HBV Resistance: A Case Study in Treatment Challenges

Q: HBV Resistance: A Case Study in Treatment Challenges

Hello Mr. <br>John： You may first check for HBV drug resistance (out-of-pocket, available only at a few medical centers). <br>If drug resistance is present, you may consider switching medications (though there is a risk of developing resistance again) or, depending on the situati

HBV-DNA

My son is 24 years old and studying for his master's degree in America.
He is HBe positive and has a negative HBe antigen.
He has been on lamivudine since January 2008.
On December 29, 2008, his lab results showed AST 31, ALT 46, and HBV-DNA approximately 500 million copies/ml, indicating the development of drug resistance, so he switched to lamivudine plus adefovir.
On March 24, 2009, his AST was 44, ALT was 110, and HBV-DNA was approximately 450,000 copies/ml, and he continued lamivudine plus adefovir.
On June 24, 2009, his AST was 29, ALT was 78, and HBV-DNA was approximately 150,000 copies/ml (60,000 IU), and he continued lamivudine plus adefovir.
However, the doctor has the following recommendations.
Has he developed drug resistance? Thank you very much.

We did receive your son’s lab reports.
There is still HBV DNA at 60,300 International Units with liver enzymes still mildly elevated, AST at 29 (normal) and ALT at 78 (mildly elevated).
Everything else was fine.
Dr.
Jensen would like to conduct a lab test called the Hepatitis B Resistance panel.
This will help determine if the current medications are effective or if a change in treatment is necessary.

John, 20~29 year old female. Ask Date: 2009/07/02

Dr. Chen Shidian reply Gastroenterology and Hepatology

Hello Mr.
John: You may first check for HBV drug resistance (out-of-pocket, available only at a few medical centers).
If drug resistance is present, you may consider switching medications (though there is a risk of developing resistance again) or, depending on the situation, switching to interferon therapy.
Changhua Hospital is concerned about your health.
Best regards, Chen Shidian.

Reply Date: 2009/07/02

More Info

Understanding hepatitis B virus (HBV) resistance is crucial for managing chronic HBV infections effectively. In the case of your son, who has been on lamivudine since January 2008, the situation indicates a potential development of drug resistance. Lamivudine is a nucleoside analogue that is commonly used to treat chronic HBV infections, but it is known for its propensity to induce resistance over time, particularly in patients who have high baseline viral loads.

From the lab results provided, it appears that your son initially had a high HBV DNA level of approximately 500 million copies/ml, which is significantly elevated. After starting treatment with lamivudine, there was a noticeable decrease in HBV DNA levels, but the presence of elevated liver enzymes (ALT and AST) suggests ongoing liver inflammation. The fact that the HBV DNA levels are still detectable at 60,300 International Units, along with mildly elevated ALT levels, raises concerns about the effectiveness of the current treatment regimen.

The development of resistance to lamivudine is characterized by an increase in HBV DNA levels despite ongoing therapy. In your son's case, the combination of lamivudine and adefovir was initiated due to the suspicion of lamivudine resistance. Adefovir is another antiviral medication that can be used to combat HBV, particularly in cases where resistance to lamivudine is suspected. However, it is important to note that adefovir also has a risk of developing resistance, albeit at a slower rate compared to lamivudine.

To determine if your son has indeed developed resistance, Dr. Jensen's recommendation to conduct a Hepatitis B Resistance panel is a prudent step. This test can identify specific mutations in the HBV genome that confer resistance to the antiviral medications being used. If resistance is confirmed, it may be necessary to switch to a different antiviral agent, such as tenofovir, which has a higher barrier to resistance and is generally more effective in suppressing HBV replication.

In addition to the resistance testing, it is essential to monitor liver function closely. Elevated liver enzymes can indicate ongoing liver damage, and if they continue to rise, further evaluation may be warranted. In some cases, if antiviral therapy fails to control the virus and liver function deteriorates, more aggressive interventions, such as interferon therapy or even liver transplantation, may be considered.

In summary, your son's situation highlights the complexities of managing chronic HBV infections, particularly in the context of developing drug resistance. Regular monitoring of HBV DNA levels, liver enzymes, and resistance testing are critical components of effective management. If resistance is confirmed, transitioning to a more effective antiviral regimen will be essential to control the infection and protect liver health. It is also important to maintain open communication with healthcare providers to ensure that any changes in treatment are made promptly and effectively.

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