The Quantification of Radiation Fibrosis Using Clinically Indicated Magnetic Resonance Imaging for Head and Neck Cancer Patients.

Currently, no objective method exists to measure the extent of fibrosis in swallowing musculature in head and neck cancer (HNC) patients. We developed and psychometrically tested a method of quantifying fibrosis volume using magnetic resonance imaging (MRI). The overall aim of this study was to determine if clinical MRI is a reliable tool to measure fibrosis of the pharyngeal musculature in patients with HNC managed with RT and to assess its potential to capture changes in fibrosis over time. Eligible participants were adults with HNC treated with radiation therapy (RT) who received minimally two MRIs and videofluoroscopic swallow (VFS) studies from baseline (pre-RT) up to 1-year post-RT. Two neuroradiologists independently contoured fibrosis volume in batches from MRIs using Vitrea™. Sufficient inter-rater reliability was set at Intraclass Correlation Coefficient (ICC) > 0.75. Two speech-language pathologists independently rated VFSs for swallowing impairment using standardized scales, with discrepancies resolved by consensus. MRI and VFS scores were correlated using Spearman's rank coefficient. Participants included 42 adults (male = 33); mean age 59 (SD = 8.8). ICC (95% Confidence Interval) for fibrosis volume was 0.34 (0, 0.76) for batch one and 0.43 (0, 0.82) for batch two. Consensus meetings were held after each batch. Sufficient reliability was reached by batch three (ICC = 0.95 (0.79, 0.99)). Fibrosis volume increased significantly from 3 to 12 months (mean change = 1.28 mL (SD = 5.21), p = 0.006), as did pharyngeal impairment from baseline to 12 months (mean score change = 3.05 (SD = 3.02), p = 0.003). Fibrosis volume moderately correlated with pharyngeal impairment at 3 and 12 months (0.49, p = 0.004 and 0.59, p = 0.005, respectively). We demonstrated a reliable measure of fibrosis volume in swallowing musculature from existing clinical MRIs and identified that larger fibrosis volume was associated with worse swallowing function. The reliable capture of fibrosis volume offers a pragmatic method for early detection of fibrosis and concomitant dysphagia.

Suppressor of Cytokine Signaling-3 Gene Polymorphisms and the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients in Egypt.

BACKGROUND: Hepatocellular carcinoma (HCC) contributes significantly to cancer mortalities worldwide. The association between a specific single nucleotide polymorphism (SNP) located within the SOCS3 gene as well as the likelihood of hepatocellular carcinoma (HCC) progression in individuals with chronic hepatitis C virus (CHC) was found to be significant. We aimed to study SOCS3 gene polymorphisms at rs4969168 and rs4969170and HCC susceptibility in individuals with CHC. METHODS: The current prospective study involved 111 subjects divided in to three groups (HCC, HCV with and with no cirrhosis, and apparently healthy individuals). Tumor staging was done using BCLC staging system. SOCS3 (rs4969168 and rs4969170) gene polymorphisms' analysis was done utilizing real-time polymerase chain reaction (RT-PCR) (via DNA extracted from all subjects). All subjects underwent a complete history, medical examination, and laboratory and radiological data collection. RESULTS: Compared to healthy controls, homozygous AA genotypes and heterozygous GA genotypes were substantially overrepresented in  HCC patients as well as those with CHCaccompanied by cirrhosis.AFP, smoking, glucose level, and AA genotype of rs4969170 might be critical significant parameters for HCC development. CONCLUSION: SOCS3 gene polymorphisms at rs4969168 and rs4969170 are associated with HCC and liver fibrosis progression in the Egyptian population with CHC infection.

The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma.

Ribonucleic acids (RNAs) are important regulators of gene expression and crucial for the progression of hepatocellular carcinoma (HCC). This study was designed to determine the diagnostic and prognostic utility of the circulating long miscellaneous RNAs; LINC01419, AK021443, and AF070632 in HCV-related HCC patients. Real-time PCR was used to measure their relative expression levels in the plasma of 194 HCV patients, 120 HCV-related HCC patients and 120 healthy controls. LINC01419 and AK021443 expression levels had significantly increasing linear trend estimates while AF070632 was dramatically downregulated in HCC compared to HCV. Interestingly, LINC01419 and AK021443 served as more significant diagnostic biomarkers for HCC than AF070632 and AFP. Multivariate analysis with cox regression revealed that the high expression of AK021443 [HR = 10.06, CI95%: 3.36-30.07], the high expression of LINC01419 [HR 4.13, CI95%: 1.32-12.86], and the low expression of AF070632 [HR = 2.70, CI95%: 1.07-6.81] were significant potential prognostic factors for HCC. Besides, the Kaplan-Meier analysis showed that HCC patients with high LIN01419 and AK021443 and low AF070632 expression levels had shorter OS. The circulating LINC01419 and AK021443 can be used as noninvasive potential biomarkers for diagnosis and prognosis of HCV-related HCC patients than AF070632 providing new targets for limiting the progression of the disease.

Pharyngeal Residue Severity and Aspiration Risk in Stroke Patient Using Fiber-Optic Endoscopic Evaluation of Swallowing.

INTRODUCTION: Pharyngeal residue, defined as the material remaining in the pharynx post-swallow, is a sign of swallowing biomechanical impairment and a clinical predictor of aspiration. This study investigates the correlation between pharyngeal residue severity using the Mansoura FEES Residue Rating Scale (MFRRS) and penetration/aspiration scores using the penetration-aspiration scale (PAS) on FEES. METHODS: Two hundred ten (210) swallows were obtained during standard FEES assessments of thirty patients with poststroke dysphagia. Residue, in both vallecula and the pyriform sinuses' locations, and penetration/aspiration were scored using MFRRS and PAS, respectively. The Spearman's rank-order correlation was used to assess the correlation between residue and PAS scores. The significance of the obtained results was judged at the (p < 0.05) level. RESULTS: Significant strong positive correlations were demonstrated between PAS scores and each vallecular residue score (rs = 0.663, p = 0.000) and pyriform residue score (rs = 0.688, p = 0.001). CONCLUSION: There is a significant strong positive correlation between residue severity and penetration/aspiration in each anatomical site evaluated (valleculae and pyriform sinuses). Our results do not designate one site as riskier than the other because either can contribute to aspiration, but rather demonstrate penetration/aspiration to better correlate with the overall severity of the residue, perhaps as a better marker for pharyngeal inefficiency. This study offers insight into the association of residue severity with swallowing safety and efficiency.

The Gamma-glutamyl Transpeptidase to Platelet Ratio (GPR) Predict Significant Liver Fibrosis and Cirrhosis in Chronic Egyptian HCV Patients

Non- invasive parameters of liver fibrosis are being widely incorporated and adopted in clinical practice, of them, 2 ratios APRI and FIB-4 were proposed and applied. The gamma-glutamyl transferase -to platelet ratio (GPR) was developed and investigated as available test that is useful in predicting liver fibrosis stages in chronic HBV patients. We aimed to estimate the diagnostic performance of GPR compared to APRI in assessing different fibrosis stages estimated by ultrasound based Transient Elastography in chronic HCV Egyptian patients

Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C-Related Advanced Fibrosis and Cirrhosis.

BACKGROUND AND AIM: Existing data are controversial regarding the incidence of hepatitis C (HCV)-related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4). METHODS: Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined. RESULTS: The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×103/mL, and high AFP were independent risk factors of developing HCC. CONCLUSION: Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.

MELD-Sarcopenia is Better than ALBI and MELD Score in Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation.

BACKGROUND: The albumin bilirubin (ALBI) score and model of end stage liver disease (MELD) are prognostic in patients with hepatocellular carcinoma (HCC). Aim was to compare MELD-sarcopenia to MELD and ALBI scores in patients with HCC awaiting liver transplantation. METHODS: patients with HCC (n=262) were included and followed up for 12 months. Baseline MELD, ALBI and MELD-sarcopenia models were calculated. RESULTS: The average age was 59.61 ±8.09 years. Most patients were males (69.5%), CTP class A (55.7%) and BCLC stage B (54.2%). Hepatitis C virus was the main cause of liver cirrhosis in most patients (88.9%). The average MELD, MELD-sarcopenia and median ALBI score were 10.65 ±2.54, 15.11 ±6.22 and -2.12 (0.74) respectively. Sarcopenia patients had higher MELD, ALBI and MELD-sarcopenia values. Patients with sarcopenia had lower survival (10.09 months) than those without (11.72 months). The ALBI, MELD and MELD-sarcopenia were associated with mortality. ALBI had AUROC of 0.717 (95% CI: 0.659 - 0.771), MELD had AUROC of 0.656 (95% CI: 0.595 - 0.713) and MELD-sarcopenia had AUROC of 0.798 (95% CI: 0.744 - 0.845). The ALBI and MELD scores had comparable AUROC (p=0.081). The MELD-sarcopenia had superior AUROC than MELD (p=0.001) and ALBI (p=0.05). CONCLUSION: MELD-sarcopenia is better prognostic model than the ALBI and MELD scores in HCC patients awaiting liver transplantation.
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Anterior-posterior distension of maximal upper esophageal sphincter opening is correlated with high-resolution cervical auscultation signal features.

Objective. Adequate upper esophageal sphincter (UES) opening is essential during swallowing to enable clearance of material into the digestive system, and videofluoroscopy (VF) is the most commonly deployed instrumental examination for assessment of UES opening. High-resolution cervical auscultation (HRCA) has been shown to be an effective, portable and cost-efficient screening tool for dysphagia with strong capabilities in non-invasively and accurately approximating manual measurements of VF images. In this study, we aimed to examine whether the HRCA signals are correlated to the manually measured anterior-posterior (AP) distension of maximal UES opening from VF recordings, under the hypothesis that they would be strongly associated.Approach. We developed a standardized method to spatially measure the AP distension of maximal UES opening in 203 swallows VF recording from 27 patients referred for VF due to suspected dysphagia. Statistical analysis was conducted to compare the manually measured AP distension of maximal UES opening from lateral plane VF images and features extracted from two sets of HRCA signal segments: whole swallow segments and segments excluding all events other than the duration of UES is opening.Main results. HRCA signal features were significantly associated with the normalized AP distension of the maximal UES opening in the longer whole swallowing segments and the association became much stronger when analysis was performed solely during the duration of UES opening.Significance. This preliminary feasibility study demonstrated the potential value of HRCA signals features in approximating the objective measurements of maximal UES AP distension and paves the way of developing HRCA to non-invasively and accurately predict human spatial measurement of VF kinematic events.

Mansoura Fiberoptic Endoscopic Evaluation of Swallowing Residue Rating Scale (MFRRS): An Anatomically Based Tool - A Preliminary Study.

OBJECTIVE: The aim of this work was to design an anatomically based scale for judging post-swallow residue in the pharyngeal cavities, for use during the fiberoptic endoscopic evaluation of swallowing (FEES) in patients with dysphagia, and to assess its feasibility. METHODS: Two 7-point ordinal scales (one for vallecular residue and one for pyriform sinus residue), were developed using detailed anatomic landmarks to denote residue levels. Hard copy color images of a specified frame, from 210 videos of 30 adult FEES evaluations demonstrating the range of all possible residue patterns, were selected (n = 56 valleculae, 62 pyriform sinuses). Half of these images were used to train 4 raters. The remaining half of the images were randomly ordered and rated by the trained raters. Two weeks later the same images were randomized again, and each rater re-analyzed them. The inter- and intra-rater reliability and criterion validity were determined using the kappa statistics and their standard errors. The internal consistency of the items in MFRRS was examined. RESULTS: MFRRS showed strong inter-rater reliability (valleculae, κ = 0.832 ± 0.038; pyriform sinus, κ = 0.855 ± 0.034), almost perfect intra-rater reliability (valleculae, κ = 0.964 ± 0.018; pyriform sinus, κ = 0.962 ± 0.02), almost perfect concurrent validity (valleculae, κ = 0.968 ± 0.020; pyriform sinus, κ = 0.0971 ± 0.017), and excellent internal consistency (valleculae, Cronbach's α = 0.990; pyriform sinus, Cronbach's α = 0.985). CONCLUSION: MFRRS is a feasible and reliable, anatomically based tool that can provide more accurate pharyngeal residue judgments. The optimized description of residue accumulation patterns can contribute to a better overall description of the functional problem and future description of dysphagia phenotypes.

Estimation of laryngeal closure duration during swallowing without invasive X-rays.

Laryngeal vestibule (LV) closure is a critical physiologic event during swallowing, since it is the first line of defense against food bolus entering the airway. Identifying the laryngeal vestibule status, including closure, reopening and closure duration, provides indispensable references for assessing the risk of dysphagia and neuromuscular function. However, commonly used radiographic examinations, known as videofluoroscopy swallowing studies, are highly constrained by their radiation exposure and cost. Here, we introduce a non-invasive sensor-based system, that acquires high-resolution cervical auscultation signals from neck and accommodates advanced deep learning techniques for the detection of LV behaviors. The deep learning algorithm, which combined convolutional and recurrent neural networks, was developed with a dataset of 588 swallows from 120 patients with suspected dysphagia and further clinically tested on 45 samples from 16 healthy participants. For classifying the LV closure and opening statuses, our method achieved 78.94% and 74.89% accuracies for these two datasets, suggesting the feasibility of implementing sensor signals for LV prediction without traditional videofluoroscopy screening methods. The sensor supported system offers a broadly applicable computational approach for clinical diagnosis and biofeedback purposes in patients with swallowing disorders without the use of radiographic examination.

Baseline Sarcopenia is Associated with Lack of Response to Therapy, Liver Decompensation and High Mortality in Hepatocellular Carcinoma Patients.

OBJECTIVE: hepatocellular carcinoma (HCC) is a dreadful complication of liver cirrhosis. Aim was to study the effect of sarcopenia on the survival in patients with HCC. METHODS: we included 262 patients and were followed up for 12 months. Sarcopenia was calculated by skeletal muscle index (SMI). Sarcopenia was defined by SMI ≤39 cm2/m2 for women and ≤50 cm2/m2 for men. RESULTS: patients with sarcopenia (n= 113, 43.1%) were older, mainly males, Child-Pugh class B and smokers. Patients with sarcopenia had lower survival than those without (10.09 vs. 11.72 months). Survival was also lower in Barcelona clinic liver cancer stage C than B and A (9.02 vs. 11.21 vs. 11.89 months). Age and sarcopenia were hazardous of mortality (p <0.05). There was statistically significant difference of serial SMI in patients without baseline sarcopenia unlike patients with baseline sarcopenia. On follow up patients with sarcopenia had higher incidence of ascites (45% vs. 20.4%), spontaneous bacterial peritonitis (21.7% vs. 11.6%), hepatic encephalopathy (28% vs. 11.5%) and bleeding (22.9% vs. 12.7%). Totally patients with sarcopenia had higher incidence of progressive HCC (39% vs. 25.5%). CONCLUSION: Sarcopenia is associated with lack of response to therapy, liver decompensation and higher mortality in hepatocellular carcinoma patients.
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Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) in HCV-Positive Egyptian Patients Treated with Sofosbuvir.

Background: Direct-acting antivirals (DAAs) made a drastic change in the management of HCV infection. Sofosbuvir is one of the highly potent DAAs, eliminated mainly through the kidney. But concerns about renal safety during treatment may limit its use. Neutrophil gelatinase-associated lipocalin (NGAL) has been proven as a predictor of renal tubular injury. Hence, the aim of this work was to assess serum neutrophil gelatinase-associated lipocalin (NGAL) in HCV-positive patients before and after treatment with the sofosbuvir-based antiviral regimen. Methods: This prospective study included 87 Egyptian patients with chronic HCV infection treated with sofosbuvir plus daclatasvir with or without ribavirin for 12 weeks. Serum NGAL was measured before and at the end of treatment (EOT). Analysis of NGAL and estimated glomerular filtration rate (eGFR) evolution was done. Results: Our results showed a statistically significant decrease in serum NGAL (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (. Conclusions: Sofosbuvir appears to have no nephrotoxic effects and is safe to treat patients with chronic HCV infection.

Automatic Estimation of Laryngeal Vestibule Closure Duration Using High- Resolution Cervical Auscultation Signals.

Purpose: Safe swallowing requires adequate protection of the airway to prevent swallowed materials from entering the trachea or lungs (i.e., aspiration). Laryngeal vestibule closure (LVC) is the first line of defense against swallowed materials entering the airway. Absent LVC or mistimed/ shortened closure duration can lead to aspiration, adverse medical consequences, and even death. LVC mechanisms can be judged commonly through the videofluoroscopic swallowing study; however, this type of instrumentation exposes patients to radiation and is not available or acceptable to all patients. There is growing interest in noninvasive methods to assess/monitor swallow physiology. In this study, we hypothesized that our noninvasive sensor- based system, which has been shown to accurately track hyoid displacement and upper esophageal sphincter opening duration during swallowing, could predict laryngeal vestibule status, including the onset of LVC and the onset of laryngeal vestibule reopening, in real time and estimate the closure duration with a comparable degree of accuracy as trained human raters. Method: The sensor-based system used in this study is high-resolution cervical auscultation (HRCA). Advanced machine learning techniques enable HRCA signal analysis through feature extraction and complex algorithms. A deep learning model was developed with a data set of 588 swallows from 120 patients with suspected dysphagia and further tested on 45 swallows from 16 healthy participants. Results: The new technique achieved an overall mean accuracy of 74.90% and 75.48% for the two data sets, respectively, in distinguishing LVC status. Closure duration ratios between automated and gold-standard human judgment of LVC duration were 1.13 for the patient data set and 0.93 for the healthy participant data set. Conclusions: This study found that HRCA signal analysis using advanced machine learning techniques can effectively predict laryngeal vestibule status (closure or opening) and further estimate LVC duration. HRCA is potentially a noninvasive tool to estimate LVC duration for diagnostic and biofeedback purposes without X-ray imaging.

The Association of High Resolution Cervical Auscultation Signal Features With Hyoid Bone Displacement During Swallowing.

Recent publications have suggested that high-resolution cervical auscultation (HRCA) signals may provide an alternative non-invasive option for swallowing assessment. However, the relationship between hyoid bone displacement, a key component to safe swallowing, and HRCA signals is not thoroughly understood. Therefore, in this work we investigated the hypothesis that a strong relationship exists between hyoid displacement and HRCA signals. Videofuoroscopy data was collected for 129 swallows, simultaneously with vibratory/acoustic signals. Horizontal, vertical and hypotenuse displacements of the hyoid bone were measured through manual expert analysis of videofluoroscopy images. Our results showed that the vertical displacement of both the anterior and posterior landmarks of the hyoid bone was strongly associated with the Lempel-Ziv complexity of superior-inferior and anterior-posterior vibrations from HRCA signals. Horizontal and hypotenuse displacements of the posterior aspect of the hyoid bone were strongly associated with the standard deviation of swallowing sounds. Medial-Lateral vibrations and patient characteristics such as age, sex, and history of stroke were not significantly associated with the hyoid bone displacement. The results imply that some vibratory/acoustic features extracted from HRCA recordings can provide information about the magnitude and direction of hyoid bone displacement. These results provide additional support for using HRCA as a non-invasive tool to assess physiological aspects of swallowing such as the hyoid bone displacement.

Impact of new direct-acting antiviral drugs on hepatitis C virus-related decompensated liver cirrhosis.

BACKGROUND: The benefits of treatment of hepatitis C virus with direct-acting antiviral drugs in patients with decompensated liver cirrhosis (DLC) are still unclear. AIM: To evaluate the degree of improvement in hepatic decompensation events and quality of life (QOL) in treated patients with DLC. PATIENTS AND METHODS: One hundred and fifty patients with hepatitis C virus-related DLC were included; 75 of these patients received treatment (group I) [sofosbuvir (SOF) with either daclatasvir or ledipasvir for 24 weeks without ribavirin (RBV) or for 12 weeks with RBV] and 75 patients did not receive treatment as a comparable group (group II). Patients who achieved a sustained virological response at 12 weeks were assessed in terms of decompensation events, model for end-stage liver disease score, Child-Turcotte-Pugh score, biochemical changes, and QOL (applied on Mcguill QOL questionnaire) before starting treatment and 6 months after end of treatment, and were compared with untreated patients. RESULTS: Forty-two (56%) patients received SOF/daclatasvir for 24 weeks without RBV and 19 (25.3%) patients received SOF/ledipasvir for 24 weeks without RBV. The model for end-stage liver disease score improved in treated patients (mean change -1.73), but worsened in untreated patients (mean change +11.8) before and after 6 months. Also, the Child-Turcotte-Pugh score improved significantly (P<0.001). Serum albumin, prothrombin time, bilirubin, α-fetoprotein, and alanine aminotransferase improved in treated patients (P<0.001). Health-related QOL improved in treated patients (mean change +17.65) and worsened in untreated ones (mean change -18.68; P<0.001). CONCLUSION: Treated patients with DLC showed an improvement in liver tests and health-related QOL. Longer durations of follow-up for decompensation events are needed.

Developing Viscosity Modelling for Traditional Liquids in Egypt.

OBJECTIVES: The aim of this study was to develop a low-cost methodology for preparing different thickened liquids with different consistencies and viscosities that mimic the viscosities of culturally relevant traditional Egyptian liquids, which can be easily used in the fiberoptic-endoscopic evaluation of swallowing. MATERIALS AND METHODS: The textures of 9 traditional Egyptian liquids were quantified with the International Dysphagia Diet Standardisation Initiative (IDDSI) Flow Test and spanned the entire range of the IDDSI scale. We then developed texture-modified fluids that matched each dietary fluid texture for endoscopic dysphagia assessment using a regionally available, inexpensive, starch-based thickening agent. RESULTS: Our results indicate simple methods of assuring that fluids used during swallowing testing with endoscopy can be matched to dietary fluids to ensure appropriate dietary prescriptions for people with dysphagia. The changes in the thickness and viscosity of the prepared liquid samples were detected and studied separately. The measured samples include some traditional Egyptian fluids (molokhia, lentil soup) in addition to commercially available fluids and pudding. CONCLUSION: The method can be applied to develop thickened liquids with different consistencies to model the traditional, naturally thickened liquids in Egypt and many other developing countries.

Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis C genotype-4.

BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) and HCV-genotype-4 (GT4) has become very effective, it remains very expensive, and affordable options are needed, especially in limited resource countries. The aim of this study was to assess the efficacy and safety of the combination of ravidasvir (an NS5A inhibitor) and sofosbuvir to treat patients with chronic HCV-GT4 infection. METHODS: A total of 300 patients with HCV-GT4 infection were recruited in three groups: treatment-naïve patients with or without compensated Child-A cirrhosis (Group 1); interferon-experienced patients without cirrhosis (Group 2); and interferon-experienced patients with cirrhosis (Group 3). Groups 1 and 2 received ravidasvir 200 mg QD plus sofosbuvir 400 mg QD for 12 weeks and were randomized 1:1 to treatment with or without weight-based ribavirin. Group 3 patients received ravidasvir plus sofosbuvir with ribavirin and were randomized 1:1 to a treatment duration of 12 weeks or 16 weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS: A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated. CONCLUSIONS: Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02371408. LAY SUMMARY: This study evaluated efficacy and safety of the new oral hepatitis C drug ravidasvir in combination with the approved oral drug sofosbuvir in 298 patients infected with hepatitis C type 4. Our results showed that treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high response rate in patients with and without cirrhosis.