Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance

Table 1 Baseline characteristics of lamivudine treated patients

	Lamivudine resistance (n = 111)	Lamivudine no resistance (n = 117)	P value
Male, n (%)	81 (73.0)	86 (73.5)	0.928
Chinese, n (%)	107 (96.4)	108 (92.3)	0.183
Age, yr [mean (95%CI)]	46.5 (44-49)	49.6 (47-52)	0.080
Cirrhosis, n (%)	36 (32.4)	35 (29.9)	0.682
Baseline bilirubin, μmol/L [mean (95% CI)]	19 (15-23)	30 (17-43)	0.124
Baseline albumin, g/L [mean (95% CI)]	36 (34-37)	37 (36-38)	0.326
Baseline ALT, U/L [mean (95% CI)]	175 (131-219)	269 (191-348)	0.038
Baseline AST, U/L [mean (95% CI)]	132 (88-176)	197 (132-262)	0.100
HBeAg positive, n (%)	77 (70.0)	42 (35.9)	< 0.001
Baseline log HBV DNA, IU/mL [mean (95% CI)]	6.5 (6.3-6.8)	5.7 (5.4-6.1)	< 0.001
Baseline abnormal ALT, n (%)	59 (53.15)	65 (55.55)	0.716

Patients with (n = 111) and without lamivudine resistance (n = 117). ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HBV: Hepatitis B virus; HBeAg: Hepatitis B "e" antigen.

Table 2 Multivariate analysis of baseline characteristics between patients with and without lamivudine resistance

	Adjusted P value	Adjusted OR (95% CI)
Male	0.842	1.080 (0.506-2.307)
Chinese	0.343	2.099 (0.454-9.707)
Mean age, yr	0.448	0.989 (0.960-1.018)
Cirrhosis	0.977	1.011 (0.479-2.133)
Baseline bilirubin, μmol/L	0.457	0.996 (0.984-1.007)
Baseline albumin, g/L	0.108	0.950 (0.893-1.011)
Baseline ALT, U/L	0.099	0.997 (0.994-1.000)
Baseline AST, U/L	0.521	1.001 (0.998-1.005)
HBeAg positive	0.005	2.857 (1.383-5.903)
Baseline log HBV DNA, IU/mL	0.014	1.415 (1.073-1.865)
Baseline abnormal ALT	0.923	0.959 (0.405-2.27)

Baseline hepatitis B virus (HBV) DNA and hepatitis B "e" antigen (HBeAg) status were independent predictors of lamivudine resistance. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 3 Diagnostic characteristics of various alanine aminotransferase cut-off levels for detecting lamivudine resistance

ALT (U/L)	Sensitivity (%)	Specificity (%)	Positive predictive value (%)	Negative predictive value (%)	Positive likelihood ratio	Negative likelihood ratio
> 42.5	61	60	60	61	1.53	0.65
> 70	39	81	67	58	2.05	0.75
> 30 (males)	85	28	53	66	1.18	0.56
> 19 (females)	90	7	50	40	0.96	1.40

The alanine aminotransferase (ALT) value of 42.5 U/L was found to be the best curve to fit receiver operating characteristics, while the ALT value of 70 U/L was the upper cutoff limit of the normal range in our laboratory, and ALT 30 U/L and 19 U/L were the cutoff values for males and females, respectively, based on the new Association for Study of Liver Disease guidelines.