Guido Celle

Progressive Liver Functional Impairment Is Associated with an Increase in AST/ALT Ratio

The ratio of serum aspartate aminotransferase toalanine aminotransferase (AST/ALT ratio) has beenproposed as a noninvasive method of assessing liverfibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosingcirrhosis noninvasively as well as to verify theexistence of a relationship between the ratio and liverfunctional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) wereretrospectively evaluated and the AST/ALT ratio wasrelated to monoethyl glycine xylidide (MEGX) formation.Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio andindocyanine green clearance and half-life. The AST/ALTratio was able to separate patients with mild fibrosisfrom those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity,and platelet count were selected by multivariateanalysis as variables associated with cirrhosis. TheAST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine greenclearance and half-life. The alterations of indocyaninegreen kinetics, which depend upon liver blood flow anduptake, were likely due to progressive fibrosis. These findings might partially explain theincrease in the AST/ALT ratio as diseaseprogresses.

Comparison of isotope ratio mass spectrometry and nondispersive isotope-selective infrared spectroscopy for 13C-urea breath test

Objectives:The 13C-urea breath test (UBT) is a sensitive and noninvasive method to diagnose Helicobacter pylori infection, but mass spectrometry (IRMS) is very expensive. The aims of this study were to compare the new low-priced infrared spectroscopy with IRMS in detecting the infection and to assess the influence of feeding on test accuracy.Methods:One hundred thirty-four patients with dyspeptic symptoms were recruited. Of these, 74 were infected and 60 uninfected on the basis of both CLO-test and histology. A subgroup of 37 patients (22 H. pylori-positive and 15 H. pylori-negative) was studied under fasting and nonfasting conditions on two different days. Duplicate breath samples were analyzed with two IRMS systems (Breath Mat and ABCA) and an infrared spectrometer (IRIS) before, 15 min, and 30 min after ingestion of 75 mg 13C-urea with citric acid. In 37 patients the test was repeated the day after the fasted one and was performed 60 min after a meal of 800 Kcal.Results:There was a close correlation between IRIS and Breath Mat (r = 0.969 at 15 min and r = 0.977 at 30 min; p < 0.0001), IRIS and ABCA (r = 0.963 at 15 min and r = 0.985 at 30 min; p < 0.0001), and Breath Mat and ABCA (r = 0.987 at 15 min and r = 0.981 at 30 min; p= 0.0001). The sensitivity ranged from 97–100% at both times with all devices, although the specificity was slightly inferior with the infrared system than with the two IRMS machines (95%vs 98–100% at 30 min), but the difference was not significant (p= NS). Food intake produced three false negative results in all three machines and a systematic shift to lower δ values in infected patients.Conclusions:Infrared spectroscopy can be considered a valid alternative to mass spectroscopy for the diagnosis of H. pylori infection. Fasting is required to guarantee an accurate test.

Chronic hepatitis induced by Jin Bu Huan

BACKGROUND/AIMS Jin Bu Huan and other Chinese herbal products are widely taken remedies. They have been developed as a natural alternative to traditional drugs in the treatment of various ailments. Their ability to induce several side effects such as acute hepatitis has already been described. We report a case of chronic hepatic damage following administration of Jin Bu Huan Anodyne tablets. METHODS The patient, a 49-year-old man, developed biochemical signs of liver damage 2 months after beginning Jin Bu Huan intake (3 tablets/daily) including biopsy-proven chronic hepatitis with moderate fibrosis. Virological, autoimmune, metabolic or other hepatotoxic causes were excluded. Liver function impairment was resolved by discontinuing Jin Bu Huan intake. CONCLUSIONS This case reinforces the already known hepatotoxicity of this product and should make us think more about the uncontrolled use of alternative products.

Is hepatic ultrasonography a valid alternative tool to liver biopsy? report on 507 cases studied with both techniques

In order to evaluate the diagnostic potential of liver ultrasonography (US), the charts of 23 cases with normal liver, 424 patients with chronic widespread, and 60 patients with focal hepatic diseases, who had undergone both US and liver biopsy, were reviewed. The positive predictive value of US was good in all hepatic disorders (range 86.9–96.5%), while its negative predictive value was very low (range 14.1–42.5%) in the various forms of widespread liver disease and suitable for screening purposes (74%) in focal lesions. Of the 507 cases, 39 with an ultrasonically suspected liver mass also underwent an echo-guided fine-needle aspiration, which showed a high sensitivity (85%) in the 27 biopsy-proved malignant lesions and excluded tumor cells in the remaining 12 cirrhotic cases. As regards US tissue diagnosis, hepatic tumors, fatty infiltration, and fibrosis were detected in 88%, 60%, and 49% of cases, respectively. Fat and fibrous content on biopsy were similarly and significantly correlated with both echo pattern and sound attenuation. Overall results suggest that in the group of widespread hepatic disorders the usefulness of US is greatly reduced by the fact that the patients actual condition is not likely to be negative if US examination is normal and by the impossibility of differentiating fat from fibrosis. In focal lesions, the diagnostic value of US appears high and the method may frequently provide conclusive proof of the tumor if a positive cytodiagnosis on echoguided aspirated material is done.

24-hour study of intragastric acidity in duodenal ulcer patients and normal subjects using continuous intraluminal pH-metry

The circadian pattern of intragastric acidity was assessed in 19 healthy subjects and 37 patients with active, endoscopically proven duodenal ulcer using 24-hr continuous intraluminal pH-metry. The median pH 24-hr profiles showed that ulcer patients had lower postprandial pH elevations and a smaller decline in acidity during the early morning hours when compared with controls. The after-lunch and -dinner area under the curve and maximum pH values were significantly higher in controls compared to ulcer patients. In the nighttime, the median pH values in controls were significantly higher during 9 pm to 12 pm (P=0.02), 12 pm to 4 am P=0.01), and 4 am to 8 am (P=0.0008) compared to the ulcer patients. We conclude that the 24-hr acidity is higher in ulcer patients compared to healthy subjects and that the differences are particularly evident in the postprandial and nocturnal periods.

Gastric Aspiration versus Antimony and Glass pH Electrodes: A Simultaneous Comparative in Vivo Study

To carry out a simultaneous comparison of the 24-h in vivo performance of antimony and glass electrodes and the findings of intermittent gastric aspiration, a triple-probe system with closely adjacent tips was positioned in the gastric corpus of 10 subjects representing different clinical and pharmacologic conditions. We showed that pH values measured with the antimony and the glass units were well correlated to those assessed in gastric aspirates (rs = 0.87; b = 1.079; a = -0.33; and rs = 0.85; b = 1.121; a = -0.38, respectively). A proportional correlation (rs = 0.86; b = 0.97; a = 0.02) was also found between the two intraluminal pH measurements. With regard to the error frequency distributions obtained by comparing the three measuring systems two at a time, the pH pairs differed by no more than 1 pH unit in most cases (greater than 90%). It can be concluded that antimony and glass pH electrodes can be used interchangeably in 24-h intragastric acidity studies in man.

A new 1-week therapy for Helicobacter pylori eradication: rani- tidine bismuth citrate plus two antibiotics

Background: One‐week triple regimens are currently the most recommended therapy for the eradication of Helicobacter pylori. No previous study has evaluated the efficacy of a short‐term regimen combining ranitidine bismuth citrate with two antibiotics.

Variability in individual response to various doses of omeprazole. Implications for antiulcer therapy.

This study was carried out in order to perform a combined prospective assessment of the individual pharmacodynamic response and of duodenal ulcer healing in patients treated with three different doses of omeprazole. Ninety-nine patients with endoscopically proven duodenal ulcers were subdivided into three parallel groups of 33 cases, who were randomly assigned to receive orally at 0800 hr, in single blind fashion, either 10 mg, 20 mg, or 40 mg of omeprazole. All of them underwent continuous intragastric pH monitoring both in basal conditions and on the fifth day of each dose regimen; ulcer healing was then assessed endoscopically after four weeks of treatment. All three doses of omeprazole caused pH values to increase significantly (P<0.001) over the whole 24-hr period. In patients treated with omeprazole 10 mg, the individual responses showed the highest variability: the acid inhibition, expressed in terms of time spent above pH 3.0, lasted for more than 16 hr in 42% of cases, for more than 8 hr in 28%, and for less than 6 hr in 30%. In patients treated with omeprazole 20 mg, the pharmacological response was more marked and uniform and lasted for more than 16 hr in 79% of cases; however, it is worth noting it lasted for less than 6 hr in three patients (10%). In patients treated with omeprazole 40 mg, the individual response was excellent (more than 16 hr) in 94% of cases, and it lasted for less than 6 hr in only one patient (3%). The mean durations of antisecretory effect of 10, 20 and 40 mg of omeprazole were 13.21, 19.10, and 21.45 hr, and the respective four-week healing rates were 68%, 87%, and 98%. Thus, the longer-lasting the acid inhibition, the higher the healing rate (P<0.05). A dose of omeprazole as low as 10 mg produces a consistent acid inhibition in 70% of cases, and this can be associated with frequent, but unpredictable, clinical benefit. The acid suppression obtained with omeprazole 20 mg is remarkable in the majority of patients, but is poor in 10% of cases, and this finding may result in clinical nonresponse. The 40-mg dose of omeprazole produces the most uniform response and is only occasionally unsuccessful in the clinical setting.

24-H comparison between pH values of continuous intraluminal recording and simultaneous gastric aspiration.

This study was undertaken to show whether the correlation between pH values indicated by an intraluminal pH electrode and those simultaneously recorded for gastric aspirates is not only linear but also proportional, so that the two measurement techniques can be considered alternative. A 24-h intragastric pH-monitoring with an antimony electrode, to which a nasogastric tube for hourly aspiration of gastric juice was closely attached, was performed on 20 duodenal ulcer patients. Our data show that the slope of the straight line related to 335 pH pairs is virtually equal to 1, whereas the elevation is almost equal to zero, and this result strongly suggests that a proportional relationship exists between intragastric and aspirate pH levels throughout the whole 24-h period. Besides, in the majority of cases (81%) the pH pairs differ by no more than 1 pH unit. It can be concluded that these two pH monitoring methods may be alternative.

Behavior of soluble HLA class I antigens in patients with chronic hepatitis C during interferon therapy: An early predictor marker of response?

Soluble HLA class I antigens (sHLA-I),β2-microglobulin (β2-μ.) and alanine aminotransferase (ALT) serum levels have been evaluated in 16 patients affected by chronic hepatitis C treated for six months with recombinant interferon-α (rIFN-α, 3 MU three times a week). The predictor role of sHLA-I and ALT modifications with respect to the response to rIFN-α therapy was also evaluated. Six patients responded (group 1), five patients relapsed following an initial response (group 2), and five did not respond to rIFN-α treatment (group 3). The baseline serum levels of sHLA-I andβ2-μ were significantly higher in all three groups of HCV-positive patients with respect to HCV-negative controls (P<0.05). A significant increase of sHLA-I serum level with respect to baseline value (P<0.001) was observed in group 1 patients after two weeks of rIFN-α treatment. sHLA-I serum level then decreased, although remaining steadily and significantly increased with respect to baseline (P values ranging from 0.05 to 0.01) in the following five months and then returned to baseline one month after the end of rIFN-α administration. No significant variations ofβ2-μ serum levels were detected throughout the observation period. In group 1 patients ALT serum levels significantly decreased after two weeks of rIFN-α treatment (P<0.001) and then remained in the normal range throughout the observation period. In the other two groups of patients no relevant variations of sHLA-I andβ2-μ serum levels were found during and after rIFN-α therapy. The modifications of sHLA-I serum levels discriminate, as a single marker, group 1 patients from group 2 and 3 patients after two weeks of rIFN-α treatment (P<0.003). The association of sHLA-I and ALT modifications improves the discriminant power and leads to a complete differentiation of the three groups of patients after four weeks of rIFN-α treatment (P<0.0001). If confirmed in a larger series of patients, these results will provide a useful marker to predict which patients affected by chronic hepatitis C will respond to treatment and will help to avoid their ineffective treatment with an expensive and potentially harmful drug.