The refrigerator in front of the school If there hadn’t been that refrigerator in front of the school, Xiao Hong might not have been treated with interferon. Interferon is the star of this liver disease conference, representing a new idea in the treatment of hepatitis B. But it is actually an old drug, approved by the FDA for hepatitis B treatment as early as 1997. In fact, interferon is an internationally recognized classic drug for treating viral infections. All people secrete interferon when they have a cold, and most of the symptoms of a cold, including headache, fever and muscle aches, etc., are related to interferon. Zheng Lu, Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University So, how does the body know when a virus is coming? It turns out that most viruses go through a double-stranded RNA step in the replication process, as do influenza viruses, HIV and hepatitis B and C viruses, among others. Under normal circumstances double-stranded RNA is almost non-existent in the human body, so the double-stranded RNA acts as a signal for the cells to quickly start secreting large amounts of interferon to meet the challenge of the virus. What happens next is a matter of differing opinions. Some believe that interferon prompts the cells to secrete a certain protease that stops the virus from invading. Others believe that interferon promotes the cell to produce more MHC (a protein polymer), which better brings the virus hidden inside the cell to the surface for recognition by immune cells …… In short, several theories exist about the antiviral mechanism of interferon. But in any case, interferon is the most effective means of fighting viral invasion that vertebrates have evolved. ”The hepatitis B virus is smart enough that it inhibits interferon secretion in the host.” Bonino told the journal, “So we have to artificially supplement interferon to regulate the body’s immune function and help the body fight the virus.” This sounds like a sound reasoning, but in practice there are many problems. First, interferon has a strong “cold-like” side effects; second, interferon will also reduce the patient’s platelets, and even make patients appear psoriasis and other symptoms of immune dysfunction; again, interferon does not directly kill the virus, it is only an immunomodulator, must be achieved with the power of the body’s own immune system. The purpose. If the patient’s own immune system is not strong enough or is not sensitive to interferon, the efficacy of the treatment will be greatly reduced. What’s worse, interferon is a protein, which means it must be refrigerated and given by injection, not orally. Moreover, interferon is metabolized at a rapid rate in the body, and early generic interferon must be injected every two days, which causes a lot of inconvenience to patients. ”And in a country like China, where hepatitis B is heavily discriminated against, there are even more problems.” Dr. Crescent Chen told the Journal, “Many patients can’t follow the doctor’s orders to get injections on time because they are afraid of being known by others. So when the nucleoside analogs came out, many patients gave up on interferon and turned to this new drug.” As the name implies, a nucleoside analogue is a chemical that is similar in structure to a normal nucleoside (acid). Most viruses need a “reverse transcriptase” to replicate, and this enzyme is unique to viruses, and its substrate is nucleoside (acid). So, the nucleoside analog, by virtue of its structural similarity, replaces the real nucleoside (acid) and binds to the reverse transcriptase, terminating the normal process of reverse transcription, so that the virus can no longer replicate. Lamivudine was the first nucleoside analogue drug used to inhibit the hepatitis B virus, and had attracted a great deal of attention from patients and the medical community. The drug is relatively inexpensive (currently the cheapest costs only $400 a month), has essentially no side effects, is suitable for the vast majority of patients, and is highly effective, rapidly reducing viral DNA load and inhibiting viral replication in most cases. What’s more, lamivudine is an oral drug, and hepatitis B patients can start treatment without knowing it. The case of Xiao Hong back then is a good example. She took lamivudine for only six months and her hepatitis B viral load in her blood dropped by 5 Log, or 100,000 times. However, nucleoside analogs are like antibiotics, with a single mechanism of action, and the virus can easily develop resistance. After Xiao Hong took lamivudine for 14 months, the hepatitis B viral load in her blood rose by another 1,000 times, indicating that the virus in her body had developed resistance to the drug. Soon after stopping the drug, the transaminases rebounded, indicating that the immune system had started to attack the liver cells again. At that time, no new nucleoside analogues were available. If Xiao Hong’s case happened now, she would have two options: First, she could switch to a new nucleoside analogue drug. Four nucleoside analogs have been approved for marketing in China, including adefovir, entecavir and telbivudine, in addition to lamivudine. Their efficacy varies, and resistance is not generated at the same rate, but because they all work on a similar principle, many patients will sooner or later have to face the problem of resistance again. In other words, once Xiao Hong starts taking the medication, she will have to take it for a long time if serological conversion of the E antigen does not occur, and she will have to worry about the possibility of drug-resistant mutations. Secondly, she could go back on interferon. However, for a patient like Xiao Hong, who lives out of town, it would be difficult to ask her to go to the hospital every two days or to patronize the cold drink store in front of the school every other day. Fortunately, scientists have come up with a solution, which is long-acting interferon. Roche Pharmaceuticals (Roche), based in Basel, Switzerland, first synthesized peginterferon alfa-2a (Peginterferon alfa-2a, trade name “Pegasys”, Chinese name “Pyroxin”). PEG, an inactive hydrophilic compound, was mounted on the interferon molecule by Roche’s technicians to make it larger and more slowly absorbed. With the protection of PEG, interferon has less contact with proteases and is metabolized at a slower rate than regular interferon. Therefore, the concentration of Pyroxin in the bloodstream is more stable and has a longer half-life than regular interferon. Not only is the efficacy more stable, the side effects are smaller, and the duration of medication can be greatly extended, usually once a week by injection, which is greatly convenient for patients like Xiao Hong. Pyroxin entered China in 2004 and was initially used to treat hepatitis C, but some people abroad have started using it for hepatitis B treatment, so Chen decided to give it a try on Xiao Hong. Each injection of Pyroxin costs 1,350 yuan, and the recommended course of treatment is no less than 48 weeks, totaling more than 70,000 yuan,” Chen said. Although Xiaohong’s family is in a better financial position, this is not a small cost. In addition, not everyone is suitable for interferon, and the success rate of interferon treatment is not high. It is even more difficult to see results if the patients themselves do not perceive well, quit halfway or do not take the injections on time.” So, should the $70,000 be spent or not? “That depends on what the patient is after.” Chen Crescent said.