Sofosbuvir-based Therapy Research Articles

Predictors of response to daclatasvir in addition to sofosbuvir in hepatitis C virus-infected patients with stage 4 and 5 chronic kidney disease and patients on maintenance hemodialysis

BackgroundThe FDA authorized the use of sofosbuvir-based therapy in persons with chronic kidney disease (CKD) stages 4 and 5 and in those on maintenance hemodialysis (HD). It has been known that treatment efficacy might be affected by virus- and host-related parameters. The aim of this study was to identify the response rate of sofosbuvir plus daclatasvir in CKD stage 4/5 and HD patients. The secondary aim was to identify the predictors of treatment failure.MethodsThis cross-sectional study was conducted on 55 HCV-infected patients recruited from Alexandria University hospitals. The study included patients on maintenance HD or CKD stages 4–5. Baseline characteristics and SNP genotyping of the IFNL4 rs368234815 variant were addressed as possible predictors of response. The participants received sofosbuvir alongside daclatasvir with or without ribavirin for 3–6 months, according to the EASL guidelines. The response was evaluated by testing serum HCV RNA using PCR 12 weeks after treatment.ResultsOnly 29 patients achieved sustained virologic response (SVR) (52.7%). Non-responders had statistically significantly lower hemoglobin, platelets, and albumin, while they had higher INR, liver enzymes, bilirubin, and APRI scores. FIB-4 scores were significantly lower among responders (1.64 ± 0.74 versus 4.81 ± 1.82) (p < 0.001). Among those with treatment failure, 13 patients (50%) had the TT/G genotype, while only 3 patients (11.5%) of the TT/TT genotype failed to achieve SVR12. Only 13.8% of patients with the G/G genotype achieved SVR12 (P = 0.001). Multivariate regression revealed that higher FIB-4 was the only predictor of failure to achieve SVR12. FIB-4 at a cutoff level of 2.63 has a sensitivity, specificity, PPV, and NPV for prediction of treatment failure of 88.46%, 93.10%, 92%, and 90%, respectively.ConclusionsFIB-4 above 2.63 is a predictor of lower SVR rates among patients with advanced CKD stages.

Assessing the Efficacy of Novel Antiviral Therapies in Treating Hepatitis C.

Hepatitis C virus (HCV) infection is a major global health burden, with an estimated 58 million people chronically infected worldwide, according to the World Health Organization (WHO).While many people remain asymptomatic during the early stages of infection, chronic hepatitis C can cause long-term liver damage, significantly increasing the morbidity and mortality associated with the disease. The primary objective of this technical report is to find the efficacy of novel antiviral therapies in treating hepatitis C in a tertiary care hospital in Lahore. This technical report was done in Shalamar Hospital, Lahore, from June 2023 to June 2024. Data for the report were collected retrospectively from 500 patients through a review of patient medical records from the hospital. Medical and electronic health records provided the patient demographics (age, gender, ethnicity), hepatitis C genotype, liver disease stage (fibrosis or cirrhosis staging), previous treatment history, and type of antiviral therapy administered (direct-acting antivirals (DAA)).Out of 500, there were 280 (56%) male and 220 (44%) female patients. The mean age of the patients was 41.23±5.67 years. Patients were divided among mild, advanced, and post-liver transplant as 320 (64%), 150 (30%), and 30 (6%), respectively.Among the DAA regimens, sofosbuvir-based therapies had the highest sustained virologic response (SVR) rate of 95%, followed by glecaprevir/pibrentasvir at 93%. Ledipasvir/sofosbuvir and other DAAs showed slightly lower SVR rates, at 89% and 87%, respectively, indicating high overall efficacy across different therapies. This report concluded that DAAsare highly effective in treating hepatitis C, with an overall SVR rate of 92% and good tolerability across most patient groups. However, patients with genotype III, advanced liver disease, or post-liver transplant status may require personalized treatment approaches due to slightly lower efficacy.

IFNL4 genotype and other personal characteristics to predict response to 8-week sofosbuvir-based treatment for chronic hepatitis C

Shorter duration therapy for hepatitis C virus (HCV) infection might reduce treatment costs and increase the number of patients treated and cured. We determined factors associated with treatment response after an 8-week sofosbuvir-based therapy and developed a simple model to predict an individual's likelihood of treatment success. Among 2907 patients who received ledipasvir/sofosbuvir for 8 weeks, we determined failure rates by demographic and clinical characteristics, and IFNL4-∆G/TT genotype. We estimated the average IFNL4 genotype-related treatment failure rate in major ancestry groups by applying our IFNL4 genotype results to genotype distributions from reference populations. We created a treatment response model based on three personal characteristics. Overall, 4.4% of the patients failed treatment. We observed significantly lower failure rates for persons <50 years (1.6%), females (2.6%), those carrying the IFNL4-TT/TT genotype (1.8%), those with HCV RNA <5.8log10 copies/mL (2.0%) or HCV genotype-1B infection (2.6%). In a model based on ancestry, age and sex, the predicted probability of treatment failure ranged from 0.5% among females of East Asian ancestry <50 years of age to 8.5% among males of African ancestry age ≥65 years. Applying this algorithm at the point-of-care might facilitate HCV elimination, especially in low- and middle-income countries.

IL28B rs12979860 gene polymorphism and sofosbuvir-based therapy response in HCV-infected Pakistani patients

IL28B rs12979860 gene polymorphism and sofosbuvir-based therapy response in HCV-infected Pakistani patients

Prediction of response to sofosbuvir-based therapy using serum interleukin-12 and single nucleotide polymorphism of the interleukin 28B gene as predictive factors in HCV positive genotype-4 patients.

Some hepatitis-C virus patients have resistance to direct-acting-antivirals (DAAs). Genetic polymorphisms have been associated with drug resistance. This study aimed to evaluate the role of interleukin (IL)-28B gene polymorphism and IL-12 levels as predictors for a response to sofosbuvir/ribavirin (SOF/RBV) with (triple-therapy) or without (dual-therapy) Peg-alpha-interferon. 92 hepatitis C virus (HCV)/RNA (+)-patients treated with dual (n = 72) or triple (n = 20) therapy. IL28B genetic polymorphism and IL-12 level assessments. 30.4% of the patients were IL28B C/C genotype, 56.5% C/T-genotype, and 13% T/T-genotype. Mean baseline IL-12 levels were 27.5 ± 3.0 pg/mL. Rapid viral response was achieved in 86/92 patients. All patients achieved end-of-treatment virologic response. The 12- and 24-week sustained virologic responses (SVR) were achieved in 76 patients (82.6%), that is, a relapse was found in 16 patients (17.4%). 8 and 12-weeks after antiviral therapy, IL-12 levels decreased significantly, and became comparable to those of the control-group. That drop in IL-12 levels was similar across the dual- and triple-therapy patients. Finally, logistic regression analysis showed that the increase in baseline aspartate aminotransferase (AST) and T/T genotyping had an independent effect on increasing the probability a SVR failing in both dual- and triple-therapy groups (P = .0007 and P = .02, respectively). Single-nucleotide polymorphism (SNP) in IL-28B and IL-12 levels play roles as predictors in DAAs resistance.

Patient-reported outcomes with direct-acting antiviral treatment for hepatitis C in West and Central Africa (TAC ANRS 12311 trial)

Patient-reported outcomes (PROs) are poorly documented for patients with chronic hepatitis C on direct-acting antiviral (DAA) treatment in low-to-middle-income countries. We documented PROs during and after DAA treatment in participants of the TAC ANRS 12311 trial (West and Central Africa). Trial participants received a 12-week regimen containing either sofosbuvir plus ribavirin (HCV genotype 2, n= 40), or sofosbuvir plus ledipasvir (HCV genotypes 1 and 4, n= 80). Health-related quality of life (SF-12), fatigue (Piper Fatigue scale), and self-reported symptoms (35-symptom list) were assessed at enrolment (Week (W) 0), during treatment (W2, W4, W8 and W12) and after treatment (W24 and W36). These PROs were compared between W0 and W36 (Wilcoxon signed-rank or McNemar tests). Mixed-effects linear regression models helped identify correlates of physical and mental quality of life component summaries (PCS and MCS) in a longitudinal analysis. Most PROs were significantly improved 24 weeks after treatment end (W36), without significant differences between treatment groups. For the post-treatment period, multivariable analysis showed significant increases in PCS for patients with cirrhosis and in MCS for patients in the sofosbuvir plus ribavirin group. A higher number of self-reported symptoms at W0 was associated with lower PCS and MCS, older age and cirrhosis with lower PCS, and male sex and HCV cure with higher PCS. Sofosbuvir-based DAA therapy was associated with a significant improvement in PROs 6 months after treatment end in patients with chronic HCV infection from Central and West Africa. These findings may guide HCV treatment providers in low-to-middle-income countries to deliver pre-treatment information concerning the benefits of DAAs beyond viral eradication. NCT02405013. Perceptions and experiences (i.e. "patient-reported outcomes") of patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) are poorly documented in the African setting. This study shows significant improvements in health-related quality of life, fatigue, and self-reported symptoms 24 weeks after the end of a 12-week sofosbuvir-based DAA regimen in 120 patients from Central and West Africa. These findings substantially add to the body of knowledge about DAA therapy in the African setting. Treatment providers should be encouraged to inform patients of the benefits of DAAs beyond viral eradication, to increase treatment adherence and retention in care.

Interleukin 28B Polymorphism as a Predictor of Sustained Virological Response to Sofosbuvir-Based Therapy for Hepatitis C Virus Patients.

In various genome-wide correlation studies, interleukin (IL)28B gene polymorphism has been strongly correlated with both the therapeutic and spontaneous mediated clearance of hepatitis C virus (HCV). Therefore, this study aimed to evaluate the genotype and allele frequency distributions of IL28B (rs12979860) in patients with chronic hepatitis C and assess the IL28B polymorphisms as predictors of sustained virological response to SOF-based therapy for HCV in Egyptian patients. This retrospective case-control study was conducted on 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and responded to treatment with SVR12 (the responder group) as a control group, and 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and did not respond to treatment and failed to achieve SVR12 (the non-responder group) as a case group. The CC genotype frequency of IL-28B (rs12979860) was greater in the responder group (51.9%). In contrast, the TT genotype frequency was higher in the non-responder group (48.1%) (p < 0.001), and the T allele significantly increased the risk of non-responses by 3.13 fold. Therefore IL-28B (rs12979860) SNP could be used as a genetic predictor of sustained virological response to SOF+DCV ± RBV-based HCV treatment in Egyptian patients.

Sofosbuvir-based therapy for late pregnant women and infants with severe chronic hepatitis C: A case series study.

Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.

Successful Eradication of Hepatitis C Virus with Sofosbuvir based Antiviral treatment results in improvement in quality of life in cirrhotic patients

Hepatitis C virus (HCV) infection has long been a serious global public health concern; it is not only the main cause of end-stage liver disease, but it is also a leading source of liver cancer, but it also increases the risk of mortality from a variety of extrahepatic illnesses. Objective: The study's main objective is to see if successfully eradicating the Hepatitis-C virus with sofosbuvir-based antiviral therapy improves cirrhotic patients' quality of life. Methods: This cross-sectional study was conducted in Faisalabad Medical University from June 2019 to June 2020. The data was collected from 70 patients. The data was collected through a non-probability consecutive sampling technique. Results: The data were collected from 70 patients of both genders. We compared patients' quality of life. With sofosbuvir and ribavirin, 56 patients (79%) reached Sustained Virologic Response 12 (SVR12), Sofosbuvir, daclatasvir, and ribavirin were administered to 13 patients (18%), while sofosbuvir and ledipasvir were administered to two individuals (3%).Conclusions: Infection with chronic HCV, which is made worse by cirrhosis, has a major negative influence on the patient's physical, mental, social, and functional well-being, leading to a considerable reduction in their overall quality of life.

Effect of Direct-Acting Antiviral Drugs on Erectile Functions among Hepatitis C Patients: A Prospective Interventional Study.

Erectile dysfunction (ED) is one of the extrahepatic manifestations of hepatitis C virus infection that greatly affects patients' quality of life. Unfortunately, some of the drugs used for HCV treatment may have a negative impact on the patient's erectile function, such as the pegylated interferon. Currently, with the introduction of direct-acting antiviral drugs, there is scarce data in the literature about its potential impact on erectile function. In these settings, we aimed to assess the impact of sofosbuvir-based therapy on male erectile function. This prospective interventional study was carried out in Benha University hospitals between January 2019 and May 2020. The study included all consecutive HCV patients with simultaneous ED coming to the hepatology outpatient clinic. Patients were divided into a study group who received sofosbuvir-based therapy (group A) or a control group who received silymarin therapy (group B). The International Index of Erectile Function-5 (IIEF-5) was used for the assessment of erectile function at different time points (pretreatment, 6 months, and 12 months after treatment). Different variables in both groups have been statistically analyzed. Overall, 75 patients who received sofosbuvir-based therapy and a control group (n = 35) matched for age and pretreatment variables (Child-Turcotte-Pugh score and Fibrosis-4 score). There was no significant difference between both groups in the pretreatment data. On the other hand, the posttreatment IIEF-5 was significantly higher in the sofosbuvir arm compared to the silymarin arm both at six months (p<0.001) and at 12 months (p<0.001). Furthermore, the age and the stage of liver fibrosis were negatively correlated with IIEF-5 at all-time points. The age and the stage of liver fibrosis are significantly correlated with the degree of ED. Furthermore, sofosbuvir-based therapy may be associated with significant improvement in patients with erectile function.

Patient-specific genetic factors predict treatment failure in sofosbuvir-treated patients with chronic hepatitis C.

According to pivotal clinical trials, cure rates for sofosbuvir-based antiviral therapy exceed 96%. Treatment failure is usually assumed to be because of virological resistance-associated substitutions or clinical risk factors, yet the role of patient-specific genetic factors has not been well explored. We determined if patient-specific genetic factors help predict patients likely to fail sofosbuvir treatment in real-world treatment situations. We recruited sofosbuvir-treated patients with chronic hepatitis C from five Canadian treatment sites, and performed a case-control pharmacogenomics study assessing both previously published and novel genetic polymorphisms. Specifically studied were variants predicted to impair CES1-dependent production of sofosbuvir's active metabolite, interferon-λ signalling variants expected to impact a patient's immune response to the virus and an HLA variant associated with increased spontaneous and treatment-induced viral clearance. Three hundred and fifty-nine sofosbuvir-treated patients were available for analyses after exclusions, with 34 (9.5%) failing treatment. We identified CES1 variants as novel predictors for treatment failure in European patients (rs115629050 or rs4513095; odds ratio (OR): 5.43; 95% confidence interval (CI): 1.64-18.01; P=.0057), replicated associations with IFNL4 variants predicted to increase interferon-λ signalling (eg rs12979860; OR: 2.25; 95% CI: 1.25-4.06; P=.0071) and discovered a novel association with a coding variant predicted to enhance the activity of IFNL4's receptor (rs2834167 in IL10RB; OR: 1.81; 95% CI: 1.01-3.24; P=.047). Ultimately, this work demonstrates that patient-specific genetic factors could be used as a tool to identify patients at higher risk of treatment failure and allow for these patients to receive effective therapy sooner.

POS-836 REAL-WORLD EFFECTIVENESS STUDY OF SOFOSBUVIR-DACLATASVIR WITH OR WITHOUT RIBAVIRIN IN TREATING CHRONICALLY INFECTED HCV PATIENTS WITH END-STAGE KIDNEY FAILURE: AN INTERIM RESULT

Hepatitis C virus (HCV) infection is a major public health threat in Malaysia and haemodialysis is a known risk factor for its transmission. Sofosbuvir-based therapies were recently introduced in Malaysia to treat chronic HCV but evidence on its effectiveness to treat patients with end-stage kidney failure (ESKF) under usual clinical settings remains limited. We initiated the first effectiveness research in the country to evaluate the use of sofosbuvir-daclatasvir with or without ribavirin (SOF-DVC ± RBV) in the ESKF population to treat chronic HCV infection.

Occult HCV infection in liver transplanted patients: frequency and consequences.

Aim of the studyOccult hepatitis C virus (HCV) infection (OCI) is a potential source of relapse after liver transplantation with subsequent graft damage. The aim of the study was to detect OCI in patients with living donor liver transplantation (LDLT) who achieved sustained virological response (SVR) after sofosbuvir-based antiviral treatment, and to detect risk factors associated with the development of OCI as well as to determine the effect of direct acting antiviral (DAA) therapy after liver transplantation.Material and methods41 patients with living donor liver transplantation who did not receive DAAs before with recurrent HCV infection who achieved a SVR with sofosbuvir-based therapy for 12-24 weeks were recruited. These patients were tested for OCI by HCV-RNA in peripheral blood mononuclear cells (PBMNCs). Those patients with OCI were followed up every 6 months with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum HCV-RNA by PCR for 2 years.Results92.7% of treated patients achieved HCV SVR 12 weeks. OCI was detected in 4 patients. After follow-up for 18 months, 3 patients continued to have OCI, but one patient presented with progressive elevation of liver enzymes and developed overt HCV infection with positive HCV-RNA PCR in the serum. This patient was retreated with sofosbuvir 400 mg + ledipasvir 90 mg for 12 weeks with resultant negative HCV-RNA PCR in both serum and PBMNCs in addition to normalization of liver enzymes.ConclusionsOccult HCV infection is a potential source of HCV relapse after liver transplantation which should be investigated for in PBMNCs or liver biopsy.

Three regimens for re-treatment failure of Sofosbuvir-based therapy for chronic hepatitis-C genotype-4: a cohort study.

ABSTRACTDespite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.

Sofosbuvir-based antiviral therapy provided highly treatment efficacy, safety, and good tolerability for Taiwanese chronic hepatitis C patients with decompensated cirrhosis.

For patients with hepatitis C virus (HCV)-related decompensated cirrhosis, poor prognosis was documented due to the development of portal hypertension-related complications and hepatocellular carcinoma. Sofosbuvir-based direct-acting antiviral agents (DAAs) has revolutionized the treatment landscape of HCV, particularly in this subpopulation. To date, real-world efficacy, tolerability, and safety profiles for Taiwanese HCV-related decompensated cirrhosis treated by DAAs have not been reported. Between December 2015 and June 2020, 50 consecutive HCV-related Child-Turcotte-Pugh (CTP) classes B or C cirrhotics treated by sofosbuvir-based DAAs (with daclatasvir: 7, with ledipasvir: 32, with velpatasvir: 10, with ledipasvir then shifted to velpatasvir: 1) were enrolled. Forty-seven (94%) patients used DAAs in combination with low-dose ribavirin. SVR12 was defined by undetectable HCV RNA (<15 IU/mL) at treatment end and 12 weeks after the completion of therapy. The mean age of the enrolled patients was 68.1 ± 11.2 years, 18% of the patients were CTP class C, and the baseline HCV RNA level was 5.42 ± 1.2 log10 IU/mL. The genotype distribution was as follows: 1a: 3; 1b: 34; 2: 9; 6: 3; and one patient with an unclassified HCV genotype. After DAAs treatment, the rates of undetectable HCV RNA at week 4 and at the end of the treatment were 88.9% and 98.0%, respectively. Subjective adverse events were reported by 42.0% of the patients, but they were generally mild and could be relieved by medications. One patient did not finish therapy due to sepsis with multiple organ dysfunction. The overall SVR12 rate was 96.0% (CTP class B: 97.6%, CTP class C: 88.9%). A significant improvement in hepatic functional reserve was noted after successful antiviral therapy. For patients with HCV-related decompensated cirrhosis, which has been considered a contraindication for interferon-based therapy, sofosbuvir-based all-oral DAAs provided high treatment efficacy, acceptable safety, and good tolerability.

Impact of Sofosbuvir-Based Direct-Acting Antivirals on Renal Function in Chronic Hepatitis C Patients With Impaired Renal Function: A Large Cohort Study From the Nationwide HCV Registry Program (TACR)

Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. The 12,995 CHC patients treated with sofosbuvir-based (n= 6802) or non-sofosbuvir-based (n= 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P<.001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only inpatients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2; P<.001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m2; 95% confidence interval, -2.24 to -1.72; P< .001). The use of sofosbuvir was not an independent factor associated with eGFR change. Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

Sofosbuvir-based therapies in genotype 2 hepatitis C virus cirrhosis: A real-life experience with focus on ribavirin dose.

This study aimed to investigate the efficacy and safety of sofosbuvir‐based therapies for the treatment of cirrhosis from hepatitis C virus (HCV) genotype 2 infection. Data of all consecutive HCV genotype 2 cirrhotic patients who started sofosbuvir‐based treatments between January 2015 and March 2017 in eight Italian tertiary hospitals were collected retrospectively. Overall, 273 patients (Child A: 94.5%) were enrolled. In the 194 subjects treated with sofosbuvir/ribavirin, median initial ribavirin dosage was 13.9 mg/kg/day, and therapy duration was 16 weeks. Sustained virological response (SVR) rates were 93.8% in intention‐to‐treat (ITT) and 95.3% in per‐protocol (PP) analyses for the 129 treatment‐naïve patients, and 96.9% (ITT) and 98.4% (PP) for the 65 treatment‐experienced subjects. Adverse events were reported in 142 patients (73.2%), but only 1.5% discontinued treatment. Eighty‐eight subjects with treatment‐induced anemia (mild: 34.5%, moderate: 7.7%, severe: 3.1%) had to reduce ribavirin dosage, but SVR rates were comparable to the weight‐based dose group, both in ITT (95.4% and 94.3%) and PP (97.7% and 95.2%) analyses, respectively. Moreover, ITT and PP SVR rates were similar between shorter (<20 weeks) (94.1% and 96.0%, respectively) and prolonged (≥20 weeks) regimens (95.7% and 96.7%, respectively). SVR rates in the 79 subjects treated with sofosbuvir/daclatasvir (without ribavirin) were similar (ITT: 96.2%; PP: 97.4%, respectively), without de novo/worsening anemia. In conclusion, in a real‐life study centered on genotype 2 patients with well‐compensated cirrhosis, sofosbuvir‐based regimens were associated with good SVR and tolerability rates, regardless of previous antiviral treatments, without a significant impact of on treatment ribavirin dose reductions.

Sofosbuvir-Based Therapies Achieved Satisfactory Virological Response in Chinese Individuals with Genotypes 3 and 6 Infections: A Real-World Experience.

BackgroundPrevious studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection.MethodsThis is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12).ResultsOverall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred.ConclusionReal-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections.

Effect of Direct-Acting Antiviral Therapy on Thrombocytopenic Patients with Hepatitis C Virus-Related Chronic Liver Disease.

Background and Aims Thrombocytopenia is a common complication in patients with chronic hepatitis C virus (HCV) that increases the risk of bleeding. We aimed to analyze the hematologic effects of the new direct-acting antiviral (DAA) therapy, particularly on the platelet count in chronic HCV-infected patients with thrombocytopenia. Patients and Methods. One hundred thrombocytopenic patients chronically infected with HCV were included in a prospective study. All patients were eligible for receiving anti-HCV treatment with sofosbuvir-based regimens for 12 weeks, according to the protocol of the National Program for treatment of HCV in Egypt sponsored by the Ministry of Health. Results At the end of treatment (EOT), there was a highly significant increase in platelet count (p < 0.001), a significant increase in white blood cells (WBCs) count (p ≤ 0.032), and a highly significant decrease in hemoglobin level (p < 0.001) as compared to pretreatment levels. Patients with mild to moderate hepatic fibrosis had significantly higher median and interquartile range (IQR) platelet count at baseline and EOT than those with advanced fibrosis and cirrhosis (p ≤ 0.023 and p < 0.001, respectively). There was more elevation in platelet count at EOT in patients with mild to moderate fibrosis than those with advanced fibrosis and cirrhosis. Out of the hundred patients, 73% showed improvement of platelet count, while 27% showed no improvement or even decrease in the platelet count. Conclusion Sofosbuvir-based DAA therapy is a highly effective and safe treatment regimen that results in the improvement of platelet count in thrombocytopenic patients, particularly in mild to moderate stages of hepatic fibrosis.

Real-World Data from Turkey: Is Sofosbuvir/Ledipasvir With or Without Ribavirin Treatment for Chronic Hepatitis C Really Effective?

In this study, we aimed to investigate the efficacy and safety of sofosbuvir-based therapies in the treatment of chronic hepatitis C in real-world clinical practice. Data from patients with chronic hepatitis C treated with SOF/LDV ± RBV or SOF/RBV in 31 centers across Turkey between April 1, 2017, and August 31, 2018, were recorded in a nationwide database among infectious disease specialists. Demographics, clinical, and virological outcomes were analyzed. A total of 552 patients were included in the study. The mean age of the patients was 51.28 ± 14.2, and 293 (55.8%) were female. The majority had HCV genotype 1b infection (65%), 75.04% of the patients underwent treatment, and non-cirrhosis was present at baseline in 381 patients (72.6%). SOF/LDV ± RBV treatment was given to 477 patients and 48 patients received SOF/RBV according to HCV genotype. The total SVR12 rate was 99% in all patients. Five patients experienced disease relapse during the study and all of them were genotype 2. In patients infected with HCV GT2, SVR12 was 77.3%. SVR was 100% in all patients infected with other HCV genotypes. All treatments were well tolerated by patients without causing severe adverse events. Side effects and side effects-associated treatment discontinuation rates were 28.2% and 0.4%, respectively. Weakness (13.7%) was the common side effect. The present real-world data of 525 patients with HCV genotypes 1, 1a, 1b, 3, 4, and 5 who underwent SOF/LDV ± RBV treatment in Turkey demonstrated a high efficacy and safety profile. HCV GT2 patients should be treated with more efficacious treatment.