I. Mechanism of antiviral action of interferon (IFN): It blocks virus multiplication and replication, but cannot enter the host cell to kill the virus directly. Instead, it contacts with the cell membrane and produces a special protein, namely antiviral protein (AVP), in the cell, which can inhibit the transmission of viral mRNA information, thus preventing the virus from multiplying in the host cell. Interferon also induces the production of protein kinase and 2’5′ oligoadenosine synthase (2’5’AS) in virus-infected cells, which then activates an endogenous nucleic acid endonuclease to degrade viral RNA, while protein kinase inactivates enzymes necessary for ribosome synthesis2, resulting in reduced protein synthesis and inhibition of virus growth. Interferon inhibits or enhances the function of B cells under certain conditions, e.g. high concentration of interferon significantly inhibits the antibody response. The clinical application of high dose IFN-α in the treatment of chronic viral hepatitis can improve or restore the abnormal elevation of serum IgG and IgM, which is also due to the inhibition of B cells by interferon and the alleviation of the excessive production of immunoglobulin antibodies by plasma cells. The effect of interferon on effector cells is also due to the inhibition of B-cell production by interferon and the alleviation of excessive plasma cell production of immunoglobulin antibody. The effect of interferon on effector cells, it can increase the expression of histocompatibility antigen-I (HLA-1), these antigens are very important for the recognition of target cells by killer T cells. In addition, it is also confirmed that γ-interferon has increased interleukin-2 (IL-2) receptor effect, and IL-2 can increase mitogenic stimulation of lymphocytes to induce γ-IFN, so IL-2 and γ-IFN have close connection and coordination in function.
Second, the indications for interferon antiviral therapy: the application of interferon for the treatment of chronic hepatitis B aims to remove HBV-DNA and HBeAg from the body and induce the conversion of serum HBeAg into anti-HBe, the disappearance of HBcAg in the nucleus of hepatocytes, the improvement of liver histological lesions and the return of normal ALT. The efficacy of interferon in the treatment of chronic hepatitis B varies from 30-60%. Through the author’s experience in applying interferon in recent years, patients with chronic hepatitis B selected for the following conditions had a better therapeutic response to interferon treatment.
(1) Those with repeated fluctuations in serum ALT or AST or persistent elevation of enzyme activity before treatment;
(2) Abnormally low P/N value of serum HBeAg (P/N5-8) or low HBV-DNA level (<100pg/ml) before treatment;
(3) Those with a clear history of acute onset and short illness;
(4) Application of interferon dose should be large (3 million to 6 million units, subcutaneous or intramuscular injection once every other day, that is, 3-6Mu/every other day, the course of treatment should be long, generally 6-1 months as a course of treatment;
(5) liver pathology with active inflammatory lesions 9 such as debris-like necrosis) is effective;
(6) No overlapping infections (e.g., hepatitis C, hepatitis D, etc.);
(7) No HIV infection or immunosuppressive therapy;
(8) Those with low iron content in liver tissue;
(9) No interferon neutralizing antibodies in the serum during treatment;
(10) The efficacy of female patients is better than male.
Three, interferon antiviral therapy contraindications.
(1) Elevated serum bilirubin > 2 times the upper limit of normal value
(2) decompensated cirrhosis
(3) autoimmune diseases
(4) important organ lesions
IV. Criteria for evaluating the efficacy of interferon in the treatment of chronic hepatitis B.
(1) complete response (effective): ALT is normalized, HBV DNA, HBeAg, HBsAg are negative;
(2) Partial response (effective): ALT is normalized, HBV DNA and HBeAg are negative, but HBsAg is still positive;
(3) Non-response (invalid): those who do not reach the above index;
(4) Sustained response: complete response (efficacious) or partial response (effective), still efficacious or effective 6-12 months after stopping the drug;
(5) Relapse: those who are effective and effective at the end of treatment, and those with abnormal ALT and positive HBV DNA within 6 to 12 months after drug discontinuation are relapsed.
The efficacy of interferon on chronic hepatitis B has been more certain. The literature shows the results of applying α2b interferon to treat chronic hepatitis B. The negative rates of HBeAg, HBV-DNA and HBsAg were 51%-66.49%, 49%-72% and 2.5%, respectively, and the anti-HBe positive rate was 44%-62%. The rate of improvement in liver histology ranged from 24% to 60% between 3 and 6 months of treatment.
V. Adverse effects of interferon antiviral therapy.
(1) Influenza-like syndrome: fever, chills, headache, muscle pain and fatigue, etc., can be injected at bedtime IFNα, or in the injection of interferon at the same time to take antipyretic and analgesic drugs to reduce flu-like symptoms. These symptoms can be gradually reduced or disappeared as the treatment progresses.
(2) Transient myelosuppression: The main manifestation is a decrease in peripheral blood leukocytes (neutrophils) and platelets. If the absolute neutrophil count ≤ 1.0×109/L, the dose of IFNα should be reduced; recheck after 1 to 2 weeks, and if it recovers, gradually increase to the original amount. If absolute neutrophil count ≤ 0.75×109/L.