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Treatment regimens Among the 52 patients with chronic HCV genotype 4 (HCV GT-4) infection, 32 patients (61.53%) were in ledipasvir/sofosbuvir (Harvoni®) group, 12(23.07%) in ombitasvir/paritaprevir/ritonavir/dasabuvir (Viekira Pak®) group and 8 patients (15.38%) patients in sofosbuvir/velpatasvir (Epclusa®) group (Fig. 1). Figure 1 Treatment groups with different regimens. Overall virologic response to treatment and predictors The overall SVR on completion of treatment was 94.23%. SVR 12 in three treatment groups is depicted in Figure 2. In univariate analysis, it was identified that patients who achieved SVR12 as compared to those who did not achieve SVR12 had higher mean albumin value and lower mean bilirubin level (4.2 vs. 3.6; P value = 0.039 and 0.5 vs. 1.0, P value = 0.048, respectively). However, after adjusting baseline characteristics in multivariable logistic regression models, neither albumin nor bilirubin was identified as a predictor of treatment response (P value = 0.99 in both cases). SVR was not affected by HCV RNA levels and previous treatment (Table 2). Overall SVR 12 rates were high and similar in all treatment groups. Figure 2 Treatment response in all groups measured by overall SVR 12.

Overall virologic response to treatment and predictors The overall SVR on completion of treatment was 94.23%. SVR 12 in three treatment groups is depicted in Figure 2. In univariate analysis, it was identified that patients who achieved SVR12 as compared to those who did not achieve SVR12 had higher mean albumin value and lower mean bilirubin level (4.2 vs. 3.6; P value = 0.039 and 0.5 vs. 1.0, P value = 0.048, respectively). However, after adjusting baseline characteristics in multivariable logistic regression models, neither albumin nor bilirubin was identified as a predictor of treatment response (P value = 0.99 in both cases). SVR was not affected by HCV RNA levels and previous treatment (Table 2). Overall SVR 12 rates were high and similar in all treatment groups. Figure 2 Treatment response in all groups measured by overall SVR 12. Table 2 Demographic and Clinical Characteristics of Patients at Baseline by Treatment Response Characteristics All patients (n = 52) Treatment response Univariate P value Multivariate P value SVR (n = 49) No SVR (n = 3) Age (years) 52.2 (19 - 79) 51.2 (19 - 79) 68.0 (64 - 74) 0.055 NA Age group < 65 39 (75.0) 38 (77.6) 1 (33.3) 0.151 NA ≥ 65 13 (25.0) 11 (22.4) 2 (66.7) Sex Male 39 (75.0) 36 (73.5) 3 (100) 0.414 NA Female 13 (25.0) 13 (26.5) 0 BMI (kg/m2) 28.0 (17.0 - 43.7) 28.1 (17.0 - 43.7) 26.5 (25.0 - 27.4) 0.630 NA BMI (kg/m2) < 30 35 (67.3) 32 (65.3) 3 (100) 0.296 NA ≥ 30 17 (32.7) 17 (34.7) 0 HCV RNA (IU/mL) < 800,000 23 (44.2) 21 (42.9) 2 (66.7) 0.412 NA ≥ 800,000 29 (55.8) 28 (57.1) 1 (33.3) Prior treatment Naive 43 (82.7) 41 (83.7) 2 (66.7) 0.442 NA Experienced 9 (17.3) 8 (16.3) 1 (33.3) Comorbidities Diabetes 15 (28.8) 13 (86.7) 2 (13.3) 0.196 NA Hypertension 28 (53.8) 26 (92.9) 2 (7.1) 0.559 NA Coronary artery disease 2 (3.8) 2 (100) 0 0.887 NA Kidney disease 3 (5.8) 2 (66.7) 1 (33.3) 0.166 NA Chronic anemia 2 (3.8) 2 (100) 0 0.887 NA Cirrhosis Absent 42 (80.8) 41 (83.7) 1 (33.3) 0.091 NA Present 10 (19.2) 8 (16.3) 2 (66.7) MELD score < 10 44 (84.6) 43 (87.8) 1 (33.3) 0.058 NA ≥ 10 8 (15.4) 6 (12.2) 2 (66.7) Laboratory tests Hemoglobin (g/dL) 13.7 (9.0 - 17.0) 13.7 (9.0 - 17.0) 13.5 (12.5 - 14) 0.872 NA Platelets (×1000/mL) 203.4 (35 - 341) 206.3 (35 - 341) 156.7 (63 - 299) 0.228 NA Albumin (g/dL) 4.2 (3.0 - 4.7) 4.2 (3.0 - 4.7) 3.6 (3.2 - 3.9) 0.039 0.99* AST (IU/L) 41.1 (13 - 123) 40.0 (13 - 123) 58.0 (34 - 98) 0.252 NA ALT (IU/L) 55.5 (9 - 220) 56.2 (9 - 220) 45.0(16 - 92) 0.650 NA Bilirubin (mg/dL) 0.6 (0.2 - 1.9) 0.5 (0.2 - 1.2) 1.0 (0.3 - 1.9) 0.048 0.99* Data are presented as mean (range) or number (percentage). *Only variables with the P value < 0.05 in univariate analysis were assessed. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; AST: aspartate transaminase; ALT: alanine transaminase.

d as mean (range) or number (percentage). *Only variables with the P value < 0.05 in univariate analysis were assessed. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; AST: aspartate transaminase; ALT: alanine transaminase. Virologic response in Harvoni® group In this group, 93.8% achieved SVR. In univariate analysis, patients without cirrhosis had higher SVR rates compared to those with cirrhosis (100% vs. 50%, P value = 0.012). But this finding was not confirmed in multivariate analysis after adjusting for baseline characteristics (P value = 0.996). In general, other co-morbidities including diabetes, chronic kidney disease, coronary artery disease, chronic anemia, etc. did not impact SVR rates significantly (Table 3).

Introduction There are estimated 71 million people infected with chronic hepatitis C virus (HCV) worldwide, and approximately 399,000 people die each year from hepatitis C [1, 2]. Chronic HCV infection is a common cause of chronic progressive liver disease and hepatocellular carcinoma [3, 4]. In the United States, it is estimated that 2.7 million people are chronically infected with HCV infection [4, 5]. HCV genotype 4 (HCV GT-4) is responsible for about 13% of all HCV infections worldwide and only 1-2% in the United States [6]. It is common in the Middle East, North Africa, and sub-Saharan Africa and accounts for more than 90% of all HCV infections in Egypt.

Introduction There are estimated 71 million people infected with chronic hepatitis C virus (HCV) worldwide, and approximately 399,000 people die each year from hepatitis C [1, 2]. Chronic HCV infection is a common cause of chronic progressive liver disease and hepatocellular carcinoma [3, 4]. In the United States, it is estimated that 2.7 million people are chronically infected with HCV infection [4, 5]. HCV genotype 4 (HCV GT-4) is responsible for about 13% of all HCV infections worldwide and only 1-2% in the United States [6]. It is common in the Middle East, North Africa, and sub-Saharan Africa and accounts for more than 90% of all HCV infections in Egypt. Due to unequal geographic distribution and non-dominant hepatitis C genotype, the representation of HCV GT-4 in clinical trials and other studies is sparse. Thus, the efficacy and safety data of direct-acting antivirals (DAAs) in patients with HCV GT-4 infection are limited [5]. Most of the clinical trials and studies that evaluated the effect of DAAs were done on patients with hepatitis C genotype 1(HCV GT1), and many of the findings were generalized to all genotypes. HCV GT-4 patients have limited representation in all the existing literature. In our community, HCV genotype 4 also seems prevalent besides genotype 1 probably due to Egyptian community coming for the treatment. We sought to 1) characterize the population characteristics for HCV GT-4 infection receiving DAAs; 2) evaluate the efficacy, tolerability, and safety of second-generation DAA-based three different combination regimens and assess the indicators that impact sustained virologic response (SVR) rates.

ing for the treatment. We sought to 1) characterize the population characteristics for HCV GT-4 infection receiving DAAs; 2) evaluate the efficacy, tolerability, and safety of second-generation DAA-based three different combination regimens and assess the indicators that impact sustained virologic response (SVR) rates. Patients and Methods The study protocol was approved by the Institutional Review Board (IRB) and the patients were recruited from two specialty clinics attached to the two large community hospitals: Interfaith Medical Center and New York-Presbyterian Brooklyn Methodist Hospital. Patients A total of 61 patients with chronic HCV genotype 4 were treated with DAAs between January 2014 and October 2017. Nine patients were excluded from the study for various reasons including insufficient documentation of viral load during the treatment and failure to follow-up at the end of treatment. Decompensated cirrhosis and HIV co-infection were also excluded from the study. None of the patients included in this study discontinued the treatment due to adverse events associated with treatment medications.

ufficient documentation of viral load during the treatment and failure to follow-up at the end of treatment. Decompensated cirrhosis and HIV co-infection were also excluded from the study. None of the patients included in this study discontinued the treatment due to adverse events associated with treatment medications. The 52 remaining patients included in this retrospective cohort study received at least 12 weeks of treatment with one of the recommended combination regimens in standard doses for chronic HCV infection. Three different treatment regimens were used in our study. The choice of treatment regimens used was made on the basis of the American Association for the Study of Liver Disease. Ledipasvir 90 mg/day + sofosbuvir 400 mg/day (Harvoni®), ledipasvir 90 mg/day + Sofosbuvir 400 mg/day + ribavirin 1,000 mg/day if < 75 kg and 1,200 mg/day if ≥ 75 kg (Harvoni® + RBV), (ombitasvir 12.5 mg + paritaprevir 75 mg + ritonavir 50 mg) two tablets twice daily + dasabuvir 250 mg twice daily (Viekira Pak®), ombitasvir 12.5 mg + paritaprevir 75 mg + ritonavir 50 mg two tablets twice daily plus dasabuvir 250 mg twice daily + ribavirin 1,000 mg/day if < 75 kg and 1,200 mg/day if ≥ 75 kg (Viekira Pak® + RBV), and sofosbuvir 400 mg/day + velpatasvir 400 mg/day (Epclusa®). Duration of the treatment period ranged from 12 weeks (n = 44) to 24 weeks (n = 8) depending on their status of prior treatment and cirrhosis.

dasabuvir 250 mg twice daily + ribavirin 1,000 mg/day if < 75 kg and 1,200 mg/day if ≥ 75 kg (Viekira Pak® + RBV), and sofosbuvir 400 mg/day + velpatasvir 400 mg/day (Epclusa®). Duration of the treatment period ranged from 12 weeks (n = 44) to 24 weeks (n = 8) depending on their status of prior treatment and cirrhosis. Study assessments Pretreatment baseline characteristics (Table 1), laboratory studies, baseline HCV viral load, treatment efficacy with SVR at 12 weeks after completion of treatment (SVR 12) were assessed. The safety and tolerability of antiviral drug regimens were assessed by reviewing the documented common or serious adverse events, treatment completion rate, and reduction in the medication dosage or discontinuation of medications.

ment efficacy with SVR at 12 weeks after completion of treatment (SVR 12) were assessed. The safety and tolerability of antiviral drug regimens were assessed by reviewing the documented common or serious adverse events, treatment completion rate, and reduction in the medication dosage or discontinuation of medications. Table 1 Demographic and Clinical Characteristics of Patients at Baseline with Treatment Regimen Characteristics All patients (n = 52) Treatment regimens P value Harvoni® (n = 32) Viekira Pak® (n = 12) Epclusa® (n = 8) Age (years) 52.2 (19 - 79) 53.5 (22 - 79) 49.3 (19 - 70) 51.1 (36 - 72) 0.698 Sex Male 39 (75.0) 25 (78.1) 8 (66.7) 6 (75.0) 0.737 Female 13 (25.0) 7 (21.9) 4 (33.3) 2 (25.0) BMI (kg/m2) 28.0 (17.0 - 43.7) 27.8 (18.0 - 43.7) 27.6 (17.0 - 37.0) 29.6 (20.0 - 39.0) 0.683 HCV RNA (IU/mL) < 800,000 23 (44.2) 16 (50.0) 5 (41.7) 2 (25.0) 0.435 ≥ 800,000 29 (55.8) 16 (50.0) 7 (58.3) 6 (75.0) Prior treatment Naive 43 (82.7) 26 (81.3) 11 (91.7) 6 (75.0) 0.591 Experienced 9 (17.3) 6 (18.8) 1 (8.3) 2 (25.0) Comorbidities Diabetes 15 (28.8) 8 (53.3) 5 (33.3) 2 (13.3) 0.535 Hypertension 28 (53.8) 16 (57.1) 7 (25.0) 5 (17.9) 0.768 Coronary artery disease 2 (3.8) 1 (50.0) 1 (50.0) 0 0.601 Kidney disease 3 (5.8) 0 2 (66.7) 1 (33.3) 0.073 Chronic anemia 2 (3.8) 0 1 (50.0) 1 (50.0) 0.169 Cirrhosis Absent 42 (80.8) 28 (87.5) 11 (91.7) 3 (37.5) 0.003* Present 10 (19.2) 4 (12.5) 1 (8.3) 5 (62.5) MELD score < 10 44 (84.6) 29 (90.6) 10 (83.3) 5 (62.5) 0.142 ≥ 10 8 (15.4) 3 (9.3) 2 (16.7) 3 (37.5) Laboratory tests Hemoglobin (g/dL) 13.7 (9.0 - 17.0) 13.8 (10.0 - 17.0) 13.1 (9.0 - 16.0) 13.9 (10.0 - 16.0) 0.476 Platelets (×1000/mL) 203.4 (35 - 341) 201.8 (63 - 341) 245.5 (152 - 330) 146.6 (35 - 199) 0.004* Albumin (g/dL) 4.2 (3.0 - 4.7) 4.2 (3.2 - 4.7) 4.1 (3.0 - 4.6) 3.9 (3.0 - 4.7) 0.224 AST (IU/L) 41.1 (13 - 123) 39.2 (14 - 92) 35.3 (13 - 107) 57.1 (21 - 123) 0.154 ALT (IU/L) 55.5 (9 - 220) 51.1 (9 - 165) 50.3 (10 - 220) 81.2 (48 - 141) 0.154 Bilirubin (mg/dL) 0.6 (0.2 - 1.9) 0.6 (0.2 - 1.9) 0.5 (0.2 - 0.9) 0.6 (0.2 - 1.1) 0.762 Data are presented as mean (range) or number (percentage). *P value < 0.05: statistically significant. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; AST: aspartate transaminase; ALT: alanine transaminase.

0.2 - 1.1) 0.762 Data are presented as mean (range) or number (percentage). *P value < 0.05: statistically significant. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; AST: aspartate transaminase; ALT: alanine transaminase. Liver fibrosis assessment was performed with invasive liver biopsy in some cases and noninvasive testing with a fibro sure test and the aspartate aminotransferase (AST)-to-aspartate platelet ratio index (APRI) score. Patients who had clinical, laboratory, and radiological evidence of cirrhosis were treated without any further assessment of fibrosis. The diagnosis of liver cirrhosis was based on clinical symptoms, laboratory parameters including FibroSURE score ≥ 0.75, imaging modalities (Ultrasonography and Computed Tomography Scan) and histopathology whenever indicated. Compensated cirrhosis was defined as the absence of ascites, jaundice, hepatic encephalopathy and variceal bleeding as defined by American Association for the Study of Liver Disease. Treatment response was assessed with HCV RNA viral load (IU/ mL) at 4 weeks after initiation of treatment, at the end of treatment, and 12 weeks after completion of treatment. The test was performed using COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, v2.0 (Roche molecular diagnostics) with the lower limit of quantification (LLOQ) of HCV RNA 15 IU/mL. SVR 12 was defined as the undetectable viral load at 12 weeks after the end of treatment.

and 12 weeks after completion of treatment. The test was performed using COBAS® AmpliPrep/COBAS® TaqMan® HCV Quantitative Test, v2.0 (Roche molecular diagnostics) with the lower limit of quantification (LLOQ) of HCV RNA 15 IU/mL. SVR 12 was defined as the undetectable viral load at 12 weeks after the end of treatment. Statistical analysis The SPSS® statistics software package (IBM SPSS® statistics version 21, USA) was used for statistical analysis. Values were expressed as mean ± SD, and mean quantitative values were analyzed using Student’s t-test. Differences in qualitative values were analyzed by Chi-square test. All P values were two-tailed and P value < 0.05 was considered significant. One-way analysis of variance (ANOVA) was used to determine whether there were differences among the group means. Univariate was used for assessing factors related to SVR12. Multivariable logistic regression was performed only in variables with a P value < 0.05 in univariate analysis.

< 0.05 was considered significant. One-way analysis of variance (ANOVA) was used to determine whether there were differences among the group means. Univariate was used for assessing factors related to SVR12. Multivariable logistic regression was performed only in variables with a P value < 0.05 in univariate analysis. Results Baseline characteristics Baseline characteristics are shown in Table 1. Mean age of the patients in the study of the cohort was 52 years with ranging from 19 to 79 years. Majority of the patients were males 39 (75%) and treatment-naive (82.7%). Ten patients (19.2%) had compensated cirrhosis and nine patients (17.3%) had HCV/HIV co-infection. Nine patients (17.30%) had received prior treatment. Fifteen patients (28.8%) had a history of diabetes; three patients (5.76%) had kidney disease. However, none of the patients had hepatocellular carcinoma, prior liver transplant or decompensated cirrhosis. There was no statistical difference in the baseline of the three treatment groups except for the Epclusa® group (higher number of cirrhotics and low platelet count). Treatment regimens Among the 52 patients with chronic HCV genotype 4 (HCV GT-4) infection, 32 patients (61.53%) were in ledipasvir/sofosbuvir (Harvoni®) group, 12(23.07%) in ombitasvir/paritaprevir/ritonavir/dasabuvir (Viekira Pak®) group and 8 patients (15.38%) patients in sofosbuvir/velpatasvir (Epclusa®) group (Fig. 1). Figure 1 Treatment groups with different regimens.

50%, P value = 0.012). But this finding was not confirmed in multivariate analysis after adjusting for baseline characteristics (P value = 0.996). In general, other co-morbidities including diabetes, chronic kidney disease, coronary artery disease, chronic anemia, etc. did not impact SVR rates significantly (Table 3). Table 3 SVR 12 Rates in Patients Receiving Harvoni® by Population Subgroup Response SVR 12 rate Univariate P value Multivariate P value Overall 30/32 (93.8) Age group < 65 22/23 (95.7) 0.490 NA ≥ 65 8/9 (88.9) Sex Male 23/25 (92.0) 1.000 NA Female 7/7 (100) BMI (kg/m2) < 30 21/23 (91.3) 1.000 NA ≥ 30 9/9 (100) HCV RNA (IU/mL) < 800,000 14/16 (87.5) 0.242 NA ≥ 800,000 16/16 (100) Prior treatment Naive 25/26 (96.2) 0.345 NA Experienced 5/6 (83.3) Comorbidities Diabetes 7/8 (87.5) 0.444 NA Hypertension 15/16 (93.8) 1.000 NA CAD 1/1 (100) 1.000 NA Kidney disease 0 N/A NA Chronic anemia 0 N/A NA Cirrhosis Absent 28/28 (100) 0.012 0.996* Present 2/4 (50) ALT (IU/L) < 40 15/17 (88.2) 0.486 NA ≥ 40 15/15 (100) Data presented as number/total number (percent). *Only variables with the P value < 0.05 in univariate analysis were assessed. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; ALT: alanine transaminase. Virologic response in Veikira Pak® group Patients treated in this group (ViekiraPak®), 91.7% achieved SVR as shown in Table 4. Similar to Harvoni® group, there was no difference in SVR between cirrhosis and non-cirrhosis patients (100% vs. 90.9%, P value = 1.0).

Table 3 SVR 12 Rates in Patients Receiving Harvoni® by Population Subgroup Response SVR 12 rate Univariate P value Multivariate P value Overall 30/32 (93.8) Age group < 65 22/23 (95.7) 0.490 NA ≥ 65 8/9 (88.9) Sex Male 23/25 (92.0) 1.000 NA Female 7/7 (100) BMI (kg/m2) < 30 21/23 (91.3) 1.000 NA ≥ 30 9/9 (100) HCV RNA (IU/mL) < 800,000 14/16 (87.5) 0.242 NA ≥ 800,000 16/16 (100) Prior treatment Naive 25/26 (96.2) 0.345 NA Experienced 5/6 (83.3) Comorbidities Diabetes 7/8 (87.5) 0.444 NA Hypertension 15/16 (93.8) 1.000 NA CAD 1/1 (100) 1.000 NA Kidney disease 0 N/A NA Chronic anemia 0 N/A NA Cirrhosis Absent 28/28 (100) 0.012 0.996* Present 2/4 (50) ALT (IU/L) < 40 15/17 (88.2) 0.486 NA ≥ 40 15/15 (100) Data presented as number/total number (percent). *Only variables with the P value < 0.05 in univariate analysis were assessed. BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; ALT: alanine transaminase. Virologic response in Veikira Pak® group Patients treated in this group (ViekiraPak®), 91.7% achieved SVR as shown in Table 4. Similar to Harvoni® group, there was no difference in SVR between cirrhosis and non-cirrhosis patients (100% vs. 90.9%, P value = 1.0). Table 4 SVR 12 Rates in Patients Receiving Viekira Pak® by Population Subgroup Response SVR 12 rate P value Overall 11/12 (91.7) Age group < 65 9/9 (100) 0.250 ≥ 65 2/3 (66.7) Sex Male 7/8 (87.5) 1.000 Female 4/4 (100) BMI (kg/m2) < 30 7/8 (87.5) 1.000 ≥ 30 4/4 (100) HCV RNA (IU/mL) < 800,000 5/5 (100) 0.583 ≥ 800,000 6/7 (85.7) Prior treatment Naive 10/11 (90.9) 1.000 Experienced 1/1 (100) Comorbidities Diabetes 4/5 (80.0) 0.417 Hypertension 6/7 (85.7) 1.000 CAD 1/1 (100) 1.000 Kidney disease 1/2 (50) 0.167 Chronic anemia 1/1 (100) 1.000 Cirrhosis Absent 10/11 (90.9) 1.000 Present 1/1 (100) MELD score < 10 9/10 (90.0) 1.000 ≥ 10 2/2 (100) ALT (IU/L) < 40 8/8 (100) 0.333 ≥ 40 3/4 (75) Data presented as number/total number (percent). BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; ALT: alanine transaminase.

100) MELD score < 10 9/10 (90.0) 1.000 ≥ 10 2/2 (100) ALT (IU/L) < 40 8/8 (100) 0.333 ≥ 40 3/4 (75) Data presented as number/total number (percent). BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; ALT: alanine transaminase. Virologic response in Epclusa® group In this treatment group, eight (100%) achieved SVR (Table 5). This finding is encouraging but may not be truly significant due to minimal sample size. Further studies are required to confirm the real significance of these findings. Table 5 SVR 12 Rates in Patients Receiving Epclusa® by Population Subgroup Response SVR 12 rate P value Overall 8/8 (100) Age group < 65 7/7 (100) N/A ≥ 65 1/1 (100) Sex Male 6/6 (100) N/A Female 2/2 (100) BMI (kg/m2) < 30 4/4 (100) N/A ≥ 30 4/4 (100) HCV RNA (IU/mL) < 800,000 2/2 (100) N/A ≥ 800,000 6/6 (100) Prior treatment Naive 6/6 (100) N/A Experienced 2/2 (100) Comorbidities Diabetes 2/2 (100) N/A Hypertension 5/5 (100) N/A CAD 0 N/A Kidney disease 1/1 (100) N/A Chronic anemia 1/1 (100) N/A Cirrhosis Absent 3/3 (100) N/A Present 5/5 (100) MELD score < 10 5/5 (100) N/A ≥ 10 3/3 (100) ALT (IU/L) < 40 0 N/A ≥ 40 8/8 (100) Data presented as number/total number (percent). BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; ALT: alanine transaminase.

Present 5/5 (100) MELD score < 10 5/5 (100) N/A ≥ 10 3/3 (100) ALT (IU/L) < 40 0 N/A ≥ 40 8/8 (100) Data presented as number/total number (percent). BMI: body mass index; HCV: hepatitis C virus; RNA: ribonucleic acid; APRI: AST-to-platelet ratio index; MELD: model for end-stage liver disease; ALT: alanine transaminase. Safety Out of 52 patients in this study, none of the patients discontinued DAA therapy because of an adverse event. A complete list of all adverse events is shown in Table 6. Fatigue, anemia, arthralgia, nausea, and leucopenia were the most common adverse events observed. There were not any serious adverse events seen among those on all regimens. None of the adverse events were statistically significant among three groups except for anemia which was significantly observed in Viekira Pak® group. Table 6 Treatment Adverse Events Adverse event Treatment Regimen P value Harvoni® Viekira Pak® Epclusa® Fatigue 12 (37.5) 1 (8.3) 1 (12.5) 0.092 Headache 1 (3.1) 0 0 0.727 Dizziness 4 (12.5) 1 (8.3) 0 0.554 Nausea 3 (9.4) 0 2 (25.0) 0.178 Vomiting 1 (3.1) 0 0 0.727 Photosensitivity 2 (6.3) 0 1 (12.5) 0.493 Skin rash 2 (6.3) 0 0 0.522 Itching 4 (12.5) 0 0 0.258 Arthralgia 5 (15.6) 1 (8.3) 0 0.430 Anemia 3 (9.4) 5 (41.7) 1 (12.5) 0.039 Thrombocytopenia 1 (3.1) 0 1 (12.5) 0.342 Leukopenia 3 (9.4) 2 (16.7) 1 (12.5) 0.793 Data presented as number (percent).

Vomiting 1 (3.1) 0 0 0.727 Photosensitivity 2 (6.3) 0 1 (12.5) 0.493 Skin rash 2 (6.3) 0 0 0.522 Itching 4 (12.5) 0 0 0.258 Arthralgia 5 (15.6) 1 (8.3) 0 0.430 Anemia 3 (9.4) 5 (41.7) 1 (12.5) 0.039 Thrombocytopenia 1 (3.1) 0 1 (12.5) 0.342 Leukopenia 3 (9.4) 2 (16.7) 1 (12.5) 0.793 Data presented as number (percent). Discussion This study represents the data regarding the efficacy of HCV GT4 treatment in a diverse group of patients including both treatment-naive and treatment-experienced patients, and those with and without several co-morbidities including cirrhosis. We compared treatment efficacy and tolerability with the existing literature in HCV GT-4 patients. In this community-based hospital retrospective study of HCV-GT4, we observed high SVR rates in all the treatment groups. The SVR achieved in a study by El-Zayadi et al with interferon-based regimens in HCV-GT4 was between 66% to 69%, moreover the duration of treatment was even longer ranging from 24 to 48 weeks [7]. Lawitz et al showed that with the addition of DAA, especially sofosbuvir plus peginterferon and ribavirin in the open-label study for 12 weeks of treatment in a single group achieved high efficacy in treatment naive patients [8].

o 69%, moreover the duration of treatment was even longer ranging from 24 to 48 weeks [7]. Lawitz et al showed that with the addition of DAA, especially sofosbuvir plus peginterferon and ribavirin in the open-label study for 12 weeks of treatment in a single group achieved high efficacy in treatment naive patients [8]. Subsequently, Ruane et al reported that sofosbuvir and ribavirin alone for 12 to 24 weeks had a wide variation in SVR rates ranging between 59% and 100% in both HCV GT4 treatment-naive and treatment-experienced patients [9]. Another multicenter trial (PEARL-I RCT) had also shown that 12-week regimen of ombitasvir/paritaprevir/ ritonavir ± ribavirin had high SVR12 in HCV GT 4 patients [10]. This study is also comparable to our study, where patients receiving the same regimen demonstrated equal efficacy regarding SVR in all the subjects in that group. Unlike other trial, with peginterferon, our study with DAA based regimens had no impact on the pretreatment HCV RNA levels [11]. Treatment among cirrhotics also did not have an impact on SVR 12 in all the regimens.

Subsequently, Ruane et al reported that sofosbuvir and ribavirin alone for 12 to 24 weeks had a wide variation in SVR rates ranging between 59% and 100% in both HCV GT4 treatment-naive and treatment-experienced patients [9]. Another multicenter trial (PEARL-I RCT) had also shown that 12-week regimen of ombitasvir/paritaprevir/ ritonavir ± ribavirin had high SVR12 in HCV GT 4 patients [10]. This study is also comparable to our study, where patients receiving the same regimen demonstrated equal efficacy regarding SVR in all the subjects in that group. Unlike other trial, with peginterferon, our study with DAA based regimens had no impact on the pretreatment HCV RNA levels [11]. Treatment among cirrhotics also did not have an impact on SVR 12 in all the regimens. In our study, among subjects who received SOF/LDV, the overall SVR rate was as high as 93.8 %. This was similar to a study conducted by Hassanein et al where treatment with SOF/LDV for 12 weeks was evaluated in 21 treatment-naive and treatment-experienced patients [12]. This study showed that 19 of 20 (95%) achieved SVR12 which was similar to our study. In another trial (the SYNERGY trial), the overall SVR in SOF/LDV for 12 weeks was well tolerated and SVR achieved was 100% regardless of previous treatment status and underlying liver cirrhosis [13]. However, SVR 12 achieved in compensated cirrhosis was only 50% in our study, which could be attributed to small sample size with cirrhosis. El-Khayat et al in a recent real world study done on adolescents with HCV GT4 with SOF/LDV regimen also showed SVR 12 of 99 % [14]. Our study was also similar to another clinical trial by Feld et al in terms of SVR 12 with similar regimens regardless of cirrhosis and treatment-experienced status [15].

e with cirrhosis. El-Khayat et al in a recent real world study done on adolescents with HCV GT4 with SOF/LDV regimen also showed SVR 12 of 99 % [14]. Our study was also similar to another clinical trial by Feld et al in terms of SVR 12 with similar regimens regardless of cirrhosis and treatment-experienced status [15]. Currently, sofosbuvir/velpatasvir is a pan-genotypic HCV treatment option approved for 12 weeks with compensated cirrhosis, which has SVR rates of 99% in all HCV genotypes infection [13-16]. This holds true with our sofosbuvir/velpatasvir group where SVR rate was 100 % and none of the co-morbidities had affected the SVR in any subgroups in this treatment group. Adverse events seen in our study are consistent with other DAA based studies [8, 17]. None of the patients discontinued therapy due to any adverse effect in any group. This shows that patients tolerate DAA-based regimens quite well in our study. However, anemia was more frequently noted in Viekira Pak® with RBV group as these regimens include ribavirin which is well-known to cause hemolytic anemia. Our study is unique in assessing and comparing the real-world effectiveness, tolerability, and safety of different therapeutic regimens in HCV GT-4 infection. There are several limitations of our study including retrospective analysis, and a small number of patients were examined, and only subjects with compensated cirrhosis were included.

n assessing and comparing the real-world effectiveness, tolerability, and safety of different therapeutic regimens in HCV GT-4 infection. There are several limitations of our study including retrospective analysis, and a small number of patients were examined, and only subjects with compensated cirrhosis were included. Conclusions In the real-world community practice setting, DAAs are effective and well tolerated in patients with chronic HCV GT-4 infection with a high overall SVR rate of 94%. Further large-scale studies are needed to assess response in these groups. Conflict of Interest Dr. Mohanty is on the Speakers Bureau for Gilead Science, BMS, and Abbvie Pharmaceuticals. For the remaining authors, there is no conflict of interest. Funding None. Abbreviations HCVhepatitis C virus HCChepatocellular cancer DAAsdirect-acting antivirals GTgenotype SOFsofosbuvir RBVribavirin Harvoni®ledipasvir/sofosbuvir ViekiraPak®ombitasvir/paritaprevir/ritonavir/dasabuvir SPVsimeprevir LDVledipasvir Epclusa®sofosbuvir/velpatasvir SVR12sustained virologic response at 12 weeks post treatment APRIaspartate aminotransferase-to-platelet ratio index ESLDend stage liver disease ARTantiretroviral therapy