High spontaneous clearance of symptomatic iatrogenic acute hepatitis C genotype 4 infection.

Acute hepatitis C (AHC) infection resolves spontaneously in 15% to 40% of patients. Factors favoring spontaneous viral clearance remain undefined. In this study, predictors of spontaneous viral clearance in patients with symptomatic AHC were investigated. Epidemiological, clinical, and virologic parameters were also examined. Patients with symptomatic AHC were enrolled and followed up prospectively. The patients were followed up every 2 weeks in the first month and then monthly for the following 5 months, with a follow-up visit 6 months after the last hepatitis C virus (HCV)-RNA negative sample for those who had cleared the virus. Interleukin (IL)-28B.rs12979860 single-nucleotide polymorphism and HCV genotype were tested at baseline. HCV-RNA was tested during each visit. Patients who remained RNA-positive at 24 weeks were treated with pegylated interferon plus ribavirin for 24 weeks. A total of 30 patients, mostly with iatrogenically acquired AHC genotype 4 infections completed 6-months' follow-up, to either spontaneous clearance or start of treatment. The mean age of the patients was 37 ± 13 years. In total, 67% of patients were females, and the mean incubation period was 7.6 ± 3.5 weeks. Viral clearance occurred spontaneously in 19 (63.3%) patients. The average time to clearance was 24.3 ± 9.6 weeks. A total of 11 patients received therapy, and 8 (72.7%) cleared the virus and had a sustained virologic response to the treatment 24 weeks after the therapy. A total of three patients were treatment nonresponders. IL28B.rs12979860 CC genotype, female gender, and viremia level were not associated with self-limiting AHC in this cohort. In conclusion, patients with symptomatic AHC genotype 4 infection caused by an iatrogenic exposure had higher rates of spontaneous resolution than previously reported. Predicting spontaneous viral clearance after iatrogenic AHC exposure was not possible in this population.

Strong hepatitis C virus (HCV)-specific cell-mediated immune responses in the absence of viremia or antibodies among uninfected siblings of HCV chronically infected children.

BACKGROUND: Cell-mediated immune (CMI) responses to hepatitis C virus (HCV) antigens in adults without seroconversion or viremia are biomarkers for prior transient infection. We investigated HCV-specific CMI responses in seronegative children living with HCV-infected siblings. METHODS: Children 3-18 years of age living with HCV-infected siblings were screened for HCV antibodies and HCV RNA. Peripheral blood mononuclear cells (PBMCs) were evaluated for HCV-specific CMI responses by interferon γ (IFN-γ) enzyme-linked immunospot assay using 3 recombinant HCV protein antigens. Flow cytometry phenotypically characterized IFN-γ-secreting cells. RESULTS: Forty-five seronegative children and 5 seropositive viremic siblings had functionally viable PBMCs. Among the 45 seronegative siblings, 15 (33.3%) had positive HCV-specific IFN-γ responses, and subsequent RNA testing revealed that 3 were viremic. Compared with the 5 seropositive viremic children, the median number of HCV-specific spot-forming units was significantly higher in the 12 seronegative aviremic children (P = .002) and in the 3 seronegative viremic children (P = .025). Flow cytometric analysis revealed that IFN-γ was synthesized mainly by CD4(+) T cells. CONCLUSION: Strong HCV-specific CD4(+) T cell responses were detectable in higher frequency among seronegative, aviremic children compared with persistently infected siblings. Further studies are needed to determine whether these immune responses are protective against HCV infection.

Schistosomiasis does not affect the outcome of HCV infection in genotype 4-infected patients.

Although reports suggest that Schistosoma mansoni increases hepatitis C virus (HCV) morbidity and chronicity, its impact on HCV spontaneous resolution is not clear. HCV genotype, viral load, abdominal ultrasonographic findings, and HCV-specific cell-mediated immunity (CMI) were examined among 141 healthcare workers infected with HCV (68 workers with and 73 workers without S. mansoni). HCV genotype 4 was dominate, and viral loads were 2.62 ± 0.69 × 10(6) and 4.24 ± 1.4 × 10(6) IU/mL among patients with and without coinfection, respectively (P = 0.309); 23.5% with and 32.9% without coinfection had spontaneously resolved HCV infection (P = 0.297). Interferon-γ spot-forming cells/10(6) peripheral blood mononuclear cells among responding viremic patients with and without coinfection were 716 ± 194 and 587 ± 162, whereas among aviremic patients, it was 794 ± 272 and 365 ± 36 (P > 0.05), respectively. In conclusion, there was no statistical difference in HCV spontaneous resolution, viral load, liver pathology, or CMI in patients with or without S. mansoni coinfection, suggesting that it did not impact the outcome of HCV infection.

Incidence of hepatitis C virus infection among Egyptian healthcare workers at high risk of infection.

BACKGROUND: Hepatitis C virus (HCV) is a global health threat with Egypt having the highest worldwide prevalence. Evaluation of the efficacy of a preventive HCV vaccine, such as those currently in Phase I/II trials, requires a cohort with a high-risk exposure to HCV. OBJECTIVE: To identify a reliable cohort for evaluating preventive HCV vaccines, we studied HCV incidence among HCW in a hospital where almost 85% of patients are HCV-infected. STUDY DESIGN: Of 717 HCW negative for HCV-antibodies (anti-HCV) at baseline, 651 were followed up and tested for seroconversion twice annually for an average of 504 ± 154 days. Those reporting a needle-stick injury were additionally tested for both HCV antibodies and RNA monthly for a total of four months. RESULTS: Two subjects (0.31%) had anti-HCV and HCV-RNA seroconversion with an overall incidence of 2.04/1000 person-years and a 4.8% incidence among the 21 subjects who reported a needle-stick injury. Two additional subjects had viremia without detectable anti-HCV. Two of the four subjects were among 21 with reported needle-stick injuries (9.5%) and another had surgery. All four were nurses providing direct patient care. CONCLUSIONS: Our results show that both transient and persistent viremia were detectable in this high-risk cohort of HCW and suggest that absence of anti-HCV in two of the subjects may be due to low-dose viral exposures. These data indicate that HCV infections acquired from documented injuries during direct patient care are frequent in Egypt and can guide selection of eligible HCW suitable for preventive HCV vaccine trials.

Risk factors for hepatitis C virus infection among Egyptian healthcare workers in a national liver diseases referral centre.

Little is known about the prevalence of hepatitis C virus (HCV) among healthcare workers (HCW) in Egypt, where the highest worldwide prevalence of HCV exists. The prevalence of HCV, hepatitis B virus and Schistosoma mansoni antibodies was examined in 842 HCWs at the National Liver Institute in the Nile Delta, where >85% of patients are HCV antibody-positive. The mean age of HCWs was 31.5 years and they reported an average of 0.6±1.2 needlesticks/HCW/year. The prevalence of anti-HCV, hepatitis B surface antigen (HBsAg) and co-infection was 16.6%, 1.5% and 0.2%, respectively. HCV-RNA was present in 72.1% of anti-HCV-positive HCWs, and all but one subject were infected with HCV genotype 4. Schistosoma mansoni antibodies were present in 35.1%. The anti-HCV rate increased sharply with age and employment duration, but not among those with needlestick history. After adjusting for other risk factors, the anti-HCV rate was higher among older HCWs [P<0.001; risk ratio (RR) = 1.086, 95% CI 1.063-1.11], males (P=0.002; RR=1.911, 95% CI 1.266-2.885) and those with rural residence (P<0.001; RR=2.876, 95% CI 1.830-4.52). Occupation (P=0.133), duration of employment (P=0.272) or schistosomal antibody positivity (P=0.152) were not significant risk factors for anti-HCV positivity. In conclusion, although one in six HCWs had been infected with HCV, the infections were more likely to be community-acquired and not occupationally related.

Genotypic characterization of symptomatic hepatitis E virus (HEV) infections in Egypt.

BACKGROUND: Hepatitis E virus (HEV) is a common cause of acute viral hepatitis (AVH) in many developing countries. In Egypt, HEV seroprevalence is among the highest in the world; however, only a very limited number of Egyptian HEV sequences are currently available. OBJECTIVES: The objectives were to determine the HEV genotype(s) currently circulating in Egypt. STUDY DESIGN: AVH patients without serologic evidence of hepatitis A, B, and C viruses were evaluated for possible HEV infection using serologic assays for anti-HEV IgM and anti-HEV IgG and real-time PCR for HEV RNA. Stool suspensions from suspected cases were inoculated into rhesus macaques to confirm the presence of HEV. Sequence analysis was utilized to determine HEV genotype. RESULTS: Of 287 subjects with AVH enrolled, 58 had serologic evidence of acute HEV infection. Stool samples for two of these patients were repeatedly positive for HEV RNA by real-time PCR. Macaques experimentally inoculated with these human stools also developed viremia. Sequence analysis of open reading frame (ORF) 1 demonstrated that these isolates belonged to HEV genotype 1 and were 3.9-9.5% divergent from other genotype 1 isolates. ORF2 was 5.3-8.7% divergent from previously reported Egyptian isolates. CONCLUSIONS: This study strongly suggests that genotype 1 HEV related to other North African isolates is circulating in acute symptomatic patients in Egypt. Further evaluation of genotypic variability is underway in this highly endemic cohort and is considered an important component of our increased understanding of HEV pathogenesis.