Many patients with chronic hepatitis B are bewildered by their new diagnosis, worrying about the impact of the disease on their health and hoping that there is a way to get rid of the disease for good. However, there are always some patients who are in a hurry to get rid of the disease, listening to biased prescriptions and tests, and neglecting the most crucial component of chronic hepatitis B treatment: antiviral therapy. For chronic hepatitis B, antiviral drugs are the only scientifically proven effective treatment program that can improve the condition and slow down the progress of the disease, which is the real core of the treatment of chronic hepatitis B. The initial treatment choice for chronic hepatitis B is antiviral drugs. The choice of initial treatment for chronic hepatitis B is very important, and it is fair to say that this choice will have a long-term impact on the patient’s future life. At the time of diagnosis, most of the patients with chronic hepatitis B are “triple positive” patients. For “triple positive” patients with active liver inflammation, that is, patients with higher than normal ALT (usually more than twice the upper limit of ALT) and HBV DNA levels of more than 100,000 copies/mL, they will be treated with an effective treatment program. Patients with HBV DNA levels above 100,000 copies/mL should be considered for antiviral therapy. Currently there are 2 classes of antiviral drugs: long-acting interferons and nucleoside analogs. The two classes of drugs have different mechanisms of action and some differences in efficacy. The most important feature of long-acting interferon is the high e-antigen conversion rate, which can achieve lasting immune control through a limited course of treatment, but these drugs are relatively expensive and require injection. Nucleoside (acid) analogs can suppress the virus relatively quickly, are less expensive, and are easy to take orally, although the biggest problem with these drugs is that they require long-term treatment, have a higher risk of resistance, are prone to relapse, and have safety risks in long-term use. The advantages and disadvantages of the two classes of drugs are clear, but what exactly should you choose? The latest guidelines for chronic hepatitis B, such as the 2013 NICE (UK) guideline and the 2015 APASL (Asia Pacific) guideline, both recommend that long-acting interferon therapy should be considered as a first-line option for patients with chronic hepatitis B. The NICE (UK) guideline specifically advises that long-acting interferon therapy should be considered for patients with chronic hepatitis B first, and then nucleoside analogues if response to long-acting interferon therapy is poor. This recommendation is based on the fact that patients with chronic hepatitis B should be considered for long-acting interferon therapy first. The main reason for this recommendation is that if patients try long-acting interferon therapy first, they may be able to achieve a durable response after discontinuation of the drug with a limited course of treatment (usually 48 weeks), and even if the response is poor, this does not prevent them from continuing to receive nucleoside analogs, but this sequence of treatment increases the chances of durable immune control. Simply put, for patients, if they choose nucleoside (acid) analogs at the beginning, they may have to face a lifetime of medication; however, if they choose long-acting interferon therapy, they can hope to get rid of the trouble of long-term medication in the future. Of course, slow hepatitis B is a complex disease, not every patient can have a good response to long-acting interferon therapy. According to studies, one-third of patients achieve durable immune control after receiving long-acting interferon therapy. For some advantageous patients, that is, people with high ALT levels and low HBV DNA levels, this percentage is more than 60%, for these patients long-acting interferon is obviously a better choice, you can consider seizing the opportunity to strive to get rid of the disease. For patients who have chosen nucleoside (acid) analogues for treatment, they must adhere to the treatment, and must not arbitrarily stop taking the drug, so as to avoid disease progression and health hazards.