noninvasive quantification of liver function in children using salivary caffeine clearance

1
161 NONINVASIVE QUANTIFICATION OF LIVER FUNCTION IN CHILDREN USING SALIVARY CAFFEINE CLEARANCE G. Jost,*R. Gambon, *E. Rossi, R. Preisig, Departments of Clinical Pharmacology and of *Pediatrics, University of Berne, Switzerland Studies in adults have shown that measurement of hepatic microsomal function is possible using innocuous doses of caffeine and the non-invasive approach of saliva clearance. Thus, in view of the close relationship (r = 0.95; n = 54) between plasma and saliva concentrations of caffeine, overnight salivary caffeine clearance (SCC) was studied in 20 nonsmoking adult volunteers (NV) and 33 patients with biopsy documented cirrhosis (Ci) of alcoholic or posthepatitic origin following a p.o;-dose of 4 mg/kg b.w. caffeine. Compared to values in NV (I.65±SD 0.4 ml/min/kg), SCC was markedly reduced in Ci (0.58±0.4) with little overlap between groups. In addition, we were able to demonstrate a highly significant (R s = 0.84) correlation between the SCC and the aminepyrine breath test, attesting to the validity of SCC for quantification of microsomal function. Based on these findings, 7 hospitalized children (mean age 9 years) with well documented liver disease (LD: viral hepatitis, cirrhosis) and 18 liver normal controls (LN: mean age II years) were administered 3 mg/kg b.w. caffeine (dissolved in raspberry syrup) p.o. at 4 p.m. In the saliva samples collected at bedtime around 8 p.m., caffeine saliva concentrations - measured with an EMIT assay - were comparable in LN and LD; concentrations upon arising at 8 a.m. the following morning, however, differed significantly being 12.4+SD 6 ~mol/l in LD versus 2.9+2.3 in LN. SCC, calculated with a constant VD of 0.6 I/kg reflected hepatic functional impairment being reduced from 1.80±0.5 ml/min/kg in LN to 0.61±0.4 in LD. Our data suggest that SCC is suitable for routine assessment of severity of liver diseases in children, thus replacing cumbersome and expensive techniques such as the use of stable isotopes. I{DV i.IAlq/~±IS :IiBeAg A~CD a~Iti-HDe IN CHRONIC HEPATITIS: AND CII~PJIOSIS OF T}IE LIVEI( 162 J. Juszczyk r I •Beres zyz'iska I A. Glades z ~ C linio of Inf e- ctious Uiseases ,Aoade,ay of iledicine,lozna,, and xClinic of Infectious Diseases,Academy of i.!edicine,Wroolaw/Poland/ The finding of l~3e in the strut, of HBsAg+ patients has generally been cun- sidered an indication oi" active virus replication,often correlating witl; in- fectivity,a~id hepatitis ,if present ,of higher activity,in contrast to presen- ce of' anti-l~Se.0nce the patient has ceased to replicate the virus/anti-fiRe+ lJhase/,the level of inflamuatory of hepatocytes subsides and usually no the- rapy is 1,ecessary.~-,odulation of cellular or humoral ilmnunity has interesting aspects in the 'therapy of chronic hepatitis II because immunosuppression le- ads to viral .multiplication and can cause exacerbation of the disease.In pre- sent s~udy we have a~lal:,,sed the frequency of HBsAg+ to anti-iE]e+ in 87 pati- ents/29 females,5:3 li:alcs/,aged 17-75 years,with biopsy confirming the dia6~o sis ,as follows :chronic persistent hepatitis/CPli/,n=16,chronic active hepati--- tis/CA*i/,n=2o,and cirrhosis,n=17,as well as in 34 patients treated for 12-24 months with an inunumomodulator-oalf thymus extract/T~D[-"Polfa"/.Detection of i[~eAg and anti-li0e was done with EIA-ABBOTT-tests.The ohi-square test accor- ding to Nass was performed 1or statistic reason. Frequency of IIBeAg+ was b/~- er according to severity of the disease in males and older patients.In trea- ted group the proportJ on of anti-HBc+ in males alld in olde.r patients was hi- gher then in non-treated.,Proportions of IIBeAg+ to anti-fiDe+ in" primary" CPH told CI'II as supposed result of treatment were on the same level.In patients still de,~lonstrating CAH at the course of treatment the proportion of anti- |~e+ was higher then in patients with CAH before treatment.~e suggest that monitoring "e"-system hlay be helpful for the control therapy. S259

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Page 1: Noninvasive quantification of liver function in children using salivary caffeine clearance

161

NONINVASIVE QUANTIFICATION OF LIVER FUNCTION IN CHILDREN USING SALIVARY CAFFEINE CLEARANCE G. Jost,*R. Gambon, *E. Rossi, R. Preisig, Departments of Clinical Pharmacology and of *Pediatrics, University of Berne, Switzerland

Studies in adults have shown that measurement of hepatic microsomal function is possible using innocuous doses of caffeine and the non-invasive approach of saliva clearance. Thus, in view of the close relationship (r = 0.95; n = 54) between plasma and saliva concentrations of caffeine, overnight salivary caffeine clearance (SCC) was studied in 20 nonsmoking adult volunteers (NV) and 33 patients with biopsy documented cirrhosis (Ci) of alcoholic or posthepatitic origin following a p.o;-dose of 4 mg/kg b.w. caffeine. Compared to values in NV (I.65±SD 0.4 ml/min/kg), SCC was markedly reduced in Ci (0.58±0.4) with l i t t l e overlap between groups. In addition, we were able to demonstrate a highly signif icant (R s = 0.84) correlation between the SCC and the aminepyrine breath test, attesting to the val idi ty of SCC for quantif ication of microsomal function. Based on these findings, 7 hospitalized children (mean age 9 years) with well documented l i ver disease (LD: v i ra l hepatitis, cirrhosis) and 18 l i ver normal controls (LN: mean age I I years) were administered 3 mg/kg b.w. caffeine (dissolved in raspberry syrup) p.o. at 4 p.m. In the saliva samples collected at bedtime around 8 p.m., caffeine saliva concentrations - measured with an EMIT assay - were comparable in LN and LD; concentrations upon arising at 8 a.m. the following morning, however, differed s ign i f icant ly being 12.4+SD 6 ~mol/l in LD versus 2.9+2.3 in LN. SCC, calculated with a constant VD of 0.6 I/kg reflected hepatic functional impairment being reduced from 1.80±0.5 ml/min/kg in LN to 0.61±0.4 in LD. Our data suggest that SCC is suitable for routine assessment of severity of l i ver diseases in children, thus replacing cumbersome and expensive techniques such as the use of stable isotopes.

I{DV i.IAlq/~±IS :IiBeAg A~CD a~Iti-HDe IN CHRONIC HEPATITIS: AND CII~PJIOSIS OF T}IE LIVEI(

162 J. Juszczyk r I • Beres zyz'iska I A. Glades z ~ C linio o f Inf e- ctious Uiseases ,Aoade,ay of iledicine,lozna,, and

xClinic of Infectious Diseases,Academy of i.!edicine,Wroolaw/Poland/

The finding of l~3e in the strut, of HBsAg+ patients has generally been cun- sidered an indication oi" active virus replication,often correlating witl; in- fectivity,a~id hepatitis ,if present ,of higher activity,in contrast to presen- ce of' anti-l~Se.0nce the patient has ceased to replicate the virus/anti-fiRe+ lJhase/,the level of inflamuatory of hepatocytes subsides and usually no the- rapy is 1,ecessary.~-,odulation of cellular or humoral ilmnunity has interesting aspects in the 'therapy of chronic hepatitis II because immunosuppression le- ads to viral .multiplication and can cause exacerbation of the disease.In pre- sent s~udy we have a~lal:,,sed the frequency of HBsAg+ to anti-iE]e+ in 87 pati- ents/29 females,5:3 li:alcs/,aged 17-75 years,with biopsy confirming the dia6~o sis ,as follows :chronic persistent hepatitis/CPli/,n=16,chronic active hepati--- tis/CA*i/,n=2o,and cirrhosis,n=17,as well as in 34 patients treated for 12-24 months with an inunumomodulator-oalf thymus extract/T~D[-"Polfa"/.Detection of i[~eAg and anti-li0e was done with EIA-ABBOTT-tests.The ohi-square test accor- ding to Nass was performed 1or statistic reason. Frequency of IIBeAg+ was b/~- er according to severity of the disease in males and older patients.In trea- ted group the proportJ on of anti-HBc+ in males alld in olde.r patients was hi- gher then in non-treated.,Proportions of IIBeAg+ to anti-fiDe+ in" primary" CPH told CI'II as supposed result of treatment were on the same level.In patients still de,~lonstrating CAH at the course of treatment the proportion of anti- |~e+ was higher then in patients with CAH before treatment.~e suggest that monitoring "e"-system hlay be helpful for the control therapy.

S259