Premature discontinuation of interferon plus ribavirin for adverse effects: a multicentre survey in 'real world' patients with chronic hepatitis C.

BACKGROUND: Interferon-alpha plus ribavirin therapy for chronic hepatitis C is associated with adverse effects that lead to therapy discontinuation in up to 27% of patients in randomized controlled trials. AIM: To examine the causes and predictive factors for therapy discontinuation in patients treated in current clinical practice. METHODS: We retrospectively enrolled 441 consecutive patients, scheduled to receive interferon-alpha + ribavirin for chronic hepatitis C, in five centres. Patients had been treated with 3 or 6 MU interferon-alpha three times a week plus ribavirin, 800-1200 mg daily, for 6 or 12 months. RESULTS: One hundred and eight [24.5%; confidence interval (CI), 20.5-28.8%] patients failed to finish combination therapy because of adverse events. The discontinuation rate was higher during the first 6 months of treatment; anaemia was an important cause (36.1% of discontinuations); unexplained lipothymia resulted in discontinuation in 11 patients. Female gender [hazard ratio (HR) = 1.85; CI, 1.17-2.92], an interferon-alpha dose > 15 MU/week (HR = 1.79; CI, 1.12-2.86) and no previous interferon-alpha treatment (HR = 1.63; CI, 1.04-2.57) were independent factors associated with discontinuation. The simultaneous presence of these factors identified patients at high risk for discontinuation [odds ratio (OR) = 10; CI, 3.98-25.13]. CONCLUSIONS: The study identified some predictive factors for adverse event-related discontinuation, which may improve the safety profile and effectiveness of interferon-alpha + ribavirin combination therapy in chronic hepatitis C.

Type B and D viral hepatitis: epidemiological changes in Southern Europe.

The incidence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection is in rapid decline in Southern Europe, due to the improvement in hygiene and economic conditions and the vaccination campaigns against hepatitis B. These changes have led to a shift from the classic form of chronic hepatitis B due to the wild-type virus, expressing hepatitis B e antigen (HBeAg) to a liver disease due to a mutated virus which does not express the HBeAg (e-minus mutant). Very interestingly, HBV-DNA has been detected in the liver tissue and in the serum of some subjects who lack hepatitis B surface antigen (HBsAg) in serum. This "occult" infection may be responsible for the residual cases of acute hepatitis B and might influence the course of chronic liver diseases of different aetiologies. A further consequence of the control of HBV infection is a spectacular decline in HDV circulation. At present only 8% of the HBsAg carriers in Italy have anti-HDV antibodies, vs 23% in 1987. Most of the patients with HDV infection are over 40 and present a mild liver disease or a slowly progressive cirrhosis. These epidemiological data support the concept that the epidemiological changes influence the clinical pattern of chronic hepatitis.

[Mucociliary clearance after aerobic exertion in athletes]. / Il trasporto mucociliare dopo sforzo aerobico in atleti.

The Authors studied the modifications in nasal mucociliary clearance times before and after aerobic exertion in athletes. A total of 60 athletes with high-level training (age range 18-37 years) were selected for this study. Persons who smoked or had allergies, nasal sinus phlogosis or tumors, altered nasal cavity morphology (i.e. deviation of the septum and/or hypertrophy of the turbinates), fever or who were taking topic and/or systemic drugs or had previously undergone head and neck surgery were all ruled out of the study. The authors then studied the mucociliary clearance time (MCCT) in these subjects using the saccharin test. This test involves placing a small amount of saccharin on the medial face of the lower turbinate, approximately 1.5 cm from the anterior end and then evaluating the time that elapses before the patient perceives the sweet taste. This test was performed: in 30 subjects one hour prior to and 15 minutes after physical aerobic exertion; in the remaining subjects (controls) the test was performed twice with a 75 minute interval between them. The results showed that the mucociliary clearance time increased after exertion which was, on the average, 11.29 minutes. On the basis of these data, the Authors discuss the likely causes for the detected increase, and correlate it to changes in ventilation and nasal secretion viscosity during physical exercise. According to previous research, these variations are also found in untrained subjects who undergo physical exertion; for this reason, the Authors conclude that nasal clearance is not significantly affected by training.