Hepatitis Monthly
Volume:16 Issue: 2, Feb 2016

Absence of an immunocompetent mouse model of persistent hepatitis B virus (HBV) infection has hindered the research of HBV infection and the development of antiviral medications. In the present study, we aimed to develop a novel HBV genotype C mouse model by hydrodynamic injection (HI) and then used it to evaluate the antiviral activity of lamivudine. A quantity of 15 μg of HBV plasmid [pcDNA3.1 (+)-HBV1.3C], adeno-associated virus-HBV1.3C (pAAV-HBV1.3C) or pAAV-HBV1.2A) were injected into male C57BL/6 mice, by HI, accounting for a total of 13 mice per group. Then, lamivudine was administered to mice with sustained HBV viremia, for 4 weeks. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry methods were used to detect HBsAg, HBeAg, HBsAb, HBcAg and HBV DNA, in serum or liver of the mice, at indicated time points. In 60% of the mice injected with pcDNA3.1 (+)-HBV1.3C, HBsAg, HBeAg, HBcAg and HBV DNA persisted for > 20 weeks in liver, post-injection, with no HBsAb appearance. Meanwhile, no significant inflammation was observed in these mice. Compared with pAAV-HBV1.2A and pAAV-HBV1.3C, pcDNA3.1 (+)-HBV1.3C administration led to higher and longer HBV viremia. Furthermore, serum HBV DNA was significantly reduced by lamivudine, after 4 weeks administration, and returned to the original level, after ceasing administration for 1 week, in the mice. In conclusion, our observations indicated that pcDNA3.1 (+)-HBV1.3C was superior to AAV/HBV plasmid for establishment of persistent HBV infection by HI, in vivo, and this mouse model could be useful for studies of hepatitis virology and for the development of innovatory treatments for HBV infections.

Nursing students can be exposed to patients with hepatitis A virus (HAV) and can represent a vehicle of transmission both for health personnel, patients and relatives. The aim of this study was to assess the risk of HAV infection in nursing students during their internship.Patients and A seroprevalence survey on HAV infection was performed on nursing students at the Cagliari university-hospital, together with the assessment of the compliance to preventive measures to decrease the risk of infection during their internship. Blood specimens were obtained from 253 students. All serum samples were tested for anti-HAV antibodies (IgG) by the enzyme-linked immunosorbent assay (ELISA). Compliance to preventive measures was recorded by trained personnel. Overall HAV seropositivity in nursing students (mean age 24, range 17 - 45 years) was 3%. Compliance to preventive measures was not uniform (6% - 76%) and extremely low in some specific measures targeted to decrease the oral-fecal transmission. The high proportion of susceptible nursing students can contribute to an increase in the risk of nosocomial transmission, especially when specific preventive measures are not completely applied. Nursing education packages, before starting medical internship, should be implemented in order to increase their compliance to preventive measures, especially in wards at higher risk. Vaccination should be considered in wards at higher risk.

Assessment of hepatic fibrosis stage in patients with chronic hepatitis B (CHB) is indispensable for prognosis evaluation and therapeutic regime. Noninvasive tests are fast, safe and cheap and need low technical requirements for diagnosing hepatic fibrosis in CHB patients. Using the latent class model with a random-factor to estimate relative accuracy of noninvasive tests for the diagnosis of hepatic fibrosis without a gold standard in a large population with CHB.Patients and A total of 544 patients with CHB were assessed for fibrosis stage by four noninvasive tests containing liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4) and globulin and platelet (GP). The diagnostic evaluation was made by the latent class method with random effect which analyzed the clinical data above to assess the accuracy of four ways of noninvasive diagnosis. The latent class model with random effect permitted to conciliate the observed data and estimates of test performances. For significant fibrosis, the specificity/sensitivity were 83.24%/91.59% (APRI), 90.05%/95.57% (FIB-4), 75.11%/66.01% (LSM) and 71.13%/98.33% (GP), respectively. For cirrhosis, the specificity/sensitivity were 84.04%/17.91% (APRI), 89.86%/17.09 (FIB-4), 78.64%/37.07% (LSM) and 82.28%/37.07% (GP), respectively. FIB-4 confirmed the best value for diagnosis of significant fibrosis. APRI had a sub-optimal diagnosis accuracy for significant fibrosis. LSM showed the most balance diagnosis value for cirrhosis with the highest sensitivity and moderate specificity.

IL-10 can play a vital role in immune response against HBV. Three biallelic SNPs from the transcription start site control the transcription of the IL-10 gene. An association between susceptibility to HBV and IL-10 polymorphisms has been suggested in patients with HBV infection. The present study was designed to study the association between polymorphisms in interleukin-10 (-1082 A/G, -819 T/C and -592 A/C) promoter gene and chronic hepatitis B virus (HBV) infection.Patients and 221 chronically infected patients and 200 healthy control subjects were enrolled in the study. Three biallelic (-1082 A/G, -819 T/C and -592 A/C) polymorphisms in the IL-10 promoter gene were determined by PCR-RFLP method. Persistent HBV infection was associated with IL-10-1082 AG (P = 0.001) and GG (P = 0.004) genotypes and G (P = 0.000) allele. IL-10-819 T/C and -592 A/C genotype and allele frequencies did not show any correlation with the risk of chronic hepatitis B infection. These results suggest that polymorphisms in interleukin-10 gene promoter influence clinical outcome of HBV infection and susceptibility to HBV infection.

Recommendations to immunize healthcare workers (HCWs) against hepatitis B are well known. However, a proportion of individuals do not respond to the primary standard three-dose HB vaccination schedule. The current study aimed to evaluate whether a double-dose HB booster vaccine could induce better protective anti-HB titers than a single-dose booster in non-protected HCWs. This was a randomized clinical trial. A total of 91 HCWs not responding to the primary vaccine series in 2014 were enrolled. The participants were randomized into two groups that received a double dose of the HB vaccine containing 40 µg of antigen or a single dose of the HB vaccine containing 20 µg of antigen in three doses (at zero, one and six months after vaccination). Blood samples were collected before vaccinations and 28 days after the third dose to assess the seroconversion rate, according to the anti-HB antibody titer threshold of > 10 mIU/mL. The seroconversion rates were 93.2% and 87.2% after the first booster doses of the double-dose and single-dose HB vaccines, respectively (P = 0.64). In the double-dose HB vaccine group, the seroconversion rate was 97.8% compared with 89.6% in the single-dose group following the second vaccine dose (P = 0.83). All of the participants in both groups were seroprotected after the third HB vaccine dose. Both the single- and double-dose HB vaccines were adequately immunogenic, and the double-dose HB vaccine was not significantly more immunogenic than the single-dose vaccine in terms of the seroconversion rates of HCWs who had not responded to the primary vaccine series.

Hepatitis C virus (HCV) has been known as a major cause of hepatocellular carcinoma (HCC) worldwide. However, the distinct molecular mechanisms underlying the effects of HCV proteins on the HCC progression have remained unclear.. In the present study, we studied the possible role of HCV in the HCC initiation and invasion using topological analysis of protein-protein interaction (PPI) networks. After analysis with GEO2R, a PPI network of differentially expressed genes (DEGs) was constructed for both chronic HCV and HCC samples. The STRING and GeneMANIA databases were used to determine the putative interactions between DEGs. In parallel, the functional annotation of DEGs was performed using g: Profiler web tool. The topological analysis and network visualization was carried outperformed using Cytoscape software and the top hub genes were identified. We determined the hub genes-related miRNAs using miRTarBase server and reconstructed a miRNA-Hubgene network. Based on the topological analysis of miRNA-Hubgene network, we identified the key hub miRNAs. In order to identify the most important common sub-network, we aligned two PPI networks using NETAL tool. The c-Jun gene was identified as the most important hub gene in both HCV and HCC networks. Furthermore, the hsa-miR-34a, hsa-miR-155, hsa-miR-24, hsa-miR-744 and hsa-miR-92a were recognized as the most important hub miRNAs with positive correlation in the chronic HCV and HCC samples. Functional annotation of differentially expressed miRNAs (DEMs) using the tool for annotations of human miRNAs (TAM) revealed that there is a considerable overlap between miRNA gene expression profiles of HCV-infected and HCC cells. Our results revealed the possible crucial genes and miRNAs involved in the initiation and progression of HCC cells infected with HCV.

It has been found that ITPase deficiency is caused by ITPA gene polymorphisms. It was observed that ITPA polymorphisms have impact on hematological changes, including hemoglobin (Hb)-decline during treatment of chronic hepatitis C (CHC) patients with pegylated-interferon (PEG-IFN) plus ribavirin (RBV). This study aimed to assess the effect of ITPA and C20orf194 polymorphisms on hematological changes at week 4 of treatment with PEG-IFN plus RBV in patients with CHC.Patients and In this retrospective study, 168 patients with CHC (56% HCV genotype-1 and 44% HCV genotype-3) under the treatment of PEG-IFN plus RBV were genotyped for rs1127354, rs7270101 and rs6051702 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism. Hematological changes including Hb-, platelet (Plt)- and white blood cell-decline at week 4 of the treatment were assessed. In univariate analysis, rs1127354 and HCV genotypes were found to influence the Hb-decline at week 4 of the treatment. In multivariate analysis, rs1127354 CA + AA and HCV genotype-3 were found to have a great role on prevention of Hb-decline. Furthermore, rs1127354 and HCV RNA levels were found to influence the Plt-decline at week 4 of the treatment in the univariate analysis. In multivariate analysis, rs1127354 CA + AA and HCV RNA levels less than 600,000 IU/mL were found to be associated with a higher level of Plt-decline. In patients with CHC, who were treated with PEG-IFN plus RBV, Hb-decline was affected by rs1127354 and HCV genotypes. However, Plt-decline may be altered by rs1127354 and baseline HCV RNA levels.

Both primary biliary cirrhosis (PBC) and Wilson’s disease (WD) can cause copper retention in the liver, which is an important factor for liver cellular damage. Copper chelation may preserve liver cell function. It is challenging to distinguish WD from copper accumulation in patients with PBC. There have been few case reports of PBC co-occurrence with WD. Here we report a case of PBC with WD in a 55-year-old Chinese male. In addition to the typical pathological characteristics of PBC and a large number of copper depositions in the liver, the patient showed WD ATP7B gene mutations. Co-occurrence of PBC with WD is rare, which can cause diffusely intrahepatic copper deposition. Early liver biopsy and genetic testing are necessary for the diagnosis. The combination of ursodeoxycholic acid with zinc and sodium dimercaptopropane sulfonate is effective.

Occult hepatitis B virus (HBV) is defined by the presence of HBV DNA in patient sera in the absence of HBsAg. Occult HBV has been associated with hepatocellular carcinoma, reactivation during immune suppression, and transmission to others. While the hepatitis B vaccine is very effective at preventing chronic HBV infection, recent studies indicate it is less effective at preventing occult HBV following infant vaccination. No studies, however, have examined the efficacy of adult HBV vaccination at preventing occult HBV. Here, we present the first report of occult HBV following adult vaccination. A 21-year old Caucasian female presented with tricuspid valve endocarditis secondary to methicillin-susceptible Staphylococcus aureus with non-ischemic cardiomyopathy. She reported active use of intravenous drugs. Her liver enzymes were elevated (ALT = 1873 IU/mL; AST = 4518 IU/mL), and she was found to have HCV and occult HBV. HBV viral loads ranged from 4608 - 8364 copies IU/mL during hospitalization. The patient’s HBV was sequenced and found to be genotype D3 without any known diagnostic escape mutations. Immune complexes that may have prevented HBsAg detection were not observed. HBV vaccination in infancy is effective at preventing chronic HBV infection but is less effective at preventing occult HBV infection. Similar studies examining the efficacy of adult HBV vaccination in preventing occult HBV have not been performed. This case highlights the importance of carefully determining the HBV status of high-risk individuals, as vaccination history and the presence of anti-HBs may not be adequate to rule out HBV infection, even in the absence of HBsAg.