Anti-HBc screening in Egyptian blood donors reduces the risk of hepatitis B virus transmission.

Occult hepatitis B virus (HBV) in blood donors is considered as a potential risk for transmission of HBV infection. The aim of this study was to determine the prevalence of anti-hepatitis B core antibody (anti-HBC) positivity in Egyptian blood donations as well as to estimate the frequency of HBV-DNA in anti-HBc-positive donations. The study included 760 Egyptian healthy blood donors, representing 26 different Egyptian governorates screened according to routine practice for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Abs), HIV-1/2 Abs and Treponema Abs. The accepted blood units for donation were tested for the presence of total anti-HBc Abs by two tests. Positive units for anti-HBc were further tested for HBV-DNA by polymerase chain reaction. According to routine screening, a total of 48/760 units (6.3%) were rejected [38 (5%) HCV-Ab-positive units, 9 (1.18%) HbsAg-positive units and 1 (0.13%) Treponema-Ab-positive unit]. Among the accepted blood units for donation, prevalence of anti-HBc was 78/712 units (10.96%). HBV-DNA was detected in 9/78 (11.54%) of the anti-HBc-positive units, and thus, occult HBV infection was detected in 9/712 (1.26%) of the accepted blood donations. Implementing anti-HBc test to the routine assay for the forthcoming two decades would certainly eliminate possible HBV-infected units. Rejection of these units will be beneficial to decrease the risk of HBV transmission with its potential consequences particularly in immunocompromised recipients.

TT virus infection is widespread in the general populations from different geographic regions.

By PCR screening, we found an extremely high prevalence of TT virus (TTV) in the general populations from different geographic regions. This suggests that TTV may be a common DNA virus with no clear disease association in humans. TTV genotyping by phylogenetic analysis was also performed.

Prevalence of GBV-C/hepatitis G virus viraemia among blood donors, health care personnel, chronic non-B non-C hepatitis, chronic hepatitis C and hemodialysis patients in Egypt.

A new RNA virus, designated GBV-C/hepatitis G virus (HGV) has been identified recently. To evaluate the prevalence of GBV-C/HGV infection among Egyptians, five groups were enrolled in this study: group I, healthy blood donors (82); group II, health care personnel (30); group III, chronic non-B non-C hepatitis patients (63); group IV, chronic hepatitis C patients (100); group V, renal dialysis patients (79). GBV-C/HGV-RNA was detected by nested reverse transcription-polymerase chain reaction (RT-PCR) using primers derived from 5'-non coding region of GBV-C/HGV. GBV-C/HGV-RNA was detected in 57 of 354 tested sera with an overall prevalence of 16.1%. Meanwhile, isolated GBV-C/HGV infection was detected in 16/57 (28.1%), GBV-C/HGV coinfection with hepatitis C virus (HCV) in 37/57 (64.9%) and with hepatitis B virus (HBV) in 4/57 (7.6%) of cases. The highest prevalence was encountered among dialysis patients reaching 30% followed by chronic hepatitis C (14%), blood donors (12.2%), chronic non-B non-C hepatitis (11.1%), whereas the lowest prevalence rate of 6.6% was detected among health care personnel. Nucleotide sequence analysis in three Egyptians confirmed that these PCR products were derived from GBV-C/HGV genome and all isolates classified into US/European type (type 2) of GBV-C/HGV genotypes. The risk factors of all cases were non-transfusion parenteral exposure, e.g. reusing syringes, dental treatment, surgery, invasive medical maneuvers, with an exception of renal dialysis patients who have had repeated blood transfusion. It is concluded that there is a relatively high prevalence of GBV-C/HGV-RNA among different Egyptian groups compared to international figures. The main risk factors were direct percutaneous exposure rather than blood transfusion. The Egyptian GBV-C/HGV isolates are very similar to the American isolate PNF 2161.

Association of chronic hepatitis C infection and diabetes mellitus.

The aim of the study was to detect a possible aetiological association between chronic hepatitis C virus (HCV) infection and diabetes mellitus (DM). Among the 591 HCV seropositive chronic liver disease (CLD) patients, 150 (25.4%) had associated diabetes mellitus while only 25 of 223 HCV seronegatives (11.2%) were diabetics. The HCV seropositive patients were three times more likely to suffer from diabetes mellitus than those who were HCV seronegative and the results were highly significant (odds ratio = 2.7, CI = 1.7-4.4, P < 0.0001). Liver biopsy showed cirrhosis in 24 out of 53 (45.3%) HCV seropositive diabetics and 9/20 (45%) of the HCV seronegative diabetics. The association between the degree of liver disease and the development of diabetes mellitus did not differ statistically between the two groups. Islet cell antibody (ICA) was present in 44.4% of HCV seropositives compared to 73.3% of seronegative diabetics, while NIDDM showed 40% ICA positivity. Although ICA level was highest in HCV seronegative diabetics, the difference between the various groups was not significant statistically. About 29% of HCV seropositive diabetics were on insulin therapy while only 16% of HCV seronegative diabetics received insulin therapy. HCV seropositives were about 2 times more prone to require insulin therapy than HCV seronegatives (odds ratio = 2.0, CI = 1.2-5.7, P = 0.010). We conclude that chronic hepatitis C patients in Egypt are three times more likely to develop DM than HCV seronegative patients. Pancreatic beta -cells might be an extrahepatic target of HCV.

Does schistosomiasis play a role in the high sero prevalence of HCV antibody among Egyptians?

Many studies have demonstrated a very high prevalence of HCV antibodies among blood donors (BD) and chronic liver disease (CLD) patients in Egypt. This high prevalence might be attributed to cross reactivity between HCV antibodies and schistosome antibodies. We decided to study the association and cross serology between the presence of anti-HCV and Schistosomal infection among BD and CLD patients. Sera of blood donors and CLD patients were tested for anti-HCV by second generation ELISA. Antibodies to Schistosoma species were quantified by IHA test. Two tailed z score was used to detect significant difference. To test for cross reactivity between the two antibodies 20 BD and 20 CLD patients positive for both HCV-antibody and schistosome antibody were taken as controls. Another 20 samples also served as a control group; 10 of them seropositive for HCV only and 10 positive for IHA for schistosomiasis alone. All were subjected to: 1) RIBA-2 confirmatory test 2) Adsorption of schistosome antibodies using 100 microgram schistosome antigens per 100 microliters serum 3) Both HCV-ELISA-2 and RIBA-2 were checked after adsorption. The titre of schistosome antibodies in positive sera ranged from 1:128 to 1:1536. HCV seroprevalence was more pronounced among antischistosomal positive sera. This was seen in both BD and CLD patients where antischistosomal positive sera were at double risk to show positive HCV antibody. After adsorption of schistosome antibody, there was no change in reactivity of both ELISA-2 and RIBA-2. We conclude that HCV antibodies were significantly higher in schistosomal antibody positive Egyptians, there was no cross reactivity between the two antibodies and the high prevalence could be due to HCV transmission during anti-bilharzial parenteral therapy or due to depressed cell mediated immunity associated with schistosomal infection.

Use of NS-4 peptides to identify type-specific antibody to hepatitis C virus genotypes 1, 2, 3, 4, 5 and 6.

The 5' end of the NS-4 protein of different genotypes of hepatitis C virus (HCV) is highly variable in nucleotide and inferred amino acid sequence, with frequent predicted amino acid substitutions between all six of the major HCV genotypes described to date. This region has been shown to be antigenic by epitope mapping, and elicits antibody in HCV-infected individuals with a detectable type-specific component. We have used this sequence data to specify branched peptides for an indirect binding/competition assay to detect type-specific antibody to each major genotype. A total of 183 out of 210 samples (87%) from blood donors and patients with chronic hepatitis C infected with genotypes 1 to 6 showed detectable type-specific antibody to NS-4 peptides that in almost all cases (> 97 %) corresponded to the genotype detected by a PCR typing method. These findings demonstrate the existence of major antigenic differences between genotypes of HCV, and indicate how infection with different variants of HCV may be detected by a serological test.

Vascular alterations of the colonic mucosa in schistosomiasis and portal colopathy.

BACKGROUND/AIM: Portal colopathy, the occurrence of vascular-ectasia like lesions has been observed in patients with portal hypertension of variable etiology. Schistosomiasis is a major cause of liver damage and portal hypertension. In colonic schistosomiasis, vascular alterations are commonly observed. It is therefore possible that schistosomiasis may induce portal colopathy in addition to inflammatory changes directly induced by oviposition. MATERIALS AND METHODS: In order to examine this possibility, we reviewed the endoscopic data obtained in 100 consecutive patients with established bilharziosis. In addition, endoscopic biopsies from all patients were examined for the presence of inflammation, parasite eggs, granulomas and mucosal vascular congestion. The latter was assessed using immunohistochemical staining for Ulex Europaeus. RESULTS: Endoscopic abnormalities were observed in 66/100 patients. The main lesions were abnormalities in vascularisation of the mucosa, especially hyperemia, defined as the presence of numerous, prominent and irregular vessels (62%) and telangiectasia (4%). The mucosal biopsies revealed prominent vascularisation in 60% of the cases. Positivity for ulex staining was significantly correlated with the finding of hyperemia during endoscopy and with the presence of ova. No good correlation was found with the clinical presentation. The lesions were not well correlated with the presence of an increased cellular infiltrate in mucosal biopsies. CONCLUSIONS: This observation suggests that portal colopathy may explain some of the endoscopic lesions observed in the colon of patients with Schistosomiasis.

Controlled trial with interferon alfa 2-b in chronic hepatitis C patients.

Thirty-eight chronic hepatitis C (CHC) Egyptian patients with persistently elevated serum alanine aminotransferase (ALT) for 6 months were randomly allocated into 2 groups: Group I (19 patients) received 3 million units (MU) of interferon alpha - 2b (Intron-A) subcutaneously thrice weekly for 6 months. In group I, complete response (normalization of ALT by the end of treatment) was achieved in 8 patients (42.1%), partial response (decrease of ALT by at least 50% of the pretreatment values) in 7 patients (36.8%) and no response in 4 (21.1%). Sustained response for 6 months after the end of therapy was attained in 4 of the 8 (50%) complete responders. Thus attaining an overall sustained response in 4 of the 19 patients (21.1%). In group II, spontaneous normalization of ALT was established in 1 patient (5.3%). Repeat liver biopsies in 16 patients of the interferon group, revealed moderate improvement in the degree of lobular inflammation, hepatocyte necrosis and portal inflammation. We conclude from this study that treatment of CHC with 3 MU of IFN-alfa 2b thrice weekly for 6 months is associated with a low response rate (21.1%). To improve the results, escalation of the IFN dose and/or prolongation of the treatment period should be considered.

Malnutrition and immuno-incompetence in patients with liver disease.

The incidence of malnutrition and immunocompetence in 156 patients admitted to hospital with liver disease was investigated. Expected weight/height was within the normal range for all groups except those with carcinoma. Triceps skinfold thickness (TSF) was reduced in 49% of patients with cirrhosis and 55% with alcoholic disease. Hypoalbuminaemia was common in all groups, with 66% of those with chronic disease having concentrations below 35 g/dl. Lymphopenia was equally common, 65% of patients with fulminant hepatic failure (FHF) having counts below 1000 cells/mm3. Incidence of total anergy to standard skin tests was 54% overall: 93% in FHF and 60% in cirrhosis and alcoholic disease. There were significant links between reduced TSF and hypoalbuminaemia, lymphopenia and anergy, hypoalbuminaemia and anergy, and anergy and mortality. Reduced TSF was only associated with anergy in patients with chronic disease. The high incidence of immuno-incompetence may underlie the frequent occurrence of spontaneous infections in patients with liver disease, and the association between anergy and malnutrition in patients with chronic liver disease suggests that the anergy may be partly reversible by dietary measures.