Chronic liver disease represent an increasing health problem in Egypt. The high prevalence of hepatotropic viruses, especially HCV contribute to this problem. Autoimmune mechanisms have been reported to contribute to tissue damage with circulating non-organ-specific and/or liver-specific autoantibodies.Hepatitis C viruses are well-recognized causes for chronic hepatitis, cirrhosis and even for hepatocellular carcinoma. About 5% of adult patients with acute HBV infection develop chronic hepatitis B, an estimated 50% to 75% of patients with acute HCV develop chronic infection. Moreover, chronic HCV infection rarely, if ever spontaneously resolves.Hepatitis G virus is a new discovered virus. Current estimates suggest that about 0.9% to 10% of blood donors worldwide, have been or are infected with HGV.The aim of our work is to estimate the association of autoimmune markers in patients with chronic viral hepatitis and to learn whether demographic features distinguish between patients with or without autoimmune markers in our locality. Also to compare the response to INF alpha 2a and Ribavirin therapy between chronic HCV patients who were positive for autoimmune markers and those who were not.The present work was done in Microbiology & Immunology Department Faculty of Medicine, Zagazig University in the period from November 2003 to October 2004. This study was conducted on 50 patients classified as 20 patients with chronic HCV (group I), 10 patients with chronic HCV treated with interferon (group II), 10 patients with chronic HBV (group III), 10 patients with chronic HGV (group IV), and 10 normal volunteers as normal control, with age ranged from 18 to 44 years with mean age 32.7± 8.7. Regarding the age of our patients, group I ranged from 32 to 55 years with mean age 43.3 ± 7.7, group II ranged from 28 to 55 years with mean age 42.8 ± 9.1, group III ranged from 20 to 51 years with mean age 33.5± 11.5 years and lastly group IV ranged from 16 to 31 years with mean age 18.3 ± 3.5 years. All specimens in the four groups were already diagnosed as chronic viral hepatitis [hepatitis C, B or G].All cases of this study were subjected to serological examination for screening of serum autoantibodies testing for antinuclear antibody [ANA], antismooth muscle antibody [ASMA] and antimitochondrial antibody [AMA].These serological examination were done using indirect immunoflourescene technique, using autoimmune antibody screening test system containing rat, liver/stomach/kidney substrate. [ Trinity Biotech PLC. Bray, County Wicklow, Ireland]. Titres < 1/20 were considered non-significant for each of the studied antibodies.Our results showed:1. There were no statistically significant difference between the prevalence of autoantibodies and each of age, sex or residence in different hepatitis groups.2. When the prevalence of antinuclear antibodies among the hepatitis patients group was compared to the control group, it was found that the difference between HBV group and the control was statistically significant [P< 0.01] while there were no significant difference between HCV or HGV and the control group [P< 0.05].3. The prevalence of ASMA was 93.3% among chronic hepatitis C cases, 90% among chronic hepatitis B and chronic hepatitis G compared the control group.4. when we compared the prevalence of AMA among the hepatitis patients groups, and the control, we found that there is statistically significant difference between each hepatitis group [HCV, HBV or HGV] and the control [P<0.01]. On the other hand, there was no statistically significant difference between the different hepatitis patients groups.5. There is significant difference in HCV, HBV and HGV patients and control group regarding the presence of ANA, and AMA [P<0.01], and there is highly significant difference in HCV, HBV and HGV patients compared to control group regarding the presence of ASMA, P value was < 0.001.6. Regarding the treatment with INF-alpha 2a and Ribavirin, there was no significant difference in response rates in chronic HCV patients who were positive for autoantibodies [ANA, ASMA and AMA] compared to those who were not, and treatment did not worsen hepatitis.CONCLUSIONAutoimmune markers are highly prevalent in chronic viral hepatitis patients in Zagazig Governrate Egypt. Age, sex and residence have no effect on the prevalence of such autoimmune markers. Antinuclear antibodies (ANA) were more prevalent in chronic hepatitis B. while antismooth muscle antibodies (ASMA) and antimitochondrial antibodies (AMA) were prevalent in chronic viral hepatitis (C, B and G). The presence of such autoantibodies in chronic HCV dose not affect the response to treatment with INF-alpha 2a and Ribavirin which is the same in those with or without autoantibodies.Thus the great majority of patients in Egypt with chronic HCV, including those with positive markers of autoimmunity, will not suffer a worsening of hepatitis or development of autoimmune manifestations when treated with IFN alpha 2a and Ribavirin.For this aim, thirty patients with chronic hepatitis C infection were studied and their results were compared with that of 20 control subjects.All the studied patients and controls were subjected to:1- Complete clinical examination with full history taking.2- Abdominal ultrasound for assessment of chronic liver condition.3- Complete blood picture.4- Liver function tests including bilIrubin, albumin, AST, ALT, alkaline phosphatase and GGT.5- Prothrombin time.6- Detection of HCV antibodies by ELISA.7- Detection of HCV RNA by PCR for patients only.8- Serum alpha 2 macroglobulin, apolipoprotein A1, haptoglobin by immune diffusion methods.9- Liver biopsy for detection of fibrosis and necroinflammatory activity for HCV-RNA positive.The results of this study show the following:• Highly significant reduction in platelets number of the patients.• Highly significant reduction in haemoglobin concentration of the patients.• Significant changes in liver function test with the degree of fibrosis in form of increase of liver enzyme (ALT, AST), serum bilirubin, serum alkaline phosphatase, serum GGT and decrease in serum albumin.• Highly significant prolongation in PT of the patients.• Highly significant decrease in haptoglobin in patients with fibrosis.• Highly significant decrease in apolipoprotein A1 of the patients and among the stages of liver fibrosis.• Highly significant increase in alpha 2 macroglobulin of the patients, and good correlation with fibrosis.