Hepatitis C virus (HCV) infection is the most common blood-borne infection worldwide and an important health care problem (National Center for Health Statistics, 1996; National Institutes of Health, 1997), as it represents the leading indication for liver transplantation. Hepatitis C virus (HCV) is the major cause of transfusion non-A, non-B hepatitis and continues to be a major cause of human liver disease throughout the world. Approximately 20-30% of patients with chronic hepatitis C develop cirrhosis (Hoofnagle, 1997). The course of hepatitis C is variable among individuals, but it eventually can lead to chronic hepatitis, decompensated cirrhosis, and hepatocellular carcinoma.
The prevalence of HCV around the world ranges from 0.4 to 2%. Hepatitis C is gradually being recognised as a major health problem even in developing countries. Among Indian blood donors, the seroprevalence varies from 0.48% in Vellore, TN to 1.85% in New Delhi. Although it is not well established, hepatitis-C infections do not easily take place through the sexual route and is therefore regarded as a problem confined largely to drug injectors.
Researchers in India have identified, for the first time, two patients with chronic liver disease - a 46-year-old man and a 52-year-old woman, both from eastern India - who were found to be infected with hepatitis C virus genotype 6 strains. These strains have been previously reported only from Hong Kong and Southeast Asia.
Magnitude of hepatitis C virus infection in India: Prevalence in healthy blood donors, acute and chronic liver diseases. Link
Several advances in the management of chronic HCV infection have occurred in the last decade. More recent research has propelled a shift from interferon alfa monotherapy to combination therapy with pegylated interferon (peginterferon) and ribavirin as the standard treatment for chronic hepatitis C. Numerous clinical studies and review articles have been published in the recent literature, the aim of which is to investigate the efficacy of peginterferon versus standard interferon as monotherapy and combination therapy with ribavirin. Clearly defining the terminology of the treatment endpoints to better understand the clinical findings in these studies is important. An earlier review article used the following definitions:
* End-of-treatment response occurs on the basis of having no detectable HCV RNA (virologic response) at the end of the treatment.
* Sustained response occurs based on reference range ALT levels and no detectable HCV RNA at the end of the treatment and throughout the observation period after stopping the therapy. Sustained virologic response (SVR) is defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy.
* Nonresponse to treatment is when ALT levels remain abnormal at all time points evaluated during the study period or ALT levels become elevated (or HCV RNA appears) after having been in the reference range (or having no detectable HCV RNA) on treatment.
* A histologic response is defined as a reduction in the Knodell score of 2 or more points compared to the baseline (Lindsay, 1997).
Future targets of therapy
Combining peginterferons with ribavirin considerably improves efficacy but at the expense of poor tolerability attributable to ribavirin, and a significant proportion of patients in these trials did not respond to treatment. Given the significant adverse effects attributed to interferon-ribavirin therapy, patients need to be screened carefully to assess their candidacy for this therapy. Future therapeutic developments may include 1 or more of the following approaches: understanding the HCV genomic organization, elucidating the viral life cycle and HCV replication strategy, and understanding the immune mechanisms required for viral propagation or infectivity (Sookoian, 2003). Therapies under development and evaluation for patients with hepatitis C include adjunctive use of the antiviral agent amantadine and the immunomodulatory agent thymalfasin as well as novel small molecules, which include the ribavirin analogs, viramidine and levovirin, and BILN 2061, an inhibitor of HCV serine protease (Foster, 2004).
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