Virological and biochemical responses to interferon-alpha in chronic hepatitis C.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Picciotto.
Explore the source record for details and available documents.
Eighty-one patients with HCV positive chronic active hepatitis (CAH) were studied to correlate, in multivariate regression analysis, liver tests with the histological activity index (HAI). The median HAI value (9.4) divided the patients into two groups; 44 under the 9.4 value (moderate CAH) and 37 above (severe CAH). Multiple regression improved the significance of nine biochemical parameters related to HAI in univariate analysis, and backward stepwise analysis identified the combination of alanine-aminotransferase (ALT), gammaglobulins (gamma GL), gammaglutamyl transpeptidase (gamma GT) and prolyl-hydroxylase (PH) as the best relationship with HAI (R = 0.520, p < 0.0001). A biochemical activity index (BAI) calculated as: 2.304 + ALT x 0.013 + gamma GL x 1.76 + gamma GT x 0.008 + PH x 0.012 showed the higher significant difference between moderate (7.7 +/- 1.3) and severe (12.2 +/- 2) CAH (p < 0.0001). These results suggest that this BAI could be a pointer for checking activity of chronic liver diseases.
Explore the source record for details and available documents.
Evidence has accumulated that interferon therapy can be effective in reducing transaminase levels and improving liver histology in patients with chronic hepatitis C. Unfortunately, the relapse rate after discontinuing treatment remains a problem. In this study the efficacy of a low dose of interferon was investigated for preventing relapses in patients who completely responded to a 6-month course of 3 MU 3 times a week. Eighteen out of 30 patients (60%) had normal ALT at the end of the 6th month of therapy. These patients were randomly allocated to receive either 1 MU interferon 3 times a week for 6 months or no treatment. Three patients (33.3%) without maintenance schedule and 4 (44.4%) treated with 1 MU relapsed. HCV-RNA was positive in 23 tested patients at entry and became undetectable in patients with sustained response. Relapse was associated with RNA reappearance. A post-therapy liver biopsy, performed in 8 patients, showed Knodell's score improvement. In conclusion, our study confirms the efficacy of interferon at the dose of 3 MU 3 times a week for 6 months. A low maintenance dose of interferon seems to be ineffective in preventing relapse in patients with chronic HCV infection who have responded to a prior treatment course.
The effect of long-term treatment with recombinant interferon-alpha 2b (IFN-alpha 2b) on luteinizing hormone (LH), testosterone, free testosterone, and sex hormone-binding globulin (SHBG) was evaluated in 7 male patients suffering from chronic viral hepatitis. The drug was given three times a week for 6 months in a single standard dose of 3 x 10(6) units. Hormone evaluations were performed in basal conditions and every 2 months for 12 months. Serum testosterone values decreased after IFN treatment, reaching the lowest levels at the 6th month. However, testosterone values did not fall below the normal range. Serum SHBG concentrations, which were above the normal range in basal conditions, also decreased after IFN. Serum-free testosterone and LH concentrations did not change during IFN therapy. IFN-alpha 2b at the dose and schedule employed was not responsible for any measurable imbalance in male sex hormones.
Explore the source record for details and available documents.
Sera from 82 haemodialysis patients were tested for anti-HCV, HCV-RNA, and HBsAg. Alanine aminotransferase (ALT) activity was monitored weekly for 2 months. Anti-HCV was positive in 31 patients (37.8%), showing different single-peptide patterns. HCV-RNA was detected in 26 anti-HCV-positive patients (84%) and also in two of 21 anti-HCV-negative patients. Twenty-seven (87%) of the 31 anti-HCV-positive patients had persistently normal ALT values; 22 of these patients were HCV-RNA positive. The four patients with elevated ALT values had HCV viraemia. HBsAg was positive in nine anti-HCV-negative patients. The close correlation between HCV viraemia and HCV status, independently of ALT values, requires that anti-HCV dialysis patients must be considered potentially infective and dialysed with reserved machines and/or in separate shifts.
We studied 2253 consecutive dyspeptic patients, without clinical evidence of organic disease, who were referred to our open access endoscopy service. The aim was to assess whether the various clinical patterns of dyspepsia can be considered a valid guideline for the appropriate use of endoscopy. According to the symptomatological patterns, our patients were defined as sufferers from 1) ulcer-like (973 patients), 2) reflux-like (857), and 3) dysmotility-like dyspepsia (423). In our patient population, which reflects the general population of our city, the dysmotility-like type of dyspepsia was the least frequent (19%), whereas the ulcer-like (43%) and the reflux-like (38%) dyspepsia were almost equivalent. A negative endoscopy (35.7%) occurred significantly (p < 5 x 10(-4)) more often in dysmotility-like than in ulcer-like (26.3%) and reflux-like dyspepsia (25.7%). Furthermore, in dysmotility-like dyspepsia, we observed no malignancies in patients less than 60 yr old, and no gastric ulcers in patients less than 50 yr old. In the latter subgroup of patients (under 50 yr), duodenal ulcers and esophagitis were rare (occurring in only one and five, respectively, out of 145 patients). In ulcer-like and reflux-like dyspepsia, abnormal endoscopic findings occurred frequently (in 73.5% and 74.1%, respectively), and no relationship with patients' age was observed. Our data indicate that patients under 50 yr old with dysmotility-like dyspepsia can be considered a kind of population for which endoscopy is inappropriate. However, because the prevalence of dysmotility-like dyspepsia was 19% (423/2253) in our patient sample, and only 7.15% of them were under 50 yr old (161/2253), we can obtain only a small percentage of reduction in endoscopic service load if the guideline of age < 50 yr is adopted.
In this two-center, pilot trial we assessed the efficacy of single bedtime does of 150 mg ranitidine (half dose) and 300 mg ranitidine (full dose) in promoting duodenal ulcer healing by comparing the proportions of healed ulcers after 4 and 8 weeks of treatment. One hundred thirty-nine patients (106 men) were randomly allocated according to a prearranged treatment schedule to either dose and were treated single-blind (endoscopist). One hundred twenty-six patients (63 given 150 mg ranitidine and 63 given 300 mg) completed the trial. In the per-protocol analysis, 55 patients given full doses (81%) and 47 given half doses (70%) of ranitidine had healed ulcers at 4 weeks. Sixty full-dose and 55 half-dose patients (95% and 87%, respectively), had healed ulcers at 8 weeks. The difference was not significant using the chi 2 test (two-tailed), but the 95% confidence limits were in favor of the 300-mg dose. This study had a 75% power to detect a 25% difference in healing rates between the two groups.
Explore the source record for details and available documents.
We report on a case, ulcerative colitis and another of Crohn's disease. During a relapse which was unresponsive to conventional therapy, acid-fast bacilli were found in colonic biopsies. Conventional therapy was substituted with antimycobacterial chemotherapy (rifampicin, isoniazid and ethambutol) which was responsible for a marked improvement. However, a relapse occurred during chemotherapy and no acid-fast bacilli were found. The patients became responsive to sulphasalazine and corticosteroid therapy once again. It appears that Mycobacteria play a collateral role in inflammatory bowel disease and that once they have been eliminated the original disease re-emerges.
Explore the source record for details and available documents.
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 patient's 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 echo-guided aspirated material is done.
The antisecretory efficacy of a single bedtime dose of famotidine, a new potent H2-receptor antagonist, was evaluated by means of continuous 24-hour intragastric pH monitoring. Of 20 patients with duodenal ulcers, ten randomly received famotidine 40 mg at 10 PM and ten were monitored without medication for control. Famotidine regimen led to a remarkable reduction of gastric acidity in patients who were treated for duodenal ulcer and the drug-induced pH levels were significantly different (P less than .0001) from those of untreated controls. The antisecretory action lasted for 12 hours, which comprised the nocturnal period, whereas no important difference was found between the two groups for the most part of the daytime. The drug was able to keep intragastric pH above 4 units during almost 50% of the whole 24-hour period. These results confirm that famotidine is a powerful and long-acting H2 blocker that relieves gastric acidity during the night and morning hours when administered as a single bedtime dose of 40 mg.
Samples of gastric juice from variously treated subjects efficiently reduced hexavalent chromium and decreased its mutagenicity. Chromium reduction was due to thermostable components of gastric secretions and was favoured by the acidity of the intragastric environment. The circadian monitoring of pH and of chromium reduction, as assessed by colorimetric analysis at hourly intervals, showed a basal activity (less than 10 micrograms/ml gastric juice) during the night and interdigestive periods, and peaks (tens of micrograms/ml) during the 3-4-h periods after each meal. Assays in the Ames reversion test confirmed that the decrease in mutagenicity of sodium dichromate produced by gastric juice was significantly enhanced after meals. This physiological mechanism is expected to provide an important protective barrier against the oral toxicity of this metal, and may explain its lack of oral carcinogenicity.
The circadian monitoring of intragastric pH and of the mutagenicity of 440 gastric juice samples collected hourly from 22 subjects provided evidence that, irrespective of diagnosis and treatment, a weak yet consistent increase in revertants can be detected in his- Salmonella typhimurium strains during the 3-4-h periods following each meal. The recorded mutagenic activity was not related to the histidine content of gastric juice, was due to thermostable components and was not significantly inhibited by administration of vitamin C. Various genetic mechanisms were involved, which were different from those consequent to the artificial supplementation of gastric juice with sodium nitrite. Treatment with a histamine H2-receptor antagonist (famotidine), either at dinner or at bedtime, was followed by a nocturnal plateau of mutagenicity. However, such effect was not due to mutagenicity of the drug or of its derivatives, but to the therapeutic rise in pH associated with its antisecretory activity.
The expression of HLA Class II antigens by resting and phytohemagglutinin (PHA)-activated T cells and their functional properties in autologous mixed-lymphocyte reactions (MLR) were investigated in patients with chronic active hepatitis, with alcoholic cirrhosis, and with primary biliary cirrhosis. In all groups of patients the percentage of resting T cells expressing HLA Class II antigens was significantly higher than that in controls. The percentage of T cells which acquired HLA Class II antigens following PHA stimulation was reduced in patients with chronic active hepatitis, serum hepatitis B surface antigen (HBsAg) positive, and in those with alcoholic cirrhosis, HBsAg negative, although the level of [3H] thymidine incorporation was within normal limits. The degree of proliferation in autologous MLR with PHA-T cells was significantly reduced in patients with chronic active hepatitis, HBsAb positive, and in those with alcoholic cirrhosis, HBsAg positive. A reduced proliferation was also detected in autologous MLR with non-T cells, in patients with chronic active hepatitis, HBsAg positive. The abnormalities of autologous MLR are selective, since the proliferative and stimulatory activities of cells from patients with chronic liver diseases in allogeneic MLR were within normal ranges. The immunoregulatory role of HLA Class II antigens and of autologous MLR suggests that the abnormalities we have identified may play a role in the immunological dysfunctions underlying chronic liver diseases.
S9 fraction pools of liver biopsy samples, collected from 129 patients in two consecutive studies, were comparatively assayed for their ability to activate aflatoxin B1 (AFB1) and a tryptophan pyrolysate product (Trp-P-2) in a miniaturized Salmonella mutagenicity test system. Metabolic activation was not affected to a significant extent by most of the monitored variability factors, such as sex, alcohol, cigarette smoking and liver histology (minimal changes, chronic persistent (CPH) or active (CAH) hepatitis, CAH steatosis, or cirrhosis). Conversely, a significant enhancement of activation was observed for AFB1 in cases of mild CAH and especially for Trp-P-2 in hepatitis B virus carriers, irrespective of their histologic diagnosis.