Peginterferons alfa-2a -2b and ribavirin (Efficacy)

The efficacy of treatment of patients with chronic hepatitis C virus has improved markedly since the introduction of combination therapy with pegylated interferon (PEG) and ribavirin, especially in patients treated for the first time. Little information is available on treatment outcomes in individuals who do not respond adequately, although evidence suggests that certain polymorphisms may be involved.

Chronic hepatitis virus infection affects about 3% of the world's population and is one of the main causes of chronic liver disease. This infection can lead to cirrhosis in 20% to 30% of patients and to hepatocellular carcinoma in 1% to 4% of cases.

Combination treatment with antiviral drugs for a period of 12 to 24 weeks has become the standard of care for patients with hepatitis C virus (HCV) infection. The duration of treatment may vary depending on the genotype of the virus, the stage of the disease and other factors.

Antivirals to treat hepatitis C include hepatitis C protease inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors. These drugs act directly on HCV by inhibiting its replication and reducing the viral load in the body.

The treatment of boceprevir and telaprevir in combination with peginterferon alfa and ribavirin is a new therapeutic option for the treatment of chronic HCV infection. This therapy is called triple therapy and is used to treat patients with HCV genotype 1 infection.

Boceprevir and telaprevir are antiviral drugs that act directly on the virus and inhibit the virus protease, an enzyme necessary for viral replication. Peginterferon alfa belongs to the group of interferons, which are used as immunomodulators because they act on the immune system itself to stimulate the body's production of interferon, which helps fight infection. Ribavirin is an antiviral agent that helps reduce the amount of virus in the body.

There are six "classes" or subtypes of HCV, depending on the genetics of each of the strains (variants) of the virus. They are called "genotypes" and are named by number, from 1 to 6. The different genotypes condition a variable response to treatment. Genotype 1 is the most frequent (present in 75% of cases), but unfortunately these patients do not respond as well to treatment as those with the other genotypes. Traditionally, two types of therapy have been used:

  • Antivirals: they act directly on the virus, preventing its replication.
  • Interferons: these are a group of immunomodulators that act on the immune system itself, enhancing and maintaining an adequate defense against infection.

Since the two mechanisms can potentiate each other, there is a combined therapy, with two or three drugs, using both pathways at the same time.

Interferon is generally well tolerated and side effects requiring discontinuation of treatment are infrequent. However, a large proportion of patients cannot receive one of the most commonly used types of interferon because it interferes with other conditions (autoimmune, cardiac, hematological, among others), or they suffer severe adverse reactions to it. Because of this, alternative interferon-free regimens have been investigated, including the administration of combination therapy with new, more effective antivirals.

Treatment of chronic HCV infection also includes eating a well-balanced diet, drinking plenty of fluids, avoiding alcohol, and exercising. For end-stage liver disease, liver transplantation may be the only treatment option.

There is no effective vaccine that can prevent HCV infection; therefore, preventive measures should be aimed at avoiding infection with hygienic-sanitary improvements.

  • Patient prophylaxis: avoid all factors causing liver damage (alcohol, iron overload, hepatotoxic drugs). Vaccination against hepatitis A and B.
  • Environmental prophylaxis:
    • Vertical transmission: breastfeeding and type of delivery do not favor it, therefore breastfeeding should not be discouraged and pregnancy should not be contraindicated in women with chronic hepatitis due to HCV.
    • Horizontal transmission: avoid sharing shaving and depilation tools, toothbrushes, scissors, etc. In stable couples, the use of barrier methods is recommended to prevent sexual transmission due to its low incidence.

Genes analyzed

IFNL3

Bibliography

Abd Alla MDA, Dawood RM, Rashed HAE, et al. HCV treatment outcome depends on SNPs of IFNL3-Gene polymorphisms (rs12979860) and cirrhotic changes in liver parenchyma. Heliyon. 2023 Oct 19;9(11):e21194.

Muir AJ, Gong L, Johnson SG, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-α-based regimens. Clin Pharmacol Ther. 2014 Feb;95(2):141-6.

Nakamoto S, Imazeki F, Kanda T, et al. Association of IFNL3 Genotype with Hepatic Steatosis in Chronic Hepatitis C Patients Treated with Peginterferon and Ribavirin Combination Therapy. Int J Med Sci. 2017 Sep 4;14(11):1088-1093.

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