Does Hepatitis B virus antiviral

1
Does Hepatitis B virus antiviral

• Julie Sheldon, Belen Ramo

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therapy reduce hepatitis Delta vire

• s, Jose Martinez- Alarcón, Pilar Rios,Carlos

Hospital Carlos III, Madrid, Spain
3
mia in HIV coinfected patients?

• Toro, Vincent Soriano

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Introduction

• Approximately 5 of chronic HBV patients are also
  coinfected with hepatitis delta virus (HDV),
  resulting in approximately 15 million persons
  infected with HDV worldwide.
• The main route of HDV transmission is via
  infected blood and blood products. In Europe and
  the United States this is mainly confined to
  intravenous drug users.
• HDV is a subviral satellite of HBV that requires
  the HBsAg for the encapsidation of its own genome
  and uses the host cellular polymerase for
  replication. For this reason together with its
  high pathogenic potential chronic hepatitis Delta
  is challenging antiviral therapy.

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Introduction

• No specific inhibitor of HDV has so far been
  developed.
• Treatment is currently limited to intensive
  IFN-alpha therapy.
• However, the role of potent nucleos(t)ide
  analogues against chronic HDV infection has not
  been well examined.

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Aim
To study and compare quantitative HDV and HBV
viral loads, hepatic biochemical and serological
markers in chronic HDV patients coinfected with
HIV undergoing anti-HBV antiviral treatment
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Methods

• All HIV patients chronically infected with
  HBV/HDV whom attended Hospital Carlos III
  undergoing a HAART that included anti-HBV
  treatment were included in the study.
• Patients serum was analysed at yearly intervals
  for HIV RNA, HBV DNA, CD4, HCV RNA (if
  coinfected), ALT/AST levels and HDV RNA.
• HBsAg, HBeAg and anti-HBeAg, HDV Ag, total HDV
  antibodies and HDV IgM were analyzed.
• Liver fibrosis was measured using the Fibroscan.
  
• All statistical analysis was done using SPSS v12.

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Baseline Characteristics, n 18
Male Sex, n ()
15 (83)
Risk group, n ()
Intravenous drug use
15 (83)
Sexual
1 (5.5)
Horizontal
1 (5.5)
Unknown
1 (5.5)
Age, median years (range)
33 (5-41)
ALT, median IU/ml (range)
98 (31-347)
AST, median IU/ml (range)
77 (24-365)
Anti-IgM Delta, n ()
10 (55)
HBeAg positive, n ()
7 (39)
1
1
8
HBV DNA median IU/ml (range)
1.5 x 10
(
1.2 x 10
-
1.0 x 10
)
6
3
8
HDV RNA median copies/
ml (
range)
7.7 x 10
(
1.1 x 10
-
2.7 x 10
)
1
1
5
HIV RNA median copies/
ml (
range)
5.0 x 10
(
5 x 10
-
3.5 x 10
)
Anti-HCV positive, n ()
15 (83)

HCV
RNA positive, n ()
3
(
17
)
CD4, median copies/ml (range)
352 (65 1584)
CD4 (range)
17 (5 36)
Median years on anti-HBV ART (range)
6 (2-10)
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Longitudinal follow-up of Delta patients treated
with anti-HBV drugs

• Overall, 14 patients showed good response to
  anti-HBV therapy with achievement of undetectable
  HBV DNA.
• Moreover, all of them showed a statistically
  significant decrease in plasma HDV RNA (p0.038)
  and ALT levels (p 0.022)

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HDV RNA correlations with Liver Fibrosis, HBV
DNA, ALT and AST
Log HDV Log HBV AST ALT Fibrosis
Log HDV RNA - p0.005 plt0.001
plt0.001 p0.052 Log HBV DNA -
p0.019 p0.286 p0.274 AST
- plt0.001 p0.634 ALT
- p0.797
Spearman Rho correlation coefficient
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Longitudinal follow-up of Delta patients treated
with anti-HBV therapy
HDV RNA cop/ml (log10)
ALT IU/ml
Years with
Log drop HDV RNA
HBV treatment
HBV DNA
Before
After
Pt
Before
After
lt12 IU/ml
1
10
128700000 (8.1)
48600 (4.7)
114
125
3.4
LAM (6 years)
LAM TDF (4 years)
3
3
6756000 (6.8)
2989000 (6.4)
272
150
0.4
LAM TDF
4
2
5236000 (5.7)
1664000 (6.2)
78
151
0.5
LAM TDF
5
7
7190000 (6.9)
3468000 (6.5)
54
43
0.4
LAM (2 years)
6
4
2674000 (6.4)
lt100 (lt2)
159
67
gt4.4
LAM (4 years)
7
8
13170000 (7.1)
lt100 (lt2)
84
26
gt5.1
LAM (4.5 years)
LAM TDF (2.5 years)
8
7
187600 (5.3)
89060 (4.9)
79
55
0.4
LAM (4 years)
LAM TDF (3 years)
9
9
154500 (5.2)
lt100 (lt2)
113
9
gt3.2
LAM (9 years)
11
2
9948000 (7.0)
169500 (6.2)
42
46
0.8
LAM TDF (1.5 years)
FTC TDF (0.5 years)
14
3
19330 (4.3)
lt100 (lt2)
40
31
gt2.3
LAM TDF (1.5 years)
FTC TDF (1.5 years)
15
2
13680000 (7.1)
63500 (4.8)
43
35
2.3
LAM TDF (2 years)
16
5
8366000 (6.9)
1789000 (6.3)
347
74
0.6
LAM (5 years)
17
8
53510000 (7.7)
2178000 (6.3)
90
87
1.4
LAM (4 years)
LAM TDF (3 years)
LAM (1 year)
18
2
274800000 (8.4)
33010000 (7.5)
N.D.
N.D.
0.9
LAM (2 years)
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HDV RNA load in 6 patients with detectable HBV DNA
HDV RNA cop/ml (log10)
ALT IU/ml
Pt.
Log
HBV treatment
rise
Before
Before
After
4
16840 (4.2)
20890000 (7.3)
3.1
16
40
LAM (3 years) developed
LAM resistance
No treatment (2 years)
6
lt100 (lt2)
13710 (4.1)
gt2.1
67
87
LAM TDF (1 year) - bad
compliance
10
lt100 (lt2)
20600 (4.3)
gt2.3
53
32
No treatment
15
63500 (4.8)
630000 (5.8)
1
35
70
Abandoned LAM TDF
treatment (1 year)
8
187600 (5.3)
540300 (5.7)
0.4
79
83
10 month break from LAM
12
lt100 (lt2)
163400 (5.2)
gt3.2
18
33
No treatment
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Conclusions

• In HIV patients undergoing potent and successful
  anti-HBV antiviral therapy there seems to be an
  indirect benefit suppressing Delta virus
  replication, albeit not very efficient.
• Hypothetically, a significant and sustained
  reduction in serum HDV RNA may only be seen when
  a reduction in HBV HBsAg and/or cccDNA is
  achieved, which may require long periods of
  successful anti-HBV therapy.
• To our knowledge, this is the first evidence of
  benefit of potent anti-HBV nucleos(t)ide analogue
  therapy currently in use for chronic Delta
  hepatitis.

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Acknowledgements

• Clinic Laboratory
• Vicente Soriano Belen Ramos
• Pablo Barreiro Jose Martinez Alarcon
• Luz Martin-Carbonero Berta Rodes
• Pilar Garcia-Gasco Victoria Jimenez
• Ivana Maida Carlos Toro
• Pablo Labarga Ainhoa Simon
• Eugenia Vispo Norma Rallón
• Hepatology
• Javier Garcia-Samaniego
• Miriam Romero