Antiviral Agents For Chronic Hepatitis Research Articles

Noninferiority Outcomes of Besifovir Compared to Tenofovir Alafenamide in Treatment-Naïve Patients with Chronic Hepatitis B.

: Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. : We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. : A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (-0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. : BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.

Amelioration of glucose intolerance through directly acting antiviral agents in chronic hepatitis C cirrhotic patients without overt diabetes.

Hepatitis C virus (HCV) eradication through antivirals ameliorates metabolic profiles. The changes in 2-h plasma glucose (2HPG) levels by oral glucose tolerance test (OGTT), in chronic hepatitis C (CHC) patients who receive directly acting antivirals (DAAs) was elusive. Five hundred and thirty-three CHC patients who achieved sustained virological response (SVR, undetectable HCV RNA throughout 3months after the end-of-treatment) by DAAs were consecutively enrolled. Pre- and posttreatment 2HPG levels and glucose status were compared. The proportion of patients with improved, worsened, and stable 2HPG was 14.4% (n=77), 18.6% (n=99), and 67.0% (n=357), respectively. Compared with patients with worsening 2HPG, those with improved 2HPG had a higher proportion of cirrhosis (45.5% vs. 24.2%, p=0.004) and higher pretreatment 2HPG levels (175.3 vs. 129.5mg/dl, p < 0.001). High baseline 2HPG was independently associated with improved 2HPG in multivariate analysis (odds ratio [OR]/CI: 1.05/1.03-1.06, p < 0.001). When baseline 2HPG was not taken into account, cirrhosis was the only factor independently associated with improved 2HPG status (OR/CI: 2.58/1.29-5.15, p=0.007). Linear regression analysis revealed that factors independently correlated to changes in 2HPG levels were female sex (β: 8.78; 95% CI:2.34, 15.22; p=0.01), diabetes (β: -27.72; 95% CI: -50.16, -5.28; p=0.02), liver cirrhosis (β: -8.91; 95% CI: -16.75, -2.20; p=0.01), and genotype 1 of HCV (β: -0.12; 95% CI: -15.19, -2.43; p=0.01). 2HPG improved after HCV eradication by DAAs, particularly in cirrhotic patients.

Direct-acting antiviral agents for chronic hepatitis C

Direct-acting antiviral agents for chronic hepatitis C

Efficacy of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide in treatment-naive hepatitis B patients.

Antiviral agents for chronic hepatitis B (CHB) reduced the risk of hepatocellular carcinoma (HCC) development. The outcomes of entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) were compared in patients with CHB. Between 2017 and 2019, treatment-naïve patients with CHB treated with ETV, TDF, and TAF were recruited from three Korean tertiary institutes. The cumulative incidences of HCC and orthotopic liver transplantation (OLT) or mortality were calculated and compared using Kaplan-Meier analysis before and after trimatch. Among recruited 2082 patients, 43 patients developed HCC, whereas 66 developed OLT or mortality. Before trimatch, the cumulative incidence of HCC was statistically similar among patients treated with three antiviral agents (p = 0.340). However, the cumulative probability of OLT or mortality development in patients treated with ETV or TDF was significantly higher than that of patients with TAF before trimatch (all p < 0.05). On multivariate analysis, male sex [hazard ratio (HR) 2.990] and older age (HR 1.044) were independently associated with an increased risk of HCC development, whereas higher platelet count (HR 0.993) was independently associated with a decreased risk (all p < 0.05). The type of antiviral agents did not significantly influence the risk of HCC and OLT or mortality development (all p > 0.05). After trimatch, no significant difference in the cumulative probability for HCC and OLT or mortality according to antiviral agents was found (all p > 0.05). The outcomes of ETV, TDF, and TAF on the risk of HCC and OLT or mortality were statistically similar in treatment-naïve patients with CHB.

Characteristics of De novo Hepatocellular carcinoma (HCC) in Chronic HCV Egyptian patients received Direct Acting Antivirals (DAAs) therapy: A pilot study

Abstract Background Direct-acting antiviral agents for chronic hepatitis C have initiated a revolution in the management and control of this important liver disease with cure rates over 90%. However, it has been suggested that HCC may occur or recur in patients with chronic HCV infection who received DAAs therapy. Aim To compare characteristics and behavior of de novo Hepatocellular carcinoma (HCC) in chronic HCV patients who received direct acting antiviral treatment with those who didn't receive DAAs . Patients and methods The current study was conducted on patients with de novo HCC presented at HCC clinic, Tropical medicine department Ain Shams University Hospitals between December 2017 and December 2018, aged (18-70 years old) . Total number of HCC cases visited the clinic during the study period was 416 patients. 160 patients with de novo HCC were enrolled in the study fullfiling the inclusion criteria and divided to two groups, 80 patients with HCC who received Direct antiviral treatment, the other 80 patients who didn't receive Direct antiviral treatment. Results Unlike some previous concerns about increased biologic aggressiveness of HCC after DAA treatment, resulting in infiltrative pattern and multinodular HCC outside Milan criteria, our results on de novo HCC after DAAs were mostly single, small, and diagnosed in early stages, resulting in BCLC stage 0-B in the majority of patients. There were no statistical differences regarding total size of tumor,or vascular invasion or AFP, but there’s a statistical difference in largest size of HFLs that was more significant in group (A) P = 0.04 The mean Child score was 5.75 in group A, with 61 patients (76.3%) were Child class A,19 patients (23.8%) were Child class B and 0 patients were child C. For the patients in group (B) the mean Child score was 6.15, with 50 patients (62.5%) were Child class A, 26 patients (32.5%) were Child class B and 4 patients (5%) were child C. Conclusion The current study shows no differences between the 2 studied groups as regard tumor aggressiveness, but data on risk of HCC and behaviour after DAAs is still conflicting and further studies are needed

Comment on "Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience".

Comment on "Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience".

Response to direct antiviral agents in chronic hepatitis C in patients with metabolic syndrome

Response to direct antiviral agents in chronic hepatitis C in patients with metabolic syndrome

Direct antiviral agents for chronic hepatitis C virus infection improve health-related quality of life significantly in the long term.

IntroductionDirect antiviral agents (DAAs) are new drugs for the treatment of chronic hepatitis C virus (HCV) infection. These drugs are very effective and well tolerated. HCV can cause liver disease as well as extrahepatic manifestations, including a profound negative impact on health-related quality of life (HRQL).Aim of the studyTo evaluate HRQL in the long term (> 6 months after finishing treatment) after successful treatment with DAAs. To the best of our knowledge, this is the first study that evaluates quality of life in the long term after DAA treatment.Material and methodsThis is an observational study which included 100 patients treated with DAAs for chronic HCV infection between January 2015 and August 2018. Patients were assigned randomly. The average time after finishing treatment was 29.96 months. The Liver Disease Symptom Index (LDSI) 2.0 Questionnaire was used to evaluate quality of life before and after treatment.ResultsSeven of 9 parameters of the LDSI 2.0 Questionnaire showed significant improvement in the long term after successful treatment with DAAs. Two parameters (arthralgia and jaundice) did not improve significantly. Quality of life improved in both males and females similarly. Improvement did not correlate with the severity of liver fibrosis.ConclusionsTreatment with DAAs improves HRQL significantly in the long term.

Maintaining Antiviral Efficacy after Switching to Generic Entecavir 1 mg for Antiviral-resistant Chronic Hepatitis B

Other SectionsAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTFinancial supportConflict of interestFiguresTablesReferences

Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C patients with genotype-2 infection after completed treatment.

Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long-term outcomes. Several direct-acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non-SOF-based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype-2 (GT-2) patients in Taiwan. However, there is limited real-world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real-world efficacy in CHC GT-2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT-2 patients who were treated with SOF-based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non-SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT-2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.

Efficacy and safety of sofosbuvir-based pangenotypic direct-acting antiviral agents for chronic hepatitis C patients without genotype determination: Real-world experience of a retrospective study.

Several new, pangenotypic direct-acting antiviral agents (DAAs) have been approved, may reduce the need for genotyping to guide therapy decisions for patients with chronic hepatitis C (CHC).This study aimed to investigate the efficacy and safety of Sofosbuvir (SOF)-based pangenotypic DAAs therapy for CHC patients without genotype (GT determination in the real-world practice.This retrospective cohort study included treatment-naïve CHC patients without GT determination, who received SOF-based DAAs therapy, including 400 mg SOF plus 60 mg daclatasvir (DCV) daily or 400 mg SOF plus 100 mg velpatasvir (VEL) daily for 12 or 24 weeks. Clinical and laboratory data, including sustained virologic response (SVR), were obtained at baseline, end of treatment (EOT), 12 weeks after EOT, and 48 weeks after EOT.A total of 95 CHC patients, including 30 (31.58%) had liver cirrhosis were enrolled. SVR rates after 12 weeks of treatment (SVR12) was 96.84% (92/95), including 96.20% (76/79) of patients receiving SOF plus DCV and 100% (16/16) of patients receiving SOF plus VEL. For 92 patients achieving an SVR12, no virological relapse was observed at 48 weeks after EOT. Furthermore, serum evaluation of liver fibrosis aspartate aminotransferase-to-platelet ratio index and Fibrosis-4 score were decreased significantly at EOT and 12 weeks after EOT, compared to pre-treatment values (both P < .05). Treatment was well-tolerated by our patients.SOF-based pangenotypic DAAs including SOF plus DCV and SOF plus VEL, were effective and safe for CHC patients without GT determination in this study. This may provide a potential simple strategy for CHC treatment without GT determination.

Factors affecting the recovery of hepatic reserve after sustained virologic response by direct-acting antiviral agents in chronic hepatitis C virus-infected patients.

Since the advent of direct-acting antiviral (DAA) therapy, the total eradication of hepatitis C virus has been achievable with the recovery of hepatic reserve after achievement of sustained virologic response (SVR). Hence, here, we examined the factors affecting the recovery of hepatic reserve. We followed up 403 patients (male: 164, female: 239; genotype 1: 299, genotype 2: 104; median age: 69years) for at least 3years after they achieved SVR to DAA therapy. Of these patients, 75 (18.6%) had a history of hepatocellular carcinoma (HCC). Biochemical tests were periodically performed, and the hepatic reserve was evaluated based on the albumin-bilirubin grade. We examined background factors such as age, biochemical test results, HCC occurrence and portosystemic shunt by computed tomography. At the start of treatment, the albumin-bilirubin grades were grades 1, 2, and 3 in 241, 157, and 5 patients, respectively, and 3years later, 117 of 162 (72%) patients with grade 2 or 3 improved to grade 1. Multivariate analysis identified the HCC occurrence after achievement of SVR (hazard ratio [HR]: 3.08, P<0.0138), male sex (HR: 3.45, P=0.0143), hemoglobin level of <11.5g/dL (HR: 4.19, P=0.0157), the presence of a portosystemic shunt (HR: 3.07, P=0.0349), and alanine aminotransferase levels <45U/L (HR: 2.67, P=0.0425) as factors inhibiting improvement to grade 1. However, old age was not an inhibitory factor. Our results demonstrate that hepatic reserve could be improved even in elderly patients over a long course of time.

Clinical factors leading to a change in management in chronic hepatitis B patients managed in a tertiary setting.

Newer antiviral agents for chronic hepatitis B (CHB) are highly effective, with minimal risks of complications and development of resistance. To identify the proportion of patients with CHB on treatment who will not require alteration of management and the clinical factors of those who will require closer monitoring. Patients with CHB who were on entecavir and/or tenofovir between January 2011 and December 2016 were retrospectively studied. According to the initial treatment plan provided by the managing physician, any deviation in the interval of follow up, choice of investigations and alteration of medical therapy were considered a change in CHB management. We also evaluated the predictability of these changes, factors associated with higher frequency of change and the additional cost of managing stable patients with CHB in a tertiary setting. Of the patients, 75.7% (n = 87/115) did not have a change in CHB management; 85.6% of the changes in management were predictable based on liver function tests, hepatitis B virus DNA polymerase chain reaction levels and liver ultrasound. Interpreter use (OR (95% CI) = 2.41 (1.01-5.76)), liver cirrhosis (OR (95% CI) = 4.11 (1.44-11.75)) and immunosuppression (OR (95% CI) = 3.81 (1.2-12.06)) were associated risk factors. Overall, there was an incremental annual cost of AU$60 166 to manage patients who did not require alteration of their CHB management in our institution. The majority of stable CHB patients on highly potent antiviral treatment do not require alteration of management. While additional investigations are required, this study highlights the potential for a shared primary care approach in highly selected CHB patients.

Real-world experiences with direct-acting antiviral agents for chronic hepatitis C treatment.

As direct-acting antiviral (DAA) agents become more readily available for the treatment of chronic hepatitis C, it is important to understand real-world treatment experiences. In order to assess the effectiveness of DAA regimens and factors that influence sustained virologic response (SVR) rates in the Veterans Affairs healthcare system, we retrospectively identified veterans with chronic hepatitis C who were treated with DAAs from January 2014 to June 2015. We determined SVR rates and collected data on demographics, genotype (GT), previous interferon-based treatment, antiviral regimens, and co-morbidities (HIV, prior solid organ transplant, haemodialysis) for analysis. Of 15720 veterans, the majority were infected with genotype 1a (GT1a, 60.5%). Excluding the special populations, the overall cohort SVR rate was 92%. Compared to treatment-experienced patients, treatment-naïve patients had significantly higher SVR rates (90% vs 92%, P=.006). Subgroups associated with lower likelihood of achieving SVR-included African Americans (OR 0.79, 95% CI 0.69-0.91), GT3 (OR 0.65, CI 0.50-0.86), and cirrhosis (OR 0.91, CI 0.84-0.99) or decompensated cirrhosis (ascites: OR 0.78, CI 0.67-0.91, variceal bleed: OR 0.75, CI 0.57-0.99). The only treatment regimen independently associated with lower SVR rates was SOF+RBV+IFN (OR 0.65, CI 0.50-0.84). Special populations achieved high SVR rates: HIV 92%, haemodialysis 93%, liver transplant 96% and renal transplant 94%. In conclusion, overall SVR rates were comparable to those reported in clinical trials and carried over to historically more difficult-to-treat patients. Several patient- and treatment-related factors were identified as independent predictors of treatment failure and suggest subgroups to target for efforts to improve therapeutic strategies.

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.

Consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C

Approved direct-acting antiviral agents (DAA ) in chronic hepatitis C were introduced. Metabolism and pharmacokinetics data of DAAs were analyzed. Comorbidity and concomitant medications of chronic hepatitis C (CHC) patients were extracted from Chinese Health Insurance database. Drug-drug interactions (DDIs) were calculated by integrated above data and confirmed by using Liverpool DDI website. Based on those data, experts propose consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C, including pre-treatment, on-treatment, and post-treatment.

'Real-life' experience with direct-acting antiviral agents for hepatitis C virus in end-stage renal disease.

The advent of direct-acting antiviral agents promises to change the management of hepatitis C in patients with end-stage renal disease, a patient group where the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' group of patients with end-stage renal disease. We performed a single-arm, multi-centre study in a cohort (n=30) of patients with advanced chronic kidney disease (mostly on dialysis) who underwent antiviral therapy with direct-acting antiviral agents. The primary end-point was sustained virologic response (serum hepatitis C virus RNA < 15 mIU/mL, 12 weeks after treatment ended). We collected data on on-treatment adverse events, serious adverse events and laboratory abnormalities. In total, 23 (77%) and 7 (23%) patients underwent regular dialysis and had chronic kidney disease at pre-dialysis stage, respectively. Six regimens were adopted: elbasvir/grazoprevir ( n = 6), ledipasvir/sofosbuvir ± ribavirin ( n = 4), PrOD regimens ± ribavirin ( n = 10), simeprevir + daclatasvir ( n = 3), sofosbuvir + daclatasvir ± ribavirin ( n = 3), sofosbuvir + ribavirin ( n = 4). The SVR12 rate was 90% (95% confidence interval, 74%; 96%). A total of 27 (90%) patients achieved SVR12; there were three virologic failures - two were non-responders and one had a viral breakthrough while on therapy. Adverse events occurred in 53% (16/30) (95% confidence interval, 0.39; 0.73) of patients and were managed clinically without discontinuation of therapy or hospitalization. The most common adverse event was anaemia ( n = 12) that required blood transfusions in seven individuals; deterioration of kidney function occurred in one (14%). All-oral, interferon-free therapy with direct-acting antiviral agents for chronic hepatitis C virus in advanced chronic kidney disease was effective and well tolerated in a 'real-life' clinical setting. Careful monitoring of haemoglobin and serum creatinine during therapy with direct-acting antiviral agents is suggested. Studies are under way to address whether sustained viral response translates into better survival in this population.

Selection of direct-acting antiviral agents for chronic hepatitis C infection

The elimination of hepatitis C virus(HCV) infection is still a long way to go. Direct-acting antiviral agents (DAAs) can make HCV completely cured by targeting various stages of its replication life cycle and meanwhile standardize and simplify the treatment. However, those relative factors may affect efficacy and safety should be considered by specialties in choosing the suitable regimens. Therefore, this article reviews various aspects of DAAs including development history, factors correlated with efficacy and safety, therapeutic regimens domestic listed and approved.

Sa1537 - The "HCV Advisor" APP - A Web-Based Mobile Application to Identify Suitable Treatments with Direct Antiviral Agents for Chronic Hepatitis C Infection

Sa1537 - The "HCV Advisor" APP - A Web-Based Mobile Application to Identify Suitable Treatments with Direct Antiviral Agents for Chronic Hepatitis C Infection

FRI-185 - Sustained viral response following treatment with direct acting antiviral agents for chronic hepatitis C and the risk of hepatocellular carcinoma

FRI-185 - Sustained viral response following treatment with direct acting antiviral agents for chronic hepatitis C and the risk of hepatocellular carcinoma