Detection
of
genomic
viral
RNA
in
nerve
and
muscle
of
patients
with
HCV
neuropathy.
Groupe nerf-muscle, Département de pathologie, Hôpital Henri Mondor, Créteil, France. authier@univ-paris1
2.fr
Abstract
BACKGROUND:
Hepatitis C
virus
(HCV)-associated
neuropathy
is usually
associated
with mixed
cryoglobulinemia
(MC) and
vasculitis.
MC may
contain
viral RNA,
and tissues
showing
vasculitis
may contain
intracellular
HCV. Local
HCV
replication
remains to
be
evidenced.
OBJECTIVE:
To delineate
the spectrum
of
HCV-associated
neuropathy
and to
assess the
presence of
HCV in nerve
and muscle
tissues.
METHODS:
Thirty
consecutive
HCV-infected
patients
with
peripheral
neuropathy
were
included.
Genomic and
replicative
strands of
HCV RNA were
detected in
both nerve
and muscle
biopsy
samples
using
distinctive
reverse
transcription
nested PCR.
RESULTS:
Neuropathy
was
consistent
with distal
axonal
polyneuropathy
(DPN) in 25
of 30
patients,
mononeuropathy
multiplex
(MM) in 3 of
30, and
demyelinating
polyneuropathy
in 2 of 30.
Pain was
present in
18 of 30
patients and
MC in 16 of
30. Biopsy
showed
inflammatory
vascular
lesions in
26 of 30
patients
(87%),
including
necrotizing
arteritis
(6/30),
small-vessel
vasculitis
(12/30) of
either the
lymphocytic
(9/12) or
the
leukocytoclastic
(3/12) type,
and
perivascular
inflammatory
infiltrates
(8/30). All
patients
with
necrotizing
arteritis
had DPN and
positive MC
detection.
Both pain (p
< 0.03) and
positive MC
detection (p
< 0.01) were
associated
with the
presence of
vasculitis.
Positive-strand
genomic HCV
RNA was
detected in
tissues of
10 of 30
patients
(muscle 9,
nerve 3). In
contrast,
negative-strand
replicative
RNA was
never
detected.
Genomic RNA
was found in
nerve tissue
samples
showing
vasculitis
(necrotizing
arteritis 2,
small-vessel
lymphocytic
vasculitis
1).
CONCLUSION:
Painful DPN
associated
with MC and
neuromuscular
vasculitis
is the most
frequent
type of HCV
neuropathy.
The usual
detection of
MC and the
lack of
local HCV
replication
indicate
that HCV
neuropathy
results from
virus-triggered
immune-mediated
mechanisms
rather than
direct nerve
infection
and in situ
replication.
http://www.ncbi.nlm.nih.gov/pubmed?term=Detection%20of%20genomic%20viral%20RNA%20in%20nerve%20and%20muscle%20of%20patients%20with%20HCV%20neuropathy
Motor-axonal
polyneuropathy
associated
with
hepatitis
C
virus.
Abstract
The
association
between
hepatitis C
virus (HCV)
infection,
the presence
of mixed
cryoglobulinemia
and
peripheral
neuropathy
is
well-documented
(Apartis et
al., 1996).
HCV is the
chief cause
of essential
mixed
cryoglobulinemia
(type II
cryoglobulinemia)
with
cryoglobulins
present in
up to half
of patients
with HCV
infection (Akriviadis
et al.,
1997). More
recently it
has been
stated that
peripheral
polyneuropathy
may be
associated
with HCV
chronic
infection
without
mixed
cryoglobulinemia
(Lidove et
al., 2001).
Patients
usually
present with
a clinical
and
electrophysiology--predominantly
sensory
axonopathies
(Apartis et
al., 1996;
Heckmann et
al., 1999)
or less
frequently
with
fulminating
vasculitis
and
mononeuropathy
multiplex
syndrome
(David et
al.,
1996)--especially
when
associated
with
cryoglobulinemia.
We report,
for the
first time,
the
association
between pure
motor-axonal
polyneuropathy
and HCV
infection
without
cryoglobulinemia.
http://www.ncbi.nlm.nih.gov/pubmed?term=Motor-axonal%20polyneuropathy%20associated%20with%20hepatitis%20C%20virus
Peripheral
neuropathy
without
cryoglobulinemia
in
patients
with
hepatitis
C virus
infection.
BACKGROUND:
An
association
between
essential
mixed
cryoglobulinemia
and
hepatitis
C
virus
infection
has
been
documented
by
many
reports.
Some
clinical
manifestations
such
as
purpura,
arthralgia,
vascular
lesions
and
peripheral
neuropathies
are
also
connected
with
the
presence
of
detectable
cryoglobulins.
The
association
between
HCV
infection,
the
presence
of
mixed
cryoglobulinemia
and
peripheral
neuropathy
is
well
documented.
The
aim
of
this
study
was
to
define
the
possible
presence
of
peripheral
neuropathy
in
HCV
patients
without
detectable
cryoglobulins
and
the
possible
association
with
the
different
genotypes.
METHODS:
Twenty
patients
(11
females,
9
males)
with
chronic
HCV
hepatitis
and
without
detectable
cryoglobulins
were
submitted
to
neurological
and
electrophysiological
studies
to
detect
a
possible
peripheral
neurological
involvement.
In
all
patients
the
HCV
infection
was
assumed
by
the
presence
of
antibodies
to
HCV
with
ELISA
assay
and
then
confirmed
with
recombinant
immunoblot
assay.
HCV
genotyping
was
obtained
by
INNO
LIPA
in
15
out
of
20
patients.
In 4
patients
a
sural
nerve
biopsy
was
possible.
RESULTS:
Genotype
1b
was
present
in
80%
of
patients,
while
1a
in
13.3%
and
4 in
6.6%.
Thirteen
patients
had
positive
neurological
anamnesis
(65%),
while
neurological
examination
was
positive
in
40%
of
the
cases.
Electromyographic
study
was
positive
in
50%
of
subjects.
The
sural
nerve
biopsies
agreed
with
axonal
degeneration
in
amyelinated
fibres.
CONCLUSIONS:
Our
results
suggest
a
possible
peripheral
neurological
system
involvement
in
patients
with
HCV
infection
without
cryoglobulins.
http://www.ncbi.nlm.nih.gov/pubmed/11218620
Hepatitis C
virus
infection
with
peripheral
neuropathy
is not
always
associated
with
cryoglobulinaemia.
Abstract
OBJECTIVES:
To
describe
cases of
peripheral
neuropathy
associated
with
chronic
hepatitis
C virus
infection
without
mixed
cryoglobulinaemia.
METHODS:
Four
cases of
peripheral neuropathy associated with chronic hepatitis C virus
infection
with
persistent
negativity
of mixed
cryoglobulinaemia
were
found.
RESULTS:
All
patients
had
small
increases
of
transaminase
levels
and a
positive
viraemia.
Liver
biopsy
showed
chronic
active
hepatitis
in all
but one
case (Knodell
4-9,
Metavir
A0F0-A3F3).
Neuromuscular
biopsy
showed
axonal
neuropathy
associated
with
lymphoid
infiltrates
around
small
vessels
in two
cases.
Rheumatoid
factor
was
always
negative
and C4
complement
level
was
always
normal.
In three
patients,
neuropathy
improved
with
interferon
alpha,
interferon
alpha +
ursodesoxycholic
acid, or
steroids
+ plasma
exchange.
CONCLUSION:
Peripheral
neuropathy
may be
associated
with
hepatitis
C virus
infection
without
mixed
cryoglobulinaemia.
Peripheral
neuropathy
involving
cranial
nerves
in a
patient
with
hepatitis
C virus
infection
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