scholarly journals Resistance Mutations A30K and Y93N Associated with Treatment Failure with Sofosbuvir and Daclatasvir for Hepatitis C Virus Infection Non-Responder Patients: Case Reports

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1004
Author(s):  
Vanessa D. Costa ◽  
Patricia Pellegrini ◽  
Vivian Rotman ◽  
Ana Maria Pittella ◽  
Estevão P. Nunes ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Treatment Failure ◽  
Case Reports ◽  
Rescue Therapy ◽  
Combined Therapy ◽  
Virologic Response ◽  
Resistance Mutations ◽  
Viral Determinants ◽  
Direct Acting

In Brazil, hepatitis C treatment has been evolving significantly with the licensing of direct-acting antivirals (DAAs). However, viral determinants (amino acid substitutions in hepatitis C virus (HCV) genome and infective genotype) associated with host factors (hepatic condition and prior HCV therapy) might limit the achievement of sustained virologic response (SVR). Here, we described two case reports in which the occurrence of HCV NS5A mutations A30K (subtype 3a) and Y93N (subtype 1a) might have influenced daclatasvir (DCV)/sofosbuvir (SOF) combined therapy non-response. Despite high response rates for DAA combined therapies in Brazil, these case reports stated the importance of an investigation about how to manage a DAA treatment failure since a combination of factors, especially the occurrence of resistance substitutions, could impact a rescue therapy with new available antivirals in clinical routine.

Rescue Therapy for Genotype-3 DAA Non-responders, Almost all Done

2018 ◽  
Vol 17 (5) ◽  
pp. 0-10
Author(s):  
Susana Llerena ◽  
Joaquín Cabezas ◽  
Antonio Cuadrado ◽  
José Manuel Olmos ◽  
Marta González ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Case Reports ◽  
Rescue Therapy ◽  
Virologic Response ◽  
New Combination ◽  
Direct Acting Antivirals ◽  
Genotype 3 ◽  
Hcv Genotype 3 ◽  
Almost All ◽  
Direct Acting

Nowadays, the retreatment of patients with Hepatitis C virus (HCV) genotype 3 (GT3) especially cirrhotic, who have already been treated with regimens containing a NS5A inhibitor represents a challenge. Use a novel retreatment option for patients with a difficult approach. We present three case reports of retreatment with a new combination of Direct-acting antivirals (DAAs), Sofosbuvir, Elbasvir/ Grazoprevir in patients with GT3 with a previous failure with Sofosbuvir/Ledipasvir. All the cases achieved sustained virologic response (SVR) at week +12 without adverse effects. In our experience, this combo may represent an effective and safe option for these patients.

scholarly journals Detection of drug resistance mutations of hepatitis C virus in patients with failure of the treatment with direct acting antivirals

2021 ◽  
Vol 98 (1) ◽  
pp. 18-27
Author(s):  
D. E. Valutite ◽  
A. V. Semenov ◽  
Yu. V. Ostankova ◽  
K. V. Kozlov ◽  
A. G. Borisov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Treatment Failure ◽  
Chronic Hepatitis C ◽  
Direct Acting Antivirals ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Direct Acting

Background. The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C. However, there are cases showing no response to treatment. In 5% of cases, the viral breakthrough is most likely caused by DAA resistance mutations in the hepatitis C virus genome.The purpose of the study is to detect drug resistance mutations of hepatitis C virus in patients with DAA treatment failure.Materials and methods. The study was performed on plasma samples from 3 patients diagnosed with chronic hepatitis C virus infection and demonstrating DAA virological treatment failure. All isolates had genotype 1b. Drug resistance mutations were detected by using direct sequencing of NS3, NS5A, and NS5B genome regions. The detection technique was developed at the Pasteur Research Institute of Epidemiology and Microbiology.Results. Drug resistance mutations were detected in all cases. By using the Geno2pheno [hcv] 0.92 tool, nucleotide substitutions were detected in different viral genome regions and presumably caused resistance or decreased sensitivity to antivirals both present and absent in the sofosbuvir + daclatasvir combination therapy. Antiviral treatment failure in patients with chronic hepatitis C is caused by drug resistance mutations.Conclusions. The developed technique is efficient for detection of drug resistance mutations in NS3, NS5A, and NS5B regions in cases of virological failure of DAA treatment.

New Epidemiologic Data Regarding Hepatitis C Virus Infection in Romania

2017 ◽  
Vol 26 (4) ◽  
pp. 381-386
Author(s):  
Mircea Manuc ◽  
Carmen M. Preda ◽  
Corneliu P. Popescu ◽  
Cristian Baicuș ◽  
Theodor Voiosu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Users ◽  
Antiviral Agent ◽  
Virologic Response ◽  
Advanced Fibrosis ◽  
Direct Acting Antiviral ◽  
Genotype 1B ◽  
Direct Acting ◽  
End Stage

Background & Aims: Literature data suggest that HCV genotype-1b is present in 93-99% of the Romanian patients infected with hepatitis C virus (HCV). We present the genotyping tests recently performed on patients with HCV and advanced fibrosis eligible for the Direct-Acting Antiviral (DAA) therapy, as well as the prevalence of these cases across Romania.Methods: The genotyping method was performed on 7,421 HCV patients with advanced fibrosis. The detection method was automatic real time PCR platform M2000 (Abbott). Every subject was introduced into a database including age, sex, county and address.Results: Genotype 1b was almost exclusively present: 7,392/7,421 (99.6%). Genotype 1b patients were 19.6% from Bucharest, 49% were males, with a median age of 60 years. Genotype non-1b was encountered in 29/7,421 subjects (0.4%), 62% were males, 69% from Bucharest and the median age was 52 years. Most of the subjects (75%) were in the 6th and 7th age decade. The prevalence of these cases varied significantly across Romanian counties: the highest was in Bucharest (61.3/105), Bihor (47/105), Iasi (46/105) and Constanța (43/105), and the lowest in Ilfov (2.8/105), Harghita (3.7/105), Covasna (5.4/105) and Maramureș (8.8/105) (p<0.001).Conclusions: Genotype 1b is encountered in 99.6% of patients with chronic hepatitis C and advanced fibrosis from Romania. The presence of genotypes non-1b is more common in Bucharest, in males and at a younger age. There are significant differences regarding the distribution of these cases across Romania: the highest rates are in Bucharest, Bihor, Iasi and Constanta.Abbreviations: BMI: body mass index; DAA: direct-acting antiviral agent; GT: genotype; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; IDU: intravenous drug users; MELD: model for end stage liver disease; NASH: non-alcoholic steatohepatitis; SVR; sustained virologic response.

scholarly journals Real-World Outcomes of Direct-Acting Antiviral Treatment and Retreatment in United Kingdom–Based Patients Infected With Hepatitis C Virus Genotypes/Subtypes Endemic in Africa

2021 ◽  
Author(s):  
Elihu Aranday-Cortes ◽  
C Patrick McClure ◽  
Christopher Davis ◽  
William L Irving ◽  
Kazeem Adeboyejo ◽  
...  
Keyword(s):  
United Kingdom ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Treatment Failure ◽  
Antiviral Treatment ◽  
Natural Resistance ◽  
Eastern Africa ◽  
Middle Income ◽  
Hcv Genotypes ◽  
Direct Acting

Abstract Background Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) in high-income countries where a restricted range of HCV genotypes/subtypes circulate. Methods We studied United Kingdom–resident patients born in Africa to examine DAA effectiveness in LMICs where there is far greater breadth of HCV genotypes/subtypes. Viral genome sequences were determined from 233 patients. Results Full-length viral genomic sequences for 26 known subtypes and 5 previously unidentified isolates covering 5 HCV genotypes were determined. From 149 patients who received DAA treatment/retreatment, the overall SVR was 93%. Treatment failure was associated primarily with 2 subtypes, gt1l and gt4r, using sofosbuvir/ledipasvir. These subtypes contain natural resistance-associated variants that likely contribute to poor efficacy with this drug combination. Treatment failure was also significantly associated with hepatocellular carcinoma. Conclusions DAA combinations give high SVR rates despite the high HCV diversity across the African continent except for subtypes gt1l and gt4r, which respond poorly to sofosbuvir/ledipasvir. These subtypes are widely distributed across Western, Central, and Eastern Africa. Thus, in circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommended treatment option.

scholarly journals Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kao-Chi Chang ◽  
Shui-Yi Tung ◽  
Kuo-Liang Wei ◽  
Chen-Heng Shen ◽  
Yung-Yu Hsieh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Real World ◽  
Population Analysis ◽  
Virologic Response ◽  
Efficacy And Safety ◽  
Hepatitis C Virus Infection ◽  
Direct Acting Antivirals ◽  
Evaluable Population ◽  
Direct Acting

AbstractClinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.

scholarly journals Hepatitis C virus vaccine development: old challenges and new opportunities

2015 ◽  
Vol 2 (3) ◽  
pp. 285-295 ◽  
Author(s):  
Dapeng Li ◽  
Zhong Huang ◽  
Jin Zhong
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Vaccine Development ◽  
Rna Virus ◽  
Antiviral Agents ◽  
Resistance Mutations ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Hepatitis C virus (HCV), an enveloped positive-sense single-stranded RNA virus, can cause chronic and end-stage liver diseases. Approximately 185 million people worldwide are infected with HCV. Tremendous progress has been achieved in the therapeutics of chronic hepatitis C thanks to the development of direct-acting antiviral agents (DAAs), but the worldwide use of these highly effective DAAs is limited due to their high treatment cost. In addition, drug-resistance mutations remain a potential problem as DAAs are becoming a standard therapy for chronic hepatitis C. Unfortunately, no vaccine is available for preventing new HCV infection. Therefore, HCV still imposes a big threat to human public health, and the worldwide eradication of HCV is critically dependent on an effective HCV vaccine. In this review, we summarize recent progresses on HCV vaccine development and present our views on the rationale and strategy to develop an effective HCV vaccine.

scholarly journals Hepatitis C virus-associated cryoglobulinemic vasculitis: A 20-year experience with treatment

2017 ◽  
Vol 89 (5) ◽  
pp. 46-52 ◽  
Author(s):  
T M Ignatova ◽  
L V Kozlovskaya ◽  
N B Gordovskaya ◽  
O A Chernova ◽  
S Yu Milovanova ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Combined Therapy ◽  
Multivariate Logistic Regression Analysis ◽  
Virologic Response ◽  
Term Treatment ◽  
Cryoglobulinemic Vasculitis ◽  
Multidisciplinary Therapy ◽  
Long Term Treatment

Aim. To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). Subjects and methods. Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients’ survival was studied; multivariate logistic regression analysis was carried out. Results. 24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age >55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91). Conclusion. HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.

scholarly journals THERAPY OF RECURRENT HEPATITIS C AFTER TRANSPLANTATION OF THE LIVER WITH DIRECT ACTING ANTI-HEPATITIS C VIRUS DRUGS: EXPERIENCE OF THREE RUSSIAN CENTERS

2018 ◽  
Vol 23 (1) ◽  
pp. 4-14
Author(s):  
Vladimir E. Syutkin ◽  
E. N Bessonova ◽  
M. N Davydenko
Keyword(s):  
Liver Transplantation ◽  
Hepatitis C ◽  
De Novo ◽  
Virologic Response ◽  
Resistance Mutations ◽  
Virus Genotype ◽  
Serious Adverse Events ◽  
Recurrent Hepatitis ◽  
Recurrent Hepatitis C ◽  
Direct Acting

The results of a retrospective analysis of the experience of three Russian regional liver transplantation centers in relation to antiviral therapy of recurrent hepatitis C in liver recipients are presented. There were studied six different therapeutic schedules with direct antiviral drugs (DAVD) administered in 91 patients. The frequency of the persistent virologic response in 12 weeks after the completion of therapy (PVR12) amounted to 92.3%. In recipients, the use of a combination of sofosbuvir and daclatasvir seems to be the most promising as following its administration relapses observed in only 3 out of the 57 recipients were associated with drug resistance mutations to NS5A inhibitors. There were no serious adverse events related to the use of DAVD. The frequency of the reactivation of HBV infection against the background of DAVD therapy in liver recipients did not exceed the previously reported frequency of de novo hepatitis B in non-endemic regions. In recurrent hepatitis C patients after the liver transplantation effects of both the virus genotype, the pronouncement of graft fibrosis and the addition of ribavirin, on the frequency of SVO12 have not been revealed.

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