Impact Of Direct-acting Antivirals Research Articles

Real-world economic burden of hepatitis C and impact of direct-acting antivirals in France: A nationwide claims data analysis.

The economic impact of managing patients with hepatitis C virus (HCV) infection remains unknown. This study aimed to assess the economic burden of chronic HCV infection from a national health insurance perspective and the impact of direct-acting antivirals (DAAs) using nationwide real-world data. Patients with chronic HCV infection were identified from the French Health Insurance Claims Databases (SNDS) and matched for age and sex to the general population. Health resource utilization and reimbursements were summarized according to healthcare expenditure items from 2012 to 2021. The economic burden attributable to chronic HCV infection was evaluated over a 10-year period. Finally, the impact of DAAs was estimated using economic data derived from the SNDS. A total of 145 187 patients with chronic HCV infection were identified. Among the patients eligible for DAA therapy, 81.5% had received DAA by the end of 2021. Over a 10-year period, managing patients with chronic HCV infection resulted in an additional cost of €9.71 billion (95% confidence interval [CI]: €9.66-€9.78 billion) or €9191 (95% CI: €9134-€9252) per patient per year compared to the general population. After DAA therapy, patients with chronic HCV infection had a higher economic burden than the general population, with an additional cost of €5781 (95% CI: €5540-€6028) per patient at the fifth-year post-DAA therapy. A significant economic burden persists among patients with HCV infection after DAA treatment. The high proportion of patients not treated with DAA therapy supports reinforcing policies for universal access.

Impact of Direct-Acting Antivirals on Recurrence of Hepatocellular Carcinoma after Curative Treatment.

Impact of Direct-Acting Antivirals on Recurrence of Hepatocellular Carcinoma after Curative Treatment.

Impact of Direct-acting Antivirals on Hepatocellular Carcinoma and Mortality Among Medicaid Beneficiaries With Hepatitis C.

The effects of all-oral direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) and liver-related and all-cause mortality were assessed among Medicaid beneficiaries with hepatitis C virus (HCV). This cohort study used 2013-2019 Arizona Medicaid data from beneficiaries with HCV aged 18-64 years. Risks of HCC and liver-related and all-cause mortality were compared between patients with or without DAA treatment, stratified by liver disease severity, using inverse probability of treatment weighted multivariable Cox proportional hazards regression models. Of 29,289 patients, 13.3% received DAAs. Among patients with compensated cirrhosis (CC), DAA treatment was associated with a lower risk of HCC [adjusted hazard ratio (aHR), 0.57; 95% CI, 0.37-0.88] compared with untreated patients although this association was not statistically significant for patients without cirrhosis or with decompensated cirrhosis (DCC). Compared with untreated patients, DAA treatment was associated with decreased risk of liver-related mortality for patients without cirrhosis (aHR: 0.02; 95% CI: 0.004-0.11), with CC (aHR: 0.09; 95% CI: 0.06-0.13), or with DCC (aHR: 0.20; 95% CI: 0.14-0.27). Similarly, compared with untreated patients, DAA treatment was associated with lower all-cause mortality for patients without cirrhosis (aHR: 0.10; 95% CI: 0.08-0.14), with CC (aHR: 0.07; 95% CI: 0.05-0.10), or with DCC (aHR: 0.15; 95% CI: 0.11-0.20). Among Arizona Medicaid beneficiaries with HCV, DAA treatment was associated with decreased risk of HCC for patients with CC but not for patients without cirrhosis or with DCC. However, DAA treatment was associated with decreased risk of liver-related and all-cause mortality.

Analysis of the effects of donor and recipient hepatitis C infection on kidney transplant outcomes in the United States.

As Hepatitis C virus infection (HCV+) rates in kidney donors and transplant recipients rise, direct-acting antivirals (DAA) may affect outcomes. To analyze the effects of HCV+ in donors, recipients, or both, on deceased-donor (DD) kidney transplantation (KT) outcomes, and the impact of DAAs on those effects. The Organ Procurement and Transplantation Network data of adult first solitary DD-KT recipients 1994-2019 were allocated into four groups by donor and recipient HCV+ status. We performed patient survival (PS) and death-censored graft survival (DCGS) pairwise comparisons after propensity score matching to assess the effects of HCV+ in donors and/or recipients, stratifying our study by DAA era to evaluate potential effect modification. Pre-DAA, for HCV+ recipients, receiving an HCV+ kidney was associated with 1.28-fold higher mortality (HR 1.151.281.42) and 1.22-fold higher death-censored graft failure (HR 1.081.221.39) compared to receiving an HCV- kidney and the absolute risk difference was 3.3% (95%CI: 1.8%-4.7%) for PS and 3.1% (95%CI: 1.2%-5%) for DCGS at 3 years. The HCV dual-infection (donor plus recipient) group had worse PS (0.56-fold) and DCGS (0.71-fold) than the dual-uninfected. Donor HCV+ derived worse post-transplant outcomes than recipient HCV+ (PS 0.36-fold, DCGS 0.34-fold). In the DAA era, the risk associated with HCV+ in donors and/or recipients was no longer statistically significant, except for impaired PS in the dual-infected vs dual-uninfected (0.43-fold). Prior to DAA introduction, donor HCV+ negatively influenced kidney transplant outcomes in all recipients, while recipient infection only relatively impaired outcomes for uninfected donors. These adverse effects disappeared with the introduction of DAA.

Impact of direct-acting antivirals on neuropsychiatric and neurocognitive dysfunction in chronic hepatitis C patients

BackgroundHepatitis C virus (HCV) infection is associated with psychiatric and cognitive dysfunctions. We aimed to investigate depression, anxiety, and cognitive function of chronic hepatitis C (CHC) patients before and after treatment with direct-acting antivirals (DAAs). Forty CHC patients (20 non-cirrhotic and 20 cirrhotic) who had undergone DAA treatment in our outpatient clinic and ten controls. We administered the Hospital Anxiety and Depression questionnaires to measure the anxiety and depression symptoms and the Cognitive Abilities Screening Instruments (CASI) to measure the cognitive function at the beginning and 3 months after the end of the treatment.ResultsSustained virological response (SVR) was achieved in all patients. Post-treatment anxiety and depression scores showed a significant improvement than pre-treatment ones in CHC patients. Regarding CASI, before and after the treatment, a statistical significance was found in short-term memory (P = 0.001), concentration (P = 0.033), abstract thinking and judgment (P = 0.024), total (P = 0.001) in non-cirrhotic, Also, an improvement was seen in long-term memory (P = 0.015), short-term memory (P < 0.001), concentration (P = 0.024) and total (P = 0.01) in cirrhotic. However, these changes were still impaired in post-treated cirrhotic compared to controls.ConclusionsCHC patients' anxiety, depression, and cognitive function partially improved after DAA therapy. Besides, improving the status of CHC, reversibility of cognitive dysfunction in non-cirrhotic patients may indicate the importance of treatment in early stages of liver disease.

Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants.

Significant liver fibrosis regression occurs after hepatitis C virus (HCV) therapy. However, the impact of direct-acting antivirals (DAAs) on steatosis is less clear. This study was aimed at evaluating serial fibrosis and steatosis alterations in patients with HCV genotype 1, who achieved sustained virological response (SVR). We enrolled 55 HCV mono-infected and 28 HCV/HIV co-infected patients receiving elbasvir/grazoprevir from a clinical trial. Fibrosis and steatosis were assessed at baseline, follow-up week-24 (FUw24) and week-72 (FUw72) by magnetic resonance elastography (MRE) and proton density fat fraction (PDFF), respectively. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, transmembrane six superfamily member 2 (TM6SF2) rs58542926 and membrane bound O-acyltransferase domain-containing 7 (MBOAT7) rs641738 polymorphisms were determined by allelic discrimination. Overall, mean MRE decreased significantly from baseline to FUw24 and FUw72. At FUw72, patients with baseline F2-F4 had higher rate of ≥30% MRE decline compared with individuals with baseline F0-F1 (30.2%vs.3.3%, P = 0.004). In multivariate analysis, significant fibrosis was associated with MRE reduction. The prevalence of steatosis (PDFF≥5.2%) at baseline was 21.7%. Compared to baseline, there were 17 (20.5%) patients with decreased PDFF values at FUw72 (<30%), while 23 (27.7%) patients had increased PDFF values (≥30%). Regarding the overall cohort, mean PDFF significantly increased from baseline to FUw72, and displayed positive correlation with body mass index (BMI) alteration. In multivariate analysis, the presence of diabetes, PNPLA3 CG+GG genotypes and increased BMI at FUw72 were significantly associated with progressive steatosis after SVR. Other genetic variants were not related to fibrosis and steatosis alteration. This study concluded that HCV eradication was associated with fibrosis improvement. However, progressive steatosis was observed in a proportion of patients, particularly among individuals with metabolic derangement and PNPLA3 variants. The combined clinical parameters and host genetic factors might allow a better individualized strategy in this sub-group of patients to alleviate progressive steatosis after HCV cure.

Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Mapping of SARS-CoV-2 IgM and IgG in gingival crevicular fluid: Antibody dynamics and linkage to severity of COVID-19 in hospital inpatients

Impact of direct-acting antivirals on the recurrence of hepatocellular carcinoma in chronic hepatitis C

Chronic hepatitis C virus (HCV) infection is estimated to affect 56.8 million individuals globally and is a major and independent risk factor for the development of hepatocellular carcinoma (HCC). After the introduction of safe and potent direct-acting antivirals (DAAs), capable of curing HCV infection also in patients with advanced liver disease at high risk of HCC, the beneficial effect on a de novo HCC development after viral clearance has been established. However, studies addressing the relationship between DAA-induced eradication and risk of HCC recurrence (i.e., reappearance of HCC treated before starting antivirals) have produced contradictory data, suggesting either an increase or a decrease of HCC recurrence rate, while some report no effect of these treatments. Thus, there seems to be an unclear benefit of viral clearance in patients with a history of HCC curative treatment, where the recurrence rate remains worryingly high. This short review aims to summarize current evidence on the impact of DAAs on HCC recurrence rates, the pathogenic mechanisms and characteristics of HCC recurrence after DAA treatment, the predictors of tumor recurrence, and the impact of DAAs on overall survival.

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Changing Trends of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the Era of Directly-Acting Antiviral Agents.

INTRODUCTION:The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction.METHODS:Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases.RESULTS:In the DAA era (2014–2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88–0.99, P = 0.019), without change in trends of other liver diseases–related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03–1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81–0.97, P = 0.009) along with similar trends for HCV-HCC—increase in noncirrhotic cases (OR 1.35, 95% CI 1.08–1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86–0.98, P = 0.012)—were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era.DISCUSSION:Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.

The impact of direct-acting antivirals on liver fibrosis in Egyptian hepatitis C virus patients: a single center experience

Abstract Background Hepatitis C virus (HCV) infection affects approximately 170 million people worldwide, causing liver cirrhosis and hepatocellular carcinoma (HCC) and leading to liver transplantation and ultimately death. Accurate evaluation of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in noninvasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with DAAs. Objectives The aim beyond this study is to evaluate the changes in liver stiffness in hepatitis C Egyptian patients before and at least one year after treatment with DAAs using transient elastography and non-invasive liver fibrosis indices as FIB-4 and APRI scores. Patients and methods The present study was conducted on 100 patients with chronic hepatitis C patients attended to Ain Shams University Hospitals, Viral hepatitis treatment unit between October 2017 and December 2018, who were followed-up during treatment and after treatment for at least one year (retrospective and prospective study). Total number of cases during the study period was 117 patients. 17 patients were excluded from the study due to missed follow-up. Eventually, 100 patients were enrolled in the study fulfilling the inclusion criteria. Results The mean age of our patients is 47.9 years with Male predominance (52 males and 48 females). There was a significant improvement of, platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores. There was a significant improvement of liver stiffness after end of treatment, regardless of the DAA regimen used, as evidenced by Fibroscan. Conclusion Fibrosis regression –assessed by non-invasive markers of fibrosis is achievable upon removal of the causative agent.

The impact of direct-acting antivirals on hepatitis C viraemia among people who inject drugs in England; real-world data 2011-2018.

Direct‐acting antiviral (DAA) therapy for anybody with viraemic HCV infection has been scaled‐up in England since 2017. To assess early impacts, we investigated trends in, and factors associated with, HCV viraemia among people who inject drugs (PWID). We also examined trends in self‐reported treatment access. Bio‐behavioural data from an annual, national surveillance survey of PWID (2011–2018) estimated trends in viraemic prevalence among HCV antibody‐positive PWID. Multivariable logistic regression identified characteristics independently associated with viraemia. Trends in treatment access were examined for PWID with known infection. Between 2011 and 2016, viraemic prevalence among antibody‐positive PWID remained stable (2011, 57.7%; 2016, 55.8%) but decreased in 2017 (49.4%) and 2018 (50.4%) (both p < 0.001). After adjustment for demographic and behavioural characteristics, there remained significant reduction in viraemia in 2017 (adjusted odds ratio [aOR] 0.79, 95% CI 0.65–0.94) and 2018 (aOR 0.79, 95% CI 0.66–0.93) compared to 2016. Other factors associated with viraemia were male gender (aOR 1.68, 95% CI 1.53–1.86), geographical region, injecting in past year (aOR 1.26, 95% CI 1.13–1.41), imprisonment (aOR 1.14, 95% CI 1.04–1.31) and homelessness (aOR 1.17, 95% CI 1.04–1.31). Among non‐viraemic PWID with known infection, the proportion reporting ever receiving treatment increased in 2017 (28.7%, p < 0.001) and 2018 (38.9%, p < 0.001) compared to 2016 (14.5%). In conclusion, there has been a small reduction in HCV viraemia among antibody‐positive PWID in England since 2016, alongside DAA scale‐up, and some indication that treatment access has improved in the same period. Population‐level monitoring and focus on harm reduction is critical for achieving and evaluating elimination.

Impact of direct-acting antivirals (DAAs) on cardiovascular diseases in patients with chronic hepatitis C.

In the last years the Hepatitis C virus (HCV) infection was a relevant public health problem due to the large number of affected people worldwide and the impact on hepatic and extrahepatic complications. The availability of direct-acting antivirals (DAAs) and the very high rate of sustained virological response (SVR) after treatment has radically changed the course of HCV chronic infection. We searched PubMed for articles published between January 1, 1995, through December 31, 2020, in English language. Robust evidence showed a close link between HCV infection and development of cardiovascular disease (CVD), as result of the atherogenic effect of the virus. This review aimed to explore the evidence linking HCV infection with cardiovascular disease and to evaluate the impact of SVR after DAAs on cardiovascular complications.

A real-life study on the impact of direct-acting antivirals in the treatment of chronic hepatitis C in liver transplant recipients at two university centers in Northeastern Brazil.

ABSTRACTThe efficacy of direct-acting antivirals (DAAs) in the treatment of chronic hepatitis C (CHC) in liver transplant recipients is poorly understood, and several factors, including immunosuppression, drug interactions, elevated viraemia, and intolerance to ribavirin (RBV), can reduce cure rates. We conducted a real-life study on liver transplant recipients with CHC treated with a combination of sofosbuvir (SOF) and daclatasvir (DCV) or simeprevir (SIM), with or without RBV, followed-up for 12 to 24 weeks. The treatment effectiveness was assessed by determining the sustained virological response (SVR) rates at 12 or 24 weeks after the treatment cessation. Eighty-four patients were evaluated, with a mean age of 63.4 ± 7.4 years, HCV genotype 1 being the most prevalent (63.1%). Nineteen patients (22.7%) had mild fibrosis (METAVIR < F2) and 41 (48.8%) significant fibrosis (METAVIR ≥ F2). The average time between liver transplantation and the start of treatment was 4 years (2.1-6.6 years). The SOF + DCV regimen was used in 58 patients (69%). RBV in combination with DAAs was used in seven patients (8.3%). SVR was achieved in 82 patients (97.6%), and few relevant adverse events could be attributed to DAA therapy, including a patient who stopped treatment due to a headache. There was a significant reduction in ALT, AST, GGT and FA levels, or the APRI index after 4 weeks of treatment, which remained until 12/24 weeks post-treatment. DAA treatment of CHC in liver-transplanted patients achieved a high SVR rate and resulted in the normalization of serum levels of liver enzymes.

Impact of treating chronic hepatitis C infection with direct-acting antivirals on the risk of hepatocellular carcinoma recurrence

BackgroundThe impact of direct-acting antivirals (DAAs) remains a debate, whether they accelerate the recurrence rate of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after curative therapy. We evaluated the impact of direct-acting antiviral therapy on the rate of recurrence of HCV-related hepatocellular carcinoma following intervention in Egyptian patients.ResultsThe results of the study represented an HCC recurrence rate of 38% in patients who received direct-acting antiviral therapy after HCC intervention versus 62% in those who did not receive antiviral therapy. In group I, according to the Barcelona Clinic of Liver Cancer (BCLC) staging, a higher recurrence rate was observed (57.9%) among patients who were classified as BCLC stage B.ConclusionsHCC patients who did not receive direct-acting antiviral therapy after HCC intervention had a greater risk of HCC recurrence. DAAs did not increase the risk of HCC recurrence following HCC treatment; however, it did not abolish it. Close monitoring of patients after antiviral therapy is recommended.

Impact of direct-acting antivirals on de novo occurrence of hepatocellular carcinoma in hepatitis C virus patients

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

The impact of direct-acting antivirals on hepatitis C associated hepatocellular carcinoma

The impact of direct-acting antivirals on hepatitis C associated hepatocellular carcinoma

Human genetics of HCV infection phenotypes in the era of direct-acting antivirals.

The recent introduction of direct-acting antivirals (DAAs) has revolutionized hepatitis C virus (HCV) therapy by improving virus eradication rates to over 90% in most patient groups. However, the impact of DAAs on global disease burden is currently limited, and a large number of chronically infected individuals remain at risk of developing liver complications, such as liver cirrhosis and hepatocellular carcinoma (HCC). The identification of patients at risk of liver complications and a greater understanding of the biological mechanisms involved in HCV disease progression might improve disease control. Recent genome-wide association and exome sequencing studies have identified several host genetic variants influencing the progression of liver fibrosis and the development of HCC associated with HCV infection and are reviewed here. Interestingly, some of the genetic variants associated with those HCV-associated liver complications were also associated with the clinical course of non-viral chronic hepatitis. Future challenges include the incorporation of this genetic information into clinical risk models for personalized disease management and the study of emerging phenotypes such as liver fibrosis regression and HCC development after HCV eradication.

Long term renal safety of HCV direct acting antivirals in HCV positive kidney transplant recipients

Introduction and aim: General transplant outcome of HCV kidney transplant recipients (KTRs) is worse than that of non-infected one. Direct acting antivirals (DAAs) resulted efficacious also in KTRs. Drug interactions between Calcineurin inhibitors (CNI) and DAAs had been described. Immunological rejection is the Achilles heel of kidney transplantation. Thus, the impact of DAAs on CNI levels and the effect on renal function need to be evaluated.

Impact of direct-acting antivirals in the management of post-liver transplant recipients compared with the interferon-era

Introduction and Aims: Direct-acting antivirals (DAA) revolutionized HCV therapy, especially in liver transplant (LT) setting. We aimed to investigate the post-LT management during DAA-era compared with the interferon-one.