Prolonged treatment (2 years) with different doses (3 versus 6 MU) of interferon alpha-2b for chronic hepatitis type C. Results of a multicenter randomized trial.

BACKGROUND/AIMS: To examine the effect of prolonged treatment with different doses of interferon alpha-2b on the relapse rate in patients with chronic hepatitis C. METHODS: One hundred and seventy-one patients with non-cirrhotic chronic hepatitis C were enrolled in an Italian multicenter trial. All patients were treated for 3 months with 3,000,000 Units (3 MU) of interferon alpha-2b given subcutaneously three times a week (t.i.w.). Patients with abnormal alanine aminotransferase (ALT) values were given 6 MU of interferon for an additional 3 months. If ALT remained persistently abnormal, therapy was then suspended. If ALT levels were normal, therapy was continued (6 MU t.i.w.) for an additional 18 months (total=2 years). Patients with normal ALT were randomly assigned to two groups, one receiving 3 MU and the other receiving 6 MU t.i.w. for an additional 21 months (total=2 years). Follow-up continued for 2 years after therapy withdrawal. RESULTS: Seven patients stopped treatment during the first 3 months. Of the remaining 164 patients, 76 (46%) showed abnormal ALT levels after 3 months of therapy: 11 of these (14%) normalized ALT values when given 6 MU and a sustained response was maintained in eight during the follow-up. Overall, 54 and 34 patients were allocated respectively to the groups receiving the 3 MU and 6 MU long-term treatment. At the end of therapy, 35/54 patients of the group 3 MU and 21/34 patients of the group 6 MU showed normal ALT levels (65% vs 62%, p=N.S.). After 2 years of follow-up, 24/35 (69%) patients of the group 3 MU and 16/21 (76%) of the group 6 MU were still in remission (p=N.S.). In an intention-to-treat analysis, 48/171 (28%) patients showed a long-term response (normal ALT values, HCV-RNA negative). About 65% of the sustained responders showed low baseline viremia compared with 33% of non-responders (p=0.005) while genotype 1b was more frequently found among non-responders than in long-term responders (84% vs 25%, p=0.0001). CONCLUSIONS: About 14% of patients who do not respond to a 3-month course of 3 MU of interferon normalize ALT levels when given 6 MU. In prolonged treatment, there is no significant difference between 3 and 6 MU in inducing a sustained response. Patients with low baseline viremia and genotype 2a respond significantly better to prolonged interferon therapy than highly viremic patients with genotype 1b.

Treatment of early chronic delta hepatitis with lymphoblastoid alpha interferon: a pilot study.

Seven carriers of the Hepatitis B surface antigen who had acquired a form of chronic hepatitis D in the recent past were treated with lymphoblastoid alpha interferon (IFN) (10 MU three times weekly for 4 months, 6 MU three times weekly for other 8 months, with a 12 month follow-up after treatment). At the beginning of the study, these patients had a chronic active hepatitis with intrahepatic hepatitis D antigen but without signs of cirrhosis. By the end of therapy, five had normal amino-transferases and no trace of HDV-RNA in the serum. In two patients the liver enzymes and viremia relapsed during follow up; biochemical and virologic remission persisted after discontinuation of therapy in the other three patients. In the early non-cirrhotic stage of chronic hepatitis D, IFN may play a more consistent therapeutic role than in the average advanced case of the disease. Cytokine should be used as soon as a diagnosis of progressive hepatitis D is reached.

Serological diagnosis of hepatitis B and delta virus (HBV/HDV) coinfection.

Diagnosis of acute hepatitis B virus/hepatitis delta virus (HBV/HDV) coinfection is currently based on detection of anti-HD, however this antibody may be undetectable during the acute phase of hepatitis. To evaluate the entity of misdiagnosis of HBV/HDV coinfection in acute HBsAg-anti-HBc IgM positive hepatitis we examined sera from 245 consecutive patients obtained at admission and day 30, 60, 120, 210 and 400 of their follow-up. Anti-HD was detected in the serum of 26 out of 245 patients (10.6%). In 15% of cases it was present at admission, while in 92% it was found after 30 days. The combined detection of HDV-RNA, HDAg and IgM anti-HD in acute phase sera allowed a correct etiologic diagnosis in 69% of the cases. These findings suggest that the prevalence of HBV/HDV coinfection is underestimated when anti-HD is the only marker to be detected during the acute phase of disease. A correct etiologic diagnosis can only be made by testing acute phase sera for all the available markers of HDV. However, the best cost-effective procedure is to test any patient with HBV markers at presentation for anti-HD, 30-40 days after the onset of symptoms.

[Infection monitoring in orthopedics]. / La sorveglianza infettivologica in ortopedia.

The results of infection surveillance in orthopaedics are reported: the high incidence of hospital infections in patients undergoing major surgery, the paucity of microbiological data and the failure to standardise prophylaxis protocols were the most significant findings as well as providing a point of departure for programming future fields of intervention and for redefining the operating framework for continuous infection surveillance.

[Hospital infections in an emergency surgery ward]. / Infezioni ospedaliere in un reparto di chirurgia d'urgenza.

A study was conducted on hospital infections in an emergency surgery ward. The survey lasted one year and confirmed the higher incidence of infections after contaminated and dirty operations. Rates of infection were also high after clean operations due to the large number of subjects at risk among the group examined. The most commonly encountered micro-organisms in the infections of surgical wounds were, in order, E. coli, Str. faecalis and Staph. aureus, the latter being only minimally responsive to the standard antibiotics. Several proposals are advanced for prophylaxis in the attempt to halt the circulation of strains with a multiple resistance to antibiotics.

[Blood ammonia evaluation in acute hepatitis A and B]. / La valutazione dell'ammoniemia nell'epatite virale acuta A e B.

The significance of blood ammonia levels was assessed in 100 cases of viral hepatitis (82 cases of AVH B end 18 cases of AVH A). No valid correlation was noted between the course of blood ammonia levels and that of clinical symptoms or the other blood chemical parameters considered (transaminase, prothrombin time, bilirubinemia and parameters strictly related to the clinical course).

[Bacampicillin vs amoxicillin in respiratory pathology]. / Bacampicillina vs amoxicillina in patologia respiratoria.

Clinical research was conducted to evaluate the comparative therapeutic efficacy in respiratory pathology of 800 mg X 2 per diem bacampicillin v. 1000 mg X 2 per diem amoxicillin, both orally administered. The results were more or less identical and are interpreted as indicating the better constant absorption of the precursor, hence its higher concentration gradient that produces a higher antibiotic concentration in the lungs.

[Cephalosporins and enzymuria]. / Cefalosporine ed enzimuria.

Urinary enzyme excretion was studied in 56 patients treated with cephalosporins in order to evaluate their potential nephrotoxicity. Only in 4 out of 56 patients (7%) was increased NAG, gamma-GT, AlP excretion seen. A rapid return to normal values was observed just after the end of the therapy.

[Clinico-epidemiologic findings in a group of patients with acute viral hepatitis]. / Rilievi clinico-epidemiologici su una casistica di epatite virale acuta.

Certain clinical and epidemiological findings among 2262 AVH patients are reported. The patients were all admitted to the A. di Savoia Hospital for Infectious Diseases in Turin over a two-year period.

[Ceftriaxone, a long-acting cephalosporin. Microbiological, kinetic and clinical study]. / Ceftriaxone, cefalosporina "long acting". Ricerca microbiologica, cinetica e clinica.

Ceftriaxone effectively inhibited 332 out of 452 (73.45%) bacterial strains in vitro tests. 291 out of 365 (79.69%) gram negative and 41 out of 87 (47.12%) gram positive strains were inhibited. The tests showed ceftriaxone to be more effective than cephalothin, cephotaxime, cephuroxime, cephamandol and cephoxitin. Kinetic tests showed that cephtriaxone has a plasmatic half life of 7.25 hrs. 24 hours after administration of a 1000 mg venous bolus the drug was still present in the blood. Urinary elimination over a 24 hr. period amounted to means 486.8 mg (48.68%). The drug has liquor transfer capacity. 37 of the 38 patients treated showed complete clinical or clinicobacteriological cure. Improvement was noted in the 38th.

[Piperacillin: microbiological and clinical studies]. / Piperacillina: ricerca microbiologica e clinica.

A microbiological and clinical study of the action of piperacillin is presented. The drug showed an excellent in vitro antibacterial action on gram positive and gram negative microorganisms. Its in vitro action on Ps. aeruginosa (70.8% of strains inhibited) was also extremely interesting, making it the second most effective of the antibiotics tested after polymyxin B and colistin, polypeptides unsuitable for clinical use. In vivo, the administration of piperacillin achieved a clinical and bacteriological cure in 35 out of 40 patients and a clinical cure in 2 out of 40. It was only therapeutically unsuccessful in 3 cases. It is concluded that its microbiological, kinetic and tolerance features make piperacillin suitable for a wide range of therapeutic purposes.

[Microbiological, kinetic and clinical study on a new cephamycin: cefotetan]. / Ricerca microbiologica, cinetica e clinica su una nuova cefamicina: cefotetan.

Microbiological, kinetic and clinical studies were conducted on a new cephamycin, cephotetan. In vitro the antibiotic was found to be very effective against all strains tested. It had a particularly strong action against Gram negative bacteria too. Kinetically speaking, an intravenous bolus produced a high plasmatic concentration with a half life of about 4 hours. Elimination via the kidneys was fastest in the first 3 hours after administration (49.82%) and the slowed down. 82.76% of the dose administered was excreted within 24 hours. This antibiotics is particularly indicated in cases of urinary, respiratory and biliary infections.

[Pathological changes in serum bile acids in acute and chronic hepatitis]. / Modificazioni patologiche del tasso sierico degli acidi biliari nelle epatiti acute e croniche.

In view of the current interest in changes in serum bile acids during diseases of the liver, an assessment was made of their prognostic significance, following their determination with standard hospital laboratory equipment. Increases over normal values were found to be related to the degree of liver cell damage, i.e. maximal in acute forms, and decidedly lower in aggressive chronic and persistent hepatitis and silent cirrhosis. The results are regarded as an encouragement to experiment new, quicker methods of determination.