Caffeine clearance in patients with chronic viral hepatitis: before and after interferon therapy.

The purpose of this study was to evaluate caffeine clearance, a quantitative measurement of metabolizing capacity of the liver, in chronic hepatitis B and C before and after interferon treatment. Biochemical test using AST and ALT, virological test, and caffeine clearance were measured in eighteen patients with chronic hepatitis B and five patients with chronic hepatitis C at pre and post treatment with interferon. Caffeine clearance was determined in each patient using two point analysis following a 3.5 mg/kg oral administration of caffeine solution. Blood samples were subsequently collected at 12 and 16 hours after caffeine administration and assayed for serum caffeine level by HPLC technique. Clearance was calculated using the equation of Cl = Kel x Vd. It was found that caffeine clearances determined before and after interferon treatment were not significantly different in both chronic hepatitis B and C inspite of biochemical and virological responses after therapy. Caffeine clearance change in two diffferent groups of chronic hepatitis B defined as biochemical response and nonresponse were compared. Although caffeine clearance change between responders and nonresponders to interferon treatment was not significantly different, it tended to increase in those patients who had biochemical response to interferon. It appeared that metabolic capacity of the liver does not change with interferon therapy inspite of biochemical and virological responses.

Effect of omeprazole on gastric mucosa and serum levels of amoxicillin in patients with non-ulcer dyspepsia.

The aim of this study was to determine the interaction between omeprazole and amoxicillin, being common agents used in the eradication regimen for H. pylori infection. Amoxicillin concentrations in gastric mucosa and serum were quantitatively analysed in 12 patients with non-ulcer dyspepsia following the administration of one week duration of placebo as group I and omeprazole as group II. The study was a blind, cross-over design with a one week wash out period between the two treatment groups. Six antral gastric mucosa were biopsied 90 minutes after oral administration of amoxicillin. Blood samples were collected before and after administration at intervals up to 6 hours. All samples were analysed for amoxicillin concentration using the HPLC technique. Highly intersubject variations of amoxicillin concentrations were observed. The concentration of amoxicillin in gastric mucosa ranged from 0.00-1.74 and 0.00-1.25 micrograms/mg for group I and group II, respectively, with the mean concentration of 0.25 +/- 0.48 microgram/mg for group I and 0.28 +/- 0.40 microgram/mg for group II. The difference was not statistically significant (p = 0.89). Pharmacokinetic parameters of amoxicillin in serum following regimen I and regimen II were not significantly different (p > 0.05). The mean Cmax values were 14.62 +/- 5.39 and 12.65 +/- 4.76 micrograms/ml, the Tmax were 2.3 +/- 1.0 and 2.0 +/- 0.9 hour and the AUC0-6 were 40.79 +/- 13.26 and 38.75 +/- 15.04 micrograms/ml.h in the group I and group II, respectively. From these results, we concluded that omeprazole has no effect on gastric mucosa level nor serum levels of amoxicillin. The therapeutic efficacy of using these two agents in the eradication regimen of H. pylori may be related to other factors rather than pharmacokinetic interaction.

Short-term effects of branched-chain amino acids on liver function tests in cirrhotic patients.

A randomized study was conducted in 29 ambulatory cirrhotic patients to determine the short-term effects of branched-chain amino acids (BCAA) on nutritional status, biochemical liver function tests and caffeine clearance. Each patient received a 4-week period of isonitrogenous and isocaloric regimens, either a standardized diet contained 40 g protein with supplementation of BCAA 150 g daily (group I) or only a standardized diet contained 80 g protein daily (group II). At the end of treatment, only group I showed significant improvements in transaminase levels as well as the caffeine clearance test compared with those of the pre-treatment levels. Nonetheless, significant improvements in nutritional parameters and additional liver function tests were not yet detected. We conclude that the short-term nutritional supplementation of BCAA is well tolerated and leads to improvement in hepatic metabolic capacity assessed by the caffeine clearance test.

Caffeine clearance study in hepatocellular carcinoma.

The purpose of this study was to evaluate hepatic metabolic capacity in cirrhotic patients with hepatocellular carcinoma (HCC). We compared plasma caffeine clearance, calculated by two point analysis, between patients with cirrhosis alone and cirrhosis complicated with HCC. These two groups were comparable with regards to age, sex, and the severity of liver disease, graded by Child-Pugh score as compensated and decompensated cases. From our result, caffeine clearance in compensated cases was clearly higher than that of decompensated cases in both groups studied, particularly in the HCC group (p = 0.001). The mean value of caffeine clearance in HCC patients correlated well with the tumor staging as classified by Okuda's criteria. There was also a reversal correlation between tumor size and the clearance tested in compensated cases of HCC (p = 0.046), but this finding was not detected in decompensated cases (p > 0.05). We conclude that the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in cirrhotic patients complicated with HCC, and may be a useful predictor for survival outcome.