Taurine, Coenzyme Q10, and Hydrogen Water Prevents Germanium Dioxide-Induced Mitochondrial Dysfunction and Associated Sensorineural Hearing Loss in mouse.

Mitochondrial dysfunction has been implicated in numerous common diseases as well as aging and plays an important role in the pathogenesis of sensorineural hearing loss (SNHL). In the current study, we showed that supplementation with germanium dioxide (GeO2) in CBA/J mice resulted in SNHL due to the degeneration of the stria vascularis and spiral ganglion, which were associated with down-regulation of mitochondrial respiratory chain associated genes and up-regulation in apoptosis associated genes in the cochlea. Supplementation with taurine, coenzyme Q10, or hydrogen-rich water, attenuated the cochlear degeneration and associated SNHL induced by GeO2. These results suggest that daily supplements or consumption of antioxidants, such as taurine, coenzyme Q10, and hydrogen-rich water, may be a promising intervention to slow SNHL associated with mitochondrial dysfunction.

Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype.

Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity). MT-RNR1 is a gene that encodes the 12s rRNA subunit and is the mitochondrial homologue of the prokaryotic 16s rRNA. Some MT-RNR1 variants (i.e., m.1095T>C; m.1494C>T; m.1555A>G) more closely resemble the bacterial 16s rRNA subunit and result in increased risk of aminoglycoside-induced hearing loss. Use of aminoglycosides should be avoided in individuals with an MT-RNR1 variant associated with an increased risk of aminoglycoside-induced hearing loss unless the high risk of permanent hearing loss is outweighed by the severity of infection and safe or effective alternative therapies are not available. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of aminoglycosides based on MT-RNR1 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).

Assessing ototoxicity and patients' satisfaction of topical local anaesthesia in myringotomy and ventilation tube insertion.

OBJECTIVES: Animal studies have suggested that exposure of the middle ear to topical local anaesthesia may be ototoxic. This study aimed to report sensorineural hearing outcomes and patients' satisfaction in those who underwent myringotomy and ventilation tube insertion using topical local anaesthesia. METHODS: Twenty-nine patients (32 ears) were operated on. Pre- and post-operative audiology findings were compared. A Likert-type questionnaire on treatment satisfaction was completed at the end of the procedure. RESULTS: Median patient age was 55 years (range, 27-88 years). Pre- and post-operative bone conduction pure tone averages were 26.76 dB and 25.26 dB respectively (mean reduction of -1.22 dB, 95 per cent confidence interval of -5.91 to 8.13 dB; p = 0.7538). One ear (3 per cent) had a reduction in pure tone average of 10 dB. CONCLUSION: The results suggest that sensorineural hearing loss is not a complication of ear exposure to topical local anaesthesia during myringotomy and ventilation tube insertion. The procedure was well perceived.

SENS-401 Effectively Reduces Severe Acoustic Trauma-Induced Hearing Loss in Male Rats With Twice Daily Administration Delayed up to 96 hours.

HYPOTHESIS: SENS-401 (R-azasetron besylate) is effective against severe acoustic trauma-induced hearing loss. BACKGROUND: SENS-401 has calcineurin inhibiting properties and attenuates cisplatin-induced hearing loss in a rat model. Cisplatin-induced and acoustic trauma-induced hearing loss share common apoptotic pathways. METHODS: The dose-response relationship of SENS-401 (6.6 mg/kg BID, 13.2 mg/kg BID, 26.4 mg/kg QD) and treatment time-window (13.2 mg/kg BID starting 24, 72, and 96 h posttrauma) versus placebo for 28 days were evaluated in a male rat model of severe acoustic trauma-induced hearing loss (120 dB SPL, 2 h) using auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) measures followed by cochlear outer hair cell (OHC) counting with myosin-VIIa immunolabeling. RESULTS: All SENS-401 doses improved ABR threshold shift and recovery, reaching statistical significance (p < 0.05) for ABR threshold recoveries after 28-days treatment. DPOAE amplitude loss and recovery improved markedly for 13.2 mg/kg BID SENS-401, reaching significance after 14 days (p < 0.05). Significant improvements in ABR threshold shifts/recovery and DPOAE amplitude loss occurred with up to 96-hours delay in initiating SENS-401 (p < 0.05), and in DPOAE amplitude recovery with up to 72-hours delay (p < 0.05). Significantly more surviving OHCs were present after SENS-401 treatment compared with placebo after 24 to 96-hours delay posttrauma, with up to 5.3-fold more cells in the basal cochlea turn. CONCLUSIONS: In vivo data support the otoprotective potential of twice daily oral SENS-401. Improvements in hearing loss recovery make SENS-401 a promising clinical candidate for acoustic trauma-induced hearing loss, including when treatment is not initiated immediately.

Cochlear implant in Thalassemia patient - Case report.

INTRODUCTION: Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin. Iron overload occurs in thalassemia, with blood transfusion therapy being the major cause. Deferoxamine continues to be the mainstay of therapy to remove excess iron in patients requiring long-term transfusions. One of the most important complications of deferoxamine therapy is neurosensory toxicity, including sensorineural hearing loss (SNHL). Labyrinthine hemmorhage (LH) is thought to result from altered capillary hemodynamics or reperfusion injury. It is theorized that LH incites a reparative response that cascades from fibrosis to sclerosis and ultimately ossification of the inner ear structures. CASE PRESENTATION: We present a case of 3-year-old thalassemic child with bilateral profound sensorineural hearing loss. Patient was on regular blood transfusions with chelation therapy. HRCT temporal bone and MRI brain and temporal bone had features of labyrinthitis ossificans (LO). Child underwent uniateral cochlear implantation and postimplantation speech perception and production outcomes were normal. DISCUSSION: This case illustrates the unique feature of labyrinthitis ossificans in a thalassemia patient which has not yet reported in the English literature. Hearing screening of all thalassemia patients and therefore early diagnosis of SNHL prompts early intervention and improved quality of life.

Beta cell function and clinical course in three siblings with thiamine-responsive megaloblastic anemia (TRMA) treated with thiamine supplementation.

Three siblings with thiamine-responsive megaloblastic anemia (TRMA) with a homozygous c.454delGGCATinsAT mutation in SLC19A2 are described. The index case presented at 14 months' old with severe non-ketotic hyperglycemia, dehydration, seizures and sinovenous thrombosis. She was started on insulin and developed sensorineural hearing loss around 2 years old. Two siblings were found to have the same mutation and were started on thiamine. One sibling developed transient hyperglycemia after several years of thiamine supplementation of 12 mg/kg that resolved with an increased thiamine dose (23 mg/kg). A younger sibling continues to remain diabetes-free on thiamine (24 mg/kg). The clinical course in this family suggests that there is an effect of thiamine on pancreatic beta cell function in patients with TRMA given the resolution of impaired fasting glucose with increasing thiamine dose in one sibling and the lack of diabetes to date in the siblings that were treated early with thiamine.

Protective Effect of Selenium Against Cisplatin-Induced Ototoxicity in an Experimental Design.

Cisplatin is an effective chemotherapeutic agent in the treatment of several types of malignant solid tumors but its clinical use is associated with ototoxicity. In the present study, we investigated the effect of selenium administration on lipid peroxidation (malondialdehyde [MDA]) and cisplatin-induced ototoxicity in rats. Healthy wistar albino rats (n = 21) were randomly divided into 3 groups: control (C), cisplatin (Cis), cisplatin and selenium (Cis+Se). Cisplatin was administered for 3 days to Cis and Cis+Se groups. Cis+Se group received selenium 5 days before cisplatin injection and continued for 11 consecutive days. Hearing thresholds and lipid peroxidation (MDA) levels of the rats were recorded before injections and at the end of experimental protocol. The cochleas of animals were harvested for histologic and immunuhistochemical examinations. In biochemichal analyses, pretreatment with selenium prevented the elevation of MDA levels in Cis+Se group rats. Moreover, animals in Cis+Se group had better hearing threshold levels than animals in cis group. Samples obtained from the animals in Cis group revealed extensive loss of the normal microarchitecture of the organ of Corti. On the other hand, animals in Cis+Se group exhibited a preservation of the morphology of the organ of Corti and outer hair cells. In the immunohistochemical examinations of cochlear tissues stained with anti-caspase-3, a higher degree of immunopositivity was found in the Cis group. When Cis+Se group and Cis group were compared, significantly less immunopositivity occurred in the Cis+Se group (P < 0.05). Thus, it appears that pretreatment with selenium may reduce cisplatin-induced ototoxicity in rats.

Intraperitoneal curcumin and vitamin E combination for the treatment of cisplatin-induced ototoxicity in rats.

INTRODUCTION: Cisplatin ototoxicity is characterized by irreversible, progressive, bilateral sensorineural hearing loss at high frequencies, accompanied by tinnitus. The aim of this study is to demonstrate the protective action of curcumin alone or in combination with vitamin E against cisplatin-induced ototoxicity in animal models. MATERIAL AND METHODS: The study included 42 rats. Experimental animals were randomized into 6 groups. In the first group, intra-peritoneal cisplatin was administered alone. In the second group, intra-peritoneal cisplatin and curcumin were administered together. In the third group, intra-peritoneal cisplatin and vitamin E were administered together. In the fourth group, intra-peritoneal cisplatin was administered together with curcumin in combination with vitamin E. In the fifth group, intra-peritoneal curcumin was administered alone. The sixth group was sacrificed directly without administration of any drugs. A distortion product otoacoustic emission (DPOAE) test was applied to both ears of all experimental animals. Curcumin was administered 1 h before cisplatin treatment continued for three successive days. Vitamin E was administered only as a single dose 30 min prior to cisplatin. All animals were sacrificed following DPOAE testing on the 5th day of cisplatin administration. Histopathological findings included a TUNEL (TdT-mediated deoxyuridine triphosphate nick end-labeling) assay, and the percentage of apoptotic cells was calculated. DPOAE values and the percentage of apoptotic cells were compared before and after treatment and between experimental groups. RESULTS: In Group 1, DPOAE values were significantly decreased at all frequencies (3000 Hz, 4000 Hz and 6000 Hz; P < 0.05). In Groups 2, 3, 4 and 5 there was no significant difference between the pre- and post-treatment DPOAE results (p > 0.05). Apoptotic index values were lower in all treatment groups compared to the cisplatin group, however the difference was only statistically significant in group 3 (p = 0.009). CONCLUSION: In rats, cisplatin ototoxicity can be prevented with curcumin or curcumin-vitamin E combination.

Sensorineural deafness following routine transurethral resection of the prostate.

A man in his 50s presented to a rural Australian emergency department with complete unilateral hearing loss following transurethral resection of the prostate. His hearing impairment progressed from 'muffled hearing' with tinnitus on emergence from anaesthesia, to total sensorineural deafness by day three. His surgery and anaesthesia were uncomplicated and he had remained normotensive throughout. He had no pre-existing auditory disease. He had received 240 mg of intravenous gentamicin intraoperatively for surgical prophylaxis. Renal function was normal. Brain imaging was negative for structural pathology, stroke and circulatory insufficiency. Ear nose and throat advised 7 days of oral corticosteroids, transtympanic dexamethasone and hyperbaric oxygen therapy. A working diagnosis of gentamicin-induced ototoxicity was applied. Intervention has proven unsuccessful and there is no possibility for rehabilitation. The patient is permanently disabled.

Designer aminoglycosides prevent cochlear hair cell loss and hearing loss.

Bacterial infections represent a rapidly growing challenge to human health. Aminoglycosides are widely used broad-spectrum antibiotics, but they inflict permanent hearing loss in up to ~50% of patients by causing selective sensory hair cell loss. Here, we hypothesized that reducing aminoglycoside entry into hair cells via mechanotransducer channels would reduce ototoxicity, and therefore we synthesized 9 aminoglycosides with modifications based on biophysical properties of the hair cell mechanotransducer channel and interactions between aminoglycosides and the bacterial ribosome. Compared with the parent aminoglycoside sisomicin, all 9 derivatives displayed no or reduced ototoxicity, with the lead compound N1MS 17 times less ototoxic and with reduced penetration of hair cell mechanotransducer channels in rat cochlear cultures. Both N1MS and sisomicin suppressed growth of E. coli and K. pneumoniae, with N1MS exhibiting superior activity against extended spectrum ß lactamase producers, despite diminished activity against P. aeruginosa and S. aureus. Moreover, systemic sisomicin treatment of mice resulted in 75% to 85% hair cell loss and profound hearing loss, whereas N1MS treatment preserved both hair cells and hearing. Finally, in mice with E. coli-infected bladders, systemic N1MS treatment eliminated bacteria from urinary tract tissues and serially collected urine samples, without compromising auditory and kidney functions. Together, our findings establish N1MS as a nonototoxic aminoglycoside and support targeted modification as a promising approach to generating nonototoxic antibiotics.

Investigation of protective role of curcumin against paclitaxel-induced inner ear damage in rats.

OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate the potential protective effect of curcumin on paclitaxel-induced ototoxicity in rats by means of immunohistochemical and histopathological analysis and distortion product otoacoustic emissions (DPOAEs). STUDY DESIGN: Animal study. METHODS: Forty Sprague-Dawley rats were randomized into five groups. Group 1 was administered no paclitaxel and curcumin during the study. Groups 2, 3, 4 and 5 were administered 5 mg/kg paclitaxel; 200 mg/kg curcumin; 5 mg/kg paclitaxel, followed by 200 mg/kg curcumin; 200 mg/kg curcumin and a day later 5 mg/kg paclitaxel followed intraperitoneally by 200 mg/kg curcumin once a week for 4 consecutive weeks, respectively. After the final DPOAEs test, the animals were sacrificed and their cochlea were prepared for hematoxylin and eosin and caspase-3 staining. RESULTS: The DPOAEs thresholds and histopathological and immunohistochemical findings were substantially correlated in all groups. The histopathologic findings in the cochlea of the paclitaxel-treated animals showed not only changes in the organ of Corti, but also damage to the stria vascularis and spiral limbus, including nuclear degeneration, cytoplasmic vacuolization, and atrophy of intermediate cells. Additionally, cochlear changes in group 2, such as intense apoptosis, were confirmed by caspase-3 immunohistochemical staining. In group 4, coreceiving curcumin could not sufficiently prevent paclitaxel-induced ototoxicity, and the results in group 5 were similar to the control group. CONCLUSIONS: In our study, we have concluded that pre- and coreceiving curcumin can significantly protect the cochlear morphology and functions on paclitaxel-induced ototoxicity in rats. Curcumin might be considered as a potential natural product that, used as a dietary supplement, could be easily given to patients undergoing paclitaxel chemotherapy. LEVEL OF EVIDENCE: NA

Hearing Status in Pediatric Renal Transplant Recipients.

OBJECTIVES: Renal transplant provides a long-term survival. Hearing impairment is a major factor in subjective health status. Status of hearing and the cause of hearing impairment in the pediatric renal transplant group have not been evaluated. Here, we studied to evaluate hearing status in pediatric renal transplant patients and to determine the factors that cause hearing impairment. MATERIALS AND METHODS: Twenty-seven pediatric renal transplant recipients were investigated. All patients underwent audiologic assessment by means of pure-tone audiometry. The factors on hearing impairment were performed. RESULTS: Sensorineural hearing impairment was found in 17 patients. There was marked hearing impairment for the higher frequencies between 4000 and 8000 Hz. Sudden hearing loss developed in 2 patients, 1 of them had tinnitus. Decrease of speech understanding was found in 8 patients. The cyclosporine level was significantly high in patients with hearing impairment compared with group without hearing impairment. Cyclosporine levels also were found to be statistically significantly high when compared with the group with decrease of speech understanding and the group without decrease of speech understanding. Similar relations cannot be found between tacrolimus levels and hearing impairment and speech understanding. CONCLUSIONS: Sensorineural hearing impairment prevalence was high in pediatric renal transplant recipients when compared with the general population of children. Cyclosporine may be responsible for causing hearing impairment after renal transplant. We suggest that this effect is a dose-dependent toxicity.

Evaluation of ototoxicity in patients treated with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin and sodium thiosulfate.

OBJECTIVES: Ototoxic hearing loss associated with intravenous or intra-arterial administration of cisplatin is well documented. However, there is limited data regarding the ototoxic effect of cisplatin when perfused into the abdominal cavity using hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this study is to assess and describe ototoxicity in patients treated with HIPEC with cisplatin and sodium thiosulfate for peritoneal surface malignancies. DESIGN: We performed a retrospective chart review (2007-2012) of patients treated for advanced peritoneal malignancies at a tertiary care center using HIPEC with cisplatin and sodium thiosulfate infusion. Thirteen patients (12 males, 1 female) met study criteria. Audiometric thresholds were compared before and after treatment. A 20 dB loss at any single frequency, 10 dB decrease at any two adjacent frequencies, or loss of response at three consecutive test frequencies defined a significant ototoxic change (). RESULTS: Despite minimal hearing change in six patients, none of the 13 patients in our study exhibited a significant ototoxic change in hearing sensitivity post HIPEC with cisplatin at any test interval in any test frequency. CONCLUSIONS: Our findings represent the first objective assessment of ototoxic effect after HIPEC with cisplatin and sodium thiosulfate infusion. Our results suggest that peritoneal perfusion of cisplatin with intravenous perfusion of sodium thiosulfate is not associated with ototoxic changes in hearing sensitivity. Further investigation of the administration and systemic mechanism of absorption of sodium thiosulfate as a potential protection against cisplatin ototoxicity is needed to confirm these findings.

Incidence of ototoxicity in pediatric patients with transfusion-dependent thalassemia who are less well-chelated by mono- and combined therapy of iron chelating agents.

Ototoxicity due to iron chelation therapy, especially deferoxamine (DFO), is frequently observed in patients who have a higher chelation index (>0.025). However, there is limited data on patients who are less well-chelated and on other chelating regimens, including deferiprone (L1), deferasirox (DFX), and a combination of DFO and L1. To determine the incidence of ototoxicity from iron chelators, we retrospectively analyzed our clinical records from January 1997 to December 2010. All transfusion-dependent thalassemia (TDT) patients received iron chelation therapy with mono DFX, DFO, L1, or a combination. All patients underwent routine otolaryngologic examination and pure-tone audiometry before starting each chelation regimen and were regularly followed every 6 months. One hundred thalassemic patients were enrolled and analyzed (48 males and 52 females), with a mean age of 12.11 ± 4.48 years (range 2.5-22.5 years). Total summative duration of iron chelation therapy in all patients was 596.50 years. Nine patients were found to have conductive hearing loss. Sensorineural hearing loss (SNHL) was identified in seven patients but only four were determined to be associated with iron chelators; three patients were detected while undergoing DFO therapy and one patient with L1 therapy. None of patients undergoing DFO therapy had reached over the levels of chelation index. In our resource-limited setting with poor treatment compliance, there was a rather low incidence of ototoxicity after exposure to iron chelators. However, a routine audiometry remains recommended for early detection and intervention since SNHL still develops and results in a long-term morbidity.

Methylmercury exposure and neurological outcomes in Taiji residents accustomed to consuming whale meat.

Methylmercury (MeHg) is a major environmental neurotoxicant that causes damage to the central nervous system. In Japan, industrial emission of MeHg has resulted in MeHg intoxication in Minamata and Niigata, the so-called Minamata disease. Humans are exposed to MeHg derived from natural sources, primarily fish and fish predators. Therefore, MeHg continues to be an environmental risk to human health, particularly in susceptible populations that frequently consume substantial amounts of fish or fish predators such as whale. This study aimed to investigate the health effects of MeHg exposure in adults. The subjects were 194 residents (117 males, 77 females; age 20-85 years) who resided in the coastal town of Taiji, the birthplace of traditional whaling in Japan. We analyzed hair for mercury content and performed detailed neurological examinations and dietary surveys. Audiometry, magnetic resonance imaging, and electromyography were performed to diagnose neurological defects. Whole blood mercury and selenium (Se) levels were measured in 23 subjects. The geometric mean of the hair mercury levels was 14.9 µg/g. Twelve subjects revealed hair mercury levels >50 µg/g (NOAEL) set by WHO. Hair mercury levels significantly correlated with daily whale meat intake. These results suggested that residents in Taiji were highly exposed to MeHg by ingesting MeHg-contaminated whale meat. Multivariate regression analysis demonstrated no significant correlations between hair mercury levels and neurological outcomes, whereas some of the findings significantly correlated with age. A significantly positive correlation between whole blood mercury and Se levels was observed and the whole blood mercury/Se molar ratios of all subjects were <1. These findings suggested that sufficient Se intake might be one of causes of the absence of adverse effects of MeHg exposure in this study.

Pomegranate extract: a potential protector against aminoglycoside ototoxicity.

OBJECTIVE: To investigate the effectiveness of pomegranate extract as protection against aminoglycoside ototoxicity. DESIGN: Prospective, randomised, controlled, experimental study. SUBJECTS: Eighteen Wistar albino rats were randomly allocated to 5 days of either: saline injections; gentamicin injections; or pomegranate extract (100 µl/day via gavage) plus gentamicin injections. Distortion product otoacoustic emissions were tested before treatment and on day 3. After treatment, reactive oxygen species levels were measured in each rat's right cochlea and right kidney via chemiluminescence. RESULTS: Baseline emission amplitudes were similar. Post-treatment emissions differed significantly in the two treatment groups (p < 0.001). Cochlear reactive oxygen species levels were significantly higher in the gentamicin group (mean ± standard deviation, 316.6 ± 36.5 relative light units per mg) than the gentamicin plus pomegranate extract group (240 ± 24.6 relative light units per mg) (p = 0.004); control group levels were 119.1 ± 10.3 relative light units per mg. Renal reactive oxygen species levels were similar for the control and gentamicin plus pomegranate extract groups (p = 0.59) but much higher in the gentamicin group (p = 0.004). CONCLUSION: Concurrent systemic pomegranate extract administration reduced reactive oxygen species level increases and otoacoustic emission changes, following aminoglycoside injection.

Effect of low-level laser treatment on cochlea hair-cell recovery after ototoxic hearing loss.

The primary cause of hearing loss includes damage to cochlear hair cells. Low-level laser therapy (LLLT) has become a popular treatment for damaged nervous systems. Based on the idea that cochlea hair cells and neural cells are from same developmental origin, the effect of LLLT on hearing loss in animal models is evaluated. Hearing loss animal models were established, and the animals were irradiated by 830-nm diode laser once a day for 10 days. Power density of the laser treatment was 900 mW/cm(2), and the fluence was 162 to 194 J. The tympanic membrane was evaluated after LLLT. Thresholds of auditory brainstem responses were evaluated before treatment, after gentamicin, and after 10 days of LLLT. Quantitative scanning electron microscopic (SEM) observations were done by counting remaining hair cells. Tympanic membranes were intact at the end of the experiment. No adverse tissue reaction was found. On SEM images, LLLT significantly increased the number of hair cells in middle and basal turns. Hearing was significantly improved by laser irradiation. After LLLT treatment, both the hearing threshold and hair-cell count significantly improved.

Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

OBJECTIVE: To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. METHODS: From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. RESULTS: The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P < 0.05). Compared with the control group, scores of neurobehavioral function reflecting learning and memory were decreased in petrochemical workers (P < 0.05), as well as acetylcholinesterase activity. Negative correlation was shown between neurobehavioral function and acetylcholinesterase. CONCLUSIONS: Ethylbenzene exposure might be associated with hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

Distortion-product otoacoustic emissions: a useful test for monitoring ototoxicity induced by pegylated interferon and ribavirin treatment in patients with chronic hepatitis C.

Pegylated-interferon (peg-IFN) and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) infection is well known to be associated with significant adverse effects. Several studies have investigated a possible auditory pathway involvement during IFN therapy, but a method to monitor the potential auditory involvement during treatment has not yet been described. The aim of this study is to evaluate possible modifications of the outer hair cell (OHC) function in HCV patients receiving peg-IFN and ribavirin combination therapy. Thirteen adult HCV patients (8 F/5 M, mean age 52∓12 years) treated with peg-IFN and ribavirin combination therapy underwent Pure Tone Audiogram and Distortion Product Otoacoustic Emission (DPOAE) tests. We compared mean auditory thresholds (PTA) and mean DPOAE amplitude before, at month 3 during, and at the end of treatment (T0, T3, and Tend, respectively), and 3 months after treatment discontinuation (Tfu). No significant differences were found in hearing levels at the different time points analyzed. During treatment, three patients developed tinnitus, which in 2 cases resolved spontaneously after the end of therapy. Compared to T0 (19.5±0.83), a statistically significant DPOAE increase at T3 (30±1,26) and Tend (28.6±2.16) was found (p<0.05 at both time points), while DPOAEs returned to pre-treatment levels at Tfu (19.3±1.3). In our group, none of the patients reported a permanent auditory impairment, excluding one patient with persistent tinnitus. Peg-IFN could produce an increase of motility of the OHCs by means of intracellular pathways. DPOAE test could be considered a new method for monitoring ototoxicity induced by IFN. On the basis of recent literature and our audiological results, physicians should be aware of the possible ototoxic effects of peg-IFN, requiring appropriate surveillance, and the patient should be informed of the potential side effects of IFN therapy on the auditory pathway.