Korean J Gastroenterol.  2009 May;53(5):305-310. 10.4166/kjg.2009.53.5.305.

Antiviral Efficacy of Lamivudine/Adefovir Combination Therapy in Chronic Hepatitis B Patients with Resistance to Lamivudine and Adefovir Consecutively

• Suh HJ
• Park MK
• Lee HI
• Gwak GY
• Koh KC
• Paik SW
• Yoo BC
• Lee JH

• KMID: 1767689
• DOI: http://doi.org/10.4166/kjg.2009.53.5.305

Abstract

BACKGROUND/AIMS: The aim of this study was to elucidate the antiviral efficacy of lamivudine (LMV)-adefovir (ADV) combination therapy in chronic hepatitis B patients who showed resistance to LMV and ADV consecutively.
METHODS
A retrospective review was performed in eighteen patients with chronic hepatitis B who developed virologic breakthroughs during LMV-ADV sequential mono-therapy and treated with LMV-ADV combination therapy.
RESULTS
The median duration of follow up was 17 months (range, 6-27) after the start of LMV-ADV combination therapy. Mean HBV DNA level in log10 IU/mL was 6.08+/-0.95, 4.05+/-1.66, 3.17+/-1.58, 3.18+/-2.16, and 2.35+/-1.52 at 0, 3, 6, 12, and 24 months, respectively. Sixteen patients (88.9%) showed HBV DNA reduction below detection limit (<20,000 IU/mL). HBeAg seroconversion was observed in one patient (7.1%) after 8 months of combination therapy. Virologic breakthrough occurred in only one patient after 21 months of combination therapy. Viral rebound occurred in two patients at 12 months and 14 months of combination therapy. Normalization of serum ALT was achieved in twelve patients (66.7%). Primary non-response was observed in two cases (11.1%).
CONCLUSIONS
LMV-ADV combination treatment was effective in 88.9% of patients with resistance to LMV and ADV in a short-term follow up. It may be applied as a bridge therapy until another effective antiviral regimen becomes available.

Keyword

Hepatits B, Chronic; Drug therapy, Combination; Lamivudine; Adefovir

MeSH Terms

Adenine/*analogs & derivatives/therapeutic use
Adult
Antiviral Agents/*therapeutic use
DNA, Viral/analysis
Drug Resistance, Viral
Drug Therapy, Combination
Female
Genotype
Hepatitis B, Chronic/*drug therapy
Humans
Lamivudine/*therapeutic use
Male
Middle Aged
Phosphonic Acids/*therapeutic use
Time Factors

Figure

• 

  Fig. 1. A flow chart illustrating the outcome of Lamivudine-Adefovir combination therapy in HBV infected patients with sequential resistance.∗ Chronic hepatitis B, fall of HBV DNA below 20,000 IU/mL and normal alanine aminotransferase levels after 3 months of entecavir therapy. † Compensated liver cirrhosis, 5 log10 IU/mL of HBV DNA and mildly elevated alanine aminotransferase levels but no compensation during LMV/ADV combination therapy for 18 months. ADV, adefovir; LMV, lamivudine.

• 

  Fig. 2. Mean log changes in serum HBV DNA levels during Lamivudine-Adefovir combination therapy. HBV DNA declined rapidly at initial 3 months of combination therapy then slowly decreased throughout the observation period.

• 

  Fig. 3. Mean ALT changes in serum HBV DNA levels during Lamivudine-Adefovir combination therapy. ALT declined rapidly at initial 3 months of treamemt and gradually declined throughout the observation period.

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