A Randomized, Double-Blind Trial of Antroquinonol in Patients With Chronic Hepatitis B

Hepatitis B virus infection is a worldwide disease and is still the most common cause of hepatocellular carcinoma (HCC). Those carriers in China account for 33% of all chronic carriers globally. A big epidemiological study of patients with chronic hepatitis B has revealed that baseline HBV DNA level or cirrhosis is an independent predictor for the occurrence of HCC.

Antroquinonol is a new chemical entity isolated from the mycelium of Antrodia camphorata, which showed interesting anticancer and anti-inflammatory activities.Previous studies have indicated that signaling molecules, such as PI3K, AMPK, and mTOR, participate in Antroquinonol-induced cancer cell death, whereas Nrf2 and NF-kB are involved in the anti-inflammatory effects of Antroquinonol. Moreover, we also found the administration of Antroquinonol also differentially modulated T cell activity and reduced IL-18 production, but enhanced the activation of Nrf2 and, thus, suppressed oxidative stress by animal studies. These results demonstrate the potential applications of Antroquinonol in treating hepatitis B.

Inclusion criteria

• Chronic HBV infection patients between the ages of 20 and 75 years with serum hepatitis B surface antigen(HBsAg) positivity for more than 6 months
• BMI≦35
• HBsAg≧10 IU/mL and HBV DNA≧2000 IU/mL.
• AST or ALT≧25 IU and ALT<5xULN
• Female subject must use effective methods of contraception.
• No abnormal finding of clinical relevance
• Written informed consent

Exclusion criteria

• Evidence of hepatic decompensation such as:

• Coagulopathy defined as prolongation of prothrombin time greater than 3 seconds
• Total bilirubin of 2 times the upper limit of normal
• FIB-4 of 3.25 or greater
• Abnormal hematological and biochemical parameters at screening A、 White blood cell count less than 2500 cells/uL B、 Absolute neutrophil count (ANC) less than 1,000 cells/mm3 (less than 750 mm3 for African or African-American subjects) C、 Hemoglobin less than 12 g/dL for males, less than 11 g/dL for females D、 Estimated GFR less than 50 mL/min
• Suspected or confirmed liver diseases from etiologies other than HBV (such as alcohol, toxin, drug, shock, acute viral hepatitis A or E), co-infection with human immunodeficiency virus, hepatitis C virus or hepatitis delta virus, prior antiviral treatment with NUCs or interferon, and recent immunosuppressive therapy (including chemotherapy and systemic corticosteroid).
• Immunodeficiency disorders or severe autoimmune disease
• Severe pulmonary disorders or significant cardiac diseases
• Gastrointestinal disorder with post-operative condition that could interfere with drug absorption
• Significant psychiatric illness that in the judgment of the Investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent
• Any malignancy diagnosed within 5 years or evidence of hepatocellular carcinoma (e.g., α fetoprotein > 50ng/mL or radiologic evidence)
• Solid organ transplantation
• Current drug or alcohol abuse
• Pregnancy or lactation
• Under hepatitis B antiviral or interferon treatment within 3 months