Managing Chronic Hepatitis C in the Difficult-To-Treat Patient
Managing Chronic Hepatitis C in the Difficult-To-Treat Patient
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 ~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.
As the most common blood-borne pathogen in the United States, hepatitis C virus (HCV) is an escalating healthcare concern. Approximately 60-85% of patients acutely infected with HCV progress to chronic disease, defined as the presence of HCV RNA in the blood for more than 6 months. The National Center for Health Statistics recently estimated that 1.3% of the US population - or 3.2 million people - have chronic HCV infection. The prevalence of infection is highest among patients aged 40-49 years; as these individuals age and the disease progresses (Figure 1), HCV-related complications will become more evident and severe.
(Enlarge Image)
Figure 1.
Natural history of hepatitis C virus (HCV) infection. [Reprinted from Postgraduate Medical Journal, Lo Ro viii et al. "Management of Chronic hepatitis C" 2005; 81: 378; with permission from BMJ Publishing Group Ltd (4).]
Among individuals with chronic HCV infection, 15-20% progress to end-stage liver disease. Cirrhosis and hepatocellular carcinoma, in particular, are life-threatening complications, with an estimated 42% of cirrhosis and 48% of liver cancer cases in the United States, Canada and Cuba attributed to chronic HCV infection. HCV-induced liver disease results in 8000-10 000 US deaths each year.
Achieving viral eradication is the goal of antiviral therapy and is defined by sustained virological response (SVR; Table 1 ). The rates of SVR have increased with improvements in antiviral therapy. SVR rates with interferon (IFN) monotherapy are approximately 6-12%, increasing to 38-42% with conventional IFN and ribavirin (RBV), and increasing as high as 55% in major clinical trials of pegylated IFN (peg-IFN) and RBV. Regardless, the number of patients infected with HCV who are at risk for continued hepatic injury is substantial.
Although some factors that influence SVR rates, such as inadequate dosage, inappropriate management of side effects and early dose reductions, may be corrected, others, such as HCV genotype, baseline viral load, race and age, cannot be specifically modified to improve outcomes. Ongoing alcohol and substance abuse has also been shown to contribute to the failure of IFN-based treatment, as well as the development of hepatocellular carcinoma. Identifying the risk factors for poor response can aid clinicians in predicting response and making treatment and retreatment decisions. The patient who does not respond to or who fails prior therapy and is referred for new treatment options poses a particular challenge; for example, a patient who discontinues therapy because of treatment-related adverse effects would have to be carefully evaluated before starting subsequent IFN-based retreatment, especially to determine appropriate management of complications. This article describes viral and host-related risk factors for poor treatment response to initial IFN therapy, evaluates current pharmacological options for the difficult-to-treat HCV-infected population and discusses methods to predict potential treatment failure.
Abstract and Introduction
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 ~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.
Introduction
As the most common blood-borne pathogen in the United States, hepatitis C virus (HCV) is an escalating healthcare concern. Approximately 60-85% of patients acutely infected with HCV progress to chronic disease, defined as the presence of HCV RNA in the blood for more than 6 months. The National Center for Health Statistics recently estimated that 1.3% of the US population - or 3.2 million people - have chronic HCV infection. The prevalence of infection is highest among patients aged 40-49 years; as these individuals age and the disease progresses (Figure 1), HCV-related complications will become more evident and severe.
(Enlarge Image)
Figure 1.
Natural history of hepatitis C virus (HCV) infection. [Reprinted from Postgraduate Medical Journal, Lo Ro viii et al. "Management of Chronic hepatitis C" 2005; 81: 378; with permission from BMJ Publishing Group Ltd (4).]
Among individuals with chronic HCV infection, 15-20% progress to end-stage liver disease. Cirrhosis and hepatocellular carcinoma, in particular, are life-threatening complications, with an estimated 42% of cirrhosis and 48% of liver cancer cases in the United States, Canada and Cuba attributed to chronic HCV infection. HCV-induced liver disease results in 8000-10 000 US deaths each year.
Achieving viral eradication is the goal of antiviral therapy and is defined by sustained virological response (SVR; Table 1 ). The rates of SVR have increased with improvements in antiviral therapy. SVR rates with interferon (IFN) monotherapy are approximately 6-12%, increasing to 38-42% with conventional IFN and ribavirin (RBV), and increasing as high as 55% in major clinical trials of pegylated IFN (peg-IFN) and RBV. Regardless, the number of patients infected with HCV who are at risk for continued hepatic injury is substantial.
Although some factors that influence SVR rates, such as inadequate dosage, inappropriate management of side effects and early dose reductions, may be corrected, others, such as HCV genotype, baseline viral load, race and age, cannot be specifically modified to improve outcomes. Ongoing alcohol and substance abuse has also been shown to contribute to the failure of IFN-based treatment, as well as the development of hepatocellular carcinoma. Identifying the risk factors for poor response can aid clinicians in predicting response and making treatment and retreatment decisions. The patient who does not respond to or who fails prior therapy and is referred for new treatment options poses a particular challenge; for example, a patient who discontinues therapy because of treatment-related adverse effects would have to be carefully evaluated before starting subsequent IFN-based retreatment, especially to determine appropriate management of complications. This article describes viral and host-related risk factors for poor treatment response to initial IFN therapy, evaluates current pharmacological options for the difficult-to-treat HCV-infected population and discusses methods to predict potential treatment failure.
Source...