1161
viability could
result in isolated cases that are not thought to be attributable to safe products because they are so few. They are almost never reported in medical publications because all manufacturers and most clinicians would prefer to attribute them to non-therapeutic sources. Any remote epidemiological circumstance concerning the case is hierarchically placed ahead of exposure to a plasma derivative whenever a usually effective method of virus inactivation has been applied. Cash’s suggestion about HCV molecular epidemiology is interesting. The rate of mutation in chronic HCV infection seems to be very slow,4 and self reinfection with the same strain of HCV after orthotopic liver transplantation has been recorded.s Even with many plasma contributors to pooled derivatives, US HCV strains are sufficiently different to be demonstrable in Japanese haemophiliacs treated with American concentrates.6 Within more geographically limited areas, however, pooled plasma derivatives contaminated by several donors may have strains that are fairly similar but diverse enough to make judgment difficult ? Department of Medicine, University of Southern California, Los Angeles, California 90032, USA
JAMES W.
MOSLEY
1. Kreutz W, Auerswald G, Brückmann C, et al. Prevention of hepatitis C virus infection in children with hemophilia A and B and von Willebrand’s disease. Thromb Haemost 1992; 67: 184.
2. Gellis SS, Neefe JR, Stokes J Jr, et al. Chemical, clinical and immunological studies on the products of human plasma fractionation XXXVI, inactivation of the virus of homologous serum hepatitis in solutions of normal human serum albumin by means of heat. J Clin Invest 1948; 27: 239-44. 3. Brackmann H-H, Egli H. Acute hepatitis B infection after treatment with heat-inactivated factor VIII concentrate. Lancet 1988; ii: 967. 4. Ogata N, Alter HJ, Miller RH, Purcell RH. Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proc Natl Acad Sci USA 1991; 88: 3392-96. 5. Feray C, Samuel D, Thiers V, et al. Reinfection of liver graft by hepatitis C virus after liver transplantation. J Clin Invest 1992; 89: 1361-65. 6. Hijikata M, Kato N, Mori S, et al. Frequent detection of hepatitis C virus US strain in Japanese hemophiliacs. Jpn J Cancer Res 1990; 81: 1195-97. 7. Li JS, Tong SP, Vitvitski L, Lepot D, Trepo C. Evidence of two major genotypes of hepatitis C virus in France and close relatedness of the predominant one with the prototype virus. J Hepatol 1991; 13 (suppl): S33-37.
Hepatitis C viraemia with normal liver histology in symptomless HIV-1 infection SIR,-Dr Alberti and colleagues (Sept 19,
p
697) suggest that
hepatitis C virus (HCV)-RNA is a marker of liver disease in subjects with antibodies to HCV, independent of alanine aminotransferase (ALT) values, and challenge the idea of the existence of true healthy carriers of HCV. We disagree. We investigated over 6 months 19 subjects (15 were male), aged 19-37 years (mean 27), with anti-HIV-1 antibodies in serum (detected by enzyme immunoassay [EIA], Abbott, and confirmed by western blot, Du Pont de Nemours), no symptoms or signs of liver disease, and persistently normal serum ALT values. 11 subjects had been intravenous drug users, 4 were homosexual men, and 4 were female sexual partners of HIV-1-seropositive individuals. None of these 19 subjects had HIV-1-p24 antigenaemia (EIA). 12 subjects were CDC stage II (symptom-free) of HIV infection; the remaining 7 were CDC III (lymphadenopathy syndrome). Mean CD4-positive lymphocyte count was 392/1!1 (range 128-723); 11 subjects with fewer than 500 CD4-positive cells/ul had taken zidovudine (500 mg daily) for 6-17 months. With the use of a recombinant immunoblotting assay (RIBA-2, Ortho Diagnostics Systems), anti-C22 and anti-C33c reactivity was shown in all 19 subjects, with co-existing anti-ClOO positivity in 8. Serum HCV-RNA (detected by polymerase chain reaction with primers derived from the well-conserved 5’-non-coding region of HCV and nested amplification)’ was positive in all 19 subjects. Percutaneous liver biopsy (after informed consent) was done on the same day as serum samples were obtained, and specimens were tested for HCV-RNA. Liver histology was normal in 8 cases (with no evidence of inflammation, fibrosis, or hepatocyte necrosis), and showed slight changes in 2, chronic persistent hepatitis in 5, and chronic active hepatitis in 4 (with associated cirrhosis in 2 cases). Sex, age, risk group, CDC stage, number of CD4-positive serum
lymphocytes, or zidovudine histological fmdings.
treatment were not
related
to
the
These results show that active HCV infection is not invariably associated with liver disease and suggest that some HIV-1-infected individuals can be healthy carriers of HCV. It remains to be determined whether HIV co-infection affects the rate of HCV replication (as suggested by results of one small study) and why zidovudine treatment, which is associated with remission of HCV-induced chronic active hepatitis in patients with high ALT valueshas no such effect in subjects with normal ALT.
Infectious Diseases Unit, "A Pugliese" Hospital, 88060 Catanzaro, Italy, Department of Infectious Diseases, University of Verona, and 1st Department of Infectious Diseases, University of Genoa
SANDRO VENTO MARIO CRUCIANI GIOVANNI DI PERRI TIZIANA GAROFANO ERCOLE CONCIA TERESA FERRARO DANTE BASSETTI
1. Okamoto
H, Okada S, Sugiyama Y, et al The 5’-terminal sequence of the hepatitis C virus genome. Jpn J Exp Med 1990; 60: 167-77. 2. Watson HG, Zhang LQ, Simmonds P, Ludlam CA. Hepatitis C virus load increases with time after HIV infection. VIII International Conference on AIDS, Amsterdam, July 19-24, 1992, abstr PoB 3629, p B195. 3. Vento S, Garofano T, Di Perri G, Cruciani M, Concia E, Bassetti D. Zidovudine therapy associated with remission of chronic active hepatitis C in HIV-1 carriers. AIDS 1991; 5: 776.
Antibody-capture particle-adherence test for antibody to HIV-1 in urine SIR,-We have used the IgG antibody-capture particletest (GACPAT)l for antibody to HIV-1 on urine samples from intravenous drug users (IVDUs) attending methadone clinics in Hong Kong. Of 1259 samples, 66 (5 -2%) were initially and 37 (2-9%) were repeatedly reactive. Of the 37 repeatedly reactive samples, only 7 remained reactive after being heated in a water bath at 60°C for 20 min. As controls, concurrently heat-treated urine samples from confirmed HIV-positive individuals did not show any alteration in endpoint titres. The 7 repeatedly reactive samples were negative by antibody-capture adherence
enzyme immunosorbent assay and western blot.
Our observation suggests that although GACPAT is economical and simple for use in large scale anti-HIV screening,2 it can give a high number of false-positive reactions in urine samples from IVDUs. Heat treatment of repeatedly reactive samples removed non-specific reactions in most samples. The nature of the heat-labile substance in the urine of IVDUs that causes the non-specific reaction remains to be elucidated. Virus Unit,
Department of Health, Queen Mary Hospital, Pokfulam Road, Hong Kong
W. L. LIM K. C. CHENG
1. Connell
JA, Parry JV, Mortimer PP, et al. Preliminary report: accurate assays for anti-HIV in urine. Lancet 1990; 335: 1366-69. 2. Parry JV, Mortimer PP. An immunoglobulin G antibody capture particle adherence test (GACPAT) for antibody to HIV-1 and HTLV-1 that allows economical large scale screening. AIDS 1989; 3: 173-76.
Serological assessment of Helicobacter pylori eradication SIR,-Various tests are available to assess the success of therapy at eradicating Helicobacter pylori. Upper gastrointestinal endoscopy with antral biopsy is too invasive for routine use; 13C and 14C urea breath-testing are expensive and not readily available to most general practitioners; and a lack of studies on the reliability of serological examination in assessing past from current infection combined with the extravagant number of testing kits have clouded the interpretation of serological assays. However, the diagnostic value of decreasing H pylori antibody titres after eradication of the bacterium has been demonstrated by Kosunen et aP using an acid-glycine extract enzyme-linked immunosorbent assay (ELISA).1 Others2 had different opinions about the value of such serological testing. We can add data from H pylori serological testing in Busselton, a Western Australian rural community (population 9000), to support the findings of Kosunen et al.
aimed
viability could
result in isolated cases that are not thought to be attributable to safe products because they are so few. They are almost never reported in medical publications because all manufacturers and most clinicians would prefer to attribute them to non-therapeutic sources. Any remote epidemiological circumstance concerning the case is hierarchically placed ahead of exposure to a plasma derivative whenever a usually effective method of virus inactivation has been applied. Cash’s suggestion about HCV molecular epidemiology is interesting. The rate of mutation in chronic HCV infection seems to be very slow,4 and self reinfection with the same strain of HCV after orthotopic liver transplantation has been recorded.s Even with many plasma contributors to pooled derivatives, US HCV strains are sufficiently different to be demonstrable in Japanese haemophiliacs treated with American concentrates.6 Within more geographically limited areas, however, pooled plasma derivatives contaminated by several donors may have strains that are fairly similar but diverse enough to make judgment difficult ? Department of Medicine, University of Southern California, Los Angeles, California 90032, USA
JAMES W.
MOSLEY
1. Kreutz W, Auerswald G, Brückmann C, et al. Prevention of hepatitis C virus infection in children with hemophilia A and B and von Willebrand’s disease. Thromb Haemost 1992; 67: 184.
2. Gellis SS, Neefe JR, Stokes J Jr, et al. Chemical, clinical and immunological studies on the products of human plasma fractionation XXXVI, inactivation of the virus of homologous serum hepatitis in solutions of normal human serum albumin by means of heat. J Clin Invest 1948; 27: 239-44. 3. Brackmann H-H, Egli H. Acute hepatitis B infection after treatment with heat-inactivated factor VIII concentrate. Lancet 1988; ii: 967. 4. Ogata N, Alter HJ, Miller RH, Purcell RH. Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proc Natl Acad Sci USA 1991; 88: 3392-96. 5. Feray C, Samuel D, Thiers V, et al. Reinfection of liver graft by hepatitis C virus after liver transplantation. J Clin Invest 1992; 89: 1361-65. 6. Hijikata M, Kato N, Mori S, et al. Frequent detection of hepatitis C virus US strain in Japanese hemophiliacs. Jpn J Cancer Res 1990; 81: 1195-97. 7. Li JS, Tong SP, Vitvitski L, Lepot D, Trepo C. Evidence of two major genotypes of hepatitis C virus in France and close relatedness of the predominant one with the prototype virus. J Hepatol 1991; 13 (suppl): S33-37.
Hepatitis C viraemia with normal liver histology in symptomless HIV-1 infection SIR,-Dr Alberti and colleagues (Sept 19,
p
697) suggest that
hepatitis C virus (HCV)-RNA is a marker of liver disease in subjects with antibodies to HCV, independent of alanine aminotransferase (ALT) values, and challenge the idea of the existence of true healthy carriers of HCV. We disagree. We investigated over 6 months 19 subjects (15 were male), aged 19-37 years (mean 27), with anti-HIV-1 antibodies in serum (detected by enzyme immunoassay [EIA], Abbott, and confirmed by western blot, Du Pont de Nemours), no symptoms or signs of liver disease, and persistently normal serum ALT values. 11 subjects had been intravenous drug users, 4 were homosexual men, and 4 were female sexual partners of HIV-1-seropositive individuals. None of these 19 subjects had HIV-1-p24 antigenaemia (EIA). 12 subjects were CDC stage II (symptom-free) of HIV infection; the remaining 7 were CDC III (lymphadenopathy syndrome). Mean CD4-positive lymphocyte count was 392/1!1 (range 128-723); 11 subjects with fewer than 500 CD4-positive cells/ul had taken zidovudine (500 mg daily) for 6-17 months. With the use of a recombinant immunoblotting assay (RIBA-2, Ortho Diagnostics Systems), anti-C22 and anti-C33c reactivity was shown in all 19 subjects, with co-existing anti-ClOO positivity in 8. Serum HCV-RNA (detected by polymerase chain reaction with primers derived from the well-conserved 5’-non-coding region of HCV and nested amplification)’ was positive in all 19 subjects. Percutaneous liver biopsy (after informed consent) was done on the same day as serum samples were obtained, and specimens were tested for HCV-RNA. Liver histology was normal in 8 cases (with no evidence of inflammation, fibrosis, or hepatocyte necrosis), and showed slight changes in 2, chronic persistent hepatitis in 5, and chronic active hepatitis in 4 (with associated cirrhosis in 2 cases). Sex, age, risk group, CDC stage, number of CD4-positive serum
lymphocytes, or zidovudine histological fmdings.
treatment were not
related
to
the
These results show that active HCV infection is not invariably associated with liver disease and suggest that some HIV-1-infected individuals can be healthy carriers of HCV. It remains to be determined whether HIV co-infection affects the rate of HCV replication (as suggested by results of one small study) and why zidovudine treatment, which is associated with remission of HCV-induced chronic active hepatitis in patients with high ALT valueshas no such effect in subjects with normal ALT.
Infectious Diseases Unit, "A Pugliese" Hospital, 88060 Catanzaro, Italy, Department of Infectious Diseases, University of Verona, and 1st Department of Infectious Diseases, University of Genoa
SANDRO VENTO MARIO CRUCIANI GIOVANNI DI PERRI TIZIANA GAROFANO ERCOLE CONCIA TERESA FERRARO DANTE BASSETTI
1. Okamoto
H, Okada S, Sugiyama Y, et al The 5’-terminal sequence of the hepatitis C virus genome. Jpn J Exp Med 1990; 60: 167-77. 2. Watson HG, Zhang LQ, Simmonds P, Ludlam CA. Hepatitis C virus load increases with time after HIV infection. VIII International Conference on AIDS, Amsterdam, July 19-24, 1992, abstr PoB 3629, p B195. 3. Vento S, Garofano T, Di Perri G, Cruciani M, Concia E, Bassetti D. Zidovudine therapy associated with remission of chronic active hepatitis C in HIV-1 carriers. AIDS 1991; 5: 776.
Antibody-capture particle-adherence test for antibody to HIV-1 in urine SIR,-We have used the IgG antibody-capture particletest (GACPAT)l for antibody to HIV-1 on urine samples from intravenous drug users (IVDUs) attending methadone clinics in Hong Kong. Of 1259 samples, 66 (5 -2%) were initially and 37 (2-9%) were repeatedly reactive. Of the 37 repeatedly reactive samples, only 7 remained reactive after being heated in a water bath at 60°C for 20 min. As controls, concurrently heat-treated urine samples from confirmed HIV-positive individuals did not show any alteration in endpoint titres. The 7 repeatedly reactive samples were negative by antibody-capture adherence
enzyme immunosorbent assay and western blot.
Our observation suggests that although GACPAT is economical and simple for use in large scale anti-HIV screening,2 it can give a high number of false-positive reactions in urine samples from IVDUs. Heat treatment of repeatedly reactive samples removed non-specific reactions in most samples. The nature of the heat-labile substance in the urine of IVDUs that causes the non-specific reaction remains to be elucidated. Virus Unit,
Department of Health, Queen Mary Hospital, Pokfulam Road, Hong Kong
W. L. LIM K. C. CHENG
1. Connell
JA, Parry JV, Mortimer PP, et al. Preliminary report: accurate assays for anti-HIV in urine. Lancet 1990; 335: 1366-69. 2. Parry JV, Mortimer PP. An immunoglobulin G antibody capture particle adherence test (GACPAT) for antibody to HIV-1 and HTLV-1 that allows economical large scale screening. AIDS 1989; 3: 173-76.
Serological assessment of Helicobacter pylori eradication SIR,-Various tests are available to assess the success of therapy at eradicating Helicobacter pylori. Upper gastrointestinal endoscopy with antral biopsy is too invasive for routine use; 13C and 14C urea breath-testing are expensive and not readily available to most general practitioners; and a lack of studies on the reliability of serological examination in assessing past from current infection combined with the extravagant number of testing kits have clouded the interpretation of serological assays. However, the diagnostic value of decreasing H pylori antibody titres after eradication of the bacterium has been demonstrated by Kosunen et aP using an acid-glycine extract enzyme-linked immunosorbent assay (ELISA).1 Others2 had different opinions about the value of such serological testing. We can add data from H pylori serological testing in Busselton, a Western Australian rural community (population 9000), to support the findings of Kosunen et al.
aimed
