Is "hepatitis G" hepatitis?

、、、
。，，“”（HGV），，？
。

、、、
。，，“”（HGV），，？
。

：

：

，12，，CAR-T（T），，
。：0.

9×109/L，：46.
5%，：40.
1%，（PCT）：0.
32ng/mL，C（CRP）：6.
33mg/L

A 12 -year-old female, with relapsed lymphoma , developed bone marrow suppression and intermittent fever after CAR-T CAR-T (chimeric antigen receptor T cell) immunotherapy for lymphoma .
White blood cell count: immune 0.
9×109/L , neutrophil ratio: 46.

Microbial metagenomic sequencing ( mNGS ) report of blood samples: positive for Staphylococcus epidermidis, positive for HGV (ie, GB virus type C , GBvirusC in the report )

What is mNGS testing and why does this girl need mNGS testing?

What is mNGS testing and why does this girl need mNGS testing? What is mNGS testing and why does this girl need mNGS testing?

mNGS is an imported term, the full name is metagenomic next generation sequencing , translated as " metagenomic next generation sequencing "
.

The root meta- , which appeared in the meta -analysis that was popular in scientific research in the past few years , also appeared in the current popular word " metaverse " .
No matter where it is, it reflects the momentum of the beginning of " big " and " yuan " .
Swallow thousands of miles like a tiger .
If the real-time quantitative PCR technology ( real- time PCR) that is blooming everywhere today is likened to fishing with a fishing rod, mNGS is a big net.

mNGS is an imported term, the full name is metagenomic next generation sequencing , translated as " metagenomic next generation sequencing "

The first shot for the clinical application of mNGS was a case published in the New England Journal of Medicine in 2014 .

A child had meningitis when diagnostic techniques, including brain biopsy, had been exhausted and the cause could not be pinpointed .
Finally, he resorted to mNGS technology to sequence the cerebrospinal fluid DNA , and detected leptospirosis gene fragments, suggesting neuroleptospirosis, and the child recovered after 1 week of penicillin treatment .

The first shot for the clinical application of mNGS was a case published in the New England Journal of Medicine in 2014 .
A child had meningitis when diagnostic techniques, including brain biopsy, had been exhausted and the cause could not be pinpointed .
Finally, he resorted to the children's diagnostic mNGS technology to sequence the cerebrospinal fluid DNA , and detected the leptospirosis gene fragment, suggesting neural leptospirosis.
One week of penicillin treatment restored the child to health .
What accelerated the clinical application of mNGS was the epidemic that swept the world.

The disadvantage of mNGS is that it is not sensitive enough

How can we subsequently confirm that the child is infected with HGV ? How can we subsequently confirm that the child is infected with HGV ?

The mNGS results are screening results, and further diagnosis of HGV infection relies on traditional laboratory tests .

The results of mNGS are screening results, and further diagnosis of HGV infection depends on traditional laboratory tests .

HGV is a single-stranded positive-stranded RNA virus containing about 9400 nucleotide bases with only one open reading frame encoding about 2800 amino acids

• Antibodies: markers of past infection and recovery

• HGVRNA : A direct indicator of active infection and a diagnostic marker for hepatitis
G.
The amplified target gene can be located in a conserved region, such as the NS5 region
.
See picture below
.

Considering that no readily available HGV antibody reagents are available, we decided to detect HGV RNA
.
mNGS amplifies all DNA and RNA in the sample equally, even so, it still suggests that up to 1783 HGV fragments are detected , indicating that the serum HGV load will not be low and the amplification will not be too difficult .
We synthesized HGV -specific primers, and after reverse transcription ( RT ) -PCR , electrophoresis obtained bright bands, indicating that the viral load was indeed not low; then the bands were cut from gel, purified, and subjected to Sanger sequencing and sequence alignment .
The HGV sequences in the 2009-2000 have a similarity of 97% (see the figure below), which is indeed an active HGV infection .

Considering that no readily available HGV antibody reagents are available, we decided to detect HGV RNA
.
mNGS amplifies all DNA and RNA in the sample equally, even so, it still suggests that up to 1783 HGV fragments are detected , indicating that the serum HGV load will not be low and the amplification will not be too difficult .
We synthesized HGV -specific primers, and after reverse transcription ( RT ) -PCR , electrophoresis obtained bright bands, indicating that the viral load was indeed not low; then the bands were cut from gel, purified, and subjected to Sanger sequencing and sequence alignment .
The HGV sequences in the 2009-2000 have a similarity of 97% (see the figure below), which is indeed an active HGV infection .

What is the origin of HGV ?

What is the origin of HGV ? What is the origin of HGV ?

From A ( A ) liver to G ( G ) liver, named in the chronological order of discovery
.
But so far the recognized hepatitis viruses are only five brothers from A to E, and the hepatitis virus ( HFV ) (easy to be confused with B) has only been reported in a few scientific researches.
Full of ins and outs
.
In 1995 , scientists from Abbott in the United States reported in Nature Medicine that the newly discovered GBV-C virus was associated with hepatitis .
GB is derived from the initials of the patient's surname and first name, while C represents the virus strain .
Almost at the same time, GenelabsTechnologies of the United States wrote an article in "Science" and discovered a new hepatitis virus and named it HGV .
Later, it was found that GBV-C and HGV are just different strains of the same virus, which can be regarded as the same goal .

From A ( A ) liver to G ( G ) liver, named in the chronological order of discovery
.
But so far the recognized hepatitis viruses are only five brothers from A to E, and the hepatitis virus ( HFV ) (easy to be confused with B) has only been reported in a few scientific researches.
Full of ins and outs
.
In 1995 , scientists from Abbott in the United States reported in Nature Medicine that the newly discovered GBV-C virus was associated with hepatitis .
GB is derived from the initials of the patient's surname and first name, while C represents the virus strain .
Almost at the same time, GenelabsTechnologies of the United States wrote an article in "Science" and discovered a new hepatitis virus and named it HGV .
Later, it was found that GBV-C and HGV are just different strains of the same virus, which can be regarded as the same goal .

What is the prevalence of HGV in the population?

What is the prevalence of HGV in the population? What is the prevalence of HGV in the population?

Epidemiological surveys in different countries suggest that among blood donors (healthy population), the prevalence of HGVRNA is 0.
9%-5.
3% , while the prevalence of E2 antibodies is 3.
0%-42.
1% .
The positive rates of HGVRNA and antibody among blood donors in China were about 3.
91% and 3.
25% , respectively, as shown in the figure below .

Epidemiological surveys in different countries suggest that among blood donors (healthy population), the prevalence of HGVRNA is 0.
9%-5.
3% , while the prevalence of E2 antibodies is 3.
0%-42.
1% .
The positive rates of HGVRNA and antibody among blood donors in China were about 3.
91% and 3.
25% , respectively, as shown in the figure below .

Hemophilia, thalassemia, intravenous drug users, dialysis patients, HIV - infected patients, etc.
belong to the high-risk groups of HGV, and the prevalence of HGV is higher in these groups .

Hemophilia, thalassemia, intravenous drug users, dialysis patients, HIV - infected patients, etc.
belong to the high-risk groups of HGV, and the prevalence of HGV is higher in these groups .

How does HGV spread among the population?

How does HGV spread among the population? How does HGV spread among the population?

HGV spreads through various routes, including:

HGV spreads through various routes, including:

• Blood transmission: blood transfusion and blood product transmission, nosocomial transmission due to surgery and dialysis, drug use and sharing of syringes,
etc.

• Blood transmission: blood transfusion and blood product transmission, nosocomial transmission due to surgery and dialysis, drug use and sharing of syringes,
etc.

• Sexually transmitted: HGV is more sexually transmitted than HCV , which may partly explain the higher prevalence of HGV RNA among healthy blood donors, and may also explain why a high proportion of HGV co -infected patients with HIV infection through sexual transmission infection .

• Sexually transmitted: HGV is more sexually transmitted than HCV , which may partly explain the higher prevalence of HGV RNA among healthy blood donors, and may also explain why a high proportion of HGV co -infected patients with HIV infection through sexual transmission infection .

• Mother-to-child transmission

• Mother-to-child transmission

Diverse routes of transmission without screening may explain the high prevalence of HGV in the population .

Diverse routes of transmission without screening may explain the high prevalence of HGV in the population .

What is the outcome of HGV infection?

What is the outcome of HGV infection? What is the outcome of HGV infection?

HGV infection has a high self-healing rate
.
A follow-up study of blood recipients or thalassemia patients found that half of those with active HGV infection can spontaneously clear RNA within 6 years , with or without the production of E2 antibodies; the antibodies are neutralizing antibodies, but within a few years Turned negative, suggesting that the protective effect may be weakened .
There are also a small number of infected people whose RNA lasts for more than ten years .

HGV infection has a high self-healing rate
.
A follow-up study of blood recipients or thalassemia patients found that half of those with active HGV infection can spontaneously clear RNA within 6 years , with or without the production of E2 antibodies; the antibodies are neutralizing antibodies, but within a few years Turned negative, suggesting that the protective effect may be weakened .
There are also a small number of infected people whose RNA lasts for more than ten years .

Can HGV cause hepatitis or liver cancer? 

Can HGV cause hepatitis or liver cancer? Can HGV cause hepatitis or liver cancer? 

No.
_ Although the fuse of the first exposure of HGV was ignited by hepatitis patients, follow-up studies have not confirmed the causal relationship between HGV and liver disease .
Another strong evidence is the cell tropism of HGV - it mainly replicates in lymphocytes, and the level of replication in liver cells is very low, so HGV is not a hepatotropic virus, but a lymphotropic virus, so HGV competes with HIV The same colony - lymphocytes, and inhibit the latter's replication .
It can be seen that although it is called hepatitis virus, HGV and other hepatitis viruses are not brothers .

No.
_ Although the fuse of the first exposure of HGV was ignited by hepatitis patients, follow-up studies have not confirmed the causal relationship between HGV and liver disease .
Another strong evidence is the cell tropism of HGV - it mainly replicates in lymphocytes, and the level of replication in liver cells is very low, so HGV is not a hepatotropic virus, but a lymphotropic virus, so HGV competes with HIV The same colony - lymphocytes, and inhibit the latter's replication .
It can be seen that although it is called hepatitis virus, HGV and other hepatitis viruses are not brothers .

Will HGV affect the safety of blood supply?

Will HGV affect the safety of blood supply? Will HGV affect the safety of blood supply?

As mentioned earlier, although HGV infection is not uncommon in healthy people, HGV does not cause liver disease or other organ diseases
.
Based on the above facts, the US FDA has decided not to screen blood and blood products for HGV antibodies or RNA
.

As mentioned earlier, although HGV infection is not uncommon in healthy people, HGV does not cause liver disease or other organ diseases
.
Based on the above facts, the US FDA has decided not to screen blood and blood products for HGV antibodies or RNA .

We can think of another virus related to blood transfusion - transfusion-transmitted virus (TTV) , which is a circular DNA virus, and its discovery process, cell tropism, pathogenicity, prevalence and other aspects are related to HGV .
Some are similar, but also not included in the screening list - how many seemingly harmless, heterologous nucleic acids like HGV and TTV are still in our blood ? It is still unknown .

We can think of another virus related to blood transfusion - transfusion-transmitted virus (TTV) , which is a circular DNA virus, and its discovery process, cell tropism, pathogenicity, prevalence and other aspects are related to HGV .
Some are similar, but also not included in the screening list - how many seemingly harmless, heterologous nucleic acids like HGV and TTV are still in our blood ? It is still unknown .

AIDS research at the beginning of this century made HGV a little popular.
What happened?

AIDS research at the beginning of this century made HGV a little popular.
What happened?

In the mid-to-late 1990s, HGV research ushered in a climax, and domestic and foreign laboratories published articles one after another.
However, the good times did not last long.
By 1998 , important clinical studies were carried out one after another .
No causal relationship was found, and the study cooled down immediately .

In the mid-to-late 1990s, HGV research ushered in a climax, and domestic and foreign laboratories published articles one after another.
However, the good times did not last long.
By 1998 , important clinical studies were carried out one after another .
No causal relationship was found, and the study cooled down immediately .

But soon, HGV aroused attention again, because Japanese and German research teams have successively reported that compared with HIV alone, HGV/HIV co-infected patients have more CD4 cells, slower disease progression, and survival rate is also independent.
3.
7 times
the infection rate .
HGV has become a protective factor for AIDS patients, how can it be ignored
.

But soon, HGV aroused attention again, because Japanese and German research teams have successively reported that compared with HIV alone, HGV/HIV co-infected patients have more CD4 cells, slower disease progression, and survival rate is also independent.
3.
7 times
the infection rate .
HGV has become a protective factor for AIDS patients, how can it be ignored
.

The mechanism may be that the symbiosis of HGV and HIV inhibits HIV replication .
In fact, this phenomenon is not uncommon.
" One mountain cannot tolerate two tigers " , which makes sense logically.
There are many similar phenomena.
For example, when HBV /HCV co - infection , HCV can inhibit HBV replication .
, HBV/HCV co-infected patients taking DAA , HCV was killed within weeks or even days .

The mechanism may be that the symbiosis of HGV and HIV inhibits HIV replication .
In fact, this phenomenon is not uncommon.
" One mountain cannot tolerate two tigers " , and it makes sense logically.
There are many similar phenomena.
For example, when HBV /HCV is co- infected , HCV can inhibit HBV replication .
At times, HBV/HCV co-infected patients took DAA , and HCV was killed within weeks or even days .

When competitors disappear quickly, HBV will reactivate and cause liver damage.
This is why we should pay attention to monitoring HBV markers and liver function while using DAA to cure hepatitis C in co-infected patients .

When competitors disappear quickly, HBV will reactivate and cause liver damage.
This is why we should pay attention to monitoring HBV markers and liver function while using DAA to cure hepatitis C in co-infected patients .

Although some people can block HIV membrane fusion by synthesizing the HGVE2 peptide segment, compared with the progress of HIV potent antiviral drugs in recent years, the anti-AIDS effect of this simulated HGV is insignificant.
Therefore, people 's attention to HGV Gradually fell silent again .

Although some people can block HIV membrane fusion by synthesizing the HGVE2 peptide segment, compared with the progress of HIV potent antiviral drugs in recent years, the anti-AIDS effect of this simulated HGV is insignificant.
Therefore, people 's attention to HGV Gradually fell silent again .

Will mNGS promotion make HGV popular again?

Will mNGS promotion make HGV popular again? Will mNGS promotion make HGV popular again?

In the case of Wenchu, we originally hoped to find the pathogen that causes fever in children with blood diseases, but found HGV positive
.
We know that the most suitable scenario for mNGS is the investigation of intractable diseases, but if there is no threshold for clinical mNGS testing, or if NSG technology is widely used for economic purposes , it will face the problem of interpretation of complex background information .
Staphylococcus epidermidis was detected in blood, which is a normal flora for immunocompetent people, but is it the pathogen of fever for children with weakened immunity? At the same time, HGV was also detected , which was unexpected.
Fortunately, we have enough research data to prove that HGV cannot be the murderer .
By extension, how to distinguish pathogenic and non-pathogenic pathogens is one of the difficulties in the application of mNGS .  

In the case of Wenchu, we originally hoped to find the pathogen that causes fever in children with blood diseases, but found HGV positive
.
We know that the most suitable scenario for mNGS is the investigation of intractable diseases, but if there is no threshold for clinical mNGS testing, or if NSG technology is widely used for economic purposes , it will face the problem of interpretation of complex background information .
Staphylococcus epidermidis was detected in blood, which is a normal flora for immunocompetent people, but is it the pathogen of fever for children with weakened immunity? At the same time, the detection and interpretation of HGV was unexpected.
Fortunately, we have enough research data to prove that HGV cannot be the murderer .
By extension, how to distinguish pathogenic and non-pathogenic pathogens is one of the difficulties in the application of mNGS .  

This situation is similar to the preoperative infectious disease screening project.
Most of the subjects were only incidental ( incidental ) found to be " positive " for infectious disease markers , and also included a considerable number of " false positive " results.
Our clinicians interpret with caution, Avoid misdiagnosis and mistreatment .

This situation is similar to the preoperative infectious disease screening project.
Most of the subjects were only incidental ( incidental ) found to be " positive " for infectious disease markers , and also included a considerable number of " false positive " results.
Our clinicians interpret with caution, Avoid misdiagnosis and mistreatment .

So what exactly should HGV 's official name be?

So what exactly should HGV 's official name be? So what exactly should HGV 's official name be?

HGV is not the causative agent of liver disease or other diseases, and we have not found any so-called " hepatitis G " cases in clinical practice .
"HGV" and " hepatitis G " are misleading medical terms that are still used today .
Some scholars advocate the replacement of HGV with GBV-C to reduce misunderstandings, but interestingly, we now know that GBV-C is not the culprit of Mr.
GB 's hepatitis .

HGV is not the causative agent of liver disease or other diseases, and we have not found any so-called " hepatitis G " cases in clinical practice .
"HGV" and " hepatitis G " are misleading medical terms that are still used today .
Some scholars advocate the replacement of HGV with GBV-C to reduce misunderstandings, but interestingly, we now know that GBV-C is not the culprit of Mr.
GB 's hepatitis .

Fortunately, the International Committee on Taxonomy of Viruses ( ICTV ) has given HGV the official name - Pegivirus
.
Among them, pe stands for persistent; g stands for GB or G)
.
Pegivirus and more well-known viruses such as HCV , Zika virus, dengue virus, etc.
, belong to the Flaviviridae family, but belong to different genera, as shown in the figure below
.
More detailed information is available at the National Center for Biological Information ( NCBI ) in the United States
.

Fortunately, the International Committee on Taxonomy of Viruses ( ICTV ) has given HGV the official name - Pegivirus
.
Among them, pe stands for persistent; g stands for GB or G)
.
Pegivirus and more well-known viruses such as HCV , Zika virus, dengue virus, etc.
, belong to the Flaviviridae family, but belong to different genera, as shown in the figure below
.
More detailed information is available at the National Center for Biological Information ( NCBI ) in the United States
.

Summarize

summary summary

• HGV is not associated with liver disease and there is no evidence of other diseases
.

• HGV is not associated with liver disease and there is no evidence of other diseases
.

• The names of HGV and Hepatitis G are a coincidence and convention in the history of scientific discovery.
It is recommended to use its official name pegivirus
.

• The names of HGV and Hepatitis G are a coincidence and convention in the history of scientific discovery.
It is recommended to use its official name pegivirus
.

• Although " bacteremia " generally means a pathological state, " viremia " may be a physiological state -- in addition to normal flora (such as the intestinal flora that has been hotly researched in recent years), there are also Normal " toxic " groups such as pegivirus and TTV .

• Although " bacteremia " generally means a pathological state, " viremia " may be a physiological state -- in addition to normal flora (such as the intestinal flora that has been hotly researched in recent years), there are also Normal " toxic " groups such as pegivirus and TTV .

• How many such seemingly benign and harmless viruses are there in our blood? ——It seems that human understanding of the virus is far from over
.

• How many such seemingly benign and harmless viruses are there in our blood? ——It seems that human understanding of the virus is far from over
.

• The promotion and application of mNGS, a wide-spread detection technology, will inevitably detect more similar microorganisms (such as pegivirus , TTV , etc.
), are they just background plates, or are they the real culprits? A scientific and standardized interpretation is urgently needed
.

• The promotion and application of mNGS, a wide-spread detection technology, will inevitably detect more similar microorganisms (such as pegivirus , TTV , etc.
), are they just background plates, or are they the real culprits? A scientific and standardized interpretation is urgently needed
.

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