Era Of Direct-acting Antiviral Agents Research Articles

Chronic Hepatitis C Virus Infection: An Ongoing Challenge in Screening and Treatment.

With the advent of direct-acting antiviral agents (DAA) in the recent few years, hepatitis C virus (HCV) infection has become a curable infectious disease. Successful clearance of HCV could lead to improvement of both hepatic and extrahepatic outcomes, such as complications of cirrhosis, hepatocellular carcinoma, cardiovascular diseases, and incident diabetes. However, challenges persist in reaching the HCV elimination goals of the World Health Organization by 2030. Among these challenges are identifying those already infected or undiagnosed subjects, re-linking to the care of known but untreated HCV-infected subjects, and developing strategies to enhance treatment rates and compliance in specific or high-risk populations. In addition, issues of post-DAA viral clearance, including avoiding or preventing reinfection in high-risk populations and surveillance of hepatocellular carcinoma, are important to consolidate the treatment's short- and long-term efficacies. In the current DAA era, treatment is the most effective prevention strategy not only in its excellent efficacy and safety but also in preventing HCV spread. All of the surveillance or measures should center on DAA treatment in clinical practice.

Microbiota and hepatitis C virus in the era of direct-acting antiviral agents.

The gut microbiota plays a fundamental role in Hepatitis C Virus (HCV)-related liver disease. Indeed, HCV infection alters the gut microbiota, whereas intestinal dysbiosis induces an underlying inflammatory state. This status may lead to liver disease progression. The advent of direct acting antivirals (DAAs) was a turning point in the history of HCV infection, which enhances the chances of recovery. Beyond the elimination of the virus, DAA therapy can affect the gut microbiota of the HCV patient. The study of the gut microbiota in the patient with HCV-related liver disease could be the first step in understanding the etiopathogenesis of hepatopathy thereby opening the way to new therapeutic opportunities. Herein we evaluate current knowledge regarding the gut microbiota in patients with HCV infection and the impact of DAA therapy.

Chronic Hepatitis C: Acute Exacerbation and Alanine Aminotransferase Flare.

The hepatitis C virus (HCV) causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma, as well as extrahepatic manifestations such as malignant lymphoma. Currently, direct-acting antiviral agents (DAAs) against HCV infection can lead to a sustained virological response (SVR) in almost all HCV-infected patients. In this review article, we discuss acute exacerbation and alanine aminotransferase (ALT) flare in patients with chronic HCV infection. Although acute liver failure caused by HCV infection is rare, careful attention should be paid to the cases with ALT elevation during the natural course of chronic HCV infection. HCV genotype 2 infection, the use of rituximab, and a higher dose of corticosteroid are factors associated with HCV acute exacerbation and ALT flare. Treatment regimens for cancer have been interrupted or changed due to ALT flare due to HCV infection in some patients undergoing chemotherapy for cancer. The pathogenesis of HCV acute exacerbation and ALT flare could involve cellular as well as humoral immune responses. In the DAA era, the earlier introduction of DAAs may prevent chronic HCV-infected patients with acute exacerbation and ALT flare from developing into a more severe form, although DAAs may not be effective for all of them.

Low disease awareness as a contributing factor to the high prevalence of hepatitis C infection in Tzukuan, a hyperendemic area of southern Taiwan.

Understanding the barriers and tackling the hurdles of hepatitis C virus (HCV) care cascades is key to HCV elimination. The current study aimed to investigate the rates of disease awareness, link-to-care, and treatment uptake of HCV in a hyperendemic area in Taiwan. Tzukuan residents from 2000 to 2018 were invited to participate in the questionnaire-based interviews for HCV. The rates of disease awareness, accessibility, and anti-HCV therapy were evaluated in anti-HCV-seropositive participants. Among 10,348 residents, 1789 (17.3%) were anti-HCV seropositive. Of these 1789 anti-HCV-seropositive participants, data of 594 participants from questionnaire-based interviews in 2005-2018 were analyzed for HCV care cascades. Overall, 24.9% of anti-HCV-seropositive HCV participants had disease awareness, 53.9% of aware participants had accessibility, and 79.8% of assessed participants had received HCV treatment, with a community effectiveness of 10.7%. HCV prevalence decreased over time, from 21.2% in the early cohort to 9.3% in the recent cohort. Disease awareness increased over time, from 15.6% to 41.7%, with the community effectiveness increasing from 1.3% to 28.8%. Lower education levels and normal liver biochemistry were associated with a lower rate of disease awareness. Notably, 68% of participants with abnormal liver biochemistry and 69% of those with advanced fibrosis (FIB-4 > 3.25) were unaware of their HCV disease. We demonstrated huge gaps in disease awareness, link-to-care, and treatment uptake in the HCV care cascade in an HCV-hyperendemic area, even in the initial era of direct-acting antiviral agents. There is an urgent need to overcome these hurdles to achieve HCV elimination.

Are Hepatitis C Positive Female Liver Transplant Recipients Still at Increased Risk for Graft Failure? Reexamining the Disparity in the Modern Era of Direct-acting Antiviral Agents.

This study aimed to compare the outcomes of hepatitis C virus (HCV) positive (+) female liver transplant recipients to HCV negative (-) female and HCV+ male recipients before and after the direct-acting-antiviral (DAA) era. The United Network for Organ Sharing liver transplant database was retrospectively reviewed from 2002 to 2017. The DAA era was defined as ≥2014. In the pre-DAA era, HCV+ female recipients had greater risk for graft failure compared with HCV+ male (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.03) and HCV- female (HR, 1.51; 95% CI, 1.43-1.60; P < 0.001) recipients. In the post-DAA era, HCV+ female recipients had lower risk for graft failure compared with HCV+ male recipients (HR, 0.82; 95% CI, 0.70-0.97; P = 0.02) and equivalent outcomes to HCV- female recipients. HCV+ female recipients with graft failure had increased likelihood of graft failure due to disease recurrence compared with HCV+ male recipients in the pre-DAA era (odds ratio, 1.23; 95% CI, 1.08-1.39; P = 0.001) but not in the post-DAA era. Although historically HCV+ female recipients were at disproportionately increased risk for graft failure and disease recurrence, this disparity has been eliminated in the DAA era.

Prevalence and Risk Factor for Hepatocellular Carcinoma in Individuals with Hemophilia in the Era of Direct-Acting Antiviral Agents: A National Inpatient Sample Study

▪Background: Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis C virus (HCV) infection. HCV is the leading cause of liver disease in hemophilia population and was acquired with their first transfusion. While direct-acting antiviral agents (DAAs) are effective in HCV eradication, its impact on preventing HCC remains unclear. Few data on HCC in hemophilia after DAA are available. We undertook an observational study to determine the prevalence of and risk factors for HCC in hemophilia since the introduction of DAAs.Methods: We conducted an observational study including adult male discharges in the National Inpatient Sample (NIS) database from 2016-2018. Status of hemophilia (H) and non-hemophilia (NH), HCV, HCC, and other relevant medical conditions were identified using ICD-10 codes. Analysis included NIS-provided discharge-level weights to reflect national estimates. Categorical and continuous variables were assessed by Rao-Scott Chi-Square and weighted simple linear regression, respectively. Weighted multivariable logistic regression was performed to determine HCC risk factors. Variables included were age, race, HCV, HIV, alcoholism, smoking, obesity, hyperlipidemia (HLD), non-alcoholic steatohepatitis (NASH), substance abuse, transfusion, and Charlson comorbidity index (CCI).Results: In total, 7,674,969 adult male discharges, including 3,370 with H (0.04%), were identified between 2016 and 2018. Between 2016 and 2018, the diagnosis rates of HCV were 10.06% (95%CI 8.97%-11.26%) in H vs. 1.22% (95%CI 1.19%-1.25%) in NH, and the rates of HCC were 1.07% (95%CI 0.76%-1.51%) in H vs. 0.27% (95%CI 0.26%-0.28%) in NH. The diagnosis rates of HCV and HCC were similar in 2016, 2017 and 2018, for both H and NH populations. Compared with H without HCC, H with HCC were older (58.6 vs. 50.9 years-old, p<0.001), had higher CCI (mean : 6.5 ± 0.6 vs. 2.0 ± 2.0, p<0.001), and higher prevalence of HCV (36.11% vs. 9.78%, p<0.001), HBV (11.11% vs. 0.45%, p<0.001), NASH (5.56% vs. 0.12%, p<0.001), end-stage liver disease (88.89% vs. 8.61%, p<0.001), portal hypertension (27.78% vs. 2.61%, p<0.001), and platelet transfusion (11.11% vs. 1.44%, p<0.001). The prevalence of HIV infection between H with and without HCC was similar (8.33% vs. 8.82%, p=0.919). Among these with HCC, H were more likely to be younger (58.6 vs. 64.1 years-old, p=0.001), HIV (+) (8.33% vs. 1.64%, p=0.002), and less likely to have alcoholism (11.1% vs. 33.2%, p=0.018) and HLD (2.78% vs. 20.8%, p=0.008), than NH. The rates of cirrhosis, NASH, autoimmune hepatitis, and biliary cirrhosis were similar between groups. Multivariable logistic regression analysis among H patients indicated that NASH (OR 21.6, 95%CI 4.63-100.6), HCV (OR 3.96, 95%CI 1.55-10.2), and CCI (OR 1.54, 95%CI 1.39-1.72) were significant risk factors for HCC, while HIV (OR 0.02, 95% CI 0.00-0.13) and HLD (H: OR 0.07, 95% CI 0.01-0.39) were protective.Conclusion: From 2016 to 2018, the rate of HCC did not significantly decrease in discharges with hemophilia in the NIS database. Chronic HCV infection remains a significant risk factor of HCC in hemophilia despite availability of DAA therapy. NASH and Charlson comorbidity contribute to HCC risk, while HIV and hyperlipidemia appear protective. DisclosuresRagni: Takeda Therapeutics: Membership on an entity's Board of Directors or advisory committees; BioMarin Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Bioverativ (Sanofi): Membership on an entity's Board of Directors or advisory committees; Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees; Alnylam (Sanofi): Membership on an entity's Board of Directors or advisory committees; University of Pittsburgh: Research Funding.

Hepatitis C virus testing in a clinical HIV cohort in Ontario, Canada, 2000 to 2015.

BackgroundHIV‐positive individuals may acquire HCV via injection drug use (IDU) and condomless anal sex. HIV care provides opportunities for HCV testing and cure with direct‐acting antiviral agents (DAAs).MethodsWe analyzed data from the Ontario HIV Treatment Network Cohort Study. Among those not HCV‐positive or diagnosed previously (n = 4586), we used Cox regression to test the rates of ever HCV testing (serological or RNA) in HIV care by DAA era (pre‐DAA: 2000‐2010; after DAA: 2011‐2015) and compared the proportion diagnosed with HCV. We identified correlates of annual proportions of serological testing using Poisson generalized estimating equations.ResultsAfter DAA vs pre‐DAA, the hazard rate ratio (95% CI) of ever HCV testing was 1.70 (1.59, 1.81). The proportion (95% CI) tested annually increased from 9.2% (8.0%, 10.7%) in 2000 to 39.1% (37.1%, 41.1%) in 2015 (P < 0.0001). The proportion diagnosed with HCV declined by 74% pre‐DAA to 11% after DAAs. Annual testing increased per calendar year (16% steeper slope after DAA vs pre‐DAA) and was more common among men who have sex with men; those more educated (post‐secondary vs ≤ high school); and those positive for syphilis or reporting any IDU. Annual testing decreased per decade of age and time since HIV diagnosis.DiscussionAnnual HCV testing increased over time with higher testing among those reporting sexual or IDU risk factors, but fell short of clinical guidelines. Targeted interventions to boost testing may be needed to close these gaps and reach WHO 2030 HCV elimination targets.

Hepatitis C virus care cascade in persons experiencing homelessness in the United States in the era of direct-acting antiviral agents: A scoping review.

The hepatitis C virus (HCV) care cascade has been well characterized in the general United States population and other subpopulations since curative medications have been available. However, information is limited on care cascade outcomes in persons experiencing homelessness. The main objective of this study was to map the available evidence on HCV care cascade outcomes in people experiencing homelessness in the U.S. in the era of direct-acting antiviral agents (DAAs). Primary and secondary outcomes included linkage to care (evaluation by a provider that can treat HCV) and sustained virologic response (SVR) or cure. Exploratory outcomes included other cascade data, like treatment initiation, which precedes SVR. PubMed was the primary database accessed for this scoping review. We characterized the HCV care cascade in people experiencing homelessness using sources of evidence published in 2014 onwards that reported the proportions of persons who were linked to care, achieved SVR, and completed other cascade steps. We synthesized our results into a scoping review. The proportion of persons linked to care among chronically infected cohorts with unstable housing ranged from 29.3% to 88.7%. Among those chronically infected, 5%-58.8% were started on DAAs and 5%-50% achieved SVR. In conclusion, these results show that persons experiencing homelessness achieve high rates of linkage to care in non-specialist community-based settings compared to the general U.S. population pre-DAAs. However, DAA initiation was found to be a rate-limiting step along the care cascade, resulting in commensurate low rates of cure.

HCC in the Era of Direct-Acting Antiviral Agents (DAAs): Surgical and Other Curative or Palliative Strategies in the Elderly.

Simple SummaryThis study investigated HCC onset in a cohort of patients receiving DAA therapy for HCV infection. It highlights that HCC onset after HCV-clearance might show more aggressive behavior and might exclude the patient from curative treatments, such as surgery or radiofrequency ablation. Moreover, HCC may develop in livers with mild to moderate fibrosis, indicating that multiple factors (host immune response, host metabolism, etc.) may play an important role in determining the cancer onset or its recurrence after HCV eradication. It is crucial to classify long-term chronically infected patients as at high risk for HCC development and to implement strict follow-up for them after eradication.Hepatocellular carcinoma (HCC) accounts for 75–85% of primary liver malignancies, and elderlies have the highest incidence rates. Direct-acting antiviral agents (DAAs) have shown satisfying results in terms of HCV sustained viral response (SVR). However, data regarding HCC risk post-DAA-SVR is still conflicting. This study aims to consider HCC onset in moderate underlying liver disease. We conducted a retrospective study on 227 chronically infected patients (cHCV), treated with DAAs. Patients were divided into three groups: “de novo occurrent HCC”, “recurrent HCC”, and “without HCC”. Fifty-six patients aged <65 years (yDAA) were studied separately. HCC patients aged ≥65 years (DAA-HCC) were compared to a historical group of 100 elderly HCC patients, treated with peginterferon (Peg-IFN) ± ribavirin antiviral agents, non-SVR (hHCC). The HCC prevalence in DAA patients was 32.75%: “de novo occurrent’’ 18.13% and “recurrent’’ 14.62%, despite 42.85% of them having no fibrosis to mild or moderate fibrosis (F0-F1-F2). yDAA showed 5.36% “de novo occurrent” HCC. Curative procedure rates were compared between DAA-HCC and hHCC at the first and at recurrent presentation (22 (39.29%) vs. 72 (72%); 17 (30.36%) vs. 70 (70%), respectively (p < 0.001)). No significant difference was found in 3-year OS (p = 0.6). However, in cause-specific mortality analysis, HCC-related death was higher in the DAA-treated group, whereas cirrhosis-related death was more common in the historical group (p = 0.0288), considering together the two causes of death. A more accurate patient stratification according to multifactorial and new diagnostic investigations identifying HCC risk might allow an improvement in management and access to curative therapies.

Natural history of hepatitis C virus infection in a large national seroconversion cohort in the direct-acting antiviral agent era: Results from ERCHIVES.

Hepatitis C virus (HCV) natural history studies are limited by not knowing the time of infection, small numbers and non-representative populations. No studies are available from the direct-acting antiviral agents (DAA) era. We created the largest known cohort of persons with HCV with a known window of seroconversion in the DAA era. We compared the annual cumulative incident events and incidence rate/1000 person-years of follow-up for liver cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC) and mortality from the time of seroconversion among untreated and those treated and attaining a sustained virologic response (SVR). Among 12,881 persons in the final analyses, 10,417 had never been treated for HCV, 2464 (23.6%) were treated with a DAA regimen and 1836 (74.5%) attained SVR. After 9years of follow-up, cirrhosis was diagnosed in 17.4% of untreated and 13.6% of the SVR group. Overall, 29.5% in the untreated versus 3.5% in the SVR group died. Incidence rates/1000 person-years of follow-up (95% CI) for untreated versus SVR group were 22.7 (21.6, 23.9) versus 19.5 (17.0, 21.9) for cirrhosis (p=0.03), 0.1 (0.03, 0.2) versus 0.07 (-0.07, 0.2) for HCC (p=0.74) and 35.4 (34.0, 36.8) versus 4.53 (3.4, 5.7) for mortality (p<0.0001). After excluding those with alcohol-related diagnoses at baseline, the difference in cirrhosis was not statistically significant. Cirrhosis and mortality occur early and steadily increase over the first decade after acquiring HCV infection, while HCC is rarely observed. Those treated with a DAA regimen have sharply lower cirrhosis and mortality rates, particularly among those without alcohol abuse or dependence.

Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients With Hepatitis C in the Era of Direct-Acting Antiviral Agents

In the US, hepatocellular carcinoma (HCC), primarily associated with hepatitis C virus (HCV) infection, is the fastest rising cause of cancer-related death. Wider use of highly effective direct-acting antiviral agents (DAAs) substantially reduces the burden of chronic HCV infection, but the subsequent impacts with HCV-associated HCC remain unknown. To assess projected changes in the incidence rate of and surveillance burden for HCC in the era of DAA treatment for HCV. This decision analytical model study was performed from January 2019 to February 2020, using an individual-level state-transition simulation model to simulate disease progression, screening, and different waves of antiviral treatments for HCV in the US from 2012 to 2040. Current clinical management for chronic HCV infection. Model outcomes were projected temporal trends and age distribution of incident HCC cases and candidates for HCC surveillance among patients with viremia and patients with virologically cured HCV. The simulation model projected that the annual incidence of HCC among patients with viremia and patients with virologically cured HCV will continue increasing to 24 000 (95% uncertainty interval [UI], 18 000-31 000) cases until 2021. In patients with virologically cured HCV, incident HCC cases are projected to increase from 1000 (95% UI, 500-2100) in 2012 to the peak of 7000 (95% UI, 5000-9600) in 2031 with a subsequent decrease to 6000 (95% UI, 4300-8300) by 2040. The proportion of incident HCC cases that occur in individuals with virologically cured HCV is estimated to increase from 5.3% in 2012 to 45.8% in 2040. The number of candidates for HCC surveillance in the population with virologically cured HCV is projected to increase from 106 000 (95% UI, 70 000-178 000) in 2012 to the peak of 649 000 (95% UI, 512 000-824 000) in 2030 and decrease to 539 000 (95% UI, 421 000-687 000) by 2040, while the proportion of all candidates for surveillance who are virologically cured is estimated to increase from 8.5% to 64.6% during the same period. The average age of HCC incidence and surveillance candidates is estimated to increase from 55 in 2012 to 72 and 71, respectively, by 2040. The results of this study suggest that the burden of HCC will shift from patients with viremia to patients with virologically cured HCV, and to older populations. Appropriate management may be warranted for early detection of HCC in patients who may no longer be receiving specialty care for liver conditions.

Abstract 12659: Improved Heart Transplant Outcomes Among Patients With Hepatitis C Virus Infection in the Era of Direct-acting Antiviral Agents

Introduction: The effect of hepatitis C virus (HCV) infection in recipients or donors on heart transplants is less known in the era after the introduction of direct-acting antiviral agents (DAAs). Methods: Using the United Network for Organ Sharing registry, 25,581 adult heart transplant recipients between 2005 and 2019 were identified. The trend in prevalence of HCV infected recipients and in utilization of HCV infected donors and their effect on the transplant outcomes were investigated in the pre-DAAs era versus the DAAs era separated by May 13, 2011, using Cox proportional hazard regression. Results: HCV antibody positive recipients (n=532, 2.1%) had stable prevalence ( P =0.18) with a higher mortality risk in the pre-DAAs era (50.8% versus 38.8% at 10 years; hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.22-1.85; P &lt;0.001), however not in the DAAs era (25.3% versus 28.4% at 7 years; HR, 0.96; 95% CI, 0.72-1.28; P =0.79) ( P interaction&lt;0.001). Organ use from HCV antibody positive donors (n=375, 1.5%) was exclusively concentrated in the recent years ( P &lt;0.001) and provided the similar mortality up to 2 years (15.7% versus 12.4%; HR, 0.96; 95% CI, 0.65-1.43; P =0.84) regardless of the recipient HCV antibody status. The similar findings were confirmed with a subgroup cohort with positive nucleic acid amplification test (NAT). Conclusions: In the DAAs era, positive HCV antibody in recipients did not adversely affect the long-term transplant outcomes. Graft utilization from positive HCV antibody or NAT positive donors are rapidly more prevalent and appeared to be promising up to 2 years post-transplant.

Antiviral treatment for hepatitis C among injecting drug users in the era of direct-acting antiviral agents

HCV prevalence among people who inject drugs (PWID) is up to 67%. PWID is a population that needs priority attention to achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat by 2030. Although the SVR of HCV patients treated with direct-acting antiviral drugs (DAAs) can reach over 95%, especially in medical practice, there are still major obstacles to PWID treatment, because PWID is usually accompanied with concurrent infection, multiple-genotype infections, low compliance, substance abuse, methadone maintenance therapy, and risky behavior and re-infection conditions. Therefore, physicians often concern that these factors will affect the treatment efficacy, and refuse to provide hepatitis C treatment in PWID. This article reviews the relevant studies status and effects of hepatitis C treatment in PWID with different infection states and special behavior characteristics, and further highlights that the multidisciplinary cooperation for hepatitis C treatment in PWID is safe and effective, and can ensure treatment compliance.

Rheumatologic manifestations of hepatitis C in the era of direct-acting antiviral agents.

Beyond the classic hepatic complications, hepatitis C (HCV) infection is considered as a systemic disease, since extrahepatic manifestations become clinically evident in 40% to 70% of the patients and it can frequently include rheumatic ones. Furthermore, HCV can promote the production of several autoantibodies, thus complicating the differential diagnosis between primitive and HCV-related rheumatic disorders. The recent development of direct-acting antivirals (DAA) against HCV has revolutionized the field, reducing the damage stemming from systemic inflammatory phenomena and persistent immune activation associated with continuous HCV replication. Our review focuses on the main rheumatologic manifestations associated with chronic HCV infection as well as the impact of DAA interferon-free treatments on such extrahepatic clinical involvement.

Hepatitis C Virus Positivity Should Not Be Included in the Kidney Donor Profile Index Calculation When Transplanting HCV-Positive Kidneys Into Noninfected Recipients in the Era of Direct-Acting Antiviral Agents.

Hepatitis C Virus Positivity Should Not Be Included in the Kidney Donor Profile Index Calculation When Transplanting HCV-Positive Kidneys Into Noninfected Recipients in the Era of Direct-Acting Antiviral Agents.

Make platelet count great again: Direct‐acting antiviral agent therapy in patients with chronic hepatitis C

Hepatitis C virus (HCV) infection is an endemic disease in Taiwan, which causes adverse liver events, including development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Among the chronic hepatitis C (CHC) patients, sustained virological response (SVR) after antiviral therapy has been shown to be associated with prolonged overall survival and the reduced risks of HCC and liver-related mortality.1 The combination of pegylated interferon (Peg-IFN) plus ribavirin therapy was the standard of care before 2011. However, its use was limited by various disadvantages, including decrease in platelet count during therapy. With the introduction of novel direct-acting antiviral agents (DAAs) targeting the replication process of HCV, this IFN-free therapy has become the standard of care and has higher response rates and fewer side effects. Thrombocytopenia is a common complication of chronic liver diseases, but the pathophysiology of thrombocytopenia in CHC patients is not yet completely understood yet. Regardless of the underlying mechanisms, it has been reported that peripheral platelet count reflects the degree of fibrosis in CHC patients.2 In this study, Hsu et al first investigated the temporal relationship between platelet count and alanine aminotransferase (ALT) level in CHC patients who received DAA therapy. In this retrospective study, the SVR rate at 12 weeks after therapy (SVR12) was 98.7% (77/78). In patients without cirrhosis (n = 70), a 7.5% increase of mean platelet count was noted within 2 weeks after the initiation of DAA therapy. The increased platelet count remained stable throughout the treatment and follow-up periods. In contrast, no obvious changes in platelet count were noted among patients with cirrhosis (n = 8). The underlying mechanism to induce thrombocytopenia in CHC patients is complex. It has been considered that splenic congestion as a consequence of portal hypertension is the major etiology.3 Other possible mechanisms included autoimmune reaction with the production of antiplatelet antibodies, direct bone marrow suppression by HCV, decreased production of thrombopoietin, and endothelial dysfunction.4 This study demonstrated that platelet count increased within 2 weeks after DAA therapy, which has not been observed during Peg-IFN-based therapy as Peg-IFN itself causes thrombocytopenia. Such a rapid recovery could be attributed to the suppression of HCV replication instead of fibrosis regression, which usually takes years to develop. However, we still need more studies to address how suppressed viral replication induces recovery of platelet count. The most challenging issue in the DAA era is how to predict HCC development after SVR12 is achieved. Previous studies have shown that host and liver factors, such as platelet count, are important HCC predictors. Based on this study, the pretreatment platelet count can be affected by viral replication, while the posttreatment platelet count is more stable and can be more representative of the liver fibrosis severity. This also echoes the finding that posttreatment biomarkers, compared to pretreatment biomarkers, serve as better predictors for long-term HCC development in CHC patients treated with curative antivirals.5, 6 Considering all lines of data together, we believe that biomarkers measured after treatment are more appropriate in predicting long-term outcomes than those measured before treatment. There are also some limitations of this study. First, the patient number was small, and there were only eight patients with cirrhosis. The insignificant change of platelet count in cirrhotic patients could be attributed to the small patient number. Second, the study only collected information from baseline to 12 weeks after treatment. It is still unclear whether there is a consistent improvement of platelet count after a long-term follow up, which is more likely to be attributed to liver fibrosis regression. A large-scale study with a long-term follow up is needed to address this issue. In summary, DAA therapy is associated with increased platelet count shortly after suppressing HCV replication in CHC patients without cirrhosis. Further research is needed to assess the long-term effects of DAAs therapy on platelet count and the biological basis for these findings. The authors declare no conflict of interest.

Management of Hepatitis C Infection in children in the era of Direct-acting Antiviral Agents.

Chronic hepatitis C certainly is a global health burden in children as well as in adults. Spontaneous viral clearance can occur in early childhood but is uncommon thereafter. Although the majority of cases are asymptomatic during childhood and young adulthood, without an effective treatment, children who acquire HCV via vertical transmission can develop chronic liver disease and other complications including end-stage liver disease and hepatocellular carcinoma in adulthood. Efforts from worldwide health organizations, the pharmaceutical industry, and clinical and research institutions have resulted in very effective interferon-free therapy with direct-acting antiviral agents (DAAs) for HCV-infected children. In this manuscript, we will briefly review the epidemiology of HCV in children, historic treatment, current published data on DAAs in children and conclude with suggestions for management of the child with HCV in the era of DAAs.

THU-175-Eligibility and feasibility of hepatitis C treatment in the era of direct-acting antiviral agents: Our experience in real-world practice

THU-175-Eligibility and feasibility of hepatitis C treatment in the era of direct-acting antiviral agents: Our experience in real-world practice

Systematic review: economic evaluations of HCV screening in the direct-acting antivirals era.

The World Health Organization estimated that 90% of the infected people need to be diagnosed and 80% need to be treated to reach the aim of hepatitis C virus (HCV) elimination by 2030. For this reason, all possible strategies to detect and treat HCV-infected people need to be carefully evaluated to implement the best one. To review and synthesise the economic evaluations of HCV screening programs conducted in the era of direct-acting antiviral agents regimens. A systematic literature review was conducted until April 2018 to provide information on the costs and effectiveness of HCV screenings in direct-acting antiviral agents era. A critical assessment of the quality of economic evaluations retrieved was conducted. The literature search identified 716 references; 17 of them assessed cost and effectiveness of screening programs and antiviral treatments in different populations: general population (n=7), drug users (n=5), high-risk populations (n=4) and other populations (n=3). The HCV screening and direct-acting antiviral agents treatment appear to be good value for money, both in general and high-risk populations, if a cost per quality adjusted life years of $50000 is set as willingness to pay threshold. Some studies showed the value of including lower stage of fibrosis in the treatment selection criteria. Several HCV screening strategies plus direct-acting antiviral agents treatments resulted cost-effectiveness in different populations. However, there is still need of country and population-specific evaluations within the different HCV screening and treatment strategies available, in order to assess their cost-effectiveness and sustainability and fully support an evidence-informed policy for HCV elimination.

Hepatitis C Virus - Related Hepatocellular Carcinoma in the Era of Direct - Acting Antiviral Agents

Context: The emergence of direct - acting antiviral agents (DAAs) with high sustained virological responses (SVR) is an epoch - making revolution. However, the value of antiviral agents in the field of hepatitis C - related hepatocellular carcinoma (HCC) is not clear. Further, the risk of tumor occurrence or recurrence following an antiviral regimen is not yet reached a consensus. Evidence Acquisition: All scientific evidence was collected through a systematic review of studies discussing DAA regimen and hepatitis C-related HCC, in PubMed, EMBASE, and Web of Science. The relevant articles were obtained and reviewed carefully before working on the paper. Results: The current review study aimed at discussing recent studies on hepatitis C - related HCC in the era of DAAs, including application of DAAs in the field of treatment of hepatitis C virus (HCV), efficacy of DAAs on HCV-associated HCC, and the effect of DAAs on occurrence and recurrence of HCC. Conclusions: It was shown that DAAs had a relatively poor therapeutic effect on HCV patients with HCC, based on the current studies. After analyzing the existing data, the conclusion cannot yet be reached that DAA treatment influences the risk of HCC in patients with HCV infection.