Second generation direct-acting antivirals – Do we expect major improvements?

Feld, Jordan J.; Foster, Graham R.

doi:10.1016/j.jhep.2016.07.007

Cited by 38 publications

(20 citation statements)

References 76 publications

(97 reference statements)

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“…The availability of interferon-free, direct-acting antiviral regimens has led to significant improvements in treatment efficacy, in which viral eradication can be achieved in over 90% of patients regardless of hepatitis C virus genotype (Table 1). 38…”

Section: Evolution Of Hepatitis C Virus Treatmentmentioning

confidence: 99%

Medical and Behavioral Approaches to Engage People Who Inject Drugs Into Care for Hepatitis C Virus Infection

Gonzalez¹,

Fierer

Talal

2017

Addictive Disorders &Amp; Their Treatment

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Direct-acting antivirals for hepatitis C virus infection may revolutionize treatment among persons with substance use disorders. Despite persons with substance use disorders having the highest hepatitis C virus prevalence and incidence, the vast majority have not engaged into care for the infection. Previously, interferon-based treatments, with substantial side effects and the propensity to exacerbate mental health conditions, were major disincentives to pursuit of care for the infection. Direct-acting antivirals with viral eradication rates of >90%, significantly improved side effect profiles, and shorter treatment duration are dramatic improvements over prior treatment regimens that should promote widespread hepatitis C virus care among persons with substance use disorders. The major unmet need is strategies to promote persons with substance use disorders engagement into care for hepatitis C virus. Although physical integration of treatment for substance use and co-occurring conditions has been widely advocated, it has been difficult to achieve. Telemedicine offers an opportunity for virtual integration of behavioral and medical treatments that could be supplemented by conventional interventions such as hepatitis C virus education, case management, and peer navigation. Furthermore, harm reduction and strategies to reduce viral transmission are important to cease reinfection among persons with substance use disorders. Widespread prescription of therapy for hepatitis C virus infection to substance users will be required to achieve the ultimate goal of global virus elimination. Combinations of medical and behavioral interventions should be used to promote persons with substance use disorders engagement into and adherence with direct-acting antiviral-based treatment approaches. Ultimately, either physical or virtual colocation of hepatitis C virus and substance use treatment has the potential to improve adherence and consequently treatment efficacy.

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Section: Evolution Of Hepatitis C Virus Treatmentmentioning

confidence: 99%

Medical and Behavioral Approaches to Engage People Who Inject Drugs Into Care for Hepatitis C Virus Infection

Gonzalez¹,

Fierer

Talal

2017

Addictive Disorders &Amp; Their Treatment

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“…Over the past several years, all oral direct-acting antiviral (DAA) agents have replaced IFN for the treatment of HCV 24–26. The advantages of DAAs are improved tolerability, safety and utility 24–27.…”

Section: Introductionmentioning

confidence: 99%

Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct-acting Antivirals

Nguyen

Jimenez

Moghadam

et al. 2017

Journal of Clinical and Translational Hepatology

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Background and Aims: The lack of specificity has limited the role of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine whether AFP may decrease after achieving a sustained virological response (SVR) in patients with HCV-related cirrhosis. Methods: We performed a retrospective study of patients with HCV-related cirrhosis who were cured with direct-acting antiviral (DAA) therapy at the University of California, Los Angeles. Laboratory values, including serum AFP, were measured before and after completing the DAA treatment. Results: Fifty-six patients met the inclusion criteria, with median (interquartile range [IQR]) age of 67 (58-69) years and with 51.8% being male. All patients received DAA therapy without interferon. AFP decreased from median (IQR) 7.2 (4.2-13.4) ng/mL before DAAs to 4.2 (2.7-6.3) ng/mL at the end of treatment and 4.2 (2.9-6.8) ng/mL at 12 weeks after treatment (p < 0.001). Model for end-stage liver disease (MELD), fibrosis-4 (FIB4), and aspartate transaminase (AST) to platelet ratio index (APRI) scores at baseline were not significantly associated with AFP reduction. On multivariate analysis, platelet count, AST and total bilirubin at baseline were significantly correlated to AFP reduction (p = 0.04, 0.009 and 0.04, respectively). The higher the baseline AFP, the greater the reduction in AFP. There was no statistically significant correlation between baseline AFP and MELD, FIB4 or APRI scores. Conclusion: There was a significant decrease in AFP in patients with cirrhosis who achieved a SVR with DAAs. Given a reduction in AFP after DAA treatment, AFP should be further studied as a screening modality for HCC in patients with cirrhosis.

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“…Genotype 3 (G-3) is emerging as difficult to treat and very few drugs are effective for its treatment 6. Response rate for these patients with all oral therapy is at best 80-85%, much inferior to genotype 1 or 2 7.…”

Section: Introductionmentioning

confidence: 99%

Sofosbuvir based therapy in Hepatitis C patients with and without cirrhosis: Is there difference?

Sarwar¹,

Khan²

2017

Pak J Med Sci

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Objective:To compare sustained viral response to sofosbuvir/ribavirin ±interferon therapy in patients of hepatitis C with and without liver cirrhosis.Methods:This observational study of chronic hepatitis C patients was carried out at Doctors Hospital and Medical Center (DH&MC). After diagnostic workup, Sofosbuvir/ribavirin for 24 weeks or sofosbuvir/ribavirin/pegylated interferon for 12 weeks were prescribed. Primary outcome was negative HCV RNA by PCR 12 weeks after treatment completion (SVR12). Chi square χ2 and student’s t test were used to analyze data.Results:Of 216 patients included, liver cirrhosis was present in 112 (51.9%) patients and 69(31.9%) were treatment experienced. Liver disease was decompensated in 37 (17.1%) patients. Of 206 patient who completed study protocol, 173(83.1%) achieved SVR12, 89.2% (25/28) with triple therapy and 82.2% (148/180) with sofosbuvir/ribavirin therapy. Treatment response was similar between treatment naïve 86.2% (119/138) and treatment experienced 79.4% (54/68) patents. (p value 0.19) SVR12 was inferior in cirrhosis patients 75.4% (80/106) as compared to those with no cirrhosis 93% (93/100) (p value < 0.000). It was even lesser in those with decompensated liver disease 68.8% (24/35) (p value < 0.000).Conclusion:Treatment outcome with sofosbuvir/ribavirin combination therapy in cirrhosis patients is suboptimal especially in those with decompensation as compared to patients without liver cirrhosis.

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Second generation direct-acting antivirals – Do we expect major improvements?

Cited by 38 publications

References 76 publications

Medical and Behavioral Approaches to Engage People Who Inject Drugs Into Care for Hepatitis C Virus Infection

Medical and Behavioral Approaches to Engage People Who Inject Drugs Into Care for Hepatitis C Virus Infection

Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct-acting Antivirals

Sofosbuvir based therapy in Hepatitis C patients with and without cirrhosis: Is there difference?

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