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Volume 4, Supplement 1, 2004

Volume 4, Supplement 1, 2004

Table of Contents

Host Factors Affecting the Outcome of Treatment of Hepatitis C
The development of peginterferon and ribavirin combination therapy has significantly improved the sustained virologic response (SVR) rates in patients with chronic hepatitis C. However, poor patient adherence to therapy negatively influences drug levels and drug exposure, often preventing the development of an inhibitory drug level. To optimize patient adherence, the clinician must recognize factors predicting low adherence and negotiate a treatment plan that the patient understands and to which he or she commits. If adverse effects become intolerable, continuing patients on a reduced dose rather than withdrawing treatment seems to confer considerable advantage in preserving the chance for attaining an SVR. Results of a head-to-head comparison have demonstrated the possibility that, in cases of dose reduction, levels of peginterferon alfa-2a could remain above the limit of detection, whereas those of peginterferon alfa-2b might not. [Rev Gastroenterol Disord. 2004;4(suppl 1):S3-S7]
Viral Factors Affecting the Outcome of Therapy for Chronic Hepatitis C
The advent of sensitive virologic assays to quantify hepatitis C virus (HCV) RNA and to differentiate specific genotypes of HCV has greatly expanded our understanding of the pathogenesis of chronic hepatitis C. These molecular virologic techniques are regularly employed to assist with management decisions regarding antiviral therapy. Genotype is the strongest predictor of a sustained virologic response (SVR). The dynamic change of HCV RNA during treatment, defined at week 12 as early virologic response (EVR), is useful for identifying individuals who are unlikely to have an SVR. Discontinuation of therapy can be considered for those patients with genotype 1 when an EVR is not achieved. However, limitations exist regarding interpretation of EVR and treatment decisions must be individualized, particularly when other endpoints of therapy, such as histological response or treatment of extrahepatic manifestations are being considered. [Rev Gastroenterol Disord. 2004;4(suppl 1):S8-S13]
Epidemiology and Treatment Outcomes of Patients with Chronic Hepatitis C and Genotypes 4 to 9
Pivotal clinical trials of antiviral therapy for chronic hepatitis C have been conducted predominantly in Europe and the United States, where most patients are infected with genotypes 1, 2, or 3. As a result, published data on the outcomes of therapy in patients infected with genotypes 4, 5, and 6 to 9 are limited. However, a major proportion of patients with chronic hepatitis C worldwide reside in geographic areas where genotypes 4 (Africa and the Middle East), 5 (South Africa), or 6 to 9 (southern China and Southeast Asia) are prevalent or even the most common genotypes. The epidemiology of hepatitis C virus genotypes 4 to 9 is reviewed, and the studies reporting the results of antiviral therapy of these genotypes are summarized. The limited data on antiviral therapy in patients with genotypes 4 to 9 highlight the need for further and controlled treatment trials in these populations. [Rev Gastroenterol Disord. 2004;4(suppl 1):S14-S21]
Management of Patients with Chronic Hepatitis C Virus Infection and Previous Nonresponse
The treatment of patients with chronic hepatitis C virus infection has improved dramatically over the past several years. Despite this, more than half of all patients with genotype 1 fail to achieve a sustained virologic response (SVR) following therapy. The decision to retreat a nonresponder should balance two major factors: the likelihood that the patient will achieve an SVR during retreatment and the likelihood that the patient will develop progressive fibrosis and cirrhosis within the next 5 to 10 years (before more effective therapy is developed). Recent data have demonstrated that about 18% of all patients with previous nonresponse to standard interferon therapy (with or without ribavirin) will achieve an SVR when retreated with peginterferon and ribavirin. However, no therapy has been shown to be effective for patients with nonresponse to peginterferon and ribavirin. The approach to such patients is based on correcting the factors that led to this nonresponse. Maintenance peginterferon therapy is currently being explored but is likely to be of benefit in only a select group of nonresponders. The management of patients who have failed to achieve SVR is, therefore, one of the most complicated issues in the spectrum of treating chronic hepatitis C. This article reviews the factors to consider when assessing nonresponders for additional therapy and options for patients with continued nonresponse. [Rev Gastroenterol Disord. 2004;4(suppl 1):S22-S30]
Treatment of Chronic Hepatitis C in Patients with Decompensated Cirrhosis
Cirrhosis due to chronic hepatitis C is now the leading indication for liver transplantation in the United States. Current data from existing clinical trials suggest that 41% of patients with genotype 1 hepatitis C virus infection (HCV) and 73% with genotype 2 or 3 infection with advanced fibrosis or early compensated cirrhosis can achieve sustained virologic response (SVR) to antiviral therapy. However, response to therapy declines with severity of liver disease and nonresponse to prior interferon-based regimens. Although SVR rates are low in patients with decompensated cirrhosis, on-treatment clearance of HCV from blood occurs in about 30% of those with genotype 1 infection and 80% of those with genotype 2 or 3. In addition, recent reports suggest that pretransplantation clearance of HCV RNA from blood may reduce the risk of HCV recurrence after transplantation. In the absence of a virologic cure, maintenance therapy with peginterferon may slow disease progression and reduce the rate of clinical decompensation. [Rev Gastroenterol Disord. 2004;4(suppl 1):S31-S38]
Current Status of the Use of Growth Factors and Other Adjuvant Medications in Patients Receiving Peginterferon and Ribavirin
Hepatitis C virus (HCV) is the most common chronic infection in the United States, affecting almost 3.9 million Americans. The most effective treatment for chronic HCV infection is combination antiviral therapy with peginterferon and ribavirin. However, combination therapy is also associated with significant adverse effects and is contraindicated in certain patient populations. Hematological adverse effects are common and are a frequent cause of dose reduction and interruption or discontinuation of therapy. Currently there are no approved treatments for the hematological adverse events associated with HCV therapy. However, emerging data suggest that utilization of hematopoietic growth factors can provide a useful adjunct to treatment and optimize sustained virologic response rates. [Rev Gastroenterol Disord. 2004;4(suppl 1):S39-S47]
HCV and HIV: A Tale of Two Viruses
Liver disease has emerged as a major cause of morbidity and mortality in patients infected with the human immunodeficiency virus. Hepatic injury is highly associated with hepatitis C virus (HCV) infection, though hepatitis B virus and drug-induced hepatotoxicity are also important cofactors. HCV coinfection is linked to increased hepatic fibrosis progression, leading to development of cirrhosis and liver failure earlier than in HCV monoinfected patients. Initiation of highly active antiretroviral treatment regimens may paradoxically increase HCV viral loads. Some data suggest that HCV coinfection may hasten progression to AIDS, but this remains controversial. Three major randomized clinical trials demonstrate improved efficacy of peginterferon with ribavirin for treatment of HCV in coinfected subjects compared to those with HCV alone. However, response rates are lower than those observed in patients with HCV monoinfection. Sustained virologic response rates of 27% to 40% are reported. [Rev Gastroenterol Disord. 4(suppl 1):S48-S54]