Clinical, Biochemical, virological and Histopathological Assessment of Hepatic Steatosis in Egyptian Patients with HCV genotype 4 and HCV Associated HCC Mona M. Hassan*, Nihal M. El Assaly*, Naema I. El Ashry*, Mervat El Damarawy **,Shindy M. Shindy***, and Tarek S Abou Shousha**** *Clinical Chemistry Department, ** I.C.U Department, *** Tropical Medicine Department, **** Pathology Department at Theodor Bilharz Research Institute Journal:-Egyptian Medical Journal Of The National Research Center; vol. 6 (1), June 2007:27- 37. ISSN 1687-1278 Abstract: Liver steatosis is common in patients infected with hepatitis C virus (HCV), occurring in approximately 50% of biopsy specimens. This high prevalence suggests a specific interaction between HCV and lipid metabolism. The objective of this study was to assess some clinical, virological, histopathological and biochemical variables including serum adiponectin, leptin and beta-2- microglobulin (B2-MG) in relation to hepatic steatosis in Egyptian patients infected with HCV genotype 4 of early and late disease with cirrhosis and HCC.. Patients and Methodology: This study included a control group of 23 patients and 50 patients with HCV infection genotype 4 (group 1 of 25 HCV patients with early and active disease; and group 2 of 25 HCV cirrhotic patients associated with HCC) who were admitted to Theodor Bilharz Research Institute in Egypt. They were initially subjected to history; clinical examination, abdominal ultrasonography, liver function tests, HBs Ag, HCV-Ab and liver biopsy. Measurement of adiponectin, leptin, beta-2- microglobulin (done by ELISA) and lipid profile had been performed in all groups. Results: Steatosis of variable grades was detected in 80% of Egyptian patients with early active HCV genotype 4 infection and in 88% of those with cirrhosis and HCC. Steatosis was generally of higher grades in early active HCV than those with cirrhosis and HCC but the mean number of hepatocytes affected by steatosis were higher in cirrhotic patients but not significant (P>0.05). No correlation between body mass index (BMI) and the grade of steatosis in these patients (p = 0.236). No significant correlation between number of focal lesions, or their volumes and the degree of steatosis or histopathological grades; HAI (P > 0.05). Also, no significant correlation between number of focal lesions, or their volumes and all parameters studied including leptin, adiponectin and B2-MG. There was statistically significant higher viremia and HAI score in those with higher grades of steatosis than lower grades and in lower grades than those without steatosis (P < 0.05) and significant higher viremia in group 1 than group2 (P < 0.01). There were significantly lower serum triglycerides (P <0.05) and cholesterol (P < 0.01) (total, HDL, LDL) levels in both HCV groups than control group. Low triglycerides and cholesterol levels were significantly correlated with grade of steatosis (P < 0.05).There were significantly higher serum leptin (12.1± 7.35 & 11.75 ± 5..92 vs. 6.43 ± 4.13 ngm/ml) and beta 2 microglobulin (12.56 ± 3.44 & 4.73 ± 1.55 vs. 1.22) and lower adiponectin (10.40 ± 7.41 & 16.56 ±5.92 vs. 25.47 ± 12.38 micg/ml) in late and early HCV patients vs. control (P <0.001). Also, beta 2 microglobulin was significantly higher and adiponectin significantly lower in advanced patients with cirrhosis and HCC than early cases (P < 0.01). Significant correlations were found between beta 2- microglobulin concentration, adiponectin and grade of steatosis, HAI and fibrosis scores (P < 0.01). Leptin showed significant correlation only with grade of steatosis (P< 0.05). Age, level of alanine transaminase ALT (IU/L), low serum albumin, fibrosis, portal inflammation and lobular inflammation were significantly correlated with steatosis. In conclusion: In our Egyptian patients, HCV genotype 4 infection was associated with many factors that are highly linked to the development of steatosis such as high leptin and lower adiponectin serum levels. Also, beta 2 microglobulin which is a marker of more severe disease and poor outcome was significantly higher than control patients. Also steatosis is commonly seen in this genotype and its grade was associated with higher viral load, more severe inflammation and fibrosis. The steatosis in genotype 4 is probably a genotype or viral-related process with all the biochemical changes secondary to it and these changes may re-perpetuate and exaggerate the process. The significant increase of leptin and
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Clinical, Biochemical, virological and Histopathological Assessment of Hepatic Steatosis in Egyptian Patients with HCV genotype 4
and HCV Associated HCC
Mona M. Hassan*, Nihal M. El Assaly*, Naema I. El Ashry*, Mervat El Damarawy **,Shindy
M. Shindy***, and Tarek S Abou Shousha****
*Clinical Chemistry Department, ** I.C.U Department, *** Tropical Medicine Department,
**** Pathology Department at Theodor Bilharz Research Institute
Journal:-Egyptian Medical Journal Of The National Research Center; vol. 6 (1), June 2007:27-
37. ISSN 1687-1278
Abstract:
Liver steatosis is common in patients infected with hepatitis C virus (HCV), occurring in approximately 50% of biopsy specimens. This high prevalence suggests a specific interaction between HCV and lipid metabolism. The objective of this study was to assess some clinical, virological, histopathological and biochemical variables including serum adiponectin, leptin and beta-2- microglobulin (B2-MG) in relation to hepatic steatosis in Egyptian patients infected with HCV genotype 4 of early and late disease with cirrhosis and HCC.. Patients and Methodology: This study included a control group of 23 patients and 50 patients with HCV infection genotype 4 (group 1 of 25 HCV patients with early and active disease; and group 2 of 25 HCV cirrhotic patients associated with HCC) who were admitted to Theodor Bilharz Research Institute in Egypt. They were initially subjected to history; clinical examination, abdominal ultrasonography, liver function tests, HBs Ag, HCV-Ab and liver biopsy. Measurement of adiponectin, leptin, beta-2- microglobulin (done by ELISA) and lipid profile had been performed in all groups. Results: Steatosis of variable grades was detected in 80% of Egyptian patients with early active HCV genotype 4 infection and in 88% of those with cirrhosis and HCC. Steatosis was generally of higher grades in early active HCV than those with cirrhosis and HCC but the mean number of hepatocytes affected by steatosis were higher in cirrhotic patients but not significant (P>0.05). No correlation between body mass index (BMI) and the grade of steatosis in these patients (p = 0.236). No significant correlation between number of focal lesions, or their volumes and the degree of steatosis or histopathological grades; HAI (P > 0.05). Also, no significant correlation between number of focal lesions, or their volumes and all parameters studied including leptin, adiponectin and B2-MG. There was statistically significant higher viremia and HAI score in those with higher grades of steatosis than lower grades and in lower grades than those without steatosis (P < 0.05) and significant higher viremia in group 1 than group2 (P < 0.01). There were significantly lower serum triglycerides (P <0.05) and cholesterol (P < 0.01) (total, HDL, LDL) levels in both HCV groups than control group. Low triglycerides and cholesterol levels were significantly correlated with grade of steatosis (P < 0.05).There were significantly higher serum leptin (12.1± 7.35 & 11.75 ± 5..92 vs. 6.43 ± 4.13 ngm/ml) and beta 2 microglobulin (12.56 ± 3.44 & 4.73 ± 1.55 vs. 1.22) and lower adiponectin (10.40 ± 7.41 & 16.56 ±5.92 vs. 25.47 ± 12.38 micg/ml) in late and early HCV patients vs. control (P <0.001). Also, beta 2 microglobulin was significantly higher and adiponectin significantly lower in advanced patients with cirrhosis and HCC than early cases (P < 0.01). Significant correlations were found between beta 2-microglobulin concentration, adiponectin and grade of steatosis, HAI and fibrosis scores (P < 0.01). Leptin showed significant correlation only with grade of steatosis (P< 0.05). Age, level of alanine transaminase ALT (IU/L), low serum albumin, fibrosis, portal inflammation and lobular inflammation were significantly correlated with steatosis. In conclusion: In our Egyptian patients, HCV genotype 4 infection was associated with many factors that are highly linked to the development of steatosis such as high leptin and lower adiponectin serum levels. Also, beta 2 microglobulin which is a marker of more severe disease and poor outcome was significantly higher than control patients. Also steatosis is commonly seen in this genotype and its grade was associated with higher viral load, more severe inflammation and fibrosis. The steatosis in
genotype 4 is probably a genotype or viral-related process with all the biochemical changes secondary to it and these changes may re-perpetuate and exaggerate the process. The significant increase of leptin and
beta-2- microglobulin and decrease in adiponectin in HCV patients with cirrhosis could play a role in the pathogenesis of steatosis and progression of liver disease. Finally, steatosis should be considered a target for therapeutic interventions in addition to the viral and inflammatory process of the liver in such patients . Key words: Steatosis, adiponectin, B2-MG, liptin and HCV infection
Introduction:
Steatosis is defined as fat, largely triglyceride, exceeding 5% of the liver weight. It is
caused by failure of normal hepatic fat metabolism either due to a defect within the
hepatocyte or to delivery of excess fat, fatty acid or carbohydrate beyond the secretory
capacity for lipid of the liver cell. Liver biopsy and imaging procedures, such as ultrasound
and CT, are increasing the number of patients being identified with excess fat in the liver.
Liver biopsy is the best method of diagnosing steatosis, it is also the only method to
differentiate steatosis from non-alcoholic steato-hepatitis (NASH).1
Non-alcoholic fatty liver disease (NAFLD) is the term used to describe a spectrum of
disorders characterized by macrovesicular steatosis that occur in the absence of consumption
of alcohol in amounts considered to be harmful to the liver .2
Hepatitis C virus (HCV) and nonalcoholic fatty liver disease (NAFLD) are the two most
common causes of chronic liver disease.3 The spectrum of NAFLD consists of isolated
hepatic macrovesicular steatosis at one end and steatohepatitis at the other one.4, 5 Sustained
liver injury will lead to progressive fibrosis and cirrhosis in 10% to 25% of affected
individuals.2
Hepatic steatosis is frequently seen in subjects with HCV; occurring in approximately
50% of biopsy specimens. Also, the presence and severity of hepatic steatosis has emerged as
an important marker of progressive liver disease as well as virologic response to anti-HCV
therapy, it may be caused directly by the virus, as in genotype 3 infection, or be associated
with host metabolic factors.6,7 One study showed that genotype 3 was associated with greater
hepatic steatosis and inflammation than genotype 1. It was found specifically associated with
insulin resistance that was associated with a decrease in total and high molecular weight
(HMW) adiponectin levels.8 Another study found that infection with HCV genotype 3 was
associated with hepatic steatosis that appears to be a viral effect rather than a host effect, but
in most cases, with other genotypes, steatosis in hepatitis C represents the presence of 2
separate liver conditions.9
Obesity is a well-recognized risk factor for the development of steatosis in chronic
hepatitis C infection. The interaction of hepatitis C virus core protein with the lipoprotein
secretion pathways causes the characteristic alterations of lipid metabolism observed in
hepatitis C virus-related steatosis. Steatosis is a major determinant of the liver damage
progression in chronic hepatitis C (CHC), more severe or advanced hepatic fibrosis and
negatively affects the response rate to the anti-viral treatment with pegylated interferon and
ribavirin.10 Moreover, recent evidence suggests that steatosis may contribute to liver
carcinogenesis. Also, chronic hepatitis C is a recognized risk factor for type 2 diabetes and it
could be implicated into the pathogenesis of atherosclerosis. The role of hepatitis C virus
(HCV)-related steatosis in these epidemiological associations remains to be determined.5
Adiponectin is a key anti-inflammatory adipocytokine that may oppose TNF-alpha
activity in the liver, has been shown to have antifibrotic properties by reducing hepatic
stellate cell proliferation and increasing apoptosis.11 Plasma adiponectin concentrations are
reduced in patients with NASH and patients with increased insulin resistance.12 Also, HCV
genotype 3 was found specifically associated with insulin resistance that was associated with
a decrease in total and high molecular weight (HMW) adiponectin levels.8 Lack of
adiponectin enhanced the progression of NASH and exacerbated oxidative stress in mice.13
On the other hand, leptin was found to be higher in NAFLD or steatosis than in normal
controls.14 It may act as a mediator of hepatic inflammation and fibrosis, while low
adiponectin levels may contribute to the development of necroinflammation.15 Another
study in patients with both chronic HCV and steatosis showed a serum adiponectin/TNF-
alpha imbalance (with low adiponectin and high TNF-alpha) that was also associated with
insulin resistance.16 Thus, reduced adiponectin and increased leptin levels may be involved
in the pathogenesis of steatosis, which in turn accelerates progression of fibrosis in chronic
HCV.
The beta 2 microglobulin (b2-MG) concentration was also found to be elevated in HCV
in comparison to the normal values and IFN-alpha therapy caused an increase in the b2-MG.
The highest increase was observed among patients who did not eliminate the virus. A
significant increase in b2-MG during interferon therapy in patients with chronic HCV
infection is a predictor of poor outcome. Also, patients with HCC showed higher serum beta
2MG levels than did chronic hepatitis C patients or healthy subjects.17
The adipocyte-derived anti-obesity hormone leptin may prevent fat accumulation in the liver. It
was found that leptin deficiency in transgenic mice and in humans with lipodistrophies induced
severe liver steatosis (LS) and insulin resistance that are responsive to the administration of
exogenous leptin.18,19,20 In addition, hyperleptinemia has been observed to correlate with LS in
subjects with NASH and chronic hepatitis C, but the exact role of hyperleptinemia in the
pathogenesis of human NAFLD remains controversial.21,22,23,24
Finally, the presence of steatosis was found to impair the early reduction of viral load during
treatment in patients infected with HCV genotype 3 and non-3. Steatosis also, negatively affected
the final outcome of treatment mainly in patients infected with HCV genotype non-3 virus. Thus
interventions aiming at reducing hepatic steatosis prior to the onset of antiviral therapy may be of
benefit to patients infected with HCV.25 The steatosis in these patients was typically improved
following successful antiviral therapy.26,27,28
Aim of our study:
The aim of this work is to assess some clinical, virological, histopathological and biochemical
variables including serum adiponectin, leptin and beta-2- microglobulin in relation to hepatic
steatosis and liver disease severity, in Egyptian patients infected with HCV genotype 4 of early
and late disease with HCC.
Patients and Methodology:
This study included 73 individuals classified as following:
a) Control group: included 23 healthy individuals.
b) Group 1: early active HCV patients: included 25 patients with early HCV infection
genotype 4 who are not cirrhotic.
c) Group 2: cirrhotic with HCC: included 25 HCV cirrhotic patients associated with HCC
All were admitted to Theodor Bilharz Research Institute in Egypt. They were initially
subjected to history; clinical examination, abdominal ultrasonography, liver function tests,
HBs Ag and HCV Ab. Measurement of adiponectin, leptin, beta-2- microglobulin (done by
ELISA) and lipid profile had been performed in all groups.
Exclusion criteria: patients who underwent this study must not be having diabetes, alcohol
consumption, drugs causing steatosis such as NSAID’s, salicylate, corticoid, valproic acid,
amiodarone , perhexiline maleate, which are known to affect lipid metabolism at least for 6 weeks
and anti viral therapy. All HCV of genotypes other than genotype 4 were excluded from this
study. In addition, control group patients must be healthy and not obese.
activity, fig3 showing high power of fig 2 showing micro and macrovesicular hepatocytes
steatosis and fig4 showing high severity of hepatocytic steatosis.
Table 1: Clinical and ultrasonographic data of the studied groups
Reference Group 1 Group 2
No of patients 23 25 25
Age 40.23 ± 14.54 39.81 ±12.22 45.14 ±11.93
Body mass index (BMI) 25.56 ± 3.25 24.71 ± 4.36 22.83 ± 5.16
Sex (Male : Female) 14 : 9 18 : 7 19 : 6
Clinical Examination
Hepatomegaly
Splenomegaly
Ascites
-
-
-
20*
4
0
11
19*
7
Ultrasound Hepatic Picture
-Bright (Fatty)
-Fibrofatty (bright coarse)
-Coarse
-Other US signs of cirrhosis #
-Focal lesions
2
-
-
-
-
17
7
1
3
-
5
13
7
25
25
HCV Genotype 4: - 25 25
# These include, among others, shrunken liver, hypertrophied caudate lobe, dilated portal vein, porto-systemic collaterals, attenuated hepatic veins, irregular surface and borders. * P <0.05.
Table 2: Ultrasonographic grading of steatosis:
Reference Group 1* Group 2
Absent (grade 0) 0 4 6
mild (grade 1) 1 4 13
Moderate (grade 2) 1 10 8
Severe ( grade 3) 0 7 0
All groups are comparable as regards to age and sex distribution. Hepatomegaly was significantly more in patients of group 1 with early active hepatitis than those with cirrhosis and HCC. Splenomegaly on the other hand was significantly more in cirrhotic group 2. Steatosis as detected by ultrasound examination was generally of higher grades in early active HCV than those with cirrhosis and HCC. No correlation between BMI and the grade of steatosis (p = 0.236).
Ultrasonograghic echo of steatotic patient
Table 3: Some ultrasonographic, biochemical and histopathological characteristics of HCC in group
2:
One focal lesion Two focal lesions >2 focal lesions Total
Number of patients 8 13 4
Range of diameters (cm)
Mean volume Of lesions (cm3)
1.1-8.5
31.54 14.34
1.0- 11.2*
42.32 16.85*
1.2-12.8
67.64 20.26*#
Echogenecity
Isoechoeic
Hypoechoeic
Hyperechoeic
2
4
2
3
8
2
1
3
0
6
15
4
Site of focal lesion in liver
o Rt. Lobe only
o Lt. lobe only
o Both lobes
6
2
0
6
4
3
1
0
3
14
8
6
Portal vein thrombosis 1 5 2 8
Ascites 1 3 3 7
Perihepatic lymph nodes 2 2 3 7
Distant metastasis 0 0 1 (lungs) 1
Alph-feto protein 526.34 205.25 985.18 282.69* 1234.65
274.14*#
915.39359.28
Histopathology:
o Well-differentiated
o Moderately differentiated
o Poorly differentiated
3
2
3
6
3
4
2
2
0
11
7
7
* Significant difference in comparison with patients with one focal lesion (P < 0.05) # Significant difference in comparison with patients with two focal lesions (P < 0.05)
There was significant direct correlation between the number of focal lesions, the total volume of the focal lesions in each patient and alpha fetoprotein level (P < 0.05) but not with other features. No significant correlation between number of focal lesions, or their volumes and the degree of steatosis or histopathological grades; HAI (P > 0.05). Also, no significant correlation between number of focal lesions, or their volumes and all parameters studied including leptin, adiponectin and B2-MG.
Table 4: Liver function tests in the controls and the studied groups:
*P< 0.05, ** P< 0.01, *** P < 0.005; compared to the reference group.
Normal values of ALT and AST: up to 12 IU/dl. There were significantly lower serum albumin and proteins levels in HCV patients (which are highly significant in group 2); significantly higher Liver enzymes in early active HCV patients and significant hyperbilirubinemia in both groups in comparison with control group.
Table 5 Serum lipid profile in the controls and the studied groups.
*P< 0.01 and ** P< 0.05; compared to the reference group. There were significantly lower serum triglycerides and cholesterol (total, HDL, LDL) levels in Both HCV groups than control group. Low triglycerides and cholesterol levels were significantly correlated with grade of steatosis (P < 0.05).
Table 6: serum levels of leptin, adiponectin and Beta 2 microglobulins in all groups.
* Significant difference in comparison to control group (P< 0.001). # Significant difference in comparison to early HCV patients (P < 0.01). Significant correlations were found between beta 2-
microglobulin concentration, adiponectin and grade of steatosis, HAI and fibrosis scores (P < 0.01). Leptin showed significant correlation only with grade of steatosis (P< 0.05).
Age, level of ALT (IU/L), low serum albumin, serum cholesterol, low TG and chlesterol, high serum leptin, low serum adiponectin, high B2-MG, fibrosis, portal inflammation and lobular inflammation were significantly correlated with steatosis in our analysis.
Table 7: The histopathological parameters of the studied groups.
*Significant. difference from the control group (P < 0.002). The mean number of hepatocytes affected by steatosis was higher in cirrhotic patients but not significant (P>0.05)
Table 8: Relation of HAI and viremia to the grades of steatosis in group 1 patients:
Grade of Hepatocyte Steatosis
0 1-2 3-4
Number of patients
HAI total score (Mean ± S.D)
Portal inflammation
Lobular degeneration
Periportal necrosis
Fibrosis score
Viremia (copies/ml)
0
3.25 ± 0.62
2.52 ± 0.35
0.19 ± 0.12
1.05 ± 0.27
1.21 ± 0.32
651500
±1075928.53
9
5.08 ± 0.34*
2.86 ± 0.24*
1.13 ± 0.32*
1.83 ± 0.58*
1.93 ± 0.62*
1321500
±1173465.71*
13
5.94 ± 0.77*#
3.14 ± 0.97*
1.52 ± 0.81*
2.64 ± 0.59*#
2.87 ± 0.68*#
2550200
±1345645.60*#
*Significant difference with grade 0 (P<0.05). # Significant difference with grade 1-2 (P<0.05).
There was statistically significant higher viremia in those with higher grades of steatosis than lower grades and in lower grades than those without steatosis (P < 0.05).
Table 9: Relation of HAI and viremia to the grades of steatosis in group 2 patients:
Grade of Hepatocyte Steatosis
0 1-2 3-4
Number of patients 5 13 7
HAI total score (Mean ± S.D)
Portal inflammation
Lobular degeneration
Periportal necrosis
Fibrosis score
Viremia (copies/ml)
3.87 ± 0.25
2.45 ± 0.87
0.7 ± 0.13
1.82 ± 0.44
3.02 ± 0.12
412500
± 536780.55
5.76 ± 0.10*
3.13 ± 0.74*
1.25 ± 0.18*
2.66 ± 0.73*
3.37 ± 0.83*
449400
± 596733.61
6.49±0.18*#
3.74±0.38*#
1.56±0.37*#
2.72±0.95*
3.65±0.54*
956300
± 715661.61#
*Significant difference with grade 0 (P<0.05). # Significant difference with grades 1-2 (P<0.05). There was statistically significant higher viremia in group 1 than group2 (P = 0.01). There was statistically significant higher viremia in those with steatosis grade 3-4 than lower grades 2-1 (P < 0.05) but insignificant statistically between lower grades than those without steatosis (P = 0.062).
Steatosis was mild in 30 % of patients, moderate in 32 % and severe in 12 % of patients.
levels than those with other genotypes. An independent predictor of low adiponectin levels in
genotype 3 infection was the severity of steatosis. It was concluded that reduced adiponectin
levels may be involved in the pathogenesis of steatosis, which in turn accelerates progression
of fibrosis in chronic HCV. In chronic HCV patients, hypoadiponectinemia is significantly
associated with the development of liver steatosis. The fact that the plasma levels of
adiponectin inversely correlate with steatosis in HCV-infected subjects suggests that
hypoadiponectinemia may contribute to hepatic steatosis progression and liver injury in this
population. Other data which supports such assumption are that therapy to increase circulating
adiponectin concentration, such as overweight reduction or thiazolidinediones, provides the
potential to improve steatosis in chronic hepatitis C infection, 14,16 and that the logarithmic
serum adiponectin level was inversely correlated with the logarithmic levels of serum AST,
ALT and gamma GT.54 Also, the change of adiponectin levels still significantly related to the
response to IFN-alpha. In one more study, high HCV load and genotype 2 were significantly
associated with a lower serum adiponectin level.53
On the other hand, serum leptin level was found in this study to increase significantly with
the increase of steatosis and the progression of liver disease. However, its level showed
correlation only with the grade and severity of steatosis but not with inflammation or fibrosis.
In patients with chronic hepatitis C and steatosis, results of leptin serum levels in different
studies were controversial. One study showed values in these
. patients similar to healthy individuals and no relationship was found between leptin levels
and severity of steatosis.55 Other studies found that hepatic steatosis was related to genotype,
fibrosis degree, and serum leptin levels. Genotype 3 seems to have a viral specific steatogenic
effect. Leptin seems to be a link between obesity and steatosis development in HCV genotype
1–infected patients as it was found that there were correlations between HCV, leptin, body
mass index, percentage of body fat, and visceral obesity.56 In other studies, it was found that
chronic hepatitis C patients with and without steatosis were similar with respect to their serum
glucose, lipid and leptin levels and serum leptin levels were correlated with obesity and with
liver transaminases only in patients with steatosis. Also, it was found that chronic hepatitis C
patients with or without steatosis had similar leptin levels. Thus it was concluded from this
study that leptin levels were well correlated with anthropometrical parameters in chronic
hepatitis C patients and leptin levels were associated with evidence of impaired hepatic
function and may be a prognostic marker in patients with chronic HCV related steatosis.57 also,
it can have a role in the regulation of hepatic fibrosis.56
Conclusion: In our Egyptian patients, HCV genotype 4 infection was associated with many
factors that are highly linked to the development of steatosis such as high leptin and lower
adiponectin serum levels, and beta 2 microglobulin which is a marker of more severe disease
and poor outcome. Steatosis is commonly seen in genotype 4 and its extent or grade was
associated with high viral load, more severe inflammation and fibrosis. The pathogenesis of
HCV-related steatosis in general is likely to be multifactorial; probably genotype or viral-
related process with all the biochemical changes secondary to it. These factors may re-
perpetuate and exaggerate the pathological conditions. It is assumed from this study that
steatosis should be considered as a risk factor in our patients with HCV genotype 4 and should
be considered as a target for therapeutic interventions in addition to the viral and inflammatory
process of the liver. Further investigations are needed to prove the effect of such therapeutic
intervention on the prognosis of such patients.
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التقييم السريرى والكيمائى و الفيروسى والنسيجى لمرض التشمع الكبدى فى المرضى المصريين طان الكبدوكذلك المصاحب لسر ٤المصابين بالفيروس الكبدى ج النوع الوراثى
منى حسن و نهال العسالى ونعيمة العشرى و ميرفت الدمراوى وشندى محمد شندى وطارق أبو شوشة.
قسم الكيمياء االكلينيكية و قسم الرعاية المركزة و قسم األمراض المتوطنة وقسم الباثولوجى معهد تيودور بلهارس لألبحاث
ملخص البحث:
فى عينات الكبد. وهذا إنما يدل %05المصابين بالفيروس الكبدى ج وقد يصل إلى إن التشمع الكبدى شائع فى المرضى
على تداخل خاص بين هذا الفيروس والتمثيل الغذائى للدهون. وقد كان الهدف من هذا البحث هو تقييم بعض العوامل
وعالقتها بالتشمع ٢كروجلوبيولين بالسريرية والكيمائية و الفيروسية والنسيجية بما فى ذلك االديبونكتين واللبتن والمي
المبكر وكذلك المصاحب للتليف ولسرطان ٤الكبدى فى المرضى المصريين المصابين بالفيروس الكبدى ج النوع الوراثى
الكبد.
٤مريضا مصابين بالفيروس الكبدى ج النوع الوراثى ٠٥شخصا و ٢٢وقد شمل هذا البحث مجموعة مقارنة مكونة من