2016 World Hepatitis Day: A list of hepatitis breakthrough research progress
Release date: 2016-07-28
July 28th is the birthday of the late Nobel laureate Baruch Blomberg. To commemorate the hepatitis B virus discoverer, the World Health Organization decided in May 2010 that it will start the annual world hepatitis from 2011. The day was changed from May 19 to July 28. The theme of World Hepatitis Day 2016 is "Love Liver and Protect Liver and Enjoy Health".
The liver is an important organ related to the metabolic function of the human body. It plays a variety of important roles in the body such as deoxidation, storage of glycogen, and secretion of protein. Common liver diseases include hepatitis A, hepatitis B, hepatitis C, cirrhosis, nonalcoholic fatty liver, liver cancer, etc. These diseases are also the most common diseases that are extremely harmful to humans.
According to the latest WHO data, viral hepatitis causes 1.4 million deaths each year, viral hepatitis carriers are currently about 500 million, and 2 billion people worldwide are infected with hepatitis virus, killing about 1 million people each year. China's legal infectious disease system reports more than 1.3 million cases of viral hepatitis each year, accounting for one-third of the total reported cases. Viral hepatitis ranks first in the incidence of infectious diseases, of which hepatitis B accounts for 80% of all hepatitis cases. China’s direct economic losses due to hepatitis B are at least 500 billion yuan each year.
In this article, Xiaobian has taken stock of the latest developments in hepatitis research in recent years, and learns with you!
[1] Cancer Cell: Liver “Protect God†Let chronic hepatitis and liver cancer go away
Doi:10.1016/j.ccell.2015.10.001
In an article recently published in the international academic journal Cance Cell, scientists from Germany have conducted in-depth research on how apoptosis participates in the development of steatohepatitis and hepatocellular carcinoma.
In this study, the researchers found that RIPK1 mediates hepatic parenchymal cell apoptosis via a RIPK3-independent mechanism, which further triggers the development of chronic hepatitis and hepatocellular carcinoma (HCC). The study found that this role of RIPK1 is dependent on its kinase activity, and is also regulated by the NF-kB-dependent pathway and the NF-kB-independent pathway involved in NEMO molecules. Many previous studies have only shown that NEMO molecules can activate NF-kB, but whether NEMO molecules are directly involved in liver homeostasis and liver disease has not been studied.
Studies have shown that mice lacking NEMO molecules in liver parenchymal cells spontaneously form chronic hepatitis and HCC, so it is speculated that NF-kB may play an inhibitory role in liver disease and cancer development. To further validate this view, the researchers first specifically eliminated RelA, c-Rel and RelB in hepatocytes to achieve complete inhibition of NF-kB, and did not cause spontaneous HCC, which was knocked out with NEMO. The phenotype of the mice did not match. The researchers then constitutively activated NF-kB in NEMO-specific knockout mice, and the liver of the mice was protected from liver cell damage and HCC. This suggests that NEMO does not protect the liver of mice by a single pathway.
[2] PLoS Pathogens: New Progress, TGFβ Inhibits Hepatitis B Virus Replication
DOI: 10.1371/journal.ppat.1004780
Recently, the international academic journal Plos Pathogens published a recent research advancement by Japanese scientists who found that the inhibition of hepatitis B virus (HBV) replication by TGFβ is dependent on activation-induced cytosine deaminase (AID). Expression, AID can significantly inhibit HBV transcription and viral DNA synthesis, ultimately leading to inhibition of viral replication.
Hepatitis B virus (HBV) is an important predisposing factor for the development of hepatocellular carcinoma. Recent studies have found that APOBEC deaminase family members are able to exert antiviral functions by inhibiting viral replication such as HBV and HIV. Studies have shown that APOBEC3G can inhibit viral replication by promoting high mutations in viral new synthetic DNA or inhibiting reverse transcription. Another study found that AID also has the function of limiting viral replication, but the mechanism is still unclear.
[3] PNAS: intestinal flora or determine the rapid onset of hepatitis B
Doi:10.1073/pnas.1424775112
After getting hepatitis B virus (HBV) infection in adults, 95% spontaneously cleared; while >90% of newborns and about 5% of children aged 1-5 were infected with hepatitis virus but could not be cleared and developed into chronic infection. Recently, a group of scholars at Taiwan University explained that the intestinal flora is related to this age-related hepatitis attack. This study was published in the latest issue of PNAS.
The researchers found that adult mice showed the ability to clear the virus, while young mice did not. After 12-week-old adult mice were infected with HBV, the virus cleared after 5 weeks. Young mice still have a virus after 26 weeks of infection.
The researchers wanted to test whether the composition of the gut flora was associated with HBV infection. They treated some adult mice with antibiotics. Other adult and young mice were not treated with antibiotics. Under normal circumstances, the mice showed substantial changes in the intestinal flora between 6 and 8 weeks, and stabilized after 9 weeks. In the antibiotic-treated mice, almost no intestinal flora was detected during the treatment until 4 days after the end of treatment. It is worth noting that after 4 weeks of treatment, the gut microbes still did not return to levels similar to untreated adult mice.
[4] J Exper Med: reveals the function of helper T cells to protect against hepatitis A virus infection
Doi:10.1084/jem.20111906
Helper cells are generally thought to only help kill white blood cells to protect the body, but a recent study published in the International Journal of Experimental Medical pointed out that helper cells may be the "leaders" against hepatitis A infection. Hepatitis A is a highly contagious liver disease caused by hepatitis A virus. Although there are effective vaccines, millions of people in the world can get hepatitis A virus every year.
Unlike hepatitis C virus, the hepatitis A virus does not establish a period of persistent infection, but in the prognosis of the disease, 20% of patients will relapse with hepatitis A disease. The researchers revealed that well-known CD8+ killer T cells play an important role in controlling hepatitis C virus and hepatitis B virus infection, and these T cells can function by killing infected liver cells. Although the killing process is detrimental to the liver, it is important to curb viral proliferation and effective treatment of the disease.
A study 20 years ago pointed out that killer T cells can also control hepatitis A virus infection, but Professor Walker observed a very different pattern of immune effects by studying acute hepatitis A virus infection. He found that infection can be well controlled before the production of effective killer T cells. The growth of hepatitis A virus can be controlled by CD4+ helper cells, which are cells that help T cells to exert immune effects. In the body of two animals infected with hepatitis A virus, helper T cells can secrete a lot of silver to inhibit the growth of the virus, and of course, it will also cause inflammation of the liver during this process.
[5] Chinese scientists discover new anti-HBV genes
Doi:10.1038/ncomms11664
The team of researchers from the Institute of Radiation and Radiation Medicine of the PLA Academy of Military Medical Sciences led a number of research institutions in the United Nations. For the first time, from the perspectives of genetics, virology, function and molecular mechanism, an "integration factor complex" gene INTS10 was first discovered. Activates the innate immune function of the human body and plays a role in inhibiting the replication of hepatitis B virus.
This research reveals that the "integration factor complex" has a new role in inhibiting the infection of pathogenic microorganisms that has never been discovered before, opening a new direction for its research. At the same time, it helps to understand the molecular mechanism of chronic hepatitis B virus infection, and provides a theoretical basis and a new candidate biological target for effective prevention and treatment. The research results were published in the journal Nature Communication.
At present, there are about 120 million chronic carriers of hepatitis B virus in China. Prevention and treatment of chronic hepatitis B involves national economy and people's livelihood. In order to discover susceptibility genes or resistance genes associated with chronic hepatitis B virus infection, Zhou Gangqiao's research team led researchers from Guangxi Medical University, Nanjing Medical University and Sun Yat-sen University to collect more than 10,000 pieces of whole-genome data. A total of 1251 chronic hepatitis B virus infection patients and 1057 control individuals who had naturally cleared hepatitis B virus infection were screened, and the genetic differences between the two groups were systematically compared.
[6] Nature: A major breakthrough! Hepatitis B virus uses protein X to counter host self-defense!
Doi:10.1038/nature17170
Hepatitis B virus (HBV) is 100 times more infectious than HIV. HBV is mainly transmitted through blood or other body fluids. It infects liver cells. Chronic HBV infection can cause serious health problems such as cirrhosis and liver cancer. According to the World Health Organization (WHO), chronic hepatitis B affects nearly 240 million people worldwide and kills nearly 800,000 people each year. There are drugs available to treat HBV, but they rarely cure this infection, so the virus usually returns after treatment.
In a new study, researchers from the University of Geneva, the University of Lyon, France, and the American Gilead Technologies found out how our cells are self-resisting against HBV infection and how the virus fights back. This research represents an important advance in our understanding of HBV and suggests new ways to develop innovative therapeutic agents. The relevant research results were published online in the Nature Journal on March 16, 2016, and the title of the paper is "Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor".
[7] CGH: drugs can prevent pregnant women from transmitting HBV vertically
Doi:10.1016/j.cgh.2014.08.043
According to an article published in the June issue of the American Journal of Gastroenterology Clinical Practice, Clinical Gastroenterology and Hepatology, the antiviral drug telbivudine prevents hepatitis B virus (HBV) during the perinatal period. Spread.
"If we reduce the global incidence of hepatitis B, we need to address the mother-to-child transmission first, which is the main way of hepatitis B virus infection," research author Yuming Wang said. He is from the Institute of Infectious Diseases, Chongqing Southwest Hospital, China. "We found that telbivudine not only cuts off the way pregnant women pass the baby's hepatitis B virus vertically, but also that women and babies are well tolerated."
The researchers conducted a prospective study of 450 HBV-positive pregnant women (they had very high viral levels in their bodies, or had very visible hepatitis B virus in their blood). The study took place in the last two or three of pregnancy. Within the month. During the study, 279 women received telbivudine (600 mg daily) between 24 and 32 gestational weeks, and 171 women were unwilling to take antiviral drugs as controls. Six months after the birth of the baby, none of the mothers taking telbivudine were tested positive for HBV, while 14.7% of the infants in the control group were tested positive for HBV.
[8] Gene Therapy: Chinese scientists use CRISPR to destroy hepatitis B virus
Doi:10.1038/gt.2015.2
On February 5th, researchers from the Institute of Radiation and Radiation Medicine of the Academy of Military Medical Sciences, Xijing Hospital of the Fourth Military Medical University, Kyoto University of Japan and the Veterinary College of Huazhong Agricultural University published a report in the journal Gene Therapy of Nature. The latest research, entitled "Harnessing the clustered regular interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus". In this study, the researchers explored the effects of the CRISPR/CRISPR-associated Cas9 system targeting the HBV antigen (HBsAg) coding region in cell culture systems and in vivo animals. The results indicate that CRISPR/Cas9 can inhibit HBV replication and expression in vivo and in vitro, which may be a new therapeutic strategy for HBV infection.
Hepatitis B is a disease caused by hepatitis B virus (HBV), which is mainly caused by inflammatory lesions of the liver and can cause damage to multiple organs. Hepatitis B is widely prevalent in all countries of the world, mainly invading children and young adults, and a small number of patients can be converted into cirrhosis or liver cancer. Therefore, it has become a worldwide disease that seriously threatens human health, and it is also the most widespread and most harmful disease in China. Currently, treatments for hepatitis B virus (HBV) infection are limited.
[9] Immunity: Scientists discover new mechanisms of hepatitis B virus immunity
Doi:10.1016/j.immuni.2014.12.016
Hepatitis B is a high-incidence type of infectious disease in the Chinese population. Hepatitis B can cause liver dysfunction, cirrhosis and liver cancer. What causes hepatitis B is a hepatitis B virus (HBV).
The host's invasion of foreign aid pathogens has a series of resistance mechanisms. For viruses, the DNA or RNA molecules they carry can be recognized by various receptor molecules inside the cell (eg, viral 5' phosphorylation or double-stranded RNA can be recognized by RIG-I (retinoic acid-inducible gene-I) molecules) Through a series of downstream signal transmission mechanisms, a large number of type I and type III interferons are produced, which play a role in killing viruses. However, the current research on the immune mechanism of HBV is still not very clear. Previous studies have found that for HBV infection, host-derived type I interferon is far less susceptible than HCV (hepatitis C virus) infection. Recently, the Akinori Takaoka team of the Institute of Genetic Medicine of Hokkaido University in Japan published their recent research on the mechanism of host resistance to HBV infection in the journal Immunology.
[10] Gut: A new method for treating hepatitis C
Doi:10.1136/gut.2005.076646
A preliminary study found that all patients with acute hepatitis C did not detect hepatitis C virus after the next 12 weeks after six weeks of short-term direct antiviral therapy. Researchers have initiated studies that demonstrate that both sofosbuvir and ledipasvir are adequate for treating patients with acute hepatitis C virus within six weeks.
Hepatitis C virus infection usually develops into acute hepatitis C, and the infected person can remove 10% to 50% of the virus by itself. Early diagnosis of hepatitis C virus infection is rare, and the disease can usually be ignored until the patient has experienced some serious liver damage. Sofosbuvir and ledipasvir are a possible treatment for patients with chronic hepatitis C. The virological response (SVR) persisted over 95% during the 12-week treatment period.
“Given the high cost and associated side effects of sofosbuvir and ledipasvir during treatment, we may be an effective option for patients with acute hepatitis C to assess whether shortening the treatment time,†said Katja Deterding of Hannover Medical School, Germany. Studies have shown that the combination of sofosbuvir and ledipasvir is safe, patients with severe liver disease, and patients with acute liver enzymes with high liver enzymes are well tolerated and effective, and shorter treatment times seem to be Does not hinder the efficacy of the drug," said Professor Heiner Wedemeyer.
[11]Lancet Infect Dis: There are currently more than 2.3 million co-infected patients with AIDS and hepatitis C worldwide.
Doi:10.1016/S1473-3099(15)00485-5
Recently, a researcher from institutions such as the University of Bristol found that about 2.3 million HIV-infected people worldwide are also infected with hepatitis C (HCV), and the study is published in The Lancet Infectious Diseases. More than half of the patients (about 1.3 million) are injecting drug users. This study found that HIV-infected individuals are six times more likely to develop hepatitis C infection than individuals who are not infected with HIV, which suggests health. Organize a corresponding treatment policy to improve HIV/HCV co-infected people.
At present, HIV and HCV infection are the main health problems in the world. There are about 3.7 million HIV-infected people in the world and about 115 million chronic HCV patients. However, few studies on HIV/HCV co-infection have been conducted in this study. The first related study on HIV/HCV co-infection. In the article, the researchers reviewed 783 medical studies to effectively assess HIV/HCV co-infection in patients. Researcher Philippa Easterbrook said that the study not only revealed a higher risk of HIV infection in HIV patients, but also showed that injecting drug users occurred. The high prevalence of HCV is at least 80%, so it is necessary to expand the routine detection of HCV infection in HIV patients, especially high-risk individuals, and should also develop new high-healing HCV therapy.
[12]Science: Degrading viral cccDNA or providing ideas for the development of targeted therapies for the treatment of hepatitis B
Doi:10.1126/science.1243462
Hepatitis B virus (HBV) can be stored in host cells for a long time by storing its own genetic information in the host cell nucleus, and its genetic information is usually not degraded in the host, which blocks many antiviral drugs to eliminate the virus. Recently, in a research paper published in the internationally renowned magazine Science, researchers from the Technical University of Munich, Germany, reported that a new type of therapy may eliminate hepatitis B virus.
Although there are vaccines against hepatitis B virus, according to the World Health Organization, more than 240 million people worldwide are infected with hepatitis B virus each year. These people are at risk of liver cirrhosis and even liver cancer. In Germany alone, there are about 500,000 people infected. Hepatitis B virus, commonly used antiviral therapy can only control the virus, but it can not completely eliminate the virus. Once the therapy is stopped, the HBV in the patient's body will be reactivated.
HBV can survive continuously depending on the virus's own DNA, which is cccDNA, which is a covalently closed circular DNA that is usually replicated and stored in a large number of host infected cells. cccDNA can be used as a template for viral replication. Provides the virus with the genome and the proteins on which it depends. In the article, researchers have developed a technique to selectively attack and eliminate viral genetic information in host infected cells without disrupting the host's cellular function.
[13] Nat Genet: Hepatitis B virus susceptibility gene in Han population is analyzed
Doi:10.1038/ng.2809
Researchers from Nanjing Medical University, Jiangsu Provincial Center for Disease Control and Prevention, and Shanghai Jiaotong University identified two chronic hepatitis B virus (HBV) infections in Chinese Han population through genome-wide association studies (GWAS). A new susceptibility gene. Related papers were recently published in the international top professional journal Nature-Genetics.
Hepatitis B is a disease caused by HBV infection of the body. China is a big country with hepatitis B. The HBsAg carrying rate is 8%-15%, and chronic HBV infection is also the most important cause of cirrhosis and hepatocellular carcinoma. Since the host's natural immunity is critical in the body's resistance to HBV infection, in addition to viral and environmental factors, the genetic factors of the host, the host's genetic susceptibility to HBV, play a particularly important role in the pathogenesis and prognosis of hepatitis B. .
In this latest study, to identify genetic loci associated with chronic HBV infection in the Han population, the researchers designed a three-stage genome-wide association study. At the discovery stage, they analyzed 951 HBV carriers and 937 control individuals who had been naturally cleared of HBV infection. Subsequently, a set of 2248 HBV carriers and 3051 control individuals from the general population, and another group of 1982 HBV carriers and 2622 controls were correlated in the second and third repetition stages.
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