Boceprevir-based Therapy to Rescue HCV Genotype 1/HBV Infected Patients Refractory to Combination Therapy
Boceprevir-based Therapy to Rescue HCV Genotype 1/HBV Infected Patients Refractory to Combination Therapy
The aim of this study is to explore the efficacy and safety of boceprevir -based triple
 therapy to rescue HCV genotype 1 (HCV GT1)/HBV dually infected patients refractory to
 previous peginterferon (PEG-IFN) plus ribavirin (RBV) combination therapy.
Liver disease, especially viral hepatitis, is an important public health issue, which
 frequent leads to liver cirrhosis, hepatocellular carcinoma (HCC) and liver-related death.
 Around 340 to 400 million persons are infected with hepatitis B virus (HBV) and 130 to 210
 million persons are infected with hepatitis C virus (HCV) worldwide, In Taiwan, the
 prevalence of HBV infection is 15-20%, and the prevalence of HCV infection is 2-5% in general
 population. Moreover, there are some HCV-hyperendemic areas in southern Taiwan with anti-HCV
 prevalence rate of as high as 30-40%.

 HBV/HCV dual infections is not uncommon in HBV epidemic areas, such as Southeastern Asia,
 with a prevalence rate of 1.1% in southern Taiwan. Recent study showed that the risk of HCC
 incidence is even higher among HBV/HCV co-infected persons than those with HBV or HCV
 mono-infection, indicating the importance of disease control in this clinical setting.

 The PEG-IFN/RBV has been effective in the treatment of HCV-dominant, treatment-naïve patients
 with HCV/HBV dual infections. For treatment-naive HCV genotype 1 (HCV GT1)/HBV co-infected
 patients, 48 weeks of peginterferon (PEG-IFN) plus ribavirin (RBV) could achieve an HCV
 sustained virological response (SVR) rate of 72%, which was comparable to 77% for patients
 with HCV GT1 monoinfection. For treatment-naive HCV GT2 or GT3 /HBV co-infected patients, 24
 weeks of PEG-IFN plus RBV could achieve an HCV SVR rate of 83%, which was comparable to 84%
 for patients with HCV GT2/3 monoinfection . Furthermore, PEG-IFN plus RBV combination therapy
 could enhance seroclearance of hepatitis B surface antigen (HBsAg) with an HBsAg loss rate of
 upto 11%. Nevertheless, there is about 30% of HCV GT1/HBV and 20% of HCV GT2 or 3/HBV
 co-infected patients refractory to current PEG-IFN/RBV combination therapy, which remains at
 high risk of HCC and liver-related death.

 Boceprevir is an oral antiviral drug, which is NS3/4A protease inhibitor. Boceprevir has been
 approved for treating HCV GT1 infection by Food and Drug Administration (FDA) on 11 May 2011.
 For HCV GT1 mono-infected patients who refractory to previous PEG-IFN plus RBV combination
 therapy, becoprevir combined with PEG-IFN/RBV triple therapy can improve the treatment
 efficacy. The SVR rate of becoprevir-based triple therapy is about 3 times when compared to
 patients who received PEG-IFN with RBV dual therapy [14].The investigators , therefore,
 hypothesize that boceprevir plus PEG-IFN/RBV is effective in treating HCV GT1/HBV dually
 infected patients who are refractory to previous PEG-IFN/RBV combination therapy.
Inclusion Criteria:

 -  1. Patient must be 20 years or older

 -  2. Patient must have HCV GT1 infection combined with HBV infection.

 -  3. Patients must be serum HCV RNA detectable, anti-HCV positive, HBsAg positive and
 HBeAg negative.

 -  4. Patient has previously failed treatment with PEG-IFN-α 2a or 2b/RBV for minimum of
 12 weeks of treatment.

 -  5. Patient must have compensated liver disease consistent with CHC and/or CHB, and no
 other etiology. Note: patients with cirrhosis should have a liver imaging study (e.g.
 ultrasound, CT scan or MRI) within the preceding 6 months showing no evidence of
 hepatocellular carcinoma.

 -  6. Patient meets all of the requirements and none of the contra-indications for
 treatment with PEG-IFN alpha-2b/RBV or boceprevir defined in the labels for the
 PEG-IFN/RBV to be used in combination with boceprevir.

 -  7. Patient is able and willing to provide signed informed consent (prepared by and
 administered by the physician) as required by local country requirements.

 Exclusion Criteria:

 -  1. Mixed genotypes including HCV genotype other than genotype 1.

 -  2. Patient has received boceprevir, narlaprevir, telaprevir, or any other HCV protease
 inhibitor treatment.

 -  3. Patient has evidence of decompensated liver disease including but not limited to, a
 history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy.

 -  4. Patient meets any of the following exclusionary hematologic and biochemical
 criteria (documentation required) Hemoglobin <12 gm/dL for females and <13 gm/dL for
 males Neutrophils <1500/mm3 Platelets <100,000/mm3

 -  5. Patient has an organ transplant other than cornea or hair.

 -  6. Patient is co-infected with human immunodeficiency virus (HIV)

 -  7. Patient requires or is anticipated to require any of the following prohibited
 medications: midazolam, pimozide, amiodarone, flecainide, propafenone, quinidine, and
 ergot derivatives

 -  8. Patient with clinical diagnosis or evidence of substance abuse involving alcohol,
 intravenous drugs, inhalational psychotropics, narcotics, cocaine prescription or
 over-the-counter drugs.

 -  9. Patient previously demonstrated clinically significant hypersensitivity or other
 contraindication to any component of the boceprevir formulation. This drug contains
 lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp
 lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

 -  10. Serious illness, including malignancy, active coronary artery disease or cardiac
 dysfunction within 24 weeks prior to study entry, that in the opinion of the site
 investigator may preclude completion of the treatment regimen.

 -  11. Major hemoglobinopathy (e.g., thalassemia major), coagulopathy or any other cause
 of or tendency to hemolysis or bleeding