Prevalence
of Metabolic Syndrome in Patients with Chronic
Hepatitis C (CHC), Aden
.........................................................................................................................
Salem A Bin Selm MD,
PhD
Aden
Yemen
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ABSTRACT
BACKGROUND AND
OBJECTIVES: Several investigators
have suggested insulin resistance overload
as a possible explanation for the increased
prevalence of metabolic syndrome among
patients with chronic hepatitis C virus
(CHC) infection. Therefore, I performed
this study to explore the relationship
between CHC and the metabolic syndrome
and evaluate the value of insulin resistance
as a marker for risk factors in patients
with chronic hepatitis C (CHC), according
to the presence or absence of metabolic
syndrome (MS).
PATIENTS and METHODS: Seventy one
patients with CHC were prospectively studied.
Parameters of MS according to the IDF
criteria were evaluated. Insulin resistance
(IR) was established by homeostasis model
assessment (HOMA-IR]. An index 2.0 was
designated as IR.
RESULTS: MS was found in 61.97%
of cases. HOMA-IR was significantly higher
in patients with CHC and MS vs those without
MS (7.88±1.11 vs 4.29 ±
0.5, p=0.023].
CONCLUSIONS: CHC with MS associated
with a higher insulin resistance, and
chronic hepatitis C has many features
which suggest that this disease must be
viewed not only as a viral disease, but
also as a metabolic liver disease.
Key words: Chronic hepatitis C
- metabolic syndrome - insulin resistance
- Aden.
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Hepatitis C virus (HCV)
infection is not confined to the liver, but
can induce disturbances in many other organs
and systems 1, 2. Chronic hepatitis C has many
features which suggest that this disease must
be viewed not only as a viral disease, but also
as a metabolic liver disease which implies:
insulin resistance (IR) 3, high prevalence of
steatosis 4, increased prevalence of impaired
glucose tolerance 5, type 2 diabetes mellitus
6, and changes in lipid metabolism 7. These
findings together suggest that chronic HCV infection
is closely related to the metabolic syndrome
(MS]. Accordingly, CHC should be divided into
CHC with and CHC without MS. Metabolic steatosis
occurs in non-3 genotype HCV infection and is
associated with host metabolic factors: elevated
body mass index (BMI] and central adiposity
8. Insulin resistance is the main feature of
the MS. In CHC, there is a close association
between IR [9], hepatic steatosis 3, 8, 9, progression
of fibrosis 10 and a lower rate of sustained
virological response 11,12. The pathogenetic
mechanisms of metabolic steatosis are the IR
induced by direct action of HCV on the insulin
signaling pathways 1, 2 as well as the host
factors, especially obesity 9. The IDF consensus
worldwide definition of the MS was used. It
implies the presence of the central obesity
(defined as waist circumference >94
cm for men and >80 cm for women) plus
two of the following four features: raised triglyceride
levels >150 mg/dl; reduced HDL-cholesterol
< 40 mg/dl in males and < 50 mg/dl in
females; raised blood pressure: systolic >130
or diastolic > 85 mmHg; raised fasting
plasma glucose >100 mg/dl 13. To my
knowledge there are no studies from Aden who
have reported on this subject up to now, so
in this direction I tried to determine the prevalence
of metabolic syndrome among patients with chronic
hepatitis c in Aden.
A number of 71 consecutive
patients with CHC were prospectively evaluated.
CHC infection was defined by the presence of
anti-HCV for at least 6 months and a positive
HCV-viremia. Patients with other etiology of
chronic liver disease: hepatitis B, autoimmune
liver disease, Wilson disease, hemochromatosis,
1-antitripsin deficiency, patients with a history
of hepatotoxic- or steatosis-inducing drug use.
Patients with chronic alcohol consumption, as
well as those with a history of diabetes mellitus
were excluded from the study. All patients underwent
a complete clinical and anthropometric evaluation,
and an ultrasound scan of the liver, with a
HS 2000 device, using a 3.5 MHz convex probe,
and the presence of fatty liver was defined
as the increased echogenicity with a bright
pattern of the hepatic parenchyma and posterior
attenuation. The five components of the MS were
searched for in all patients, and subjects having
3 or more of the following criteria were labeled
as MS: central obesity (waist circumference
>94 cm for men and >80 cm
for women) or body mass index (BMI) (weight
in kilograms divided by the square of height
in meters) was considered as obesity (BMI >30),
plus any two of the following four factors:
triglyceride levels >150 mg/dl or current
use of fibrates; HDL-cholesterol < 40 mg/dl
(men) and < 50mg/dl (women); arterial pressure
>130/85 mmHg or pharmacologically
treated; fasting glucose >100mg/dl.
The laboratory evaluation included measurement
of the fasting blood glucose, fasting serum
triglycerides, high-density lipoprotein cholesterol
(HDL-C) levels, alaninaminotransferase (ALT)
and aspartate aminotransferase (AST). Serum
glucose, triglycerides, ALT, AST and HDL-C were
measured by enzymatic colorimetric methods,
and insulin resistance was established by homeostasis
model assessment (HOMA-IR), by the formula:
fasting insulin level (mUI/l] x fasting glucose
level (mg/dl) / 405. A HOMA-IR index value of
more than 2.0 was considered as the criterion
of insulin resistance
Viral markers HBsAg and anti-HCV were assessed
using second-generation enzyme-linked immunosorbent
assay (ELISA) tests.
Ethically a written informed consent was obtained
from each patient.
Comparison between groups was performed using
Student's t-test for continuous variables and
?2 test for categorical variables. The odds
ratio (OR), the 95% confidence intervals (CI),
and p values were calculated. A p value <
0.05 was considered significant.
According to the presence or absence of MS the
patients were divided in two groups for comparison
(Table I). In the univariate analysis, 9 variables
were significantly related to the Metabolic
Syndrome associated with CHC: female gender,
increased BMI, visceral obesity, serum triglycerides,
fasting glucose, HOMA-IR, and presence of fatty
liver (NAFLD), and the prevalence of metabolic
syndrome, obtained was 61.97% (44/71cases),
as illustrated in Table 1.
| TABLE
1: Characteristics of CHC patients according
to the presence or absence of metabolic
syndrome |
Hepatitis C and Metabolic Syndrome are common
conditions worldwide and both have IR as a key
pathogenetic factor 14. In this study we found
that Metabolic Syndrome, according to the IFD
definition was present in 61.97% (44 out of
71) patients with CHC. All of them had visceral
obesity, evaluated by waist circumference and
a significantly higher BMI as compared with
patients without Metabolic Syndrome. Low HDL-cholesterol
level (68.4%), raised plasma glucose (59.8%),
elevated blood pressure (48%) and high triglyceride
levels (30.2%) were also present in these patients.
Chronic hepatitis C and Metabolic Syndrome may
coexist in the same individual 15, but chronic
HCV infection can also generate by itself some
metabolic abnormalities characteristic for the
Metabolic Syndrome.
Insulin resistance in chronic HCV infection
could be caused by interplay between viral and
host factors 16. HCV infection per se generates
multiple defects in hepatic insulin signaling
pathways 17, 18, 19. In this study insulin resistance
was higher in patients with CHC and Metabolic
Syndrome than in those without it, and in the
univariate analysis HOMA-IR was correlated with
BMI and visceral obesity. Visceral obesity estimated
by waist circumference is viewed as the phenotypic
expression of IR 20 and we found that HOMA-IR
was almost two-fold higher in patients with
CHC and MS than in those with CHC alone.
Our study revealed a positive correlation between
IR and activity. Most investigators have demonstrated
that IR has developed before the stage of cirrhosis
and that it is higher in patients with CHC 21,
22, and suggested the link between IR and hepatic
steatosis. In concordance with these studies,
we found that Metabolic Syndrome correlated
with NAFLD in large number. This might be explained
by a higher contribution of the metabolic versus
viral factors in this study, as in other studies
23. Another unexpected finding of our study
was the correlation of IR with the necroinflammatory
activity. This is not a singular finding. Another
study found an association between IR, high
serum viral load and necroinflammation in patients
with CHC infected especially with genotype 1
or 4 24. Despite the major role played by HCV
in the development of IR and hepatic steatosis,
host metabolic factors might have a great contribution
in chronic HCV infection. A significant number
of our patients had Metabolic Syndrome, and
visceral obesity was the constant criterion
for the definition of Metabolic Syndrome. The
adipose tissue is no longer considered only
as a storage organ, but rather a very active
neuroendocrine organ, that produces and secretes
a large number of active peptides, collectively
named adipocytokines or adipokines 25, 26, 27,
with significant implications in several metabolic
processes. Among these cytokines, the role of
adiponectin in NAFLD and CHC has been largely
studied. These findings support the hypothesis
that IR is not only the result of a direct action
of the virus, but also of an imbalance of adipocytokines,
mainly in patients with Metabolic Syndrome,
confirming the role of the metabolic factors
in modulating insulin sensitivity 21,22. Our
study revealed a positive correlation between
presence of metabolic syndrome and NAFLD, in
percentage of 63% among patients with CHC, and
this result might explain the role played by
CHC in the development of fatty liver.
In conclusion CHC with Metabolic Syndrome
was associated with a higher insulin resistance,
and these findings together suggest that chronic
HCV infection is closely related to the metabolic
syndrome.
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