Search

Background and Aim: In patients with chronic hepatitis C receiving Peg interferon/ribavirin (PEG-IFN/RBV) who do not achieve ≥ 2 log-reduction in HCV-RNA at week 12 (null responders, NR) and in those with ≥ 2 log-decrease but detectable at week 24 (partial responders, PR) the probability to achieve the sustained virological response (SVR) is almost null. The aim of this study was to investigate the efficacy of individualized schedule of progressively increased RBV doses in the setting of PEG-IFN/RBV treatment., Material and Methods: PR or NR to PEG-IFN/RBV instead of discontinuing treatment were enrolled to receive increasing doses of RBV until a target theoretical concentration ([tRBV]) of ≥ 15 μmol/L (by pharmacokinetic formula based on glomerular filtration rate). HCV-RNA was assessed every 4 weeks and, if detectable, RBV dose was gradually increased until negativization. Twelve weeks later, patients with detectable HCV-RNA discontinued therapy while those with undetectable HCV-RNA continued for further 48 weeks., Results: Twenty genotype-1 patients (8 NR and 12 PR) were enrolled. After 12 weeks 9 (45%) were still HCV-RNA positive and were discontinued, while remaining 11 had undetectable HCV-RNA. One stopped treatment for side effects. Ten completed treatment. Five (all PR) achieved SVR. Side effects incidence was similar to that observed during PEG-IFN/RBV., Conclusions: In conclusion, RBV high doses, according to individualized schedule, increase SVR in PR on a similar extent to that of triple therapy but without increase of side effects. Such treatment should be considered in PR with no access or intolerant to protease inhibitors (PI).

Aim: To evaluate the safety of adding ketoprofen to pegylated-interferon (PEG-IFN) with or without ribavirin and the effect on viral kinetics, STAT1 activity and expression of 2'-5'-oligoadenylate synthetase (2'-5'OAS) in genotype 1 chronic hepatitis C in a phase II study., Methods: Forty-five patients were studied: fifteen were randomized to PEG-IFN plus ribavirin (PR), 16 to PEG-IFN plus ketoprofen and 14 to PR and ketoprofen. The molecular study of IFN-dependent signal transduction was conducted in 9 patients from each group., Results: The combination of ketoprofen and PEG-IFN with or without ribavirin was safe and well tolerated. An early activation of STAT1 was observed in ketoprofen-treated patients, but this activation was less sustained over time. Conversely, ketoprofen plus PEG-IFN and ribavirin induced an early and sustained increase of 2'-5'OAS transcription starting 24 h after the first dose until the 36th wk. These data are consistent with the clinical results, showing a better sustained virological response and a lower relapse rate in patients receiving ketoprofen plus PEG-IFN and ribavirin., Conclusion: The addition of ketoprofen to the standard therapy of chronic hepatitis C should be explored in larger randomized clinical studies.

We report here two cases of hepatocellular carcinoma (HCC) 90 and 70 months, respectively, after successful treatment with interferon (IFN) and ribavirin for hepatitis C virus (HCV)-related cirrhosis. A 50-year-old Caucasian man and a 66-year-old Caucasian woman with HCV-related cirrhosis were treated with IFN and ribavirin and in both cases a sustained virological response (SVR) was obtained with persistent normalization of serum aminotransferases and continuous disappearance of serum HCV-RNA. Both patients were subsequently followed up within an HCC surveillance programme based on biochemical and ultrasound (US) evaluation every 6 months and the appearance of HCC was detected 90 and 70 months, respectively, after discontinuation of therapy. We introduce these two cases to call attention to the importance of not underestimating the risk of HCC development even many years after complete HCV eradication, especially in the presence of established cirrhosis and concomitance of other risk factors for HCC.

Background: Efficacy and safety of interferon induction therapy alone or in combination with ribavirin or ribavirin plus amantadine were evaluated in chronic hepatitis C patients who were nonresponders to primary antiviral treatment., Methods: The study was designed to have 225 HCV nonresponder patients, but at an interim analysis the response rate difference between groups was lower than expected and the enrollment was stopped when 75 patients had been randomized to receive interferon-alpha2a (group A, n = 26), interferon-alpha2a plus 15 mg/kg per day of ribavirin (group B, n = 24), or interferon-alpha2a plus ribavirin plus 200 mg/day of amantadine hydrochloride (group C, n = 25). Treatment duration was 48 weeks. The dose of interferon was 6 MU/day for 4 weeks followed by 3 MU/day for the remaining 44 weeks., Results: On intention-to-treat, the sustained virological response at 24 weeks of follow-up was 11.5% in group A, 12.5% in group B, and 12% in group C. Therapy was discontinued because of adverse effects in three patients in group A (11.5%), three in group B (12.5%), and two in group C (8%)., Conclusions: Nonresponders with chronic hepatitis C may achieve a sustained virological response rate of approximately 12% if retreated with interferon induction treatment followed by administration of a daily dose. The addition of ribavirin or amantadine did not seem to improve the response rates.

Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal–oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results. [ABSTRACT FROM AUTHOR]

Abstract: Background: An early drop of HCV-RNA levels is useful in assessing response to antiviral treatment in chronic hepatitis C; the first recommended time point is 4 weeks after the start of therapy. Objectives: We evaluated retrospectively HCV-RNA and HCVAg levels at different time points to assess the clinical value of an early monitoring. Study design: Thirty-five patients with chronic hepatitis C infected by genotype 1b and consecutively enrolled in an open-label study on PegIFN plus Ribavirin and/or ketoprofene were tested for HCV-RNA (real-time PCR) and HCVAg (ARCHITECT) at baseline and after 1 and 2 days and 1, 2, 4 and 12 weeks after the start of treatment. Treatment response was assessed according to the EASL consensus criteria. Results: In the 17 sustained responders (SR) the median log decrease of HCV-RNA and HCVAg at the different time points was 0.40 and 0.37; 1.36 and 0.84; 1.47 and 0.97; 2.34 and 1.86; 2.51 and 2.32; 3.28 and 2.61, respectively. The best time point to predict SR was 2 weeks after the start of therapy, with a sensitivity, specificity and overall accuracy of 76.9%, 86.7% and 82.1% for HCV-RNA and 81.8%, 75.0% and 76.8% for HCVAg, respectively. Discussion: An early monitoring is at least equally effective than standard monitoring in predicting response to hepatitis C therapy. The similarity of HCV-RNA and HCVAg kinetics suggests that HCVAg may be useful in the early phases as a trigger to evaluate HCV-RNA levels at earlier time points for a personalized approach to therapy monitoring. [Copyright &y& Elsevier]