Prevalence of non-A,non-B hepatitis/hepatitis C virus antibody in human immunoglobulins.

Human intravenous immunoglobulins prepared by the cold ethanol fractionation technique of Cohn are considered safe with respect to infectivity. However, there have been several instances of transmission of both hepatitis B and non-A,non-B hepatitis viruses after administration of intravenous immunoglobulins. To determine the prevalence of hepatitis C virus antibody in intravenous immunoglobulins and protein preparations, 30 commercially available products were tested. Using the Abbott enzyme immunoassay for hepatitis C virus antibody, 27 of 30 (90%) immunoglobulins tested positive. The Ortho immunoassay showed that 28 of 30 (93%) were positive, with one discordant result between the Ortho and Abbott assays. An antigen-blocking or neutralization test (Abbott) confirmed the results of the Ortho assay. Bovine, sheep, goat, and horse sera also were tested before and after isolation of animal immunoglobulins. All results on the animal sera were negative, indicating that the fractionation process did not produce false-positive results. The high prevalence rate of hepatitis C virus antibody in intravenous immunoglobulins has important implications for follow-up of recipients, selection of serum donors, and implementation of anti-hepatitis C virus testing.     

Prevalence of hepatitis C virus antibodies among patients infected with human immunodeficiency virus.

A study was undertaken to determine the prevalence and risk factors for serological evidence of hepatitis C virus (HCV) infection in patients infected with the human immunodeficiency virus (HIV). Tests for anti-HCV antibody were carried out by enzyme-linked immunoassay (EIA) on 101 HIV-infected patients from two university-based outpatient clinics. Anti-HCV antibody reactive samples were tested by using a recombinant immunoblot assay (RIBA) for HCV antibodies. Fourteen of 101 (13.9%) HIV-infected patients were anti-HCV reactive by EIA. Of these 14, only seven were reactive by RIBA: four were intravenous drug users as a sole risk factor for HIV infection; and the remaining three acquired HIV by blood transfusion, contaminated instrument exposure or IV drug use and sexual contact. Acquisition of HIV by sexual activity alone was not associated with HCV infection. It is concluded that HCV infection is found in approximately 7% of a university HIV clinic population. False-positive anti-HCV antibody serology may lead to overestimation of the prevalence of HCV infection. Female sex and intravenous drug use are significantly associated with HCV infection among HIV-infected individuals.     

Predicting factors of present hepatitis C virus infection among patients positive for the hepatitis C virus antibody

Background/Aims

To identify the predicting factors of present hepatitis C virus (HCV) infection among patients with positivity for antibodies to HCV (anti-HCV).

Methods

We analyzed patients who showed positive enzyme immunoassay (EIA) results and performed an HCV RNA test as a confirmatory test at Kyung Hee University Hospital at Gangdong from June 2006 to July 2012. The features distinguishing the groups with positive and negative HCV RNA results were reviewed.

Results

In total, 490 patients were included. The results of the HCV RNA test were positive and negative in 228 and 262 patients, respectively. The index value of anti-HCV, mean age, platelet counts, total bilirubin, prothrombin time international normalized ratio, albumin and alanine transaminase (ALT) levels differed significantly between the two groups. On multivariable analysis, an index value of anti-HCV >10 [odds ratio (OR)=397.27, P<0.001), ALT >40 IU/L (OR=3.64, P=0.001), and albumin <3.8 g/dL (OR=2.66, P=0.014) were related to present HCV infection.

Conclusions

Although EIA is not a quantitative test, considering the anti-HCV titer with ALT and albumin levels may be helpful in predicting present of HCV infection.     

Prevalence of hepatitis C virus infections among heterosexuals with multiple partners

A study among heterosexual men and women with multiple sexual partners was carried out to assess the seroprevalence of antibody against hepatitis C virus (HCV). The 468 participants were recruited among visitors to the Clinic for Sexually Transmitted Diseases in Amsterdam. Sera were tested by an enzyme-linked immunosorbent assay (ELISA; Ortho), a recombinant-based immunoblot assay (RIBA; Chiron), and the polymerase chain reaction (PCR). A total of 468 persons were tested, and seven (1.5%) were found ELISA positive. Another 25 (5%) were ELISA indeterminate. Six of the seven ELISA-positive cases were RIBA positive. Further serum samples from five HCV ELISA-positive persons were tested by PCR, and four were found to be positive. The HCV ELISA-positive/RIBA-indeterminate reaction was PCR negative. None of the 17 RIBA-tested sera of the ELISA-indeterminate group yielded a positive result. There was a good correlation between an ELISA optical density/cut-off ratio greater than 2 and a positive RIBA result. The risk factor for HCV appeared to be the type of sexual partner, i.e., belonging to a "high-risk" group for human immunodeficiency virus infection and origin from hepatitis B-endemic countries. It is concluded that HCV may be transmitted through heterosexual contact but probably with low efficiency.     

Prevalence and significance of antibodies to hepatitis C virus among Saudi haemodialysis patients.

Seventy-four patients who were maintained on chronic haemodialysis in King Khalid University Hospital, Riyadh, Saudi Arabia were tested using the recently available ELISA to determine the prevalence of antibodies to hepatitis C virus (anti-HCV) in a haemodialysis unit. The prevalence rate of anti-HCV antibodies of 41.9% in the haemodialysis patients was significantly higher than the rate of 3.9% detected in 488 asymptomatic blood donors who were similarly tested. In the haemodialysis patients, anti-HCV positivity was related to previous blood transfusion (greater than 5 units of blood) and to the duration of haemodialysis (greater than 4 years); but was unrelated to sex, age, positive HBV markers or to past or current elevation of serum ALT. The results indicate a relatively higher prevalence of anti-HCV antibodies in our patients compared to rates of 1-20% reported from Europe and the U.S.A. An effective control strategy for HCV infection in this high risk group is urgently indicated.     

Prevalence of hepatitis C virus infection among long-term hemodialysis patients: Detection of hepatitis C virus RNA in plasma

Two hundred and twelve urine specimens, from several clinical groups, were examined for BK virus (BKV) using the polymerase chain reaction (PCR) to detect the VP1 region of BKV DNA. Positive results were obtained on 14 specimens from 44 post-transplant patients (31.8%), 10 specimens from 39 pregnant women (25.6%), and 5 specimens from 100 children (5%) but not on any specimens from 29 laboratory staff. Twentyeight of the amplified BKV genomes, 19 from urine specimens, eight from culture fluid of inoculated tissue, and also one from a throat washing were directly sequenced from single-stranded templates immobilized via a biotinylated primer; it was possible to assign all to one of the four subtypes of BKV which had previously been identified on the basis of variation in nucleotide sequence of the VP1 region. Serological subgroup classification correlated with the genomic subtyping results in 21 of the isolates. The distribution of the BKV subtypes and the clinical status of the infected individuals are discussed.     

Prevalence of hepatitis C virus antibodies and hepatitis C virus-RNA in an urban population.

Several studies had been carried out on anti-hepatitis C virus (HCV) prevalence in populations with blood exposure risks and in blood donors. New tests are now available which allow the investigation to extend to other parameters such as antibody type and HCV-RNA. In this study the prevalence of anti-HCV c100-3 and the associated epidemiological, clinical, and virological markers were evaluated in subjects from an urban population located in central Italy. In positive cases the time persistence of HCV-RNA and anti-HCV antibody pattern was studied. For this purpose, sera from 1,484 randomly sampled individuals, aged 30-69 years, collected in 1985 and stored at -80 degrees C were retrospectively tested. The prevalence was 0.87% (i.e., 13 anti-HCV c100-3 positive cases). A significant association was observed with raised alanine transaminase (ALT) levels (P less than 0.001). Paired serum samples from 11 out of the 13 subjects collected in 1985 and 1991 were tested by nested polymerase chain reaction (PCR) using primers from the 5' non-coding region and by 4-RIBA. Concordant RIBA patterns between 1985 and 1991 were observed in the majority of positive paired sera (7/9) as well as for HCV-RNA (6/9). HCV-RNA was present in sera simultaneously positive to both types of antibody or to anti-c100-3 or anti-c22 alone. A wide spectrum of viral and antibody patterns in anti-HCV c100-3 positive sera was observed in this urban population and persisted for at least 6 years.     

Lack of anti-GOR antibody among subjects with GB virus C/hepatitis G virus RNA

Homologies were sought between the putative amino acid sequences of GB virus C/hepatitis G virus (GBV-C/HGV) and the GOR epitope or the liver/kidney microsome-1 (LKM-1) epitope, which share partial sequence identity with the hepatitis C virus (HCV) polyprotein. Anti-GOR antibody (anti-GOR) was assayed among 100 subjects with GBV-C/HGV RNA. Twenty-one and 25 subjects were coinfected with hepatitis B virus (HBV) or HCV, respectively. Homologies were found between the NS5 or E2 polyproteins of GBV-C/HGV and the GOR epitope or the LKM-1 epitope, respectively. These segments of GBV-C/HGV polyproteins sharing identity with the GOR or the LKM-1 epitope were well conserved among three genotypes of GBV-C/HGV. However, only 1 of 55 subjects (1.8%) with GBV-C/HGV RNA, but not with HBV or HCV, was positive for anti-GOR. The positivity for anti-GOR among the group with GBV-C/HGV RNA alone was significantly lower than that among the groups with HCV RNA (P < 0.01 and P < 0.05, respectively). Only 2 of 55 subjects (3.6%) with GBV-C/HGV RNA alone exhibited elevation of alanine aminotransferase. The incidence of liver dysfunction among the group with GBV-C/HGV RNA alone was significantly lower than the incidence among the groups with GBV-C/HGV RNA and hepatitis B surface antigen (HBsAg) or HCV RNA (P < 0.01 and P < 0.01, respectively). These data indicate that 1) there is no association between GBV-C/HGV infection and the presence of anti-GOR, and 2) GBV-C/HGV infection is not related to chronic liver dysfunction. J. Med. Virol. 55:129–133, 1998. © 1998 Wiley-Liss, Inc.     

Prevalence and factors associated with hepatitis C virus infection among Myanmar blood donors

We studied the prevalence of hepatitis C virus infection among blood donors from 3 hospitals of Central Myanmar and 7 hospitals of Lower Myanmar in the Yangon area, and analyzed the factors associated with the infection. The study period was from November, 2005 to June, 2007. A pre-tested questionnaire was used to obtain information on age, ethnic group, marital status, tattooing, body piercing, history of receiving transfusions, and liver diseases in self and in sexual partners. Data on seropositivity to hepatitis C, hepatitis B and human immunodeficiency virus infections were recorded. A total of 65,240 blood donors participated in the study. Their ages ranged from 18 years to 60 years (mean±SD=29.5±9.3). The male-to-female ratio was 6:1. The prevalence of the antibody to hepatitis C was found to be 0.95% with varying rates (0.34 to 2.03) among hospitals. Females had a slightly higher rate (1.06%) than males (0.93%) (p=0.237). Multivariate analyses revealed the following factors to be related to HCV infection:HIV infection, odds ratio (OR)=3.0 (p=0.003); history of liver disease, OR=8.9 (p=0.001);and age 30 years and above, OR=2.6 (p=0.001). We discuss the varying prevalences of HCV around the world.     

Prevalence of antibody to hepatitis C virus in HBsAg-negative chronic liver disease in Hong Kong using different assays.

The prevalence of anti-HCV antibodies in Chinese patients with HBsAg-negative chronic liver diseases was studied retrospectively. Anti-HCV was detected by two different ELISAs. In 97 patients with HBsAg-negative chronic liver disease, 26 (27%) were anti-HCV positive. Of 157 control subjects, only 1 (0.6%) was anti-HCV positive (P less than 0.001). Anti-HCV was detected in 18 of 27 (67%) patients with post-transfusion non-A, non-B (PTNANB) chronic hepatitis or cirrhosis, 5 of 25 (20%) patients with cryptogenic chronic hepatitis or cirrhosis, 2 of 33 (6%) patients with alcoholic liver disease, 1 of 5 (20%) patients with autoimmune chronic active hepatitis (AICAH), none of 4 patients with primary biliary cirrhosis (PBC), and none of 3 patients with fatty liver. The prevalence in this group of patients was lower when compared to reports from other countries. The addition of a urea washing step reduced false-positivity in alcoholic and AICAH groups. The ELISA that employs three recombinant HCV antigens confirmed all positive results by another ELISA with the exception of one weakly positive result in the AICAH group and one in the alcoholic group. One patient in the PTNANB group was detected in addition by the second generation assay. In conclusion, ELISA with a urea wash proved to be useful in reducing false-positivity, and the second generation assay proved to be a sensitive and specific test for anti-HCV antibody.     

Prevalence of hepatitis C in patients with primary antibody deficiency

Concern over sporadic hepatitis C virus (HCV) infection from treatment with contaminated immunoglobulin in patients with immunodeficiency prompted us to screen serum from 44 patients for HCV RNA. We found no evidence of either horizontal or iatrogenic infection in our Clinic, except in two patients known to have received contaminated batches, and in one who had had regular plasma infusions. Thus, common variable immunodeficiency (CVID) patients in England do not have a high incidence of HCV infection despite exposure to various immunoglobulin products. This contrasts with the recently reported high prevalence in similar patients in Italy. Although our data reinforce the impression that both intramuscular and current licensed i.v. preparations in the UK are safe, manufacturers should be encouraged to PCR screen all batches of immunoglobulin for HCV.     

Reduced antibody reactivity to hepatitis C virus antigens in hemodialysis patients coinfected with hepatitis B virus.

Antibody reactivities to hepatitis C virus (HCV) antigens and to synthetic peptides derived from different parts of the HCV genome (core, NS4, and NS5) were evaluated in HCV-infected hemodialysis patients. In the RIBA 3 assay, NS5 was significantly less recognizable by sera of hemodialysis patients compared to other HCV-infected subjects. Among hemodialysis patients, those coinfected with hepatitis B virus (HBV) (positive for hepatitis B surface antigen [HBsAg+]) showed a reduction in reactivity to C33 and C100. Sera of only 23% of the hemodialysis patients (37 of 161) reacted with more than three of eight peptides tested, significantly fewer than the 60% (12 of 20) of the sera of other HCV-infected patients tested (P = 0.001). This immunosuppression was also manifested by a reduced frequency of recognition of additional peptides on follow-up. An even more reduced reactivity was observed among the HBV-coinfected patients (HBsAg+). The low-responder hemodialysis patients were not infected with any particular genotype of HCV, and the same HCV genotypes observed in the whole group of hemodialysis patients (1a, 1b, 2a, and 3a) were found circulating in the low-responder group. Even in this low-responder population, the good performance of two peptides (peptide 716, corresponding to a portion of the core, and peptide 59, corresponding to a portion of NS4) corroborates the immunodominance of the conserved epitopes within these peptides.     

Prevalence of antibody to hepatitis E virus among wild sika deer, Cervus nippon, in Japan

Summary We examined 976 sika deer serum samples, 159 liver tissue samples and 88 stool samples collected from 16 prefectures in Japan, and performed ELISA and RT-PCR assays to detect antibodies to HEV and HEV RNA, respectively. Although 25 (2.6%) of 976 samples were positive for anti-HEV IgG, the antibody titers were very low. The OD values ranged between 0.018 and 0.486, forming a single distribution rather than a bimodal distribution, suggesting that the antibody detected in this study was not induced by HEV infection, or that deer have low sensitivity to HEV. HEV RNA was not detected in these samples, also suggesting that deer may not play a role as an HEV reservoir.     

Study on reliability of commercially available hepatitis C virus antibody tests.

The serodiagnosis of hepatitis C virus (HCV) infection was analyzed by a recombinant immunoblot assay (RIBA) with recombinant proteins encoded by the viral RNA isolated from our patients in Hamburg, Germany. The HCV RNA was amplified by PCR, and proteins encoded by the viral core and the NS3, NS4, and NS5 regions were expressed subsequently in Escherichia coli. The results obtained with our UKE RIBA were compared with the results of the Abbott HCV second-generation enzyme immunoassay (EIA). Serum samples from 270 patients, which were sent to us on the suspicion of HCV hepatitis and which were negative for hepatitis A virus and hepatitis B virus antibodies, were examined. In 227 cases (84.1%), there were identical positive (204 cases, 75.6%) or negative (23 cases, 8.5%) results in both tests. In 32 cases (11.9%), the reactive Abbott second-generation HCV EIA results could not be confirmed by the UKE RIBA and the HCV PCR. In follow-up studies conducted over 1 year, these results did not change. In three cases (1.1%), the UKE RIBA presented a positive result while the Abbott second-generation HCV EIA was negative. All three cases were positive in the HCV PCR and showed seroconversion in an HCV EIA 4 to 6 weeks later. In addition, 33 patient serum samples were examined by UKE RIBA in parallel with the Ortho RIBA 2.0. In three cases (9.1%), a positive Ortho RIBA 2.0 result could not be confirmed by the UKE RIBA and the HCV PCR. All three patients were free of complaints. The UKE RIBA showed also a smaller number of indeterminate results (3.0%) than the Ortho RIBA 2.0 (24.2%). This comparison study demonstrates that the commercially available HCV antibody tests should be further improved.     

Confirmation of hepatitis C virus antibody in blood donors

Of 103,203 donations collected in Scotland and Northern Ireland over a 3-month period and screened for HCV antibody by Ortho or Abbott second-generation ELISAs, 340 were found repeatedly reactive. Supplementary testing with RIBA-2 resulted in 77 being classified as positive, 130 as indeterminate, and 133 as negative. PCR analysis of the positives and indeterminates indicated viraemia in 65 (84%) of the positives and 7 (5.5%) of the indeterminates. To determine if PCR analysis could be eliminated or reduced by further serological testing, all RIBA-2 positives and indeterminates were tested by UBI and Wellcozyme ELISAs and Innolia and RIBA-3 immunoblots. All RIBA-2 positives with bands to more than 1 gene product were detected in all 4 systems, but >60% of RIBA-2 indeterminates were negative in those tests that contain either recombinant antigens or synthetic peptides derived independently from those used by Ortho/Abbott tests. A comparison of data from the 79 reactive with the core (c22) region revealed only 16 samples reactive in all 4 systems as well as Ortho and Abbott. These 16 included all 6 of the PCR positives in the 79 c22 indeterminate samples. ELISAs and immunoblots using independently derived antigens can offer a useful method of screening out nonspecific reactions in Ortho or Abbott ELISAs, hence reducing the need for PCR testing. Some caution is required as all such tests do not contain identical mixes of antigenic material.     

Prevalence of hepatitis B virus infection among alcoholic patients with liver disease.

The aim of this investigation was to elucidate a possible role of hepatitis B virus (HBV) in the pathogenesis of liver diseases in alcoholics. Two hundred and fifty-three alcoholics with liver disease were admitted to two medical departments in Copenhagen during a 15 months period. Seventy-nine patients (31%) showed serological signs (HBsAg, anti-HBs) of previous or active HBV infection. This is a significantly higher prevalence than found in an age-matched control population. Among the 79 patients with HBV markers, a total of 11 was found to be HBsAg-positive. From these 11 patients liver specimens were available for re-evaluation in nine cases. In only three of these liver biopsies, morphological changes indicating alcohol as the aetiological cause were found. In conclusion, different or concomitant aetiology must be considered in alcoholics with liver disease.     

Prevalence of amino acid mutation in hepatitis C virus core region among Japanese volunteer blood donors

It is not known whether there is a trend of increasing or decreasing incidence of new hepatitis C virus (HCV) infections in Japan. From the treatment point of view, it is important to verify HCV genotypes and the prevalence of treatment-resistant clones of HCV. At the Japanese Red Cross blood centers, all blood samples obtained from blood donation have been screened using serological methods and the minipool nucleic acid amplification testing. One hundred and fourteen donors have been identified over the past 10 years to be HCV RNA-only positive without detectable anti-HCV and were considered to be in the acute phase of HCV infection. There was a trend of decreasing incidence of such new infections among the blood donors. HCV RNA-only-positive samples were examined further for genotyping and HCV RNA quantitation. Genotype 2 (2a plus 2b) was predominant (78.2%) among them followed by genotype 1b (21.2%). Direct sequencing was carried out to detect the possible treatment-resistant mutant clones 70Q and 91M, clones with amino acid substitutions at positions 70 and 91 of the HCV core protein, respectively. 70Q and 91M were found regularly in donors with genotype 1b, but not in those with other genotypes. No particular endemic areas for the mutant clones were identified. There was no significant difference in the mean viral titer between the 70Q mutant type and the non-70Q wild-type. Even in newly infected people, the mutant clone 70Q was detected frequently.