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IS SERUM ALUMINIUM MONITORING USEFUL IN EVALUATING ALUMINIUM INTOXICATION?
656 IS SERUM ALUMINIUM MONITORING USEFUL IN EVALUATING ALUMINIUM INTOXICATION?
SIR.—An international workshop held in Luxembourg
LONG-LASTING ABATEMENT OF HBsAg SYNTHESIS INDUCED BY ACUTE DELTA INFECTION
July,
SIR,—A chronic carrier of hepatitis B surface antigen rarely clears
1982, concluded that the monitoring of serum aluminium levels was
HBsAg.When HBsAg to anti-HBsAb seroconversion does occurit
the best approach to preventing the development of aluminium toxicity in individual patients. However, our observations suggest
is usually preceded by production of anti-HBe and progressive decline in the serum concentration of HBsAg.2 Little is known about the factors involved in the termination of this long-lasting infection. We have investigated a chronic HBsAg carrier in whom an intercurrent acute hepatitis was associated with a transient
in
that serum aluminium levels may not reflect the cumulative amount of aluminium in uraemic patients, at least in patients treated with aluminium-free dialysates. Using flameless atomic absorption spectrophotometry, we have measured aluminium concentrations in the serum of 128 uraemic patients who were on long-term dialysis, three times a week for 3-5 h, with dialysates prepared with deionised water. All patients received aluminium hydroxide orally in doses adjusted to prevent
hyperphosphataemia. Serum aluminium levels were 29 - 7±25 - 7 ug/1 in the patients on haemodialysis and were significantly higher (p<0.01, MannWhitney U test) than levels in 44 healthy individuals living in the study area (14.1±12.2jig/1). However, there was no correlation between
serum
aluminium concentration and time
on
dialysis
(r= 0-147). To evaluate the effect of aluminium hydroxide further, we selected 38 of the 128 haemodialysis patients and measured serum aluminium levels twice, 30-36 months apart. The 38 patients, who had been on haemodialysis for 1-56 months, were chosen for their good compliance in taking aluminium hydroxide. Aluminium levels were determined every 2 weeks in water treated by deionisation and in dialysates but concentrations in deioinised water and in final dialysates were always below 3 µg/l (undetectable). Paired serum aluminium levels are shown m the figure. The posttreatment mean (38. 2±24. 5 pig/1) was higher than the baseline
Ug/All
0
6
12
16
24
30
36
42
46
54
60 66 72 78 84 90
months
Serum aluminium concentrations in 38 uraemic patients before and after 30-36 months of treatment with aluminium hydroxide. mean (32. 8±30. 5 µg/l) but there was no consistent pattern. The aluminium concentrations did not seem to be related to treatment with vitamin D or its analogues and were certainly not related to parathyroid hormone levels. Thus, although serum aluminium levels rise in patients treated with aluminium-free dialysates but taking aluminium hydroxide, they do not reflect the cumulative amount of aluminium ingested and would not readily help to predict the risk of aluminium accumulation. Our findings suggest that, to avoid exposure to aluminium, concentrates should be monitored and water treated by deionisation or reverse osmosis; furthermore aluminium-containing phosphate binders should be used with caution, even though we have no clear proof of aluminium intoxication in patients taking aluminium salts.
disappearance of HBsAg from serum; HBsAg reappeared subsequently but at 100-fold lower concentration. A young boy with severe haemophilia A, born in 1963, came to our centre in 1974. HBsAg was detected in his serum (subtype ayw3) and persisted, at yearly check-ups, at the same titre (1:16, about 160 µg/ml). Serum aminotransferase values were consistently normal. In 1977 he was anti-HBe positive and anti-HBs negative. From 1978, the patient required an increased frequency of replacement therapy, with four infusions (20 U/kg) on average per month of lyophilised cryoprecipitate or factor VIII concentrate prepared from volunteer blood donors. No drugs were taken regularly. On Oct 22, 1979, after a few days of fatigue and mild fever, the patient presented with jaundice and moderate hepatomegaly. Serum bilirubin, alkaline phosphatase, and alanine aminotransferase activities were increased (table). HBsAg disappeared from the patient’s serum for 7 weeks. Very low levels of anti-HBs activity were detected over a period of 10 days, during which replacement therapy provided some 2000 IU of anti-HBs antibodies.
subsequent check-ups, at various times after factor VIII infusion, anti-HBs antibodies remained undetectable. The episode of hepatitis was well tolerated and clinical recovery occurred within a fortnight. A laboratory check-up 5 months later revealed a minor, secondary rise in serum alanine aminotransferase. Liver biopsy seemed unwarranted because of the underlying coagulation deficiency. When the patient was last seen he still had slight hepatomegaly but there were no clinical signs of portal hypertension and liver function tests were normal. Recurrent hepatitis is often encountered in multitransfused patients. The chronic HBsAg carrier state, which is frequent in this population, does not preclude infections with other hepatotropic viruses3,4 but puts the patients at great risk of chronic 6 infection. 5,6 In this case, recent exposure to hepatitis A, non-A non-B, and Epstein-Barr viruses was ruled out by serological and At
immunofluorescence tests and a second HBV infection with another subtype seemed unlikely in the presence of persisting anti-HBe antibody, so we looked for markers ofa infection to confirm that the reduction of HBsAg was the consequence of competition for HBsAg coat between HB and a viruses. Anti-6 antibodies, detected at threshold level in serum during clinical illness, reached typical post6-infection titres 5, 16, and 32 months after the acute hepatitis
(table). This clinical case illustrates the sequence of events reported in experimental infection in chimpanzees-namely, inhibition, during the acute phase of&dgr; infection, of the synthesis of pre-existing HBf gene products.7 However, in this anti-HBe carrier HBsAg remained thereafter at a very low level, most probably because of persisting 6
1
2 3
4.
Dormeyer HH, Arnold W, Schonborn H, et al. The significance of serologic. histologic, and immunohistologic findings in the prognosis of 88 asymptomatic carriers of hepatitis B surface antigen. J Infect Dis 1981; 144: 33-37. Hoofnagle JH, Dusceiko GM, SeefLB, et al. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis Ann Intern Med 1981; 94: 744-48. Kim HC, Said P, Ackley A, Bringelsen KA, Gocke DJ. Prevalence of type B and non-A non-B hepatitis in hemophilia: Relationship to chronic liver disease Gastroenterology 1979; 79: 1159-64. Viola LA, Barrison IC, Coleman JC, Murray-Lyon IM. The clinical course of acute type A hepatitis in chronic HBsAg carriers—a report of 3 cases Postgrad Med J
1982; 58: 80-81 A, Dentico P, Zanetti A, et al Infection with delta (&dgr;) agent in chronic HBsAg carriers. Gastroenterology 1981; 81: 992-97. 6 Rizzetto M, Morello C, Mannucci PM, et al Delta infection and liver disease in hemophilic carriers of hepatitis B surface antigen J Infect Dis 1982, 145: 18-22 7 Rizzetto M, Canese MG, Gerin JL, London WT, Sly DL, Purcell RH Transmission 5. Smedile
Department of Nephrology, Arciapedale S Anna, 44100 Ferrara, Italy
P. GILLI F. MALACARNE
Laboratory of Analytical Chemistry, University of Ferrara
F. FAGIOLI
of the hepatitis B virus-associated delta antigen 141: 590-602
to
chimpanzees J Infect Dis
1980
SIR.—An international workshop held in Luxembourg
LONG-LASTING ABATEMENT OF HBsAg SYNTHESIS INDUCED BY ACUTE DELTA INFECTION
July,
SIR,—A chronic carrier of hepatitis B surface antigen rarely clears
1982, concluded that the monitoring of serum aluminium levels was
HBsAg.When HBsAg to anti-HBsAb seroconversion does occurit
the best approach to preventing the development of aluminium toxicity in individual patients. However, our observations suggest
is usually preceded by production of anti-HBe and progressive decline in the serum concentration of HBsAg.2 Little is known about the factors involved in the termination of this long-lasting infection. We have investigated a chronic HBsAg carrier in whom an intercurrent acute hepatitis was associated with a transient
in
that serum aluminium levels may not reflect the cumulative amount of aluminium in uraemic patients, at least in patients treated with aluminium-free dialysates. Using flameless atomic absorption spectrophotometry, we have measured aluminium concentrations in the serum of 128 uraemic patients who were on long-term dialysis, three times a week for 3-5 h, with dialysates prepared with deionised water. All patients received aluminium hydroxide orally in doses adjusted to prevent
hyperphosphataemia. Serum aluminium levels were 29 - 7±25 - 7 ug/1 in the patients on haemodialysis and were significantly higher (p<0.01, MannWhitney U test) than levels in 44 healthy individuals living in the study area (14.1±12.2jig/1). However, there was no correlation between
serum
aluminium concentration and time
on
dialysis
(r= 0-147). To evaluate the effect of aluminium hydroxide further, we selected 38 of the 128 haemodialysis patients and measured serum aluminium levels twice, 30-36 months apart. The 38 patients, who had been on haemodialysis for 1-56 months, were chosen for their good compliance in taking aluminium hydroxide. Aluminium levels were determined every 2 weeks in water treated by deionisation and in dialysates but concentrations in deioinised water and in final dialysates were always below 3 µg/l (undetectable). Paired serum aluminium levels are shown m the figure. The posttreatment mean (38. 2±24. 5 pig/1) was higher than the baseline
Ug/All
0
6
12
16
24
30
36
42
46
54
60 66 72 78 84 90
months
Serum aluminium concentrations in 38 uraemic patients before and after 30-36 months of treatment with aluminium hydroxide. mean (32. 8±30. 5 µg/l) but there was no consistent pattern. The aluminium concentrations did not seem to be related to treatment with vitamin D or its analogues and were certainly not related to parathyroid hormone levels. Thus, although serum aluminium levels rise in patients treated with aluminium-free dialysates but taking aluminium hydroxide, they do not reflect the cumulative amount of aluminium ingested and would not readily help to predict the risk of aluminium accumulation. Our findings suggest that, to avoid exposure to aluminium, concentrates should be monitored and water treated by deionisation or reverse osmosis; furthermore aluminium-containing phosphate binders should be used with caution, even though we have no clear proof of aluminium intoxication in patients taking aluminium salts.
disappearance of HBsAg from serum; HBsAg reappeared subsequently but at 100-fold lower concentration. A young boy with severe haemophilia A, born in 1963, came to our centre in 1974. HBsAg was detected in his serum (subtype ayw3) and persisted, at yearly check-ups, at the same titre (1:16, about 160 µg/ml). Serum aminotransferase values were consistently normal. In 1977 he was anti-HBe positive and anti-HBs negative. From 1978, the patient required an increased frequency of replacement therapy, with four infusions (20 U/kg) on average per month of lyophilised cryoprecipitate or factor VIII concentrate prepared from volunteer blood donors. No drugs were taken regularly. On Oct 22, 1979, after a few days of fatigue and mild fever, the patient presented with jaundice and moderate hepatomegaly. Serum bilirubin, alkaline phosphatase, and alanine aminotransferase activities were increased (table). HBsAg disappeared from the patient’s serum for 7 weeks. Very low levels of anti-HBs activity were detected over a period of 10 days, during which replacement therapy provided some 2000 IU of anti-HBs antibodies.
subsequent check-ups, at various times after factor VIII infusion, anti-HBs antibodies remained undetectable. The episode of hepatitis was well tolerated and clinical recovery occurred within a fortnight. A laboratory check-up 5 months later revealed a minor, secondary rise in serum alanine aminotransferase. Liver biopsy seemed unwarranted because of the underlying coagulation deficiency. When the patient was last seen he still had slight hepatomegaly but there were no clinical signs of portal hypertension and liver function tests were normal. Recurrent hepatitis is often encountered in multitransfused patients. The chronic HBsAg carrier state, which is frequent in this population, does not preclude infections with other hepatotropic viruses3,4 but puts the patients at great risk of chronic 6 infection. 5,6 In this case, recent exposure to hepatitis A, non-A non-B, and Epstein-Barr viruses was ruled out by serological and At
immunofluorescence tests and a second HBV infection with another subtype seemed unlikely in the presence of persisting anti-HBe antibody, so we looked for markers ofa infection to confirm that the reduction of HBsAg was the consequence of competition for HBsAg coat between HB and a viruses. Anti-6 antibodies, detected at threshold level in serum during clinical illness, reached typical post6-infection titres 5, 16, and 32 months after the acute hepatitis
(table). This clinical case illustrates the sequence of events reported in experimental infection in chimpanzees-namely, inhibition, during the acute phase of&dgr; infection, of the synthesis of pre-existing HBf gene products.7 However, in this anti-HBe carrier HBsAg remained thereafter at a very low level, most probably because of persisting 6
1
2 3
4.
Dormeyer HH, Arnold W, Schonborn H, et al. The significance of serologic. histologic, and immunohistologic findings in the prognosis of 88 asymptomatic carriers of hepatitis B surface antigen. J Infect Dis 1981; 144: 33-37. Hoofnagle JH, Dusceiko GM, SeefLB, et al. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis Ann Intern Med 1981; 94: 744-48. Kim HC, Said P, Ackley A, Bringelsen KA, Gocke DJ. Prevalence of type B and non-A non-B hepatitis in hemophilia: Relationship to chronic liver disease Gastroenterology 1979; 79: 1159-64. Viola LA, Barrison IC, Coleman JC, Murray-Lyon IM. The clinical course of acute type A hepatitis in chronic HBsAg carriers—a report of 3 cases Postgrad Med J
1982; 58: 80-81 A, Dentico P, Zanetti A, et al Infection with delta (&dgr;) agent in chronic HBsAg carriers. Gastroenterology 1981; 81: 992-97. 6 Rizzetto M, Morello C, Mannucci PM, et al Delta infection and liver disease in hemophilic carriers of hepatitis B surface antigen J Infect Dis 1982, 145: 18-22 7 Rizzetto M, Canese MG, Gerin JL, London WT, Sly DL, Purcell RH Transmission 5. Smedile
Department of Nephrology, Arciapedale S Anna, 44100 Ferrara, Italy
P. GILLI F. MALACARNE
Laboratory of Analytical Chemistry, University of Ferrara
F. FAGIOLI
of the hepatitis B virus-associated delta antigen 141: 590-602
to
chimpanzees J Infect Dis
1980