Monday, October 4, 2010

Hepatitis C Treatment: Long-Term Effects

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For people treating HCV who reach SVR, the question often asked is *What are the long term benefits of reaching SVR, and or will HCV return years down the road.

Below I have highlighted the study : Click Here To Read The Full Paper.

"A comparison of hepatic histology before and 1 to 6.2 years after completion of interferon therapy showed improvement in 94% of patients"
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Long-Term Effects of Antiviral Therapy in Patients with Chronic Hepatitis C
Received 22 June 2010; Accepted 25 July 2010

The primary goal of treatment of chronic hepatitis C is to prevent late liver-related morbidity and mortality, and measurement of SVR is the short-term surrogate used to predict the long-term efficacy of antiviral therapy. The purpose of this concise paper is to summarize current knowledge on the impact of antiviral therapy on persistence of SVR and long-term outcomes, including impact on hepatic fibrosis, incidence of HCC, and life expectancy. These data provide a rationale for the early use of antiviral therapy not only to achieve an SVR but also to favorably impact the long-term prognosis of chronic hepatitis C.

Sustained Virological Response Persists Long Term
The earliest study demonstrating that a sustained response to antiviral therapy was associated with long-term biochemical and virological responses as well as histologic improvement was reported by Marcellin and colleagues from France. In this study of 80 patients who had a 6-month sustained biochemical and virologic response, mean followup of 4 years showed that 93% of patients had a persistently normal alanine aminotransferase (ALT) level, and 96% had undetectable serum HCV RNA. A comparison of hepatic histology before and 1 to 6.2 years after completion of interferon therapy showed improvement in 94% of patients, and HCV RNA was undetectable in the liver in 1 to 5 years after treatment in all 27 patients tested. In an analysis of 4 large trials in which 395 patients were followed after achieving an SVR with interferon alfa-2b with or without ribavirin, the actuarial likelihood of maintaining response after a mean 5-year followup was 99%    1%, with overall 10 patients (2.5%) developing detectable HCV RNA and all within 2 years of followup.

Thus, this analysis of a large study database confirmed that late relapse is rare in patients who remain HCV RNA negative 24 weeks after completion of interferon-based therapy. Multiple other studies, including one small study with a 10-year mean followup , showed that SVR predicts a high likelihood of long-term SVR.

One of these studies followed 344 patients for a median duration of 3.3 years (range, 0.5 to 18 years) after completion of interferon-based therapy with an SVR, and showed that serum HCV RNA remained undetectable in 1300 samples, indicating that none had a relapse with up to 18 years of followup . It is unclear if late detection of serum HCV RNA after an SVR in a small number of patients represents true relapse, especially if the detection occurs only once or is intermittent and with use of a very sensitive assay. Although additional followup studies may provide further clarification of this distinction, an SVR appears for now to be durable and an accurate reflection of a cure.

Conclusions

The long-term benefit of antiviral therapy, including reduction in hepatic fibrosis, lower incidence of HCC, and prolonged life expectancy, appears to be limited primarily to patients able to achieve an SVR.

A recent systematic review showed that health-related quality-of-life was also improved and that antiviral treatment is reasonably cost effective in treatment-naïve patients as well as relapsers and nonresponders . Therefore, clinicians should aim to treat with antiviral therapy, with the goal of achieving an SVR early in the natural history of chronic hepatitis C.

Direct acting antiviral (DAA) agents are expected to provide new treatment options for management of chronic hepatitis C in the near future. Telaprevir, an HCV NS3 protease inhibitor, in combination with peginterferon and ribavirin, induced SVR in approximately 70% of treatment-naïve genotype 1 patients and in 51% of patients who failed previous peginterferon plus ribavirin therapy .
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The increase in SVR rate using DAA agents may provide a long-term benefit to a wider variety of patients, including nonresponders to peginterferon and ribavirin therapy, and further improve the long-term outcomes of therapy including slowed fibrosis progression, reduced incidence of HCC, and prolonged life expectancy.

;The Study Covers:

Sustained Virological Response Persists Long Term

Natural History of Chronic Hepatitis C

Antiviral Therapy Improves Hepatic Fibrosis and Inflammation

Antiviral Therapy Is Associated with a Reduced Incidence of Hepatocellular Carcinoma

Life Expectancy Is Prolonged with Interferon-Based Therapy

Impact of Antiviral Therapy in Patients with Chronic Hepatitis C and Cirrhosis

Preventive Effect of Interferon on Recurrence of Tumor after Treatment of HCC

Impact of Maintenance Therapy on Outcomes of Chronic Hepatitis C with Advanced Fibrosis



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