Does infection with hepatitis A virus provide protection against hepatitis E virus?

Hepatitis A virus (HAV) and hepatitis E virus (HEV) share some common epidemiologic features, but the dramatic age-related difference in their disease prevalences suggests that the immune response to HAV may provide some cross-protection against HEV.     

Is the course of perinatal hepatitis B virus infection influenced by genetic heterogeneity of the virus?

We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to antihepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3–4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G + A), indicating a mixture of wild-type and "e minus"variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity. © 1993 Wiley-Liss, Inc.     

Countering hepatitis B virus infection using RNAi: how far are we from the clinic?

Globally, persistent HBV infection is a significant cause of public health problems. Currently available HBV therapies have variable efficacy and there is a need to develop improved treatment to prevent cirrhosis and hepatocellular carcinoma. Although RNA interference (RNAi)-based approaches have shown promise, accomplishing safe and sustained silencing by RNAi activators, as well as their efficient delivery to hepatocytes have hampered clinical translation of this very promising technology. Expressed silencers may be produced in a sustained manner from stable DNA templates, which makes them suited to treatment of chronic HBV infection. DNA expression cassettes can be incorporated into both viral and non-viral vectors, but in vivo delivery of these cassettes with non-viral vectors is currently inefficient. Synthetic short interfering RNAs (siRNAs), which may be chemically modified to improve stability, specificity and efficacy, are more conveniently delivered to their cytoplasmic sites of action with synthetic non-viral vectors. However, the short duration of action of this class of RNAi activator is a drawback for treatment of chronic HBV infection. Despite the impressive progress that has been made in developing highly effective HBV gene silencers, challenges continue to face implementation of RNAi-based HBV therapy. This review will discuss the current status of the topic and consider the developments that are required to advance RNAi-based HBV therapy to clinical application.     

Performances of NeuMoDx™, a random-access system for hepatitis B virus DNA and hepatitis C virus RNA quantification

ObjectiveMonitoring of viral loads (VL) for hepatitis B and C viruses (HBV; HCV) is essential to evaluate disease progression and treatment response. Automated, random-access rapid systems are becoming standard to provide clinicians with reliable VL. The aim of this study was to evaluate the analytical performances of the recently launched NeuMoDx™ for HBV-DNA and HCV-RNA quantification.MethodsClinical samples routinely quantified on the Beckman–Veris system were either retrospectively (frozen samples; HBV n = 178, HCV n = 249), or in parallel (fresh primary tubes; HBV n = 103, HCV n = 117) tested using NeuMoDx™. Linearity range was assessed on serial dilutions of high-titre plasmas containing different genotypes for HBV (A–E, n = 9) and HCV (1a,1b,2–5, n = 12).ResultsOverall test failure, mostly internal control amplification failure, was 2.3% and was not influenced by matrix types (fresh or frozen). For HBV VL, κ agreement was 74%, with 27 (12.6%) discrepancies. Correlation between HBV assays on 72 quantified samples by both methods was excellent (r = 0.963) with a mean bias (NeuMoDx™–Veris) of 0.21 log IU/mL. For HCV VL, κ agreement reached 94%, with 9 (2.8%) discrepancies. The r correlation factor between assays on 104 samples was 0.960 with a mean bias of –0.14 log IU/mL (NeuMoDx™–Veris). Serial dilutions confirmed the claimed linear ranges for all analysed HBV and HCV genotypes. The mean turnaround time was 72 minutes (range 55–101 minutes) for HBV and 96 minutes (range 78–133 minutes) for HCV.ConclusionResults obtained on the NeuMoDx™ confirmed the overall good functionality of the system with a short turn-around-time, full traceability and easy handling. These results on HBV and HCV VL look promising and should be challenged with further comparisons.     

Guillain-Barré syndrome following varicella-zoster virus infection

We describe the frequency, clinical features, and electrophysiological and immunological phenotypes of Guillain-Barré Syndrome (GBS) patients treated at a single institution in Bangladesh who had preceding chicken pox (primary Varicella-zoster virus [VZV] infection) within 4 weeks of GBS onset. A literature review of GBS cases preceding VZV infection is also provided. Diagnosis of GBS was based on the National Institute of Neurological Disorders and Stroke criteria for GBS. Serum anti-VZV IgM and IgG antibodies were quantified by indirect chemiluminescence immunoassay (CLIA); anti-Campylobacter jejuni IgG, IgM, and IgA antibodies and anti-ganglioside GM1 IgM and IgG antibodies, by enzyme-linked immunosorbent assays. Neurophysiologic subtypes were categorized following the Hadden criteria. Of 536 patients with GBS, 7 (1.3%) had chicken pox within 4 weeks before GBS onset. Four of the seven cases were male (age range, 23 to 40 years old). All seven patients were bed-bound, six had sensory symptoms, and three required mechanical ventilation for respiratory failure. All seven patients had CSF albuminocytologic dissociation and evidence of demyelination in nerve conduction studies. Anti-VZV IgM antibodies were present and anti-GM1 and anti-Campylobacter jejuni lipo-oligosaccharides (LOS) were negative in all cases. All patients had excellent outcome at 1 year (able to run). A systematic literature review of GBS cases related to VZV revealed 39 previously reported patients with comparable clinical presentations and outcomes, of which 36 had neurophysiologic evidence of demyelination. VZV infection is associated with the demyelinating subtype of GBS, clearly distinct from the axonal form of GBS that predominate in countries like Bangladesh.     

High rate of hepatitis C virus infection in an isolated community: Persistent hyperendemicity or period-related phenomena?

We investigated underlying risks for hyperendemic hepatitis C virus (HCV) infection among the 1853 inhabitants of a mountainous village in Eastern Taiwan with high prevalence of HCV and hepatitis B virus (HBV). Among the 80 selected adults, we found that having resided away from the village before 1985 was protective against HCV infection, while residing in the village after 1985 posed little risk for HCV infection to children and young adults < 30 years of age. Among the 559 school children 7 through 14 years of age, anti-HCV prevalence was 1.9%, and the HBV carrier rate was 29%. Following up 270 children 1 year later, we found that new HCV infection occurred in 0.74% and new or repeated HBV infection occurred in 6.5% of the children, indicating distinct transmission patterns between HBV and HCV. Children of anti-HCV-positive mothers were either anti-HCV-negative or were infected by distinct genotypes of HCV from those infecting their mothers; most married couples in whom both were infected, were infected by HCV of discordant genotypes, indicating negligible importance of sexual or vertical HCV transmission. A case-control study comparing 13 anti-HCV-positive and 53 anti-HCV-negative children showed that having received parenteral medication in local clinics was a significant risk for HCV infection. Our data indicate that, unlike the case of HBV, HCV transmission by vertical or sexual route, or through casual contact are extremely inefficient, and our data further suggest that HCV hyperendemicity is unlikely to persist as a result of the more stringent practice of parenteral precautions in nearly all aspects of daily life. J. Med. Virol. 52:370–376, 1997. © 1997 Wiley-Liss, Inc.     

Characterisation of an epidemic of hepatitis A virus involving intravenous drug abusers—infection by needle sharing?

An epidemic of hepatitis A virus (HAV) among intravenous drug abusers in Oslo involved 144 serologically confirmed cases. Another 26 patients (non-drug abusers), of whom 14 were derived from a single nosocomial outbreak, were associated with the epidemic. Sequencing of the VP1/P2A junction revealed that viruses associated with the epidemic were completely identical, whereas other HAV samples collected during the same period differed by up to 10 %. HAV was detected in the serum of 48 of 100 patients by a nested PCR. Viremia was observed as early as 25 days before the onset of clinical hepatitis, and up to 30 days after. The large number of patients within the drug abuser group, and the few secondary cases, raised the question of whether the virus could be transmitted by the use of needles. To establish whether viral contamination of drugs did contribute appreciably to maintaining the epidemic, we examined heroin and amphetamine confiscated during the period, using immunomagnetic separation coupled to nested PCR, but failed to detect any virus. Antibodies against hepatitis B virus and hepatitis C virus were common among the HAV infected drug abusers (43% and 81%, respectively), suggesting widespread sharing of needles. This observation and the large number of patients with a demonstrable viremia suggest that needle sharing may contribute to the dissemination of HAV. J. Med. Virol. 53:69–75, 1997. © 1997 Wiley-Liss, Inc.     

Chronic delta hepatitis: Is the prognosis worse when associated with hepatitis C virus and human immunodeficiency virus infections?

Eighty-six patients were followed for 6.5 years to study the epidemiological, virological, and histological course of chronic delta hepatitis and the relationship of this disease with HIV and HCV infection. Patients were classified into four groups according to simultaneous HCV and/or HIV infection: group 1, HDV infection (20 cases); group 2, HDV and HCV infection (11 cases); group 3, HDV and HIV infection (12 cases), and group 4, HDV, HCV, and HIV infection (43 cases). All but 14 patients were asymptomatic at presentation. Liver histology showed chronic active hepatitis in 53 cases and cirrhosis in 19 cases. During follow-up, 52 patients remained asymptomatic, 34 developed hepatic dysfunction, 28 died, and 1 received a liver transplant. Among the 28 patients who died, 4 had HDV infection; 3 HDV and HCV infection; 3 HDV and HIV infection; and 18 HDV, HCV, and HIV infection. Death was due to liver failure in 16 (57%), AIDS in 10 (36%), and was unrelated to liver disease in 2 (8%) cases. There results demonstrate that chronic delta hepatitis is a severe disease, especially among drug users with HIV and HCV infection. The high morbidity and mortality of chronic delta hepatitis justifies the use of antiviral therapy to modify the natural course of the disease. © 1996 Wiley-Liss, Inc.     

Helicobacter infection and cirrhosis in hepatitis C virus carriage: is it an innocent bystander or a troublemaker?

Since it has been shown that Helicobacter hepaticus causes both chronic hepatitis and hepatocellular carcinoma (HCC) in mice, it is suggested that differences in the progression of chronic hepatitis C may be due to a cofactor stemming from co-infection by bacteria, especially Helicobacter pylori, and/or other Helicobacter species. An assessment was made of the prevalence of H. pylori infection in HCV-positive cirrhotic patients. The presence of Helicobacter species (spp). was evaluated in resected liver tissue from HCC patients. Serum anti-H. pylori IgG antibodies were determined in 70 males with a clinical and/or histological diagnosis of cirrhosis and HCV infection and in 310 age-matched male blood donors. The prevalences of H. pylori antibody were 77% (54/70) and 59% (183/310) (P 0.004). Primers identifying 26 Helicobacter species were used to determine the presence of the genomic 16S rRNA of this genus in liver tissue resected from 25 cirrhotic HCC patients. Genomic sequences corresponding to H. pylori and H. pullorum were identified in 23 of these 25 livers. Together, these findings support the proposal that H. pylori is implicated in the pathogenesis and progression of cirrhosis, particularly in HCV-infected individuals. Involvement of Helicobacter spp. in HCC also seems highly possible.     

Prevalence of Herpes simplex virus infection in pregnant women in Yopougon (Côte d'Ivoire)

A transversal survey on 150 pregnant women was carried out at the P.M.I. center in Yopougon, in order to determine the prevalence of genital herpes and to estimate the frequency of asymptomatic excreting of Herpes simplex virus (HSV) in pregnant women. The viral isolation and the direct immuno-fluorescence (IF) assay of the genital secretions were found to have a prevalence of 12.7% Among the women who tested positive (the majority of whom were from modest socio-economic origin and young), 10% had antecedents of genital herpes, 2.7% showed an asymptomatic excretion and 36.8% had an acute episode during their pregnancy including a primary infection in the 20th week. In these women an unexpected recurrence will constitute the major risk for maternal transmission and an emergence of neonatal herpes.     

Development of TaqMan-based qPCR method for detection of caprine arthritis–encephalitis virus (CAEV) infection

A specific and sensitive two-step TaqMan real-time PCR has been developed for rapid diagnosis of caprine arthritis-encephalitis virus (CAEV) infection by using a set of specific primers and a TaqMan probe targeting a highly conserved region within the gene encoding the viral capsid protein (CA). The assay successfully detected CAEV proviral DNA in total DNA extracts originating from cell culture, whole blood samples and isolated PBMCs, with a lower detection limit of 10² copies and a linear dynamic range of 10⁵ to 10¹⁰ copies/ml. There was no cross-reaction with other animal viruses (e.g., goat pox virus, bovine leukemia virus, bovine mucosal disease virus, swine influenza virus and Nipah virus). When applied in parallel with serological AGID and conventional PCR for detection of CAEV in field samples, this assay exhibited a higher sensitivity than these traditional methods, and 7.8 % of the 308 specimens collected in the Shanxi and Tianjin regions of China from 1993 to 2011 were found to be positive. Thus, the TaqMan qPCR assay provides a fast, specific and sensitive means for detecting CAEV proviral DNA in goat specimens and should be useful for large-scale detection in eradication programs and epidemiological studies.     

Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university‐affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications. J. Med. Virol. 85:43–48, 2012. © 2012 Wiley Periodicals, Inc.