title: Possible contribution of serum activin A and IGF-1 in the development of hepatocellular carcinoma in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis.
abstract: OBJECTIVE
  The present study evaluated the role of activin A, insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) in Egyptian patients suffering from combined hepatitis C virus (HCV) infection and hepatic schistosomiasis.
  
  
  METHODS
  Four groups were included in the present study. Group I: 30 healthy subjects were included as controls; Group II (HCV): 30 patients with chronic liver disease due to HCV infection without evidence of schistosomiasis; Group III (SHF + HCV): 30 patients with combined disease, chronic schistosomal hepatic fibrosis (SHF) and chronic hepatitis C infection; Group IV (HCC): 30 patients with hepatocellular carcinoma associated with chronic hepatitis C virus and schistosomal infection.
  
  
  RESULTS
  Patients with HCV, HCV + SHF and those with HCC had a significantly higher serum activin A compared with the control group (P < 0.001). Serum activin A level (mean +/- SD) was 5.7 +/- 2.76, 10.59 +/- 3.59, 15.39 +/- 4.61 and 19.93 +/- 5.43 ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Serum IGF-1 was significantly lower in HCV patients, HCV + SHF patients and HCC patients compared to the control group (P < 0.001). Serum IGF-1 was 121.7 +/- 73.4, 76.7 +/- 23.5, 35.7 +/- 17.6 and 39.9 +/- 25.9 ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Similarly, serum IGFBP-3 was significantly lower in HCV patients, HCV + SHF patients and HCC patients compared to the control group (P < 0.001). Furthermore, serum insulin-like growth factor binding protein 3 (IGFBP-3) was significantly lower in patients with HCC compared to patients with HCV or those with HCV + SHF (P < 0.01 and P = 0.024, respectively). The median (range) of serum IGFBP-3 was 4452 (352.2-8965), 3457 (1114-6000), 2114 (867-5901) and 1202 (576-3994) ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Serum activin A correlated positively with Child-Pugh scoring in patients with HCV, HCV + SHF and those with HCC. The correlation coefficient was significant, at 0.001, in total cases.
  
  
  CONCLUSIONS
  We conclude that patients with HCV, HCV + SHF and those with HCC have a significantly higher serum activin A when compared with controls. Serum activin A level was significantly higher in patients with HCV + SHF compared to those with HCV alone (P < 0.01) with a significant positive correlation between the serum activin A level and Child-Pugh scoring in patients with HCV, HCV + SHF and those with HCC. Furthermore, serum IGF-1 and IGFBP-3 levels were significantly reduced in patients with HCV, HCV + SHF and those with HCC compared to the control group. We suggest that this pattern (high activin A and low IGF-1 and its binding protein 3) may play a role in development of HCC in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis.
authors.affiliation: Department of Chemical Pathology, Medical Research Instituitre, Alexandria University, Alexandria, Egypt. myelsammak@hotmail.com
authors.forename: Mohamed Yousry
authors.initials: MY
authors.lastname: Elsammak
authors.forename: Gamal M
authors.initials: GM
authors.lastname: Amin
authors.forename: Gehan M
authors.initials: GM
authors.lastname: Khalil
authors.forename: Wafaa S
authors.initials: WS
authors.lastname: Ragab
authors.forename: Mona M
authors.initials: MM
authors.lastname: Abaza
mesh_terms: D028341:Activins / Q000097:blood*; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000150:complications*; D004534:Egypt; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000150:complications*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008113:Liver Neoplasms / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012552:Schistosomiasis / Q000097:blood / Q000150:complications*
chemical_list: C422405:activin A; D028341:Activins; D007334:Insulin-Like Growth Factor I; D028322:Inhibin-beta Subunits