What are the side effects of long-term use of anti-hepatitis B drugs? Can't stop eating? Don't go wrong! The director talks about liver disease

Author: Wang Sheng, Department of Infectious Diseases, Danzhou People's Hospital, Hainan Medical College

This article is authorized by the author to be published by Yimaitong, please do not reprint without authorization.

As soon as many people hear that anti-hepatitis B virus requires long-term medication, they are very resistant, not only troublesome, but also worried about side effects, and some people hear that once they take anti-hepatitis B drugs, they cannot stop, so they dare not start anti-hepatitis B treatment, delaying the disease, and finally being taken away by liver cirrhosis, liver cancer, and liver failure, which also leads to the loss of family happiness, which makes people regret.

Are the side effects of long-term anti-hepatitis B drugs really big? Once you eat it, you can't stop? In fact, this is not the case, it is all said by people with insufficient knowledge, don't be misled.

What are the side effects of long-term use of primary anti-hepatitis B drugs?

You can think about it, which chronic disease such as hypertension, diabetes, coronary heart disease, and cerebral infarction should not be used for life? And those diseases usually require several medications to be taken at the same time. Anti-hepatitis B virus drugs usually only need to be eaten, and the time is relatively fixed, which is more simple and convenient to use, unlike hypertension and diabetes, which often need to adjust the dose, and even take 2~3 times a day.

In fact, anti-hepatitis B drugs not only rarely have adverse effects on the liver, but can also reduce the occurrence of severe hepatitis, liver cirrhosis, and liver cancer, which is actually the protection of the liver. Diabetes, hypertension, and cardiovascular and cerebrovascular diseases usually require several drugs to be taken at the same time, and the probability of affecting the liver is actually greater.

Everyone can accept long-term medication for hypertension, diabetes, cardiovascular and cerebrovascular diseases, but is very resistant to the use of anti-hepatitis B virus, in fact, this is a very unclear understanding, I hope everyone can wake up from this simple example, do not be deceived by wrong ideas and delay the disease.

Can I stop taking secondary antibodies for hepatitis B?

At present, there is no drug that can directly kill the hepatitis B virus in liver cells, and most hepatitis B infected people and patients do need long-term oral anti-hepatitis B virus drugs (NAs) treatment to inhibit the reproduction and activity of the virus, so as to significantly reduce (or even avoid) the occurrence of liver cirrhosis, liver cancer, and liver failure, but it does not mean that once you take anti-hepatitis B drugs, you can't stop.

Based on the latest relevant guidelines and my own clinical practice experience, the author has concluded that there are 6 types of people who can actually stop taking the drug. In order to help you better understand and recognize, I will list the groups that can be discontinued and the corresponding discontinuation criteria as follows:

(1) Those who have achieved clinical cure.

Many people do not pay attention to learning and understanding the new advances in medicine, and do not know that some hepatitis B can now be clinically cured.

The 2019 edition of the Expert Consensus on Clinical Cure (Functional Cure) of Chronic Hepatitis B, and the 2019 and 2022 editions of the Guidelines for the Prevention and Treatment of Chronic Hepatitis B clearly point out that more than 30% of people can be clinically cured by injection of peginterferon α (Peg-IFN-a), or sequential or combined optimized regimen treatment with nucleotide analogues (NAs) and pegylated interferon α. And the total course of treatment generally only takes 48~96 weeks - that is, long-acting interferon monotherapy can be used, or oral nucleos(t)ide analogues (NAs) such as entecavir, tenofovir fumarate, tenofovir alafenol, emitenofovir and injection of long-acting interferon can be discontinued, and the total course of treatment is generally not more than 2 years.

Which people belong to the dominant group that can be clinically cured, the author in the previous popular science article "After half a year of anti-hepatitis B, the surface antigen is still very high, what should I do?" Teach you clinical healing! and the younger the age, the easier it is to obtain clinical cure, and the clinical cure rate in children is much higher than that of adults.

In other words, those who have achieved clinical cure can stop taking the drug, and not all hepatitis B patients need to take anti-hepatitis B drugs for life once they take them, so don't be misled by people with insufficient knowledge.

(2) People with hepatitis B "big three yangs".

Hepatitis B "big three yang", that is, hepatitis B two and a half positive items 1, 3, 5 positive infections and patients - if they do not meet the clinical cure advantage of this kind of people, most of them need long-term medication, until HBsAg (hepatitis B two and a half item 1) turns negative to avoid recurrence, but if you want to stop the drug for various reasons, there are also criteria for early discontinuation.

According to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition), the criteria for discontinuation of such people who were "hepatitis B big three yang" before treatment are: after 1 year of treatment with oral nucleos(t)ide analogues (such as entecavir, tenofovir fumarate, tenofovir alafenol, emitenofovir), if the high-sensitivity hepatitis B virus DNA (HBV DNA) is lower than the lower limit of detection, the alanine aminotransferase (ALT) is normal, and the hepatitis B major sanyang turns into a small sanyang, the consolidation therapy will continue for at least 3 years (rechecked every 6 months) will remain unchangedand HBsAg < 100 IU/ml, discontinuation can be tried.

From the above, it can be seen that even if hepatitis B is a big three yang, even if there is no dominant group of people who meet the clinical cure of hepatitis B, they can also be treated with oral anti-hepatitis B virus drugs - the fastest is after 4 years of drug observation, not like the legendary "you can't stop after eating".

In addition, patients with other types of hepatitis B infection who were HBeAg positive (hepatitis B two-and-a-half item 3 positive) prior to treatment were also discontinued.

(3) People with hepatitis B "Xiao Sanyang" and "Xiao Eryang".

Hepatitis B "small three yang" refers to the positive items 1, 4, and 5 of the two halves of hepatitis B; "Xiao Eryang" refers to the positive items 1 and 5 of the two halves of hepatitis B.

Infected and patients who were "Xiao Sanyang" or "Xiao Eryang" of hepatitis B before treatment also have discontinuation criteria: after treatment with oral nucleos(t)ide analogues (such as entecavir, tenofovir fumarate, tenofovir alafenol, emitenofovir or double), the virus is undetectable in high-sensitivity hepatitis B virus DNA, and two pairs of HBsAg negative or anti-HBs are positive (or both positive for item 1 and item 2), If the hepatitis B virus is still not detected after 6 months of continuous consolidation therapy, the drug can be discontinued for follow-up.

In addition, patients with other types of hepatitis B infection who were HBeAg-negative (hepatitis B two-and-a-half item 3 negative) prior to treatment were also discontinued.

It can be seen that hepatitis B Xiaosanyang and Xiaoeryang also do not have to take medication for life, but there are criteria for stopping medication, but here I would like to remind everyone that many people may think that Xiaosanyang and Xiaoeryang are easier to treat than Dasanyang, but in fact, they are not. In fact, the time required to treat the minor three yang and the small two yang is usually longer than that of the big three yang.

From the discontinuation criteria, we can see that the discontinuation criteria for Xiao Sanyang and Xiao Eryang require HBsAg to turn negative or (and) be positive for anti-HBs, which is actually more difficult, so it takes longer, because HBsAg turning negative is equivalent to almost reaching the height of clinical cure. Although hepatitis B surface antigen (HBsAg) does not turn negative, it is also difficult to discontinue the drug if the hepatitis B surface antibody (anti-HBs) is positive.

If the drug is a big three yang before treatment, the discontinuation standard is to require a small three yang, and there is no requirement for HBsAg to turn negative or (and) anti-HBs to be positive, which shows that the big three yang patients are easier to meet the discontinuation criteria than the small three yang and small two yang patients, and the small three yang and small two yang are usually converted from the big three yang, so it is recommended that everyone should be treated as soon as possible when the big three yang.

In short, no matter what type it is, it can be seen from the above that almost all hepatitis B virus infected people and patients have criteria for stopping the drug, and it is not necessary to take the drug for life, unless it has developed into special circumstances such as liver cirrhosis.

(4) Pregnant women in the immune tolerance period.

The hepatitis B immune tolerance period usually refers to a state in which the hepatitis B virus coexists with the human body and has no obvious effect on each other, when the liver function is normal, and the liver has no obvious inflammation, necrosis and fibrosis, but the hepatitis B virus DNA is usually high and very contagious.

Because if the HBV DNA > 2×105 IU/ml in the second and third trimesters, the risk of mother-to-child transmission is high, and some are already transmitted to the fetus during pregnancy.

Therefore, in order to block the transmission of hepatitis B virus from mother to child, pregnant women in the immune-tolerant period with HBV DNA > 2×105 IU/ml should start anti-hepatitis B virus therapy at 24~28 weeks of gestation.

If the age is not more than 30 years old, there is no family history of liver cirrhosis and liver cancer, and the liver function has been normal, and only for the mother-to-child blockade of anti-hepatitis B drugs in the immune tolerance period of pregnant women, they can stop taking the drug immediately after giving birth or continue to take it for 1~3 months after observation.

(5) HBsAg-negative and anti-HBc-positive patients who need to be treated with chemotherapy, targeted drugs and immunosuppressants due to other diseases.

If hepatitis B has turned negative with hepatitis B surface antigen (HBsAg) in two pairs, only item 5 (anti-HBc) is positive, and the virus is not detectable in high-sensitivity hepatitis B virus DNA, it means that the hepatitis B virus has been previously infected and has recovered, but because the hepatitis B virus in the liver cells cannot be cleared, the anti-HBc usually remains positive for life.

If such people are combined with other diseases (such as lung cancer, etc.) and need to receive chemotherapy, targeted drugs and immunosuppressants, it may lead to reactivation of hepatitis B virus, and liver failure may occur in severe cases, so those who are ready to receive chemotherapy, targeted drugs and immunosuppressants should start anti-hepatitis B virus therapy at least 1 week in advance, and those who need urgent treatment can be treated with anti-hepatitis B virus treatment at the same time.

For patients on prophylactic anti-hepatitis B virus therapy, after the end of chemotherapy, targeted drugs and immunosuppressant therapy, after continuing anti-hepatitis B virus treatment for 6~12 months, if HBsAg is not activated and becomes positive, and the virus is not detectable in high-sensitivity hepatitis B virus DNA, anti-hepatitis B drugs can be discontinued for observation.

In addition, HBsAg-negative, anti-HBc-positive patients who have received B lymphocyte monoclonal antibodies, have undergone hematopoietic stem cell transplantation, or have advanced liver fibrosis/cirrhosis should also be treated with prophylactic anti-HBc. Such patients can continue oral anti-hepatitis B virus drugs for more than 18 months after completing corresponding treatment, and if HBsAg remains negative and the virus is not detectable in high-sensitivity hepatitis B virus DNA, the anti-hepatitis B drugs can be discontinued for observation.

(6) Patients infected with hepatitis B virus with anti-hepatitis C virus treatment.

The Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition) state that all people with hepatitis B virus infection should be screened for hepatitis C antibody (anti-HCV), and if positive, further HCV RNA quantification is required. All patients with positive HCV RNA quantification require anti-HCV therapy.

However, there is a risk of HBV reactivation during HCV therapy, so concomitant HBV therapy is required during HCV treatment and for 3 months after completion of HCV therapy to prevent HBV reactivation.

Hepatitis B virus (HBV) patients who could have been treated orally with anti-hepatitis B drugs in order to cooperate with anti-hepatitis C treatment can stop anti-hepatitis B drugs for observation after 12 weeks of anti-hepatitis C treatment.

summary

In summary, long-term oral anti-hepatitis B virus drugs are not as big as the legendary side effects, compared with chronic diseases such as hypertension, diabetes, coronary heart disease, cerebral infarction, etc., anti-hepatitis B virus drugs are simpler and more convenient, and the side effects are not necessarily greater. As long as you follow the standard medication and re-examination, if there is drug resistance or side effects, you can adjust it in time, and you don't have to worry.

If you want to stop the drug early, in the absence of liver cirrhosis and other special circumstances, almost all hepatitis B virus infected people and patients have a standard for stopping the drug, and it is not that you cannot stop the anti-hepatitis B drug once you take it, so don't be misled by people who don't know it well.

If you are worried about the side effects of taking medicine for a long time, aren't you worried about the possible adverse consequences of not taking medicine? You must know that the side effects of drugs are usually short-term, but once liver cirrhosis and liver cancer occur without taking medicine, it will affect the physical state for a long time and even shorten the life expectancy! Everyone should boldly establish confidence in the correct use of drugs, respond optimistically, avoid delaying the disease, and avoid tragedy.

Finally, I wish you all a speedy recovery!

References:[1]Chinese Society of Infectious Diseases, Chinese Society of Hepatology. Guidelines for the prevention and treatment of chronic hepatitis B (2022 edition), Chinese Journal of Hepatology, 2022, 30(12): 1309-1331. [2] Chinese Society of Infectious Diseases, Chinese Society of Hepatology. Guidelines for the prevention and treatment of chronic hepatitis B (2019 edition). Chinese Journal of Clinical Infectious Diseases,12(6):401-428. [3] Chinese Society of Infectious Diseases, Chinese Society of Hepatology. Expert consensus on clinical cure (functional cure) of chronic hepatitis B[J].Journal of Clinical Hepatobiliary Diseases, 2019(008):035. [4] Wang Shengsheng, after half a year of anti-hepatitis B, the surface antigen is still very high, what should I do? Teach you clinical healing!.Yimaitong Hepatology.2023-08-29: https://mp.weixin.qq.com/s/iJbue8oU5E4sfWkgRfWh4g[5]李兰娟,Ren Hong. Infectious Diseases(9th Edition).People's Medical Publishing House,2018-09 . [6] Li Lanjuan .Advanced Course in Infectious Diseases. Chinese Medical Electronic Audio-visual Press.:2021-05.

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