Patient description: A 53-year-old man presents with chronic HCV infection for the past 2 years. His past medical history is only significant for inguinal hernia surgery when he was 20 years old. He is on IFN (100 mg/week) plus RBV (400 mg/day) combination therapy for the past 9 months. Direct antiviral drugs were added to his treatment 6 months ago. His medical record shows previous positive HCV RNA tests as well as positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Cirrhosis Chronic Hepatitis C Hepatitis C Hepatitis C, Chronic FOR BOTH 1a and 1b: 1. Adults, ages 18 and above 2. Chronic hepatitis C (HCV RNA in serum for more than 6 months) 3. HCV Genotype 1 4. HCV RNA in serum above 10,000 IU/mL 5. Non-response to previous therapy with peginterferon and ribavirin categorized as null-response as defined by a less than 1 log IU/mL decline in HCV RNA at treatment week 4 or a less than 2 log IU/mL decline in HCV RNA at treatment week 12; and partial response as defined by a greater than or equal to 2 log decrease in HCV RNA at treatment week 12 but continued detection of HCV RNA at treatment week 24 6. No contraindications to agents being used (asunaprevir, daclatasvir, peginterferon and ribavirin). 7. No evidence or history of hepatic decompensation. 8. Females of childbearing potential must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study drug. 9. Women of childbearing potential (WOCBP) and men must use highly effective methods of birth control to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 24 weeks after the last dose of P/R. Birth control requirements are or WOCBP and men who are sexually active with WOCBP 10. Women must not be breastfeeding 11. Fully informed, written consent to the study including repeat liver biopsy. FOR 1a 1) Liver biopsy showing Ishak stages 0-2 or 5-6 within 12 weeks of initiating therapy OR a prior biopsy performed within 96 weeks of screening visit WITH saved tissue. Up to 10 subjects who do not fulfill the entry histologic will be allowed to participate in the trial at the discretion of the investigator. FOR 1b 1. Baseline sequence analysis of the NS5A region to presence of mutations known to confer resistance to daclatasvir. FOR GT 1b WHO AT THE OF THE (THESE MUST BE PRIOR TO PEG INFa/RBV Important: In addition to the listed above, the following apply to all Rescue Subjects: a) Subject met a definition of virologic breakthrough or treatment futility, defined as: i) Any confirmed > 1 log10 increase in HCV RNA from nadir, OR; ii) Any confirmed HCV RNA greater than or equal to Lower Limit of quantification (LLOQ) after confirmed HCV RNA <LLOQ Target Not Detected while on treatment, OR; iii) Any confirmed HCV RNA greater than or equal to LLOQ at Week 8. Measurements should be confirmed within 2 weeks of the Week 8 result; b) HCV RNA < 400,000 IU/mL at the last assessment; This cut-off was chosen because it is felt that peginterferon and ribavirin would be ineffective at higher viral loads in prior non-responders to peginterferon and ribavirin with viral breakthrough. c) Women of childbearing potential (WOCBP)1 and men must use highly effective methods of birth control to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 24 weeks after the last dose of P/R. Birth control requirements are or WOCBP (see Section C.5 for the definition of WOCBP) and men who are sexually active with WOCBP; i) Two (2) forms of birth control are required from time of screening throughout the duration of the on-treatment study period and for at least 24 weeks after the last dose of RBV (or the duration specified by the country-specific RBV label, whichever is longer), in such a manner that the risk of pregnancy is minimized. Examples of highly effective birth control -condom with spermicide; -diaphragm and spermacide; -cervical cap and spermacide female condom intrauterine devices (IUDs); Oral contraceptive pills (OCPs) may be used in this study but cannot be considered as an effective form of contraception for WOCBP subjects. ii) Exceptions 1. WOCBP who are not heterosexually active or who have male partners who have been vasectomized for a minimum of 6 months with a history of confirmed azoospermia; 2. Sexually active men who are vasectomized for a minimum of 6 months with a history of confirmed azoospermia. d) WOCBP must have a negative serum or urine pregnancy test [minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)] within 24 hours prior to the start of P/R. Female subjects must agree to the pregnancy testing requirements of this protocol; e) Women must not be breastfeeding; f) Male Subjects: Requirements (based on RBV label): i) Male subjects (unless vasectomized for at least 6 months with a history of confirmed azoospermia) with female partners who are WOCBP must agree to inform their female partners of the protocol-specified effective birth control methods requirement and pregnancy testing recommendations during treatment and post-treatment (i.e., two forms of effective methods of birth control and monthly pregnancy testing while the subject is enrolled in the study and 6 months following discontinuation of RBV [or for the post-treatment duration specified in the country-specific RBV label]), and agree to adhere to these recommendations both on-treatment and during the post-treatment follow-up period; ii) Male subjects must confirm that their female sexual partners are not pregnant at the time of screening  for Genotypes 1b: 1. Medical History and Concurrent Diseases 1. Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair; 2. Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment 3. Documented or suspected HCC, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed) 4. Evidence of decompensated liver disease including, but not limited to, radiologic a history or presence of ascites, bleeding varices, or hepatic encephalopathy 5. Evidence of a medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) 6. History of chronic hepatitis B virus (HBV) as documented by HBV serologies (eg, HBsAg-seropositive). Subjects with resolved HBV infection may participate (eg, HBsAb-seropositive with concurrent HBsAg-seronegative) 7. Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug. (Subjects who have had cholecystectomy are permitted to enter the study) 8. History of HIV infection 9. Hemophilia 10. Uncontrolled diabetes (any subject with a confirmed screening HgA1c greater than or equal to 8.5 must be excluded) 11. Confirmed, uncontrolled hypertension (any screening systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 100 mmHg should be excluded unless discussed with the central medical monitor) 12. Any other medical and/or social reason, including active substance abuse as defined by DSM-IV, Diagnostic for Drug and Alcohol Abuse, which in the opinion of the investigator would make the candidate inappropriate for participation in this study 13. History of severe psychiatric disorders including but not limited to, schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder, mania, etc. 14. Inability to tolerate oral medication; 15. Poor venous access 2. Physical and Laboratory Test Findings Note: Growth factors must not be used to achieve criteria. 1. ALT greater than or equal to 10 times ULN 2. Total bilirubin greater than or equal to 34 micromoles per liter (greater than or equal to 2 mg/dL) unless the subject has documented history of Gilbert s disease 3. Albumin < 3.5 g/dL (35 g/L) 4. Creatinine clearance (CrCl) less than or equal to 50 ml/min (as estimated by Cockcroft and Gault) 5. Platelets < 50 times 10(9) cells/L 6. ANC < 0.5 times 10(9) cells/L 7. Hemoglobin < 8.5 g/dL 8. INR greater than or equal to 1.7 9. Alpha-fetoprotein (AFP): i) AFP > 100 ng/mL OR ii) AFP greater than or equal to 50 ng/mL and less than or equal 100 ng/mL requires a liver ultrasound and subjects with findings suspicious for HCC are excluded j) QTcF or QTcB > 500 msec 3. Allergies and Adverse Drug Reaction a) History of hypersensitivity to drugs with a similar biochemical structure to asunaprevir or daclatasvir. 4. Prohibited Treatments and /or Therapies 1. Exposure to any investigational drug or placebo within 4 weeks of study drug administration; 2. Prior exposure to any HCV DAA; 3. Prior exposure to pegIFN or RBV within 12 weeks prior to screening; 4. Subjects receiving all tricyclic anti-depressants (TCAs) including amitriptyline, clomipramine, desiprmine, dosepin, imipramine, nortriptyline, protriptyline; OR selective serotonin reuptake inhibitors (SSRIs) including fluoxetine, fluvoxamine, paroxetine and sertraline; OR additional agents including venlafaxine, duloxetine, aripiprazole and mirtazapine within 2 weeks prior to Day 1; (subjects may switch to non-prohibited antidepressant therapies (eg citalopram, escitalopram and bupropion) within 2 weeks prior to Day 1). The study of subjects on any anti-depressant not listed above, may be considered after a consultation with the central medical monitor, prior to Day 1; 5. Sex and Reproductive Status 1. Sexually active men whose partners are pregnant at screening are excluded from this study 6. OTHER a) Prisoners or subjects who are involuntarily incarcerated b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness C.5 for Gt 1a subjects and 1b subjects who receive rescue therapy at discretion of the investigator (Prior to initiation of PegIFN /ribavirin therapy): Important: In addition to the listed above WITH THE OF THE TESTS IN C.4.2 A-H, the following apply to all Gt 1a and rescue subjects: a) Severe psychiatric disease that would prohibit use of peg-IFN -2a as judged by the investigator including but not limited to: i) Moderate or severe depression; Beck Depression Score greater than or equal to 15 during screening ii) History of depression associated with hospitalized for depression, electroconvulsive therapy, or depression resulting in a prolonged absence from work and/or significant disruptions from daily functions; iii) Suicidal or homicidal ideation and/or attempt; iv) History of severe psychiatric disorders including but not limited to, schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder, mania, etc.; b) History of hemoglobinopathies (e.g., thalassemia major or sickle cell anemia), diagnoses associated with an increased baseline risk for anemia (e.g., spherocytosis), hemolytic anemia, or diseases in which anemia would be medically problematic, or hemophilia; c) Pre-existing ophthalmologic disorders considered clinically significant on eye exam, including retinal, examination. Note: all subjects with a history of diabetes or hypertension must have a documented eye exam within 12 months prior to initiation of P/R; d) Thyroid-stimulating hormone (TSH) < 0.8 times LLN or > 1.2 times ULN of the laboratory reference range, unless i) The subject is clinically euthyroid as determined by the investigator, AND ii) Free T4 is greater than or equal to 0.8 times LLN and less than or equal to 1.2 times ULN e) History of chronic pulmonary disease associated with functional limitation such as clinically significant chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidois, etc; f) History of cardiomyopathy, coronary artery disease (including angina), interventional procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery), ventricular arrhythmia, congestive heart failure, pulmonary hypertension, cardiomyopathy, or other clinically significant cardiac disease; g) Historical or current ECG findings indicative of cardiovascular instability, including but not limited to evidence of significant myocardial ischemia, unstable re-entry phenomena, other significant dysarrhythmias and/or uncontrolled hypertension; h) Immunologically-mediated disease (eg, inflammatory bowel disease [Crohn s disease, ulcerative colitis], celiac disease, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, sarcoidosis, severe psoriasis requiring oral or injected treatment, or symptomatic thyroid disorder). i) Any known contraindication to peg-IFN -2a or ribavirin, not otherwise specified. j) Alanine aminotransferase (ALT) greater than 10 times ULN; k) Total Bilirubin greater than or equal to 34 mol/L (greater than or equal to 2 mg/dL), unless subject has a documented history of Gilbert s disease; l) INR greater than or equal to 1.7; m) Albumin < 3.5 g/dL (35 g/L); n) Platelets < 70 times 10(9) cells/L; o) ANC < 1,500 cells/mm3 (confirmed ANC < 1,200 cells/mm3 for Black/African-Americans); p) Hemoglobin < 12 g/dL (120 g/L) for women and < 13 g/dL (130 g/L) for men; q) Creatinine Clearance (CrCl) less than or equal to 50 mL/min (as estimated by Cockcroft and Gault); r) History of hypersensitivity to drugs with similar biochemical structure to pegIFN alpha or ribavirin s) QTcF or QTcB > 500 msec