Antiviral drug resistance increases hepatocellular carcinoma: A prospective decompensated cirrhosis cohort study

Table 1 Rescue therapy strategies in drug resistance patients

DR patients	Rescue therapyprescriptions	HBN DNA after rescue therapy 12 w
		< 500 copies/mL (n)	> 500 copies/mL (n)
LAM	+ ADV (n = 6)	4	2
(n = 11)	→ETV + ADV (n = 5)	3	2
ADV	+ ETV (n = 5)	4	1
(n = 12)	+ LAM (n = 7)	6	1
LDT	+ ADV (n = 6)	4	2
(n = 8)	→ETV + ADV (n = 2)	2	0
ETV	+ ADV (n = 2)	2	0
(n = 2)
LAM+ADV	→ ETV + ADV	1	1
(n = 2)	(n = 2)
LDT+ADV	→ ETV + ADV	1	0
(n = 1)	(n = 1)

+: Add-on; →: Altered drug. DR: Drug resistance; LAM: Lamivudine; ADV: Adefovir; LDT: Telbivudine; ETV: Entecavir; HBV: Hepatitis B virus.

Table 2 Clinical characterizations of the enrolled patients at baseline n (%)

	DR (n = 36)	CVR (n = 162)	Control (n = 39)
Gender n (male/female)	23/13	109/53	24/15
Age, mean ± SD (yr)	56.9 ± 14.6	58.4 ± 11.2	52.2 ± 10.8
Family history of HCC	6 (16.7)	21 (12.9)	7 (17.9)
Alcohol abuse	4 (11.1)	22 (13.5)	10 (10.2)
HBeAg positive	20 (55.6)	95 (58.6)	22 (56.4)
Child-Pugh Score, mean ± SD	9.0 ± 2.8	8.6 ± 2.3	7.9 ± 2.1
qHBV DNA (log), mean ± SD	5.4 ± 2.3	4.9 ± 2.5	4.9 ± 1.7
PTINR, mean ± SD	1.98 ± 0.87	2.24 ± 1.29	2.03 ± 1.16
BUN, mean ± SD (mmol/L)	8.3 ± 3.7	9.1 ± 4.2	8.0 ± 2.5
Cr, mean ± SD (μmol/L)	87.6 ± 39.3	77.4 ± 45.8	74.8 ± 20.4
Ascites	21 (58.3)	90 (55.6)	20 (51.3)
Encephalopathy	0 (0)	2 (1.2)	1 (2.6)
Variceal bleeding	17 (47.2)	85 (52.4)	18 (46.1)

SD: Standard deviation; HCC: Hepatocellular carcinoma; DR: Drug-resistant; CVR: Complete virologic response; BUN: Blood urea nitrogen; Cr: Creatinine; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen.

Table 3 Comparison of drug-resistant mutations between successful and failed rescue therapy n (%)

Mutations	Successful rescue therapy (n = 27)	Failed rescue therapy (n = 9)	P value
rtM204V			0.443
+	1 (3.7)	1 (11.1)
-	26 (96.3)	8 (88.9)
rtM204I			0.333
+	4 (14.8)	3 (33.3)
-	23 (85.2)	6 (66.7)
rtA181T			0.006
+	2 (7.4)	5 (55.6)
-	25 (92.6)	4 (44.4)
rtL180M			0.255
+	2 (7.4)	2 (22.2)
-	25 (92.6)	7 (77.8)
rtL80I			0.057
+	0 (0)	2 (22.2)
-	27 (100)	7 (77.8)
rtN236T			0.057
+	0 (0)	2 (22.2)
-	27 (100)	7 (77.8)
rtT184I			0.250
+	0 (0)	1 (11.1)
-	27 (100)	8 (88.9)
rtS202G			1.000
+	1 (3.7)	0 (0)
-	26 (96.3)	9 (100)
rtA181T + rtM204I			0.443
+	1 (3.7)	1 (11.1)
-	26 (96.3)	8 (88.9)
rtA181T + rtL180M			1.000
+	1 (3.7)	0 (0)
-	26 (96.3)	9 (100)
rtM204V + rtL180M			1.000
+	1 (3.7)	0 (0)
-	26 (96.3)	9 (100)
rtA181T + rtN236T			0.057
+	0 (0)	2 (22.2)
-	27 (100)	7 (77.8)
rtA181T + rtL80I			0.250
+	0 (0)	1 (11.1)
-	27 (100)	8 (88.9)
rtA181T + rtM204I + rtT184I			0.250
+	0 (0)	1 (11.1)
-	27 (100)	8 (88.9)
rtM204I + rtL180M + rtL80I			0.250
+	0 (0)	1 (11.1)
-	27 (100)	8 (88.9)

+: DR mutations positive; -: DR mutations negative; DR: Drug resistance.