HCV New Drug Research

During HCV therapy dry mouth is a common irritating side effect, known clinically as xerostomia.

Xerostomia can lead to an increased risk for dental problems such as tooth decay, gum problems, mouth sores and other infections in the mouth.

Other drugs such as antidepressants also cause dry mouth, however, giving up that antidepressant during therapy just isn't going to happen. Unless you want channel your inner child, or Charlie Sheen, which isn't all that attractive. Well, either is interferon.

Interferon = Ugly
A point to ponder : Who remains attractive during therapy?

Not me! Interferon made this blogger so ugly that fear quickly engulfed my three teenagers. I celebrated, as each adolescent became increasingly kind to me - all at the same time, and it wasn't even Christmas! Who knew being under the "influence"of interferon would have its advantages?

Anyhoo, today on the blog are a few tips for dealing with that annoying side effect, and some insight into what happens to the salivary gland during therapy. I figured the gland just sort of died, but apparently it comes back to life after treatment.

So tell me, which drug is the culprit?

Well folks, from the December 2011 issue of Hepatitis Monthly we have a brief report entitled Ribavirin Impairs Salivary Gland Function in Hepatitis C Patients During Combination Treatment With Pegylated Interferon Alfa-2a, ya think?

To read the full text Click Here , or read the discussion provided below.

If you have mouth sores that cause you pain and discomfort, talk with your doctor. Side effects of magic mouthwash may include problems with taste, a burning or tingling sensation in the mouth, drowsiness, constipation, diarrhea, and nausea.
Click Here For More Information


Available Over The Counter

What Is Biotène?

Biotene Products:
Biotene Moisturizing Mouth Spray
Biotene Oral Balance Liquid
Biotene Oral Rinse
Biotene Dry Mouth Toothpaste
Biotene Dry Mouth Gum
Biotene Oral Balance Gel

The strength of the Biotène products lies in their ingredients: they contain antibacterial enzymes found naturally in human saliva. Together, these ingredients re-create the natural oral protection found in the mouth, providing antibacterial and healing properties. Only Biotène's bio-enzyme products can help maintain a healthy balance of oral flora, reducing harmful bacteria while sustaining beneficial bacteria. Recommended for everyone susceptible to cavities, bad breath, mouth sores, and gum disease.

Biotène contains three primary enzymes - Glucose Oxidase, Lactoperoxidase, and Lysozyme, which are carefully balanced for a special function in boosting and replenishing saliva's own defenses. When used daily, Biotène reduces harmful bacteria, but leaves beneficial bacteria necessary for healthy teeth and oral tissues.

Ribavirin Impairs Salivary Gland Function in Hepatitis C Patients DuringCombination Treatment With Pegylated Interferon Alfa-2a


Alessio Aghemo 1, Maria Grazia Rumi 2*, Sara Monico 1, Matteo Banderali 3, Antonio Russo 4,Francesco Ottaviani 3, Mauro Vigano 2, Roberta D’Ambrosio 1, Massimo Colombo 11 Migliavacca Center for Liver Disease, Division of Gastroenterology 1, IRCCS Fondazione Ca’ Granda Hospital, University of Milan, Milan, Italy2 Department of Hepatology, St. Joseph’s Hospital, University of Milan, Milan, Italy 3 Department of Clinical Sciences, “L. Sacco “Hospital, University of Milan, Milan, Italy4 Departments of Epidemiology and Biostatistics, San Carlo Borromeo Hospital, Milan, Italy

Hepat Mon.2012;11(11) :in press. DOI: 10.5812/kowsar.1735143X.733

A B S T R A C T

Background: Xerostomia is a common adverse event of unknown etiology
observed during pegylated interferon (PegIFN)/Ribavirin (Rbv) treatment.

Objectives: To assess the frequency and mechanisms of xerostomia
during PegIFN/Rbv therapy.

Patients and Methods: Thirty-one naïve patients with chronic hepatitis C
consecutively received PegIFN-α2a (180 αg/week) plus Rbv (800–1200 mg/day).
The controls were 10 patients with chronic hepatitis B who received PegIFN-α2a (180 αg/week). During treatment and follow-up, all patients underwent basal and masticatory stimulated sialometry, otorhinolaryngoiatric (ORL) examination, and a questionnaire survey to subjectively assess symptoms of oral dryness.

Results: Twenty-seven patients on PegIFN/Rbv and 4 on PegIFN
(87% vs. 40%, P = 0.006) reported xerostomia.

Thirty patients on PegIFN/Rbv combination therapy and 2 patients on monotherapy had ORL signs of salivary gland hypofunction (97% vs. 20%, P less then 0.0001). Mean basal (A) and stimulated (B) salivary flow rates mL/min)progressively decreased during PegIFN/Rbv treatment (A, 0.49 at baseline vs. 0.17 at the end of treatment, P less then 0.0001; B, 1.24 at baseline vs. 0.53 at the end of treatment, P = 0.0004).

At week 24 following PegIFN/Rbv treatment, salivary flow rates were similar to baseline (A, 0.53 at the end of follow-up vs. 0.49 at baseline; B, 1.19 at the end of follow-up vs. 1.24 at baseline). Salivary function was unaffected in monotherapy patients.

Conclusions:Rbv causes salivary gland hypofunction in hepatitis C patients receiving PegIFN/Rbv therapy,which promptly reverts to normal upon cessation of treatment.

Discussion Only

Click Here For PDF

Approximately 12% of all patients with HCV infection receiving PegIFN/Rbv therapy ultimately develop xerostomia, which in turn increases the risk of symptoms like dental cavities, nausea, and constipation.

Our study demonstrates that dry mouth occurring during anti-HCV
therapy results from a reversible inhibition of salivary gland function.
At the same time, we show that symptoms of mouth dryness are enhanced in HCV patients receiving PegIFN/Rbv therapy compared to HBV patients receiving monotherapy with PegIFN, indicating a direct role of Rbv.

Indeed, patients receiving PegIFN monotherapy showed no salivary dysfunction, while only a few of them reported mild and transient symptoms of mouth dryness. This is consistent with reports of the effects of other drugs such as antidepressants,where, similar to our PegIFN monotherapy patients, xerostomia is not directly caused by salivary gland impairment, as the secretory function of salivary glands is preserved (17).

In our study, no HCV or HBV patient required treatment with antidepressant drugs, ruling out any influence of these drugs on observed salivary flow rates.
While we ignore the pathogenetic mechanisms of Rbv-induced hyposialia, we may speculate that the changes in salivary flow in patients receiving PegIFN/Rbv might result from an alteration of exocytosis and/or liquid transport of the exocrine glands (18).

However,we acknowledge that unfortunately our study cannot provide any
information on this matter, as it was not designed for this endpoint. Moreover, we believe that the exact pathogenic mechanisms behind this observation can be unraveled only through studies evaluating sialochemistry and eventually by salivary gland biopsies in patients undergoing Pe-gIFN/Rbv therapy. Whatever the underlying mechanisms of Rbv-induced hyposialia, the absence of a correlation between hyposialia and Rbv dosing discourages Rbv dose-adjustment for patients with this undesired effect. Moreover, the recognition that salivary gland function is only temporarily impaired during PegIFN/Rbv treatment encourages counseling and treatment of the symptoms of hyposialia with oral hydration or administration of saliva substitutes.

Treatment of xerostomia by ORL specialists may improve the patient’s quality of life by attenuating the impairment of the sense of taste, halitosis, and interference with functions such as speech, chewing, and swallowing (19), thereby not ompromising adherence to Rbv dosing.

This finding has important clinical implications, since maintaining high Rbv doses will be essential in the future to maximize the antiviral effect of protease inhibitors of HCV replication, as recently shown by Phase II and III trials (20-23). While we acknowledge that the present study was conducted on a relatively small number of patients, we think that the prospective enrollment and the presence of a control group receiving PegIFN monotherapy allows the data generated here to be confidently extrapolated to clinical practice (24).
Moreover, the risk of intrapatient variations due to age, smoking or other unrecognized environmental factors was attenuated by the saliva flow tests carried out at different time points, and the risk of interpatient variation was eliminated by the 100% compliance of the study participants (25).

The enrollment of a control group of HCV patients receiving Rbv monotherapy in our study would have further reinforced our findings, effectively eliminating the possibility that HCV itself might play a role in the development of xerostomia, whilst also allowing us to precisely determine which drug is the causal agent of salivary gland hypofunction.

However,in the study design process we considered incorporating such a control group unethical, due to the minimal to no antiviral effect associated with Rbv monotherapy, coupled with the potentially serious adverse events linked to its intake (18).

In conclusion, this study demonstrates that Rbv is responsible for xerostomia occurring during anti-HCV therapy, causing transient salivary gland hypofunction that does not appear to be dose-dependent and is promptly reverted upon cessation of treatment.