Antiviral therapy in HCV-infected decompensated cirrhotics.

Decompensated cirrhosis has traditionally been considered a contraindication to interferon and ribavirin therapy. Whereas, the same may be true for advanced cirrhosis, which is only successfully amenable to liver transplantation (LT), there are reports in the literature in which antiviral therapy was given successfully in selected cases of early hepatic decompensation with an aim to attain sustained viral clearance, halt disease progression, and expect potential (though, often, partial) recovery of hepatic metabolic activity. Antiviral therapy may also be instituted to prevent hepatitis C recurrence after LT (it has even caused removal of some patients from the waiting list for LT). Thus, decompensation per se is no more an absolute contraindication to antiviral therapy. Nonetheless, considering that a large proportion of such patients have pre-existing hematological cytopenias, modifications in antiviral dose regimens and close monitoring is required in order to prevent worsening of the same. Although the final sustained virological response rates attained in these patients are relatively low, successful antiviral therapy is potentially lifesaving which explains the need to go for it. In this article, the pros and cons of antiviral therapy in decompensated liver cirrhosis are reviewed with special emphasis on how to avoid antiviral dose reductions/withdrawals secondary to the development of hematologic side effects by using hematopoietic growth factors.

Managing HCV infection in pediatric age group: suggested recommendations.

Hepatitis C virus (HCV) infection in children is different from the adult infection in many ways, like natural course of the disease; duration, therapeutic response and side effects profile of the drug therapy; and prognosis. Special considerations include consideration on what could be the appropriate time to investigate a suspected child, when to institute drug therapy and how to prevent vertical transmission. Although over the past one decade many landmark studies have greatly increased our insight on this subject, yet we are far from developing a consensus statement. In this article, a concise yet comprehensive review of HCV infection in children - diagnosis and treatment - is given, followed by suggested recommendations at the end. It is hoped that these recommendations will help develop local guidelines on this subject.

Considerations in the management of hepatitis C virus-related thrombocytopenia with eltrombopag.

Thrombocytopenia is a common clinical problem in HCV-infected cases. Multiple studies have consistently shown a rise in platelet count following a successful HCV treatment thus proving a cause-effect relationship between the two. Although, many therapeutic strategies have been tried in the past to treat HCV-related thrombocytopenia (e.g. interferon dose reductions, oral steroids, intravenous immunoglobulins, splenectomy etc), the success rates have been variable and not always reproducible. After the cessation of clinical trials of PEG-rHuMGDF due to immunogenecity issues, the introduction of non-immunogenic second-generation thrombopoietin-mimetics (eltrombopag and Romiplostim) has opened up a novel way to treat HCV-related thrombocytopenia. Although the data is still sparse, eltrombopag therapy has shown to successfully achieve the primary endpoint platelet counts of >/=50,000/muL in phase II& III, randomized, double-blind, placebo-controlled trials. Likewise, though it is premature to claim safety of this drug especially in high-risk patient groups, reported side effects in the published literature were of insufficient severity to require discontinuation of the drug. Based on the current and emerging evidence, a review of the pharmacologic basis, pharmacokinetics, therapeutic efficacy, safety profile and future considerations of eltrombopag in the context of HCV-related thrombocytopenia is given in this article. A MEDLINE search was conducted (1990 to August 2009) using the search terms eltrombopag, HCV, thrombocytopenia.

Role of hematopoietic growth factors as adjuncts in the treatment of chronic hepatitis C patients.

Drug-induced hematotoxicity is the most common reason for reducing the dose or withdrawing ribavirin (RBV) and interferon (IFN) therapy in chronic hepatitis C, which leads to the elimination of a possible cure for the patient. Traditionally, severe anemia and neutropenia have been considered as absolute contraindications to start antiviral therapy. This has not however, been the case since the advent of adjunct therapy with hematopoietic growth factors (erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF)). Some recent landmark studies have used this adjunct therapy to help avoid antiviral dose reductions. Although the addition of this adjunct therapy has been shown to significantly increase the overall cost of the treatment, this extra cost is worth bearing if the infection is cured at the end of the day. Although more studies are needed to refine the true indications of this adjunct therapy, determine the best dose regimen, quantify the average extra cost and determine whether or not the addition of this therapy increases the sustained virological response rates achieved, the initial reports are encouraging. Therefore, although not recommended on a routine basis, some selected patients may be given the benefits of these factors. This article reviews the current literature on this subject and makes a few recommendations to help develop local guidelines.