Introduction Of Direct-acting Antiviral Agents Research Articles

Analyzing risk factors and developing a stratification system for hepatocellular carcinoma recurrence after interferon-free direct-acting antiviral therapy in chronic hepatitis C patients.

The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence. Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models. The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR 12 ), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR 12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors. This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR 12 , posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes.

Hepatitis C Virus Infection in the Elderly in the Era of Direct-Acting Antivirals: Evidence from Clinical Trials and Real Life.

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug-drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

Introduction of direct-acting antiviral agents alters frequencies of anti-GPIIb/IIIa antibody-producing B cells in chronic hepatitis C patients with thrombocytopenia

The pathogenesis of thrombocytopenia in chronic hepatitis C (CHC) conceivably involves autoimmunity; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear. In this study, we examined the changes in the frequency of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells and the levels of plasma B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and interleukin (IL)-21 following treatment of CHC with direct-acting antiviral agents (DAA). We recruited 28 patients with CHC who underwent treatment with DAA for 8–12 weeks and subsequently tested negative for serum hepatitis C virus RNA. Thirty healthy controls were recruited for comparison. Platelet counts increased significantly (p = .016), and the frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly (p = .002) in CHC patients with thrombocytopenia at the end of treatment (EOT) than before DAA treatment (baseline). However, these changes were not observed in CHC patients without thrombocytopenia. Plasma BAFF levels in CHC patients with thrombocytopenia significantly decreased from baseline to EOT (p = .002). Anti-GPIIb/IIIa antibody-producing B cells were positively correlated with plasma BAFF levels in these patients (r = 0.669, p = .039). These results suggest that DAA treatment suppresses the autoimmune response against platelets and improves thrombocytopenia.

Mortality among Alaska Native Adults with Confirmed Hepatitis C Virus Infection Compared with the General Population in Alaska, 1995-2016.

Background Hepatitis C virus (HCV) infection incidence rates in the United States have increased since 2010 as a byproduct of the opioid crisis despite the introduction of direct-acting antiviral agents in 2013. HCV infection is associated with higher rates of liver-related and nonhepatic causes of death. Methods This study compared demographic characteristics and age-adjusted death rates from 1995 to 2016 among Alaska Native (AN) adults infected with HCV (AK-HepC) to rates among the AN and non-AN adult populations living in Alaska. Liver-related disease (LRD) and other disease-specific age-adjusted death rates were compared between the populations. Results The all-cause death rate among the AK-HepC cohort was 2.2- and 3.4-fold higher than AN and non-AN adults, respectively, and remained stable over time in all populations. The LRD death rate among the AK-HepC cohort was 18- and 11-fold higher than the non-AN and AN, respectively. The liver cancer rate among the AK-HepC cohort was 26-fold higher compared to the Alaska statewide population. The AK-HepC cohort had elevated rates of death associated with nonhepatic diseases with circulatory disease having the highest rate in all populations. Among liver cancer deaths in the AK-HepC cohort, 32% had HCV listed as a contributing cause of death on the death certificate. Conclusions Death rates in the AK-HepC cohort remained stable since 1995 and higher compared to the general population. People with HCV infection had an elevated risk for all-cause, liver-related, and nonhepatic causes of death. Hepatitis C infection may be underrepresented as a cause of mortality in the United States.

Effect of Hepatitis C Virus Infection on Heart Transplants in the Current Era

The effect of hepatitis C virus (HCV) infection in recipients or donors on heart transplants is less known in the current era after the introduction of direct-acting antiviral agents (DAAs) in 2011. Using the United Network for Organ Sharing registry, 24 871 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 past era versus the current era separated by 2011, using Cox proportional hazard regression. HCV antibody-positive recipients (n = 520, 2.1%) had stable prevalence (P = 0.18). They had a lower survival estimate when compared with HCV antibody-negative recipients in the past era (55.3% versus 70.9% at 7 y; hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.27-1.91; P < 0.001), however not in the current era (73.1% versus 71.5% at 7 y; HR, 1.00; 95% CI, 0.75-1.32; P = 0.98) (Pinteraction < 0.001). Organ use from HCV antibody-positive donors (n = 371, 1.5%) was concentrated in the recent years (P < 0.001) and provided the similar survival estimate up to 2 y (84.2% versus 87.6%; HR, 0.97; 95% CI, 0.65-1.44; P = 0.87). The similar findings were confirmed with a subgroup cohort with positive nucleic acid amplification test. Positive HCV antibody in recipients did not adversely affect the long-term transplant outcomes in the current era. Graft utilization from positive HCV antibody or nucleic acid amplification test-positive donors are rapidly more prevalent and appeared to be promising up to 2 y posttransplant.

Safety &amp; Efficacy of Directly Acting Antivirals (Sofosbuvir &amp; Daclatasvir) in Treatment of Chronic HCV in HIV-HCV Co-Infected Egyptian Patients

Abstract Background The introduction of direct-acting antiviral agents, has revolutionized the treatment for chronic HCV with higher cure rates, shorter duration of treatment and more tolerability have been achieved. Objectives The aim of our study is to estimate the efficacy and safety of DAAs in treatment of chronic HCV in patients co-infected with HIV. Patients and Methods This study of previously untreated patients with HCV and HIV co- infection conducted at Abbasia Fever Hospital, from July 2019 to February 2020. Patients included those who are chronic HCV infection and receiving antiretroviral therapy with a CD4 T-lymphocyte count of 200 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed during treatment by combination of daclatasvir 90mg and sofosbuvir 400mg+/- ribavirin 800mg daily for 12 weeks. Results In this study, AST &amp; ALT were significantly decreased at end of treatment and 12 weeks after treatment, CD4 count was significantly increased. Otherwise there are no significant changes in both hematological and biochemical laboratory results. The demographic features of the patients and HIV disease characteristics were not predictors of HCV treatment failure. Conclusion More studies on larger numbers of patients are required for proper evaluation of the safety and efficacy of direct acting antiviral agents generally and sofosbuvir plus daclatasvir combination particularly in HIV/HCV coinfected patients. Longer follow-up studies are still recommended to fully understand the impact of sustained virological response on dynamics of liver fibrosis, biochemical profile and rate of relapse.

Direct-acting antiviral regimens in Egyptian patients with chronic hepatitis C virus infection: A real-world single-center experience

Background and study aims:Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles. Patients and methodsIn total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed. ResultsThe overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree. ConclusionThe interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.

HIPPOCRATES® project: A proof of concept of a collaborative program for hepatitis C virus micro-elimination in a prison setting.

BACKGROUNDIn the last few years we have witnessed a revolution in the treatment of hepatitis C virus (HCV) infection. With the introduction of direct-acting antiviral agents (DAAs), sustained virological response (SVR) is achieved in more than 95% of the patients. The focus is now being turned to the global targets set by the World Health Organization, with the aim of achieving HCV elimination by 2030. Prison inmates constitute one of the high-risk groups, and receive treatment less frequently due to several barriers in access to health care.AIMTo describe the management and follow-up of a cohort of HCV monoinfected patients treated with DAA in the prison setting, where tertial referral liver center specialists locally provide, on-site assessment and treatment for the prisoners.METHODSA prospective observational study was conducted from April 2017 to March 2020, which included all HCV monoinfected prison inmates in the largest Northern Portugal prison. Demographic, clinical, and laboratory data, as well as transient elastography measurements, were collected onsite by the medical team and prospectively recorded. Patients were treated with DAA according to international guidelines. The primary endpoint was SVR at post-treatment week 12. RESULTSThere were 98 monoinfected HCV male inmates (mean age, 42.7 ± 8.6 years) included in the analysis. Injecting drugs or tattooing were reported in 74.5%, with 38.8% of the latter being done in prison. Alcohol consumption of more than 30 g/d was referred in 69.4%. The most prevalent genotype was 1a (54.1%), followed by 3 (27.6%), 4 (9.2%) and 1b (6.1%). Pretreatment fibrosis degree was mild-to-moderate (F0-F2) in 77.6% and severe in 22.4% (F3-F4). Treatment regimens chosen were: 45.9% elbasvir/grazoprevir, 29.6% sofosbuvir/velpatasvir, and 12.2% sofosbuvir/ledispavir and glecaprevir/pibrentasvir. No major adverse events were observed. SVR at post-treatment week 12 was 99%.CONCLUSIONIn a population considered to be both hard-to-access and a cornerstone for HCV elimination, the onsite evaluation and treatment of HCV-infected prisoners, achieved an exceptional highly effective success rate. This type of collaborative program should be considered to be expanded, to support hepatitis C elimination efforts.

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.

Uptake and predictors of direct-acting antiviral treatment for hepatitis C among people receiving opioid agonist therapy in Sweden and Norway: a drug utilization study from 2014 to 2017

BackgroundTreatment with direct-acting antiviral agents (DAAs) offers an opportunity to eliminate hepatitis C virus (HCV) endemic among people who inject drugs (PWID) and people enrolled in opioid agonist therapy (OAT) programs. The objective of this study was to estimate and to compare HCV treatment uptake after the introduction of DAAs among patients receiving OAT in Sweden and Norway. We also aimed to evaluate predictors of DAAs treatment among OAT patients in both countries.MethodsThis observational study was conducted with data from The Swedish Prescribed Drug Register and The Norwegian Prescription Database. We studied dispensed medications to calculate HCV treatment among OAT patients from 2014 to 2017 in Sweden and Norway. HCV prevalence was estimated from primary and secondary sources. Dispensations of medicines from different therapeutic areas, which served as proxy for co-morbidities in 2017, were conditionally adjusted for age, gender, and OAT medications. Logistic regression was used to evaluate these parameters.ResultsIn total 3529 individuals were identified with dispensed OAT in the Swedish cohort and 7739 individuals in the Norwegian cohort. HCV treatment was utilized by 407 persons in Sweden and 920 in Norway during the study period. Annual HCV and DAA treatment uptake increased in both countries. The estimated cumulative HCV treatment uptake at the end of 2017 was 31% in Norway and 28% in Sweden. DAA treatment was associated with increased age (aOR 1.8; 95% CI 1.0–3.2) and the dispensation of drugs used for diabetes (aOR 3.2; 95% CI 1.8–5.7) in Sweden. In Norway, lipid modifying agents and antibacterials were associated with decreased odds (aOR 0.4; 95%CI 0.2–0.9, aOR 0.8; 95%CI 0.6–1.0).ConclusionsAn increase in DAA treatment and HCV treatment uptake was observed among Swedish and Norwegian OAT patients whilst introducing new direct-acting antiviral treatment regimens. However, more than two thirds of the OAT population in Norway and Sweden were untreated at the beginning of 2018. A further scale-up is crucial in order to control and eliminate the HCV endemic among OAT patients.

Evaluation of Pharmaceutical Intervention at Hepatitis C Medication Therapy Adherence Clinic in North Borneo, Malaysia (Epic MTAC)

Introduction: Hepatitis C virus (HCV) is a worrying public health issue worldwide. The introduction of direct-acting antiviral agents (DAAs) brings revolution to HCV treatment. Pharmacists’ role in Malaysia is significant since the implementation of Medication Therapy Adherence Clinic (MTAC). This study aims to determine the sustained virological response (SVR12) for HCV patients treated with Sofosbuvir and Daclatasvir and/or Ribavirin. Besides, it evaluates adherence rate, types of pharmaceutical intervention and physicians’ acceptance rate.

Postsustained Virological Response Management in Hepatitis C Patients.

The introduction of direct-acting antiviral agents (DAA) has revolutionized management and care of patients with chronic hepatitis C virus (HCV) infection, leading to cure rates higher than 90% in patients with advanced liver disease as well. Viral eradication has been associated with longer survival, reduced mortality from both hepatic and extrahepatic causes, improvement in liver function, and reduced incidence of HCV-related extrahepatic diseases. While patients with mild fibrosis can safely be discharged after achievement of a sustained virological response, patients with advanced fibrosis and cirrhosis remain at risk of developing complications of liver disease, thus requiring regular and life-long surveillance. Major complications of cirrhosis that need to be monitored are hepatocellular carcinoma onset and development or progression of clinically significant portal hypertension.

Essential updates 2018/2019: Liver transplantation.

Among the recent topics in the field of liver transplantation (LT), one of the significant therapeutic breakthroughs is the introduction of direct‐acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection. With cure rates close to 100%, a better proportion of LT candidates and recipients can be cured of HCV infection by DAA therapies that are simple and well‐tolerated. Other critical topics include the issue of indication of LT for patients with hepatocellular carcinoma, which has been continuously studied. Several expanded criteria beyond the Milan criteria with acceptable results have been recently reported. The role of donor‐specific antibodies (DSAs) in intractable rejection is also an important matter that has been studied. Although long recognized as an important factor in antibody‐mediated rejection and even graft survival in renal transplantation, the impact of DSAs on graft and patient survival in LT remains to be elucidated. Including the issues described above, this article focuses on recent advances in LT, management to avoid recurrence of primary diseases, optimization of immunosuppressive treatment, and extended donor criteria.

2278 Rapidly Progressive Hepatitis C After Liver Transplantation Treated With Glecaprevir/Pibrentasvir

INTRODUCTION: Hepatitis C recurrence following liver transplantation occurs in all patients with chronic HCV infection who have detectable serum HCV RNA levels prior to transplant. Less than 10% of these patients develop an acute and severe phenotype called fibrosing cholestatic hepatitis, which often involves fibrosis, rapid graft loss and decreased survival. The introduction of direct-acting antiviral agents (DAAs) have changed the paradigm of treatment of these patients. CASE DESCRIPTION/METHODS: A 62-year-old woman with a medical history of hepatitis C infection, hepatocellular carcinoma status post orthotropic liver transplantation, diabetes mellitus and hypertension who was hospitalized for fatigue and elevated liver chemistries following her liver transplantation. Laboratory tests showed a white cell count 6.67 × 103/μL, creatinine 1.1 mg/dL, aspartate aminotransferase 592 U/L, alanine aminotransferase 504U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL, albumin 2.9 g/dL. Acute hepatitis work up showed a positive hepatitis C virus antibodies with genotype 1B, with a viral load of 80 million IU/mL HCV RNA. HBsAg, HBc IgG, HBc IgM, and hepatitis A virus IgM were negative. Evaluation for Epstein-Barr virus, cytomegalovirus and herpes simplex virus were negative. Ultrasound of the abdomen revealed that the liver is normal in size, echotexture and contours. No focal hepatic lesions. Normal hepatic blood flow. The patient underwent liver biopsy that showed lymphocytic portal inflammation with frequent lobular apoptosis consistent with active chronic hepatitis C (MHAI: 5-6/18). Mild portal fibrosis (ISHAK FIBROSIS STAGE: 1/6) and minimal evidence of acute t cell-mediated rejection (rejection activity index: 1/9). During the patient hospitalization her liver chemistries significantly worsened and peaked to aspartate aminotransferase 740 U/L, alanine aminotransferase 511U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL. We decided to start the patient on Glecaprevir/Pibrentasvir for acute and severe hepatitis. Fourteen days after starting Glecaprevir/Pibrentasvir, the patient viral load decreased to 782 IU/mL HCV RNA and normalized liver chemistries with AST19 and ALT 27. The patient denied any adverse events due to the treatment. DISCUSSION: To our knowledge, this is the first case report of treating early and aggressive form of HCV recurrence with Glecaprevir/Pibrentasvir. The dramatic improvement of the patient suggest that DAA might be safe and effective in this situation.

Successful Treatment With Direct-Acting Antiviral Agents of Hepatitis C in Patients With End-Stage Renal Disease and Kidney Transplant Recipients.

The introduction of direct-acting antiviral agents has allowed significant chances for treatment for difficult-to-treat populations. This study aimed to investigate the efficacy, tolerability, and safety of these therapies in both patients with end-stage renal disease and kidney transplant recipients with chronic hepatitis C virus infection. This study was a retrospective analysis with prospective follow-up of patients. The antiviral combination of ombitasvir 25 mg, paritaprevir 75 mg, ritonavir 50 mg, and dasabuvir 50 mg was prescribed to patients with end-stage renal disease or kidney transplant recipients with noncirrhotic or compensated cirrhotic liver disease. The other antiviral combination consisted of sofosbuvir 400 mg and ledipasvir 90 mg, which was recommended to patients with decompensated cirrhosis or those who could not tolerate the first combination regimen. Ribavirin was given to all patients with genotype 1a hepatitis C virus infection. All clinical and laboratory data were recorded at week 4, at end of the treatment, and at 12 weeks after completion of treatment. In terms of efficacy, sustained virologic response at 12 weeks was achieved in 94% of patients in the end-stage renal disease group and 92% of patients in the kidney transplant group. In terms of tolerability, antiviral treatment was well tolerated in both groups. Cardiac arrest and cerebrovascular accident were seen in the end-stage renal disease group; severe mucositis and glossitis were seen in the kidney transplant group. Hospitalization was needed in 2 patients for treatment of drug interactions with tacrolimus and sirolimus. Renal allograft function worsened in 2 patients, with 1 patient having biopsyproven antibody-mediated rejection. We observed great efficacy and safety in both kidney transplant recipients and patients with end-stage renal disease with these agents in treatment of chronic hepatitis C. However, clinicians should remain aware of drug interactions and adverse events in this fragile patient population.

The HIPPOCRATES Project: A Proof of Concept Promoting HCV Microelimination Strategy Plan in Prisons

Background & Aims: In the last few years we have witnessed a revolution in the treatment of hepatitis C virus (HCV) infection. With the introduction of direct-acting antiviral agents (DAA), sustained virological response (SVR) is achieved in more than 95% of the patients. The focus is now being turned on to high-risk groups, with the aim of achieving HCV elimination by 2030. Prison inmates constitute one of the high-risk groups, and they receive treatment less frequently due to barriers in access to health care. The aim of this study is to describe the management and follow-up of a cohort of HCV monoinfected patients treated with DAA in the prison setting. Methods: A prospective observational study was performed including all prison inmates monoinfected with HCV, from April 2017 to March 2018 in a Portuguese prison. Demographic, clinical and laboratorial data, as well as transient elastography measurements, were collected onsite by the medical team and prospectively recorded. Patients were treated with DAA according to international guidelines. SVR rates and adverse events were analyzed. Results: 67 monoinfected HCV male inmates (mean age of 42,4 ±8,1 years) were enrolled. 72% reported history of injecting drugs or tattooing, with 44% of the latter being made in prison. 78% referred alcohol consumption of more than 30 g/day. The most prevalent genotype was 1a (54%), followed by 3 (30%) 4 (9%) and 1b (8%). Pretreatment fibrosis degree was mild-to-moderate (F0-F2) in 78% and severe in 22% (F3-F4). Treatment regimens chosen were: 52% elbasvir/grazoprevir, 30% sofosbuvir/velpatasvir and 18% sofosbuvir/ledispavir. No major adverse events were observed. SVR rate was 100%. Conclusions: In a population considered hard-to-access and a cornerstone for HCV elimination, the doctors' visits to the prison setting, as well as the assisted medication administration lead to a 100% rate of SVR. Funding Statement: The authors declare: None. Declaration of Interests: The authors declare: None. Ethics Approval Statement: This study was conducted according to the Declaration of Helsinki. The ethical approval for this study was obtained from the Ethics Committee of Centro Hospitalar Sao Joao and Porto's correctional system. Informed consent was obtained from each patient before each treatment.

Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C in Taiwan: Real-world data.

Treatment of chronic hepatitis C (CHC) has entered a new era since the introduction of direct-acting antiviral agents (DAAs). Numerous clinical trials have shown that treatment response as well as tolerability of DAAs are superior to those of conventional therapy with pegylated interferon and ribavirin. However, the results of clinical trials may not be directly applied to real-world practice. Therefore our study tried to investigate the effectiveness of various DAA regimens in Taiwanese patients with chronic hepatitis C. We performed a retrospective study on 400 CHC patients. The primary endpoint was undetectable HCV RNA (an HCV RNA level of <25 IU/mL) at 12 weeks posttreatment (SVR12). The results were stratified by different DAAs and HCV genotypes. Genotype 1b was the major genotype (297, 74.3%), followed by genotype 2 (65, 16.3%). The patients were treated according to HCV genotype, clinical practice and reimbursement guidelines. The SVR12 rates of 57 patients treated with sofosbuvir and ribavirin, 107 treated with ledipasvir/sofosbuvir with or without ribavirin, 60 treated with daclatasvir/asunaprevir with or without ribavirin, 129 treated with ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin, 12 treated with sofosbuvir/daclatasvir with or without ribavirin, and 35 treated with elbasvir/grazoprevir were 98.2%, 97.2%, 85.0%, 97.7%, 100.0%, and 100.0%, respectively. The overall SVR12 rates in our study were comparable with those in previous pivotal trials. DAAs are generally safe. The interaction of HBV and HCV during DAA therapy and the observation of de novo HCC development and HCC recurrence during or after DAAs warrants additional studies.

Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows.

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum “not well-defined” follow-up: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection.

An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens

ABSTRACTBackground: A large Egyptian treatment program for HCV was launched in2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres.Methods: The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report.Results: A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results.Conclusions: All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.

Pre-emptive Treatment of HCV after Living Donor Liver Transplantation with Direct-Acting Antiviral Agents

BackgroundHepatitis C virus (HCV) universally recurs after liver transplantation (LT). Although the introduction of direct-acting antiviral agents (DAAs) has revolutionized the treatment of HCV infection, no optimal treatment for HCV recurrence after LT has been developed. MethodsThis study retrospectively evaluated the efficacy of DAAs as a pre-emptive treatment for recurrent HCV infection after living donor liver transplantation (LDLT). From January 2010 to December 2016, 70 patients received pegylated interferon (PegIFN) and 35 patients were treated with DAA-based regimens to treat recurrent HCV after LDLT. All antiviral treatments were pre-emptive. ResultsGenotype 1b was the most common HCV type (61.9%). Twenty-two recipients in the DAA group were treated with ledipasvir/sofosbuvir, nine received daclatasvir plus asunaprevir, three received sofosbuvir, and one received sofosbuvir plus daclatasvir. All 35 patients (100%) in the DAA group achieved a sustained virologic response (SVR), a percentage significantly higher than that (71.4%) in the PegIFN group (p<0.001). In the PegIFN group, the 1-, 3-, and 5-year graft survival rates were 85.7, 73.9, and 70.7%, respectively, whereas those in the DAA group were 100, 100, and 100%, respectively (p=0.008). ConclusionDAA-based regimens are an effective treatment for HCV recurrence after LDLT, resulting in an improved SVR and better graft survival than PegIFN.