Adefovir was approved in 2002 for the treatment of chronic hepatitis B at a therapeutic dose of 10 mg/d. By 2008, the number of people taking adefovir worldwide was about 410,000 patient-years, and it was approved in 2008 for the treatment of children aged 12 to 17 years. Because adefovir can treat patients who are resistant to lamivudine and because adefovir is relatively inexpensive in China, the estimated number of patients using adefovir is similar to that of lamivudine. The main adverse effect of adefovir is potential renal damage. So far, no reports of causing myopathy and rhabdomyolysis have been retrieved from the national and international literature. In clinical trials, doctors found that the renal damage of adefovir was dose-related, with 8% of patients treated with 30 mg per day for 1 year experiencing renal damage, while the incidence of renal damage was 0 when the dose was reduced to 10 mg per day for 1 year; the incidence of renal damage was 3% to 8% after 5 years of continuous treatment, and it improved after stopping or reducing the dose. So far there is only one case of acute tubular necrosis after taking adefovir in a kidney transplant patient worldwide. This indicates that the nephrotoxicity of adefovir is very mild. The renal damage of adefovir is mainly manifested by the decrease of blood phosphorus and the increase of serum creatinine. As long as the patients taking the drug pay attention to check the kidney function and blood phosphorus can be detected in time, it will not cause serious consequences. Let’s take a look at entecavir. Entecavir was approved for the treatment of chronic hepatitis B in 2005. It was marketed in China and abroad almost simultaneously. The instructions for entecavir mention that it has found an increased incidence of tumors in some animals in animal trials, thus causing many patients to be nervous. In fact, if we read the instructions carefully, we can find that the doses used in animal trials are often several times or even dozens of times the highest recommended dose for humans (1.0 mg/day). Patients who participated in pre-marketing clinical trials with entecavir have now been taking entecavir for 7-8 years and no increase in tumorigenesis has been observed. Entecavir has been on the market for 5 years, and because of its strong antiviral effect and rarely causes viral resistance, by 2008, there have been 125,000 patient-years on entecavir treatment, but no increase in human tumors was found. 3 years ago, the U.S. FDA joined forces with a number of countries, including China, to participate in a clinical trial, in which 12,000 hepatitis B patients participated, and entecavir was compared with Entecavir was clinically controlled with other drugs to specifically observe tumorigenesis, and so far there is no association between entecavir and tumorigenesis. Searching the domestic and international literature, only one German author found 5 cases of lactic acidosis in liver disease patients with advanced cirrhosis and very poor liver and kidney function after entecavir use. Only one case of entecavir-induced thrombocytopenic purpura and one case of entecavir-induced peripheral nerve damage in the upper limbs were reported in China, and no cases of myopathy and rhabdomyolysis lysis were reported. This also indicates that long-term entecavir use is safe. Finally, let’s talk about telbivudine. Tebivudine was approved for the treatment of chronic hepatitis B in 2006 and launched in China in 2007. Tebivudine is a very effective drug for hepatitis B. It has a stronger antiviral effect than lamivudine, is comparable to entecavir, and is approved by the US FDA as a Class B drug with a safe level of use during pregnancy. By 2009, it was estimated that approximately 95,231 patient-years were treated with telbivudine worldwide. Tebivudine does have the potential to cause myopathy and (http://ditancaihaodong.blog.sohu.com/146207544.html). In clinical studies, the incidence of myopathy at 2 years of treatment ranged from 0.3% to 0.88%; the total number of muscle-related adverse events reported at 4 years of treatment was 4%, including 3% myalgia and 1% myositis, with most patients improving after discontinuation of the drug and no cases of rhabdomyolysis. In other words, myopathy or rhabdomyolysis does not occur in more than 95% of patients taking telbivudine. However, a few cases of rhabdomyolysis have occurred in China after the introduction of telbivudine. Why is the occurrence of myopathy after the marketing of telbivudine more severe than that observed clinically before the marketing? After a new drug is marketed, many physicians do not know enough about it and do not conduct strict regular monitoring and follow-up during treatment like patients in clinical trials, and some patients also think that their liver function is normal and their viral replication is negative after taking the drug, so they do not go to the hospital regularly for examination, which leads to the occurrence of myopathy in patients who are not detected in time and aggravated. In addition, the occurrence of myopathy is related to many therefore. Some patients have underlying myopathy themselves. One of our patients died of rhabdomyolysis after taking telbivudine, and post-death investigation revealed that he was in cyclic paralysis (a myopathy) prior to treatment with telbivudine. Many drugs (e.g., statin-based blood-lowering drugs) can also cause myopathy, and even heavy alcohol consumption can lead to rhabdomyolysis. Post-marketing patients are complex, often with concurrent use of multiple drugs, and may also consume alcohol. Some doctors even combine tibivudine with interferon in order to enhance the antiviral effect. Interferon can not only increase the toxicity of tibivudine to muscle, but also increase the risk of peripheral neuropathy, the incidence of which is 16.7%, while the incidence of peripheral neuropathy is only 0.3% when treated with tibivudine alone. CK is found mainly in cardiac and skeletal muscle, but also in some brain and thyroid cells. It is found in very small amounts in the blood of normal people. However, when the muscle and heart are damaged, it is released from the cells and runs into the blood, raising the CK level in the blood. For example, CK levels in the blood of patients with diseases such as myocardial infarction, myositis, rhabdomyolysis, and hypothyroidism are significantly elevated. Do not panic if you experience elevated CK during the course of tebivudine treatment, but observe it first. It is common for CK to rise more than 7 times the upper limit of normal during tibivudine, about 12% to 14%, but more than 10% are transient elevations that automatically drop to normal within 3 months, and myopathy may occur in only 3% to 4% of patients. Therefore, whether to discontinue or change medication depends mainly on the presence of muscle symptoms. Myopathy generally presents with significant muscle symptoms, such as muscle pain and muscle weakness. If CK is elevated to more than 5 times the upper limit of normal value and accompanied by myalgia, or if there are no muscle symptoms but CK continues to be elevated to more than 5 times the upper limit of normal value for 3 months without recovery or progressive elevation, immediately discontinue the use of telbivudine and switch to or temporarily switch to other effective antiviral drug therapy. The diagnosis of myopathy is usually done by a neurologist. In addition to elevated CK, the physician will examine the patient’s whole body muscles, check muscle strength and muscle induration, determine the severity of myopathy, and perform electromyography and muscle biopsy pathology if necessary. Mild myopathies usually recover gradually after stopping the medication, and patients with slow recovery after stopping the medication can be treated with coenzyme Q10. Severe myopathy requires immediate hospitalization to avoid serious complications. Overall, of the four nucleoside (acid) analogs for the treatment of chronic hepatitis B, lamivudine and entecavir have the fewest adverse reactions, adefovir requires monitoring of renal function, and telbivudine requires monitoring of CK, but long-term application is safe in more than 95% of people, and a minority of people can completely avoid adverse reactions as long as they are monitored regularly at the hospital. There is no need to worry too much about this “Notice” from the FDA, and don’t blindly stop the medication after seeing the “Notice”, as it is likely to lead to aggravation of liver disease after stopping the medication; and don’t casually change the medication, as it is likely to increase the chance of virus resistance and the difficulty of future treatment. The consequences of randomly stopping or changing medication may be greater than the risk of adverse reactions! “It’s a medicine with three toxins”, but current antiviral therapy can effectively inhibit hepatitis B virus replication, promote normalization of liver function, improve liver fibrosis, reduce the occurrence of cirrhosis and liver cancer, and improve the quality of life of hepatitis B patients. The benefits for patients with chronic hepatitis B are significantly higher than the risk of those rare or even rare adverse reactions. We should not just notice the risk of individual adverse reactions occurring and forget the risk that the hepatitis B virus poses to our bodies in giving up effective antiviral therapy.