World Hepatitis Day 2020
The liver, both an organ and the largest gland in the body, is essential for blood detoxification, metabolism and immune function. Hepatitis, which broadly refers to inflammation of the liver, can result in cirrhosis, liver failure, liver cancer, or ultimately death depending on severity. Liver inflammation may stem from alcohol abuse, chemical or drug exposure, and autoimmune disorders; however, the term hepatitis is most commonly used to describe liver disease caused by hepatitis virus infections.
History of viral hepatitis
Although specific mentions of hepatitis A and B did not occur until 1947, descriptions of epidemic jaundice (a yellowing of the skin, eyes and mucous membranes that often results from hepatitis) from as far back as Babylonia and ancient China suggest that medical practitioners have been aware of this disease since antiquity. Viral hepatitis may have been responsible for crippling medieval armies and soldiers of World Wars I and II, but today, many forms of hepatitis are preventable or treatable.
World Hepatitis Day is observed on July 28, commemorating the birthday of physician Baruch “Barry” Blumberg and bringing focus to the global impact of hepatitis infections. Blumberg discovered hepatitis B as an unexpected finding from a study he designed to investigate the genetic basis of disease susceptibility. Four years later, Blumberg and Irving Millman developed the first vaccine against hepatitis B, leading to the prevention of millions of new cases of viral hepatitis and ultimately winning Blumberg half of the Nobel Prize in Physiology or Medicine in 1976.
Prevalence and disease
Viral hepatitis results from infection with one of at least five types of viruses: hepatitis A, B, C, D and/or E. Hepatitis A and E are typically transmitted through food or water that has been contaminated with even trace amounts of infected stool, while B, C and D can be contracted through blood and thus are risks associated with intravenous drug use.
Although viral hepatitis can result in damage to the liver, the viruses themselves do not cause the death of hepatocytes (the most common cell type in the liver) that they infect. Instead, the body’s own immune system mediates the destruction of infected cells in an effort to clear the virus from the body.
Hepatitis A infections are often acute and may resolve after weeks or months, but in the case of hepatitis B and C, infections can result in chronic illness. Prolonged infections with the hepatitis B and C viruses (HBV and HCV, respectively) increase an individual’s risk for developing liver cancer and can lead to severe liver failure that requires liver transplant to prevent fatal illness.
Vaccines are available to prevent hepatitis A and B. However, in the U.S., new infections of HBV have been on the rise. In most cases, HBV infections do not present with any symptoms or only mild flulike symptoms, so individuals may go undiagnosed until years later when the disease can become more severe.
Therapies to manage chronic HBV are available, but once infected, there is no current treatment to cure individuals of HBV. Therefore, screening to identify HBV infection and prevention of new infections is key.
The Centers for Disease Control and Prevention recommend that all children up to age 18 get the vaccine and have expanded this suggestion to include high-risk groups, such as sexually active adults, injection drug users, healthcare and public safety workers, and people with HIV, HCV, diabetes or chronic liver disease. Importantly, no one needs to fit a specific risk category to be eligible receive the vaccine. Anyone who wants to protect themselves from HBV can!
Unlike hepatitis A and B, there is no effective vaccine to prevent HCV. Like HBV, many new infections of HCV do not present with symptoms, so screening is important to identify the current prevalence of the disease. The CDC reports approximately 170 million people worldwide are living with chronic HCV, with 3.5 million cases in the US.
Thankfully, there are therapies available to cure most individuals of HCV. However, approximately half of those living with HCV in the U.S. are unaware of their status, and approximately 30,000 new infections occur each year. Absent the development of an effective vaccine, increased screening and treatment of newly diagnosed HCV cases may help make it a rare disease.
Below are a few hepatitis research highlights from ASBMB journals.
In a report published in the Journal of Biological Chemistry, investigators at the University of Melbourne developed a strategy to drive the in vitro multimerization of a fragments of the hepatitis C virus E2 glycoprotein. The resulting high-molecular-weight protein complexes mimicked the surface of the E2 glycoprotein that is targeted by broadly neutralizing antibodies and promoted the development of neutralizing antibodies when injected into guinea pigs. This method may prove useful in producing large quantities of protein antigen for a future HCV vaccine.
Nucleotide analogs are molecules that mimic the building blocks of RNA or DNA. Many existing HCV therapies target NS5B, the RNA polymerase responsible for replicating the HCV genome, using nucleotide analogs. Although NS5B is able to counteract the effect of current nucleotide analog treatments, a group from the University of Texas at Austin found that this RNA polymerase is more sensitive to UMP-based nucleotide analog treatments. This work, also published in the Journal of Biological Chemistry, may aid the design of future HCV therapies.
Many serum glycoproteins, or proteins with sugar molecules attached to them, are produced in the liver and play important roles in health and disease; however, we lack a comprehensive understanding of how glycoproteins change in liver disease. Researchers from the Institutes of Biomedical Sciences at Fudan University performed multiple-reaction monitoring mass spectrometry to characterize glycoprotein levels in hepatitis B-related liver disease. The authors report two glycosylated forms of IgA2, an antibody involved in the protection of secretory tissues and mucous membranes, that increase upon HBV infection and HBV-related liver cirrhosis. Read the paper in the journal Molecular & Cellular Proteomics.
Inflammation that co-occurs with fat accumulation in the liver is termed hepatosteatosis and may lead to the development of liver cirrhosis even in the absence of alcohol abuse or viral infection. A study from Wake Forest University in the Journal of Lipid Research characterized how fat buildup in the liver correlates with the expression of GDPD3, a protein that catalyzes the synthesis of an important intermediate in the production of triacylglycerol, which is the key fatty molecule that builds up hepatic steatosis. GDPD3 overexpression led to fatty acid uptake and deposition in livers, indicating this gene may be important to understanding how dietary fat consumption is linked to some incidences of liver disease.
A good place for us to start
In 2010, the Journal of Biological Chemistry unveiled a thematic series of reviews that showcases advances in understanding the hepatitis C virus. Then-Associate Editor Charles Samuel, who organized the series, noted that two of the authors later shared the Lasker prize for their hepatitis C work. Read the reviews here.
Read our World Hepatitis Day 2018 observance, which includes even more research highlights, here.
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