Chronic hepatitis B: Advances in treatment

Table 1 European Association for the Study of the Liver guidelines compared to other international guidelines

Criteria	EASL 2012[6]	AASLD 2009[7]	APASL 2012[8]
HBV DNA treatment threshold
HBeAg(+) (IU/mL)	2000	20000	20000
HBeAg(-) (IU/mL)	2000	2000-20000	2000
ALT treatment threshold	> ULN	> 2 × ULN	> 2 × ULN
Liver biopsy	Moderate to severe necroinflammation or fibrosis	Not applicable (consider in certain groups)

ULN: Upper limits of normal; HBeAg: Hepatitis B e antigen; ALT: Alanine aminotransferase; AASLD: American Association for the Study of Liver Diseases; APASL: Asia Pacific Association for the Study of the Liver; EASL: European Association for the Study of the Liver; HBV: Hepatitis B virus.

Table 2 Main advantages and disadvantages of pegylated interferon alpha and nucleos(t)ides analogues in chronic hepatitis B[6]

	Peg-IFN	Nucleos(t)ides analogues
Advantages	Finite duration (usually 48 wk)	Potent antiviral effect
	Higher rates of anti-HBe and anti-HBs seroconversion with 12 mo of therapy	Excellent tolerance, good safety
	Absence of resistance	Oral administration (once daily)
		No contraindication for treatment
Disadvantages	Moderate antiviral effect	Unknown (perhaps indefinite) duration of treatment
	Inferior tolerability	Rare HBsAg loss
	Risk of adverse events	Risk of viral resistance
	Subcutaneous injections	Unknown long-term safety
	Contraindications in specific patient subgroups

Peg-IFN: Pegylated interferon; HBsAg: Hepatitis B surface antigen.

Table 3 Cross-resistance data for the most frequent resistant hepatitis B virus variants[43]

HBV variant	LVD	LdT	ETV	ADV	TDF
Wild-type	S	S	S	S	S
M204I/V	R	R	I	S	S
L180M + M204V	R	R	I	S	S
A181T/V	R	R	S	R	I
N236T	S	S	S	R	I
A181T/V + N236T	R	R	S	R	R
L180M + M204V/I ± I179T ± T184G ± S202I/G ± M250I/V	R	R	R	S	S

HBV: Hepatitis B virus; LVD: Lamivudine; LdT: Telbivudine; ETV: Entecavir; ADV: Adefovir; TDF: Tenofovir; S: Sensitive; I: Intermediate/reduced susceptibility; R: Resistant.

Table 4 European Association for the Study of the Liver 2012 Guidelines recommendations in resistant patients[6]

Resistance	Action
LAM resistance	Switch to TDF (add ADV if TDF not available)
ADV resistance	If patient was NA naive before ADV: switch to ETV or TDF;
	ETV may be preferred in such patients with high viremia
	If patient had prior LAM resistance: switch to TDF and add a nucleoside analogue
LdT resistance	Switch to or add TDF (add ADV if TDF not available)
ETV resistance	Switch to or add TDF (add ADV if TDF not available)
TDF resistance	TDF resistance not detected to date: add a nucleoside analogue
	Switch to ETV if patient had no prior LAM resistance or add ETV in patients with LAM resistance

LAM: Lamivudine; ADV: Adefovir dipivoxil; TDF: Tenofovir; LdT: Telbivudine; ETV: Entecavir.