Update on rescue therapies in patients with lamivudine-resistant chronic hepatitis B

Figures & data

Table 1 Mutations associated with resistance to antiviral medications

Drug name	Known mutations
Lamivudine	rtM204V/I/S, rtL80V, rtV174 L, rtL180M
Telbivudine	rtM204I, rtL229W/V
Entecavir	rtM204V/I + rtL180M ± rtL169T ± rtS184G ± rtS202G/I ± rtM250V; rtT184A/G/I/S
Lamivudine and entecavir	V173L, L180M, M204I, M204V
Adefovir	rtA181T/V, rtN236T, rtI244V
Tenofovir	None confirmed

Note: data acquired from references^12,60–63.

Table 2 Summary of rescue therapies in LAM resistant CHB

Rescue therapy regimen	Efficacy	Concerns	Clinical application
Switch to ADV monotherapya	Able to achieve virologic and biochemical response in a significant number of LAM resistant patients^Citation43^–^Citation45	ADV resistance with virologic breakthrough occurred in >20% in multiple studies^Citation46	Not recommended
Switch to ETV monotherapy	Better than ADV monotherapy in reduction of HBV DNA and normalization of ALT^Citation8,Citation46^–^Citation48	Virologic breakthrough due to development of ETV resistance (8%–10%);^Citation52,Citation53 not recommended by treatment guidelines^Citation3,Citation35	Not recommended
Add ADV to LAM (ADV plus LAM)b	Similar to or greater efficacy compared to ETV monotherapy; significantly less multidrug resistance and virologic breakthrough compared to ADV and ETV monotherapy; recommended by the AASLD and EASL for LAM-resistant CHB (second line by the latter)^Citation8,Citation47^–^Citation50	Requires access to and long-term compliance with two medications	Recommended, if TDF not available
Switch to ADV and ETV (ADV plus ETV)	Highest rates of virologic and biochemical response with almost no resistance^Citation54,Citation55	Fewest number of patients tested; expensive	High cost, may not be practical
Switch to TDF monotherapy	Switching to TDF from ADV in LAM resistant CHB led to further improvement in HBV DNA reduction;^Citation10,Citation50^–^Citation52 recommended by the AASLD and EASL for LAM-resistant CHB (first line by the latter); similar price to ADV^Citation3,Citation35	Newest medication, may not be as readily accessible globally; ADV resistance reduces efficacy^Citation57	Highly recommended

Notes:

a “Switch” implies stopping Lamivudine;

b “add on” implies continuing Lamivudine.

Abbreviations: AASLD, American Association for the Study of Liver Diseases; ADV, Adefovir; ALT, alanine aminotransferase; CHB, chronic hepatitis B; EASL, European Association for the Study of the Liver; ETV, Entecavir; HBV, hepatitis B virus; LAM, Lamivudine; TDF, Tenofovir.

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