1. Comparison of the Biochemical Responses between TAF and TDF in CHB
목요세미나
Comparison of the Biochemical Responses between TAF and TDF in CHB
분당서울대병원 소화기내과
장은선

2. 만성 B형간염의 치료 목표 Virologic response Functional cure
HBV DNA undetectable, HBsAg+ in serum
Functional cure
HBsAg & HBV DNA in serum: undetectable
Resolution of residual liver injury
Reduction of risk of HCC
Complete sterilizing cure
HBsAg in serum: undetectable
Eradication of HBV DNA including intrahepatic cccDNA and integrated HBV DNA
Biochemical response

3. ALT levels & mortality in CHB pts.
Men
Women
Best cut-off values for liver-related mortality :
>34 U/L in men and >30 U/L in women
Liver Int 2018;38:

4. Similar virologic response btw TAF and TDF

5. Lancet Gastroenterol Hepatol 2016; 1: 185–95

6. (B) Proportion of patients achieving ALT normalisation by
central laboratory (Covance) criteria by study week (≤43 U/L for men and
≤34 U/L for women <69 years of age; ≤35 U/L for men and ≤32 U/L for women
>69 years of age). (C) Proportion of patients achieving ALT normalisation by
American Association for the Study of Liver Diseases (AASLD) criteria (≤19 U/L
for women and ≤30 U/L for men) by study week
Lancet Gastroenterol Hepatol 2016; 1: 196–206

7. Virologic response  biochemical response??
7.1%

8. 만성 B형간염에서 간경변증/간세포암 발생 연관인자

9. Metabolic syndrome in HBV-related HCC
Dig Dis Sci 2018;63:

11. Possible causes?
BMI
Alcohol
Drug
….?

12. Real-world data to compare TAF, TDF and ETV in SNUBH

13. Baseline characteristics
Variable
TAF (n = 73)
TDF (n = 564)
ETV (n=453)
p-value
Age (years)*
46.7 (11.6)
50.4 (11.4)
55.1 (11.1)
<0.0001 
Male
41 (56.2%)
94 (63.5%)
261 (57.6%)
 0.12
BMI (m2/kg)*
24.3 (3.2)
24 (3.6)
23.8 (3.3)
0.403 
Alcohol (g/day)*
3.4 (7.1)
7.6 (17.1)
6.1 (13.9)
0.631 
Underlying liver disease
0.117 
Chronic hepatitis
64 (87.8%)
457 (81%)
353 (77.9%)
Liver cirrhosis
9 (12.3%)
107 (19%)
100 (22.1%)
Other underlying disease
DM, yes
6 (8.2%)
71 (12.6%)
78 (17.2%)
0.035
HTN, medication
4 (5.4%)
68 (13%)
79 (17.4%)
0.017
Bone disorder,
osteoporosis
0 (0%)
30 (5.3%)
12 (2.6%)
0.018
CKD
0.009
Grade 1-2
72 (100%)
552 (98.8%)
435 (96.2%)
≥Grade 3
7 (1.2%)
17 (3.8%)
NAFLD, yes
18 (24.7%)
96 (17%)
64 (14.1%)
0.064
Laboratory findings
AST (IU/L)*
91.6 (108.6)
117.2 (247.2)
99.4 (202.8)
0.365 
ALT (IU/L)*
145 (221.6)
162.7 (341.3)
132.5 (311.7)
 0.34
WBC (x 103/µl)*
5.29 (1.16)
5.42 (1.93)
5.50 (1.99)
0.631
Hemoglobin (g/dL)*
14.2 (1.8)
14.5 (1.7)
14 (2)
 0.0001
Platelet (count/µl)*
207.5 (67.1)
178.4 (66.9)
181.3 (67.2)
 0.003
Calcium (mg/dL)*
9.4 (0.3)
9 (0.5)
<0.0001
Phosphate (mg/dL)*
3.4 (0.5)
3.4 (0.6)
0.216
BUN (mg/dL)*
13.3 (3.9)
14 (4)
14.5 (6.9)
Cr (mg/dL)*
0.79 (0.17)
0.81 (0.18)
0.82 (0.32)
0.603
eGFR by MDRD (mL/min)*
97.5 (17.3)
98.1 (21)
95.8 (24.7)
0.245
Total cholesterol (mg/dL)*
183.8 (31.3)
171.7 (35.9)
169.7 (36.8)
Total protein (g/dL)*
7.4 (0.4)
7.3 (0.5)
7.2 (0.6)
0.014
Total bilirubin (mg/dL)*
2.1 (10.15)
1.2 (0.75)
1.03 (0.84)
0.006
Proteinuria, ≥2+
0/63 (0%)
11/447 (2.5%)
25/325 (7.7%)
PIVKA-II*
16.2 (5.6)
15.9 (5.1)
13.9 (4.8)
0.008

14. P = 0.091
P=0.473
P = 0.054
P<0.001

15. Multivariable Cox analyses
ALT response
AST response
Virologic response
HR (95% CI)
P value
Age
0.997
( )
0.434
0.978
( )
<0.0001
0.999
( )
0.798
ALT
1.000
( )
AST*
HBV DNA
0.795
( )
HBeAg
0.793
( )
0.013
0.837
( )
0.055
0.492
( ) DM
0.874
( )
0.397
1,053
( )
0.725
0.984
( )
0.894
Drug
TAF
TDF
0.884
( )
0.520
1.095
( )
0.638
1.058
( )
0.752
ETV
1.253
( )
0.251
1.575
( )
0.021
0.939
( )
0.735

16. Summary & Conclusion
Biochemical response is an important prognostic factors in CHB patients, but not always linked with virologic response in the era of potent antiviral drugs.
TAF is not the best antiviral drugs in a real-world practice so far.
The mechanism of different biochemical response of TAF and TDF should be studied in a large scale study.