Five powerful hepatitis viruses, can you beat them? | World Hepatitis Day Special

Since ancient times, viral hepatitis has been a group of brothers, each with their own evil plans, endangering the world...

Written by Li Qingchao (Shandong Normal University)

In Rick and Morty, the big villain Hepatitis C killed the little villain Hepatitis A. In reality, Hepatitis C is the big villain, but any co-infection of two hepatitis viruses will only aggravate the condition. 丨Source: Rick and Morty Stills

Hepatitis refers to an inflammatory disease of the liver, which can manifest as fatigue, loss of appetite, aversion to oil, jaundice, vomiting, diarrhea, abdominal pain and other symptoms. Severe cases may develop into liver failure. Hepatitis symptoms that end within 6 months are acute hepatitis, and those that last for more than 6 months are chronic hepatitis. Chronic hepatitis will lead to liver fibrosis, cirrhosis, and even develop into liver cancer. There are many factors that can cause hepatitis, including infectious, metabolic (such as drugs, toxins, alcohol, etc.), ischemic, autoimmune, and genetic factors, the most common of which are viruses. Certain bacteria, protozoa, and parasitic worms can also cause hepatitis. For example, Clonorchis sinensis and Fasciola hepatica like to parasitize in the liver.

Viral hepatitis is the most common type of hepatitis in the world. It is a viral infectious disease caused by five major viruses that infect the liver. According to the order of discovery, they are named hepatitis A (i.e. hepatitis A), hepatitis B, hepatitis C, hepatitis D and hepatitis E, and in English they are named Hepatitis A, B, C, D, E, and the corresponding viruses are HAV, HBV, HCV, HDV, HEV (many viruses such as cytomegalovirus and Epstein-Barr virus can also cause liver inflammation, but this is only part of the systemic symptoms caused by the above-mentioned viral infection and is not included in the scope of viral hepatitis research).

Among them, hepatitis A and hepatitis E tend to pass through the anus (commonly known as the anus), and are generally acute hepatitis; hepatitis B and hepatitis C are blood-thirsty, and are also acute hepatitis, but are more dangerous and will turn into chronic hepatitis, and then develop into cirrhosis or even liver cancer; hepatitis D tends to mix with hepatitis B, and can double the fighting power of hepatitis B.

The most powerful are hepatitis B and hepatitis C. According to WHO estimates, 1.1 million people die from hepatitis B or C infection each year worldwide, one person dies from hepatitis-related diseases every 30 seconds, and 3 million new cases of infection are reported each year[1].

Catching hepatitis virus on the tip of a needle

Small needle, big hole The prevalence and discovery of viral hepatitis are inseparable from the development of modern medicine. At the beginning of the 20th century, modern medicine developed rapidly, and the invention and use of syringes and injections, and modern blood transfusion technology for supportive or compensatory treatment of excessive blood loss in trauma and surgery have saved countless lives.

However, success or failure is due to the transfusion of whole blood, red blood cells or platelets, or blood products containing human blood components such as vaccines, human albumin, human immunoglobulin, and human coagulation factor VIII. While saving lives and healing the wounded, they also open the door to blood-borne diseases. The small injection needle has become a big loophole in human health. According to known research, there are more than 60 blood-borne diseases. It is in this context that viral hepatitis has entered the field of vision of researchers.

In the late 19th and early 20th centuries, the use of vaccines containing human serum, such as autologous vaccines, to treat smallpox, measles, syphilis, or trypanosomiasis, combined with poor medical practices such as repeated use of syringes, led to many outbreaks of jaundice. Because jaundice is transmitted through the blood, it was named "serum hepatitis"[2]. During World War II, measles and yellow fever vaccinations also led to a series of jaundice outbreaks. For example, in 1942, the U.S. military used a yellow fever vaccine containing human serum, causing jaundice in about 50,000 people[3]. Researchers speculated that acute liver damage caused by viral hepatitis caused jaundice, but at the time, people did not know that there were several hepatitis viruses.

Tips: Jaundice, the liver’s distress signal

Jaundice is one of the signs of liver dysfunction caused by hepatitis. When the body has bilirubin metabolism disorder, the bilirubin concentration in the serum increases, causing the skin and sclera to turn yellow. As early as 400 BC, Hippocrates described "epidemic jaundice", and the Yellow Emperor's Classic of Internal Medicine also recorded jaundice and other symptoms of hepatitis. Jaundice is a physical signal that cannot be ignored. The liver calls.

In 1947, British hepatologist FO MacCallum divided viral hepatitis into two categories based on epidemiological research data: hepatitis A, which is transmitted by oral and fecal infection, and hepatitis B, which is transmitted by blood. At that time, the proportion of hepatitis caused by blood transfusion in the United States was as high as 30%, but blood safety testing could only be carried out if the hepatitis pathogen was identified.

Hepatitis B virus and the mysterious non-A, non-B hepatitis

Since then, researchers in the biomedical field have embarked on a long journey of pursuit. In 1964, Baruch Blumberg (1976 Nobel Prize winner) discovered the "Australia antigen" in the blood of Australian Aborigines (later confirmed to be hepatitis B surface antigen HBsAg) [4], and humans officially discovered the hepatitis B virus HBV.

In 1971, the U.S. FDA issued the first blood supply inspection order in history to blood banks, requiring all blood banks in the United States to implement mandatory hepatitis B surface antigen screening for blood donors and begin systematic elimination of viral hepatitis caused by blood transfusions.

By the mid-1970s, Blumberg's colleague Harvey James Alter (2020 Nobel Prize winner) noticed that blood banks had conducted rigorous testing for HAV and HBV, but there were still a considerable number of cases of hepatitis after blood transfusion.

Alter collected serum from these cases of post-transfusion hepatitis—both HAV and HBV tests were negative—and inoculated them into chimpanzees, which resulted in hepatitis in the chimpanzees. This showed that there was indeed a new type of viral hepatitis circulating in the human population. Because the pathogen had not been identified at the time, this new type of hepatitis was called "non-A, non-B hepatitis" (NANBH) [5]. Unfortunately, traditional methods of looking for specific antibodies or directly observing viral particles to study the pathogen of NANBH have repeatedly failed.

Discovery of Hepatitis C virus fills the blood transfusion loophole

In 1982, virologist Michael Houghton (2020 Nobel Prize winner) led the study of non-A, non-B hepatitis pathogens and worked with research partners to use molecular cloning methods to try to directly find the virus's genetic material - nucleic acid. Finally, in 1987, they discovered a sequence of the new virus, and followed the clues to successfully find almost the entire genome sequence, and named the new virus hepatitis C virus (HCV) [6, 7].

From the introduction of the concept of "non-A, non-B hepatitis" to the discovery of HCV, to the invention of HCV detection methods and comprehensive blood transfusion screening, the loophole of hepatitis transmission caused by blood transfusion has finally been filled. The risk of hepatitis infection related to blood transfusion in the United States has been reduced from 30% in 1970 to zero infection in 2000.

Readers who are interested in learning more about this tortuous history can review the article “The Liver God is Above: Who Can Save 70 Million Chronic Hepatitis C Patients?” Now, blood can only be safely transfused after pathogen testing, and liver function and viral hepatitis are mandatory tests when donating blood.

Discovery of other hepatitis viruses In 1977, scientists discovered a new antigen in seriously ill hepatitis B patients, which was then thought to be an antigen of hepatitis B, called delta antigen. However, subsequent experiments on chimpanzees found that delta antigen was actually part of the antiviral particle structure of hepatitis D virus HDV. The amazing thing is that HDV can only produce defective viruses with complete viral particles with the help of HBV infection, that is, only hepatitis B patients will suffer from hepatitis D. By 1986, the HDV genome was successfully cloned and sequenced.

The discovery of hepatitis E began in 1978. At that time, an epidemic of jaundice broke out in Kashmir, affecting 600,000 people in 200 villages, causing about 52,000 people to be infected and 1,700 people to die. Strangely, pregnant women were more affected in this jaundice epidemic. Subsequent epidemiological investigations found that this was a new, enterically transmitted hepatitis.

In 1983, Dr. Mikhail S Balayan ingested stool extracts from nine such patients in a self-experiment and developed severe acute hepatitis with jaundice and elevated liver function on the 36th day. His stool samples were examined using an immunoelectron microscope and virus-like particles were found [8]. Scientists obtained the full-length genome sequence of HEV in 1991.

Tips: Failed "drug" members

Hepatitis G virus (HGV) was first discovered in 1966. It mainly replicates in peripheral blood mononuclear cells. So far, the mechanism of its induction of hepatitis is still unclear, and its hepatotropism is still controversial. The so-called hepatitis F reported in 1994 is actually a variant of hepatitis B. Therefore, these two hepatitis viruses are not included in the register.

The five poisons of hepatitis: unique skills and weaknesses

Hepatitis viruses are hepatotropic viruses. The five types of hepatitis viruses mentioned above, A, B, C, D, and E, all harm the liver, but in fact they have no relationship at all. In terms of classification, they are not related, and the virus particle structure, the type and structure of the genomic nucleic acid are also different. Among them, the hepatitis B virus HBV is an enveloped virus with a reverse transcription process in its replication cycle, containing a partially double-stranded and partially single-stranded circular DNA genome. Hepatitis A virus HAV, hepatitis C virus HCV, and hepatitis E virus HEV are all single-stranded positive-strand RNA viruses, but HAV and HEV do not have an envelope, while HCV has an envelope. The most peculiar is the hepatitis D virus HDV, whose genome is a single-stranded negative-strand RNA, and is a circular RNA connected end to end. It is not a true virus at all, but a subvirus that parasitizes in the replication process of HBV. The virus particles are dressed in the outer coat of HBV, and it is the smallest "virus" that infects the human genome.

Virological characteristics of various hepatitis viruses. (Drawn by the author) (Click to see the larger image)

"One Punch Man" Hepatitis A virus Hepatitis A virus HAV belongs to the genus Hepadnavirus of the family Picornaviridae. It is a non-enveloped +ssRNA virus with only one serotype. Humans are the natural host of HAV. About 40% of acute viral hepatitis is caused by HAV. Almost everyone infected with hepatitis A can fully recover and gain lifelong immunity, but a small number of hepatitis A patients will die from severe hepatitis.

spread

The HAV virus has strong environmental resistance and can resist detergents, acids (down to pH 1) and organic solvents (such as ether, chloroform). It is resistant to drying and high temperatures (60 ° C), and can survive in fresh water and salt water for months. Therefore, HAV is often transmitted efficiently after feces contaminates water or food. The transmission route is generally oral-fecal, or direct contact with an infected person (of course, including some sexual contact).

Poor sanitation and overcrowding make it particularly easy for waterborne or foodborne hepatitis A to break out. In some underdeveloped areas, more than 90% of children under the age of 10 have been infected with hepatitis A, but most infected children do not have any symptoms.[9] Eating shellfish from waters contaminated by feces increases the risk of infection. In 1988, Shanghai experienced a major outbreak of hepatitis A, which infected 310,000 people and killed 31 people. It caused social panic and put great pressure on Shanghai's health and epidemic prevention system at the time.[10] At that time, most Shanghai citizens ate half-cooked razor clams. They scalded the clams with boiling water, pried open the shells, poured seasoning on them, and ate them directly. The large amount of bacteria and hepatitis A virus adsorbed on the razor clam's gills easily infected the liver through the oral cavity and the digestive tract.

prevention

HAV is highly resistant to the virus and spreads efficiently among people. However, for each individual, it is like a one-punch man and can only hit once. Natural infection with hepatitis A can provide lifelong immunity after self-healing. Therefore, hepatitis A vaccine is also very effective. my country currently has attenuated and inactivated vaccines available. ① Improving environmental hygiene, ② Ensuring food safety and ③ Vaccination are the most effective ways to resist hepatitis A.

treat

There is no specific treatment for hepatitis A. After infection, symptoms may resolve slowly over weeks or months. Do not take unnecessary medications during this time, but stay comfortable and get proper nutrition, and replace fluids lost through vomiting and diarrhea. If you have signs of acute liver failure, you should be hospitalized promptly.

"Gong Dou Wizard" Hepatitis E virus Hepatitis E virus HEV belongs to the genus Orthohepevirus of the family Hepatitisviridae. Its full name is "Orthohepevirus A", and it is also a non-enveloped +ssRNA virus. Hepatitis E is also transmitted through the oral-fecal route. It is usually self-limiting and can heal itself in 2-6 weeks. Occasionally, it develops into severe hepatitis (acute liver failure) and can lead to death in some patients. It is estimated that 20 million people are infected with hepatitis E virus each year worldwide, of which an estimated 3.3 million will develop hepatitis E symptoms, often in East Asia and South Asia [11].

HEV and HAV are similar in transmission routes and pathogenic mechanisms, but HEV infection is particularly unique. After all, it is a genius in palace fighting - it is particularly cruel to pregnant women.

"Ulanala Hepatitis E" harms pregnant women

Compared with other populations, HEV infection in pregnant women can show more severe toxicity. It is reported that the proportion of liver failure and death after HEV infection in pregnant women in developing countries is 20% to 25%. HEV can also cause premature birth, miscarriage, stillbirth and neonatal death.

It is not clear why HEV has such infectious characteristics. It may be related to the increase in viral replication and the impact of hormonal changes on the immune system, or it may be related to the fact that HEV can replicate in the placenta.

"Niu Hulu·Hepatitis E" strategic monastic life

HEV can be divided into multiple genotypes. Genotypes 1 and 2 only infect humans and usually occur in developing countries with poor sanitary conditions, causing large-scale outbreaks and epidemics; genotypes 3 and 4 can infect humans, pigs and other animal species, and can cause sporadic cases of hepatitis E in both developing and developed countries.

If the meat or meat products of HEV-infected animals are not cooked thoroughly, eating them will also cause HEV infection. In other words, hepatitis E is a zoonosis that can use animals as natural virus reservoirs. Even if hepatitis E is eliminated in humans, humans may be re-infected with HEV when they come into contact with or eat wild animals.

The treatment and prevention of hepatitis E are basically similar to those of hepatitis A. my country already has the only hepatitis E vaccine available in the world.

"Tianshan Tonglao Plus" Hepatitis B virus and hepatitis D virus Hepatitis B virus HBV belongs to the Hepadnaviridae family and contains a partially single-stranded and partially double-stranded covalently closed circular DNA genome. Its replication cycle has a reverse transcription process. In addition to causing acute infection, it can also cause chronic infection, leading to chronic hepatitis, and then to cirrhosis and hepatocellular carcinoma (a primary liver tumor). According to WHO estimates, in 2015, more than 250 million people worldwide suffered from chronic hepatitis B, resulting in 887,000 deaths [12].

my country used to have a high rate of hepatitis B infection. According to a national serological epidemiological survey in 1992, the hepatitis B virus infection rate in the population reached 60%, the surface antigen carrier rate was 9.75%, and there were about 120 million hepatitis B virus carriers in the country. Due to the high HBV infection rate, hepatitis B has become a major disease affecting the health of the Chinese people; and because of its long course and difficulty in curing, hepatitis B is also a disease that can make families impoverished, and will seriously affect the national economy and social development. Therefore, the State Council and the Ministry of Health have listed it as a key disease for control [13].

spread

HBV is mainly transmitted through blood or body fluids. In areas with a high incidence of hepatitis B, the most common route of infection is perinatal infection or contact with other people's blood during childhood. In other areas, hepatitis B is mainly transmitted through intravenous drug use and sexual behavior. Unregulated medical care or beauty procedures that cause skin damage, such as tattoos and acupuncture, can also cause HBV transmission.

Hepatitis B is essentially a blood-borne disease. Holding hands, sharing eating utensils, kissing, hugging, coughing, sneezing or breastfeeding will not cause HBV transmission.

Life and Death Talisman-Chronic Hepatitis

Chronic hepatitis refers to a persistent, progressive hepatitis state that cannot heal itself for more than 6 months. The essence is that the virus continues to exist and replicate, and the liver is always in a state of chronic inflammation. Chronic hepatitis can cause liver cell damage and progressive fibrosis. Eventually, the liver tissue is replaced by scar tissue, the liver is permanently damaged and unable to work, and it becomes cirrhosis of late-stage hepatitis. Repeated stimulation of inflammation can eventually cause hepatocellular carcinoma.

Therefore, chronic viral hepatitis is a more dangerous form of hepatitis than acute viral hepatitis. Less than 5% of adults infected with HBV develop chronic hepatitis, whereas infection during infancy and childhood results in approximately 95% of cases of chronic hepatitis[14].

The main harmful modes of hepatitis viruses: chronic viral hepatitis and its course (illustration by the author)

The integration, recurrence and carcinogenesis of HBV:

HBV infection can cause the body's specific immune response, which can eliminate the virus to a certain extent and reduce the viral content. However, HBV can also integrate into the liver cell genome and become low-expression but more stable HBV DNA! HBV integrated into the genome can persist in the body and evade elimination by the immune system. When immunity is low or stimulated by alcohol or drugs, this integrated HBV can enter an active replication state again, causing the condition to suddenly worsen. In addition, integrated HBV DNA is also an important driving force for hepatocellular carcinoma, which can further promote the occurrence of cancer. Why is it a daunting challenge to treat hepatitis B and completely eliminate the hepatitis B virus? It is because HBV has this characteristic of being able to integrate and recur.

Plus-Hepatitis D: Hepatitis D virus (HDV) was discovered during the study of HBV. It was later proven that it is a defective virus that depends on HBV for its existence. HDV itself cannot exist independently. In other words, only patients with hepatitis B can be infected with hepatitis D. It is estimated that nearly 5% of chronic hepatitis B virus-infected people worldwide are also infected with hepatitis D virus [15].

HDV is transmitted in the same way as HBV, through blood or body fluids. Co-infection with these two viruses is considered the most serious form of chronic viral hepatitis because HDV accelerates the development of hepatocellular carcinoma caused by HBV and promotes liver death.

Figure: Virus particle structure and antigens of HBV and HDV. Detection of any viral component indicates that the patient is in a virus-carrying state; detection of surface antigen HBsAg and E antigen HBeAg (non-viral particle component, free existence) generally indicates that the patient is in a period of rapid viral replication and strong infectivity. The weakening or disappearance of HBeAg and HBsAg indicates that the condition is improving. HDV contains its own viral nucleocapsid, but the envelope comes from HBV. If Delta antigen or HDV nucleic acid is detected, it indicates that the patient is also infected with HDV. (Drawn by the author) (Click to see a larger image)

Tips: What are big triple positive and small triple positive?

HBsAg, HBeAg, and hepatitis B core antibody (anti-HBcAb) are all positive, which is called "big three positives", indicating that the virus replication in the body is relatively active.

A positive test for HBsAg, hepatitis B e antigen antibody (HBeAb), and hepatitis B core antibody (anti-HBcAb) is called "small three positives", indicating that the case is a HBV carrier.

prevention

Prevention of hepatitis B and D can be carried out by targeting their transmission routes. HBV is mainly transmitted through blood, and its transmission ability is higher than HIV. We have popularized knowledge about HIV and talked about prevention measures for blood-borne or sexually transmitted diseases, so we will not repeat them here (see "Where does HIV hide? To enjoy a happy sex life, you must avoid these high-risk actions | AIDS Day Special" for details).

The simplest and most effective way to prevent hepatitis B is to get vaccinated. All newborns should be vaccinated with hepatitis B vaccine as soon as possible after birth (preferably within 24 hours), and the second and third doses of hepatitis B vaccine should be given 1 month and 6 months after birth to complete the vaccination program. After adulthood, the HBsAb content in the blood can be tested. When the antibody concentration is lower than 10 international units/liter (i.e., below the effective concentration), the hepatitis B vaccine can be injected again for immune reinforcement. As for hepatitis D, if you prevent HBV, you will not be infected with HDV.

Mother-to-child transmission is another important route of HBV transmission, which is mainly divided into three transmission periods: intrauterine infection, delivery process, and post-delivery. Patients with active hepatitis B or HBeAb-positive hepatitis B should not get pregnant and should be given antiviral treatment. They can only get pregnant after hepatitis B enters the stable period and HBeAb is negative. Hepatitis B carriers should regularly check liver function and HBV DNA copy number during pregnancy. If liver function is abnormal, hepatitis B is active, or the DNA copy number is significantly increased, antiviral treatment during pregnancy is generally required (interferon cannot be used during pregnancy, and pregnancy is not suitable during interferon treatment) to prevent direct mother-to-child transmission. After the fetus is born, in addition to the hepatitis B vaccine, hepatitis B immunoglobulin should also be injected. Hepatitis B carriers can have natural childbirth and breastfeed.

treat

The purpose of hepatitis B treatment is to suppress HBV replication, reduce the level of liver inflammation, and slow down the progression of liver fibrosis and cirrhosis. Two approaches can be used: liver protection therapy or inhibition of viral replication. Clinically, interferon or antiviral small molecule drugs are generally used to inhibit viral replication. HBV is difficult to eliminate and generally requires lifelong medication.

"Mystique" Hepatitis C virus Hepatitis C virus (HCV) belongs to the Flaviviridae family and is an enveloped RNA virus. HCV is mainly transmitted through blood and causes chronic hepatitis. It is estimated that 71 million people are infected with chronic hepatitis C worldwide, and nearly 400,000 people died from hepatitis C in 2016 [16]. Similar to hepatitis B, the main way hepatitis C causes harm is through chronic infection, which can lead to cirrhosis and even liver cancer.

spread

HCV can be transmitted through blood. Sharing syringes for drug use, irregular medical practices, unscreened blood and blood products, and sexual activities that can lead to blood contact can all potentially spread HCV.

HCV cannot be transmitted through food or water, so as long as you do not come into contact with the patient's blood, there is almost no risk of infection when living with a hepatitis C patient (do not share items that can cause trauma, such as razors). The number of newly reported cases of HCV in my country is increasing year by year, and considering the hidden nature of HCV infection, the number of infected people is far greater than the number of reported cases.

The number of people infected with hepatitis B in my country is relatively high, and the increase in the number of people infected with hepatitis C cannot be ignored [17].

HCV is highly variable

Compared with other viruses, HCV is highly diverse and variable. Based on its sequence differences, HCV can be divided into 7 different genotypes and up to 67 subtypes, with the nucleotide differences between genotypes as high as 30% to 35%[18] (this level of difference would have long been separated in other viruses and would not be considered a single subtype). In contrast, the difference between different HBV genotypes is only about 8%. This is because the RNA polymerase encoded by HCV lacks proofreading function and has a high mismatch rate. Even HCV virus particles in the same patient may contain multiple genomes with different sequences.

HCV's high variability enables it to escape the body's specific immune response. In addition, HCV itself has many ways to evade natural immunity. As a result, the chronicity rate of hepatitis C is as high as over 80%[19], far exceeding that of hepatitis B. High variability also increases the difficulty of HCV research, treatment, and vaccine development.

Figure: HCV belongs to the Flaviviridae family, which includes a large number of pathogens. (Chart by the author)

prevention

According to the transmission characteristics of HCV, the main idea of ​​prevention is to avoid contact with blood containing the virus, seek standardized medical behavior, do not take drugs, avoid contact with blood during sexual intercourse, etc., which is basically the same as the prevention measures for hepatitis B. Unfortunately, there is currently no vaccine available for hepatitis C.

treat

In the early days, people used interferon, a cytokine that enhances the body's antiviral ability, to treat hepatitis C. Later, it was discovered that the combination of interferon and ribavirin could improve the cure rate. However, this therapy can cause serious side effects such as fever, fatigue, and muscle aches. In addition, the course of treatment lasts for more than half a year, and patients often have poor compliance and find it difficult to complete the entire course of treatment. Even if the treatment is successfully completed, there is a risk of relapse.

To this end, scientists have developed a large number of HCV-specific antiviral drugs, which generally work against HCV's NS5B RNA replicase, NS3 protease and NS5A. In 2007, Michael J. Sofia and his team successfully developed the drug sofosbuvir [20], and conducted the first human trial in 2010, proving that it is very effective against many HCV genotypes. In October 2013, an HCV drug with sofosbuvir as the main active ingredient was approved by the US FDA as a "breakthrough therapy" and entered clinical trials. The use of sofosbuvir has some immediate benefits for patients: liver function improves, the virus is no longer contagious, and the risk of cirrhosis or liver cancer is greatly reduced. In the treatment of individual HCV genotypes, sofosbuvir can even achieve an astonishing cure rate of 98%. The development and use of sofosbuvir marks that humans can truly cure a viral infectious disease. (Review of "The Liver God is Above: Who Can Save 70 Million Chronic Hepatitis C Patients?")

Conclusion

July 28 is World Hepatitis Day (Fun fact: this day is Blumberg’s birthday), and this year’s theme is “Eliminating Hepatitis is Urgent”. We should know about various hepatitis viruses, their hazards and effective prevention and treatment measures. But we should understand that the world is not flat, and public health and medical resources are not evenly distributed around the world. To eliminate global hepatitis by 2030, the most important issue to be solved is the large differences in testing and treatment coverage around the world. At the same time, we must also understand that the world is flat, and as long as viral hepatitis is still prevalent, it is likely to make a comeback.

For us personally,

1) Be careful when traveling and avoid all high-risk behaviors that may cause infection.

2) We should add any buffers we can and promptly cooperate with and utilize existing disease prevention and control measures.

3) Don’t be afraid even if you have committed a crime. Testing will be lenient and treatment will be strict. People with high-risk behaviors should take the initiative to test whether they are infected and actively cooperate with treatment to avoid the progression of the disease.

4) Develop good living habits to protect your liver: quit smoking and limit alcohol consumption, stay up late less and exercise more, do not eat expired or spoiled food, and do not use medication indiscriminately.

5) Like, read, save and forward this article.

References

[1] https://www.who.int/zh/campaigns/world-hepatitis-day

[2] Findlay, GM & MacCallum, FO Hepatitis and Jaundice Associated with Immunization against Certain Virus Diseases. J Roy Soc Med 31, 799–806 (1938).

[3] Seeff, LB et al. A Serologic Follow-up of the 1942 Epidemic of Post-Vaccination Hepatitis in the United States Army. New Engl J Medicine 316, 965–970 (1987).

[4] ALTER, HJ & BLUMBERG, BS Further Studies on a “New” Human Isoprecipitin System (Australia Antigen). Blood 27, 297–309 (1966).

[5] Tabor, E. et al. TRANSMISSION OF NON-A, NON-B HEPATITIS FROM MAN TO CHIMPANZEE. Lancet 311, 463–466 (1978).

[6] Choo, Q. et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244, 359–362 (1989).

[7] Kuo, G. et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244, 362–364 (1989)

[8] Balayan MS, Andjaparidze AG, Savinskaya SS Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology. 1983;20:23–31.

[9] "Hepatitis A Fact sheet N°328". World Health Organization. July 2013. Archived from the original on 21 February 2014. Retrieved 20 February 2014.

[10] Halliday ML, Kang LY, Zhou TK, Hu MD, Pan QC, Fu TY, Huang YS, Hu SL. J, An epidemic of hepatitis A attributable to the ingestion of raw clams in Shanghai, China. Infect Dis. 1991 Nov;164(5):852-9.

[11] https://www.who.int/zh/news-room/fact-sheets/detail/hepatitis-e

[12] https://www.who.int/zh/news-room/fact-sheets/detail/hepatitis-b

[13] http://www.chinacdc.cn/jkzt/crb/zl/bdxgy/yxbdxgy/201301/t20130106_75114.html

[14] https://www.who.int/zh/news-room/fact-sheets/detail/hepatitis-b

[15] https://www.who.int/zh/news-room/fact-sheets/detail/hepatitis-d

[16] https://www.who.int/zh/news-room/fact-sheets/detail/hepatitis-c

[17] National Center for Disease Control and Prevention, Overview of the National Notifiable Infectious Diseases, http://www.chinacdc.cn/tjsj/fdcrbbg/

[18] https://www.wikiwand.com/en/Hepatitis_C_virus#/Genotypes

[19] https://www.who.int/news-room/fact-sheets/detail/hepatitis-c

[20] Sofia, MJ et al. Discovery of a β-d-2′-Deoxy-2′-α-fluoro-2′-β-C-methyluridine Nucleotide Prodrug (PSI-7977) for the Treatment of Hepatitis C Virus. J Med Chem 53, 7202–7218 (2010).