dynamic image plus alpha fetoprotein (AFP) > 400 ng/ml

The change of short form(SF)-36 from baseline

Change of proportion of participants with cryoglobulinemia from baseline cryoglobulinemia from baseline)

Number of participants without DM develop DM assessed by Ac sugar > 126 g/ml

Change of homeostatic model assessment (HOMA-IR), assessed by Glucose x insulin/22.5 from baseline

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

the change of the estimated glomerular filtration rate (eGFR) from baseline

patients with hepatitis c nephropathy detected by lab and renal biopsy

needle biopsy will be taken from the kidney tissue then, diagnosed

Hepatitis c associated glomerulonephritis is an immune complex disease that occurs in 21% of patients who have HCV infection.

Hepatitis C virus infection is a major public health problem with an estimated global prevalence of 3% and an estimated 5-20% of infected patients will develop liver cirrhosis .The Prevalence of Hepatitis C infection in end stage renal disease is greater than in the general population especially in those on hemodialysis which reflects nosocomial transmission of the disease in the hemodialysis environment.

Hepatitis C associated glomerulonephritis is an immune complex disease that occurs in 21% of patients who have HCV infection. It most commonly presents as membranoproliferative and mixed cryoglobulinemia It characterized by an indolent course in one third of patients , remission in another third and relapsing course in the remaining patients with potential progression to advanced chronic kidney disease.

mechanism of injury : Chronic Hepatitis C is primarily associated with type II cryoglobulinemia , in which the primary mechanism of injury is vasculitis that occurs via immune complex deposition.

hepatitis C virus related glomerular disease :

Type I membranoproliferative was the most common finding associated with mixed cryoglobulinemia but other forms of glomerulonephritis were associated with Hepatitis c like mesangial glomerulonephritis,focal and segmental glomerulonephritis,minimal change nephropathy,membranous nephropathy , Fibrillary glomerulonephritis,immunotactoid glomerulopathy,IgA nephropathy, vasculitic renal involvement ,poly arteritis nodosa and interstitial nephritis .

Pathology of Hepatitis c Nephropathy

Different Histopathological Patterns in Patients With HCV Nephropathy

prevalence of histopathological pattern in patients with hepatitis C virus

Active clinical trials for "Cryoglobulinemia"

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

Pathology of Hepatitis c Nephropathy

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