Anti-hepatitis G E2 Antibody Detection and Its Relation to Serum HGV-RNA in Patients with Clotting Disorders: High Prevalence of HGV Infection and Spontaneous Remission

Summary

In a previous study, we have determined the prevalence of serum HGV-RNA in patients with congenital clotting disorders. Twenty-six (15%) of 175 patients investigated were serum HGV-RNA positive. In addition, HGV-RNA was detectable in peripheral blood mononuclear cells (PBMC) in ten percent of the cases, three of these patients were serum HGV-RNA negative.

In the present study, we have determined the prevalence of anti-HGV-E2 antibodies in the same patient population. Anti-HGV-E2 as determined by ELISA was detected in 45 patients (25.7%). Forty of these patients were serum HGV-RNA negative.

Ninety-two percent of the 26 HGV viremic patients and all but one patient (44 patients) with detectable anti-HGV-E2 had coinfection with the hepatitis C virus (HCV). Of these coinfected patients, 62.5% of HGV viremic patients and 53% of anti-HGV-E2 positive patients showed elevated serum ALT levels. Anti-HGV-E2 seroconversion is thus not associated with HCV infection. Two patients who were solely infected with HGV had normal serum ALT levels. In a retrospective longitudinal study, we have observed in 15 patients that serum HGV-RNA persisted during one to 19 years of follow-up, while anti-HGV-E2 was repeatedly negative. Five additional patients who were anti-HGV-E2 positive with concomitant detectable HGV-RNA (4 patients in serum and 1 patient in PBMC) became HGV-RNA negative during follow-up, ranging from 1 to 8 years after the first detection of anti-HGV-E2 antibodies. Two patients had lost anti-HGV-E2 antibodies 3 to 6 years after the seroconversion without the re-appearance of serum HGV-RNA. From these findings, it is clear that the prevalence rate of HGV infection in patients with clotting disorders as determined by PCR assay for HGV-RNA and anti-HGV-E2 by ELISA is actually higher than the prevalence of HGV viremia. Although HGV viremia may persist for longer than 19 years, most of the patients infected with HGV may clear the viremia spontaneously. The clearance of viremia is usually associated with seroconversion to anti-HGVE2. In addition, anti-HGV-E2 may be lost during years of follow-up without the reappearance of the HGV-RNA. Although HGV infection does not seem to influence the fate of HCV infection and does not induce increased levels of serum ALT, the clinical significance of long-term infection remains to be established.

^* C.V. is Research Assistant of the Fund for Scientific Research Flanders (Belgium)

• References

• 1 Linnen J, Wages Jr J, Zhang-Keck Z-Y, Fry KE, Krawczynski KZ, Alter H, Koonin E, Gallagher M, Alter M, Hadziyalnis S, Karayiannis P, Fung K, Nakatsuj Y, Shih JW-K, Young L, Piatak Jr M, Hoover C, Fernandez J, Chen S, Zou J-C, Morris T, Hyams KC, Ismay S, Lifson JD, Hess G, Founc SKH, Thomas H, Bradley D, Margolis H, Kim JP. Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science 1996; 271: 505-8.
• 2 Simons JN, Leary TP, Dawson GJ, Pilot-Matias TJ, Muerhoff AS, Schlauder GG, Desai SM, Mushahwar IK. Isolation of novel virus-like sequence associated with human hepatitis. Nat Med 1995; 1: 564-9.
• 3 Simons JN, Pilot-Matias TJ, Leary TP, Dawson GJ, Desai SM, Schlauder GG, Muerhoff AS, Erker JC, Buijk SL. Identification of two flavivirus-like genome in the GB hepatitis agent. Proc Natl Acad Sci USA 1995; 92: 3401-5.
• 4 Zückerman AT. Alphabet of hepatitis viruses. Lancet 1996; 347: 558-9.
• 5 Yoshiba M, Okamoto H, Mishiro S. Detection of the GBV-C hepatitis virus genome in serum from patients with fulminant hepatitis of unknown aetiology. Lancet 1995; 346: 1131-2.
• 6 Aikawa T, Sugai Y, Okamoto H. Hepatitis G infection in drug abusers with chronic hepatitis C. N Eng J Med 1996; 344: 195-6.
• 7 Heringlake S, Osterkamp S, Trautwein C, Tillmann HL, Böker K, Muerhoff S, Mushahwar IK, Hunsmaan G, Manns MP. Association between fulminant hepatic failure and a strain of GBV virus C. Lancet 1996; 348: 1626-9.
• 8 Heringlake S, Tillman HL, Manns MS. New hepatitis viruses. J Hepatol 1996; 25: 239-47.
• 9 Sheng L, Soumillion A, Peerlinck K, Verslype C, van Pelt J, Hess G, Vermylen J, Yap SH. Hepatitis G viral RNA in serum and in peripheral blood mononuclear cells and its relation to HCV-RNA in patients with clotting disorders. Thromb Haemost 1997; 77 (05) 868-72.
• 10 Tacke M, Kiyosawa K, Stark K, Schlueter V, Ofenloch-Heahnle B, Hess G. Detection of antibodies to a putative hepatitis G virus envelope protein. Lancet 1997; 349: 318-20.
• 11 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt Biochem 1987; 162: 156-9.
• 12 Makris M, Preston FE, Triger DR, Underwood JCE, Choo QL, Kuo G, Houghton M. Hepatitis C antibody and chronic liver disease in hemophilia. Lancet 1990; 335: 1117-9.
• 13 Benvegnù L, Fattovich G, Noventa F, Tremolada F, Chemello L, Cecchetto A, Alberti A. Concurrent hepatitis B and hepatitis C virus infection and risk of hepatocellular carcinoma in cirrhosis. Cancer 1994; 74 (04) 2442-8.
• 14 Willems M, Peerlinck K, Moshage H, Deleu I, Van den Eynde C, Vermylen J, Yap SH. Hepatitis C virus-RNAs in plasma and in peripheral blood mononuclear cells of hemophiliacs with chronic hepatitis C: evidence for viral replication in peripheral blood mononuclear cells. J Med Virol 1994; 42: 272-8.
• 15 Jarvis LM, Davidso F, Hanley JP, Yap PL, Ludlam CA, Simmonds P. Infection with hepatitis G virus among recipients of plasma products. Lancet 1996; 348: 1352-5.
• 16 Garcia-Trevijano ER, López-Alcorocho JM, Quintana M, Hernández F, Carreño V. HGV in coagulation-factor concentrates. Lancet 1996; 348: 1032.
• 17 Dille BJ, Surowy TK, Gutierrez RA, Coleman PF, Kingge MF, Carrick RJ, Aach RD, Hollinger FB, Stevens CE, Barbosa LH, Nemo GJ, Mosley JW, Dawson GJ, Mushahwar IK. An ELISA for detection of antibodies to the E2 protein of GB virus C. J Inf Dis 1997; 175: 458-61.
• 18 Cornu C, Jadoul M, Loute G, Goubau P. Hepatitis G virus infection in haemodialysis patients: epidemiology and clinical relevance. Nephrol Dial Transplant 1997; 12: 1326-9.