Interferon Alpha 2b Plus Ribavirin for Chronic Hepatitis B
Interferon Alpha 2b Plus Ribavirin for Chronic Hepatitis B
Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute
 hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of
 individuals infected with this virus has been estimated to be as high as 350 million. Thus,
 in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is
 also needed.

 Currently, there are no effective antiviral treatments to cure HBV infection in patients with
 chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B
 at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated
 IFN alpha and recently entecavir. Overall, satisfactory virologic and serologic responses
 could be achieved using pegylated IFN alpha alone in around 20-44% of these patients.
 Nevertheless, better treatment options are still needed for the remaining >50%
 non-responders.

 Although the best treatment choice for chronic hepatitis B is not clarified yet, certain
 therapeutic concepts could be derived from the experience of treating patients with chronic
 hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the
 development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor
 sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin
 combination therapy, in contrast, results in much improved treatment outcomes. In our
 previous study and others, sustained remission rate after cessation of therapy were
 significantly higher in patients receiving combination therapy than those receiving IFN
 alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the
 standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and
 IFN combination for the treatment of dual chronic hepatitis B and C, and the results also
 revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV
 infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found
 that a significant portion (21%) of the responsive patients also cleared HBsAg. These
 findings imply that this combination regimen might be also effective for the control of
 chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study
 in patients with HBeAg-positive chronic hepatitis B.
Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute
 hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of
 individuals infected with this virus has been estimated to be as high as 350 million. Thus,
 in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is
 also needed.

 Currently, there are no effective antiviral treatments to cure HBV infection in patients with
 chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B
 at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated
 IFN alpha and recently entecavir. Conventional IFN alpha monotherapy has a narrow range of
 efficacy. Lamivudine, is relatively cheaper, better tolerated, and has been shown to be
 effective in patients with both hepatitis B e antigen (HBeAg)-positive and -negative chronic
 hepatitis B. However, virologic response to lamivudine is not as durable as that occurred
 spontaneously or induced by IFN treatment. In addition, prolonged lamivudine treatment is
 commonly associated with the emergence of drug-resistance HBV mutants accompanied by the
 development of breakthrough hepatitis. Adefovir is potent and has been approved for the
 treatment of chronic hepatitis B in several countries, but is nephrotoxic at daily doses
 higher than 10 mg and is still not available widely. Entecavir, a carbocyclic deoxyguanosine
 analog, which is active against both lamivudine- and adefovir dipivoxil-resistant HBV, is the
 most potent anti-HBV agent ever discovered,11 however, its long-term efficacy remains to be
 evaluated. Pegylated IFN alpha has recently been shown to be superior to conventional IFN
 alpha and lamivudine, and has also been approved for the treatment of chronic hepatitis B.
 Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN
 alpha alone in around 30-44% of these patients. Nevertheless, better treatment options are
 still needed for the remaining >50% non-responders.

 Although the best treatment choice for chronic hepatitis B is not clarified yet, certain
 therapeutic concepts could be derived from the experience of treating patients with chronic
 hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the
 development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor
 sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin
 combination therapy, in contrast, results in much improved treatment outcomes. In our
 previous study and others, sustained remission rate after cessation of therapy were
 significantly higher in patients receiving combination therapy than those receiving IFN
 alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the
 standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and
 IFN combination for the treatment of dual chronic hepatitis B and C, and the results also
 revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV
 infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found
 that a significant portion (21%) of the responsive patients also cleared HBsAg. These
 findings imply that this combination regimen might be also effective for the control of
 chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study
 in patients with HBeAg-positive chronic hepatitis B.
Inclusion Criteria:

 -  Adult male or female, 18 to 60 years of age chronic hepatitis B patients Patient must
 have documented positive serum HBsAg for a minimum of 6 months prior to entry into
 study.

 Patients must show evidence of HBV replication and hepatitis documented by Positive serum
 HBV-DNA within 3 months prior to entry (HBV-DNA > 2.5 pg/ml) Positive serum HBeAg within 3
 months prior to entry. Documented presence of abnormal alanine aminotransferase (ALT) twice
 within 3 months prior to entry (2 to 10 fold above the upper normal level) Liver biopsy
 finding shows chronic hepatitis without liver cirrhosis

 Compensated liver disease with the following minimum hematological and serum biochemical
 criteria:

 -  Hemoglobin values of ≥ 12 gm/dL for both sexes

 -  WBC ≥ 3,000/mm3

 -  Neutrophil count ≥ 1,500/ mm3

 -  Platelets ≥ 100,000/ mm3

 -  Total bilirubin ≤ 2 mg/dL

 -  Albumin ≥ 3.5 g/dL

 -  Uric acid within normal ranges

 -  Serum creatinine ≤ 123.76 mmol/L (≤1.4 mg/dL)

 -  Fasting blood sugar ≤ 6.38 mmol/L (≤115 mg/dL) for non-diabetic patients

 -  Hemoglobin ≤ 8.5% for diabetic patients (whether on medication and/or controlled with
 diet) Thyroid Stimulating Hormone (TSH), T3 & T4 within normal limits Negative serum
 antibody to hepatitis C Negative antibody to human immunodeficiency virus (anti-HIV)
 ELISA method If the patient has a history of diabetes or hypertension, a baseline
 ocular examination will be required.

 Alfa-fetoprotein within normal range Written informed consent

 

 Exclusion Criteria:

 -  Patients older than 60 years of age

 Any cause for the liver disease based on patient history or biopsy (where applicable) other
 than chronic hepatitis B, including but not limited to:

 Co-infection with HCV and/or HIV Hemochromatosis (iron despistion > 2 + in liver
 parenchyma) Alpha-1 antitrypsin deficiency Wilson's disease Renal or liver transplant
 patients Autoimmune hepatitis Alcoholic liver disease Obesity related liver disease Drug
 related liver disease Evidence of decompensated liver disease such as history or presence
 of ascites, bleeding varices, hepatic encephalopathy.

 Any known pre-existing medical condition that could interfere with the patient's
 participation in and completion of the treatment such as:

 Pre-existing psychiatric condition, especially severe epression, or a history of severe
 psychiatric disorder CNS trauma or active seizure disorders requiring medication. Patients
 with any history of cardiovascular dysfunction. Patients with any hemoglobinopathy
 including but not limited to thalassemia major and minor Poorly controlled diabetes
 mellitus Chronic pulmonary disease Immunologically mediated disease Clinical gout Sexually
 active females of childbearing potential must be practicing adequate contraception,
 Sexually active males must be practicing acceptable methods of contraception (vasectomy,
 condom + spermicide, monogamous relationship with a female partner who practices an
 acceptable method of contraception) during the treatment period and for 6 months after
 discontinuation of therapy.

 Female patients must not breast feed during the treatment period. Patients must agree to
 limit the drinking of alcohol during the course or the treatment.

 Patients receiving Chinese herbal medication during the past 3 months prior to study entry.

 Patient who did not respond to previous interferon therapy or who relapsed after a previous
 course of Interferon therapy.

 Patients who have been enrolled in any clinical trial for the treatment of chronic
 hepatitis B.