Polyethylene glycol interferon α-2a has both direct antiviral and immunomodulatory effects, and is able to achieve high HBeAg seroconversion and HBsAg clearance rates through a limited course of treatment, giving patients the opportunity to achieve clinical cure and safely discontinue the drug. All authoritative guidelines recommend pegylated interferon alpha-2a as a treatment option for chronic hepatitis B. However, since pegylated interferon α-2a is a biological agent, there are certain adverse reactions in its use. However, after a long period of clinical practice and a large number of clinical studies, the adverse reactions of pegylated interferon α-2a have been very clear, can be effectively controlled and handled, and for the vast majority of patients will not affect the normal treatment. Then what are the main adverse reactions of PEGylated Interferon alpha-2a? And how should they be handled? The most common adverse reactions to PEGylated Interferon alpha-2a are flu-like symptoms, mainly manifested as fever and chills, headache, muscle pain, fatigue and other symptoms. They usually appear at the beginning of the first or second treatment with pegylated interferon alfa-2a, and can be gradually reduced or even disappeared with the prolongation of treatment. In order to minimize the occurrence of flu-like symptoms and discomfort, you can choose to inject PEGylated Interferon α-2a before going to bed; if flu-like symptoms occur, you can drink plenty of water and use spritz baths to physically cool down the temperature when the temperature is lower than 38.5°C; if the body temperature is higher than 39°C, you need to take bed rest and take antipyretic and analgesic drugs to relieve the symptoms. Another common type of adverse reaction is blood abnormalities. Early in the treatment of polyethylene glycol interferon α-2a may occur in the peripheral blood leukocytes and platelets decrease, most of them can be self-recovery will not affect the treatment. Downward adjustment of the drug dose is usually necessary only if the total number of leukocytes is ≤1.5 x 109/L or if the neutrophil count is ≤0.75 x 109/L or the platelet count is ≤50 x 109/L. Patients with significant blood abnormalities, such as a significant drop in white blood cells, may also receive leukocyte-boosting drugs. In order to detect adverse reactions in time, patients should follow the doctor’s instructions before starting treatment and during treatment, and insist on weekly routine blood tests to understand the situation of blood, so as to detect the problem in time and actively deal with it. In addition, similar to other medications, digestive symptoms such as nausea, vomiting, diarrhea, dyspepsia, anorexia, and weight loss, as well as problems such as pharyngitis, dry mouth, mouth ulcers, bleeding gums, dry skin, itchy rashes, hair loss, and excessive sweating, may also occur during treatment with pegylated interferon alpha-2a. However, most of these problems are hopefully not serious and can be improved through timely symptomatic treatment. Of particular note is the issue of elevated ALT during treatment with pegylated interferon alpha-2a. Transient elevations of ALT are very common with pegylated interferon alpha-2a therapy for chronic hepatitis B, and can be up to ten times above the upper limit of normal. Studies have shown that an increase in ALT early in the treatment is the result of the immune mobilization of PEGylated Interferon alfa-2a, and that these patients have even better outcomes. Instead of stopping the drug at this time, the treatment should be continued. In conclusion, the adverse reactions of pegylated interferon alfa-2a are clear and can be well controlled and handled, and most of them will not affect the normal treatment. Before using PEGylated Interferon α-2a for the treatment of chronic hepatitis B, patients should have good communication with their doctors to understand the course of treatment, efficacy, and to have a clear idea of the possible adverse reactions and preventive treatment methods. Communicate with your doctor in a timely manner during the treatment process, and do not easily stop taking the medication to ultimately achieve better efficacy.