Use Of Direct-acting Antivirals Research Articles

Virus infection and direct-acting antivirals in pregnancy

Objective: Antiviral therapy during pregnancy has always presented difficulties in clinical practice. This review covers the safety and efficacy of the direct use of antivirals during pregnancy. Mechanism: We conducted literature research to summarize the available evidence on the use of direct-acting antivirals during pregnancy for infections due to influenza, hepatitis B and C, human immunodeficiency, herpes simplex virus, cytomegalovirus, varicella-zoster virus, Ebola, and Zika viruses, and human coronavirus. Findings in brief: To support further the rational use of antivirals during pregnancy, the discussion includes the influence of pregnancy on pharmacokinetics, safety, and transplacental permeability, and the protection of mothers and children from vertical transmission. Conclusion: Data on the use of antiviral drugs during pregnancy are currently insufficient. Promoting research on the ethics of drug experimentation, and pharmacokinetics, drug metabolism, and pharmacological effects of pregnancy, is essential to improve the care of pregnant women and even save lives during current and future outbreaks.

Direct-acting antiviral regimens and HCV treatment failure and re-treatment in sub-Saharan Africa

Today, most patients chronically infected with hepatitis C virus (HCV) can comfortably clear their infection after a 12-week course of direct-acting antivirals, which are easy to administer, well tolerated, and effective when administered as combination therapies.1 However, treatment failure after the use of direct-acting antivirals for HCV infection, which can be recurrent, is an emerging worldwide problem and a threat to the global elimination of chronic HCV infection. Predictors of failure of direct-acting antiviral treatment include HCV genotypes, subtypes, and viral adaptations.

Improvements in liver transplant outcomes in patients with HCV/HIV coinfection after the introduction of direct-acting antiviral therapies.

In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting antivirals (DAAs) has had on post-liver transplant (LT) outcomes has not been evaluated. We investigated the impact of DAAs introduction on post-LT outcome in patients with HCV/HIV coinfection. Using Organ Procurement and Transplant Network/United Network for Organ Sharing data, we compared post-LT outcomes in patients with HCV and/or HIV pre- and post-DAAs introduction. We categorized these patients into two eras: pre-DAA (2008-2012 [pre-DAA era]) and post-DAA (2014-2019 [post-DAA era]). To study the impact of DAAs introduction, inverse probability of treatment weighting was used to adjust patient characteristics. A total of 17215 LT recipients were eligible for this study (HCV/HIV [n=160]; HIV mono-infection [n=188]; HCV mono-infection [n=16867]). HCV/HIV coinfection and HCV mono-infection had a significantly lower hazard of 1- and 3-year graft loss post-DAA, compared pre-DAA (1-year: adjusted hazard ratio [aHR] 0.29, 95% confidence interval (CI) 0.16-0.53 in HIV/HCV, aHR 0.58, 95% CI 0.54-0.63, respectively; 3-year: aHR 0.30, 95% CI 0.14-0.61, aHR 0.64, 95% CI 0.58-0.70, respectively). The hazards of 1- and 3-year graft loss post-DAA in HIV mono-infection were comparable to those in pre-DAA. HCV/HIV coinfection had significantly lower patient mortality post-DAA, compared to pre-DAA (1-year: aHR 0.30, 95% CI 0.17-0.55; 3-year: aHR 0.31, 95% CI 0.15-0.63). Post-LT outcomes in patients with coinfection significantly improved and became comparable to those with HCV mono-infection after introducing DAA therapy. The introduction of DAAs supports the use of LT in the setting of HCV/HIV coinfection.

Treatment and monitoring of children and adolescents with hepatitis C in Russia: Results from a multi-centre survey on policy and practice

BackgroundThe Russian Federation has the largest paediatric hepatitis C virus (HCV) disease burden in the World Health Organization European region with an estimated 118,000 children living with HCV viraemia. Direct-acting antivirals (DAAs) have been available for adults in Russia since 2015 and approved for treatment of adolescents aged ≥12 years since 2019. We evaluated DAA availability and uptake for HCV treatment of children and adolescents and clinical practices on diagnosis and management of paediatric HCV in Russia. MethodsA survey was distributed to regional ministries of health in 85 administrative regions during September 2020. The survey consisted of 22 items collecting data on: type of facility, aggregate patient characteristics, HCV testing practices for children and pregnant women and HCV management and treatment practices for children. ResultsSurvey responses were received from 37 of the 85 regions in Russia (response rate 44%). 2159 children and adolescents with chronic HCV were in follow-up; 1089 (50%) were female. Of 2080 children with available data on age-groups, 134 (6%) were <3 years, 336 (16%) 3-<6 years, 718 (35%) 6-<12 years and 892 (43%) 12-<18 years. 134 (15%) of 892 adolescents ≥12 years received DAAs, 96 (72%) glecaprevir/pibrentasvir, 26 (19%) sofosbuvir, 8 (6%) daclatasvir and 4 (3%) sofosbuvir/ledipasvir. ConclusionsThis study provides a baseline of DAA uptake in early stages of rollout for children and adolescents. The use of DAAs for treatment of adolescents in Russia presents a unique opportunity for HCV micro-elimination in this population.

Hepatitis C Virus Treatment Response to Direct-acting Antivirals Among Adolescents With HIV/HCV Coinfection: Real-world Data From Ukraine.

Direct-acting antivirals (DAAs) have been approved for treating chronic hepatitis C virus (HCV) in children and adolescents. Although DAAs have been used in real-world settings for the treatment of HCV monoinfected adolescents, few reports of real-world use of DAAs in children and adolescents who are coinfected with human immunodeficiency virus (HIV) are available. We evaluated the real-world safety and effectiveness of DAAs in HIV/HCV coinfected adolescents from the Ukraine Paediatric HIV Cohort Study including all those for whom treatment outcomes were available by April 2021. Overall, 6 coinfected adolescents had received DAA treatment; 4 with sofosbuvir/ledipasvir (SOF/LDV), 1 with SOF/LDV+ribavirin, and 1 with SOF/daclatasvir. No patient discontinued treatment due to adverse events and no serious adverse events were reported. All 6 patients achieved sustained virologic response by 12 weeks after the end of therapy. DAA treatment was well tolerated and effective in adolescents with HIV/HCV coinfection in a real-world setting.

Targeting non-structural proteins of Hepatitis C virus for predicting repurposed drugs using QSAR and machine learning approaches

Hepatitis C virus (HCV) infection causes viral hepatitis leading to hepatocellular carcinoma. Despite the clinical use of direct-acting antivirals (DAAs) still there is treatment failure in 5–10% cases. Therefore, it is crucial to develop new antivirals against HCV. In this endeavor, we developed the “Anti-HCV” platform using machine learning and quantitative structure–activity relationship (QSAR) approaches to predict repurposed drugs targeting HCV non-structural (NS) proteins. We retrieved experimentally validated small molecules from the ChEMBL database with bioactivity (IC50/EC50) against HCV NS3 (454), NS3/4A (495), NS5A (494) and NS5B (1671) proteins. These unique compounds were divided into training/testing and independent validation datasets. Relevant molecular descriptors and fingerprints were selected using a recursive feature elimination algorithm. Different machine learning techniques viz. support vector machine, k-nearest neighbour, artificial neural network, and random forest were used to develop the predictive models. We achieved Pearson’s correlation coefficients from 0.80 to 0.92 during 10-fold cross validation and similar performance on independent datasets using the best developed models. The robustness and reliability of developed predictive models were also supported by applicability domain, chemical diversity and decoy datasets analyses. The “Anti-HCV” predictive models were used to identify potential repurposing drugs. Representative candidates were further validated by molecular docking which displayed high binding affinities. Hence, this study identified promising repurposed drugs viz. naftifine, butalbital (NS3), vinorelbine, epicriptine (NS3/4A), pipecuronium, trimethaphan (NS5A), olodaterol and vemurafenib (NS5B) etc. targeting HCV NS proteins. These potential repurposed drugs may prove useful in antiviral drug development against HCV.

Quality improvement to evaluate and provide treatment for chronic hepatitis C postpartum

BackgroundChronic hepatitis C virus (HCV) infections are increasing among reproductive age individuals. Direct acting antivirals (DAAs) can cure HCV, but the use of DAAs is not currently recommended during pregnancy and breastfeeding. Individuals with HCV commonly have inadequate prenatal and postnatal care. ObjectivesThe purpose of our study was to demonstrate the success of a quality improvement program to increase evaluation during pregnancy and ensuring access to DAA treatment medication during the postpartum period for individuals with chronic HCV to achieve cure 12 weeks after completing therapy. The primary outcome was documented HCV cure rate compared among individuals who received immediate treatment with DAA after delivery or after weaning or a traditional approach of referral to an infectious diseases specialist or hepatologist. The secondary outcome was the proportion of infants exposed to HCV evaluated. MethodsAn interdisciplinary team developed a program to increase evaluation and HCV treatment for postpartum individuals. Individuals who received prenatal care from March 2017 to May 2021 were eligible. Individuals with chronic HCV had a laboratory evaluation before delivery, and appropriate DAAs were selected for postpartum treatment. The health system specialty pharmacy dispensed DAA prescriptions immediately after delivery to those who were not breastfeeding. Individuals who did breastfeed had the option to begin treatment after weaning. Cure was defined as a sustained viral response or undetectable HCV RNA collected 12 weeks after completing DAA treatment. ResultsWe demonstrate the success of an interdisciplinary team to ensure access to therapy for the treatment of postpartum chronic HCV. Only 3 infants (25%) with mothers referred were evaluated at our institution compared with 44% of infants (n = 10) whose mothers were treated after delivery. ConclusionAn interdisciplinary team for HCV treatment improves access to treatment therapy with DAAs leading to the cure of chronic HCV after delivery.

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

Crushing and Splitting Direct-Acting Antivirals for Hepatitis C Virus Treatment: A Case Series and Literature Review.

Limited data exist regarding the use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) in patients who are unable to swallow tablets. This case series describes HCV treatment in patients requiring tablet manipulation, providing evidence for safety and effectiveness of HCV DAA tablet manipulation.

P-37 EXPERIENCE IN MEXICO WITH DIRECT ACTING ANTIVIRALS AS A TREATMENT FOR HEPATITIS C

It is considered that globally, 71 million people have chronic infection caused by the virus of Hepatitis C (HCV). It is estimated that in 2016 approximately 399,000 people died due to it. Among the infected people 70% develop a chronic infection caused by HCV. In Mexico, it was reported that 6% of them is type C, and the most common genotype is 1. Interferon and ribavirin, hardly ever used in developed countries, are still recommended in Mexico for treating this infection. To assess the effectiveness of direct acting antivirals (DAA) in Mexican population with HC. In a retrospective, multicenter study in 20 hospitals in Mexico, information of patients with HC and treated with DAA was gathered. A total of 913 patients were included. The gender distribution was 599 women and 314 men, the mean age was 58.88 ± 12.10 years old. The most frequent genotype was genotype 1. It was found that there is 99% of sustained viral response in genotype 1. Presented side effects were slight. We found a very high SVR rate, 99%, which is why applying DAA immediately after a patient is diagnosed with Hepatitis C to avoid further complications is recommended. Core tip: In Mexico, a large sample of patients was documented, where it was concluded that DAA should be used without the fear of adverse events, and to be certain about an SVR to the most frequent genotype in our population. However, the use of pangenomic DAA must be considered.

Screening and prevention of hepatitis C virus reactivation during chemotherapy.

Hepatitis C virus (HCV) reactivation occurs in 23% of HCV-infected cancer patients receiving chemotherapy. Forty-three percent of the patients with reactivation of HCV during chemotherapy develop a hepatitis flare. Most of the cancer patients with HCV reactivation have an unremarkable clinical course following an HCV-related hepatitis flare during chemotherapy. However, 26%–57% of the cancer patients developing an acute flare of chronic hepatitis C during chemotherapy require unanticipated discontinuation or dose reduction of chemotherapy, which results in deleterious changes in the cancer treatment plan. Although an optimal strategy for HCV screening in cancer patients receiving chemotherapy has not been established, universal pre-chemotherapy HCV testing for patients with hematological malignancies is recommended by current guidelines. All the currently approved direct-acting antivirals (DAAs) can be used in cancer patients, but the use of DAAs during chemotherapy should avoid drug–drug interactions between chemotherapy and antiviral agents. If there are no contraindications or anticipated drug–drug interactions, DAAs treatment can be administered before, during, or after chemotherapy. In conclusion, HCV reactivation occurs in approximately one-fourth of HCV-infected cancer patients receiving chemotherapy. An HCV-related hepatitis flare during chemotherapy may lead to the discontinuation of potentially life-saving chemotherapy. Currently, universal HCV screening is recommended in hematological malignancy patients before chemotherapy, but there is no evidence-based guideline for other cancer patients. DAAs treatment can cure HCV infection and prevent HCV reactivation during chemotherapy.

Association of the Extension for Community Healthcare Outcomes Project With Use of Direct-Acting Antiviral Treatment Among US Adults With Hepatitis C

Direct-acting antiviral (DAA) medications are highly effective in treating hepatitis C virus (HCV) infection. However, use of DAAs in rural and underserved areas is low owing to limited access to specialist physicians with experience in care of HCV infection. Project ECHO (Extension for Community Healthcare Outcomes) is a distance education model that trains primary care physicians to improve access to care for underserved populations with complex diseases such as HCV infection. Evidence on whether Project ECHO is associated with increased DAA use is limited. To examine the association between Project ECHO and use of DAA treatment in patients with HCV infection. This cohort study used data from Medicare beneficiaries who newly sought care for HCV infection between January 1, 2014, and December 31, 2017. Data were analyzed between September and December 2020. Project ECHO. Use of DAA treatment. Discrete-time hazard models with state and year fixed effects were used to examine the association between Project ECHO and DAA use in rural areas and areas with low specialist density. A total of 267 908 patients (mean [SD] age, 60.7 [11.5] years; 57.9% male; 66.6% White patients) were included in the analysis. For every 100 clinicians attending a Project ECHO training, the odds of DAA treatment initiation among patients with HCV infection increased by 9% (adjusted odds ratio [OR], 1.09; 95% CI, 1.07-1.11; P < .001) in nonrural areas with specialist density equaling 0. The association between DAA use and Project ECHO was stronger in areas with lower vs higher specialist density. For every additional 100 Project ECHO participants, the odds of DAA use decreased by 1% as specialist density in the area increased (adjusted OR, 0.99; 95% CI, 0.98-1.00; P = .03). There was no association between Project ECHO and the odds of receiving DAAs among patients in rural vs urban areas (adjusted OR, 1.01; 95% CI, 0.99-1.02; P = .49). In this cohort study, implementation of Project ECHO was associated with increased DAA use in areas with few specialist physicians, suggesting that Project ECHO may enhance access to DAA treatment through expanding the capacity of primary care physicians to treat HCV infection, especially in underserved areas.

Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals.

Chronic infection with hepatitis C virus (HCV) may complicate with hepatocellular carcinoma (HCC), especially in patients with cirrhosis. Although the achievement of a sustained virological response (SVR) had been associated with a reduction in the risk of HCC already in the Interferon era, some concerns initially raised following the use of direct-acting antivirals (DAA), as their use was associated with increased risk of HCC development and aggressiveness. However, studies demonstrated that the risk of HCC was strongly influenced by pre-treatment fibrosis stage and, eventually, prior HCC history more than the type of antiviral therapy. According to published studies, rates of de-novo HCC ranged between 1.4% and 13.6% in patients with cirrhosis or advanced fibrosis vs 0.9% and 5.9% in those with chronic hepatitis C (CHC). Conversely, rates of recurrent HCC were higher, ranging between 3.2% and 49% in cirrhotics vs 0% and 40% in CHC patients. Most studies tried to identify predictors of HCC development, either de-novo or recurrent, and some authors were also able to build predictive scores for HCC risk stratification, which however still need prospective validation. Whereas some clinical features, such as age, gender, presence of comorbidities and fibrosis stage, may influence both de-novo and recurrent HCC, previous tumour burden before DAA seems to prevail over these features in recurrent HCC risk prediction.

Progress in hepatitis C virus management in chronic kidney disease.

The current review highlights advances in the use of direct-acting antiviral (DAA) agents in the treatment of hepatitis C virus (HCV) in chronic kidney disease (CKD) stages G4-5, end-stage renal disease, and kidney transplantation. The use of DAA to facilitate kidney transplantation of HCV negative recipients with kidneys from HCV-infected donors and in the management of HCV-related cryoglobulinemia are also reviewed. DAA treatment results in rates of viral clearance (sustained virological response or SVR) of 90-100% in all studied CKD populations, comparable to SVR rates in the general population. DAA treatment allows safe and effective transplantation of HCV viremic kidneys into uninfected recipients. The high SVR results achieved with DAA allow successful treatment of previously under-treated CKD populations, and encouraged innovative interventions such as the use of HCV-infected donor kidneys to uninfected kidney transplant recipients.

Evaluation of the Renal Safety of Direct Acting Antivirals in Chronic Hepatitis C Patients

Objective:Direct acting antivirals (DAA) is a class of antivirals that hasbeen extensively used in chronic hepatitis C virus (HCV) patients over the past 6 years.Despite the excellent therapeutic benefits of DAA, there is a knowledge gap regardingthe safety of this class. Several reports of possible renal toxicity associated with DAAadministration can be found in the literature. The aims of this study are: to assess therenal safety of DAA used for the treatment of chronic HCV infection and to quantify the odds ofdeveloping renaltoxicityin patients withchronicHCV viralinfection.&#x0D; Study Design: Disproportionalityanalysiswasusedtodetectsignalsofpotentialsideeffects.&#x0D; Place andDuration: Amman –Jordan,One year study since September 2017 to march 2018.&#x0D; Methods: The method that was applied in the current study is obtaining the data from United States (US) food and drug administration(FDA)adverseeventreportingsystem(FAERS).DatabetweenJuly,2014andSeptember,2017werecombinedandexplored.Disproportionalityanalysiswasconducted to reports from chronic HCV patients to explore possible association betweenDAA administrationand renalsideeffects.&#x0D; Results: This study showed that a total of 3,837,418 safety reports were available in the period between July,2014 and September, 2017. Patients with chronic HCV infection represent 22,022 cases.When considering all DAA as drug of interest, the use of DAA alone or in combinationwith interferon and/or ribavirin did not increase the risk of having renal side effects.Exploring individual DAA demonstrated a significant association between the incidenceofrenalsideeffectsandtheadministrationoftelapreviranddasabuvir.ConsideringrenalsideeffectsindividuallyshowedasignificantassociationbetweenDAAadministrationand chronickidney disease.&#x0D; Conclusions: In this study, we reported a significant association between DAA administration andchronic kidney disease and between telaprevir or dasabuvir and renal side effect. Thesefindings are used for hypothesis generation rather than testing.

Successful treatment by on-demand glecaprevir and pibrentasvir for hepatitis C flare during R-CHOP in patients with diffuse large B-cell lymphoma: a case report

BackgroundIn patients with hepatitis C virus (HCV) and malignant lymphoma, hepatitis C flare during R-CHOP can result in discontinuation of treatment. However, appropriate therapeutic strategies for managing hepatitis C flare during R-CHOP have not been established, and this issue is complicated by conflicting results regarding the use of direct-acting antivirals in patients with uncontrolled malignancies.Case presentationWe report the first case of effective and safe treatment with on-demand 8-week glecaprevir and pibrentasvir for hepatitis C flare during R-CHOP in a patient with diffuse large B-cell lymphoma (DLBCL). The patient completed five additional courses of R-CHOP without hepatic toxicity. A complete response of DLBCL and a sustained virological response were observed at 24 weeks after glecaprevir and pibrentasvir completion.ConclusionOn-demand, direct-acting antivirals could be a novel strategy for managing hepatitis C flare during R-CHOP.

Evolution of estimated glomerular filtration rate in human immunodeficiency virus and hepatitis C virus-coinfected patients receiving sofosbuvir-based direct-acting antivirals and antiretroviral therapy.

The nephrotoxicity of sofosbuvir (SOF) on human immunodeficiency virus and hepatitis C virus (HIV/HCV)-coinfected patients receiving antiretroviral therapy (ART) remains controversial. We prospectively compared the estimated glomerular filtration rate (eGFR) changes in 167 patients receiving SOF-based direct-acting antivirals (DAAs) who also received tenofovir disoproxil fumarate (TFV)-based (n=116) and TFV-free ART (n=51). The eGFR was assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and the eGFR changes between ART regimens were compared by the generalized estimated equation. During DAA treatment, participants on TFV-based ART had a higher eGFR decline than those on TFV-free ART (slope coefficient difference: -0.82ml/min/1.73m2 /month [95% CI: -1.21 to -0.43]; p<0.001), whereas the eGFR changes did not differ between groups (slope coefficient difference: 0.13ml/min/1.73m2 /month [95% CI: -0.32 to 0.58]; p=0.42) after discontinuing DAAs. Participants on TFV TDF-based ART had a higher eGFR decline than those on TFV alafenamide fumarate (TAF)-based ART (slope coefficient difference: -0.31ml/min/1.73m2 /month [95% CI: -0.50 to -0.12]; p=0.01). After discontinuing DAAs, the eGFR changes did not differ between groups (slope coefficient difference: 0.06ml/min/1.73m2 /month [95% CI: -0.98 to 1.10]; p=0.91). In conclusion, HIV/HCV-coinfected patients on TFV-based ART had a slight eGFR decline compared to those on TFV-free ART during SOF-based DAA therapy. A similar trend between TDF-based and TAF-based ART was also observed. Because the differences of eGFR changes are limited, the physicians should not discourage the use of SOF-based DAAs in HIV-positive patients on TFV-based ART.

Evaluation of a specialty hepatitis C virus telephone pharmacy service.

Direct-acting antivirals (DAAs) used to treat hepatitis C virus (HCV) infection are associated with significant drug-drug interactions (DDIs). Pharmacists are well positioned to identify and mitigate these DDIs. Data to guide assessment of the impact of HCV specialty pharmacy services on identifying and addressing DDIs with DAAs are lacking. The overall purpose of the study described here was to determine the incidence and severity of DDIs identified by specialty pharmacists among patients treated with DAAs prior to and 1 month into therapy. An observational, retrospective study was conducted to evaluate the impact of specialty pharmacy services in mitigating DDIs associated with use of DAAs. Adult patients with HCV infection (n = 200) who received DAAs and were enrolled with a specialty pharmacy service over a 1-year period were included. Endpoints included number, severity, and type of DDIs and DDIs per patient at baseline and 1 month into therapy, pharmacists' interventions, and safety and clinical outcomes. Fifty-nine percent of patients had at least 1 DDI. A total of 170 DDIs were identified (137 at baseline and 33 at 1-month follow-up), and the mean number of DDIs per patient significantly decreased from baseline to 1-month follow-up (from 1.38 to 0.16, P < 0.0001). The rate of "potentially clinically significant" or "critical" interactions was significantly lower at 1-month follow-up vs baseline assessment (69.6% vs 81.7%, P < 0.0001). The most commonly identified DDIs involved acid suppressive medications (49.6% and 66.6% of DDIs at baseline and follow-up assessment, respectively) and cardiovascular medications (26.2% and 21.2%, respectively). Total number of DDI interventions was 131, with an acceptance rate of 85%. Most common intervention was patient education and monitoring. Approximately 60% of patients had DDIs with DAAs. Implementing HCV specialty pharmacy services significantly decreased DDIs while maintaining SVR12.

Enhanced immune responses, PI3K/AKT and JAK/STAT signaling pathways following hepatitis C virus eradication by direct-acting antiviral therapy among Egyptian patients: a case control study.

The use of direct-acting antivirals (DAAs) therapy for the treatment of hepatitis C virus (HCV) results in a high-sustained virological response (SVR) and subsequently alters liver immunologic environment. However, hepatocellular carcinoma (HCC) may occur after DAAs treatment. We aimed to clarify changes of immune responses, PI3K/AKT and JAK/STAT signaling pathways in HCV-induced liver diseases and HCC following DAAs treatment. Four cohorts were classified as chronic HCV patients, HCV-related cirrhosis without HCC, HCV-related cirrhosis and HCC, and healthy control group. The patient groups were further divided into treated or untreated with DAAs with SVR12. Increased percentages of CD3, CD8 and CD4, decreased CD4/FoxP3/CD25, CD8/PD-1 and CD19/PDL-1 were found in DAAs-treated patients in the three HCV groups. Following DAAs therapy, the levels of ROS, IL-1β, IL-6, IL-8 and TNF-α were significantly decreased in the three HCV groups. Treated HCV patients showed up regulation of p-AKT and p-STAT5 and down regulation of p-STAT3, HIF-1α and COX-2. In conclusion, DAAs enhance the immune response in chronic HCV and liver cirrhosis, hence our study is the first to show change in PI3K/AKT and JAK/STAT signaling pathways in different HCV-induced liver diseases after DAAs. In chronic HCV, DAAs have better impact on the immune response while in liver cirrhosis not all immune changes were prominent.

Paradigm-Shifting Research in Gastroenterology, Hepatology, and Nutrition: A Top 20 List of Articles Published in 2020

Paradigm-Shifting Research in Gastroenterology, Hepatology, and Nutrition: A Top 20 List of Articles Published in 2020