HBsAg Inhibits the Translocation of JTB into Mitochondria in HepG2 Cells and Potentially Plays a Role in HCC Progression

Background and Aims: The expression of the jumping translocation breakpoint (JTB) gene is upregulated in malignant liver tissues; however, JTB is associated with unbalanced translocations in many other types of cancer that suppress JTB expression. No comprehensive analysis on its function in human hepatocellular carcinoma (HCC) has been performed to date. We aimed to define the biological consequences for interaction between JTB and HBsAg in HCC cell lines. Methods: We employed the stable transfection to establish small HBsAg expressing HepG2 cell line, and stably silenced the JTB expression using short hairpin RNA in HepG2 cell line. The effects of JTB and small HBsAg in vitro were determined by assessing cell apoptosis and motility. Results: Silencing of JTB expression promoted cancer cell motility and reduced cell apoptosis, which was significantly enhanced by HBs expression. Expression of HBsAg inhibited the translocation of JTB to the mitochondria. Furthermore, silencing of the JTB resulted in an increase in the phosphorylation of p65 in HepG2 cells and HepG2-HBs cells, whereas HBsAg expression decreased the phosphorylation of p65. The silencing of JTB in HepG2-HBs cells conferred increased advantages in cell motility and anti-apoptosis. Conclusion: HBsAg inhibited the translocation of JTB to the mitochondria and decreased the phosphorylation of p65 through the interaction with JTB, After JTB knockdown, HBsAg exhibited a stronger potential to promote tumor progression. Our data suggested that JTB act as a tumor suppressor gene in regards to HBV infection and its activation might be applied as a therapeutic strategy for in control of HBV related HCC development.National Natural Science Foundation of China [30971362, 81072013]; Fundamental Research Funds for the Central Universities in China [2010111082]; Key Projects for Technology Plan of Fujian Province in China [2009D020]; Foundation of Health Bureau of Fujian in China [2007CXB8, 3502z20077046]; Foundation of Health Bureau of Xiamen in China [2007CXB8, 3502z20077046

ОСОБЕННОСТИ ПОЛИМОРФИЗМА ГЕНОВ ИНТЕРФЕРОНА III ТИПА У БОЛЬНЫХ ВИРУСНЫМ ГЕПАТИТОМ С НА СОПРЕДЕЛЬНЫХ ТЕРРИТОРИЯХ РОССИИ И МОНГОЛИИ

Aims: determine the structure of IFNL3/IFNL4 interferon genes’ polymorphism in healthy people and in HCV patients and the frequency of spontaneous viral clearance in ethnic groups of Caucasians and Mongolians, living in the Asian part of Russia (Irkutsk Region) and in Mongolia. Materials and methods: population genetic studies were conducted at 669 patients with hepatitis C, including 567 representatives Caucasian and 102 Mongoloid races. The control group consisted of 1520 healthy individuals, blood donors (800 Caucasians and 720 Mongoloids). Results: it was found that in Caucasians patients with chronic hepatitis C were significantly less common CC genotype rs12979860, TT genotype rs8099917 and TT/TT genotype rs368234815, than in the general population. However, in patients with chronic hepatitis C, the representatives of the Mongoloid race, compared with healthy individuals, significant differences were found only in relation to the TT genotype rs8099917 IFNL3 gene. Spontaneous clearance of the virus was significantly more common in the Mongoloid race than in Caucasians. Conclusions: the spontaneous viral clearance after clinical evidence or latent suffering hepatitis C was significantly more common in the Mongoloid race than in Caucasians that genetically determined high rate of prevalence in the population of the Mongols CC genotype rs12979860, TT genotype rs8099917 and TT/TT genotype rs368234815 polymorphisms of interferon type III genes.Цель исследования: определить структуру полиморфизма генов интерферона IFNL3/IFNL4 у здоровых лиц и больных вирусным гепатитом С и частоту спонтанного клиренса вируса в этнических группах европеоидов и монголоидов, проживающих в азиатской части России (Иркутская область) и Монголии. Материалы и методы: популяционно-генетические исследования проводились у 669 больных хроническим гепатитом С, в том числе у 567 представителей европеоидной и 102 монголоидной рас. Контрольную группу составили 1520 практически здоровых лиц, доноров крови (800 европеоидов и 720 монголоидов). Результаты: обнаружено, что у больных хроническим гепатитом С, представителей европеоидной расы, значимо реже встречались СС-генотип rs12979860, ТТгенотип rs8099917 и ТТ/ТТ-генотип rs368234815, чем в общей популяции здоровых лиц. Вместе с тем, у больных хроническим гепатитом С, представителей монголоидной расы, по сравнению со здоровыми лицами, значимые отличия обнаружены только в отношении ТТ-генотипа rs8099917 гена IFNL3. Спонтанный клиренс вируса значимо чаще (в 1,6 раза) встречался у представителей монголоидной расы, чем у европеоидов. Заключение: спонтанный клиренс вируса после клинически выраженного или латентно перенесенного гепатита С значимо чаще встречается у представителей монголоидной расы, чем у европеоидов, что генетически детерминировано высокой частотой распространенности в популяции монголов СС-генотипа rs12979860, ТТ-генотипа rs8099917 и ТТ/ТТ-генотипа rs368234815 полиморфизмов генов интерферонов III типа

Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories

BACKGROUND & AIMS: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. METHODS: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. RESULTS: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. CONCLUSIONS: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened. IMPACT AND IMPLICATIONS: There is a great deal of uncertainty surrounding the prevalence of hepatitis delta virus among people living with hepatitis B virus at the population level. In this study, we aimed to better understand the burden in 25 countries and territories, to refine techniques that can be used in future analyses. We found a lower prevalence in the majority of places studied than had been previously reported. These data can help inform policy makers on the need to screen people living with hepatitis B virus to find those coinfected with hepatitis delta virus and at high risk of progression, while also highlighting the pitfalls that other researchers have often fallen into

PECULIARITIES OF THE III TYPE INTERFERON GENES’ POLYMORPHISM IN HCV PATIENTS ON THE CROSS-BORDER REGIONS OF RUSSIA AND MONGOLIA

Aims: determine the structure of IFNL3/IFNL4 interferon genes’ polymorphism in healthy people and in HCV patients and the frequency of spontaneous viral clearance in ethnic groups of Caucasians and Mongolians, living in the Asian part of Russia (Irkutsk Region) and in Mongolia. Materials and methods: population genetic studies were conducted at 669 patients with hepatitis C, including 567 representatives Caucasian and 102 Mongoloid races. The control group consisted of 1520 healthy individuals, blood donors (800 Caucasians and 720 Mongoloids). Results: it was found that in Caucasians patients with chronic hepatitis C were significantly less common CC genotype rs12979860, TT genotype rs8099917 and TT/TT genotype rs368234815, than in the general population. However, in patients with chronic hepatitis C, the representatives of the Mongoloid race, compared with healthy individuals, significant differences were found only in relation to the TT genotype rs8099917 IFNL3 gene. Spontaneous clearance of the virus was significantly more common in the Mongoloid race than in Caucasians. Conclusions: the spontaneous viral clearance after clinical evidence or latent suffering hepatitis C was significantly more common in the Mongoloid race than in Caucasians that genetically determined high rate of prevalence in the population of the Mongols CC genotype rs12979860, TT genotype rs8099917 and TT/TT genotype rs368234815 polymorphisms of interferon type III genes

Comparison of vaccination schedules for foot-and-mouth disease among cattle and sheep in Mongolia

Vaccines are a critical tool for the control strategy for foot-and-mouth disease (FMD) in Mongolia where sporadic outbreaks regularly occur. A two-dose primary vaccination course is recommended for most commercial vaccines though this can be logistically challenging to deliver among nomadic pastoralist systems which predominate in the country. Although there is evidence that very high potency vaccines can provide prolonged duration of immunity, this has not been demonstrated under field conditions using commercially available vaccines. This study compared neutralizing titres to a O/ME-SA/Panasia strain over a 6-month period following either a two-dose primary course or a single double-dose vaccination among Mongolian sheep and cattle using a 6.0 PD50 vaccine. Titers were not significantly different between groups except in sheep at six-months post vaccination when the single double-dose group had significantly lower titers. These results indicate the single double-dose regimen may be a cost-effective approach for vaccination campaigns supporting FMD control in Mongolia

CLINICAL AND EPIDEMIOLOGICAL MANIFESTATION OF HEPATOCELLULAR CARCINOMA IN PATIENTS BELONGING TO ETHNIC GROUPS OF CAUCASIANS AND ASIANS OF NORTH-EAST ASIA

Aim. The current study is aimed at determining differences of epidemiological and clinical profiles associated with HCC in patients belonging to ethnic groups of Asians from Mongolia and Caucasians from Asian region of Russia. Materials and methods. The studies were carried out in the cross-border regions of Mongolia and Asian part of Russia (Irkutsk region). 300 patients with hepatocellular carcinoma (HCC) of the Caucasian and Mongolian races were enrolled in the study. The level of alpha-fetoprotein (AFP) in the serum was determined by the chemiluminescence technique. Results. The long-term dynamics of the HCC incidence shows more unfavourable trends in the territory of Mongolia compared to Irkutsk region. In both groups, male patients over 60 years of age predominated. Patients from Mongolia often have a history of jaundice and alcohol abuse. Out of the etiological factors, HCC is more often associated with the hepatitis B virus in Mongolia than in the Asian part of Russia. At the same time, in Caucasians, HCC develops primarily on the background of liver cirrhosis. In patients with HCC, AFP level higher than 20 ng / ml were significantly more frequent in the ethnic group of Caucasoids than in Mongoloids. Conclusions. Mongolia in terms of the incidence of HCC belongs to the hyperendemic regions of the world. In this country, among the risk factors for the development of the disease, hepatitis B virus plays a major role, which significantly differs from the Asian part of Russia. For the purpose of early diagnosis of HCC, it is necessary to search for new molecular markers or their combinations due to the insufficient diagnostic efficiency of AFP determination