|Year : 2017 | Volume
| Issue : 1 | Page : 21-26
Anticardiolipin antibody in egyptian patients with chronic hepatitis c in correlation with liver injury
Mahmoud H Hemida MD 1, Shaaban S Alazhari2, Ahmed El Borae Kabil2, Abd El Halim Assem Elsherif2, Mohamed Abd El Hameed Khedr3
1 Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Tropical Medicine, Al-Azhar University, Cairo, Egypt
3 Department of Clinical Pathology, Al-Azhar University, Cairo, Egypt
|Date of Submission||12-Nov-2016|
|Date of Acceptance||16-Mar-2017|
|Date of Web Publication||23-Aug-2017|
Mahmoud H Hemida
Department of Internal Medicine, Al-Azhar University, Cairo
Source of Support: None, Conflict of Interest: None
The presence of anticardiolipin (ACL) antibodies in chronic hepatitis C may be owing to induction of neoantigens by chronic viral infection, which may be because of disruption of liver cell membranes. The occurrence of these ACL antibodies may be observed because of recognition of these neoantigens by the immune system.
The aim of the work was to study the prevalence and clinical significance of ACL antibodies in chronic hepatitis C infection and their relationship with disease progression.
Participants and methods
Our study was performed on 90 individuals recruited from Gastroenterology and Hepatology Outpatient Clinics and Internal Medicine Department of Kafr Sheikh Institute. The participants were divided into the following three groups: group A consisted of 30 patients with chronic hepatitis C virus (HCV) infection with compensated liver cirrhosis, group B consisted of 30 patients with chronic HCV infection with decompensated liver cirrhosis, and group C consists of 30 individuals as control. All patients and control were subjected to full history taking, full clinical examination, complete blood count, liver function tests, renal profile, pelvis–abdominal ultrasound, and serum levels of ACL immunoglobulin G and α-fetoprotein.
The results showed that seven (23%) of the HCV-positive patients in group A and 18 (60%) of the HCV-positive patients in group B were ACL immunoglobulin G-positive in comparison with none in the control group (0%).
The prevalence of ACL antibodies is increased during HCV infection, and HCV should be regarded as a possible causative factor in the antiphospholipid syndrome.
Keywords: anticardiolipin antibodies, antiphospholipid syndrome, cirrhosis, hepatitis c, thrombosis
|How to cite this article:|
Hemida MH, Alazhari SS, Kabil AE, Elsherif AA, Khedr MA. Anticardiolipin antibody in egyptian patients with chronic hepatitis c in correlation with liver injury. Al-Azhar Assiut Med J 2017;15:21-6
|How to cite this URL:|
Hemida MH, Alazhari SS, Kabil AE, Elsherif AA, Khedr MA. Anticardiolipin antibody in egyptian patients with chronic hepatitis c in correlation with liver injury. Al-Azhar Assiut Med J [serial online] 2017 [cited 2019 Sep 22];15:21-6. Available from: http://www.azmj.eg.net/text.asp?2017/15/1/21/213590
| Introduction|| |
Antiphospholipid antibodies are autoantibodies with an affinity for anionic phospholipids .They are organ nonspecific antibodies that have been reported in various clinical conditions such as deep venous thrombosis, arterial occlusive events (e.g. stroke and myocardial infarction), recurrent fetal loss, and thrombocytopenia .
They are also associated with vasospastic phenomena such as migraine, Raynaud’s phenomenon, and transient ischemic attack. However, the pathogenesis and clinical significance of these antibodies are still unclear .
Antiphospholipid antibodies have been detected in various infectious diseases particularly of viral origin, such as HIV, hepatitis A, and mumps .
These antibodies are not usually associated with thrombotic events, as happens with autoimmune diseases, in which these antibodies need the presence of β2 glycoprotein I (β2GPI), which bears the epitope(s) for anticardiolipin (ACL) antibodies .
There are several kinds of antiphospholipid antibodies. The two most commonly measured are lupus anticoagulant and ACL antibody. Lupus anticoagulant and ACL antibody are closely related but are not the same antibody, which means that a person can have one and not the other .
For example, in various studies, 8–65% of people with lupus have the lupus anticoagulant and 25–61% have ACL antibody; these antibodies can also be found in people who do not have lupus .
There are other antiphospholipid antibodies but are not routinely measured. These include anti-β2GPI, antiprothrombin, and the one seen in ‘false-positive’ test for syphilis .
The WHO has declared hepatitis C as a global health problem, with ∼3% of the world’s population (roughly 170–200 million people) infected with hepatitis C virus (HCV). In the USA, approximately three million people are chronically infected; many of whom are still undiagnosed. In Egypt, the situation is quite worse, as the national prevalence rate of HCV antibody positivity has been estimated to be between 10 and 13% in 2002, and it contains the highest prevalence of HCV in the world .
The estimated prevalence rate in Egypt is ∼15% .
The mechanisms whereby HCV circumvents immune response and establishes persistent infection are currently undefined. It is well known that the specific immune response to any viral infection is primed by macrophages and dendritic cells that present viral proteins to B cells, helper T cells, and cytotoxic T cells. Progression to persistent infection and immunologic mechanisms of liver injury are caused because of complicated interactions between the virus and the host. Identification of immunologic correlates of viral clearance may contribute to the development of an effective vaccine and better therapy for HCV infection .
The aim of this study was to evaluate the prevalence and clinical significance of ACL antibody in chronic hepatitis C infection and their relationship with disease progression.
| Participants and methods|| |
This study was performed on 90 individuals recruited from the Gastroenterology and Hepatology and Internal Medicine Outpatient Clinics of Kafr El Sheikh Institute during the period from December 2013 to October 2014.
The participants were divided into the following three groups:
- Group A: it consists of 30 patients with chronic HCV infection with compensated liver cirrhosis.
- Group B: it consists of 30 patients with chronic HCV infection with decompensated liver cirrhosis.
- Group C: it consists of 30 individuals as control.
All patients and control were subjected to the following:
- Full history talking was done with special emphasis on risk factor, duration of disease, and alcohol intake.
- Full clinical examination was performed with special emphasis on the presence of signs of chronic liver disease (spider naevi, palmar erythema, level of consciousness, flapping tremors, ascites, splenomegaly, and jaundice).
- Routine laboratory investigations, including complete blood count, serum creatinine and blood urea nitrogen, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum alkaline phosphatase, total and direct bilirubin, serum albumin and total proteins, prothrombin time, and urine analysis were conducted.
- Abdominal ultrasonography was used to confirm the presence of liver cirrhosis, ascites, splenomegaly, portal vein diameter, and detect portal vein thrombosis.
- Serum level of ACL antibody immunoglobulin G (IgG) was evaluated.
- HCV antibodies were assessed using enzyme-linked immunosorbent assay, and HCV RNA qualitative analysis was done to prove HCV infection, supplied by Roche Ampliform.
- Presence of HBsAg was detected.
- Liver biopsy was performed.
Statistical presentation and analysis of the present study were done using mean, SD, and Student’s t-test (unpaired), paired t-test, linear correlation coefficient (r), and χ2-analysis of variance.
| Results|| |
This study included 90 participants: 30 patients with chronic hepatitis C (group A) with compensated liver cirrhosis, 30 patients with decompensated liver cirrhosis (group B), and 30 healthy individuals (group C) as control.
There were no statistically significant difference regarding age, sex, prothrombin time, α-fetoprotein, ALT, AST, white blood cells, and hemoglobin and highly statistical significant difference regarding platelet count, albumin, platelet, bilirubin, portal vein diameter, splenic vein diameter, and child score among the three groups. Regarding the level of serum ACL IgG, it is found that the number of positive patients in group A is seven (23.33%) and negative is 23 (76.67%); in group B, the number of positive patients is 18 (60%) and negative is 12 (40%); and in group C, the number of positive patients is 0 (0.00%) and negative is 30 (100%). Of the 60 patients with chronic hepatitis infection, 41% were positive for ACL IgG. There is a highly significant statistical difference among the four groups (P<0.001) ([Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6],[Table 7],[Table 8]).
|Table 1 Comparison between different groups regarding the mean level of anticardiolipin antibody immunoglobulin G|
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|Table 2 Relation between Child classification and positive and negative anticardiolipin antibodies|
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|Table 3 Relation between prothrombin time and positive and negative anticardiolipin antibodies|
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|Table 4 Relation between liver enzymes and positive and negative anticardiolipin antibodies|
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|Table 5 Relation between albumin level and positive and negative anticardiolipin antibodies|
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|Table 6 Relation between direct bilirubin and positive and negative anticardiolipin antibodies|
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|Table 7 Relation between portal vein diameter and positive and negative anticardiolipin antibodies|
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|Table 8 Comparison of statistical data of anticardiolipin antibodies immunoglobulin G-positive and immunoglobulin G-negative patients in different groups|
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| Discussion|| |
Notably, viral infections (including hepatitis B and C, HIV, cytomegalovirus, Epstein–Barr virus, varicella zoster virus, adenovirus, and parvovirus B19) and neoplastic diseases may induce the production of antiphospholipid antibodies .
Regarding chronic viral hepatitis, several reports have described a high prevalence of ACL antibodies in patients with chronic hepatitis C infection .
It has been proposed that the release of procoagulant products consisting of membrane fragments and negatively charged macromolecules (that may bind with β2GPI) from HCV-infected cells might stimulate the synthesis of ACL antibodies .
The presence of ACL antibodies in chronic hepatitis C may be because of induction of neoantigens by chronic viral infection owing to disruption of liver cell membrane. The occurrence of ACL antibodies may be because of recognition of these neoantigens by the immune system . Alternatively, the stimulation of apoptosis by the virus may lead to redistribution of plasma membrane phospholipids and therefore lead to their overexpression on the apoptotic cell membrane surface, which may result in ACL antibodies synthesis .
In chronic hepatitis C, antiphospholipid antibodies have also been found to be associated with advanced disease and fibrosis progression  and with the presence of low platelet count .
Jose et al.  suggested that antiphospholipid antibodies may participate in the process of fibrogenesis by promoting thrombosis in small stimulation of fibroblasts.
Although this is an intriguing possibility, the higher prevalence of ACL antibodies in advanced cirrhosis might be also explained by the fact that the processes stimulating fibrogenesis, such as lipid peroxidation, may also facilitate the production of antiphospholipid antibodies .
In this study, we focused on evaluating the presence of ACL antibodies including ACL IgG. In patients with chronic hepatitis C infection, the presence of these antibodies correlated with grade of the disease, ranging from mild form to cirrhosis.
There were three groups:
- Group A: it consisted of 30 patients with chronic HCV infection with compensated liver. There were six male and 24 female patients, and their ages ranged from 19 to 76 years, with mean age of 51.4±11.1 years.
- Group B: it consisted of 30 patients with chronic HCV infection with decompensated liver. There were seven male and 23 female patients, with age ranging from 29 to 63 years. The mean age was 48.8±9.2 years.
- Group C: it consisted of 30 healthy individuals as control. There were 21 female and nine male individuals, with age ranging from 34 to 59 years. The mean age was 49.1±8.4 years.
In the present study, there was no significant statistical difference among groups A, B, and control regarding age and sex, which agrees with the study by Wilson et al.  who stated that the four groups in their study were similar for age and sex.
Regarding the level of serum ACL IgG, the number of positive patient in group A is seven (23.33%) and negative is 23 (76.67%); in group B, positive is 18 (60%) and negative is 12 (40%); and in group C, positive is 0 (0.00%) and negative is 30 (100%). Of the 60 patients with chronic hepatitis infection, 41% were positive for ACL IgG, whereas no individual in control group was positive (0% positive); there is a highly statistical significant difference between the three groups (P<0.001). This difference was in agreement with Sthoeger et al. , who stated a highly significance difference between the HCV group (44% were positive for ACL IgG) and control group (0% positive) ; with Cojocaru et al. , who stated that there is a highly significance difference between HCV group (46% positive) and control group (5% positive) ; with Zachou et al. , who stated a highly significance difference between HCV group (22% positive) and control group (1.12% positive), and finally with Romero Gómaz et al. , who stated a highly significance difference between HCV group (22% positive) and control group (3.2% positive).
Regarding the correlation of level of ACL IgG in Child classification, ACL IgG level shows a highly significant statistical difference between Child B score and Child A and C scores together, being higher in the classes A and C; levels of ACL IgG according to Child A, B, and C scores were 38.33, 28.33, 33.33%, respectively, that is, it is about twice as high as in classes A and C that in class B (P=0.001). However, there was a nonsignificant difference between Child scores A and C (P=0.075).
These results agree with Mangia et al. , who stated that in patients with liver cirrhosis regardless of the presence of hepatocellular carcinoma, liver failure (assessed by Child–Pugh score) appeared to influence the rate of ACL-positive patients; the positive values were twice as higher in classes A and C than in class B (P=0.009). Moreover, the results agree with Romero Gómaz et al. , who stated a significant difference between Child classes and ACL antibodies.
Regarding the coagulation profile in groups A and B, none of the antibodies show a significant statistical correlation with prothrombin time; this agrees with Harada et al. , who stated that ACL IgG is not significantly correlated with prolonged partial thromboplastin time or international normalized ratio and also agrees with Habibagahi et al. , who also stated no significant correlation between the antiphospholipid antibodies and coagulation profile.
Regarding the level of serum albumin in group A, mean level is 3.47±0.255, group B is 2.29±0.206, and group C is 4.6±0.288. ACL IgG shows highly significant correlation (P<0.001). This agrees with Romero Gómaz et al. , who stated high significant correlation between ACL IgG and albumin level, but disagrees with Harada et al. , who stated a nonsignificant correlation between ACL antibodies and albumin level (P>0.05); this may be attributed to very low number of patients with cirrhosis who have hypoalbuminemia in their study (40 patients with HCV with a mean serum albumin level of 3.9±1).
Regarding the portal vein diameter, the mean value in group A is 10.13±0.86, group B is 13.16±0.986, and group C is 9.20±1.35.
All the antibodies show highly significant statistical correlation with ACL IgG (f=171.50, P<0.001). This agrees with Romero Gómaz et al. , who stated a highly significant correlation between portal vein diameter and portal hypertension with ACL IgG.
Regarding splenic vein diameter in group A, the mean value is 12.76±0.858, group B is 16.1±1.539, and group C is 10.0±0.667. ACL IgG shows a highly significant correlation with splenic vein diameter. This agrees with Romero Gómaz et al.  who stated a highly significant correlation between splenic vein diameter and ACL IgG, but disagree with Harada et al. , who stated no significance correlation between the ACL-positive patients and splenic vein diameter; the discrepancy in these results may be because of different age groups and duration of the disease.
Concerning the platelet count, there is a highly significant correlation between ACL IgG antibodies and platelet count, with mean level in group A being 179.8±4.49, group B 95.5±4.45, and group C 250.6±17.16. This agrees with Mackworth-Young et al. , who stated significant correlation between ACL IgG and platelet count (P<0.001), but disagrees with Mangia et al. , who stated that ACL antibodies were not associated with thrombocytopenia (P=0.28), and also disagrees with Zachou et al. , who stated that mean value of ACL IgG in HCV patients was 17.38±7.37; only 12 patients of 36 had thrombocytopenia, and this was because of number of patients being low, no decompensate cases, and difference in demographics and genetic background.
No statistically significant correlation was found regarding liver enzymes (AST and ALT) and ACL IgG. This finding agrees with Zachou et al. , who stated that neither AST nor ALT were correlated with the level of ACL antibodies, with Mangia et al. , who stated that raised ALT level is not correlated with ACL antibodies (121.6±94) (P=0.52), and finally with Habibagahi et al. , who stated that there is no association between ALT and ACL antibodies, where only eight patients of the ACL-positive patients were less than 40 IU and only 18 patients were at least 40 IU of 53 patients with HCV.
Bilirubin level had a statistically significant correlation with ACL IgG. This finding agrees with Zachou et al. .
Ordi-Ros et al.  found that ACL antibody concentrations were significantly higher in patients with cirrhosis; thus, they concluded that ACL antibodies play a role in the development of cirrhosis.
In the present study, no statistical significance was present between hemoglobin and white blood cell levels and ACL IgG.
The present study clearly revealed that ACL antibodies are one of the most common autoantibodies found in patients with chronic liver disease (mainly in chronic viral hepatitis). The prevalent concept is that, in most cases, ACL antibodies are nonpathogenic, and therefore, their routine determination is not justified. However, in particular, patients with special immune reactivity or with abnormal hemostatic regulation, ACL antibodies may exert a procoagulant effect and be involved in the genesis of thrombotic events. The question as to whether ACL antibodies are purely neutral epiphenomena autoantibodies or whether they have a role in disease progression or in the pathogenesis of extrahepatic manifestations of viral hepatitis, as yet, is an unresolved issue.
| Conclusion|| |
The prevalence of ACL antibodies is increased in HCV infection, but their pathogenetic role and the mechanisms that stimulate their production have not yet been clarified, and HCV should be regarded as a possible causative factor in the antiphospholipid syndrome.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]