Hepatitis Monthly
Volume:17 Issue: 3, Mar 2017

The natural history of chronic hepatitis B (CHB) infection is divided into different phases including immune tolerance (IT), immune clearance (or immune active [IA]), inactive carrier (IC), and reactivation. Despite utilizing high-throughput data, the distinct immunological mechanisms of these phases have been insufficiently investigated.
The aim of the present study was to determine candidate disease-associated genes and significantly altered biological processes for each phase of CHB infection.
The gene expression profiles of 83 CHB patients (22 IT, 50 IA, and 11 IC phases) were obtained from gene expression omnibus (GEO dataset: GSE65359) and analyzed by bioinformatics tools. Several plugins of Cytoscape software were used to construct protein-protein interaction (PPI) networks and measure their topological properties. Subsequently, functional annotation and signaling pathway enrichment were carried out using the database for annotation, visualization and integrated discovery (DAVID) and Kyoto encyclopedia of genes and genomes (KEGG).
449 and 452 deregulated genes were identified in IT-IA and IA-IC patients, respectively. Gene ontology and KEGG pathway analyses showed that several immune response-associated genes and signaling pathways (i.e. cytokine-cytokine receptor interaction, chemokine signaling pathway and T cell receptor signalling pathway) were upregulated in the IA phase, but downregulated in the IC phase. The LCK (encoding a tyrosine kinase) was determined as the most important hub gene of both constructed PPI networks. Furthermore, other immune response-associated genes such as CXCR3, VCAN, MYC, and STAT1 were found to be the important hub genes in clinical phases of CHB.
The immune response-related pathways were found to be up and downregulated in the immune clearance phase and inactive carrier phase of CHB, respectively. The LCK hub gene might help the pathogenesis of different phases of CHB and serve as a therapeutic target for the treatment of hepatitis B virus.

Cirrhosis is recognized by a reduction in hepatocyte proliferation with an increase in fibrous tissue, which may ultimately lead to the development of cancerous nodules. Liver biopsy has remained the gold standard for confirming liver fibrosis stages, but there are not any nonreversible and specific therapeutic targets in advanced cirrhosis. In the present study, we used the NMR method to find potential therapeutic markers in serum of HCV - cirrhotic patients with advanced stage.
A metabolic profiling study was conducted using 2 groups: decompensated HCV-cirrhosis patients (n = 21) and healthy controls (n = 18). 1H nuclear magnetic resonance (NMR) approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by the multivariate principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Moreover, metabolic pathways were determined using MetaboAnalyst 3.0.
Specifically, 16 metabolites showed alteration between the 2 groups. Compared with healthy controls, a number of metabolites showed increased concentration in serum of decompensated HCV-cirrhosis such as succinic acid, isovaleraldehyde, citrulline, propanal and cinnamaldehyde, while several others were observed in decreased levels in the decompensated HCV-cirrhosis such as valine, glutamine, trimethylamine, lactate, proline, aspartate, lipid, VLDL, isoleucine, fucose, and glutamate. Aminoacyl-tRNA biosynthesis, alanine, aspartate, glutamate metabolism and arginine, and proline metabolism are the most significant pathways associated with advanced HCV- cirrhosis.
Metabolomic profiling through NMR can identify the metabolic disturbances in advanced HCV-cirrhosis. Aberrant amino acid biosynthesis may be the hallmark with increasing severity of cirrhosis as well as alterations in energetic metabolism.

Hepatitis B virus (HBV) can cause cirrhosis of the liver and hepatocellular carcinoma. Due to the lack of sufficient immune response in whole population, several studies have been conducted to improve the efficacy of alum- based HBV vaccine. Here, naloxone/alum mixture as adjuvant was used for the hepatitis B surface antigen HBsAg vaccine and immune parameters evaluated in immunized mice.
The present study aimed at investigating the effect of naloxone/alum mixture for the HBsAg vaccine and comparing to Fendrix vaccine.
Female Balb/c mice were vaccinated at day 0, 14, and 28 with alum- based vaccine or naloxone/alum mixture vaccine in different doses. Naloxone/alum vaccine groups received a dose of 3, 6, or 10 mg/kg of naloxone (NLX) in the vaccine formulation. One group received routine HBsAg alum vaccine and another group received Fendrix vaccine. Some groups received naloxone plus HBsAg without alum and a group received HBsAg without adjuvant. Phosphate buffered saline (PBS), naloxone, and alum were also injected into the control groups separately. Finally, the naloxone/alum formulated vaccine was compared with the Fendrix and routine alum- based vaccine with respect to the levels of total anti-HBS antibody, IFN-γ, IL-4, IgG1, IgG2a, and the level of lymphocyte proliferation.
The level of total anti-HBS antibody in naloxone formulated vaccine was comparable with Fendrix. Meanwhile, IFN-γ/IL-4 ratio level was significantly higher in naloxone formulated vaccine groups versus mere vaccine group. IgG2a was also higher in the naloxone formulated vaccine groups.
Based on the data presented in the present study, it was found that naloxone/alum mixture has the ability to shift the immune response towards Th1 pattern and potentially increase immunity against infections.

This study aimed to assess the knowledge of junior doctors on the 2015 chronic hepatitis B (CHB) guideline recommended by Chinese society of infectious diseases and Chinese society of hepatology, Chinese medical association.
Junior doctors, who were already engaged in the field of CHB, were invited to complete a questionnaire-based survey between May and June 2016. The questionnaire consisted of 28 items focusing on knowledge in the following three sections: mother-to-child transmission (MTCT) prevention, response-guided therapy (RGT) strategies, and special patients’ antiviral therapy.
Responses were received from 562 out of 600 participants. Among those 562 junior doctors, about 10%~30% were not familiar with the use of hepatitis B vaccine and hepatitis B immunoglobulin (HBIG), and 18.8% did not know that newborn with HBsAg-positive mother could be breastfed after giving HBIG and vaccine. About 20.6% of junior doctors did not know the possible withdrawal indications recommended by the guideline. For HBeAg-positive patients receiving low genetic barrier drugs, about 30% of junior doctors did not know that the antiviral strategies should be adjusted according to HBV DNA levels at treatment week 24. For CHB patients receiving chemotherapy, about 25% of participants did not know antiviral therapy should be started at least 1 week earlier, and about 20% did not know that adefovir dipivoxil or tenofovir disoproxil fumarate should be avoided in patients with kidney diseases or high-risk of developing kidney diseases.
The knowledge on CHB guideline was rather unsatisfactory in junior doctors. Our finding highlights the urgent need for strengthening junior doctors to gain a greater understanding of CHB guideline.

Hepatitis B virus (HBV) genotypes have been shown to have virological, clinical, and therapeutic implications. Knowledge about HBV genotype distribution in Slovenia is scarce. This study was the first to determine various characteristics of patients with chronic HBV infection with regard to HBV genotypes at the national level.
HBV genotype determination was performed on randomly selected patients out of 1,729 patients from all Slovenian regions who tested positive for HBV surface antigen (HBsAg) at the national reference laboratory for viral hepatitis between January 1997 and December 2010. Demographic, epidemiological, virological, and clinical data were extracted from the medical records and statistically analyzed with regard to HBV genotypes.
A total of 186 HBsAg positive patients with the mean age of 40.1 years were identified from whom, 65.1% were male. 157 (84.4%) cases presented with genotype D, 23 (12.4%) with genotype A, and 6 (3.2%) with other HBV genotypes. Sexual transmission was more significantly associated with lower odds for HBV genotype D infection compared to blood-related risk factors (P = 0.023). Genotype A was significantly more common in men who had sex with men (P = 0.043). Compared to females with genotype D, genotype A positive women presented unknown risk factors more significantly (P = 0.002).
HBV genotype D is the most prevalent genotype in Slovenia. However, future changes might be expected due to recent massive immigrations to Europe. Routine HBV genotyping is recommended in patients with certain risk factors prior to initiation of hepatitis B treatment.

A 49-year-old male patient was referred to our institution for acute liver failure (ALV). Apart from cholestasis, coagulopathy, and hepatic encephalopathy (HE) I°, laboratory studies revealed a significant increase in liver enzymes with an alanine aminotransferase (ALT) level of 4’108 U/L and an aspartate aminotransferase (AST) level of 3’878 U/l (normal

Hepatitis C virus (HCV) multiple infections can influence the course of the disease, either by boosting hepatocellular injury or by increasing the frequency of exacerbations. Their prevalence ranges from 5% to 39% in individuals with HCV infection, with a higher impact on injection drug users (IDUs), or in prison settings.
The current paper reported a case of dual HCV infection in a 31-year-old female, with a referred vertical transmission of HCV infection and also a history of IDU, who harbored a subtype 4d since youth. Treatment failure, after a 24-week course of sofosbuvir/ledipasvir, prompted a reevaluation of present and past HCV status. HCV genotype was determined by INNO-LiPATM HCV II kit (LiPA II) (Innogenetics, Ghent, Belgium) and sequencing of NS5B region (nucleotide 8281 - 8679). Direct-acting antivirals (DAAs) resistance profile was investigated by NS3/4, NS5A and NS5B sequencing with specific primers. The Sentosa® SQ next generation sequencing (NGS) workflow was further performed in the baseline and failure samples. Unexpectedly, a subtype 4d in the pretreatment sample and a subtype 1a in the posttreatment were identified. No resistance associated mutations (RAS) were detected in the subtype 4d, although the 170AV and 174S in the NS3/4 gene, the 30R in the NS5A gene, and the 444D in the NS5B gene were detected in the subtype 1a virus from the failure sample.
Two main hypotheses were raised: a reinfection with a new subtype 1a virus during the treatment with a wild type strain, which developed RAS after infection or with an already mutated virus; and a pretreatment hidden dual subtype 4d plus 1a infection.