Use Of Direct-acting Antiviral Agents Research Articles

Trends in Mortality From Extrahepatic Complications in Patients With Chronic Liver Disease, From 2007 Through 2017

Trends of mortality associated with extrahepatic complications of chronic liver disease might be changing. We studied trends in mortality from extrahepatic complications of viral hepatitis, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease in the United States. We performed a population-based study using US Census and the National Center for Health Statistics mortality records from 2007 through 2017. We identified trends in age-standardized mortality using Joinpoint trend analysis with estimates of annual percent change. The liver-related mortality among patients with hepatitis C virus (HCV) infection increased from 2007 through 2013 and then decreased once patients began receiving treatment with direct-acting antiviral (DAA) agents, from 2014 through 2017. Among patients with HCV infection, the age-standardized mortality for extrahepatic cancers was 2.6%, for cardiovascular disease was 1.9%, and for diabetes was 3.3%. Among individuals with hepatitis B virus infection, liver-related mortality decreased steadily from 2007 through 2017. During the study, age-standardized mortality from hepatitis B virus-related extrahepatic complications increased by an average of 2.0% each year. Although liver-related mortality from ALD continued to increase, mortality from extrahepatic complications of ALD did not change significantly during the 11-year study. Among patients with nonalcoholic fatty liver disease, the cause of death was most frequently cardiovascular disease, which increased gradually over the study period, whereas liver-related mortality increased rapidly. In an analysis of US Census and the National Center for Health Statistics mortality records, we found that after widespread use of DAA agents for treatment of viral hepatitis, cause-specific mortality from extrahepatic cancers increased, whereas mortality from cardiovascular disease or diabetes increased only among patients with HCV infection. These findings indicate the need to reassess risk and risk factors for extrahepatic cancer, cardiovascular disease, and diabetes in individuals successfully treated for HCV infection with DAA agents.

Increase in Incidence of Hepatocellular Carcinoma in Chronic Hepatitis C Chinese After Sustained Virologic Response with Direct Acting Antiviral Agents as Compared to Pegylated Interferon Plus Ribavirin Therapy: A Prospective Open-Label Study

Background: The incidence of hepatocellular carcinoma (HCC) decreased significantly in persons with chronic hepatitis C (CHC) who achieved sustained virologic response (SVR) after pegylated-interferon plus ribavirin (PR) therapy. It remains controversial whether there is any difference in HCC incidence after SVR using direct-acting antiviral agents (DAAs), as compared to PR therapy. We report a prospective observational study which compare the SVR and post-SVR HCC incidence in CHC Chinese who had completed either DAAs or PR therapy. Methods: This prospective observational study (NCT02578693) was conducted at two sites in Beijing and Hong Kong, to evaluate SVR in CHC Chinese with completion of DAAs or PR therapy. Those with SVR were followed up at 12-24 weekly intervals with surveillance for HCC performed by ultrasonography and alpha-fetoprotein at each visit. Multivariate Cox analysis was used to explore factors associated with post-SVR occurrence of HCC. Findings: Between October 2015 and May 2017, SVR was observed in 519 of the 533 (97.4%) and 817 of 1202 (68.0%) CHC patients with completion of anti-HCV therapy (p = 0.0001), respectively. Subjects that achieved SVR were followed with a median duration of 3 years. During the follow-up period, HCC developed in 28 (5.8%) and 25 (3.3%) post-SVR patients treated with DAAs and PR therapy, respectively (p = 0.036). The use of DAAs, older age (≥55 years), diabetes mellitus, higher LSM (≥17.5 kPa), and higher AFP level (≥30 ng/ml) at SVR were associated with increased risk of HCC (hazard ratios: 1.9, 3.1, 3.9, 4.9 and 5.2 respectively). Interpretation: After a median follow-up of 3 years, a lower incidence of HCC was observed in CHC patients who had SVR with PR therapy compared to those treated with DAAs. HCC surveillance in CHC patients with SVR should be performed more stringently in those with high risk factors and treated with DAAs. Clinical Trial Registration: The clinical protocol was registered at ClinicalTrials.gov (NCT02578693). Funding Statement: This is an investigator-initiated study supported by Chinese medical association (Grant No.13071110496) and capital characteristic clinic project of the Beijing municipal science and technology commission (Grant No. Z181100001718034). RFS is supported by the Emory Center for AIDS Research NIH grant 2P30-AI-050409. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Approval was obtained from the Ethics Committees in Hong Kong (Hong Kong Clinical Research Ethics Committee, HKCREC) and Beijing (Ethics Committee of Beijing 302 hospital). Informed consent was obtained from all patients and the study was conducted in compliance with the 1975 Declaration of Helsinki, Good Clinical Practice guidelines, and local regulatory requirements.

Regional and Rural-Urban Differences in the Use of Direct-acting Antiviral Agents for Hepatitis C Virus: The Veteran Birth Cohort.

Veterans with hepatitis C virus (HCV) infection may face geographic obstacles to obtaining treatment. We studied the influence of region and rural versus urban residence on receipt of direct-acting antiretroviral (DAA) medications for HCV. Veterans receiving care within Veterans Affairs Healthcare System born between 1945 and 1965. This is a observational study using national electronic health record data. Receipt of DAAs was defined as ≥1 filled prescription from January 1, 2014 to December 31, 2016. Region (South, Northeast, Midwest, and West) and residence (urban, rural-micropolitan, small rural towns, and isolated rural towns) variables were created using residential zone improvement plan codes and rural-urban commuting area (RUCA) codes. Multivariable models were adjusted for age, race, sex, severity of liver disease, comorbidities, and prior treatment experience. Among 166,353 eligible patients 64,854 received, DAAs. Variation by rural-urban residence depended on region. In unadjusted analyses, receipt varied by rural-urban designations within Midwest, and West regions (P<0.05) but did not vary within the South (P=0.12). Southern rural small town had the lowest incidence of DAA receipt (40.1%), whereas the incidence was 52.9% in Midwestern isolated rural towns. In adjusted logistic analyses, compared with southern urban residents (the largest single group), southern rural small town residents had the lowest odds ratio, 0.85 (95% confidence interval, 0.75-0.93), and Midwestern residents from isolated and small rural towns had the highest odds (odds ratio, both 1.27) to receive treatment. Substantial geographic variation exists in receipt of curative HCV treatment. Efforts are needed to provide more equitable access to DAAs.

Predictors of hepatocellular carcinoma recurrence associated with the use of direct-acting antiviral agent therapy for hepatitis C virus after curative treatment: A prospective multicenter cohort study.

BackgroundPrevious studies have suggested an association between the use of direct‐acting antiviral agents (DAAs) for treating hepatitis C virus (HCV) infection and the resulting decrease in the incidence of hepatocellular carcinoma (HCC); however, it is unclear whether DAAs prevent the recurrence of HCC after curative treatment for HCC. This study aimed to prospectively investigate HCC recurrence and its predictors after curative treatment for HCC.MethodsA total of 3012 patients with chronic HCV infection, with or without cirrhosis, who were treated with DAAs were enrolled between January 1, 2015 and January 31, 2017 as per the institutional review board approved study protocol at 15 institutions, including 10 university hospitals and five high‐volume centers in the Kyusyu area of Japan. Of the 3012 patients, 459 patients who had HCC but were cured with surgery or ablation therapy (curative treatment) before the use of DAAs were included in the analysis.ResultsDuring a mean follow‐up period of 29.4 months, 217 (47.2%) patients developed HCC recurrence. The median time to recurrence was 34.0 months, and the 1‐, 2‐, and 3‐year cumulative HCC recurrence rates were 27.1%, 43.4%, and 50.8%, respectively. The risk factors for HCC recurrence were the α‐fetoprotein (AFP) level before DAA therapy (P = 0.0047) and the number of curative treatments for HCC before DAA therapy (P < 0.0001).ConclusionsA high AFP level and multiple occurrences of HCC before DAA therapy are associated with a high risk for HCC recurrence after curative treatment. Follow‐up after DAA therapy should include special attention to the abovementioned risk factors.

Impact of the direct-acting antiviral agents (DAAs) on chronic hepatitis C in Sardinian patients with transfusion-dependent Thalassemia major

Background and aimsDirect antiviral agents (DAAs) have revolutionised the standard of care for the treatment of hepatitis even in patients with hemoglobinopathies. The aim of this study is to show how, thanks to DAAs, HCV infection has been substantially eradicated in one of the biggest Centres for the management of Thalassemia in Europe. MethodsThalassemia major patients regularly transfused and iron chelated in Cagliari (Italy) who were HCV-RNA positive were evaluated for the potential prescription of antiviral therapy. ResultsA total of 99 patients, 26 of whom had been diagnosed with cirrhosis, were treated with at least one dose of DAAs, which proved to be safe and well tolerated. Two of the patients died during the treatment after becoming HCV-RNA negative while another voluntarily interrupted the therapy. The final SVR in the patients who completed the treatment was 100%, while measuring 97% (96/99) in the Intention-to-Treat analysis. After DAAs, no new cases of hepatocellular carcinoma have been reported. ConclusionsThe use of DAAs in patients suffering from beta-Thalassemia major with chronic hepatitis C or cirrhosis can be considered safe and effective. Close monitoring for hepatocellular carcinoma development is, in any case, recommended indefinitely post-SVR.

Unexplained Reactive Leukocytosis Associated to the Use of DAA for the Treatment of Chronic HCV

Infection with hepatitis C virus (HCV) is the most common cause of chronic liver disease (CLD) in the United States. Those infected are at risk for cirrhosis, liver cancer and death. HCV treatment with oral direct-acting antiviral agents (DAA) has been proven to be highly effective and relatively safe. The rates of serious adverse events have been reported as minimal. However, we present a case of an unexplained reactive leukocytosis associated to the use of DAA. This is a case of a 57-year-old man with history of chronic HCV, genotype 1b, cirrhotic and treatment naïve, who was started on Ombitasvir, Paritaprevir, Ritonavir and Dasabuvir for 12 weeks. On week 6, a routine lab test showed leukocytosis of 41,000 ul. He was recalled and asked to come to the hospital for evaluation. While in transit to the hospital he had an uneventful motor vehicle accident due to loss of consciousness and was admitted to a local community hospital. Two days later he was transferred to our institution. Upon evaluation, he referred a 2-week history of tingling sensation in the tip of his fingers associated to general malaise and unquantified fever. He denied use of any other prescribed or over the counter medication. Upon evaluation, his vital signs were within normal limits. His physical examination was unremarkable. Laboratory workup showed persistent neutrophilia and immature cells. Blood and stool cultures, urinalysis and chest X ray were negative for infection. DAA were discontinued and the patient was admitted to Hematology-Oncology ward due to suspected chronic myelogenous leukemia. Bone marrow aspirate was negative for a myeloproliferative disorder and cytogenetics were normal. Leukocytosis and symptoms resolved after 5 days of discontinuing therapy. HCV viral load was undetectable at the time of discontinuation of therapy. HCV eradication was confirmed 6 months later. A final diagnosis of reactive leukocytosis secondary to HCV treatment was made. The new DAA therapies have transformed HCV treatment and improved the quality of life of patients with chronic HCV. Nonetheless, patients receiving treatment should be monitored closely since unexpected side effects, might alter the course of the disease and have a great impact in their lives. After ruling out infection and malignancy, we identified this DAA as the possible culprit of reactive leukocytosis. Fortunately, patient achieved sustained viral response despite premature interruption of therapy.

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.

Chronic hepatitis C: achievement, challenge and strategy to eliminate as a public health threat

The use of direct-acting antiviral agents (DAAs) in the treatment of chronic hepatitis C and its approval in China applying the goal proposed by the World Health Organization is an important step towards eliminating viral hepatitis as public health threat by 2030. However, we also need to create a model that is suitable and short duration therapy for the Chinese patients. On the other hand, it is also essential to study the reverse hepatic fibrosis and the emerging problems of hepatitis C-related liver cancer.

Hepatitis C and liver transplantation in direct acting antiviral era

Chronic hepatitis C virus (HCV) infection remains a principle causative factor for cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation world-wide. The inevitable HCV recurrence of the engrafted liver was associated with the worst post-liver transplant survival outcome as compared to other etiologies in the interferon era. The inception of direct acting antiviral agents (DAAs) has changed the paradigm of HCV management in the liver transplant setting. These highly effective agents can cure HCV infection even in advanced cirrhosis with adequate safety. The future appears promising for HCV with expected decline in hepatic decompensation and incidence of HCC, but a significant proportion of patient with cirrhosis will remain at risk for HCC despite HCV cure. Use of DAAs has not affected the global transplant activity due persistent gap between the donors and the potential recipients. Curing HCV may improve the liver transplant outcome by controlling the co-morbidities like diabetes and chronic kidney disease in patients transplanted for HCV.

Histological assessment of the liver explant in transplanted hepatitis C virus patients achieving sustained virological response with direct-acting antiviral agents.

The use of direct-acting anti-viral agents (DAAs) has resulted in extremely high sustained virological response (SVR) rates in patients being treated while on liver transplantation (LT) waiting lists. The aim of this study was to evaluate the histological findings of hepatitis C virus (HCV) patients who achieved SVR after receiving DAA treatment [SVR(+)] prior to LT, and compare them with HCV patients who had not achieved SVR [SVR(-)]. Fifty-eight adult HCV patients who underwent LT at our institution from 2014 to 2016 were included in the study. Two pathologists, blinded to SVR status, simultaneously evaluated the histological sections. Assessment included the Histology Activity Index (HAI/modified Knodell score), fibrosis stage (Ishak score), and Laennec cirrhosis stage. The study group comprised 25 SVR(+) patients (56% male; mean age, 63.8 years), and the control group comprised 33 SVR(-) patients (69% male; mean age, 61.7 years). There was no significant difference in HAI between the groups (P = 0.414). Patients who achieved SVR also did not show less portal inflammation (P = 0.787), interface hepatitis (P = 0.999), confluent necrosis (P = 0.627) or spotty necrosis (P = 0.093) than the control group. There was a trend towards a higher degree of inflammation in patients who achieved SVR in <24 weeks (P = 0.07). The degree of focal lytic necrosis/apoptosis and portal inflammation was more prominent in SVR(+) patients with shorter SVR-LT intervals. Our study is the first to report persistent inflammation in HCV patients who received DAAs prior to LT. This supports the notion that inflammation is immunologically driven and that inflammation persists despite the absence of virus.

Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates.

Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

Hepatitis C-related hepatocellular carcinoma and the treatment with direct-acting antiviral agents

With the wide use of direct-acting antiviral agents (DAAs), more and more patients with chronic hepatitis C achieve sustained virological response; however, no consensus has been reached on the application of DAAs in the treatment of hepatitis C virus-related hepatocellular carcinoma (HCC). This article summarizes and evaluates related issues in this field, including whether antiviral therapy with DAAs in patients with hepatitis C can increase the incidence or recurrence rate of HCC, as well as whether DAAs can be used for hepatitis C in HCC patients after antitumor treatment and the efficacy of DAAs in such patients.

Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents.

Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin. As achieving sustained virological response becomes increasingly attainable for a majority of HCV-infected patients, concerns have been raised regarding the optimal timing of treatment for HCV infection in the setting of end-stage liver disease and during the peri-transplant period. On one hand, HCV treatment may improve hepatic function and negate the need for LT in some, which is crucial given the scarcity of donor organs and mortality on the waiting list in certain regions. On the other hand, HCV treatment may result in lowering the priority for LT without improving quality of life, thereby delaying potentially curative LT surgery. This review evaluates the evidence supporting the use of direct-acting antiviral agents in the period before and following LT.

Characterization of Naturally Occurring NS5A and NS5B Polymorphisms in Patients Infected with HCV Genotype 3a Treated with Direct-Acting Antiviral Agents.

Hepatitis C virus (HCV) genotype (GT)3 is associated with increased risk of steatosis, development of cirrhosis and hepatocellular carcinoma. Limited data are available regarding genetic variability and use of direct-acting antiviral agents in these patients. non-structural protein 5A (NS5A) and non-structural protein 5B (NS5B) sequencing was performed on 45 HCV GT3-infected Italian patients subsequently treated with sofosbuvir ± daclatasvir (SOF ± DCV). Novel GT3a polymorphisms were observed by Sanger sequencing in three NS5A (T79S, T107K, and T107S) and three NS5B (G166R, Q180K, and C274W) baseline sequences in patients who achieved sustained virological response (SVR). Baseline NS5A resistance-associated substitutions (RASs) A30K and Y93H were detected in 9.5% of patients; one patient with A30K did not achieve SVR. Phylogenetic analyses of sequences showed no distinct clustering. Genetic heterogeneity of NS5A and NS5B was evaluated using ultra-deep pyrosequencing (UDPS) in samples longitudinally collected in patients not achieving SVR. Some novel NS5A and NS5B polymorphisms detected at baseline may not impact treatment outcome, as they were not enriched in post-failure samples. In contrast, the clinically novel GT3 NS5A-L31F RAS emerged in one treatment failure, and I184T, G188D and N310S, located on the same NS5B haplotype, became predominant after failure. These findings suggest a potential impact of these novel substitutions on the treatment outcome; however, their significance requires further investigation.

Direct-acting antiviral agents in the therapy of hepatitis C virus-related mixed cryoglobulinaemia: a single-centre experience

BackgroundThe efficacy and safety of direct-acting antiviral agents (DAAs) were evaluated in a cohort of prospectively enrolled patients with hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC), an immune complex-mediated vasculitis of small and medium vessels in which the pathogenetic role of HCV has been clearly established.MethodsTwenty-two patients received DAAs. Clinical and laboratory features were recorded at baseline, every 4 weeks until the end of treatment (EoT), and 12 weeks afterwards. Primary efficacy endpoints were (a) sustained virological response 12 weeks after therapy completion (SVR12), (b) regression of symptomatology (clinical response) and (c) cryoglobulin disappearance or cryocrit reduction ≥50% (immunological response). Complete response (CR) was defined as the occurrence of all three primary endpoints; partial response (PR) was defined as the occurrence of SVR12, with or without either immunological or clinical response; and no response was defined as missing the achievement of all three endpoints.ResultsAll patients reached SVR12. Compared with basal values, mean cryocrit values were significantly decreased at EoT and SVR12. A significant reduction of alanine transaminase and a parallel increase of complement component C4 levels were also detected. Rheumatoid factor activity was significantly reduced at EoT but not at SVR12. At SVR12, a CR was established in 14 patients (63.7%) and a PR in 8 patients (36.3%). In one patient with small lymphocytic lymphoma, the tumour progressed despite viral clearance. Mild adverse events were recorded in nine patients (40.9%).ConclusionsThe response rates induced by the use of DAAs in patients with MC were remarkably higher than those previously achieved with pegylated interferon-α/ribavirin, with or without rituximab. A much longer follow-up is desirable to achieve useful information in terms of persistent viral clearance and clinical response.

Dual therapy of grazoprevir and elbasvir for the treatment of hepatitis C infection

ABSTRACTThe impact of chronic hepatitis C (HCV) worldwide is expected to increase as the population infected with HCV ages and more undiagnosed individuals are identified and linked to care through nation-wide initiatives. The development of interferon-free regimens involving the use of direct-acting antiviral agents, which disrupt key steps in viral replication, has revolutionized the treatment of chronic HCV infection. However, there remains a great medical need for HCV therapy that is of shorter duration, all-oral, with a high barrier to resistance, and highly effective for all patient populations including those with end-stage renal disease (ESRD) and cirrhosis. Grazoprevir, an HCV NS3/4A protease inhibitor and elbasvir, an NS5A inhibitor, have broad in vitro activity against most HCV genotypes and retain in vitro activity against many clinically relevant resistance-associated variants. The once daily regimen is well-tolerated and highly efficacious across wide-ranging patient populations including those with ESRD on hemodialysis.

Sofosbuvir treatment and hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a "chain terminator". Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy.

The hepatitis C revolution part 1: antiviral treatment options.

The rapid evolution in the therapeutic landscape of hepatitis C presents a minefield to clinicians seeking to optimize therapy for their patients. Efficacy, evidence-base, side-effects, and drug combinations must be tailored to individual patients, taking into account comorbidities, degree of fibrosis, evidence of hepatic decompensation, and life expectancy. The review article aims to discuss novel hepatitis C virus (HCV) treatments with an overview of recent breakthrough research validating their potential. It is hoped that this systematic evaluation will clarify best available evidence for clinicians treating patients with HCV on a regular basis. With greater understanding of the HCV life cycle and viral genome, the last decade has seen the emergence of novel direct-acting antiviral (DAA) agents, which specifically target proteins responsible for viral replication. Landmark clinical trials have offered robust evidence supporting the use of DAA agents as pioneer treatments, alone, or in combination with standard pegylated interferon (peg-IFN) and ribavirin (RBV)-based regimens. DAAs have proved highly efficacious, with pan-genotypic activity, shortened treatment duration, and an improved side-effect profile when compared with historical peg-IFN/RBV treatment. Recent phase 3 studies have provided proof-of-concept that all-oral, IFN-free DAA regimens can yield high rates of sustained virological response across most HCV genotypes. The ability of DAAs to dramatically improve virological clearance heralds a new era in clinical therapeutics, as the unprecedented prospect of cure for a chronic viral infection becomes tangible. However, myriad clinical challenges remain before global eradication of HCV can become reality.

Pros and Cons: Usage of organs from donors infected with hepatitis C virus – Revision in the direct-acting antiviral era

Should organs from hepatitis C antibody positive donors (HCVD+) be used for transplantation? Organ shortage forces transplant teams to use donors with extended criteria. The decision to transplant a HCVD+ graft is a balance between the risk of transmission of a virus that could lead to end-stage liver diseases and the benefit of access to transplantation, specifically in patients with life-threatening disease. The other issue is the impact of HCV-related liver fibrosis in the donor graft on the long-term outcome in the recipient. Thus, the use of HCVD+ demonstrated a shorter meantime on the waiting list in kidney transplantation. When a HCVD+ graft is transplanted, the risk of HCV transmission depends on; 1) the quality of screening of the donor; 2) the presence of viral replication in the donor at the time of transplantation and the ability to detect it; and 3) the HCV status of the recipient but also the type of transplanted organ. In liver transplantation, the use of HCVD+ graft is usually restricted to recipients with a chronic HCV infection. Several reports showed some competition between HCV donor and recipient strain without deleterious impact on graft and patient survival. Controversies are still pending regarding the quality of the graft and the progression of fibrosis. The recent approval of direct-acting antiviral agents (DAA) dramatically changes the landscape of HCV infection treatment. After transplantation, combinations of DAA show high efficacy and good safety profile. In the near future, extensive use of DAA should reduce the number of HCVD+ with a positive HCV RNA, limiting the risk of transmission but also the number of patients on waiting lists for a disease related to HCV.

Treatment of Chronic Hepatitis C Using Newly Developed Oral Antiviral Agents

Standard care for chronic hepatitis C has been a combination of pegylated interferon-alpha and ribavirin, although this treatment has suboptimal antiviral efficacy and significant adverse events. The hepatitis C virus treatment landscape has been transformed recently by the development of direct-acting antiviral agents (DAAs) that target NS3 protease, NS5A protein, and NS5B polymerase. Several DAAs showed potent antiviral activity leading to increased rates of sustained virological response (SVR), even in difficult- to-treat patients such as older patients and those with advanced liver disease and prior failed peg-interferon/ribavirin treatment. Use of multiple DAAs without pegylated interferon has shown dramatically high SVR rates (up to nearly 100%) with negligible side effects. Interferon-free regimens are close to becoming the new standard of care for patients with chronic hepatitis C in USA and Europe. Similarly, several DAAs are near clinical use in Korea. This review discusses DAAs that have been approved or are under investigation for approval in Korea. (Korean J Med 2015;88:635-642)