Relationship of aminotransferases to liver histological status in chronic hepatitis C.

OBJECTIVES: Serum aminotransferase levels characteristically fluctuate in chronic hepatitis C, but their relationship to grade (i.e., inflammatory activity) and stage (i.e., degree of fibrosis) of liver disease is uncertain. We therefore correlated aminotransferase levels and liver biopsy findings in 90 patients with serologically confirmed chronic hepatitis C. METHODS: Mode of transmission; disease duration; symptoms and signs of liver disease; alcohol intake; autoantibody, HIV, and hepatitis B virus status; and liver biochemistries were obtained from records. Liver biopsies were 1) given a morphological diagnosis, 2) evaluated for features of chronic hepatitis C, and 3) scored with a histological activity index. RESULTS: Individual aminotransferase levels were not related to clinical or laboratory variables, nor were they reliably predictive of morphological diagnosis. No histological characteristics were associated with a particular range of aminotransferase values, except aminotransferases > 350 U/L, which were associated with piecemeal necrosis. Although mean values of aminotransferases were significantly lower among patients with chronic persistent hepatitis (CPH) (i.e., with minimal activity) compared with chronic active hepatitis (CAH) (mild to moderate activity) (ALT 110 U/L +/- 71 SD vs 256 +/- 211; AST 57 U/L +/- 34 vs 123 +/- 88) and in the absence of piecemeal necrosis compared with in its presence (ALT 133 +/- 84 vs 207 +/- 149; AST 73 +/- 47 vs 120 +/- 83), overlap of values was considerable between different histological groups. CONCLUSION: Aminotransferases do not predict liver histological status in chronic hepatitis C, although > or = 10-fold elevations suggest that piecemeal necrosis is present.

Effect of nitrous acid on lung function in asthmatics: a chamber study.

Nitrous acid, a component of photochemical smog and a common indoor air pollutant, may reach levels of 100 ppb where gas stoves and unvented portable kerosene heaters are used. Nitrous acid is a primary product of combustion and may also be a secondary product by reaction of nitrogen dioxide with water. Because the usual assays for nitrogen dioxide measure several oxides of nitrogen (including nitrous acid) together, previous studies of indoor nitrogen dioxide may have included exposure to and health effects of nitrous acid. To assess the respiratory effects of nitrous acid exposure alone, we carried out a double-blinded crossover chamber exposure study with 11 mildly asthmatic adult subjects. Each underwent 3-hr exposures to 650 ppb nitrous acid and to filtered room air with three 20-min periods of moderate cycle exercise. Symptoms, respiratory parameters during exercise, and spirometry after exercise were measured. A statistically significant decrease in forced vital capacity was seen on days when subjects were exposed to nitrous acid. This effect was most marked at 25 min and 85 min after exposure began. Aggregate respiratory and mucous membrane symptoms were also significantly higher with nitrous acid. We conclude that this concentration and duration of exposure to nitrous acid alters lung mechanics slightly, does not induce significant airflow obstruction, and produces mild irritant symptoms in asthmatics.

Indomethacin and methacholine tolerance in normal subjects. Role of prostaglandin synthesis in the attenuation of methacholine's effect during repeated inhalation challenges.

Within hours, tolerance occurs to repeated methacholine challenge in normal subjects, and this study examines whether prostaglandin synthesis produces this phenomenon. On two separate study days, ten nonasthmatic non-smoking subjects with measurable baseline responsiveness to methacholine performed five sequential methacholine challenge tests over 6 h. Pretreatment before each day consisted of either placebo tablets or 50-mg tablets of indomethacin given three times daily for 48 h prior to testing. Medications were administered in a single-blind crossover fashion, with study days assigned in random order and separated by at least 1 wk. Methacholine challenge tests were summarized by the PD20FEV1 (the provocative dose in cumulative breath units [cbu] required to produce a 20 percent fall in FEV1). Indomethacin pretreatment had no effect on baseline spirometry between the two study days; however, the baseline geometric mean PD20FEV1 fell from 145 +/- 2 cbu (+/- percent SD) after placebo pretreatment to 65 +/- 1 cbu (+/- percent SD) on the indomethacin day (p = 0.046). This effect of indomethacin on baseline airway responsiveness persisted when an additional ten subjects were studied to further investigate this finding. Significant tolerance to repeated methacholine challenges occurred on both study days, with geometric mean PD20FEV1 rising approximately 16-fold (p less than 0.0001) regardless of pretreatment received. This study demonstrates that the attenuation of methacholine's effect with repeated testing is not due solely to prostaglandin synthesis and must involve, in part, other mechanisms, such as changes in methacholine deposition, agonist-receptor interactions, or postreceptor responses. In addition, prostaglandin inhibitors may increase baseline methacholine responsiveness in healthy nonasthmatic subjects.