Oral Direct-acting Antivirals Research Articles

Cost–utility of sofosbuvir/velpatasvir versus other direct-acting antivirals for chronic hepatitis C genotype 1b infection in China

ObjectiveThis study aimed to estimate the cost–utility of sofosbuvir/velpatasvir (SOF/VEL) compared with other direct-acting antivirals (DAAs) in Chinese patients with hepatitis C virus (HCV).DesignA Markov model was developed to estimate...

Cost-effectiveness of Universal Hepatitis C Screening in Pregnant Women: A Systematic Review.

Hepatitis C virus (HCV) epidemiology has shifted from the baby-boomer generation to young women of childbearing age. The health benefits and cost-effectiveness (CE) of screening pregnant women remain controversial. To systematically review published studies evaluating the CE of screening pregnant women for HCV in the era of direct-acting antivirals (DAAs). We conducted a systematic literature search of CE studies evaluating the costs and benefits of screening pregnant women for HCV. Pertinent information including antiviral agent, drug costs, incremental cost-effective ratio (ICER), and infant care was collected. The authors' definition of the threshold price at which screening was deemed CE was also recorded. The quality of studies was assessed using the Consolidated Health Economic Evaluation Reports Standards (CHEERS) checklist. We identified 5 studies that evaluated the ICER of screening pregnant women for HCV. Of these, 2 utilized all oral DAAs, with universal screening CE. The ICER of these 2 studies was $3000 and $41,000 per quality of life-years gained. The remaining studies were interferon-based regimens. Most studies did not include screening of infants. Universally screening pregnant women for HCV was CE in studies that utilized oral DAAs. Most pharmacoeconomic studies failed to incorporate the impact of vertical transmission on infants.

Highly effective treatment response and well tolerability by all oral direct acting antivirals for chronic hepatitis C patients post organ transplantation.

Immunosuppressant-related acceleration of fibrosis has been documented in chronic hepatitis C (CHC) patients who receive organ transplantation (Tx), and sustained virological response (SVR) rates for these patients by pegylated interferon (IFN)-based therapy are generally poor and associated with unfavorable safety profiles. In addition, IFN treatment varies by patient and poses a high risk of post-renal Tx graft rejection. This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for CHC patients following organ Tx. A total of 32 organ Tx (liver: 17, kidney: 13, kidney then liver: 1, and heart: 1) patients with CHC on an oral DAA (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 11, daclatasvir and asunaprevir: 4, sofosbuvir-based: 17) were enrolled in the study. DAAs regimen was based by genotype/subtype, patient characteristics, drug interaction profiles, and health insurance coverage. Mean patient age was 61.4 ± 9.5 years, 50.0% male, and 15.6% with cirrhosis. Fourteen (43.7%) patients experienced unsuccessful IFN treatment. Genotype distribution was as follows: 1a: 6, 1b: 17, 2: 7, 3: 1, and 6: 1. Mean time between Tx and DAAs therapy was 77.3 ± 11.0 months. Baseline HCV RNA before DAAs was 6.20 ± 0.19 log10 IU/mL. After DAAs, the distribution of week 2 HCV RNA was as follows: <15 IU/mL (53.1%), 15 to 50 IU/mL (15.6%), 50 to 100 IU/mL (6.3%), and >100 IU/mL (25.0%), respectively. The rates of undetectable HCV RNA (<15 IU/mL) at week 4 and end-of-treatment were 93.8% and 100%, respectively. Subjective adverse events during therapy were generally mild, with no treatment terminations. After posttreatment follow-up, all 32 patients (100%) achieved SVR12. Highly responsive treatment and favorable tolerability were achieved by all oral DAAs in this difficult-to-treat patient population.

Hepatitis C Virus Treatment Status and Barriers among Patients in Methadone Maintenance Treatment Clinics in Guangdong Province, China: A Cross-Sectional, Observational Study.

We aimed to evaluate the status and barriers related to hepatitis C virus (HCV) treatment among Chinese methadone maintenance treatment (MMT) clients, and the willingness and barriers of patients to accept directly observed treatment (DOT) service and oral direct-acting antivirals (DAAs). We conducted a cross-sectional survey from July to October 2017 in Guangdong Province, China, involving 678 HCV antibody-positive MMT patients. If they reported being infected with HCV, then their HCV treatment experience, willingness to use DOT and DAAs, along with any barriers, were collected. Logistic regression analysis was used to identify the correlates of initiating HCV treatment. Among those reporting HCV infection (54%, 366/678), 39% (144/366) initiated treatment; however, 38% (55/144) interrupted and 55% (79/135) delayed treatment for 15 months. Seventy-five percent (273/366) and 53% (195/366) were willing to use DOT and DAAs, respectively. Unaffordable medical costs and insignificant symptoms were the major barriers to HCV treatment and accepting DOT or DAAs. The lack of a stable residence, being a woman, and having ever injected drugs were all associated with a low probability of initiating treatment (p < 0.05). This study highlights a limited uptake of HCV treatment among MMT patients, and a need to strengthen the popularity of DOT and DAAs and integrate them into Chinese MMT clinics.

977 Predictors of Response to Direct Acting Anti-Viral Therapy in Patients With Decompensated Hepatitis C Cirrhosis

INTRODUCTION: The introduction of direct-acting antiviral (DAA)-based therapies for chronic hepatitis C virus (HCV) infection has revolutionized the approach to HCV treatment, resulting in highly efficacious and well-tolerated therapy for nearly all patients. Patients with a history of decompensated cirrhosis represent a unique subset of patients with a worse response to HCV therapy compared with those who have compensated cirrhosis or chronic HCV infection. Decompensated cirrhosis due to HCV is a difficult to treat population. At present, there is no gold standard predictors of response to Direct Acting Anti-virals (DAA). We conducted this study to look for factors responsible for improvement in state of decompensation post DAA therapy, i.e. attainment of Child-Turcotte-Pugh (CTP) class A from CTP class B or C. METHODS: Retrospective analysis was conducted for patients of decompensated HCV cirrhosis (48 patients of CTP class B and 14 patients of CTP class C). We collected demographic, clinical, treatment response, and laboratory data from patients, which included age, BMI, LFT, INR, GFR, MELD score, response to therapy (SVR12), presence of ascites, encephalopathy were noted for recruited decompensated HCV cirrhosis and tested their associations with patient outcomes at 24 weeks post-treatment. Patients were given Sofosbuvir combination treatment with Daclatasvir / Ledipasvir / Velpatasvir and/or Ribavirin according to genotype, for 12 weeks, where Ribavirin was used and rest 24 weeks. RESULTS: Total 62 patients of decompensated HCV cirrhosis patients recruited, with males 54%, Median age 48 years. 48 patients were CPT class B whereas 14 patients of CPT class C. Patients with MELD score &lt; 10, 10–15 and &gt;15 were 21 (33.8%), 28 (45.1%) and 13 (21.1%) in pre-treatment and 23 (37%), 30 (48.3%) and 9 (14.7%) in post-treatment period respectively. Post-treatment 34 patients (54.8%) turned into CTP class A, 25 (40.3%) and 3 (4.9%) remained in CTP class B &amp; C. Factors associated with favorable prognosis were male sex, baseline albumin, bilirubin, MELD score, presence of ascites. CONCLUSION: This study showed that oral DAAs were able to reverse liver dysfunction in patients with decompensated HCV cirrhosis in more than half of our patient cohort and favoured use of treatment in such patients. The longer term benefits of therapy need to be ascertained though.

Short Course of Treatment for Hepatitis C in Adolescents

Source: El-Khayat H, Kamal EM, Yakoot M, et al. Effectiveness of 8-week sofosbuvir/ledipasvir in the adolescent chronic hepatitis C-infected patients. Eur J Gastroenterol Hepatol. 2019; 31(8): 1004– 1009; doi: 10.1097/MEG.0000000000001360Investigators from multiple institutions in Egypt conducted a randomized trial assessing the efficacy and safety of sofosbuvir/ledipasvir (SOF/LVD) for 8 weeks, compared to 12 weeks, for treatment of genotype 4 hepatitis C virus (HCV) infection in adolescents 12–17 years old. Study patients were randomized to a single daily dose of a combination of SOF 400 mg and LVD 90 mg for either 8 or 12 weeks. At baseline, participants underwent a FibroScan to assess liver fibrosis using a standardized classification system. Laboratory screening was conducted at baseline and throughout the 12-week study period to measure HCV RNA and assess for possible adverse events; study participants reported adverse events. The primary study outcome was the sustained virologic response (SVR) rate, defined as undetectable HCV RNA at week 12. Secondary outcomes included SVR rates at 4 weeks and adverse events.A total of 157 patients were enrolled in the study: 73 were randomized to 8 weeks of SOF/LVD treatment and 84 to 12 weeks of treatment. The mean age of study patients was 14 years, the mean (standard deviation) HCV RNA at baseline was 5.80 (0.17) IU/L, and 68% had no to mild liver fibrosis at baseline. The source of HCV infection was considered to be perinatal infection in 73% of patients, surgical or dental procedures in 10%, and unknown in 17%. Patient characteristics were similar in the 2 treatment groups.The SVR rate at 12 weeks was 98.6% (95% CI, 93%–100%) for those treated for 8 weeks and 97.6% (95% CI, 96%–100%) for patients treated for 12 weeks. SVR rates at 4 weeks were 63% and 58%, respectively, for adolescents in the 8-week and 12-week treatment groups. Adverse events were reported by 7% of those in the 8-week group, including fatigue (2 patients), and headache, epigastric tenderness, and nausea in 1 patient each. Among patients randomized to 12 weeks of treatment, 8.3% reported an adverse event, including fatigue (1 patient), epigastric tenderness (1 patient), diarrhea (2 patients), nausea (1 patient), and rash (2 patients). Laboratory screening did not reveal any significant adverse events.The authors conclude that 8 weeks of SOF/LVD is as effective as 12 weeks of treatment in adolescents with HCV infection.Dr Rosenthal has disclosed the following financial relationships relevant to this commentary: Research grant support from Gilead, AbbVie, and Merck. This commentary does contain a discussion of an unapproved/investigative use of a commercial product/device.With the advent of highly effective direct-acting antiviral (DAA) drugs for HCV therapy, chronic HCV infection is no longer the leading indication in adults requiring liver transplant.1 Although therapies for HCV in children lag behind the regimens approved in adults, all oral DAA regimens in children are also now approved by the US Food and Drug Administration (FDA) and available.2 Regimens are so effective that cure can be anticipated in 8–12 weeks of therapy. The current investigators found that an 8-week course of SOF/LVD therapy was as effective and safe as the classic 12-week course in curing adolescents of genotype 4 HCV.In the United States, approximately 75% of chronic HCV infections are caused by HCV genotype 1; 15%–20% by genotype 2 or 3; and <5% by genotypes 4, 5, or 6.3 The FDA has approved 12-week combination SOF/LVD for the treatment of pediatric patients ≥12 years of age who weigh at least 35 kg and have HCV genotype 1 infection; they can be treatment naive without cirrhosis or with compensated cirrhosis or treatment experienced without cirrhosis.4 The FDA also approved its use for 12 weeks of therapy in adolescents with genotypes 4, 5, or 6 who are treatment naive or who are treatment experienced without cirrhosis or with compensated cirrhosis.4 In treatment-experienced adolescents with genotype 1 HCV and compensated cirrhosis, therapy should consist of 24 weeks of SOF/LVD. If SOF/LVD is used, 2 warnings need to be heeded.4 Patients with HCV and hepatitis B virus coinfection need to be monitored for hepatitis B virus reactivation and hepatitis flare during HCV treatment and posttreatment follow-up. Coadministration of amiodarone with SOF/LVD is not recommended because serious bradycardia with symptoms may occur.4DAA therapies for HCV infection are approved for use in adolescents. Regimens are effective and safe.At first glance, it would appear that therapy for HCV infection is solely within the purview of gastroenterologists. Pediatricians, however, can ensure that HCV screening is performed in patients at high risk, such as children of mothers who are HCV positive, and that potentially hepatotoxic agents (eg, alcohol) are avoided in those with HCV infection. (See AAP Grand Rounds. 2019;41[4]:45.5)

Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium.

One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia. Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25IU/mL 12week post-therapy). A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5years, p < 0.0001), had lower body mass indices (22.9kg/m2 vs. 24.6kg/m2, p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes. In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.

Treatment Outcomes of Hepatitis C-Infected Patients in Specialty Clinic vs. Primary Care Physician Clinic: A Comparative Analysis.

Background Oral direct-acting antivirals (DAAs) provide an exceptional opportunity to treat hepatitis C virus (HCV) infection. Goals We compared the treatment outcomes between specialty and primary care physician (PCP) clinics for patients treated with DAAs. Methods We performed a retrospective analysis of patients treated for HCV in our PCP clinics and specialty; liver and gastroenterology clinics and gastroenterology clinics. We used the two-sided t-test and the chi-square test to compare the means of continuous and categorical variables, respectively. Results Data from a total of 377 patients was analyzed (PCP clinic: n = 185 and specialty clinic: n = 192). There was no significant difference between age, race, and gender. Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores were comparable at baseline. Greater than 90% of the patients achieved sustained virological response (SVR) with no difference between the groups. Conclusions Uncomplicated patients can be treated for hepatitis C by their PCPs with DAAs with similar treatment outcomes to specialty clinics. There should be explicit guidelines on patient eligibility for treatment by PCPs vs. specialists.

HIV infection does not increase the risk of liver complications in hepatitis C virus-infected patient with advanced fibrosis, after sustained virological response with direct-acting antivirals.

To assess the impact of HIV coinfection on the risk of developing liver-related complications in HCV-infected patients with advanced fibrosis treated with direct-acting antivirals (DAA) after sustained virological response (SVR). Prospective cohort study. Multicenter. Patients from the GEHEP and HEPAVIR cohorts were selected if they fulfilled the following criteria: treatment against HCV with all oral DAA combination; SVR achievement, defined as undetectable plasma HCV RNA 12 weeks after the end of therapy; pretreatment liver stiffness equal to or higher than 9.5 kPa; liver stiffness measurement at the time of SVR. The primary variable was the time until the development of a liver complication or requiring liver transplant. Seven hundred and seventeen patients were included and 507 (71%) were coinfected with HIV. After a median follow-up time of 21 (14-25) months, 15 (2.1%) patients developed a liver complication and/or underwent a liver transplant and 15 (2.0%) died. The probability of remaining free of hepatic complications or transplant at 1 and 2 was, respectively, 99 and 96% in HCV-monoinfected patients and 99 and 98% in coinfected patients (P = 0.648). In a multivariate analysis, in which nonliver-related death was considered as a competing event, HIV coinfection was not associated with the appearance of hepatic complications or requiring liver transplant [hazard ratio = 0.24; 95% CI (0.03-1.93), P = 0.181]. Having presented hepatic decompensation prior to SVR [hazard ratio = 29.06; 95% CI (3.91-216.16), P < 0.001] and the value of liver stiffness at the SVR time-point (hazard ratio = 1.12; 95% CI (1.07-1.18), P < 0.001] were associated with a higher probability of development of liver events. HIV coinfection is not associated with a higher probability of developing liver complications in HCV-infected patients with advanced fibrosis, who achieved SVR with interferon-free regimens.

State of the Art HCV Treatment in Children

Hepatitis C infection is a global issue with an estimated 5 million children with active HCV infection worldwide. The advent of oral direct-acting antiviral (DAA) regimens has revolutionized treatment in adults with excellent efficacy and tolerability. There are limited data and few approved therapies in children. The aim of this review is to discuss the currently approved regimens for children and the recently reported results of clinical trials of DAA in children. DAA regimens are currently approved only for children ≥ 12 years. For most children < 12 years, it is recommended that HCV therapy be deferred until patients are eligible for oral DAA therapies. For treatment-naive adolescents with HCV genotype 1, 4, 5, or 6, treatment with ledipasvir/sofosbuvir for 12 weeks has been reported to have sustained virologic response at 12 weeks of 98%. For treatment-naive adolescents with genotype 2 or 3 HCV, sofosbuvir- ribavirin combination therapy (12 weeks for genotype 2 and 24 weeks for genotype 3) has been reported to have SVR12 of 100% and 97%, respectively. There are promising, recently published studies showing excellent SVR12 rates for ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in adolescents with HCV genotype 1 or 4, and sofosbuvir/daclatasvir in children/adolescents with HCV genotype 4. Finally, ledipasvir/sofosbuvir ± ribavirin for children age 6–12 years with genotypes 1, 3, 4, 5, and 6 treated for either 12 or 24 weeks is reported to have an SVR12 rate of 99%. HCV treatment in children is rapidly evolving. There are now highly effective all-oral, interferon-free regimens for children ≥ 12 years. Clinical trials are on-going for adolescents and children < 12 years with a variety of pangenotypic ribavirin-free regimens, with anticipated approvals in the near future.

Non-invasive Fibrosis Assessment of Patients with Hepatitis C: Application of Society Guidelines to Clinical Practice

Chronic hepatitis C (CHC) infection remains a significant global public health burden and is associated with significant morbidity and mortality due to complications of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). All oral direct-acting antivirals (DAAs) are associated with high rates of sustained virologic response (SVR). Pre-treatment assessment for liver fibrosis remains of high importance as it may impact treatment choice, treatment duration, and signal the presence of cirrhosis for which variceal screening and HCC surveillance are warranted. Non-invasive fibrosis assessment tools have largely replaced gold standard liver biopsy in routine clinical practice. Herein, we review key modalities of noninvasive testing with serum and imaging biomarkers, summarize current guideline recommendations, and propose an algorithm for real-world application in clinical practice. Careful history and exam, laboratory assessment, liver imaging, and a two-test noninvasive fibrosis strategy can reliably identify cirrhosis in patients with CHC infection.

501 – Occurrence and Relapse of Hepatocellular Carcinoma in Hepatitis C Patients Treated with All Oral Direct-Acting Antivirals

501 – Occurrence and Relapse of Hepatocellular Carcinoma in Hepatitis C Patients Treated with All Oral Direct-Acting Antivirals

Preoperative Treatment of Hepatitis C Is Associated With Lower Prosthetic Joint Infection Rates in US Veterans

BackgroundHepatitis C virus (HCV) is associated with poorer outcomes in total joint arthroplasty (TJA). Recently, oral direct-acting antivirals (DAAs) have become available for HCV curative treatment. The goal of this study is to determine if HCV may be a modifiable risk factor in TJA by comparing postoperative complications among patients with and without preoperative treatment for HCV. MethodsUS Department of Veterans Affairs dataset of all consecutive primary TJAs performed between 2014 and 2018, when DAAs were available, was retrospectively reviewed. HCV-infected patients were identified using International Classification of Diseases, Ninth and Tenth Revision codes and laboratory values. HCV-infected patients treated prior to TJA with DAA were included in the “treated” group. HCV-infected patients untreated preoperatively were assigned to the “untreated” group. Medical and surgical complications up to 1 year postoperatively were identified using International Classification of Diseases, Ninth and Tenth Revision inpatient and outpatient codes. ResultsIn total, 42,268 patients underwent TJA at Veterans Affairs Hospitals between 2014 and 2018. About 6.0% (n = 2557) of TJA patients had HCV, 17.3% of whom received HCV treatment preoperatively. When evaluating inpatient and outpatient codes, implant infection rates were statistically lower at 90 days and 1 year postoperatively among HCV-treated patients than among those untreated. Odds ratios (ORs) favor lower infection rates in HCV-treated patients (90-day OR: 3.30, P = .045; 1-year OR: 2.16, P = .07). ConclusionPreoperative HCV treatment was associated with lower periprosthetic infection rates among US veterans undergoing TJA. Further investigation is necessary for definitive conclusions.

All Oral Interferon-free Direct-acting Antivirals as Combination Therapies to Cure Hepatitis C.

Chronic hepatitis C (CHC) virus infection and associated hepatic diseases are still challenging, and the disease burden remains significant around the world. Overall treatment rates for the chronically infected patients have been "dismally poor" and that treatment completion of dual-therapy- pegylated interferon (PEG-IFN) and ribavirin (RBV) is suboptimal in the real-world clinical settings. The approval of first, second and next-generation direct-acting antivirals (DAAs) represents a major breakthrough in hepatitis C virus (HCV) therapeutics to treat CHC infected individuals. Such therapeutic regimens in a fixed dose combination (FDC) or along with RBV have proven their clinical efficacy against different HCV genotypes, and harder-to-treat special populations. We continue to see the development of novel pan-genotypic anti-HCV regimens with very high sustained virologic response (SVR; undetectable viral load at week 12 or at the end of therapy) rates, high barrier to drug resistance, low frequency of adverse events, and fewer drug-drug interactions as compared to some older RBV based triple DAA therapies. Oral interferon-free DAAs seem highly successful strategic treatment approaches against hepatitis C and impulse health policy makers to establish the treatment priorties and policies to reduce the rate of hepatitis C-related morbidity and mortality. This review article comprehensively overviews interferon-free anti-HCV regimens, which have totally shifted the treatment paradigms for hepatitis C with some additional benefits to galvanize our efforts to achieve the global goal of HCV elimination in near future.

Glecaprevir/pibrentasvir for the treatment of chronic hepatitis C virus infection.

In recent years, management of chronic hepatitis C virus (HCV) infection has been revolutionized by the availability of oral direct-acting antivirals (DAAs), which have significantly better efficacy and safety profiles than interferon-containing regimens. Simple, short-duration DAA therapies will facilitate expansion of HCV treatment to nonspecialist providers, which will be vital to achieve the WHO target of eliminating chronic HCV as a major public health threat by 2030. Coformulated glecaprevir/pibrentasvir is the only 8-week, pan-genotypic, 2-DAA regimen recommended by international guidelines as a first-line regimen in treatment-naive, noncirrhotic HCV genotype 1-6 patients. This review provides a comprehensive summary of the pharmacodynamic and pharmacokinetic parameters, efficacy, safety and place in the HCV treatment paradigm for glecaprevir/pibrentasvir.

Real-world impact of direct acting antiviral therapy on health-related quality of life in HIV/Hepatitis C co-infected individuals.

Clinical trial results of direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) have shown improvements in health-related quality of life (HR-QoL). However, the extent to which these results are broadly generalizable to real-world settings is unknown. We investigated the real-world impact of oral DAA therapy on HR-QoL among individuals coinfected with HIV/HCV. We used data from the Canadian HIV/HCV Co-Infection Cohort Study that prospectively follows 1795 participants from 18 centres. Since 2007, clinical, lifestyle, and HR-QoL data have been collected biannually through self-administered questionnaires and chart review. HR-QoL was measured using the EQ-5D instrument. Participants initiating oral DAAs, having at least one visit before treatment initiation and at least one visit after DAA treatment response was ascertained, were included. Successful treatment response was defined as a sustained viral response (SVR). Segmented multivariate linear mixed models were used to evaluate the impact of SVR on HR-QoL, controlling for pretreatment trends. 227 participants met our eligibility criteria, 93% of whom achieved SVR. Before treatment, the EQ-5D utility index decreased 0.6 percentage-point/y (95% CI, -0.9, -0.3) and health state was constant over time. The immediate effect of SVR resulted in an increase of 2.3-units (-0.1, 4.7) in patients' health state and 2.0 percentage-point increase (-0.2, 4.0) in utility index. Health state continued to increase post-SVR by 1.4 units/y (-0.9, 3.7), while utility trends post-SVR plateaued over the observation period. Overall using real-world data, we found modest improvements in HR-QoL following SVR, compared to previously published clinical trials.

The burden of HBV infection in HCV patients in Italy and the risk of reactivation under DAA therapy

BackgroundThere is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs). AimTo provide figures on the prevalence of HBV markers in HCV-RNA-positive subjects in Italy, where these findings are lacking. MethodsAll subjects aged ≥18 years with CLD consecutively referring to Italian liver units located throughout country were prospectively enrolled in two national surveys in 2001 and 2014. ResultsThe total number of HCV-RNA-positive cases was 6984; 356 (5.1%) subjects vaccinated against HBV were excluded. A total of 6628 cases were evaluated. The prevalence rates of HBsAg, isolated anti-HBc and anti-HBc/anti-HBs-positivity were 2.9%, 8.1% and 14.7%, respectively. Among the estimated one million HCV-RNA-positive subjects in Italy, a substantial number of subjects are at risk of HBV reactivation due to DAA therapy. The prevalence of liver cirrhosis was higher than that of CLD in HBsAg-positive subjects (4.4% vs. 2.6%, p < 0.01) but not in those positive for other HBV markers. ConclusionsThese findings outline the burden of HBV markers among HCV-RNA-positive subjects in Italy, where in 2017 reimbursement for DAA therapy by the National Health System became universal for all patients with chronic HCV infection. HBV vaccination coverage should be greatly extended, since nearly two thirds of subjects in this study resulted negative for any HBV marker.

Circulating microRNA-636 is associated with the elimination of hepatitis C virus by ombitasvir/paritaprevir/ritonavir.

Hepatitis C virus (HCV) infection causes sustained inflammation and fibrosis. Several oral direct-acting antivirals (DAAs) including ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) were recently developed for HCV elimination. The combination of DAAs brought a higher sustained viral response (SVR) rate to anti-HCV therapy compared to interferon (IFN)-based regimens. However, 5% of hepatitis C patients who undergo DAA therapy still suffer from a sustained HCV infection. MicroRNA (miRNA) is essentially interfering, endogenous noncoding RNA that has been investigated as a new biomarker for the response to DAA in hepatitis C patients. Here we used a miRNA array and real-time polymerase chain reaction (PCR) to determine the targetable miRNA before and 12 weeks after OBV/PTV/r treatment for refractory hepatitis C. We used replicon cells, in which genotype 1b type HCV is stably transfected in Huh7 cells, to determine whether miRNA can inhibit HCV replication. Among 2,555 miRNAs, three were significantly up-regulated and eight miRNAs were down-regulated in serum 12 weeks after OBV/PTV/r treatment. An unsupervised hierarchical clustering analysis, using Pearson's correlation, showed that the miRNA profiles between before and 12 weeks after OBV/PTV/r treatment were clustered separately. At 12 weeks after OBV/PTV, miR-636 was targeted among the eight down-regulated miRNAs, and the expression level of circulating miR-636 was significantly diminished. The amount of HCV-RNA was significantly diminished 48 hours after miR-636 inhibitor transfection in HCV replicon cells. In conclusion, miR-636 might be one of the essential targetable molecules in HCV patients who undergo DAA therapy and still suffer from a sustained HCV infection.

Similar Sustained Virologic Response in Real-World and Clinical Trial Studies of Hepatitis C/Human Immunodeficiency Virus Coinfection

Clinical trials evaluating efficacy of direct-acting antiviral (DAA) therapies demonstrate sustained virologic response (SVR) rates greater than 90% in patients infected with hepatitis C (HCV) and human immunodeficiency virus (HIV). However, generalizability of this data to real-world coinfected populations is unknown. We aim to compare efficacy data from clinical trials to effectiveness data of real-world observational studies that evaluate oral interferon-free HCV treatment regimens in patients infected with HIV and HCV. We included English-language studies on PubMed and MEDLINE databases from inception until October 2017. Eight clinical trials and 11 observational studies reporting on efficacy data and effectiveness data, respectively, of interferon-free oral DAA regimens in HCV/HIV coinfected patients, were included. Of patients in the eight clinical trials evaluated, 93.1% (1218/1308) achieved SVR12; of the 11 real-world observational studies, 90.8% (2269/2499) achieved SVR12. Relative risk between those treated in clinical trials versus observational studies was 0.98. Patients with genotype 1 infection, African-American patients, cirrhotic patients, and patients with prior HCV treatment experience had similar rates of SVR in real-world and clinical trial cohorts. SVR among real-world HCV/HIV coinfected populations treated with DAA regimens is similar to SVR of patients studied in clinical trials. Historically negative predictors of achieving SVR during the era of interferon-based treatments, such as those with cirrhosis, prior HCV treatment failure, GT1 infection, and African-American race, are not associated with a significantly lower SVR in real-world populations treated with various DAA regimens.

Late relapse of hepatitis C virus in patients with sustained virological response after daclatasvir and asunaprevir therapy.

The optimal term of follow-up for patients who achieve sustained virological responses (SVR) is an important topic because of the widespread use of direct-acting antivirals (DAA), which achieve a high SVR rate. Investigations of long-term follow-up among patients with SVR after interferon (IFN) therapy have reported that approximately 80%-100% of patients maintained SVR. However, the long-term durability of SVR to DAA treatment is unknown. The aim of this study was to evaluate the incidence of late relapse in patients who achieved SVR with daclatasvir (DCV) and asunaprevir (ASV). Four hundred and thirteen patients infected with hepatitis C virus (HCV) genotype 1b who completed ASV and DCV treatment and achieved SVR were selected. Patients who were persistently negative for serum HCV RNA at 24weeks after withdrawal of DCV and ASV were considered to have SVR24. Mean follow-up period was 21.5months (range, 4.8-30.3months) after SVR24. Four patients redeveloped HCV RNA in serum at 6, 12, 12 and 26months, respectively, after achieving SVR24. Results of molecular analysis by phylogenetic tree of HCV nonstructural protein 3 and 5A regions from late relapse indicated that the same strain was present at pretreatment and late relapse. In conclusion, late relapse by the original HCV strain was confirmed by direct sequencing in 4 of 413 patients with SVR to ASV and DCV. Although a few patients may develop late relapse, SVR achieved with all oral DAA therapy is as durable as that with IFN therapy.