Article

Managing chronic hepatitis C in the difficult-to-treat patient

Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, United States
Liver international: official journal of the International Association for the Study of the Liver (Impact Factor: 4.85). 01/2008; 27(10):1297-310. DOI: 10.1111/j.1478-3231.2007.01613.x
Source: PubMed

ABSTRACT

Patients with chronic hepatitis C virus (HCV) infection and disease-related complications - among them cirrhosis and liver failure - pose a particular management challenge. Some of these patients may fail to respond to current therapy (non-responders), and some are affected so severely that treatment puts them at an unacceptable risk for complications. Treatment with pegylated interferon (peg-IFN) plus ribavirin improves hepatic enzyme levels and eradicates the virus in approximately 50% of patients; however, a significant number of patients do not respond to therapy or relapse following treatment discontinuation. Several viral, hepatic and patient-related factors influence response to IFN therapy; many of these factors cannot be modified to improve long-term outcomes. Identifying risk factors and measuring viral load early in the treatment can help to predict response to IFN therapy and determine the need to modify or discontinue treatment. Retreatment options for patients who have failed therapy are limited. Retreatment with peg-IFN has been successful in some patients who exhibit an inadequate response to conventional IFN treatment, particularly those who have relapsed. Consensus IFN, another option in treatment-resistant patients, has demonstrated efficacy in the retreatment of non-responders and relapsers. Although the optimal duration of retreatment and the benefits and safety of maintenance therapy have not been determined, an extended duration is likely needed. This article reviews the risk factors for HCV treatment resistance and discusses the assessment and management of difficult-to-treat patients.

Download full-text

Full-text

Available from: PubMed Central · License: CC BY
  • Source
    • "Clinical studies show that CIFN is effective for HCV infection [15,16]. Furthermore, several large multi-centre studies showed that patients with hepatitis C who do not respond to ordinary IFN-alpha therapy may benefit from re-administration of CIFN [17,18]. However, none of the the large clinical trials currently underway with CIFN for chronic hepatitis B have yet been reported. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Consensus interferon (CIFN) is a newly developed type I interferon. This multicentre, controlled trial was conducted to determine the efficacy of CIFN and to compare it with alpha-1b-interferon (IFN-alpha1b) in the treatment of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. 144 Patients were randomly assigned to receive 9 microg CIFN (CIFN group) or 50 microg INF-alpha1b (IFN-alpha group) subcutaneously 3 times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) levels and the non-detectability of serum hepatitis B virus DNA or HBeAg at the end of treatment and 24 weeks after stopping treatment. There was no statistically significant difference in the serological, virological and biochemical parameters between CIFN and IFN-alpha1b groups at the end of the therapy and follow-up period (p > 0.05). Overall, at the end of treatment, 7.0% (5/71) and 35.2% (25/71) of patients in the CIFN group showed a complete or partial response compared with 7.4% (5/68) and 33.8% (23/68) of the IFN-alpha group (p = 0.10). At 24 weeks after stopping treatment, 6.9% (5/72) and 37.5% (27/72) of patients in the CIFN group showed complete response or partial response compared with 7.1% (5/70) and 34.3% (24/70) of the IFN-alpha group (p = 0.10). These findings suggest that 9 microg CIFN is effective in the treatment of patients with HBeAg-positive chronic hepatitis B. It can gradually induce ALT normalization and HBV DNA clearance and HBeAg loss or HBeAg/HBeAb seroconversion.
    Full-text · Article · Feb 2009 · Virology Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: More than 3% of the world population is chronically infected with hepatitis C virus. Brazilian prevalence is about 2%. Nowadays the best treatment for chronic hepatitis C is the combination of Peg Interferon a plus ribavirin with 55% of patients presented viral clearance after 6 or 12 months of therapy. Side effects are very frequent, occurring in 20-30% of patients. Nutritional status is well recognized as a prognostic factor to these patients. Aim: The aim of this study was evaluate the nutritional status of hepatitis C patients submitted to antiviral therapy with Peg Interferon á and ribavirin. Methods: Twenty nine patients with agebetween 18 and 70 years with chronic hepatitis C or compensated cirrhosis were followed nutritional parameters were evaluated: subjective global assessment (adjusted to liver disease), weight, high, body mass index, muscle arm circumference and triceps skinfold thickness. Biochemical tests as glucose and hemoglobin were evaluated too. Results: During therapy 93.1% of the patients lose weight. In according to fat stores all male patients were eutrophics whereas 25% of female showed signs of malnutrition. Considering the somatic protein compartment 84.6% of male were malnourished compared to 37.5% of females. Patients with depression and nauseas lost more weight. Conclusion: Hepatitis C patients on antiviral treatment lose weight and show malnutrition signs evaluated through the fat and proteic stores meas urements. Nutritional treatment should be made during antiviral therapy reducing the side effects impact and improving the final results.
    No preview · Article ·
  • [Show abstract] [Hide abstract]
    ABSTRACT: Specific antibodies against poly(ethylene glycol) (anti-PEG) were induced in animals following exposure to PEG-conjugated proteins and particles, resulting in rapid clearance of PEG-conjugated agents. In humans, induction of anti-PEG was observed following exposure to a PEG-conjugated drug, and pre-existing anti-PEG was identified in over 25% the healthy population. In clinical studies, the presence of anti-PEG was strongly associated with rapid clearance of PEG-asparaginase and PEG-uricase. PEGylation of therapeutic agents will continue to be of significant value in medicine to reduce immunogenicity, antigenicity and toxicity as well as markedly reducing renal clearance, while maintaining drug efficacy. It is important to recognize that PEG itself may possess antigenic and immunogenic properties. Further comprehensive studies are warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents and if confirmed in a prospective trial, patients should be screened and monitored for anti-PEG, and strategies developed to overcome the potential negative effect of anti-PEG on drug clearance to improve the effectiveness of therapy.
    No preview · Chapter · Jan 1970
Show more