الفهرس 
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Abstract
C
hronic hepatic C virus infection is a major health problem worldwide (Bria et al., 2017). In Egypt resides one of the highest hepatitis C virus (HCV) prevalences in the world, it is (10%) among persons who are 15-59 years old (Thrift et al., 2016 and Kandeel et al., 2017).
Until a few years ago, there were only two drugs approved by USA Food And Drug Administration (FDA) for chronic hepatitis C treatment, pegylated interferon and ribvirin (Sulejmani and Jafri, 2018).
The expenses and plenty of that treatment adverse effects dragged a great concern about studying its response predictors (Shalaby et al., 2012).
In normal liver, hepatic progenitor cells (HPCs) are facultative stem cells located at terminal bile canaliculi (Ker et al., 2011). Upon injury, it becomes active and proliferate in the form of ductular reaction (DR) located in periportal area and within fibrous septa, and isolated progenitor cells (IPCs) located within the parenchyma (D’Ambrosio et al., 2012).
HPCs histologically are oval small cells with high neucleocytoplasmic ratio (Tsamandas et al., 2006). Ductular reactions composed of heterogenic population of cells expressing wide range of immunohistochemical markers including stem cells markers (e.g.: CD56 (NCAM) and CD133), markers of immature hepatocytes and markers of immature cholangiocytes (Tsamandas et al., 2006, Tsuchiya et al., 2009 and Sancho-Bru et al., 2012).
The current study was conducted to investigate the potential role of immunoexpression of hepatic progenitor cells markers (CK19 and CD56 (NCAM)) in the pretreatment liver biopsies in predicting the response of chronic HCV Egyptian patient to pegylated interferon plus ribavirin therapy. Paraffin embedded blocks and hematoxylin and eosin (Hx&E) stained slides of pretreatment liver biopsies were retrieved from pathology department, El Doaa Hospital, Cairo, Egypt.
The current study was a retrospective one, including 120 chronic HCV who were submitted to pretreatment liver biopsies and have been treated by pegylated interferone plus ribavirin for 48 weeks.
All cases were studied according to the following lines:
I. Clinical studies: by reviewing the files of the patients for age and gender.
II. Laboratory data: pretreatment serum HCV-RNA level was classified into low viremia (<600,000 IU/ML) and high viremia (≥600,000 IU/ML).
III. Histopathologic study: Grade of activity and stage of fibrosis were evaluated based on the scoring system of METAVIR and the degree of steatosis was assessed according to Brunt’s scale.
IV. Virological response: patients were divided into responders and non responders. The latter group included patients with no virological response, patients with viral break through and patients with viral relapse.
V. Immunohistochemical study: chronic HCV liver cores were examined for HPCs expression using CK19 and CD56 (NCAM). The median of HPCs expression was assessed for DR form and IPCs form. Immunohistochemical staining succeeded in 110 cases using CK19 and in 62 cases using CD56 (NCAM). Normal liver biopsies were stained by both markers as a control.
Then statistical analysis was done to find the relationship between each of the following:
• The virological response and the demographic, laboratory and histopathological findings.
• The relationship between virological response and hepatic progenitor cells.
• The relationship between hepatic progenitor cells and other demographic, laboratory and pathologic variables.
• The correlation between CK19 and CD56 (NCAM) expression in hepatic progenitor cells.
• Finally the value of expression of HPCs in predicting the virological response.
The results revealed non-significant relationship between virological response and other demographic, laboratory and histopathologic findings.
Immunohistochemical study revealed that, proliferation of HPCs was a constant findings in all successfully stained cases using CK19 and CD56 (NCAM).
The median of HPCs expression (in both DR and IPCs forms) was significantly higher in responder group compared to non responder group by CK19 while there was non-significant differences between both groups using CD56 (NCAM).
The median expression of HPCs showed non-significant differences in studied demographic and laboratory data. On the contrary, the differences in the median expression of both HPC forms (DR and IPCs) were statistically significant between grades of activity and stages of fibrosis using METAVIR scoring system, as well as between degrees of steatosis using Brunt’s system, excluding the differences in the IPCs form by CK19 between grades of activity which was insignificant.
In the present study, it was noted that DR and IPCs are always present together in all sucssisfully stained liver biopsies and they showed a highly significant positive correlation to each other by CK19 (P= <0.001), as well as by CD56 (NCAM) (P= <0.001).
The expression of DR by CK19 showed a significant positive correlation with the one by CD56 (NCAM) (P<0.001), and the same was found as regard IPCs (P<0.001).
Moreover, step wise multi-regression analysis was done and revealed that both decreased DR (CK19) with increased IPCs CD56 (NCAM) are the most sensitive predictors of response (F- Ratio= 5.7, P<0.001).
C
hronic hepatic C virus infection is a major health problem worldwide (Bria et al., 2017). In Egypt resides one of the highest hepatitis C virus (HCV) prevalences in the world, it is (10%) among persons who are 15-59 years old (Thrift et al., 2016 and Kandeel et al., 2017).
Until a few years ago, there were only two drugs approved by USA Food And Drug Administration (FDA) for chronic hepatitis C treatment, pegylated interferon and ribvirin (Sulejmani and Jafri, 2018).
The expenses and plenty of that treatment adverse effects dragged a great concern about studying its response predictors (Shalaby et al., 2012).
In normal liver, hepatic progenitor cells (HPCs) are facultative stem cells located at terminal bile canaliculi (Ker et al., 2011). Upon injury, it becomes active and proliferate in the form of ductular reaction (DR) located in periportal area and within fibrous septa, and isolated progenitor cells (IPCs) located within the parenchyma (D’Ambrosio et al., 2012).
HPCs histologically are oval small cells with high neucleocytoplasmic ratio (Tsamandas et al., 2006). Ductular reactions composed of heterogenic population of cells expressing wide range of immunohistochemical markers including stem cells markers (e.g.: CD56 (NCAM) and CD133), markers of immature hepatocytes and markers of immature cholangiocytes (Tsamandas et al., 2006, Tsuchiya et al., 2009 and Sancho-Bru et al., 2012).
The current study was conducted to investigate the potential role of immunoexpression of hepatic progenitor cells markers (CK19 and CD56 (NCAM)) in the pretreatment liver biopsies in predicting the response of chronic HCV Egyptian patient to pegylated interferon plus ribavirin therapy. Paraffin embedded blocks and hematoxylin and eosin (Hx&E) stained slides of pretreatment liver biopsies were retrieved from pathology department, El Doaa Hospital, Cairo, Egypt.
The current study was a retrospective one, including 120 chronic HCV who were submitted to pretreatment liver biopsies and have been treated by pegylated interferone plus ribavirin for 48 weeks.
All cases were studied according to the following lines:
I. Clinical studies: by reviewing the files of the patients for age and gender.
II. Laboratory data: pretreatment serum HCV-RNA level was classified into low viremia (<600,000 IU/ML) and high viremia (≥600,000 IU/ML).
III. Histopathologic study: Grade of activity and stage of fibrosis were evaluated based on the scoring system of METAVIR and the degree of steatosis was assessed according to Brunt’s scale.
IV. Virological response: patients were divided into responders and non responders. The latter group included patients with no virological response, patients with viral break through and patients with viral relapse.
V. Immunohistochemical study: chronic HCV liver cores were examined for HPCs expression using CK19 and CD56 (NCAM). The median of HPCs expression was assessed for DR form and IPCs form. Immunohistochemical staining succeeded in 110 cases using CK19 and in 62 cases using CD56 (NCAM). Normal liver biopsies were stained by both markers as a control.
Then statistical analysis was done to find the relationship between each of the following:
• The virological response and the demographic, laboratory and histopathological findings.
• The relationship between virological response and hepatic progenitor cells.
• The relationship between hepatic progenitor cells and other demographic, laboratory and pathologic variables.
• The correlation between CK19 and CD56 (NCAM) expression in hepatic progenitor cells.
• Finally the value of expression of HPCs in predicting the virological response.
The results revealed non-significant relationship between virological response and other demographic, laboratory and histopathologic findings.
Immunohistochemical study revealed that, proliferation of HPCs was a constant findings in all successfully stained cases using CK19 and CD56 (NCAM).
The median of HPCs expression (in both DR and IPCs forms) was significantly higher in responder group compared to non responder group by CK19 while there was non-significant differences between both groups using CD56 (NCAM).
The median expression of HPCs showed non-significant differences in studied demographic and laboratory data. On the contrary, the differences in the median expression of both HPC forms (DR and IPCs) were statistically significant between grades of activity and stages of fibrosis using METAVIR scoring system, as well as between degrees of steatosis using Brunt’s system, excluding the differences in the IPCs form by CK19 between grades of activity which was insignificant.
In the present study, it was noted that DR and IPCs are always present together in all sucssisfully stained liver biopsies and they showed a highly significant positive correlation to each other by CK19 (P= <0.001), as well as by CD56 (NCAM) (P= <0.001).
The expression of DR by CK19 showed a significant positive correlation with the one by CD56 (NCAM) (P<0.001), and the same was found as regard IPCs (P<0.001).
Moreover, step wise multi-regression analysis was done and revealed that both decreased DR (CK19) with increased IPCs CD56 (NCAM) are the most sensitive predictors of response (F- Ratio= 5.7, P<0.001).