Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin Versus Pegylated Interferon Alfa-2a Alone for Treatment-naïve Hemodialysis Patients With Chronic Hepatitis C
Brief Summary: Chronic hepatitis C virus (HCV) infection is common in dialysis patients. Interferon (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in immunocompetent patients. In dialysis patients, treatment with conventional or pegylated interferon has also received much attention recently. Two meta-analyses evaluating the efficacy and safety of conventional IFN alfa monotherapy showed that the sustained virologic response (SVR) rates were 37% and 33%, respectively; and the corresponding dropout rates were 17% and 29.6%, respectively.The efficacy and safety of pegylated IFN alfa-2a and 2b in treating dialysis patients showed conflicting results, with a more favorable outcome of patients treated with pegylated IFN alfa-2a (135-180 μg/week: SVR 33-75%, well tolerated) than those treated with pegylated IFN alfa-2b (0.5-1.0 μg/week: SVR 12.5%, poorly tolerated. Currently, IFN-based therapy to treatment HCV infection should be initiated in dialysis stages, because the use of IFN in RT patients harbors high risks of acute graft rejection,and have low response rates under the concomitant use of immunosuppressive agents.

Ribavirin, which has been used in combination with IFN to treat chronic hepatitis C in the general patients and achieve a higher SVR rate than IFN monotherapy, is considered contraindicated in dialysis patients with chronic hepatitis C due to the risk of severe hemolytic anemia. However, some pilot studies evaluating combined conventional IFN alfa plus low dose ribavirin (170-300 mg/day) showed SVR rates of 17%-66% after 24-48 weeks of treatment. In addition, a recent study including 6 patients with combination of pegylated IFN alfa plus low dose ribavirin also showed a SVR rate of 50%. In this study, treatment with pegylated IFN alfa-2a plus low dose ribavirin achieved a higher SVR rate that that with pegylated IFN alfa-2b plus low dose ribavirin (100% vs. 25%).

Based on the long-term favorable outcome in dialysis patients who eradicate HCV, and the superior response of pegylated IFN alfa-2a plus low dose ribavirin to pegylated IFN alfa-2b plus low dose ribavirin in treating dialysis patients with chronic hepatitis C, the aim of the study is to evaluate the efficacy and safety of pegylated IFN alfa-2a plus low dose ribavirin versus pegylated interferon alfa-2a alone in treatment naïve dialysis patients with chronic hepatitis C.


Options:
A: Inclusion Criteria:

* Documented chronic (at least 6 months) HCV GT 1 infection (with no evidence of mixed genotypes or genotype that cannot be assigned a type)
* Evidence or no evidence of liver cirrhosis based on one of the following:
* Liver biopsy performed within 24 months of Day 1 (if participant is cirrhotic then there is no time restriction on biopsy)
* Fibroscan performed within 12 months of Day 1 of this study
* Fibrosure™ (Fibrotest™) plus aspartate aminotransferase to platelet Ratio Index \[APRI\] obtained during the screening period)
* Has HCV status that is one of the following:
* Treatment naïve
* Prior interferon or pegylated interferon with or without ribavarin failures (null responder, partial responder, or relapser)
* Intolerant to prior interferon or pegylated intereferon with or without ribavarin regimen
* Chronic kidney disease (defined as glomerular filtration rate \[eGFR\] \<=29) non-dialysis dependent or on hemodialysis for at least 3 months, including individuals awaiting kidney transplant and those with failed kidney transplants but no longer on immunosuppressant therapy)
* Female participant of reproductive potential must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception from at least 2 weeks prior to Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations

Exclusion Criteria:

* Evidence of decompensated liver disease
* On peritoneal dialysis for management of kidney disease
* Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
* History of malignancy \<=5 years prior to signing informed consent
* Clinical diagnosis of substance abuse
* Pregnant, breast-feeding, expecting to conceive or donate eggs, or donate sperm from Day 1 through 14 days after the last study dose, or longer if dictated by local regulations
* Organ transplant (including hematopoietic stem cell transplant) other than kidney, cornea, and hair
* Conditions requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
* Uncontrolled or poorly controlled hypertension
* Significant cardiovascular disorder (e.g. myocardial infarction or unstable angina) or cardiovascular procedure within 3 months prior to signing informed consent
* New or worsening signs or symptoms of congestive heart failure within 3 months of signing informed consent
* Severe active peripheral vascular disease
* Recent (within 3 months prior to signing informed consent) episode or recurrence of stroke, transient ischemic attack (TIA) or neurological disorder, including but not limited to seizures
* Evidence or history of chronic hepatitis not caused by HCV
B: Inclusion Criteria:

* HBV-positive patients

  * Chronic hepatitis B defined by a positive HBsAg ( surface antigen of the hepatitis B virus) for at least 6 months
  * Acute hepatitis B defined as a recent appearance (\<6 months) of detectable HBs Ag,
  * Chronic hepatitis B with serological remission HbsAg-negative , HB DNA-negative,
  * With or without association with acute or chronic hepatitis D.
* HCV-positive patients

  * Chronic hepatitis C defined by the positivity for anti-HCV antibodies for at least 6 months and positive HCV-RNA
  * Acute hepatitis C defined by the recent appearance of HCV RNA (less than 6 months) in patients with risk factors (with or without positive antibodies)
  * Patients with cured hepatitis C defined by long-term eradication, either spontaneous, a positive anti-HCV antibodies associated to a negative RNA at two collection - 6 months interval time; either treatment defined by negative viremia 3 month after end of treatment.

Exclusion Criteria:

* HIV co-infected patients are not eligible to the cohort.
* So-called vulnerable populations (minors, people under guardianship or protection, or a private individual under protection from making legal or administrative decisions)
* Treatment ongoing hepatitis C during or stopped since less than 3 months
* Patients end of life
* Woman whose pregnancy is known
C: Inclusion Criteria:

* Age 18-65 years old
* Creatinine clearance (Ccr) \< 15 ml/min/1.73 m2
* Anti-HCV (Abbott HCV EIA 3.0, Abbott Diagnostic, Chicago, IL) positive \> 6 months
* Detectable serum quantitative HCV-RNA (Cobas Taqman HCV test, version 2, Roche Diagnostics) with a dynamic range of 25-391000000 IU/ml

Exclusion Criteria:

* Receiving interferon-based therapy for chronic hepatitis C
* Severe anemia (hemoglobin \< 10 g/dL) or hemoglobinopathy
* Neutropenia (neutrophil count, \<1,500/mm3)
* Thrombocytopenia (platelet \<90,000/ mm3)
* Co-infection with HBV or HIV
* Chronic alcohol abuse (daily consumption \> 20 g/day)
* Autoimmune liver disease
* Decompensated liver disease (Child classification B or C)
* Neoplastic disease
* An organ transplant
* Immunosuppressive therapy
* Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
* Evidence of drug abuse
* Unwilling to have contraception
D: Inclusion Criteria:

* Chronic hepatitis C virus (HCV) infection
* Screening laboratory results indicating HCV genotype 1 - 6 (GT1 - 6) infection.
* Subject must be HCV treatment-naïve or have failed previous HCV treatment.
* Subjects with underlying chronic renal impairment (estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 as estimated by the MDRD method at screening, including those requiring dialysis).
* Non-cirrhotic subjects must have documented absence of cirrhosis and subjects with cirrhosis must have documented compensated cirrhosis.

Exclusion Criteria:

* History of severe, life-threatening or other significant sensitivity to any excipients of the study drug.
* Female who is pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner is pregnant or planning to become pregnant during the study.
* Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator.
* Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab).
* HCV genotype performed during screening indicating co-infection with more than 1 HCV genotype; HCV GT3 infected, treatment-experienced subjects were excluded.
* Patients who failed a previous regimen containing protease inhibitor (PIs) and/or nonstructural protein 5A (NS5A) inhibitors.

Answer: C