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Could New Antivirals Allow Patients With Previous Hepatitis C To Take Oral Antifungals?

While appropriate workup and liver function testing are key when considering oral antifungal use, this author says new medications for hepatitis C could open up the possibility of oral antifungal use for patients who previously could not take the medication. 

A major component of podiatric practice is the treatment of fungal infections. When using oral antifungals, one would thoroughly explore the past medical history of the patient, and any liver diseases would exclude the patient from taking oral antifungals. The patient’s medication history could also preclude the patient from taking oral antifungals if there are any strong drug-drug interactions involved.

Clinicians should also consider the standard precautions in regard to social history and alcohol use if necessary. We also educate the patient on the side effects of oral antifungals.

If the patient has no contraindications in his or her history, then one would order the standard chemistry panels and complete blood cell (CBC) counts. If liver function tests (LFTs) are normal, then the patient is a good candidate for the oral antifungals. If a patient has an abnormality in the LFTs, obtain a second set of LFTs to confirm the abnormalities. If the tests confirm the abnormalities, refer the patient to a hepatologist/gastroenterologist. This paradigm is clear. However, there is a new consideration with emerging hepatitis C antivirals.

What You Should Know About New Antivirals For Hepatitis C

Patients with chronic hepatitis C have options that offer a total cure. Interferons, which physicians have long used as treatment for chronic hepatitis B, D and C, are still available as a treatment in varying forms in combination with ribavirin. However, patient adherence to therapy is problematic as there are many side effects with interferon. Additionally, interferon therapy may aggravate preexisting autoimmunity, unmask silent autoimmune processes or even induce de novo autoimmune diseases.1 Resistance is also a problem with interferon therapy.

Direct acting antivirals, which disrupt viral replication and infection, are the latest class of drugs that target specific nonstructural proteins of hepatitis C. Like the antiretroviral therapy associated with HIV treatment, there are different classes of drugs including protease inhibitors, non-nucleoside polymerase inhibitors, nonstructural protein 5A polymerase inhibitors, and nonstructural protein 5B polymerase inhibitors.2

These drugs are available in varying combinations to optimize effectiveness and decrease the potential for resistance. Some of these medications include ledipasvir/sofosbuvir (Harvoni, Gilead Sciences), sofosbuvir/velpatasvir (Epclusa, Gilead Sciences) and glecaprevir/pibrentasvir (Mavyret, AbbVie).

The goal of antiviral therapy in patients with chronic hepatitis C virus has always been to eradicate the virus’ RNA. Attainment of a sustained virologic response (SVR), defined as an undetectable RNA level 12 weeks following the completion of therapy, determines an eradicated hepatitis C virus RNA.3 The HCV genotype, evidence of structural damage and previous treatment with any therapy determine the direct acting antiviral combination as the Food and Drug Administration’s indications are not the same for every drug.

After the patient attains a total fungus cure, monitor the patient’s LFTs, especially if there were any structural changes or damage to the liver as a result of the chronic viral infection.

Final Thoughts

The question is: should there be a change in our approach in the oral antifungal workup? The answer is no. One should treat those patients no different than a person without hepatitis C.4,5 However, given the direct acting antivirals, the end of the hepatitis C virus may be near. For podiatrists, a previously excluded group of patients do not have to automatically be excluded anymore from the use of oral antifungals.

Dr. Williams is a Diplomate of the American Board of Podiatric Medicine. She is in private practice in Bronx, NY.

References

1. Spengler U. Principles of interferon therapy in liver disease and the induction of autoimmunity. UpToDate. Available at  https://www.uptodate.com/contents/principles-of-interferon-therapy-in-liver-disease-and-the-induction-of-autoimmunity . Published Dec. 22, 2017.

2. Pockros P. Direct-acting antivirals for the treatment of hepatitis C virus infection. UpToDate. Available at https://www.uptodate.com/contents/direct-acting-antivirals-for-the-treatment-of-hepatitis-c-virus-infection . Published Aug. 24, 2017.

3. Jazwinski AB, Muir AJ. Direct-acting antiviral medications for chronic hepatitis C virus infection. Gastroenterol Hepatol. 2011; 7(3):154–162.

4. Vachon ML, Dieterich DT. The era of direct-acting antivirals has begun: the beginning of the end for HCV? Semin Liver Disease. 2011; 31(4):399-409.

5. Salvatore L. Personal communication, April 26, 2018.

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By Alecia Williams, DPM
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