Hepatitis G

Viral hepatitis G is a viral infection with a parenteral mechanism of transmission, taking place in an asymptomatic form.

ICD-10 code

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Epidemiology of hepatitis G

Epidemiological data and clinical observations show that viral hepatitis G is an infection with the parenteral mechanism of transmission of the pathogen. It has now been established that HGV RNA is often found in people who have undergone blood transfusion and parenteral interventions (found in 20.8% of those surveyed). In donor volunteers, RNA HGV is rarely recorded (1.3%), while those who give blood often - more often (12.9%). Transmission of the pathogen in this case occurs through the blood or its preparations. When testing commercial plasma for the preparation of blood products selected in different countries, HGV RNA was detected in 7-40% of plasma samples.

HGV is ubiquitous without significant age and sex differences: in Germany - 2-4.7% of the population, in Russia - 3.3-8, in France - 2-4.2. In Italy - 1,5, in Spain - 3, in the Netherlands - 0,1 - 1,5, in Japan - 0,9, in Israel - 5, in South Africa - 20, in the USA - 1,5-2% .

The virus will be transmitted exclusively parenterally. Detection of HGV RNA is associated with hemotransfusions, as well as with a rich parenteral history. Drug addicts who use narcotic substances intravenously, the virus is found in 24% of cases. In patients receiving hemodialysis, the frequency of detection of the virus varies from 3.2 to 20%. In volunteers - blood donors in the US, the proportion of HGV infection is from 1 to 2%, which is considered very high. For example, the detectability of HBV and HCV in the US population is significantly lower. According to domestic researchers, hepatitis G virus is detected in blood donors with a frequency of 3.2-4%, in patients on hemodialysis - in 28, in somatic patients - in 16.7, in patients with HCV infection - in 24.2, in patients with hemophilia - in 28% of cases.

There is evidence of the existence of sexual and vertical transmission of infection. According to C. Trepo et al. (1997), the incidence of HG viremia in France among those suffering from sexually transmitted diseases (syphilis, HIV infection, chlamydia) is 20, 19 and 12%, respectively, which is higher than in the general population. K. Stark et al (1996) reported that the incidence of HGV RNA in homosexuals and bisexuals not taking drugs is 11% in Germany, higher than in the general population; while the frequency of detection of HGV RNA was greater in people with a greater number of sexual partners. The creature of the vertical vertical transfer pathway of the HGV is currently under study. The literature data show that in children born from HGV-positive mothers, HGV RNA is found in 33.3-56% of cases, and the transmission of the virus does not depend on the titer of HGV RNA in the mother's blood serum. At the same time, children born as a result of surgical delivery (caesarean section) were RNA HGV-negative, and some naturally born, HGV-negative RNA in the early days and weeks of life of the children became RNA HGV-positive later. In addition, HGV was not detected in cord blood. All this indicates a greater likelihood of intrapartum and postnatal infection.

A study was made of plasma and blood serum from patients with various liver diseases (acute and chronic hepatitis, autoimmune hepatitis, primary biliary cirrhosis, hepatocellular carcinoma, etc.) from various parts of the world.

Practically for all liver diseases cases with presence of HG-viremia were detected. With the highest frequency, HGV RNA was detected in patients with CHC (in 18 of 96 patients from Europe); with a lower frequency - in patients with chronic hepatitis "neither A. Nor B, nor C"

(in 6 out of 48 patients from South America, 9 out of 110 from Europe), as well as in autoimmune patients (in 5 out of 53 patients from Europe) and alcoholic hepatitis (5 out of 49 patients from Europe).

According to Russian clinicians, in patients with chronic liver disease, HGV RNA is detected in the serum of blood with a very high frequency (in 26.8% of cases).

Among patients with CHB, individuals with concomitant HGV viremia were identified, but this combination was significantly less common than concurrent chronic HCV infection and HGV infection.

Of great interest after the discovery of HCV are the results of testing for HCV RNA at risk groups for parenteral infection. As well as from donor volunteers.

The frequency of HG viremia in patients at high risk of parenteral infection and in volunteer donors (linnen J. Et al., 1996)

Contingent of examined	Region	Number obsledo bathrooms	Frequency of detection of HGV
			Total HGV	Only HGV	HGV + HBV	HGV + HCV	HGV + HBV + HCV
Groups of patients at high risk of parenteral infection
Hemophilia	Europe	49	9	0	0	8	1
Patients with anemia	Europe	100	18	Eleven	1	6th	0
Drug addicts	Europe	60	20	6th	1	Eleven	2
Donor-volunteers
Donors donating blood	USA	779	13	13	0	0	0
Donors suspended from delivery of fresh blood (ALT> 45 VI E / ml)	USA	214	5	4	0	0	1
Donors suspended from donating blood for freezing (ALT> 45 IU / ml)	USA	495	6th	4	0	1	1

As follows from the data presented, about the same frequency in hemophiliacs (in 9 out of 49) and patients with anemia (in 18 out of 100) receiving multiple blood transfusions, HG-viremia is found.

Among addicts, every third person has HGV infection. And in all risk groups there is a considerable number of patients with a mixed infection caused by two, and sometimes also rattling hepatotropic viruses. The most common combination is in the form of HCV and HGV infection.

The results of screening of donor blood are interesting. Donor-volunteers could be divided into two categories. The first group included donors considered healthy, and their blood was used for transfusions. To the second category - other donors, in whose serum ALT activity was detected (more than 45 U / L), and therefore they were removed from blood donation.

As a result of testing, it was revealed that among 779 first-class donors, 13 (1.7%) sera were positive for HGV RNA.

At the same time, among the donors of the second category (709 people,) with approximately the same frequency - 1.5% of cases (11 people), sera with the presence of RNA HGV

Consequently, among donors with both normal and increased activity of transaminases in serum, the proportion of people with HG viremia, capable of transfusing blood to the recipients of hepatitis G virus, was the same.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Causes of hepatitis G

Hepatitis G virus (HGV GBV-C) is classified as a family of flaviviruses. It was discovered in 1995 in the blood of a sick surgeon who suffered acute viral hepatitis of unknown etiology. Its genome consists of single-stranded RNA: at one end are located structural genes (region 5). And on the other - non-structural (area 3). The length of the HGV RNA ranges from 9103 to 9392 nucleotides. Unlike HCV RNA, HGV lacks a hypervariable region responsible for the diversity of genotypes. Perhaps, there are three genotypes and several subtypes of the virus.

[11], [12], [13], [14], [15], [16],

The pathogenesis of hepatitis G

Pathobiological features of persistence of HGV in humans have not been studied, due to its recent identification, low incidence of viral hepatitis G and frequent co-infection with viral hepatitis B, viral hepatitis C and viral hepatitis D. There is still no place for replication of the virus in the body, although RNA of HGV is found in peripheral blood lymphocytes, including when it is absent at this time in the serum. In recent years, it has been shown that in patients with HIV infection, the disappearance of HGV on the background of its interferon therapy for chronic hepatitis C leads to a decrease in life expectancy and earlier death in the stage of AIDS. An analysis of the mortality of HIV-infected patients at this stage of the disease significantly showed a high mortality among patients who did not have the HGV virus, and especially among those who lost the virus during the observation. It is believed that the G virus blocks access to the pathogen of HIV infection in the cell. The proposed substrate (CCR5 protein) and the blocking mechanism are not established.

An important aspect of the problem is the evidence of the ability of HGV to cause acute hepatitis and induce chronic hepatitis. Taking into account the detection of this agent in patients with acute and chronic liver damage with seronegativity on other hepatitis viruses, it can be assumed that this ability is due to the hepatitis G virus. However, there is no clear evidence, and the available indirect data are contradictory.

It is known that, getting into the body parenterally, the virus circulates in the blood. RNA of HGV begins to be detected in the blood serum 1 week after the transfusion of the infected blood components. The duration of viremia corresponds to a maximum follow-up period of 16 years. More than 9-year examinations of patients with persistent HGV infection have shown that high (up to 107 / md) and low (up to 102 / ml) RNA titers are observed, while titres can remain constant during the period under study or are noted wide variations (up to six orders of magnitude), as well as the periodic disappearance of HGV RNA in serum samples.

HGV RNA was detected in the hepatic tissue (Kobayashi M. Et al., 1998). However, as it turned out, not every case of confirmed HG viremia in the liver showed HGV RNA. However, there is very little information on this extremely important issue in the literature. In vitro studies have shown that the virus is grafted on cell cultures of hepatocytes and hepatoma cells and does not multiply on the culture of lymphoma cells. Experimental infection of HGV primates does not cause liver damage in chimpanzees, whereas in game (marmozeg) there were intralobular necrosis-inflammatory changes and inflammatory infiltration of the ported tracts.

From the HG virus. Cultured on C C0 cells, protein E2 was isolated and partially purified, on the basis of which an ELISA test was prepared to detect antibodies to HGV-anti-E2 in the serum of the blood. Studies have shown that anti-E2 appear in the blood serum of patients after the disappearance of HGV RNA from them and recovery from hepatitis of this etiology.

Antibodies to the hepatitis G virus are antibodies to the surface glycoprotein E2 of the HGV class IgG and are now designated as anti-E2 HGV. They can relatively briefly be detected in the blood simultaneously with HCV RNA, but in the future, PHK HGV disappears, and only anti-E2 HGV is identified in serum. Therefore, anti-E2 HGV serves as a marker for the body's sanitation against the hepatitis virus G.

Symptoms of hepatitis G

To date, cases of acute viral hepatitis C have been described. The disease occurs both with an increase in the activity of aminotransferases and subsequent detection in the blood serum of patients with HGV RNA and in asymptomatic form. This pathology may also occur in the form of fulminant hepatitis, since approximately half of cases of this nosology can not be attributed to either viral hepatitis A or viral hepatitis E. However, the role of hepatitis G virus in the development of fulminant form of infection is inconsistent and not exactly established.

Perhaps acute hepatitis G is prone to transition into chronic course. The frequency of detection of HGV RNA among patients with cryptogenic chronic viral hepatitis is 2-9%. In West Africa, these figures are even higher. It should be noted that for this causative agent, coinfection with viruses B, C and D is most common, especially in patients at risk (parenteral, genital transmission). Its presence in patients with other chronic hepatitis does not affect the symptoms and severity of the course, the outcome of the disease, including the results of antiviral therapy.

Despite the above data, the role of HGV in the emergence of clinically significant and vivid forms of hepatitis is still challenged and questioned. The normal level of ALT activity and the absence of other signs of hepatitis in people infected with the virus, once again prove this. The high incidence of HGV in patients with hepatocellular carcinoma appears to be related to the incidence of HCV coinfection.

Taking into account the results of epidemiological studies, although still limited, it can be stated that the detection of HGV infection is combined with a wide spectrum of liver damage: from acute cyclic hepatitis and chronic forms to asymptomatic carriers.

Studies by H. Alter et al, (1997) found that about 15% of HGV-infected blood recipients do not have clinical and biochemical signs of hepatitis.

According to the same researchers, in some established cases of hepatitis, when only HGV was identified in the serum and no other known hepatotropic viruses were detected, an increase in ALT activity was insignificant, and there was practically no correlation between the level of detectable HGV RNA and ALT values

However, in other studies (Kobavashi M, et al., 1998, Kleitmian S., 2002) there is a clear correlation between the detection of HGV RNA and the clinical and biochemical manifestation of acute hepatitis.

In the literature, single descriptions of cases of acute hepatitis G are given. Thus, J. Lumen et al. (1996) gives a graphic example of posttransfusion development of hepatitis G in a patient, undergoing an operation with blood transfusion.

Four weeks after the operation, the patient had an increase in ALT activity, reaching a peak of 170 U / ml (45 U / ml) 12 weeks after the operation. After 1 month, the activity of transaminases normalized and remained the same during the next 17 months of follow-up and beyond. Results of serological tests for hepatitis A, B viruses.

C were negative, while at the time of elevation of ALT activity and further against the background of its normalization in the serum of the patient, the PCR method revealed PHK HGV. Negative results on HGV were recorded with persistently normal ALT activity rates between the 62nd and 84th week of observation (11 months after the decrease in ALT activity).

A retrospective study of the donor's blood serum, irradiated to this patient, showed the presence of HGV RNA in it.

Screening of blood sera from 38 patients with sporadic "no A or E" hepatitis from 4 US states (over the period 1985-1993) HGV RNA was detected in 5 (13%), and from 107 patients with acute hepatitis C - in 19 (18%). A comparison of the clinical picture of hepatitis G as a monoinfection with a picture of coinfection due to hepatitis C and G viruses showed no difference between them (Alter M. And et al, 1997). Other studies have also shown the absence of a significant effect of HG virus infection on the course of viral hepatitis A, B and C when combined.

At the same time, the hepatitis G virus is more often detected in the blood of patients with hepatitis B or C (acute and chronic). Thus, 1 out of 39 (2.6%) patients with acute hepatitis B, 4 out of 80 (5%) patients with chronic hepatitis B, 5 out of 57 (18.8%) patients with chronic hepatitis C and 1 of 6 children with chronic hepatitis B + -C.

Diagnosis of hepatitis G

The diagnosis of acute or chronic viral hepatitis C is made when other etiological causes of hepatitis are excluded. HGV detection is currently carried out by amplification with a preliminary reverse transcription step (RT-PCR). Two firms Boehring Mannheim Gmbh and ABBOTT produce test systems for the detection of HGV RNA, but they are recommended only for scientific research. Many laboratories, including Russia, use self-made systems. They can determine the discrepancy between the results of the serum test for the content of HGV RNA. An immunoenzymatic test has been created, with the help of which it is possible to determine the presence in the serum of anti-HGV IgG class to the E2 protein. Representing, perhaps, the main target for a humoral response. Attempts to create a test system for the detection of anti-E2 class IgM have so far been unsuccessful. Studies have shown that anti-E2 is detected if there is no HGV RNA in serum. A small frequency of detection of anti-E2 is established in blood donors (3-8%), much higher this figure in plasma donors (34%). And the highest frequency was registered among drug addicts (85.2%). These data indicate a higher incidence of spontaneous recovery from this infection.

Specific diagnostics of HG-viral infection is based on detection by PCR in the serum of HGV RNA. The primers used for setting up the PCR are specific to 5NCR, NS3 nNS5a regions of the viral genome as being the most conserved. Primers for setting PCR on HGV are produced by Abbott (USA) and Boerhmger Mannheim (Germany). Domestic Amplisens (Epidemiology Research Institute) and a number of others produce primers for setting up ERP on HGV.

Another method of diagnosing HGV infection is a test for the detection of antibodies to the surface glycoprotein E2 HGV. Based on ELISA, test systems have been developed for the detection of anti-E2 HGV, for example the Abbott test system (USA).

[17], [18], [19], [20], [21], [22],

Differential diagnostics

Since there is as yet no convincing evidence of the possible role of HGV in the development of clinically significant forms of hepatitis in humans, differential diagnosis remains open, and the diagnostic significance of HGV RNA detection is still unclear.

[23], [24]

Treatment of hepatitis G

When detecting the acute phase of viral hepatitis C, the same treatment should be used as in acute HBV and HCV infections. In patients with chronic hepatitis B and chronic hepatitis C, infected simultaneously with HGV, when interferon therapy was administered, the sensitivity of the causative agent to this drug and to ribavirin was found. At the end of the course of treatment, 17-20% of interferon-treated HGV RNA was not detected in the blood. A positive response was associated with low serum RNA levels prior to initiation of therapy. Despite the obtained data, the scheme of treatment of chronic viral hepatitis C has not been developed.