Effectiveness Of Direct-acting Antivirals Research Articles

Effect of direct-acting antivirals on the titers of human pegivirus 1 during treatment of chronic hepatitis C patients.

Human pegivirus 1 coinfections are common in hepatitis C virus (HCV) patients, persisting for years. However, little is known about how pegivirus coinfections are affected by treatment with pangenotypic direct-acting antivirals (DAAs) against HCV. We identified human pegivirus by metagenomic analysis of chronic HCV patients undergoing protease, NS5A, and polymerase inhibitor treatment, in some patients with the addition of pegylated interferon, and followed viral kinetics of both viruses to investigate treatment effects. Only during HCV DAA treatment regimens that included the more broad-spectrum drug sofosbuvir could we detect a consistent decline in pegivirus titers that, however, rebounded to pretreatment levels after treatment cessation. The addition of pegylated interferon gave the highest effect with pegivirus titers decreasing to below the assay detection limit, but without clearance. These results reveal the limited effect of frontline HCV drugs on the closest related human virus, but sofosbuvir appeared to have the potential to be repurposed for other viral diseases.

Sustained Virological Response After Early Discontinuation of Hepatitis C Treatment.

To date, the effectiveness of direct-acting antivirals (DAAs) discontinued before 4 weeks has not been analysed in routine clinical practice. The study aimed to determine whether such a short therapy will enable achieving a sustained virological response under real-world experience. The study population of 97 patients who discontinued DAA therapy and had data enabling analysis of patient and disease characteristics, and assessment of treatment effectiveness was selected from 16,815 patients registered in the EpiTer-2 database. The most common reason for discontinuation was hepatic decompensation (20.6%) or the patient's personal decision (18.6%). Patients who discontinued treatment were significantly older, more frequently therapy-experienced, more likely to have cirrhosis, a history of decompensation and a Child-Pugh B or C classification than those who completed treatment. SVR was achieved by 93.5% of patients who discontinued treatment after 4 weeks, 60.9% if discontinued at 3 or 4 week and 33.3% at Week 1 or 2. Patients receiving pangenotypic but not genotype-specific treatment who discontinued after 4 weeks were as likely to achieve SVR as those who completed therapy. Patients who responded to treatment that lasted no longer than 2 weeks had a low baseline viral load (<400,000 IU/mL). Despite discontinuation of therapy after Week 4, the chances of SVR are high. Very early discontinuation does not preclude therapeutic success, especially in patients with low baseline viral load.

Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007–2021: a nationwide, multicentre, retrospective cohort study

It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p<0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p<0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p<0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p<0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p<0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p<0.0001). Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. The Korea Disease Control and Prevention Agency.

Elucidating the association between direct-acting antivirals and Parkinson's disease in patients with hepatitis C virus infection

BackgroundSome epidemiological studies have found an increased association between Parkinson's disease (PD) and chronic hepatitis C virus (HCV) infection. Although a few studies have also found a decreased risk of PD with interferon-α therapy, the effect of direct-acting antivirals (DAAs) on Parkinson's disease remains unclear. The current study seeks to assess and elucidate the association between DAAs and PD in patients newly diagnosed with chronic HCV infection. MethodsWe conducted a retrospective cohort study of patients ≥18 years diagnosed with HCV using MarketScan Commercial and Medicare Supplemental database (2012–2019). Follow-up started with the initiation of DAA (or randomly assigned date for the non-DAA group) and ended at occurrence of PD, disenrollment, or end of the study period. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals. ResultsWe identified 48,356 patients diagnosed with HCV. The mean follow-up time of the cohort was 1.31 years. The incidence rate of PD was 53 per 100,000 person-years for the DAA group and 48 per 100,000 person-years for the non-DAA group. The adjusted HR was 1.24 (95% CI = 0.56–2.73). Results were consistent across sensitivity and subgroup analyses. ConclusionThis study did not find an association between DAAs and PD among patients with HCV infection.

Real-world Safety and Effectiveness of 24-week Sofosbuvir and Ribavirin Treatment in Patients Infected with Rare Chronic Hepatitis C Virus Genotypes 3, 4, 5, or 6 in Japan.

Objectives Real-world evidence on the safety and effectiveness of direct-acting antivirals in patients infected with chronic hepatitis C virus (HCV) genotypes (GTs) 3, 4, 5, or 6 in Japan is limited. This prospective observational study assesses the real-world safety profile and treatment effectiveness among patients prescribed sofosbuvir with ribavirin (SOF+RBV) for HCV GT3-6 infection in Japan. Methods Adults receiving 24-week SOF+RBV treatment for HCV GT3-6 infection were prospectively enrolled and observed through 24 weeks post-treatment for treatment-emergent adverse events (AEs) considered related to SOF and/or RBV by treating physicians and for a sustained virologic response at 12 and 24 weeks post-treatment (SVR12, SVR24). Incidence rates of related AEs and serious AEs (SAEs) were calculated. Proportions of patients experiencing related AEs/SAEs and those achieving SVR12 and SVR24 were assessed overall and by baseline characteristics, including treatment experience and cirrhosis status. Results Among the 50 patients included in the safety analysis, 92% had GT3 infection. The incidence rates of related AEs and SAEs were low overall (1.52 and 0.25 per 100 person-weeks, respectively), with 6.0% and 14.0% patients experiencing AEs related to SOF or RBV, respectively. There were no marked differences in the occurrence of related AEs/SAEs by patient baseline characteristics. SVR12 and SVR24 were achieved in 83.7% (41/49) and 82.2% (37/45) of patients, respectively. Lower effectiveness was observed among treatment-experienced patients and patients with cirrhosis at baseline. Conclusions This study demonstrated that SOF+RBV treatment for HCV GT3-6 infection was safe, effective, and an important treatment option for this difficult-to-treat patient population in Japan.

Human pegivirus viremia in HCV/HIV co-infected patients: Direct acting antivirals exert anti-pegivirus effects.

Human pegivirus (HPgV) is a single-stranded RNA virus​ thatis closely related to hepatitis C virus (HCV)​. HPgVhasalsobeen shown to infect patients with human immunodeficiency virus (HIV). The mechanisms and disease outcomes of HPgV infections are largely unknown, although it has been implicated in both cancer and neurological diseases. There are no established therapies for HPgV. To estimate the prevalence of HPgV in a cohort of HCV/HIV co-infected patients undergoing treatment for HCV with direct acting antivirals (DAA) and investigate the effectof DAA therapy on HPgV infection. RNA was extracted from plasma samples collected at time points before, during, and after DAA. HPgV RNA abundance was quantified by droplet digital PCR assays targeting theNS5Aand 5'UTR domains and confirmed by RT-qPCR. Clinical, demographic and treatment data were analysed. HPgV RNA was detected and quantified in 26 of 100 patients' plasma (26%) before starting DAA. Patients with detectable HPgV were more likely to be male, had higher peak HIV plasma levels, and a history of injection drug use. Patients receiving sofosbuvir/ledipasvir (n=9) displayed significantly lower HPgV levels at time of DAA completion and had lower post-DAA HPgV rebound​ levels compared to patients receiving sofosbuvir/velpatasvir (n=11) although both regimens significantly reduced viremia directly following DAA completion. Sustained suppression of HPgV was​also observed among patients (n=2) receiving pegylated-interferon. HPgVRNA ​wasfrequently detected in HCV/HIV co-infected patients and ​was​supressed by DAA and pegylated interferon therapies with sofosbuvir-ledipasvir showing greatest antiviral activity. These findings suggest potential treatment strategies for HPgV infections​.

Safety and effectiveness of direct-acting antivirals in patients with chronic hepatitis C and chronic kidney disease.

Background/AimsTo evaluate the effectiveness and safety of direct acting antivirals (DAAs) available in chronic kidney disease (CKD) patients with hepatitis C virus (HCV) infection in Korea.MethodsIn a retrospective, multicenter cohort study, 362 patients were enrolled from 2015 to 2019. The effectiveness and safety of DAAs including glecaprevir/pibrentasvir, sofosubvir/ribavirin, ledipasvir/sofosbuvir, and daclatasvir/asunaprevir were analyzed for patients according to CKD stage. We evaluated sustained virologic response at week 12 after treatment (SVR12) as primary endpoint. The effectiveness and safety were also evaluated according to CKD stage.ResultsAmong 362 patients, 307 patients completed DAAs treatment and follow-up period after end of treatment. The subjects comprised 87 patients (62 with CKD stage 3 and 25 with CKD stage (4–5), of whom 22 were undergoing hemodialysis). HCV patients with CKD stage 1 and 2 (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2) showed SVR12 of 97.2% and 95.4% respectively. SVR12 of CKD stage 3 and 4–5 (eGFR < 60 mL/min/1.73 m2) patients was 91.9% and 91.6% respectively. Patients undergoing hemodialysis achieved SVR12 (90.9%). Treatment failure of DAAs in stage 1, 2, 3, and 4–5 was 2.8%, 2.7%, 1.6%, and 4%. DAAs showed good safety profile and did not affect deterioration of renal function.ConclusionsDAAs shows comparable SVR12 and safety in CKD patients (stage 3, 4, and 5) with HCV compared with patients with stage 1 and 2. The effectiveness and safety of DAAs may be related to the treatment duration. Therefore, it is important to select adequate regimens of DAAs and to increase treatment adherence.

Changes in Liver Steatosis Using Controlled Attenuation Parameter among Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals Therapy Who Achieved Sustained Virological Response.

Chronic hepatitis C virus (HCV) infection induces hepatic steatosis due to viral and host factors. However, information regarding the effects of direct-acting antivirals (DAAs) therapy on liver steatosis and fibrosis is limited. Vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) represents a non-invasive method, which has been used in the last few years for the detection of hepatic steatosis and fibrosis before and at a sustained virological response at 12 weeks (SVR12). The aim of this study was to assess the modifications of liver steatosis and fibrosis in HCV-infected patients who achieved SVR12. Consecutive patients with chronic HCV infection that were treated with DAAs in a tertiary gastroenterology center from Romania were included. Demographics, laboratory data, and VCTE evaluation were recorded in all patients. Patients with previous hepatic decompensation and those who did not achieve SVR were excluded. Two hundred and eighty patients (67.1% females) who achieved SVR12 were included. Regarding the changes in biological parameters, including liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), reduced to normal levels at SVR12 compared to the baseline (28.72 ± 24.71 U/L vs. 40.72 ± 27.34 U/L for ALT, p < 0.013 and 27.21 ± 11.15 U/L vs. 33.35 ± 23.37 U/L for AST, p = 0.029). On the contrary, the levels of triglycerides increased significantly from the baseline to SVR12 (124.03 ± 113.49 mg/dL to 153.78 ± 94.53, p = 0.004). Regarding hepatic steatosis by CAP evaluation, at SVR12, 186 (66.4%) of the individuals had a CAP score of ≥248 dB/m, an increase of 4.6% from the baseline. After viral eradication with DAAs, we observed an increase in hepatic steatosis. Hence, a long-term follow-up is mandatory to identify HCV-infected patients with hepatic steatosis post-SVR and the risk factors for more severe outcomes.

Effectiveness of Direct-Acting Antivirals in Treatment of Elderly Egyptian Chronic Hepatitis C Patients

Background: Hepatitis C virus treatment has dramatically improved by direct-acting antiviral (DAA) therapy. The aim of this study was to assess the efficacy and safety of DAA in elderly Egyptian chronic hepatitis C (CHC) patients. Methods: The study was carried out on 327 CHC elderly patients &gt;60 years; patients were divided into 3 age subgroups (&lt;65, 65–75 and &gt;75 years) on DAA therapy for 12 weeks. Ninety-one patients (27.8%) were treated with dual therapy, 234 patients (71.6%) with triple therapy and 2 patients (0.6%) with quadrable therapy. Results: All patients achieved end-of-treatment virological response (100%). ALT levels normalized during therapy. The follow-up rate of sustained virological response at 12 weeks after the end of treatment (SVR12) was 100%. One hundred and two patients had missed SVR12 data due to being lost tofollow-up. Two hundred twenty-two adverse events were reported (67.8%), including anemia in 30 patients (9.1%), leucopenia in 129 patients (39.4%) and thrombocytopenia in 63 patients (19.2%). No serious side effects led to discontinuation of therapy. No hepatic decompensation was observed, and no patients died. Conclusion: Age does not influence the success of DAA treatment and all DAA regimens are well tolerated, safe and highly efficacious, even in those aged 75 years or older.

RELATION BETWEEN DEGREE OF LIVER STIFFNESS AND DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS C VIRUS PATIENTS

Background: Hepatocellular carcinoma is the fifth most common tumor worldwide and the second most common cause of cancer-related death. Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and hence the development of hepatocellular carcinoma (HCC). Egypt has the highest HCV prevalence worldwide. The introduction of new direct acting antiviral agents in the past 5 years has dramatically improved the outcomes of HCV treatment response with > 90% of patients achieving a sustained virological response (SVR) after 12 weeks of end treatment. However, the effect of direct-acting antivirals (DAAs) induced HCV clearance on HCC recurrence after HCC treatment has emerged as a topic of controversy. Objective: To evaluate the relation between liver stiffness as measured by fibro scan and development of HCC in chronic HCV patients. Patients and methods: A prospective study was done at Kafar Alshaykh National Hepatology Institute conducted in collaboration with the Gastroenterology Unit Department of Internal Medicine, Al-Hussein University Hospital, and Cairo Egypt. The study included 150 patients with proven liver cirrhosis secondary to chronic hepatitis C (CHC) they were further sub classified into three equal groups: Group I with chronic hepatitis C, liver cirrhosis and HCC, Group II with CHC and HCC that appeared after treatment with DAA, and Group III (control group) with cirrhotic chronic hepatitis C (CHC) without HCC. Results: In this study, there was a statistically significant difference between group I (30.38 ± 11.32 kPa) and controlled group (25.0 ± 13.34 kPa), regarding fibro scan results (P = 0.004). On other hand there was no significant difference between group II (23.24 ± 7.69 kPa) and controlled group regarding LS. Conclusion: Fibro scan can be a good technique for detection of HCC high-risk cirrhotic patients not treated by DAA and can be of great added value if incorporated in the current HCC screening protocols in hepatitis C cirrhotic patients. On the other hand, LS tended to decrease dramatically after the treatment with DAA. Using TE in these patients would therefore be misleading liver stiffness measurement (LSM), the risk of HCC remains because advanced fibrosis or cirrhosis, which is the most important risk factor for liver cancer, not completely resolved by antiviral treatment. As a matter of fact, the degree of liver fibrosis seems to be a strong predictor of the risk of HCC development.

Effectiveness of direct-acting antivirals in maintenance hemodialysis patients complicated with chronic hepatitis C.

Hepatitis C virus (HCV) infection is very common in maintenance hemodialysis patients, causing high morbidity and mortality. This study aimed to evaluate the effectiveness and adverse events of direct-acting antivirals (DAAs) in maintenance hemodialysis patients complicated with chronic hepatitis C in real-world clinical practice.In this retrospective observational study, hemodialysis patients with chronic hepatitis C infection in the Third Central Hospital of Tianjin outpatient were screened, and appropriate treatment plans were selected accordingly. Totally 25 patients diagnosed with chronic hepatitis C and treated with DAAs for 12 weeks or 24 weeks were included. The sustained virologic response (SVR) rate obtained 12 weeks post-treatment (SVR12) was evaluated. Laboratory indexes and adverse reactions during the treatment process were also assessed.A total of 25 cases met the eligibility criteria and provided informed consent. Except for 1 patient who discontinued the treatment due to gastrointestinal bleeding, the remaining 24 cases completed the treatment cycle with 100% rapid virologic response (RVR) and 100% SVR12, with no serious adverse reactions recorded.Maintenance hemodialysis patients complicated with chronic hepatitis C in Chinese real-world setting tolerate DAAs very well, with a viral response rate reaching 100%.

Systematic review with meta-analysis: the efficacy and safety of direct-acting antivirals in children and adolescents with chronic hepatitis C virus infection.

The effect of direct-acting anti-virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18years, have been enrolled in clinical trials, and some data come from observational studies. To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection. We performed a systematic review and meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects <18years of age. We considered the sustained virological response at post-treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post-treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman-Tukey double arcsine transformation. Random effects model was used for all analyses. Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post-treatment week 12 was 100% (95% confidence interval: 100-100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon. Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults.

Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort.

Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAAtreatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated withunachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). From 2167 patients (55.2% with cirrhosis) who initiated DAAtherapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAAfailure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01). In this real-life setting, higher DAAtreatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time-point of DAAtreatment (NCT03775798; www. gov).

Hemodynamic effects of direct-acting antivirals in patients with hepatitis-C virus-associated cirrhosis and portal hypertension non responsive to beta-blockers

Hemodynamic effects of direct-acting antivirals in patients with hepatitis-C virus-associated cirrhosis and portal hypertension non responsive to beta-blockers

Effect of direct-acting antivirals on corrected QT interval and cardiac functions in patients with chronic hepatitis C virus infection

BackgroundHepatitis C virus (HCV) infection is a major public health problem in Egypt. The use of direct-acting antivirals (DAAs) in such patients has been shown to be highly effective. The cardiac safety of such antivirals remains uncertain. This study aimed to assess the effect of the novel DAAs on corrected QT (QTc) interval and on cardiac function using trans-thoracic echocardiography.ResultsThis was a prospective cohort study performed on 100 patients suffering from chronic HCV infection. Patients were into two equal groups according to the presence of liver cirrhosis. The group without liver cirrhosis received a daily combination of sofosbuvir 400 mg and daclatasvir 60 mg for 12 weeks while that with liver cirrhosis (Child-Pugh score A or B) received a daily combination of sofosbuvir 400 mg, daclatasvir 60 mg, and ribavirin 600 mg for 12 weeks. Surface ECG and trans-thoracic echocardiography were performed prior to the start of treatment and after 12 weeks of treatment.At the end of treatment, no changes were observed in QTc interval in those with (p = 0.48) or without (p = 0.048) liver cirrhosis. In patients without liver cirrhosis, right ventricular global longitudinal strain (RV GLS) decreased from 22 (−30 to −17) to −21 (−27–18), p = 0.024. In patients with liver cirrhosis, lateral mitral E’ velocity was reduced from 14.38 ± 3.59 to 13.62 ± 3.21 cm/s, p = 0.02 and indexed left atrial volume (LAVI) was increased from 25.96 ± 3.96 to 26.86 ± 4.12 ml/m2, p = 0.032. There were no changes in both groups regarding left ventricular (LV) dimensions, ejection fraction, trans-mitral E/A ratio, E/E’ ratio, deceleration time, right ventricular (RV) systolic pressure, mean pulmonary artery pressure, RV fractional area change, tricuspid annular plane systolic excursion, and LV GLS.ConclusionThe current national protocol of HCV infection treatment with direct-acting antiviral agents used in Egyptian patients has a good cardiac safety profile. Such treatments have no effect on QTc interval, left and right ventricular functions except for a decrease in RV GLS in those with no liver cirrhosis and a reduction in lateral mitral E’ velocity in those with liver cirrhosis both remained within the normal reference range.

Direct acting antivirals treatment for hepatitis C virus infection does not increase the incidence of de novo hepatocellular carcinoma occurrence: Results from an Italian real-life cohort (LINA cohort).

The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection is ascertained. However, some authors raised the issue of an increased incidence of de novo hepatocellular carcinoma (HCC) in patients treated with DAAs. Aim of the study was to evaluate the rate of HCC occurrence in a real-life cohort of patients who received anti-HCV treatment with DAAs.A prospective multicentre study was conducted. All adult patients with HCV infection who received treatment between March 2015 and December 2017 in 4 hospital of Campania region (South Italy) with at least 6 months of follow-up were enrolled.A total of 323 patients were included in the study. Most patients had HCV genotype 1b (61.8%). The overall SVR12 rate was 95.5%. Median time of observation was 10 months. The incidence rate of HCC was 0.2 per 100 person-months (crude incidence rate 3.4%, 95 confidence interval: 1.5%–5.3%). The median time for HCC occurrence was 11 months. HCC occurrence rate was significantly higher among patients who did not achieve SVR12 compared with patients who did (28.6% vs 2.8%, P < 0.05). No patient with F0-F3 fibrosis developed HCC. Among patients with cirrhosis, at the multivariate time-to-event analysis, no covariates were independently associated with the risk of HCC occurrence.Treatment with DAAs did not increase the risk of HCC occurrence. Patients who achieved SVR12 had a lower rate of HCC occurrence. Further studies are needed to estimate the incidence and the risk for HCC in the long-term follow-up among patients undergoing treatment with DAAs.

Effect of direct-acting antivirals on elastographic measures in patients with chronic hepatitis C virus infection

BackgroundHepatitis C virus (HCV) infection is a worldwide health problem. Liver fibrosis has been a major topic of research for decades. However, recent data have shown the occurrence of fibrosis fall in a wide spectrum of chronic liver diseases.AimWe aimed to evaluate the changes in transient elastography (TE) values of different direct-acting antivirals regimens in HCV chronic liver disease patients.Settings and designThis observational analytic study was carried out at the Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.Participants and methods100 Egyptian chronic hepatitis C patients were recruited into this study. All participants were included according to the inclusion criteria approved by the national committee in Egypt for control of viral hepatitis. They were subjected to a thorough assessment of history and clinical examination, routine investigations, ECG, radiological examination, and TE 2 weeks before treatment initiation, at the end of the course, and 6 months after treatment.ResultsThere was a significant improvement in liver stiffness (LS) values in cirrhotic patients, but they still had cirrhosis, with lower LS values than pretreatment values. This study reported a significant decrease 12 weeks after the end of treatment for LS measurements and validated fibrosis scores such as FIB-4 and APRI. Patients with F4 grade fibrosis showed a significant improvement in the score, and the percentage decreased from 56% before treatment to 42 and 38% after sustained virological response 1 and sustained virological response 2, respectively.ConclusionDirect-acting antivirals based treatment results in a significant improvement in hepatic fibrosis measures, indicated by TE as well as noninvasive fibrosis scores such as fibrosis score (FIB-4) and APRI.

Development and Validation of a New LC-MS/MS Analytical Method for Direct-Acting Antivirals and Its Application in End-Stage Renal Disease Patients.

The effectiveness of direct-acting antivirals (DAAs) is not well established in end-stage renal disease (ESRD) patients. Assessment of the plasma concentrations may support understanding of their therapeutic outcomes in this population. The aim of this study is to develop a direct, yet matrix-effect tolerant, analytical method for determining DAAs in the plasma of ESRD patients while maintaining a moderate cost per sample and with an improved analyte extraction recovery. In this study, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the analysis of ombitasvir (OMB), paritaprevir (PRT) and ritonavir (RIT) in plasma. Sample preparation was performed using the liquid-liquid extraction (LLE) method. Isocratic separation was performed using a mixture of methanol and 10mM ammonium acetate (79:21, v/v) followed by MS/MS detection. The method was validated and applied to determine DAAs in the plasma of ESRD patients (n = 7). The developed method was linear (r2 > 0.995), accurate (89.4 ± 7.8 to 108.3 ± 3.0) and precise (% CV 0.9-15.0) and showed improved recovery (> 80) over previously published ones in the range 5-250, 30-1,500, 20-1,000ng/mL for OMB, PRT and RIT, respectively. Relative matrix effect was absent, and the method accurately determined the three DAAs in real-life samples (n = 7). An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent.

Effect of Direct-Acting Antivirals on Lipid and Glucose Metabolism in Chronic HCV Patients

Effect of Direct-Acting Antivirals on Lipid and Glucose Metabolism in Chronic HCV Patients

Influence of drug–drug interactions on effectiveness and safety of direct-acting antivirals against hepatitis C virus

ObjectivesDirect-acting antivirals are the recommended treatment for hepatitis C-infected patients. Drug–drug interactions with concomitant treatments can cause lack of effectiveness and/or safety. The objective of this study is to characterise...