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Hepatitis G virus (HGV) and liver diseases Ramia S, Al Faleh FZ - Saudi J Gastroenterol
Saudi Journal of Gastroenterology
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REVIEW ARTICLE Table of Contents   
Year : 1999  |  Volume : 5  |  Issue : 2  |  Page : 50-55
Hepatitis G virus (HGV) and liver diseases

Sami Ramia1, Faleh Zaid Al Faleh2
1 Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia

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Date of Submission 29-Dec-1997
Date of Acceptance 27-Jan-1999
 

   Abstract  

Recently, a new flavi-like virus, provisionally named hepatitis GBV-C or hepatitis G virus (HGV), has been described and was initially thought to be the major etiological agent of non-A-E hepatitis. HGV does not induce an immune response that is consistently detectable by using recombinant proteins from prokaryotic expression and hence prevalence studies have been conducted by using polymerase chain reaction (PCR)-based system. HGV-RNA has been detected in many human populations. This article reviews what has been investigated about HGV from normal blood donors, patients with liver disease, patients at risk of acquiring the infection to possible perinatal and sexual transmission of the virus. Based on the conclusions that can be drawn from these studies conducted so far, the association between HGV infection and liver disease is still not certain. It is possible that HGV might play a role in other diseases not involving the liver, but at the present time HGV can be considered as an orphan flavivirus still looking for a human disease.

How to cite this article:
Ramia S, Al Faleh FZ. Hepatitis G virus (HGV) and liver diseases. Saudi J Gastroenterol 1999;5:50-5

How to cite this URL:
Ramia S, Al Faleh FZ. Hepatitis G virus (HGV) and liver diseases. Saudi J Gastroenterol [serial online] 1999 [cited 2014 Mar 3];5:50-5. Available from: http://www.saudijgastro.com/text.asp?1999/5/2/50/33509


Following the molecular cloning, identification and recognition of hepatitis C virus (HCV) [1],[2] , it became apparent that this virus accounted for more than 90% of the non-A, non-B hepatitis cases [3] . Tbe residual cases which could not be attributed to hepatitis A, B, C, D or E viruses and collectively referred to as the non-AE hepatitis group, were presumed to be caused by yet an unknown etiological agent or agents. Among the candidate non-A-E hepatitis agents that have been extensively investigated in animal models was the GB hepatitis agent [4] . The abbreviation GB stands for the initials of a surgeon who suffered acute sporadic hepatitis and whose serum on the third day of jaundice induced hepatitis in tamarins [5] . Initially, two GB hepatitis agent-like viruses, GBV-A and GBV-B have been identified and isolated from the inoculated tamarins but both were absent in humans and are thought to be of tamarin origin [6],[7],[8] . Recently, two groups of investigators described independently the isolation of a new virus from the serum of patients with hepatitis. This virus is provisionally named hepatitis GBV-C [9],[10] or hepatitis G virus [11] . Both viruses are positive single-stranded RNA viruses containing approximately 9400 nucleotides and have a genomic organization resembling that of the Flaviviridae [10],[11] . Studies revealed that the two viruses are quite distinct from HCV but have more than 90% and 95% homology at the nucleotide and amino-acid level, respectively [10],[11] and therefore they are isolates of one and the same virus. The nomenclature of this virus has not been decided yet, but for the purpos of this article, it will be referred to as HGV.

Since the discovery of HGV, many investigators in different parts of the world tried to explore the rate of HGV infection through blood transfusion, in different groups at risk for parenteral viral infection as well as in patients wtih non-A-E hepatitis, chronic liver disease or liver cancer. Furthermore, there were many investigations into the possible role of HGV CO-infection on the outcome of chronic HCV or HBV carriers. The aim of this article therfore, is to review what has been investigated about HGV, the preliminary conclusions that can be drawn at this stage and whether this newly discovered virus is really the etiological agent for the non-A-E hepatitis group.


   Detection of HGV   Top


In all published work, HGV detection in serum relied on polymerase chain reaction (PCR) amplification of HGV-RNA by reverse transcription (RT) [9],[11] . To date, there are no serological tests available for the detection of HGV and only recently an enzyme-linked immunosorbent assay (ELISA) has been developed to detect antibody to E2, an envelope protein of HGV [12] . It must be stressed then, that the detection of HGV-RNA or viremia does not necessarily reflect the actual exposure rate to the virus, and HGV infection is probably more frequent than studies of the prevalence of HGV­ RNA would suggest.


   Prevalence of HGV in blood donors   Top


[Table - 1] summarizes the prevalence of HGV-RNA in healthy adults and blood donors in various parts of the world. The lowest prevalence was reported in one study from China (0.7%) compared to 5.7% in Vietnam. Overall, the prevalence of HGV-RNA among blood donors ranged from 1.2% in most countries. However, the HCV and HCV-RNA positive blood donors have the highest prevalence of HCV-RNA.

Prevalence of HGV in patients with liver diseases

Data on the frequency of HGV in patients with various forms of liver disease are depicted in [Table - 2]. In patients with acute non-A-E hepatitis, the prevalence of HGV ranged from 2-14.6%, a range similar to that found among patients with chronic non-A-E hepatitis (4-17.9%). However, among patients with acute A, B or C hepatitis, the prevalence of HGV-RNA virus ranged from 9.5-41%. In patients with chronic HBV the prevalence of HGV-RNA ranged from 3.2-9.8% compared to 8.2-21% in patients with chronic HCV hepatitis. In patients with fulminant non-A-E hepatitis, only one study reported HGV-RNA in patients with hepatocellular carcinoma was about 6% and in patients with alcoholic or autoimmune hepatitis was close to 10%.

Prevalence of HGV in patients at risk of acquiring HGV

A relatively high prevalence of HGV-RNA was found among patients who underwent liver or bone marrow transplantation and in some reports the prevalence could exceed 60%. In hemodialysis patients, the prevalence of HGV-RNA ranged from 10-57.5% compared to 10-75.3% in intravenous drug users (IVDU) and ranged from 18.4-30% in hemophiliacs compared to 4.7-20.0% in patients with hematological malignancies [Table - 3].

Transmission of HGV by perinatal and sexual routes

Perinatal transmission of HGV was reported among HGV-RNA-positive mothers in Sweden (12.5%), Germany (33.3%) and was confirmed in one infant in Australia. In homosexual and bisexual men who denied any IVDU, the prevalence of HGV­RNa was 11% compared to 21% in prostitutes [Table - 4].

Based on the data generated on HGV infection during the past 2-3 years, important conclusions can be drawn and intriguing questions remain.

1. HGV has a world-wide distribution and ranges from 0.9-5.7% in blood donors, a prevalence rate which is usually higher than that of HCV infection in this particular group. This finding, in addition to the relatively high prevalence of HGV infection (10-20%) found in patients with a history of blood transfusion [20],[51] emphasizes that HGV is frequently transmitted by blood transfusion.

2. HGV accounts only for a minority (4-17.9%) of acute or chronic non-A-E hepatitis cases, a prevalence similar to that found in control patients with non-viral liver disease but higher than HGV infection in blood donors. It seems therefore, that the etiological agent of acute or chronic non-A-E hepatitis remains to be identified. Also the role of HGV in fulminant non-A-E hepatitis is still controversial [32],[52].

3. HGV was reported to cause apparent acute hepatitis in a small number of cases. However, the persistence of viremia long after clinical and biochemical recovery suggests that these patients may have been chronic carriers of HGV and acute hepatitis was of yet unidentified etiology.

4. The majority of prospectively followed HGV infected patients showed no evidence of associated liver disease. In the few cases of hepatitis where HGV was the sole agent identified the relation between HGV-RNA levels and ALT levels were often asynchronous. Long persistence upto 16 years without liver disease has been confirmed in dialysis patients [41].

5. Patients at high risk of acquiring HGV infection are similar to those at risk of acquiring HCV and include those with a history of intravenous drug use, patients undergoing hemodialysis, hemophiliacs, patients who underwent transplantation and those with hematological malignancies. No relationship between the presence of HGV-RNA and the presence of liver disease was documented in these patients.

6. HGV infection was often seen in patients who were also infected with HCV. In these co-infected patients HGV had no apparent influence on the clinical course or clinical outcome of the disease and ALT levels parallel those of HCV-RNA rather than those of HGV-RNA. Furthermore, the rates of response to interferon-∞ therapy in patients with chronic HCV infection co-infected with HGV did not differ between patients with and those without HGV infection [26],[38],[30] .

7. HGV can be transmitted by sexual contact (11-21 %) and from mother to infant (up to 33%). In this aspect HGV is similar to HBV but unlike HCV where sexual and intrafamilial transmission is usually low [53] .

After extensive research during the past few years, the question of whether there is a causative relationship between HGV and liver disease still awaits a clear answer. Almost all clinical studies failed to show a specific disease association independent of confounding epidemiological factors. In addition, HGV does not seem to replicate primarily in the liver. This observation is supported by the absence of disease in chimpanzees that were intravenously inoculated by HGV and also by the data from prospective studies of transfusion recipients where the rates of HGV infection were similar among persons in whom hepatitis developed and in those in whom it did not. It can be concluded, therefore, that the appellation "hepatitis" has been applied to this agent prematurely [54] and perhaps more accurately the agent is an orphan flavivirus still looking for a human disease [55].

 
   References   Top

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50. Wu JC, Sheng WY, Huang YH, et al. Prevalence and risk factor analysis of GBV-C/HGV infection in prostitutes. J Med Virol. 1997;52:83-5.  Back to cited text no. 50    
51. Wang JT, Tsai FC, Lee CZ, et al. A prospective study of transfusion-transmitted GB virus C infection: Similar frequency but different presentation compared with hepatitis C virus. Blood. 1996;88:1881-6.  Back to cited text no. 51    
52. Harrison TJ. Genetic variation in hepatitis B virus. Eur J Gastroenterol Hepatol. 1996;8:306-11.  Back to cited text no. 52    
53. Arif M, Al-Swayeh M, Al-Faleh FZ, Ramia S. Risk of hepatitis C virus (HCV) infection among household contacts of Saudi patients with chronic liver disease. J Viral Hep. 1996;3:97-101.  Back to cited text no. 53    
54. Alter HJ. The cloning and clinical implications of HGV and HGBV-C. N Engl J Med. 1996;334:1536-7.  Back to cited text no. 54    
55. Theodore D, Lemon SM. GB virus C, hepatitis G virus or human orphan flavivirus. Hepatology. 1997;25:1285-6.  Back to cited text no. 55    

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Correspondence Address:
Faleh Zaid Al Faleh
Department of Medicine (38), College of Medicine, King Saud University, P.O. Box. 2925, Riyadh 11461
Saudi Arabia
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