Search

To determine whether the aminopyrine breath test can be used to document the presence of cirrhosis in patients with cholestatic liver disease, 19 patients (13 primary biliary cirrhosis, 4 sclerosing cholangitis and 2 chronic extrahepatic bile duct obstruction) underwent clinical and biochemical evaluations, liver biopsies and an aminopyrine breath test. Results were compared with those in 10 patients with biopsy-proven chronic active hepatitis with bridging and/or cirrhosis and in 22 healthy subjects. The aminopyrine breath test results in the 10 cholestatic patients with cirrhosis were not significantly different from the results in precirrhotic cholestatic patients (mean +/- S.D., 11.2 +/- 5.0 vs. 11.6 +/- 2.8% dose per 2 hr, p greater than 0.05) or healthy subjects (11.5 +/- 2.9% dose per 2 hr). In contrast, the results in the patients with chronic hepatitis were markedly depressed (3.2 +/- 1.9% dose per 2 hr, p less than 0.05). The aminopyrine breath test results did not correlate with results of conventional liver function tests in the cholestatic patients. These results demonstrate that the aminopyrine breath test is not clinically useful in identifying the presence of cirrhosis in patients with cholestatic liver disease, and provide further evidence that decreased microsomal enzyme function is a late feature of cholestatic liver disease.

Different methods of expressing the results of the aminopyrine CO2 breath test (ABT) were compared to determine the method that would be most sensitive for evaluating liver function. The patient population included health controls (n = 22); patients with mild (4), moderate (9), and severe (7) alcoholic liver disease; and patients with chronic persistent hepatitis (7), chronic active hepatitis (18), chronic active hepatitis with bridging (18), and chronic active hepatitis with cirrhosis (17). The ABT was performed with 2 micro Ci [14C]aminopyrine or 2 mg per kg [13C]aminopyrine, and the results were expressed as the instantaneous labeled CO2 excretion rates at 30, 60, 90, and 120 min after the dose, the maximum excretion rate, and the 120-min cumulative excretion. The 30-min parameter had the highest sensitivity toward moderate alcoholic hepatitis, severe alcoholic hepatitis, chronic active hepatitis with bridging, and chronic active hepatitis with cirrhosis (96%); however, when the ABT was repeated in six normal controls with 225 ml of orange juice, the 30-min rate was significantly reduced (7.8 +/- 1.3 vs. 5.6 +/- 1.2% dose per hr), and the rate of false-positive test results was increased (0 of 6 vs. 2 of 6) indicating that gastric delay influenced the 30-min parameter. The 60-min excretion rate, maximum rate, and 120-min cumulative excretion were the next most sensitive expressions of the ABT, and were not altered by the small gastric load. Of these three expressions, the 60-min parameter was the most convenient because it required fewer samples and a shorter test period.

A randomized, double-blind, controlled trial of insulin and glucagon infusion was conducted in 50 patients with acute alcoholic hepatitis. Twenty-five treatment patients received 24 U regular insulin and 2.4 mg glucagon over 12 h daily for 3 wk. Twenty-five control patients received 200 ml dextrose solution in identical bottles over the same time period. Six control and 2 treatment patients died from liver failure during study, and another treatment patient died from hypoglycemia. In the 34 patients with prothrombin times greater than 3 s prolonged, fewer deaths occurred among the insulin- and glucagon-infused patients (p less than 0.10). Clinical features of liver disease on entry into the study were similar in the two groups, and total serum bilirubin and prothrombin time improved more rapidly in the treatment group (p less than 0.05). Insulin and glucagon infusion is a promising treatment of alcoholic hepatitis and merits further study in the most severely ill patients.

The phenacetin breath test (PBT) has been proposed as an alternative to the aminopyrine breath test (ABT) for the assessment of hepatic function. To investigate the clinical utility of the PBT, we compared the PBT with the ABT in 9 healthy subjects and 18 patients with biopsy-proven liver disease. We also investigated the effects of cytochrome P-450 inducers in humans and rats, and the effect of cobaltous chloride (CoCl2) in rats on the PBT to elucidate the relationship between the rate of phenacetin deethylation and exhaled labeled CO2 derived from phenacetin. In humans with abnormal ABTs, the PBT correlated with the ABT (r = 0.77), but in healthy humans there was no correlation between the two breath tests. Rifampin pretreatment in healthy humans induced the ABT by 27%, but did not induce the PBT. In rats the PBT was not induced by 3-methylcholanthrene pretreatment at phenacetin doses of 1 mg per kg, but was induced by both 3-methylcholanthrene (178%) and phenobarbital (142%) at 10 mg per kg phenacetin. Pretreatment of rats with CoCl2, which reduces cytochrome P-450 content, decreased the PBT by 40% and the ABT by 84%. The insensitivity of the PBT to induction except at high doses of phenacetin suggests that phenacetin deethylation is not the rate-limiting process modulating exhaled labeled CO2 in healthy subjects, and that the PBT does not generally reflect normal or induced phenacetin dealkylation rates. The PBT, however, did reflect hepatic damage and may even be better than the ABT for grading the severity of hepatic damage.

To determine whether the aminopyrine breath test (ABT) and serum bile acid concentrations reflect histologic severity of chronic hepatitis, 56 patients were prospectively evaluated with liver biopsies and ABTs, and the results were compared to results of standard liver chemistry tests; 44 of these patients also had fasting and 2-hr postprandial serum bile acid measurements. Mean values for the ABT were significantly lower, and serum bile acids were significantly higher in patients with chronic active hepatitis with bridging or cirrhosis than in patients with mild chronic active hepatitis or chronic persistent hepatitis. Thirty of 35 patients with bridging or cirrhosis had ABTs less than 5.7% (mean of controls -2 S.D.) and 21 of 25 with mild chronic active hepatitis or chronic persistent hepatitis had values greater than 5.7% (sensitivity 0.86, specificity 0.84). Fasting and 2-hr postprandial bile acids were also more sensitive than standard chemistries in identifying patients with bridging or cirrhosis. Thus, the ABT and serum bile acids reflect histologic severity in chronic hepatitis patients and may be helpful in selecting patients for liver biopsy.

To determine whether the aminopyrine breath test reflects the presence of increased pericentral fibrosis, steatonecrosis, and cirrhosis following jejunoileal bypass, 21 patients were evaluated with liver biopsies, liver chemistry tests, 45-min bromosulfothalein retention tests, and aminopyrine breath tests prior to bypass and at 3, 6, and 12 months thereafter. Following bypass, 15 biopsies demonstrated increased pericentral fibrosis, steatonecrosis, or cirrhosis, and 35 biopsies revealed increased fatty infiltration alone. Although the aminopyrine breath test results were significantly lower in patients with increased pericentral fibrosis, steatonecrosis, and cirrhosis at 6 and 12 months following bypass (P less than 0.05), this test had a positive predictability of only 0.67. An abnormal AST had a positive predictability of 0.87. Other liver function tests were less reliable in identifying patients with potentially progressive lesions following bypass. Thus, the AST is more useful than the aminopyrine breath test in reflecting increased pericentral fibrosis, steatonecrosis, and cirrhosis following jejunoileal bypass. The nonspecific effects of obesity and increased fatty infiltration of the liver following jejunoileal bypass may account for the low predictability of the aminopyrine breath test.