Doctor, can I stop taking my hepatitis B antiviral treatment?

This is the 4722nd article of Da Yi Xiao Hu

When Dr. Fang is on outpatient duty, one of the most common questions patients ask is: Doctor, can I stop taking my hepatitis B antiviral treatment? Will my disease relapse after I stop taking it? Will my disease get worse after a relapse?

This is the most common concern of patients before taking antiviral drugs, especially after the release of the new version of the chronic hepatitis B prevention and treatment guidelines, the indications for antiviral treatment have been relaxed. According to the guidelines, more and more patients have met the indications for antiviral treatment, but when they hear that antiviral treatment has no fixed course and requires long-term medication, most patients find it difficult to accept psychologically, thinking that long-term treatment is equivalent to life imprisonment or like having an incurable disease. On the other hand, patients are also worried that if they stop taking the medication, the disease will relapse and there will be serious consequences.

Therefore, before patients receive antiviral treatment, doctors need to patiently and carefully explain the situation to patients, so that they know why long-term treatment is needed, the possible harms of not receiving treatment, when they can stop taking the medication, and how to manage the medication scientifically after stopping it, so that patients can make the transition from resisting treatment at the beginning to being willing to accept treatment.

At present, antiviral treatment for hepatitis B is still a long-term process. Once the medication is taken, it is not recommended to stop the medication at will. If you need to stop the medication, you must do so under the guidance of a hepatologist. The guidance of hepatologists emphasizes that medication can only be stopped if certain standards are met. On the other hand, it emphasizes scientific management after medication is stopped. After the patient stops the medication, regular checkups are guided so that recurrence can be discovered in time and timely treatment can be given if necessary to avoid serious adverse consequences.

The "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition)" formulated by the Chinese Medical Association's Hepatology Branch and the Chinese Medical Association's Infectious Diseases Branch in 2022 provides recommendations on the course of antiviral treatment. The guidelines suggest that most patients require long-term oral antiviral drug treatment. Let's take a look at what the new version of the guidelines says about the course of antiviral treatment.

What kind of drug treatment should patients with “big three positive” choose? What is the course of treatment?

Recommendation No. 13 of the Guidelines states that patients with chronic hepatitis B who are positive for “big three positives” are recommended to receive oral antiviral treatment first (entecavir, tenofovir fumarate, tenofovir alafenamide fumarate or tenofovir alafenamide treatment (A1 level recommendation)). Most patients require long-term medication, and it is best to stop the medication until the hepatitis B surface antigen disappears. If you want to stop the medication for various reasons, it is recommended that after one year of treatment, the hepatitis B virus replication level is lower than the detection limit, alanine aminotransferase returns to normal, and the “big three positives” are converted to “small three positives”, and consolidation treatment is continued for at least 3 years (recheck once every 6 months) and remains unchanged, and the surface antigen is <100 IU/ml, you can try to stop the medication, but you should be closely monitored after stopping the medication, and extending the course of treatment can reduce recurrence (Note: A1 level represents the highest level of evidence recommendation).

However, for most patients with "big three positives", years of treatment may not necessarily meet the above standards, and only a very small number of patients can meet the above-mentioned drug discontinuation criteria. Therefore, for most patients, antiviral treatment requires long-term treatment.

Recommendation 14 states that patients with "big three positive" can also be treated with pegylated interferon. At 24 weeks of treatment, if the HBV DNA level decreases less than 100 times and the surface antigen quantification is still greater than 2×104IU/ml, it is recommended to stop interferon treatment and switch to oral antiviral drug treatment.

This recommendation is that patients with "big three positive" can use interferon for initial treatment, and a small number of patients may achieve limited treatment with interferon. However, if the treatment is not effective after one year, it is recommended to stop using interferon and use oral antiviral drugs instead.

What kind of drug treatment should patients with “small three positive” choose? What is the course of treatment?

Recommendation 15 states that oral antiviral drugs (entecavir, tenofovir fumarate, tenofovir alafenamide fumarate or tenofovir alafenamide (A1 level recommendation) are the first choice for patients with "small three positive" hepatitis B virus. It is recommended to treat until the surface antigen disappears and/or the surface antibody is positive, and the hepatitis B virus DNA is undetectable. If the hepatitis B virus DNA is still undetectable after 6 months of consolidation treatment, the drug can be discontinued for follow-up.

In this recommendation, patients with "small three positive" should be treated until the surface antigen turns negative before stopping the drug. However, for most patients, it may not be possible to achieve the goal of "small three positive" surface antigen turning negative in a lifetime. Therefore, for most patients, long-term antiviral treatment is required. Studies have found that about 50-60% of patients with "small three positive" will experience virological relapse one year after stopping the drug. The longer the antiviral treatment time, the lower the surface antigen level before treatment and when stopping the drug, and the younger the age of the patient, the lower the chance of relapse after stopping the drug (Gut, 2022, 71(8): 1629-1641; International Journal of Infectious Diseases 86 (2019) 201–207).

Recommendation 16 states that patients with "small three positive" can also be treated with pegylated interferon. After 12 weeks of treatment, if the hepatitis B virus DNA decreases less than 100 times, or the surface antigen quantitative decreases less than 10 times, it is recommended to stop interferon treatment and switch to oral drug treatment.

In this recommendation, patients with "small three positive" can also start with interferon treatment, but if the treatment is not effective after one year, it is recommended to switch to oral drug treatment.

Which patients are the preferred group to actively pursue clinical cure as recommended by the guidelines? What is the course of treatment?

Recommendation 17 states: In some eligible patients, if the HBV DNA quantification is below the detection limit, the e antigen turns negative, and the surface antigen is <1500 IU/ml after oral antiviral treatment, the addition of pegylated interferon treatment can be considered in combination with the patient's wishes to achieve clinical cure. After 24 weeks of treatment, if the surface antigen is <200 IU/ml or decreases by >10 times, it is recommended to continue oral antiviral drugs combined with pegylated interferon treatment for 48 to 96 weeks; after 24 weeks of treatment, if the surface antigen is still ≥200 IU/ml, interferon can be discontinued and oral antiviral treatment can be continued.

What medications are used for patients with cirrhosis? What is the course of treatment?

Recommendation 18 states: For patients with compensated hepatitis B cirrhosis, oral antiviral drugs are recommended for long-term antiviral treatment; if pegylated interferon is used for treatment, related adverse reactions need to be closely monitored (A1 level recommendation).

Recommendation 19 states: For patients with decompensated hepatitis B cirrhosis, long-term treatment with oral antiviral drugs is recommended, and pegylated interferon treatment is contraindicated (A1 level recommendation).

Will patients with active liver disease and cirrhosis relapse after stopping antiviral treatment? Are there risks after relapse?

The above are the guidelines' opinions on the course and discontinuation of hepatitis B antiviral treatment. They are mainly aimed at people with active liver disease and cirrhosis, that is, the liver disease is in an active state before treatment. The active state means that the patient's liver function is abnormal, or although the liver function is normal, other tests indicate that the liver disease is active. More than 60% of these people will have a virological relapse one year after discontinuation of medication, and some patients may experience clinical relapse after virological relapse. Clinical relapse refers to the occurrence of liver function damage, or even severe liver decompensation or liver failure, so it is not recommended to stop the drug at will. Patients with cirrhosis will also experience a relapse of the disease after discontinuation of medication, and the risk of adverse consequences is very high, so long-term treatment is required.

Can patients who do not have obvious liver damage before treatment stop taking the drug? What is the risk of relapse after stopping the drug? Will the relapse cause serious consequences?

Some of the patients who are included in the expanded antiviral treatment in the new guidelines may not have evidence of active liver damage before treatment. For example, the new guidelines stipulate that antiviral treatment is recommended for people over 30 years old as long as viral replication is detected, regardless of the viral level or transaminase level. Although the virus may be actively replicating in these people, the transaminase level is normal, and other tests do not indicate clear evidence of liver damage. There is currently no evidence-based medicine to determine what the results will be if the antiviral treatment is discontinued after several years. However, based on personal clinical experience, these patients with relatively mild liver damage at baseline will not necessarily suffer from serious consequences such as liver decompensation and liver failure even if there is a virological relapse after discontinuation of the drug. However, some patients with occult progressive liver lesions may continue to occultly progress due to virological relapse.

In general, the fundamental treatment measure for chronic hepatitis B is antiviral treatment, which is a long-term process. The purpose of antiviral treatment is to stop the progression of the disease and prevent the occurrence of adverse prognoses such as cirrhosis, liver failure and liver cancer. Because current antiviral drugs, especially oral antiviral drugs, are difficult to guarantee no recurrence after discontinuation of medication, long-term treatment is required. Now the first-line antiviral drugs have a more definite effect, relatively few side effects, and are relatively cheap. They only need to be taken once a day, which is convenient for long-term use and has better feasibility for long-term treatment. If the virus is well controlled and the disease is stable and does not progress, the patient's quality of life and life expectancy will not be affected like other people.

I hope that all patients will listen to the doctor's advice, combine their actual situation, and start antiviral treatment in time when needed. It is recommended not to stop the medication on your own during treatment. If you have a strong desire to stop the medication, you can stop the medication under the guidance of a specialist. After stopping the medication, scientific management can be carried out. Even if virological recurrence occurs, it can be discovered in time, and it is safe to restart the treatment if necessary.

Author: Shenzhen Third People's Hospital

Wang Fang, Department of Hepatitis and Cirrhosis