Drug Resistance in Hepatitis B Treatment: A Case Study

Antimicrobial resistance

My son is 24 years old and is studying for his master's degree in America.
He is HBe positive and HBe negative.

1.
He has been on lamivudine since January 2008.
2.
On December 29, 2008, his lab results showed AST 31, ALT 46, and HBV-DNA approximately 500 million copies/ml, which indicated the development of drug resistance, so he switched to lamivudine plus adefovir.
3.
On March 24, 2009, his lab results showed AST 44, ALT 110, and HBV-DNA approximately 450,000 copies/ml, and he continued lamivudine plus adefovir.
4.
On June 24, 2009, his lab results showed AST 29, ALT 78, and HBV-DNA approximately 150,000 copies/ml (60,000 IU), and he continued lamivudine plus adefovir.
However, the doctor has the following recommendations.
Could you please confirm if he has 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.

Frank, 50~59 year old female. Ask Date: 2009/07/02

Dr. Lin Minghui reply Gastroenterology and Hepatology

Hello, for patients with chronic hepatitis B who have been on Lamivudine for one year and show an increase in viral load, there is a possibility of developing Lamivudine resistance.
When Lamivudine resistance occurs, the current recommendation is to use Lamivudine in combination with Adefovir.
Adefovir can combat resistant viral strains, but its efficacy in reducing viral load is limited.
The primary benefit of combining Lamivudine with Adefovir is to reduce the likelihood of developing Adefovir resistance.
Based on clinical experience, the chance of developing Adefovir resistance with Lamivudine and Adefovir combination therapy is low within the first six months.
The viral load reduction with Lamivudine and Adefovir is not rapid and may require long-term treatment.
If resistance is suspected, polymerase chain reaction (PCR) can be used to detect amino acid sequences.
Generally, when there is an increase in viral load and liver enzyme levels, resistance should be suspected.
When the hepatitis B virus is active, long-term treatment is necessary, and regular monitoring of HBV-DNA is recommended.
If the treatment is ineffective, switching medications should be considered (in the U.S., there is a drug similar to Adefovir, Tenofovir, which has a stronger antiviral effect).
Wishing you good health, Dr.
Lin Ming-Hui, Taoyuan Hospital, Department of Health.

Reply Date: 2009/07/02

More Info

Understanding drug resistance in the treatment of Hepatitis B is crucial for managing the disease effectively, especially in cases where patients have been on antiviral therapy for extended periods. In your son's case, he has been on lamivudine since January 2008, and it appears that he has developed resistance to this medication.
Lamivudine is a nucleoside analog that is commonly used to treat chronic Hepatitis B virus (HBV) infection. While it can be effective in reducing viral load and improving liver function, one of the significant drawbacks of lamivudine is the development of drug resistance. This resistance typically occurs due to mutations in the HBV genome, which allow the virus to replicate despite the presence of the drug. In your son's case, the presence of HBV DNA at high levels (approximately 5 billion copies/ml initially) and the subsequent need to switch to a combination therapy of lamivudine and adefovir suggest that the virus has indeed developed resistance to lamivudine.

The combination of lamivudine and adefovir is a common strategy to combat this resistance. Adefovir is another antiviral medication that can be effective against lamivudine-resistant strains of HBV. However, it is important to note that adefovir has a slower onset of action and may not reduce viral load as quickly as lamivudine. The lab results you provided indicate that while the HBV DNA levels have decreased over time, they remain elevated, and liver enzymes (ALT) are still mildly elevated, which suggests ongoing liver inflammation.

The recommendation from Dr. Jensen to conduct a Hepatitis B Resistance panel is a prudent step. This test will help identify specific mutations in the HBV that confer resistance to the current antiviral medications. Understanding the resistance profile of the virus is essential for tailoring the treatment regimen. If resistance to both lamivudine and adefovir is confirmed, alternative antiviral therapies, such as tenofovir, may be considered. Tenofovir is a potent antiviral agent with a lower likelihood of resistance development compared to lamivudine and adefovir.

In summary, your son’s situation highlights the importance of monitoring for drug resistance in chronic Hepatitis B treatment. The presence of elevated HBV DNA and liver enzymes despite antiviral therapy suggests that resistance may be a factor. The next steps should include the Hepatitis B Resistance panel to guide further treatment decisions. If resistance is confirmed, switching to a more effective antiviral therapy like tenofovir could be beneficial. Regular follow-up and monitoring of liver function and viral load are critical in managing chronic Hepatitis B effectively.

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