%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Yi-Jie Huang, Chi-Sen Chang, Yen-Chun Peng, Hong-Zen Yeh, Sheng-Shun Yang
On-treatment HBV DNA dynamics predict virological breakthrough in entecavir-treated HBeAg-positive chronic hepatitis B
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 12 0 R/Contents 13 0 R/TrimBox[0 0 612 792]>>
endobj
12 0 obj
[14 0 R 15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R]
endobj
14 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref001)>>
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref003)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref004)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref005)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref004)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref006)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref007)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref004)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref008)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref005)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref009)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref010)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref005)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref009)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref011)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref012)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref013)>>
endobj
31 0 obj
<>/Border[0 0 0]/A 32 0 R>>
endobj
32 0 obj
<>
endobj
13 0 obj
[33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R]
endobj
33 0 obj
<>stream
q
0.83 0.64 0.02 0 k
333.6378 635.9811 m
338.4 635.9811 l
h
f*
343.5591 635.9811 m
348.3213 635.9811 l
h
f*
479.8488 610.0157 m
484.611 610.0157 l
h
f*
489.0898 610.0157 m
493.852 610.0157 l
h
f*
223.8236 583.9937 m
228.5858 583.9937 l
h
f*
233.0646 583.9937 m
237.8268 583.9937 l
h
f*
242.2488 583.9937 m
247.011 583.9937 l
h
f*
504.2268 571.011 m
508.989 571.011 l
h
f*
513.4677 571.011 m
518.2299 571.011 l
h
f*
285.7323 532.0063 m
290.4945 532.0063 l
h
f*
294.9732 532.0063 m
299.7354 532.0063 l
h
f*
304.1575 532.0063 m
313.6819 532.0063 l
h
f*
411.874 493.0016 m
416.6362 493.0016 l
h
f*
421.0583 493.0016 m
425.8205 493.0016 l
h
f*
430.2992 493.0016 m
439.7669 493.0016 l
h
f*
421.3984 466.9795 m
430.9228 466.9795 l
h
f*
435.3449 466.9795 m
444.8693 466.9795 l
h
f*
0 g
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 706.0535 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 689.1023 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(standard)Tj
3.7247 0 Td
(treatment)Tj
4.1329 0 Td
(strategies)Tj
3.9231 0 Td
(for)Tj
1.389 0 Td
(chronic)Tj
3.2881 0 Td
(hepatitis)Tj
3.6114 0 Td
(B)Tj
0.805 0 Td
(\(CHB\))Tj
2.9083 0 Td
(include)Tj
3.1861 0 Td
(lamivudine,)Tj
4.9606 0 Td
(adefovir,)Tj
-33.7093 -1.3039 Td
(entecavir)Tj
3.8607 0 Td
(\(ETV\),)Tj
2.9934 0 Td
(telbivudine,)Tj
4.9322 0 Td
(tenofovir,)Tj
4.1102 0 Td
(and)Tj
1.7235 0 Td
(pegylated)Tj
4.0082 0 Td
(interferon.)Tj
4.49 0 Td
(Recent)Tj
2.9537 0 Td
(studies)Tj
2.982 0 Td
(demonstrated)Tj
-32.0539 -1.2982 Td
(that)Tj
1.7744 0 Td
(antiviral)Tj
3.5433 0 Td
(therapy)Tj
3.2485 0 Td
(could)Tj
2.4491 0 Td
(ameliorate)Tj
4.4447 0 Td
(liver)Tj
1.9842 0 Td
(injury,)Tj
2.8744 0 Td
(progression)Tj
4.9209 0 Td
(of)Tj
1.0148 0 Td
(cirrhosis,)Tj
3.9004 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4684 0 Td
(develop-)Tj
-33.3522 -1.2983 Td
(ment)Tj
2.3073 0 Td
(of)Tj
1.0148 0 Td
(HCC,)Tj
2.5399 0 Td
(and)Tj
1.7291 0 Td
(could)Tj
2.4548 0 Td
(also)Tj
1.7688 0 Td
(reduce)Tj
2.914 0 Td
(hepatocellular)Tj
5.8506 0 Td
(carcinoma)Tj
4.4447 0 Td
(\(HCC\))Tj
2.9934 0 Td
(recurrence)Tj
4.5297 0 Td
(among)Tj
-32.5471 -1.3039 Td
(patients)Tj
3.3675 0 Td
(with)Tj
1.9956 0 Td
(HBV-related)Tj
5.3404 0 Td
(HCC.[)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(])Tj
-9.5073 -1.2983 Td
(Virological)Tj
4.6488 0 Td
(breakthrough)Tj
5.6805 0 Td
(\(VBT\))Tj
2.7837 0 Td
(could)Tj
2.4547 0 Td
(be)Tj
1.1509 0 Td
(the)Tj
1.4683 0 Td
(most)Tj
2.2054 0 Td
(important)Tj
4.2803 0 Td
(clinical)Tj
3.0784 0 Td
(hint)Tj
1.8595 0 Td
(for)Tj
1.389 0 Td
(long-term)Tj
-32.1957 -1.2982 Td
(nucleos\(t\)ide)Tj
5.4538 0 Td
(\(NUC\)-treated)Tj
6.1625 0 Td
(hepatitis)Tj
3.6169 0 Td
(B)Tj
0.7994 0 Td
(patients)Tj
3.3675 0 Td
(with)Tj
1.9956 0 Td
(drug)Tj
2.1147 0 Td
(resistance.[)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
5.3971 0 Td
(5)Tj
0 g
(])Tj
1.0318 0 Td
(The)Tj
1.7858 0 Td
(most)Tj
2.2053 0 Td
(common)Tj
-33.9304 -1.304 Td
(causes)Tj
2.7495 0 Td
(of)Tj
1.0148 0 Td
(VBT)Tj
2.1033 0 Td
(in)Tj
1.0375 0 Td
(NUC-treated)Tj
5.4822 0 Td
(CHB)Tj
2.2337 0 Td
(patients)Tj
3.3675 0 Td
(are)Tj
1.4457 0 Td
(genotypic)Tj
4.1272 0 Td
(resistance)Tj
4.1329 0 Td
(and)Tj
1.7291 0 Td
(medication)Tj
4.7338 0 Td
(adher-)Tj
-34.1572 -1.2982 Td
(ence.[)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
3.3051 0 Td
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
0.9184 0 Td
(7)Tj
0 g
(])Tj
1.0375 0 Td
(Once)Tj
2.3641 0 Td
(resistance)Tj
4.1272 0 Td
(confirmed,)Tj
4.6261 0 Td
(the)Tj
1.4684 0 Td
(treatment)Tj
4.1329 0 Td
(strategy)Tj
3.3278 0 Td
(is)Tj
0.8504 0 Td
(shifted)Tj
2.914 0 Td
(to)Tj
1.0205 0 Td
(high)Tj
2.0125 0 Td
(potency)Tj
-32.1049 -1.2983 Td
(antiviral)Tj
3.5376 0 Td
(agent)Tj
2.3924 0 Td
(without)Tj
3.3278 0 Td
(cross-resistance)Tj
6.5083 0 Td
(should)Tj
2.9197 0 Td
(be)Tj
1.1452 0 Td
(added)Tj
2.6646 0 Td
(as)Tj
1.0148 0 Td
(soon)Tj
2.1429 0 Td
(as)Tj
1.0148 0 Td
(possible.[)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
4.6772 0 Td
(8)Tj
0 g
(])Tj
1.0318 0 Td
(Thus,)Tj
2.4774 0 Td
(the)Tj
-34.8545 -1.2983 Td
(standard)Tj
3.719 0 Td
(of)Tj
1.0148 0 Td
(care)Tj
1.8765 0 Td
(involves)Tj
3.4809 0 Td
(on-treatment)Tj
5.5389 0 Td
(monitoring)Tj
4.8245 0 Td
(of)Tj
1.0148 0 Td
(data,)Tj
2.1373 0 Td
(including)Tj
4.0422 0 Td
(hepatic)Tj
3.1124 0 Td
(panel,)Tj
2.6136 0 Td
(hepatitis)Tj
-33.3749 -1.3039 Td
(markers)Tj
3.4979 0 Td
(and)Tj
1.7291 0 Td
(serum)Tj
2.7212 0 Td
(HBV)Tj
2.2621 0 Td
(DNA,)Tj
2.6022 0 Td
(which)Tj
2.6532 0 Td
(were)Tj
2.1203 0 Td
(also)Tj
1.7688 0 Td
(recommended)Tj
6.0377 0 Td
(to)Tj
1.0205 0 Td
(be)Tj
1.1509 0 Td
(used)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(follow-up)Tj
4.0932 0 Td
(the)Tj
-34.7355 -1.2982 Td
(treatment)Tj
4.1328 0 Td
(responses.[)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
5.3632 0 Td
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
0.9184 0 Td
(10)Tj
0 g
(]Now,)Tj
3.668 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3754 0 Td
(is)Tj
0.8448 0 Td
(the)Tj
1.474 0 Td
(standard)Tj
3.719 0 Td
(and)Tj
1.7291 0 Td
(important)Tj
4.286 0 Td
(tools)Tj
2.1373 0 Td
(for)Tj
1.3889 0 Td
(follow-)Tj
-34.2989 -1.2983 Td
(up)Tj
1.2642 0 Td
(during)Tj
2.9253 0 Td
(NUC)Tj
2.3584 0 Td
(treatment.)Tj
4.3597 0 Td
(On-treatment)Tj
5.7826 0 Td
(HBV)Tj
2.2621 0 Td
(DNA)Tj
2.3754 0 Td
(monitoring)Tj
4.8189 0 Td
(is)Tj
0.8503 0 Td
(associated)Tj
4.2577 0 Td
(with)Tj
1.9955 0 Td
(the)Tj
1.4684 0 Td
(effect)Tj
-34.7185 -1.3039 Td
(of)Tj
1.0147 0 Td
(treatment,)Tj
4.3597 0 Td
(including)Tj
4.0422 0 Td
(HBsAg)Tj
3.0784 0 Td
(and)Tj
1.7291 0 Td
(HBeAg)Tj
3.1408 0 Td
(seroclearance/seroconver)Tj
10.1139 0 Td
(sion,)Tj
2.126 0 Td
(drug)Tj
2.1146 0 Td
(resistance,)Tj
4.354 0 Td
(and)Tj
-36.0734 -1.2983 Td
(determination)Tj
5.9527 0 Td
(of)Tj
1.0148 0 Td
(cessation)Tj
3.8437 0 Td
(long-term)Tj
4.252 0 Td
(NA)Tj
1.6384 0 Td
(treatment.[)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
5.4028 0 Td
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
0.9241 0 Td
(11)Tj
0 g
(])Tj
-21.8323 -1.2982 Td
(ETV)Tj
2.0976 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.6519 0 Td
(high-potency)Tj
5.5332 0 Td
(NUC)Tj
2.3528 0 Td
(capable)Tj
3.2088 0 Td
(of)Tj
1.0148 0 Td
(achieving)Tj
4.0308 0 Td
(viral)Tj
1.9899 0 Td
(suppression)Tj
4.9833 0 Td
(and)Tj
1.7291 0 Td
(resistance)Tj
4.1329 0 Td
(to)Tj
1.0261 0 Td
(ETV)Tj
2.0977 0 Td
(is)Tj
-36.8955 -1.304 Td
(rarely)Tj
2.5171 0 Td
(observed)Tj
3.7984 0 Td
(in)Tj
1.0375 0 Td
(long-term)Tj
4.2462 0 Td
(treatment-na)Tj
/F10 1 Tf
[()]TJ
/F6 1 Tf
(ve)Tj
6.6047 0 Td
(patients.)Tj
3.5943 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(13)Tj
0 g
(]However,)Tj
5.3688 0 Td
(the)Tj
1.474 0 Td
(association)Tj
4.6261 0 Td
(with)Tj
-35.0019 -1.2982 Td
(dynamic)Tj
3.6963 0 Td
(change)Tj
3.0387 0 Td
(of)Tj
1.0148 0 Td
(on-treatment)Tj
5.5446 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3754 0 Td
(and)Tj
1.7291 0 Td
(VBT)Tj
2.109 0 Td
(in)Tj
1.0318 0 Td
(ETV-treated)Tj
5.2214 0 Td
(CHB)Tj
2.2337 0 Td
(patients)Tj
3.3675 0 Td
(has)Tj
1.542 0 Td
(not)Tj
-35.1663 -1.2983 Td
(been)Tj
2.1203 0 Td
(clearly)Tj
2.8176 0 Td
(elucidated.)Tj
4.5467 0 Td
(Thus,)Tj
2.4718 0 Td
(the)Tj
1.474 0 Td
(aim)Tj
1.7405 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
1.6724 0 Td
(study)Tj
2.3868 0 Td
(was)Tj
1.7007 0 Td
(to)Tj
1.0262 0 Td
(determine)Tj
4.3256 0 Td
(the)Tj
1.4684 0 Td
(factors)Tj
2.9026 0 Td
(associated)Tj
-31.6684 -1.2983 Td
(with)Tj
1.9955 0 Td
(VBT)Tj
2.1033 0 Td
(in)Tj
1.0375 0 Td
(ETV-treated)Tj
5.2214 0 Td
(CHB.)Tj
2.4604 0 Td
(We)Tj
1.6044 0 Td
(aimed)Tj
2.6929 0 Td
(to)Tj
1.0262 0 Td
(determine)Tj
4.3256 0 Td
(the)Tj
1.4683 0 Td
(association)Tj
4.6262 0 Td
(of)Tj
1.0148 0 Td
(on-treatment)Tj
5.5445 0 Td
(HBV)Tj
-35.121 -1.3039 Td
(DNA)Tj
2.3754 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(occurrence)Tj
4.6658 0 Td
(of)Tj
1.0148 0 Td
(VBT)Tj
2.1033 0 Td
(during)Tj
2.931 0 Td
(ETV)Tj
2.092 0 Td
(treatment)Tj
4.1385 0 Td
(in)Tj
1.0375 0 Td
(HBeAg-positive)Tj
6.582 0 Td
(CHB)Tj
2.2337 0 Td
(patients.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 386.022 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F0 1 Tf
-6.4961 -1.4976 Td
(Patients)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 351.0425 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(We)Tj
1.61 0 Td
(conducted)Tj
4.4277 0 Td
(a)Tj
0.652 0 Td
(retrospective)Tj
5.3574 0 Td
(cohort)Tj
2.8573 0 Td
(study)Tj
2.3924 0 Td
(including)Tj
4.0366 0 Td
(consecutive)Tj
4.8812 0 Td
(naive)Tj
2.3471 0 Td
(adult)Tj
2.2563 0 Td
(patients)Tj
3.3676 0 Td
(with)Tj
-34.1856 -1.2982 Td
(CHB,)Tj
2.4547 0 Td
(who)Tj
1.9389 0 Td
(had)Tj
1.7121 0 Td
(received)Tj
3.532 0 Td
(NUC)Tj
2.3584 0 Td
(treatment)Tj
4.1329 0 Td
(and)Tj
1.7291 0 Td
(whose)Tj
2.7269 0 Td
(treatment)Tj
4.1329 0 Td
(protocol)Tj
3.6 0 Td
(was)Tj
1.6951 0 Td
(followed)Tj
3.651 0 Td
(up)Tj
1.2642 0 Td
(regu-)Tj
-34.9282 -1.3039 Td
(larly.)Tj
2.194 0 Td
(Between)Tj
3.6056 0 Td
(August)Tj
3.0841 0 Td
(2008)Tj
2.1203 0 Td
(and)Tj
1.7291 0 Td
(May)Tj
2.0012 0 Td
(2015,)Tj
2.3471 0 Td
(a)Tj
0.6577 0 Td
(total)Tj
2.0012 0 Td
(of)Tj
1.0148 0 Td
(162)Tj
1.6497 0 Td
(consecutive)Tj
4.8756 0 Td
(ETV-treated)Tj
5.2214 0 Td
(HBeAg-pos-)Tj
-32.5018 -1.2983 Td
(itive)Tj
1.9275 0 Td
(CHB)Tj
2.2337 0 Td
(patients)Tj
3.3675 0 Td
(\(95)Tj
1.5137 0 Td
(men)Tj
2.0069 0 Td
(and)Tj
1.7348 0 Td
(67)Tj
1.1679 0 Td
(women;)Tj
3.4299 0 Td
(mean)Tj
2.4434 0 Td
(age,)Tj
1.7688 0 Td
(43.1)Tj
/F10 1 Tf
[()]TJ
/F6 1 Tf
(13.4)Tj
4.0932 0 Td
(years\))Tj
2.6079 0 Td
(who)Tj
1.9389 0 Td
(were)Tj
2.1203 0 Td
(followed)Tj
3.651 0 Td
(up)Tj
-36.0054 -1.2983 Td
(for)Tj
1.3832 0 Td
(every)Tj
2.3471 0 Td
(1224)Tj
2.6419 0 Td
(weeks)Tj
2.6079 0 Td
(were)Tj
2.1259 0 Td
(included)Tj
3.7077 0 Td
(in)Tj
1.0375 0 Td
(this)Tj
1.6724 0 Td
(study.)Tj
2.6192 0 Td
(The)Tj
1.7802 0 Td
(patients')Tj
3.5829 0 Td
(demographics)Tj
5.8677 0 Td
(were)Tj
2.1203 0 Td
(regularly)Tj
-33.4939 -1.3039 Td
(recorded)Tj
3.7927 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(hepatitis)Tj
3.6113 0 Td
(B)Tj
0.7994 0 Td
(treatment)Tj
4.1385 0 Td
(protocol,)Tj
3.8211 0 Td
(composing)Tj
4.6375 0 Td
(underlying)Tj
4.5977 0 Td
(diseases)Tj
3.3789 0 Td
(including)Tj
4.0422 0 Td
(liver)Tj
-34.4917 -1.2982 Td
(cirrhosis,)Tj
3.9004 0 Td
(fatty)Tj
1.9956 0 Td
(liver,)Tj
2.2053 0 Td
(body)Tj
2.2167 0 Td
(weight,)Tj
3.1124 0 Td
(hepatitis)Tj
3.617 0 Td
(B)Tj
0.7994 0 Td
(e)Tj
0.6406 0 Td
(antigen)Tj
3.2031 0 Td
(\(HBeAg\),)Tj
4.0479 0 Td
(HBV)Tj
2.262 0 Td
(DNA,)Tj
2.6022 0 Td
(hepatic)Tj
3.1124 0 Td
(panel)Tj
-33.715 -1.2983 Td
(\(albumin)Tj
3.9117 0 Td
([Alb],)Tj
2.5625 0 Td
(alanine)Tj
3.1181 0 Td
(aminotransferase)Tj
7.1093 0 Td
([ALT],)Tj
2.9593 0 Td
(total)Tj
2.0069 0 Td
(bilirubin)Tj
3.7304 0 Td
(\(Bil-T\),)Tj
3.1805 0 Td
(and)Tj
1.7291 0 Td
(alkaline)Tj
3.3165 0 Td
(phospha-)Tj
-33.6243 -1.2983 Td
(tase)Tj
1.7347 0 Td
(\(ALP\),)Tj
2.9084 0 Td
(platelet)Tj
3.1067 0 Td
(count,)Tj
2.7496 0 Td
(prothrombin)Tj
5.4652 0 Td
(time)Tj
2.0239 0 Td
(\(PT\),)Tj
2.296 0 Td
(spleen)Tj
2.744 0 Td
(size,)Tj
1.9105 0 Td
(renal)Tj
2.2394 0 Td
(function)Tj
3.6283 0 Td
(test)Tj
1.6044 0 Td
(including)Tj
-32.4111 -1.3039 Td
(Creatinine)Tj
4.4617 0 Td
(Clearance)Tj
4.1895 0 Td
(Rate)Tj
1.9956 0 Td
(\(CCr\),)Tj
2.8233 0 Td
(and)Tj
1.7348 0 Td
(alpha)Tj
2.3754 0 Td
(fetoprotein)Tj
4.6715 0 Td
(\(AFP\).)Tj
2.897 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3754 0 Td
(and)Tj
1.7291 0 Td
(HBeAg)Tj
3.1408 0 Td
(were)Tj
-34.6561 -1.2983 Td
(routinely)Tj
3.8607 0 Td
(assessed)Tj
3.4753 0 Td
(every)Tj
2.347 0 Td
(36)Tj
1.6895 0 Td
(months)Tj
3.2825 0 Td
(at)Tj
0.9524 0 Td
(Taichung)Tj
4.0252 0 Td
(Veterans)Tj
3.7757 0 Td
(General)Tj
3.3789 0 Td
(Hospital.)Tj
-25.591 -1.2982 Td
(Patients)Tj
3.4129 0 Td
(were)Tj
2.1203 0 Td
(excluded)Tj
3.787 0 Td
(if)Tj
0.7767 0 Td
(they)Tj
1.9219 0 Td
(had)Tj
1.7121 0 Td
(previous)Tj
3.6453 0 Td
(antiviral)Tj
3.5433 0 Td
(treatment)Tj
4.1386 0 Td
(for)Tj
1.3833 0 Td
(hepatitis)Tj
3.617 0 Td
(B,)Tj
1.0204 0 Td
(HBeAg)Tj
3.1408 0 Td
(sero-)Tj
-35.4158 -1.3039 Td
(clearance)Tj
3.9458 0 Td
(within)Tj
2.8119 0 Td
(24)Tj
1.1735 0 Td
(weeks)Tj
2.6079 0 Td
(after)Tj
2.0353 0 Td
(ETV)Tj
2.0976 0 Td
(treatment,)Tj
4.3596 0 Td
(coinfection)Tj
4.7225 0 Td
(with)Tj
1.9956 0 Td
(hepatitis)Tj
3.617 0 Td
(C)Tj
0.8787 0 Td
(virus,)Tj
2.4321 0 Td
(hepatitis)Tj
3.6114 0 Td
(D)Tj
-36.2889 -1.2983 Td
(virus,)Tj
2.4264 0 Td
(or)Tj
1.0998 0 Td
(human)Tj
3.0784 0 Td
(immunodeficiency)Tj
7.7556 0 Td
(virus.)Tj
2.4264 0 Td
(The)Tj
1.7802 0 Td
(study)Tj
2.3924 0 Td
(was)Tj
1.6951 0 Td
(approved)Tj
3.9741 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4684 0 Td
(Institutional)Tj
5.159 0 Td
(Review)Tj
-34.4407 -1.2983 Td
(Board)Tj
2.6362 0 Td
(of)Tj
1.0148 0 Td
(our)Tj
1.627 0 Td
(institution)Tj
4.4107 0 Td
(\(VGHTC)Tj
4.0138 0 Td
(CE16037B\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 139.011 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Definition)Tj
4.3275 0 Td
(of)Tj
1.0441 0 Td
(virological)Tj
4.5969 0 Td
(breakthrough)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 122.0031 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(occurrence)Tj
4.6658 0 Td
(of)Tj
1.0148 0 Td
(VBT,)Tj
2.3301 0 Td
(defined)Tj
3.2258 0 Td
(as)Tj
1.0148 0 Td
(any)Tj
1.6554 0 Td
(increase)Tj
3.4752 0 Td
(in)Tj
1.0375 0 Td
(serum)Tj
2.7213 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3754 0 Td
(by)Tj
/F11 1 Tf
0 Tc
1.1849 0 Td
(>)Tj
/F6 1 Tf
-0.004 Tc
(1)Tj
1.4626 0 Td
(log10)Tj
2.3925 0 Td
(from)Tj
2.2053 0 Td
(nadir)Tj
-34.8035 -1.2982 Td
(or)Tj
1.0941 0 Td
(redetection)Tj
4.7338 0 Td
(of)Tj
1.0148 0 Td
(serum)Tj
2.727 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3754 0 Td
(at)Tj
0.9524 0 Td
(levels)Tj
2.3755 0 Td
(10-fold)Tj
3.0897 0 Td
(the)Tj
1.4683 0 Td
(lower)Tj
2.4548 0 Td
(limit)Tj
2.1147 0 Td
(of)Tj
1.0148 0 Td
(detection)Tj
3.9401 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(viral)Tj
-34.1005 -1.3039 Td
(load)Tj
1.9332 0 Td
(after)Tj
2.0352 0 Td
(HBV)Tj
2.2621 0 Td
(DNA)Tj
2.3754 0 Td
(was)Tj
1.7008 0 Td
(undetectable.)Tj
5.5275 0 Td
(Genotypic)Tj
4.3766 0 Td
(resistance)Tj
4.1273 0 Td
(\(GR\))Tj
2.2393 0 Td
(was)Tj
1.7008 0 Td
(defined)Tj
3.2258 0 Td
(as)Tj
1.0148 0 Td
(detection)Tj
3.9345 0 Td
(of)Tj
-36.4533 -1.2983 Td
(signature)Tj
3.9174 0 Td
(resistance)Tj
4.1272 0 Td
(mutation)Tj
3.9231 0 Td
(by)Tj
1.1793 0 Td
(direct)Tj
2.5341 0 Td
(sequencing.)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 380.5795 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(HBV)Tj
2.2535 0 Td
(DNA)Tj
2.3032 0 Td
(dynamics)Tj
4.3725 0 Td
(and)Tj
1.8567 0 Td
(virological)Tj
4.5709 0 Td
(breakthro)Tj
4.1457 0 Td
(ugh)Tj
1.8567 0 Td
(in)Tj
0.9779 0 Td
(CHB)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01740)Tj
4.089 0 Td
(46)Tj
0 g
2.0906 0 Td
(March)Tj
2.9622 0 Td
(28,)Tj
1.5874 0 Td
(2017)Tj
34.3562 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
34 0 obj
<>stream
endstream
endobj
35 0 obj
<>stream
endstream
endobj
36 0 obj
<>stream
endstream
endobj
37 0 obj
<>stream
endstream
endobj
38 0 obj
<>stream
endstream
endobj
39 0 obj
<>stream
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
BT
66.402 0 Td
(11)Tj
ET
Q
endstream
endobj
50 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 51 0 R/Contents 52 0 R/TrimBox[0 0 612 792]>>
endobj
51 0 obj
[53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R]
endobj
53 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.ref014)>>
endobj
54 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.t001)>>
endobj
55 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.s002)>>
endobj
56 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.s001)>>
endobj
57 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.g001)>>
endobj
58 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.t002)>>
endobj
59 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174046.t002)>>
endobj
60 0 obj
<>/Border[0 0 0]/A 61 0 R>>
endobj
61 0 obj
<>
endobj
52 0 obj
[62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R]
endobj
62 0 obj
<>stream
q
0.83 0.64 0.02 0 k
382.9039 560.4661 m
392.4283 560.4661 l
h
f*
274.3937 326.4378 m
303.5339 326.4378 l
h
f*
485.348 287.4331 m
519.3071 287.4331 l
h
f*
538.8094 287.4331 m
563.1307 287.4331 l
h
f*
376.0441 261.4677 m
395.6031 261.4677 l
h
f*
200.0126 133.9087 m
229.2094 133.9087 l
h
f*
203.4142 81.9213 m
232.5543 81.9213 l
h
f*
0 g
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 706.0535 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Laboratory)Tj
4.9417 0 Td
(methods)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 689.1023 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3754 0 Td
(was)Tj
1.7008 0 Td
(determined)Tj
4.8472 0 Td
(by)Tj
1.1849 0 Td
(real-time)Tj
3.8551 0 Td
(PCR)Tj
2.0636 0 Td
(assay)Tj
2.262 0 Td
(\(Roche)Tj
3.0614 0 Td
(CobasTaqMan)Tj
6.1228 0 Td
(HBV)Tj
2.262 0 Td
(Test\).)Tj
2.4775 0 Td
(HBsAg)Tj
-34.4747 -1.3039 Td
(and)Tj
1.7291 0 Td
(HBeAg)Tj
3.1407 0 Td
(were)Tj
2.1203 0 Td
(determined)Tj
4.8529 0 Td
(by)Tj
1.1792 0 Td
(electrochemilumin)Tj
7.5685 0 Td
(escence)Tj
3.2428 0 Td
(immunoassay)Tj
5.7543 0 Td
(\(Roche)Tj
3.0671 0 Td
(Diagnostics,)Tj
-32.6549 -1.2982 Td
(Mannheim,)Tj
4.9039 0 Td
(Germany\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 630.5385 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Tests)Tj
2.6504 0 Td
(for)Tj
1.3748 0 Td
(antiviral)Tj
3.6142 0 Td
(drug)Tj
2.1921 0 Td
(resistance)Tj
4.7245 0 Td
(mutations)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 613.5874 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3754 0 Td
(was)Tj
1.7008 0 Td
(extracted)Tj
3.8834 0 Td
(from)Tj
2.2054 0 Td
(serum)Tj
2.7212 0 Td
(sample)Tj
3.0217 0 Td
(of)Tj
1.0148 0 Td
(patients)Tj
3.3732 0 Td
(by)Tj
1.1792 0 Td
(High)Tj
2.245 0 Td
(Pure)Tj
2.1033 0 Td
(Viral)Tj
2.2337 0 Td
(Nucleic)Tj
3.2655 0 Td
(Acid)Tj
2.126 0 Td
(Kit)Tj
-35.7106 -1.3039 Td
(\(Roche\))Tj
3.4015 0 Td
(and)Tj
1.7291 0 Td
(then)Tj
2.0183 0 Td
(determined)Tj
4.8529 0 Td
(by)Tj
1.1792 0 Td
(real-time)Tj
3.8551 0 Td
(PCR)Tj
2.0636 0 Td
(assay)Tj
2.2677 0 Td
(\(QuantiTect)Tj
5.1363 0 Td
(SYBR)Tj
2.5285 0 Td
(Green)Tj
2.7042 0 Td
(PCR)Tj
2.0637 0 Td
(Kit\)\(Qia-)Tj
-33.8001 -1.2982 Td
(Gene\))Tj
2.6702 0 Td
(for)Tj
1.3833 0 Td
(mutation)Tj
3.9231 0 Td
(detection.)Tj
4.1612 0 Td
(All)Tj
1.4003 0 Td
(samples)Tj
3.3789 0 Td
(were)Tj
2.126 0 Td
(also)Tj
1.7688 0 Td
(tested)Tj
2.5512 0 Td
(for)Tj
1.3833 0 Td
(antiviral)Tj
3.5432 0 Td
(drug)Tj
2.109 0 Td
(resistance)Tj
4.1329 0 Td
(muta-)Tj
-34.5314 -1.2983 Td
(tions)Tj
2.1996 0 Td
(by)Tj
1.1849 0 Td
(a)Tj
0.652 0 Td
(line)Tj
1.7064 0 Td
(probe)Tj
2.5455 0 Td
(assay,)Tj
2.4888 0 Td
(INNO-Lipa)Tj
4.8869 0 Td
(HBV)Tj
2.262 0 Td
(DR)Tj
1.5761 0 Td
(v.3)Tj
1.3776 0 Td
(\(Innogenetics)Tj
5.7146 0 Td
(NV,)Tj
1.8766 0 Td
(Gent,)Tj
2.4321 0 Td
(Belgium\))Tj
-30.9031 -1.3039 Td
(according)Tj
4.1839 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.474 0 Td
(manufacturer's)Tj
6.2589 0 Td
(instructions.[)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(])Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 529.0582 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Statistical)Tj
4.4504 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 512.0503 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Statistical)Tj
4.0195 0 Td
(tests)Tj
1.9672 0 Td
(were)Tj
2.1203 0 Td
(performed)Tj
4.4674 0 Td
(by)Tj
1.1848 0 Td
(SPSS)Tj
2.2054 0 Td
(\(version)Tj
3.4922 0 Td
(13.0;)Tj
2.0977 0 Td
(Chicago,)Tj
3.7303 0 Td
(IL,)Tj
1.3266 0 Td
(USA\).)Tj
2.6816 0 Td
(Categorical)Tj
4.7508 0 Td
(variables)Tj
-34.0438 -1.2982 Td
(were)Tj
2.1203 0 Td
(compared)Tj
4.2462 0 Td
(by)Tj
1.1792 0 Td
(Chi-squared)Tj
5.1817 0 Td
(test.)Tj
1.8255 0 Td
(Continuous)Tj
4.9776 0 Td
(variables)Tj
3.7191 0 Td
(were)Tj
2.1203 0 Td
(expressed)Tj
4.0932 0 Td
(as)Tj
1.0148 0 Td
(mean)Tj
/F10 1 Tf
[()]TJ
/F6 1 Tf
(SD,)Tj
4.456 0 Td
(and)Tj
-34.9339 -1.3039 Td
(compared)Tj
4.2406 0 Td
(by)Tj
1.1848 0 Td
(MannWhitney)Tj
6.6444 0 Td
(U)Tj
0.9581 0 Td
(test.)Tj
1.8255 0 Td
(The)Tj
1.7801 0 Td
(cumulative)Tj
4.6432 0 Td
(rates)Tj
2.1089 0 Td
(of)Tj
1.0148 0 Td
(HBeAg)Tj
3.1408 0 Td
(seroclearance)Tj
5.6126 0 Td
(and)Tj
1.7291 0 Td
(HBV)Tj
-34.8829 -1.2983 Td
(DNA)Tj
/F11 1 Tf
0 Tc
2.3754 0 Td
(<)Tj
/F6 1 Tf
-0.004 Tc
(100)Tj
2.4207 0 Td
(IU/mL)Tj
2.9821 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(VBT)Tj
2.1033 0 Td
(were)Tj
2.1259 0 Td
(calculated)Tj
4.2066 0 Td
(using)Tj
2.3868 0 Td
(the)Tj
1.4683 0 Td
(KaplanMeier)Tj
5.9697 0 Td
(method.)Tj
3.549 0 Td
(The)Tj
-35.841 -1.2983 Td
(log)Tj
1.4343 0 Td
(rank)Tj
2.0749 0 Td
(test)Tj
1.5987 0 Td
(was)Tj
1.7008 0 Td
(used)Tj
2.058 0 Td
(to)Tj
1.0261 0 Td
(compare)Tj
3.7134 0 Td
(the)Tj
1.474 0 Td
(cumulative)Tj
4.6431 0 Td
(rate)Tj
1.7461 0 Td
(of)Tj
1.0148 0 Td
(HBeAg)Tj
3.1408 0 Td
(seroclearance)Tj
5.6069 0 Td
(and)Tj
1.7348 0 Td
(HBV)Tj
-32.9667 -1.3039 Td
(DNA)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F6 1 Tf
-0.004 Tc
(100)Tj
4.575 0 Td
(IU/mL)Tj
2.9821 0 Td
(in)Tj
1.0374 0 Td
(different)Tj
3.6567 0 Td
(groups;)Tj
3.1918 0 Td
(Cox)Tj
1.8538 0 Td
(proportional)Tj
5.3178 0 Td
(hazard)Tj
2.9253 0 Td
(model)Tj
2.744 0 Td
(was)Tj
1.7007 0 Td
(performed)Tj
4.4674 0 Td
(to)Tj
1.0262 0 Td
(ana-)Tj
-35.4782 -1.2982 Td
(lyze)Tj
1.7574 0 Td
(factors)Tj
2.9027 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(VBT,)Tj
2.33 0 Td
(and)Tj
1.7292 0 Td
(significant)Tj
4.388 0 Td
(factors\(P)Tj
/F11 1 Tf
0 Tc
3.804 0 Td
(<)Tj
/F6 1 Tf
-0.004 Tc
0.9921 0 Td
(0.05\))Tj
2.2111 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(univariate)Tj
4.2462 0 Td
(analysis)Tj
-33.1197 -1.2983 Td
(were)Tj
2.1203 0 Td
(subjected)Tj
3.9684 0 Td
(to)Tj
1.0262 0 Td
(multivariate)Tj
5.0626 0 Td
(analysis)Tj
3.3279 0 Td
(to)Tj
1.0261 0 Td
(determine)Tj
4.32 0 Td
(independent)Tj
5.278 0 Td
(predictive)Tj
4.1896 0 Td
(factors.)Tj
3.1295 0 Td
(Statistical)Tj
-33.4486 -1.3039 Td
(significance)Tj
4.9379 0 Td
(was)Tj
1.6951 0 Td
(defined)Tj
3.2258 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(P)Tj
0.7767 0 Td
(value)Tj
2.3074 0 Td
(of)Tj
1.0148 0 Td
(less)Tj
1.6101 0 Td
(than)Tj
2.0295 0 Td
(0.05.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 375.5338 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Results)Tj
/F0 1 Tf
0 -1.5023 Td
(Patients')Tj
4.0063 0 Td
(characteristics)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 340.4976 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(demographic)Tj
5.5048 0 Td
(data)Tj
1.9163 0 Td
(of)Tj
1.0147 0 Td
(ETV-treated)Tj
5.2214 0 Td
(HBeAg-positive)Tj
6.5877 0 Td
(CHB)Tj
2.228 0 Td
(patients)Tj
3.3676 0 Td
(with)Tj
2.0012 0 Td
(VBT)Tj
2.1033 0 Td
(and)Tj
1.7291 0 Td
(without)Tj
-33.4542 -1.2982 Td
(VBT)Tj
2.1032 0 Td
(are)Tj
1.4514 0 Td
(shown)Tj
2.8459 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(Table)Tj
2.4435 0 Td
(1)Tj
0 g
(.)Tj
0.9184 0 Td
(A)Tj
0.9014 0 Td
(total)Tj
2.0069 0 Td
(of)Tj
1.0148 0 Td
(162)Tj
1.6441 0 Td
(na)Tj
/F10 1 Tf
[()]TJ
/F6 1 Tf
(ve)Tj
2.3414 0 Td
(HBeAg-positive)Tj
6.5877 0 Td
(CHB)Tj
2.228 0 Td
(patients)Tj
3.3675 0 Td
(received)Tj
3.5376 0 Td
(ETV)Tj
-34.4293 -1.2983 Td
(treatment.)Tj
4.3596 0 Td
(Eighteen)Tj
3.7417 0 Td
(\(11.11%\))Tj
3.7871 0 Td
(ETV-treated)Tj
5.2214 0 Td
(patients)Tj
3.3675 0 Td
(experienced)Tj
5.0343 0 Td
(VBT)Tj
2.109 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(other)Tj
2.3471 0 Td
(144)Tj
-33.1651 -1.3039 Td
(\(88.8%\))Tj
3.3108 0 Td
(patients)Tj
3.3675 0 Td
(did)Tj
1.5421 0 Td
(not)Tj
1.5704 0 Td
(experience)Tj
4.507 0 Td
(VBT)Tj
2.109 0 Td
(during)Tj
2.9253 0 Td
(follow-up.)Tj
4.32 0 Td
(Only)Tj
2.2167 0 Td
(one)Tj
1.7007 0 Td
(\(5.5%\))Tj
2.8347 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(VBT-expe-)Tj
-32.8873 -1.2983 Td
(rienced)Tj
3.2031 0 Td
(patients)Tj
3.3675 0 Td
(had)Tj
1.7121 0 Td
(confirmed)Tj
4.3937 0 Td
(GR)Tj
1.5591 0 Td
(with)Tj
1.9955 0 Td
(L180M)Tj
3.0784 0 Td
(and)Tj
1.7292 0 Td
(M204V)Tj
3.2371 0 Td
(mutation)Tj
3.9175 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(S1)Tj
1.5136 0 Td
(Table)Tj
0 g
2.4435 0 Td
(and)Tj
0.83 0.64 0.02 0 k
1.7291 0 Td
(S1)Tj
1.1679 0 Td
(Fig)Tj
0 g
(\).)Tj
-35.0473 -1.2982 Td
(Among)Tj
3.2428 0 Td
(the)Tj
1.4683 0 Td
(VBT-experienced)Tj
7.2737 0 Td
(patients,)Tj
3.5943 0 Td
(10)Tj
1.1678 0 Td
(patients)Tj
3.3676 0 Td
(\(55%\))Tj
2.6078 0 Td
(had)Tj
1.7121 0 Td
(no)Tj
1.2756 0 Td
(GR.)Tj
1.7802 0 Td
(Another)Tj
3.5829 0 Td
(7)Tj
0.6974 0 Td
(patents)Tj
-31.7705 -1.2983 Td
(\(38.8%\))Tj
3.3108 0 Td
(did)Tj
1.542 0 Td
(not)Tj
1.5704 0 Td
(receive)Tj
3.0104 0 Td
(mutation)Tj
3.9174 0 Td
(check-up)Tj
3.9118 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8199 0 Td
(1)Tj
0 g
(\);)Tj
1.2585 0 Td
(1)Tj
0.6974 0 Td
(patient)Tj
3.0103 0 Td
(suspected)Tj
4.0819 0 Td
(of)Tj
1.0148 0 Td
(poor)Tj
2.1203 0 Td
(compliance)Tj
-31.2659 -1.3039 Td
(according)Tj
4.1839 0 Td
(to)Tj
1.0261 0 Td
(medical)Tj
3.3619 0 Td
(record,3)Tj
3.5489 0 Td
(patients)Tj
3.3676 0 Td
(experienced)Tj
5.0343 0 Td
(VBT)Tj
2.1032 0 Td
(with)Tj
2.0013 0 Td
(low)Tj
1.6554 0 Td
(serum)Tj
2.7213 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3754 0 Td
(\(less)Tj
1.9559 0 Td
(than)Tj
-35.5972 -1.2983 Td
(130)Tj
1.644 0 Td
(IU/mL\);)Tj
3.549 0 Td
(3)Tj
0.6973 0 Td
(patients)Tj
3.3675 0 Td
(was)Tj
1.7008 0 Td
(loss)Tj
1.6951 0 Td
(to)Tj
1.0262 0 Td
(follow-up.)Tj
4.3199 0 Td
(There)Tj
2.5739 0 Td
(were)Tj
2.1259 0 Td
(no)Tj
1.27 0 Td
(significant)Tj
4.3936 0 Td
(differences)Tj
4.5638 0 Td
(in)Tj
1.0375 0 Td
(gender,)Tj
-33.9645 -1.2982 Td
(fatty)Tj
1.9899 0 Td
(liver,)Tj
2.211 0 Td
(and)Tj
1.7291 0 Td
(liver)Tj
1.9842 0 Td
(cirrhosis)Tj
3.6737 0 Td
(between)Tj
3.532 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7121 0 Td
(groups.)Tj
3.1918 0 Td
(There)Tj
2.5795 0 Td
(were)Tj
2.1203 0 Td
(significant)Tj
4.388 0 Td
(differences)Tj
4.5638 0 Td
(in)Tj
1.0374 0 Td
(age)Tj
-36.1811 -1.304 Td
(between)Tj
3.5262 0 Td
(the)Tj
1.4684 0 Td
(VBT)Tj
2.1089 0 Td
(group)Tj
2.6079 0 Td
(and)Tj
1.7291 0 Td
(non-VBT)Tj
4.0592 0 Td
(group)Tj
2.6079 0 Td
(\(p)Tj
1.0771 0 Td
(=)Tj
0.805 0 Td
(0.016\).)Tj
2.9084 0 Td
(The)Tj
1.7858 0 Td
(baseline)Tj
3.4299 0 Td
(laboratory)Tj
4.3483 0 Td
(data)Tj
1.9162 0 Td
(includ-)Tj
-34.3783 -1.2982 Td
(ing)Tj
1.5023 0 Td
(pre-treatment)Tj
5.794 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
2.3811 0 Td
(level,)Tj
2.2394 0 Td
(platelet)Tj
3.1067 0 Td
(count,)Tj
2.7496 0 Td
(spleen)Tj
2.7382 0 Td
(size,)Tj
1.9106 0 Td
(ALT,)Tj
2.279 0 Td
(ALP,)Tj
2.228 0 Td
(total)Tj
2.0013 0 Td
(bilirubin,)Tj
3.9571 0 Td
(PT,)Tj
-35.1493 -1.2983 Td
(Alb,)Tj
1.8821 0 Td
(CCr,)Tj
2.143 0 Td
(and)Tj
1.7291 0 Td
(AFP)Tj
1.99 0 Td
(were)Tj
2.1259 0 Td
(not)Tj
1.5704 0 Td
(significantly)Tj
5.091 0 Td
(different)Tj
3.6567 0 Td
(between)Tj
3.5262 0 Td
(the)Tj
1.4741 0 Td
(two)Tj
1.7064 0 Td
(groups.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 151.9937 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Multivariate)Tj
5.2677 0 Td
(analysis)Tj
3.7843 0 Td
(of)Tj
1.0441 0 Td
(association)Tj
5.1591 0 Td
(with)Tj
1.9748 0 Td
(virological)Tj
4.5969 0 Td
(breakthrough)Tj
ET
Q
q
0.83 0.64 0.02 0 k
1 j
1 J
0 w
10 0 0 10 200.0125 134.9858 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Table)Tj
2.4377 0 Td
(2)Tj
0 g
0.6973 0 Td
(shows)Tj
2.6589 0 Td
(the)Tj
1.474 0 Td
(univariate)Tj
4.2463 0 Td
(and)Tj
1.7291 0 Td
(multivariate)Tj
5.0627 0 Td
(analysis)Tj
3.3278 0 Td
(of)Tj
1.0148 0 Td
(association)Tj
4.6261 0 Td
(with)Tj
1.9956 0 Td
(VBT.)Tj
2.3301 0 Td
(In)Tj
1.1112 0 Td
(the)Tj
1.4683 0 Td
(univari-)Tj
-34.1799 -1.2982 Td
(ate)Tj
1.3719 0 Td
(analysis,)Tj
3.5546 0 Td
(failure)Tj
2.778 0 Td
(to)Tj
1.0261 0 Td
(achieve)Tj
3.1748 0 Td
(HBV)Tj
2.262 0 Td
(DNA)Tj
/F11 1 Tf
0 Tc
2.3754 0 Td
(<)Tj
/F6 1 Tf
-0.004 Tc
(100)Tj
2.4151 0 Td
(IU/mL)Tj
2.9877 0 Td
(at)Tj
0.9525 0 Td
(week)Tj
2.245 0 Td
(48)Tj
1.1735 0 Td
(and)Tj
1.7292 0 Td
(nadir)Tj
2.3697 0 Td
(response,)Tj
3.9571 0 Td
(HBeAg)Tj
-34.3726 -1.2983 Td
(seroclearance)Tj
5.6068 0 Td
(and)Tj
1.7348 0 Td
(age)Tj
1.5421 0 Td
(were)Tj
2.1203 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(VBT.)Tj
2.33 0 Td
(The)Tj
1.7858 0 Td
(multivariate)Tj
5.0627 0 Td
(analysis)Tj
3.3278 0 Td
(showed)Tj
3.2485 0 Td
(HBeAg)Tj
-33.012 -1.3039 Td
(seroclearance)Tj
5.6068 0 Td
(was)Tj
1.7008 0 Td
(significantly)Tj
5.091 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(VBT)Tj
2.1033 0 Td
(\(HR)Tj
1.9502 0 Td
(=)Tj
0.7994 0 Td
(0.25,)Tj
2.0976 0 Td
(CI)Tj
1.2246 0 Td
(=)Tj
0.7993 0 Td
(0.070.94,)Tj
4.269 0 Td
(p)Tj
0.737 0 Td
(=)Tj
0.7994 0 Td
(0.04\))Tj
-33.4316 -1.2983 Td
(\()Tj
0.83 0.64 0.02 0 k
(Table)Tj
2.7779 0 Td
(2)Tj
0 g
(\))Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 380.5795 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(HBV)Tj
2.2535 0 Td
(DNA)Tj
2.3032 0 Td
(dynamics)Tj
4.3725 0 Td
(and)Tj
1.8567 0 Td
(virological)Tj
4.5709 0 Td
(breakthro)Tj
4.1457 0 Td
(ugh)Tj
1.8567 0 Td
(in)Tj
0.9779 0 Td
(CHB)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01740)Tj
4.089 0 Td
(46)Tj
0 g
2.0906 0 Td
(March)Tj
2.9622 0 Td
(28,)Tj
1.5874 0 Td
(2017)Tj
34.3562 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
63 0 obj
<>stream
endstream
endobj
64 0 obj
<>stream
endstream
endobj
65 0 obj
<>stream
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
endstream
endobj
70 0 obj
<>stream
endstream
endobj
71 0 obj
<>stream
endstream
endobj
72 0 obj
<>stream
endstream
endobj
73 0 obj
<>stream
endstream
endobj
74 0 obj
<>stream
BT
66.402 0 Td
(11)Tj
ET
Q
endstream
endobj
75 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 81 0 R/Contents 82 0 R/TrimBox[0 0 612 792]>>
endobj
80 0 obj
<>stream
JFIF C
$, !$4.763.22:ASF:=N>22HbINVX]^]8EfmeZlS[]Y C**Y;2;YYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY *"
} !1AQa"q2#BR$3br
%&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz
w !1AQaq"2B #3Rbr
$4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ? (
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(/3N˼Vxϊ"7:*L3hY 1z
P ¯'&/ |Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ uh?
P ®O ~ ߱@G&h A ?r ߱G*$ PQ A(Z?0%\*$ Q
/ ?a J֏L4 C/
/ ?®O ~ u?'e5J'ojmi4 Zg-f!ր=YNE-5NxN((((((((((((((((((((((((((((((((((((((((((((((((((sZ ?{x %( J . QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QEOV Mqo^gn Z[A7ſy¿
@:RREPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEP^9J?ҽsZ ? {-%- QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE QE Sտy \[W+ q隷o?*? ?ր=^
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
kJQ u _I(ةi)h Iw *34x .# =AT..ΟyQVqM, F쌊 u(Rf :hlxpQL2(#HdGlP4ilUUى;;)0=(hh!lP!`Z uPj u"ޙgڀi`;U#s4 )4 )3Mi@,gM >Ώ)"E&h$
Z)