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Biomedical subjects

E Sagnelli

Publications and source records attributed to E Sagnelli.

At least 55 records · Page 3Linked to original sources

Prolonged treatment of children with chronic hepatitis B with recombinant alpha 2a-interferon: a controlled, randomized study.

A prospective study was conducted to evaluate the efficacy and tolerance of alpha-interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti-delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a-interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10 patients per group). Five patients receiving IFN showed a marked decrease or negativization of HBV-DNA during treatment. At the end of the study (after 18 month), three patients lost HBV-DNA permanently, and two of them seroconverted to HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of aminotransferase values. In the control group, one patient had spontaneous clearance of HBV-DNA with conversion to HBeAb and normalization of aminotransferase levels. All treated patients had a febrile reaction in the first month of treatment. The dose of IFN had to be decreased in two patients and was discontinued for persistent intolerance in one of them. Patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders. The data suggest that IFN treatment may favorably influence the progression of chronic B hepatitis in children with a history of acute hepatitis and active chronic disease.

Adolescent↗

Influence of HDV infection on clinical, biochemical and histological presentation of HBsAg positive chronic hepatitis.

In an attempt to identify some characteristics of HDV infection in the different forms of HBsAg positive chronic hepatitis (CH), we evaluated numerous clinical, biochemical and histological aspects in 203 consecutive HBsAg positive CH patients. The presence of hepatitis delta antigen (HD-Ag) in the liver tissue was the criterion used to identify HDV infection. HD-Ag was observed in none of the 7 patients with non-specific reactive hepatitis, in 14.6% of the 48 with chronic persistent hepatitis (CPH), in 36.4% of the 44 with chronic lobular hepatitis (CLH), in 36% of the 25 with mild chronic active hepatitis (CAH), in 52% of the 36 with severe CAH and in 30.2% of the 43 with inactive or moderately active cirrhosis. Compared with the 139 HD-Ag negative patients in this study, the 64 HD-Ag positive patients more frequently had severe CAH (29.7 vs. 12.2%, p less than 0.01) and less frequently CPH (10.9 vs. 29.5%, p less than 0.01). Of the 139 HD-Ag negative patients, 80 were anti-HD positive and 59 anti-HD negative. The 59 patients with no HD-Ag or anti-HD showed severe CAH less frequently than the 64 HD-Ag positive patients (6.8 vs. 29.7, p less than 0.01) and CPH more frequently (44.1 vs. 10.9, p less than 0.001). Both in CPH and CLH the presence of HD-Ag in the hepatocytes identified subgroups of patients who frequently showed high serum levels of aminotransferases and gammaglobulins and more extended areas of circumscribed lobular necrosis. HD-Ag positive CAH was characterized by a more frequent occurrence of eosinophilic degeneration of hepatocytes without peripolesis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pharmacokinetics of ciprofloxacin in impaired liver function.

The pharmacokinetics of ciprofloxacin after a single 500 mg oral dose was studied in one group of healthy volunteers and in patients affected by liver cirrhosis and classified into three groups according to Child-Turcotte criteria. The serum concentrations were determined by an agar well diffusion assay 0.5, 1, 3, 6, 12 and 24 h after the administration of the drug. No significant differences were noticed in Cmax, Tmax, T1/2 and AUCtot in the group A and B of patients and in the control group. Class C patients showed on the other hand a Cmax 15-25% higher than in other groups (2.74 mcg/ml), a T1/2 1.12-1.42 hours longer than in other groups and a consequent much higher AUCtot (17.70 mcg/h/ml). The concomitant administration of diuretics of anti-H2 drugs was also evaluated as possible factors affecting the ciprofloxacin pharmacokinetics, but no significant differences were noticed. A mild or moderate impairment of the liver function did not affect the pharmacokinetics of ciprofloxacin, but the severe impairment of the liver function could affect its Cmax and serum half-life, so that further studies with multiple doses will be needed to evaluate if any dosage adjustment would be required in these patients.

Adult↗

Multicenter trial on the efficacy of HBIG and vaccine in preventing perinatal hepatitis B. Final report.

In an attempt to interrupt perinatal transmission of hepatitis B, 92 infants born to HBsAg carrier mothers (49 to HBeAg-positive mothers, 30 to anti-HBe-positive with abnormally elevated ALT levels, and 13 to HBeAg/anti-HBe-negative mothers) received 0.5 ml/kg BW of HBIG at birth and at 1 month of age. Three IM injections of hepatitis B vaccine were given at 3, 4, and 9 months of life. All babies who were given the three doses of vaccine developed an active anti-HBs response: of these, 53 (62.3%) had antibody titers higher than 1,000 mIU/ml, 29 (34.2%) had levels between 100 and 1,000 mIU/ml, and the other three (3.5%) were below 100 mIU/ml. At the end of the 2-year follow-up, these three poor responders became anti-HBs negative, whereas the others still had antibody. All but three babies were protected by HBIG plus vaccine treatment. Two chronic HBV infections occurred within 6 months of life presumably because the babies were already infected when prophylaxis started. The third baby became an HBsAg carrier at 9 months of age in spite of a previous response to the vaccine. Simultaneous presence of HBsAg of y specificity and anti-HBs (anti-a) was still detectable at 24 months of age. The vaccine was well tolerated. Passive plus active immunization is an effective procedure for preventing perinatally transmitted HBV infection.

Carrier State↗

Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies.

This paper reviews the complications that arose after 68 276 percutaneous liver biopsies performed from 1973 to 1983. The complications are analyzed in relation to the underlying liver disease and to the type of needle used. Death was infrequent (9/100 000); it was always due to haemoperitoneum and occurred only in patients with malignant diseases or cirrhosis. Complications were less frequent in AVH (44/100 000) than in other liver diseases (from 125 to 278/100 000). Death, serious haemorrhagic complications, pneumothorax and biliary peritonitis were more frequent after biopsy with the Trucut needle than after biopsy with Menghini's needle (3/1000 against 1/1000). Sixty-one percent of complications were discovered within two hours of biopsy and 96% within one day. The data indicate a post biopsy observation period of at least 24 hours. The day-case procedure should be reserved for patients not presenting liver tumour or cirrhosis.

Biopsy, Needle↗

Acute hepatitis B in children with papular acrodermatitis.

Thirteen children who had repeated liver biopsies over a period of 2-16 years after the onset of papular acrodermatitis (PAC) were studied retrospectively. Six patients, rebiopsied within 36 months after the onset of PAC, had histologic evidence of chronic periportal hepatitis. However, repeated biopsies in 3 of the patients revealed a normal liver or chronic portal hepatitis. Whereas all patients had at the end of the observation markers of hepatitis B virus infection, 8 of the 10 patients studied had HBs antigenemia. These data indicate that severe active liver disease may regress without treatment in patients who have had PAC. However, the high frequency of a chronic HBsAg-carrier state among these patients suggests either an inefficient clearance of the virus or an altered immune reaction.

Acrodermatitis↗

Detection of two forms of HBeAg (free-and IgG-bound HBeAg) in patients with HBe antigenemia using staphylococcus bearing protein A.

Protein A-bearing Staphylococcus aureus organisms (STA) were used to separate free HBeAg from IgG-bound HBeAg. Free HBeAg was detected in the supernate while IgG-bound HBeAg could be liberated from the pellets using MgCl2 or a glycine buffer. HBeAg was determined by radioimmunoassay and the results expressed as patient's cpm/normal control's cpm ratio (S/N ratio). This ratio was demonstrated to be proportionate to the antigen concentration and used as a titer of HBeAg. Sera of 40 HBsAg-negative healthy volunteers and 82 HBeAg-positive patients who were either asymptomatic HBsAg carriers or had various diseases including chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), and renal disease undergoing hemodialysis, were tested for free HBeAg and IgG-bound HBeAg. Patients with CAH from two different countries were compared. Free HBeAg was detected in all patients but one, IgG-bound HBeAg was detected with similar prevalences (from 56% to 67%) in HBsAg asymptomatic carriers, hemodialysis patients, CPH and Italian CAH patients. In contrast, all CAH patients from New York, who had frequently been exposed to HBV infection, had detectable levels of IgG-bound HBeAg, with the highest S/N ratios observed in the study, and frequently showed an unfavorable outcome. In AVH due to HBV and delta agent co-infection, IgG-bound HBeAg was detected in two of four patients only in the initial stage of the disease. The data reported indicate that a separate determination of free- and IgG-bound HBeAg may have clinical value.

Adolescent↗

Delta agent infection: an unfavourable event in HBsAg positive chronic hepatitis.

To investigate the clinical value of delta agent infection in HBsAg positive chronic hepatitis, we detected anti-delta antibody (anti-delta) in serum and delta antigen (delta-Ag) on sequential liver biopsies of nine patients with HBsAg-positive CPH and 45 patients with HBsAg-positive CAH without cirrhosis observed for at least 2 years. The initial group of patients with CAH was composed of 54 patients who were consecutively either left untreated or treated with 15 mg of prednisolone daily. Nine patients dropped out. Delta-Ag was searched by the direct immunofluorescence technique. HBsAg, anti-delta, HBeAg and anti-HBe were detected by RIA. All CPH patients were delta-Ag negative in the 1st liver biopsy and anti-delta negative in serum. Out of these nine patients, seven remained delta-Ag negative CPH throughout the observation and the remaining two became delta-Ag positive, anti-delta positive and developed CAH. The 73% of patients with CAH were delta-Ag positive on the 1st biopsy and anti-delta positive in serum. The patients in the delta-Ag positive group (24 were always delta-Ag positive and two became delta-Ag positive during the observation) more frequently than those in the delta-Ag negative group (10 were always delta-Ag negative and nine became delta-Ag negative during the study) showed deterioration or died (77 vs. 16%; P less than 0.001). Neither in the delta-Ag positive group nor in the delta-Ag negative group did prednisolone modify the course of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunosuppressive therapy in chronic active hepatitis (CAH). A multicentric retrospective study on 867 patients. A report from a study group for CAH of the Italian Association for the study of the liver.

We retrospectively reviewed the clinical, biochemical and histological features of 867 patients with biopsy-proven CAH observed in 12 Italian Liver Units for at least one year. Either HBsAg positive or HBsAg negative patients (473 and 394 patients, respectively) were left untreated, or were treated with one of the following regimens: a) prednisolone or prednisone 10 to 30 mg daily, referred to as Steroids; b) azathioprine 50 to 100 mg daily; c) prednisolone or prednisone 10 to 20 mg daily associated with azathioprine 50 to 100 mg daily, referred to as Combination. The outcome was evaluated on the basis of clinical, biochemical and histological parameters. Among the 473 patients with HBsAg positive CAH those treated with combination, as compared to those untreated, more frequently, improved (P less than 0.001), and less frequently deteriorated (P less than 0.001). Under Steroids or Azathioprine improvement was more frequent than in untreated patients, but deterioration was not prevented. The results were similar among the 394 HBsAg negative patients. The data indicate that combination is effective in treating either HBsAg positive CAH or HBsAg negative CAH.

Adolescent↗

In vitro synthesis of IgG and IgM in patients with HBsAg-positive and HBsAg-negative chronic active hepatitis.

Spontaneous and PWM-driven IgG and IgM synthesis was investigated in the PBMC of 15 patients with HBsAg-negative CAH and six HBsAg-positive patients with CAH. PBMC from patients with HBsAg-positive CAH show an impaired IgG synthesis upon stimulation with PWM but an IgM increase similar to that of control subjects. In contrast, PBMC from HBsAg-negative patients with CAH show a trend to spontaneous increased synthesis of IgG and a decrease or lack of IgG and IgM synthesis upon PWM stimulation. Steroid treatment seems to ameliorate these alterations. No differences were found among the three groups of HBsAg-negative chronic active hepatitis (autoimmune, HBsAg-related and cryptogenic). These results indicate that differences of B-cell functions may exist in the two groups of CAH patients, not only in spontaneous B-cell activation or PWM-induced Ig synthesis but also in the different classes of Ig.

Adult↗

Circulating complement fixing immune complexes in chronic hepatitis. Use of anti-C3 enzyme immunoassay to define antibody class and nature of antigen.

An anti-C3 enzyme immunoassay (anti-C3 EIA) was used to identify the antigen and antibody of immune complexes (IC). HBsAg, liver cell membrane antigens (LSP and LP-2), IgA, IgG and IgM were determined in IC of 258 patients with chronic active hepatitis (CAH) and 31 patients with chronic persistent hepatitis (CPH). IC that contained an antibody of either IgG, IgM or IgA class were detected in all types of CAH and CPH investigated. IC were seen more frequently in patients with cirrhosis than in CAH patients without cirrhosis and patients with CPH. LSP and LP-2 in IC were detected in 50% of patients with CAH and, infrequently, in CPH patients. In a group of 56 patients with CAH, followed for two to nine years, those patients treated with steroids showed a tendency to clear IC, whereas no variation was seen in untreated patients. While the presence of IC seems to indicate a decreased clearance of IC, a damaging activity of IC on the liver or the immune system remains to be demonstrated.

Antigen-Antibody Complex↗

Geographic differences in HBV related, autoimmune, and cryptogenic chronic active hepatitis.

To clarify the importance of ethnic and geographic factors in chronic active hepatitis (CAH), HBV markers and autoantibodies (AMA, ANA, SMA), have been compared in 158 patients with biopsy-proven CAH from New York City and in 92 patients with CAH from Milan. HBsAg-positive CAH was more frequently observed in Milan (49%) than in New York City (27%). However, among HBsAg-positive patients, HBcAg, HBeAg, and epidemiologic risk factors for acquisition of HBV infection were more frequently found in New York than in Italy. The prevalence of HBsAg-negative, anti-HBc-positive CAH and cryptogenic CAH was similar in the two cities, while autoimmune CAH was more frequently observed in New York (20%) than in Milan (2%). In particular, the prevalence of autoimmune hepatitis was higher among Jewish patients than among patients of Anglo-Saxon or Latin ethnic background in New York. Thus, environmental and/or ethnic factors may influence the prevalence of the four major types of CAH.

Antibodies↗

Radioimmunoassay for hepatitis B core antigen.

Serum hepatitis B core antigen (HBcAg) is an important marker of hepatitis B virus replication. We describe an easy, sensitive radioimmunoassay for determination of HBcAg in detergent-treated serum pellets containing Dane particles. Components of a commercial kits for anti-core determination are used, and HBcAG is measured by competitive inhibition of binding of 125I-labeled antibodies to HBcAg with HBcAg-coated beads. We assayed of HBcAG in the sera of 49 patients with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis, 50 patients with HBsAg-negative chronic hepatitis, and 30 healthy volunteers. HBcAg was detected in 41% of patients with HBsAg-positive chronic hepatitis but not in patients with HBsAg-negative chronic hepatitis. Hepatitis Be antigen (an antigen closely associated with the core of Dane particles) determined in the same sera by radioimmunoassay, was not detected in 50% of HBcAg-positive sera.

Cross Reactions↗

Treatment of chronic active hepatitis (CAH): a retrospective review of 130 patients.

The authors review the course of disease in 130 patients (87 HBsAg-positive and 43 HBsAg-negative) with chronic active hepatitis (CAH) observed in the last six years. Patients were treated with prednisone (36 HBsAg-positive an 8 HBsAg-negative), azathioprine (7 HBsAg-positive and 12 HBsAg-negative) or a combination of prednisone and azathioprine (23 HBsAg-positive and 14 HBsAg-negative), or remained untreated (21 HBsAg-positive and 9 HBsAg-negative). Among HBsAg-positive patients improvement was observed in 54% of the 66 patients treated, and in none of the 21 untreated patients (P less than 0.001). Treatment did not modify the course of the disease in HBsAg-negative patients with CAH; this is probably related either to the small number of patients in each treatment group, or to geographical differences. Furthermore treatment was not effective in patients older than 40 years, whether HBsAg-positive or HBsAg-negative. Three out of 87 HBsAg-positive patients, and two out of the 43 HBsAg-negative patients had died by the end of the observation period irrespective of treatment. Full remission with clearance of HBsAg was observed only in one patient after 4 years of treatment with steroids.

Adolescent↗