ABSTRACT
Soluble intercellular adhesion molecule-1 [sICAM-1] is a marker of inflammation and tissue damage. To determine the serum level of sIC AM-1 in patients with chronic HCV and to correlate the results with the histopathological changes. The study included thirty subjects divided into two groups: group I [GI] comprising 20 patients [mean age 39.7 +/- 8.5 years] with chronic hepatitis C virus infection and group II [Gil] of 10 healthy age and sex-matched control subjects [mean age 37.8 +/- 10.52 years]. Serum concentrations of sICAM were measured by enzyme linked immunosorbent assay [ELISA] kit as per manufacturer's instructions [R and D Systems, Europe, Abingdon, UK]. Diagnosis of HCV was done by detection of HCV-antibodies by 3[rd] generation ELISA, detection of HCV-RNA using a quantitative automated nested reverse transcriptase PCR assay [COBAS AMPLICOR HCV MONITOR Test, v 2.0., Roche Molecular Systems, Switzerland] and histopathological examination of Liver biopsy. Histological grading and staging were assessed with reference to modified histological activity index [HA1] scoring system. The level of sICAM in GI [mean 1046.5 +/- 1059.5 ng/ml] was significantly higher than Gil [mean 233.8 +/- 115.65 ng/ml] [t = 2.4; P = 0.02]. The levels of sICAM correlated positively in GI with serum bilirubin [r=0.65, P=0.003], ALT [r=0.63, P=O.OI], AST [r=0.64, P=0.02], grade and stage of hepatitis [r=0.75, 0.68; P=O.OOI, 0.005 respectively]. There was a significant negative correlation between sICAM and both serum albumin [r=-0.71; P=0.001] and prothrombin activity [r=-63; P=0.01]. However, sICAM was not correlated with the levels of HCV-RNA [r=0.38; P=0.1]. The level of HCV-RNA was not correlated to any of the liver function tests as well as grade and stage of hepatitis. The severity of liver disease was independent of serum level of HCV-RNA; the measurement of sICAM-1 serum levels in chronic hepatitis C patients can be considered as a useful non-invasive marker for monitoring liver disease activity
Subject(s)
Humans , Male , Female , Intercellular Adhesion Molecule-1/blood , Enzyme-Linked Immunosorbent Assay , Hepatitis C Antibodies , Polymerase Chain Reaction , Disease Progression , Liver Function Tests , Biopsy , HistologyABSTRACT
Hemodialysis patients are particularly vulnerable to infection by blood borne viruses including TT-virus and HBV. The continuous HBV infection in these patients in spite of the exclusion of HBs antigen positive patients to separate hemodialysis centers may be contributed by the presence of occult HBV [serum HBs antigen negative but HBV DNA positive]. This study was carried out on 116 chronic hemodialysis patients and 50 healthy controls. After collecting blood from each patient for routine virological assays [HBs antigen, HCV antibodies and HIV1, 2 antibodies], serum was collected and tested for TT-virus DNA by seminested PCR, anti HBc by ELISA and HBV DNA by PCR. In addition, healthy controls were tested for serum TT-virus DNA by seminested PCR. Thirty three [28.4%] hemodialysis patients were positive for TT-virus DNA compared to 8% of the healthy controls [P=0.004]. However, the prevalence of detection of HBV DNA, HBs antigen and anti HBc was 6%, zero% and 12.9%, respectively. In addition, a high prevalence of HCV seropositivity [65.5%] was detected. None of the patients was positive for HIV1, 2 antibodies. TT-virus DNA positive patients had higher mean number of previously received blood transfusions than TT-virus DNA negative patients [P=0.016]. No statistically significant differences were present between TT-virus positive and negative patients regarding age, sex, duration of hemodialysis, prevalence of HBV DNA, anti HBc and anti HCV positivity or mean ALT level and prevalence of elevated ALT. The eight patients with TT-virus infection alone [negative for HCV antibodies and HBV DNA] had normal ALT levels and no clinical evidence for hepatic disease. However, coinfection by HCV could account for ALT elevation in patients with TT-virus infection. We detected 7 [6%] hemodialysis patients with occult HBV infection. Among these patients, anti HBc seropositivity was detected in 5 patients [71.4% versus 9.2% in patients without occult HBV infection, P=<0.001]. No statistically significant differences were found between patients with and without occult HBV infection concerning age, sex, number of previously received blood transfusions, duration of hemodialysis, prevalence of TT-virus DNA and anti HCV positivity or mean ALT level and prevalence of elevated ALT. Only one patient with occult HBV infection had elevated serum ALT level. However, this patient was also positive for HCV antibodies. We concluded that TT-virus infection is common in Egyptian hemodialysis patients. Apart from the number of previously received blood transfusions, no demographic, clinical or virological factor was found to be significantly correlated with TT-virus infection. TT-virus does not seem to cause a significant liver disease. However, other studies are needed to investigate the possible enhancing effect of this virus on hepatic disease caused by HCV in these patients. Moreover, occult HBV infection occurs at a low frequency in Egyptian hemodialysis patients with no association with demographic or clinical findings, TT-virus or anti HCV positivity. Anti HBc testing does not seem to be valuable in detecting occult HBV infection. Screening of hemodialysis patients for HBV DNA is recommended for more strict control of HBV infection in these patients
ABSTRACT
The mechanism of lymphomagenesis by HCV is still obscure. The present study was carried out on 64 untreated patients previously diagnosed as having chronic liver disease due to HCV infection, 30 patients with HCV negative chronic liver disease [CLD] and 30 healthy controls. Serum cryoglobulins were tested in all subjects. In addition, the presence of immunoglobulin heavy chain gene [IgH] rearrangement and Bcl-2-JH translocation in peripheral blood mononuclear cells [PBMC] were assessed by seminested and nested polymerase chain reaction [PCR], respectively. Percutaneous liver biopsies were performed in 61 of the 64 patients with HCV related CLD and 26 of the 30 patients with HCV negative CLD to determine the severity of chronic liver injury. None of the patients received immunomodulatory drugs or had hepatocellular carcinoma, lymphoma or other malignancies. Cryoglobulinaemic and non-cryoglobulinaemic chronic HCV infected patients had significantly higher rates of monoclonal IgH rearrangement than patients with HCV negative CLD [P=0.006 and 0.047, respectively] and healthy controls [P=0.001 and 0.005, respectively].There were no statistically significant differences between chronic HCV infected patients with and without monoclonal IgH rearrangement with respect to age, sex, mean ALT and AST levels. Furthermore, the frequency of monoclonal IgH rearrangement in PBMC did not differ significantly according to histologic severity of chronic liver injury. On the other hand, cryoglobulinaemic and non-cryoglobulinaemic chronic HCV infected patients had significantly higher rates of Bcl-2-JH translocation than non HCV infected CLD patients [P=0.0002 and 0.001, respectively] and healthy controls [P=0.0002 and 0.001, respectively]. There were no statistically significant differences between chronic HCV infected patients with and without Bcl-2-JH translocation with respect to age, sex, mean ALT and AST levels. Moreover, the frequency of Bcl-2-JH translocation in PBMC did not differ significantly according to histologic severity of liver injury. Interestingly, the frequency of coexisting monoclonal IgH rearrangement and Bcl-2-JH translocation was significantly higher in cryoglobulinaemic than non-cryoglobulinaemic chronic HCV infected patients [P=0.05], HCV negative CLD patients [P=0.009] and healthy controls [P=0.009]. We concluded that patients with chronic HCV infection are more liable to develop monoclonal IgH rearrangement or Bcl-2-JH translocation in PBMC. Moreover, coexisting monoclonal IgH rearrangement and Bcl-2-JH translocation is a frequent finding in cryoglobulinaemic patients with chronic HCV infection suggesting that these aberrations may be involved, at least in part, in the complex multistep mechanisms occurring in HCV infected patients ending in B cell lymphoproliferative diseases [LPD]. Further studies are needed to establish whether determination of these aberrations in PBMC of chronic HCV infected patients could be useful as non invasive molecular markers for the predisposition to acquire cryoglobulinaemia and/or other B cell LPD
ABSTRACT
Hemodialysis patients are one of the high risk groups for blood borne viral infection including HTLV1/2. This study was carried out on 171 chronic hemodialysis patients. From each patient, a serum sample and EDTA anticoagulated blood were collected. Serum was tested for anti HTLV1/2 antibodies by ELISA. Positive patients were confirmed by whole blood-PCR for detection of HTLV1/2 proviral DNA. Two [1.17%] patients were positive for both HTLV1/2 antibodies [by ELISA] and HTLV1/2 proviral DNA [by whole blood-PCR]. Interestingly, these two patients received more than 30 blood transfusions and were on hemodialysis for more than one year. Among patients who received 30 or more blood transfusions and those on hemodialysis for one year or more, the prevalence of HTLV1/2 positivity [by both ELISA and PCR] was 4.8% and 1.6%, respectively. A high frequency of HCV seropositivity [76%] was detected among our patients. Nevertheless, this frequency was not affected by the number of previously received blood transfusions [x[2] =3.48, P=0.481] or duration of hemodialysis [x[2] =3.21, P=0.073]. Two [1.17%] patients were positive for HBs antigen and they were transferred to the Fevers Hospital Hemodialysis Centre. This probably represents the tip of the iceberg as serum HBs antigen screening in the present setting is done every three months. Therefore, these two patients converted to HBs antigen seropositivity within the last three months only. Fortunately, none of our patients was anti HIV1/2 positive. These results suggest that HTLV1/2 infection occurs in hemodialysis patients in Egypt and the prevalence becomes more among those receiving 30 or more blood transfusions and those on hemodialysis for one year or more. Therefore, we recommend screening of blood for HTLV1/2 antibodies before transfusion to chronic hemodialysis patients. In addition, proper infection control should be stressed in hemodialysis centres. Interestingly, a high prevalence of HCV positivity occurred in our patients in spite of routine anti HCV screening of blood prior to transfusion. Therefore, exclusion of anti-HCV positive patients to separate hemodialysis centres is recommended to control the rapid spread of HCV infection among these vulnerable patients