TTV infection

The name "transfusion transmitted virus", a virus transmitted by transfusion (TTV), indicates its initial detection in patients with post-transfusion hepatitis. TTV is referred to the family Circoviridae. The virion is a particle without a shell, 30-50 nm in size, consisting of a single-stranded DNA ring structure containing 3852 nucleotides. The presence of hypervariable and conserved sections of the virus DNA was established.

Analysis of nucleotide sequences of TTV isolates obtained in various regions of the world made it possible to identify genotypes (up to 16) and several subtypes of this virus. The relationship between the circulation of a specific TTV genotype with a specific territory has not been identified. The most common genotypes are Gla and Gib. In the same patient, several TTV genotypes can be detected at once, which is associated either with multiple infection with this virus or with mutations occurring in the DNA of the virus.

Epidemiology of TTV infection

TTV is ubiquitous, but uneven. The prevalence among the population of European countries is 1.9-16.7%, in Asian countries - 11-42%. In the US and Australia, detection rates are 1-10.7% and 1.2%, respectively. Most often TTV is found among the population of African countries (in 44-83% of the surveyed). The frequency of TTV detection increases with the age of those surveyed, and especially among certain population groups. Thus, the percentage of TTV DNA detection in donor blood is much higher than in the population (Scotland - 46%, Finland - 73%, Singapore - 98%). The group with an increased risk of TTV infection includes drug addicts, prostitutes, homosexuals; patients with hemophilia and patients on chronic hemodialysis, i.e. Persons with an increased risk of infection with hepatitis viruses with parenteral and genital transmission routes of the pathogen.

Despite the detection of TTV for the first time in patients with parenteral hepatitis, further studies have shown that TTV can be transmitted through the fecal-oral mechanism. The presence of the virus in the bile, feces, including simultaneously with its presence in the blood serum was proved. TTV is found in the blood of some agricultural (bulls, pigs, chickens, sheep) and domestic animals (dogs, cats). Testing for TTV DNA of animal milk has yielded positive results. Finally, in China, an outbreak of acute hepatitis with a fecal-oral transmission mechanism was recorded, in the event of which the role of known hepatotropic viruses was excluded. At the same time, in all 16 patients tested for TTV DNA, it was found in the blood, suggesting the etiological role of TTV in the onset of this outbreak.

The obtained data testify to the multiplicity of mechanisms of TTV transmission. Information on the susceptibility to TTV is not available.

As established by T. Nishizawa et al. (1997), as well as N. Okamoto et al. (2000), TTU is detected with high frequency in patients with chronic hepatitis "neither A nor G" (46%), in patients with hemophilia (68%), in addicts (40%), in hemodialysis patients (46%), as well as blood donors (12%).

Detection of TTV DNA in serum from various pears in Japan (Okamoto N. Et al, 1998)

Group	Number of surveyed	Frequency of DNA detection
Fulminant hepatitis "neither A nor G"	19	9 (47%)
Chronic liver diseases "neither A nor G"	90	41 (46%)
Chronic hepatitis	32	15 (48%)
Cirrhosis of the liver	40	19 (48%)
Hepatocellular carcinoma	18	7 (39%)
Hemophilia	28	19 (68%)
Drug addicts using intravenous drugs	35	14 (40%)
Patients on hemodialysis	57	26 (46%)
Blood donors	290	34 (12%)

A high frequency of detection of TTV (47%) in patients with fulminant hepatitis, chronic liver disease of unknown etiology and a relatively low detection rate in blood donors (12%) is noticeable. This fact may be indicative of hepatotrophy of TTV. In addition, there is indirect evidence of possible hepatitis of TTV: in patients with post-transfusion hepatitis in serum and liver, TTV DNA was detected at the same concentration, and sometimes the concentration of TTV DNA was higher in the liver (Okamoto H. Et al., 1998),

The discovery of TTV by Japanese scientists served as the basis for a series of studies in other countries. First of all, I was interested in the extent to which this virus was involved in liver damage in other regions of the world.

Doctors from the London Institute of Hepatology (Naumov N. Et al, 1998) found TTV DNA in 18 of 72 patients (25%) with chronic liver disease and 3 of 30 healthy people (10%). However, in the majority of patients with chronic liver diseases and the presence of TTV DNA in the serum, no significant biochemical changes and histological signs of significant liver damage were detected. Genotyping of 9 isolates showed the presence of the same genotypes as in Japan: 3 patients were infected with genotype 1, which had a 4% variability of nucleotide sequences, and 6 - had genotype 2 with 15-27% divergence of nucleotides.

Researchers from the University of Edinburgh (Simmonds P. Et al., 1998) found only 17 (1.9%) of 1000 voluntary regular blood donors, with TTV infection only in elderly donors (mean age 53 years) . The contamination of the coagulation factor concentrates with this virus proved to be high - 56% (10 of 18 samples). TTV infection was verified in 4 (19%) of 21 patients with fulminant hepatic insufficiency of unknown etiology. And in 3 out of 4 cases, TTV was detected at the onset of the disease, and therefore its etiological role in the development of severe hepatitis can not be ruled out.

According to American researchers (Charlton M. Et al., 1998), TTV infection was detected in 1% of blood donors (1 in 100), in 15 (in 5 of 33) in patients with cryptogenic cirrhosis of the liver, in 27 (in 3 out of 11) - in patients with idiopathic fulminant hepatitis, 18 (in 2 of 11) - in patients who received blood transfusion and 4% (in 1 of 25) - in patients without parenteral manipulation in the anamnesis. Thus, the presence of a history of blood transfusions is associated with a high risk of infection with TTV infection (relative risk 4.5).

It has been proved that TTV can be transmitted not only parenterally, but also fecal-oral (Okamoto H. Et al, 1998), as well as by airborne and sexual transmission (Yzebe D, et al., 2002).

[1], [2], [3], [4], [5], [6], [7]

Pathogenesis of TTV infection

Experimental infection of chimpanzees and marmosets led to the appearance and subsequent disappearance of TTV DNA in the blood serum of all monkeys and was not accompanied by an increase in ALT and ACT activity or morphological changes characteristic of acute hepatitis.

The cases of appearance of TTV DNA in patients, its persistence and further disappearance are documented. In patients with post-transfusion hepatitis, neither A nor G, the growth and decrease in the TT-virus titers were associated with an increase and decrease in ALT and ACT activity. When the activity of aminotransferases was normalized, the TT virus was not detected. Indirect confirmation of hepatotropicity of this virus is the fact of detection of TT-virus in liver tissue in concentrations exceeding those in blood serum 10-100 times. At the same time, prolonged persistence of TTV DNA (for 22 years) without biochemical and morphological changes in the functions and structure of the liver was detected. The possibility of integrating TTV DNA into the hepatocyte genome is being rejected. At the same time, there is no explanation for the mechanism ensuring long-term preservation of the virus in the human body.

Symptoms of TTV infection

The high frequency of detection of TTV in patients with fulminant hepatitis and cirrhosis of the unspecified etiology (cryptogenic) allowed to initially assume the role of this virus in the occurrence of acute viral hepatitis with severe course and frequent outcome in cirrhosis of the liver. However, numerous further studies have not revealed any clinical features of the course of hepatitis depending on the detection of TTV, therefore the etiological role of the TT virus in the development of acute or chronic hepatitis, cirrhosis and primary hepatoma needs further study.

There are single descriptions of the symptoms of acute, predominantly post-transfusion hepatitis TTV in adult patients. The incubation period varies from 6 to 12 weeks. The disease begins with an increase in body temperature, mainly within 38 C, the appearance of asthenodyspeptic syndrome, increase in liver size and hyperfermentemia - increasing the activity of ALT, ACT, GGTP, etc. (Kanda T., 1999). In most cases, acute TTV hepatitis occurs in an icteric form.

The co-infection of TTV-hepatitis with other viral hepatitis is much more frequent than the TT virus monoinfection (Hayaski K. Et al., 2000).

In the available literature, there are no publications on TTV infection in children.

Diagnosis of TTV infection

Diagnosis of TTV infection is carried out on the basis of detection in the blood serum (in the liver) of TTV DNA by PCR. The importance of antibodies to TTV is not established.

[8], [9], [10], [11], [12]

How is TTV prevented?

TTV infection is prevented in the same way as other viral hepatitis.