Pseudouridine for Monitoring Interferon Treatment of Patients with Chronic Hepatitis C

Peer Reviewe

Muscular damage during telbivudine treatment in a chronic hepatitis B patient

Muscle tissue damage might be related to metabolic and mechanical factors. Certain drugs have been associated with increased blood levels of creatin phospho kinase (CPK) and myoglobin that are biochemical markers of musculoskeletal damage. An increase of CPK plasma levels might suggest severe rhabdomyolysis with possible resulting renal failure. Telbivudine is an antiviral drug indicated for the treatment of chronic hepatitis B (CHB) in adult patients. An increase in CPK plasma levels has been recently described in some telbivudine-treated CHB patients without muscle-skeletal symptoms. In this paper we report a CHB patient that developed a severe increase of CPK plasma levels during telbivudine-treatment. Pharmacological evaluation, using the Naranjo probability scale, indicated a probable relationship between telbivudine and CPK increase, so telbivudine was discontinued and replaced with entecavir with a complete resolution of laboratory findings. In conclusion, telbivudine treatment can induce muscular damage in the absence of skeletal injury, therefore we suggest to closely monitor the muscular function of the patients treated with this drug in order to prevent possible major complications

Pegylated Interferon Alfa-2b Plus Ribavirin in the Retreatment of Interferon-Ribavirin Nonresponder Patients

Background & Aims: Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy with pegylated IFN-α-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated. Methods: One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-α-2b 1.5 μg/kg per week and ribavirin 1000-1200 mg/day for 48 weeks and followed up for 24 weeks. Results: By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low γ-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6-79.6) and low viral load (OR, 3.8; 95% CI: 1.1-12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3). Conclusions: Retreatment with pegylated IFN-α-2b and ribavirin of multiexperienced and "difficult to treat" nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low γ-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR. © 2006 American Gastroenterological Association Institute