Hepatitis G Virus: an Agent in Search of a Disease?

Hepatitis G Virus: an Agent in Search of a Disease?

by David W. Sharp

WHAT'S HOT IN MEDICINE...

Rank	Paper	Citations This Period Jan- Feb 98	Rank Last Period Nov- Dec 97
1	R.V. Considine, et al., "Serum immunoreactive-leptin concentrations in normal-weight and obese humans," New Engl. J. Med., 334(5): 292-5, 1 February 1996. [Thomas Jefferson U., Philadelphia, PA; Eli Lilly Res. Labs., Indianapolis, IN] *TV695	39	1
2	J.W. Mellors, et al., "Prognosis in HIV-1 infection predicted by the quantity of virus in plasma," Science, 272(5265):1167-70, 24 May 1996. [U. Pittsburgh, PA; Chiron Corp., Emeryville, CA] *UM889	39	2
3	F.M. Sacks, et al., "The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels," New Engl. J. Med., 335(14):1001-9, 3 October 1996. [8 U.S. and Canadian institutions] *VL459	35	4
4	A. Schomig, et al., "A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents," New Engl. J. Med., 334(17):1084-9, 25 April 1996. [Technical U. Munich, Germany] *UG457	30	8
5	W.P. McGuire, et al., "Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer," New Engl. J. Med., 334(1):1-6, 4 January 1996. [9 U.S. institutions] *TM482	24	10
6	N.G. Stephens, et al., "Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)," The Lancet, 347(9004):781-6, 23 March 1996. [Cambridge U., U.K.; Papworth Hosp., Cambridge, U.K.; St. Thomas' Hosp., London, U.K.; Brunel U., Uxbridge, U.K.] *UB153	24	5
7	G. Maschio, et al., "Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency," New Engl. J. Med., 334(15):939-45, 11 April 1996. [10 institutions worldwide] *UD596	24	†
8	M. Packer, et al., "The effect of carvedilol on morbidity and mortality in patients with chronic heart failure," New Engl. J. Med., 334(21): 1349-55, 23 May 1996. [7 U.S. institutions] *UL251	23	6
9	G.S. Omenn, et al., "Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease," New Engl. J. Med., 334(18):1150-5, 2 May 1996. [8 U.S. institutions] *UG831	22	7
10	C.H. Hennekens, et al., "Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease," New Engl. J. Med., 334(18):1145-9, 2 May 1996. [Brigham and Women's Hosp., Boston, MA; Harvard Sch. Publ. Hlth., Boston, MA; Harvard U. Sch. Med., Boston, MA; U. Oxford, U.K.] *UG831	22	†

SOURCE: ISI's Hot Papers Database. Read the full legend.

To an outsider the nomenclature of hepatitis viruses will be baffling, for there is a veritable alphabet soup of varieties. Hepatitis A (the food-borne one that travelers often protect themselves against by immunization or a dose of immunoglobulin) and hepatitis B (HBV) are well recognized. For years physicians and epidemiologists had to content themselves with "non-A, non-B" (NANB) to cover other viral causes of hepatitis, then C (HCV) came along to fill some of the gap. D is somewhat off the main route, E is a bit like A, and F is an unresolved loner. When G was recognized in 1995, two groups had a hand in the discovery, leaving us with the choice of hepatitis G virus (HGV) or, confusingly, GB virus type C (GBV-C). It is now more or less accepted that we are talking of two strains of the same novel flavivirus.

But what does HGV "do" clinically? (And not just clinically, for every new hepatitis virus raises the question of whether blood donations should be screened for it.)

A paper by Harvey J. Alter and colleagues (see New Engl. J. Med., 336[11]:747-54, 13 March 1997; 19 citations this period) is, at #13, only warm in the latest listing, but it was "red hot" in 1997 as a whole, coming in at #20 for the year with 29 citations (see Science Watch, 9[2]:1-2, March/April 1998).

This group, based at the National Institutes of Health, Bethesda, Maryland, has for many years been studying transfusion-associated liver disease. For their investigations of HGV RNA they had five main sets of serum samples. In transfusion-associated NANB hepatitis, 9 out of 79 sera were HGV-positive, but in 6 of these there was coinfection with HCV; of 281 transfused patients without hepatitis the HGV frequency was 12/100 for those with slightly disturbed liver enzymes and 14/181 in the others; in 157 non-transfused control sera only 1 was positive, and only 7/500 blood donor sera were positive.

Other studies have shown HGV to be present in 1-3% of blood donations (the frequency was 1.4% in this series and 1.7% in another report from the NIH team). However, those findings are in sera already screened to exclude HBV and HCV, and the true population prevalence will be greater. So, here we have a virus that is quite common in the population but seldom causes disease, especially chronic hepatitis; it can be transmitted via transfusion but again not with severe or frequent consequences; it does not replicate in the liver.

Should it be called a "hepatitis virus" at all?, ask Alter and colleagues. Daniel W. Bradley, formerly of the Centers for Disease Control, Atlanta, Georgia, and co-discoverer of HGV, agrees. "HGV/GBV-C is a red herring of sorts when it comes to human hepatitis...I think it's a virus in search of a disease. I do not see HGV becoming a huge player in the viral hepatitis field in 1998," he tells Science Watch. Bradley believes that the newly described TT virus (no, we have not skipped past H to S; TT are the initials of a Japanese patient) may be more important than HGV. What is needed, Bradley reckons, is for "laboratories to collaborate on a massive scale and to arrive at a consensus on both HGV/GBV-C and TTV." But he fears that commercial interests and the publication chase will prevent that happening.

In the transfusion hepatitis data set of Alter and colleagues, hepatitis with no known viral cause was far more common (10 cases) than hepatitis associated with HGV alone (3 cases). In a companion paper, Miriam J. Alter and her coworkers looked at community-acquired acute hepatitis (see New Engl. J. Med., 336[11]:741-6, 1997). Among 45 cases of non-A-E (i.e., not hepatitis viruses A, B, C, D, or E) only 4 were positive for HGV.

It is not clear why the H.J. Alter paper should have 29 citations in 1997 while the M.J. Alter article, which opened the same NEJM issue for March 13, 1997, attracted fewer. Citations apart, no commentary that I have read concludes that screening of blood donations for HGV is warranted on current evidence.