Case 21

Chronic hepatitis C (HCV) infection may be completely asymptomatic until the patient presents with complications of end-stage liver disease. Hence, anti-HCV testing should be performed on any patient with risk factors, which includes a raised alanine aminotransferase. Following diagnosis of chronic HCV infection, it is essential to know the genotype of the infecting virus, and whether or not the patient has underlying cirrhosis, as both of these factors will be important in determining the optimal therapeutic regimen. Direct-acting antiviral agents target 3 different viral non-structural proteins. The success of these drugs in achieving sustained virologic response (SVR) in well over 90% of patients in clinical trials has ended the era of interferon-based therapy for this infection. Therapy for most patients comprises one co/multiply-formulated tablet taken orally per day for 8 or 12 weeks.

The efficacy and safety of direct-acting antiviral agents in patients with chronic HCV infection and UGT1A1*28 polymorphism

Clinical Microbiology and Antimicrobial Chemotherapy ◽

10.36488/cmac.2020.1.71-80 ◽

2020 ◽

Vol 22 (1) ◽

pp. 71-80

Author(s):

S.P. Lukashyk ◽

I.A. Karpov ◽

M.G. Siniauskaya ◽

N.G. Danilenko ◽

L.A. Anisko ◽

...

Keyword(s):

Liver Cirrhosis ◽

Antiviral Agents ◽

Hcv Infection ◽

Efficacy And Safety ◽

Svr12 Rate ◽

Direct Acting Antiviral ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting ◽

Objective. To determine the efficacy and safety of direct-acting antiviral agents (DAA) in patients with chronic HCV infection and UGT1A1*28 polymorphism. Materials and Methods. An open-label, non-randomized, observational study to assess efficacy and safety of DAA in patients (n = 143) with chronic hepatitis C (CHC) and liver cirrhosis and UGT1A1*28 polymorphism was performed. A total of 139 patients with chronic HCV infection were included in the efficacy analysis (absence of HCV RNA in blood by PCR) by the rate of sustained virologic response at week 12 (SVR12). Results. The SVR12 rate in patients with CHC and HCV-CP was 92.5% and 87.9%, respectively (p = 0.508), regardless of the presence of UGT1A1*28 polymorphism. The SVR12 rate in patients with chronic HCV infection and (TA)7/(TA)7 was 84.8%, with (TA)6/(TA)7 – 92.2% compared with (TA)6/ (TA)6 – 90,5% (p = 0.518). The rate of SVR12 in patients with CHC and (TA)7/(TA)7 or (TA)6/(TA)7 was 80% and 95%, respectively, with (TA)6/(TA)6 – 95.2%. The rate of SVR12 in patients with liver cirrhosis and (TA)7/(TA)7 or (TA)6/(TA)7 was 92.3% and 87.5%, respectively, with (TA)6/(TA)6 – 85.7%. The rate of SVR12 in patients with 12- and 24-week treatment duration was 88.2% and 96.6%, respectively (p = 0.30). As many as 96.2% of patients with the previous treatment with interferon and ribavirin had SVR12 compared to 88.5% of patients who have not previously taken antiviral drugs (p = 0.486). Grade 1 adverse events (AE) occurred in 24% of patients with chronic HCV infection treated with DAA; two patients developed Grade 4 AE. Conclusions. The treatment with DAA was shown to be effective and safe in patients with chronic HCV infection and UGT1A1*28 polymorphism.

Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients

Frontiers in Endocrinology ◽

10.3389/fendo.2021.799382 ◽

2022 ◽

Vol 12 ◽

Author(s):

Chun-Han Cheng ◽

Chia-Ying Chu ◽

Huan-Lin Chen ◽

I-Tsung Lin ◽

Chia-Hsien Wu ◽

...

Keyword(s):

Glucose Homeostasis ◽

Antiviral Agents ◽

Hcv Infection ◽

Treatment Experience ◽

Factors Associated ◽

Direct Acting Antiviral ◽

Chronic Hcv Infection ◽

Hcv Genotype 1 ◽

Chronic Hcv ◽

Background and AimsChronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies.MethodsWe screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients’ baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment.ResultsHigh IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039).ConclusionsThere were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.

Cost-effectiveness of second-generation direct-acting antiviral agents in chronic HCV infection: a systematic literature review

Antiviral Therapy ◽

10.3851/imp3290 ◽

2019 ◽

Vol 24 (4) ◽

pp. 247-259 ◽

Cited By ~ 2

Author(s):

László Szilberhorn ◽

Zoltán Kaló ◽

Tamás Ágh

Keyword(s):

Cost Effectiveness ◽

Literature Review ◽

Systematic Literature Review ◽

Second Generation ◽

Antiviral Agents ◽

Direct Acting Antiviral ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting ◽

Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection

Gut ◽

10.1136/gutjnl-2017-313832 ◽

2017 ◽

Vol 67 (7) ◽

pp. 1342-1350 ◽

Cited By ~ 6

Author(s):

Hung-Yu Sun ◽

Pin-Nan Cheng ◽

Chiung-Ying Tseng ◽

Wei-Jen Tsai ◽

Yen-Cheng Chiu ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Sustained Virological Response Rate ◽

Antiviral Agents ◽

Density Lipoprotein ◽

Antiviral Agent ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

ObjectiveLipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the clinical manifestation and mechanistic relevance of plasma triglyceride (TG), cholesterol (Chol), lipoproteins and apolipoproteins (apos) after DAA treatment.DesignTwenty-four patients with chronic genotype 1 (GT1) HCV treated with elbasvir/grazoprevir or ledipasvir/sofosbuvir for 12 weeks, and followed-up thereafter, were recruited. Their TG, Chol, apoAI and apoB levels were quantified in plasma samples and individually fractionated lipoprotein of various classes. Liver fibrosis was evaluated using the FIB-4 Score. The TG and Chol loading capacities were calculated with normalisation to apoB, which represents per very low density lipoprotein (VLDL) and LDL particle unitResultsDAA treatment achieved a sustained virological response rate of 91.7% and reduced the FIB-4 Score. Relative to the baseline, the plasma TG level was reduced but the Chol level increased gradually. Plasma apoB levels and apoB/apoAI ratio were transiently downregulated as early as the first 4 weeks of treatment. The TG and Chol loading capacities in VLDL were elevated by ~20% during the period of DAA treatment and had steadily increased by 100% at follow-up. Furthermore, the TG-to-Chol ratio in VLDL was increased, while the ratio in LDL was reduced, indicating an efficient catabolism.ConclusionThe DAA treatment of patients with chronic hepatitis C might lead to efficient HCV eradication and hepatic improvement concomitantly evolving with favouring lipoprotein/apo metabolisms.

Additional Inhibition of Wnt/β-Catenin Signaling by Metformin in DAA Treatments as a Novel Therapeutic Strategy for HCV-Infected Patients

Cells ◽

10.3390/cells10040790 ◽

2021 ◽

Vol 10 (4) ◽

pp. 790

Author(s):

Dong Lin ◽

Venu Reddy ◽

Hanadi Osman ◽

Adriana Lopez ◽

Ali Riza Koksal ◽

...

Keyword(s):

Antiviral Agents ◽

Hcv Infection ◽

Novel Therapy ◽

Direct Acting Antiviral ◽

Chronic Hcv Infection ◽

Gsk 3Β ◽

Chronic Hcv ◽

Signaling Activation ◽

Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). Although HCV clearance has been improved by the advent of direct-acting antiviral agents (DAA), retrospective studies have shown that the risk of subsequent HCC, while considerably decreased compared with active HCV infection, persists after DAA regimens. However, either the mechanisms of how chronic HCV infection causes HCC or the factors responsible for HCC development after viral eradication in patients with DAA treatments remain elusive. We reported an in vitro model of chronic HCV infection and determined Wnt/β-catenin signaling activation due to the inhibition of GSK-3β activity via serine 9 phosphorylation (p-ser9-GSK-3β) leading to stable non-phosphorylated β-catenin. Immunohistochemical staining demonstrated the upregulation of both β-catenin and p-Ser9-GSK-3β in HCV-induced HCC tissues. Chronic HCV infection increased proliferation and colony-forming ability, but knockdown of β-catenin decreased proliferation and increased apoptosis. Unexpectedly, Wnt/β-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3β-mediated β-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/β-catenin signaling for HCV-infected patients.

Eradication of HCV Infection with the Direct-Acting Antiviral Therapy in Renal Allograft Recipients

BioMed Research International ◽

10.1155/2019/4674560 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Armando Calogero ◽

Evangelista Sagnelli ◽

Massimiliano Creta ◽

Silvia Angeletti ◽

Gaia Peluso ◽

...

Keyword(s):

Antiviral Agents ◽

Virologic Response ◽

Hcv Infection ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Direct Acting Antiviral ◽

Increased Risk ◽

The Subject ◽

Direct Acting ◽

Hepatitis C virus (HCV) infection unfavorably affects the survival of both renal patients undergoing hemodialysis and renal transplant recipients. In this subset of patients, the effectiveness and safety of different combinations of interferon-free direct-acting antiviral agents (DAAs) have been analyzed in several small studies. Despite fragmentary, the available data demonstrate that DAA treatment is safe and effective in eradicating HCV infection, with a sustained virologic response (SVR) rates nearly 95% and without an increased risk of allograft rejection. This review article analyzes the results of most published studies on this topic to favor more in-depth knowledge of the readers on the subject. We suggest, however, perseverating in this update as the optimal DAA regimen may not be proposed yet, because of the expected arrival of newer DAAs and of the lack of data from large multicenter randomized controlled trials.

Hematological Changes in HCV Patients Treated with Different Sofosbuvir-Based Regimens

International Journal of TROPICAL DISEASE & Health ◽

10.9734/ijtdh/2020/v41i1230337 ◽

2020 ◽

pp. 10-17

Author(s):

Ahmed Abdel Khalek ◽

Abdel Raouf El-Deib ◽

Gamal Tawfik ◽

Nashaat Soliman ◽

Mohamed Mosaad

Keyword(s):

Antiviral Agents ◽

Hemoglobin Level ◽

Direct Acting Antiviral ◽

End Of Treatment ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting ◽

Hematological Changes ◽

Introduction: Treatment of HCV with direct acting antiviral agents (DAAs) with the different regimen dramatically changed the outcomes of the disease beside its eradication. In the same time hematological concerns as anemia, thrombocytopenia, and leucopenia were a major factor before initiation, or during treatment with the antiviral drugs. Aim: To demonstrate hematological changes during and after treatment with different regimen of DAAs. Methods: Follow up the hematological changes before, during and after treatment for 100 patients with chronic HCV treated with five different sofosbuvir-based regimen; using interferon, ribavirin, simeprevir and daclatasvir. Results: There are no similar linear changes regarding anemia, leucopenia or thrombocytopenia, however, combination therapy using sofosbuvir with simeprevir or daclatasvir significantly increase platelets count, WBCs, and hemoglobin level during and after end of treatment, versus regimens uses sofosbuvir with ribavirin and or interferon that showed significantly decreased hematological values during and after treatment. Conclusion: Sofosbuvir-based regimen has favorable hematological changes in patients with chronic HCV infection during and after treatments especially with sofosbuvir and daclatasvir.

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

SSRN Electronic Journal ◽

10.2139/ssrn.3393711 ◽

2019 ◽

Author(s):

Dong Ji ◽

Guo-feng Chen ◽

Ping Han ◽

Cheng Wang ◽

Qing Shao ◽

...

Keyword(s):

Antiviral Agents ◽

Pegylated Interferon ◽

Virologic Response ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Direct Acting Antiviral ◽

Pegylated Interferon Plus Ribavirin ◽

Direct Acting ◽

When Coadministration Cannot Be Avoided: Real World Experience of Direct Acting Antivirals for the Treatment of Hepatitis C Virus Infection in Patients on First Generation Anticonvulsants

Journal of Pharmacy Practice ◽

10.1177/0897190020977762 ◽

2020 ◽

pp. 089719002097776

Author(s):

Kayla M. Natali ◽

Humberto R. Jimenez ◽

Jihad Slim

Keyword(s):

Drug Interaction ◽

Hepatitis C ◽

Clinical Cure ◽

First Generation ◽

Virologic Response ◽

Hcv Infection ◽

Direct Acting Antivirals ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Background Coadministration of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection and first generation anticonvulsants is currently not recommended due to a drug-drug interaction that could potentially lead to subtherapeutic DAA levels and subsequent treatment failure. Currently, there is limited data evaluating this interaction and timely treatment of HCV infection with DAAs is imperative to prevent liver-related morbidity and mortality. Methods A retrospective case series evaluating clinical cure of chronic HCV infection, defined as sustained virologic response (SVR) 12 weeks after completion of DAA therapy, in patients from three inner-city clinics who remained on first generation anticonvulsants during the treatment course. Results A total of five patients received standard dose DAAs for treatment of chronic HCV infection while being maintained on first generation anticonvulsants. The most common HCV genotype was 1a (80%), followed by 1b (20%). The majority of patients were treated with glecaprevir/pibrentasvir (80%) for eight weeks and one patient was treated with ledipasvir/sofosbuvir for 12 weeks. Anticonvulsant regimens consisted of carbamazepine, phenytoin, phenytoin plus phenobarbital, phenytoin plus levetiracetam, and phenobarbital plus lacosamide. All five patients achieved sustained virologic response (SVR) despite this drug-drug interaction. Conclusion Although every effort to prevent concomitant use of DAAs and potent inducers should be made, clinical cure may still be achieved in patients whom cannot avoid this coadministration.