Critical role of triglycerides for adiponectin levels in hepatitis C: a joint study of human and HCV core transgenic mice

Abstract Background Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive. Methods A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice. Results Of 427, 358 had completed a course of DAA therapy and 353 had SVRs. At baseline, male sex (95% CI β: − 1.44 to − 0.417), estimated glomerular filtration rate (eGFR) (− 0.025 to − 0.008), triglycerides (− 0.015 to − 0.005), and fibrosis-4 levels (0.08–0.297) were associated with adiponectin levels; BMI (0.029–0.327) and triglycerides levels (0.01–0.03) were associated with homeostatic model assessment for insulin resistance (HOMA-IR) in HCV-infected patients. At 24-week post-therapy, in SVR patients, male sex (− 1.89 to − 0.5) and eGFR (− 0.02 to − 0.001) levels were associated with adiponectin levels, levels of BMI (0.094–0.335) and alanine transaminase (0.018–0.078) were associated with HOMA-IR; compared with baseline levels, adiponectin levels decreased (6.53 ± 2.77 vs. 5.45 ± 2.56 μg/mL, p < 0.001). In 12-month-old HCV core transgenic mice with hepatic steatosis, triglyceride levels (0.021–0.111) were associated with adiponectin levels, and hepatic adipopnectin expression was comparable with that of control mice. Conclusions Triglycerides and hepatic fibrosis are associated with HCV-specific alteration of adiponectin levels, and adiponectin may affect insulin sensitivity through triglycerides during HCV infection. In DAA-treated patients, after SVR, adiponectin levels decreased and the linking function of triglycerides between adiponectin and insulin sensitivity vanished. Moreover, HCV core with hepatic steatosis might affect extrahepatic adiponectin expression through triglycerides.

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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 ◽

Direct Acting

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.

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Considering treatment-as-prevention scale-up for Australian prisons: a qualitative sub-study of expert stakeholders from the Australian ‘surveillance and treatment of prisoners with hepatitis C’ project (SToP-C)

Harm Reduction Journal ◽

10.1186/s12954-021-00494-4 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Jake Rance ◽

◽

Lise Lafferty ◽

Carla Treloar

Keyword(s):

Hepatitis C ◽

Primary Prevention ◽

Critical Role ◽

Scale Up ◽

Treatment As Prevention ◽

Structured Interviews ◽

Hcv Treatment ◽

Public Health Response ◽

Direct Acting ◽

Levels Of Support

Abstract Background With direct-acting antivirals dramatically reshaping the public health response to the hepatitis C virus (HCV), prisons are set to play a critical role in elimination efforts. Despite the theoretical demonstration of HCV treatment-as-prevention in prison in mathematical modeling, limited empirical data exist. The Australian ‘Surveillance and Treatment of Prisoners with Hepatitis C’ project (SToP-C) is the world’s first trial of HCV treatment-as-prevention in prison. Drawing on interviews with HCV expert stakeholders, this paper explores the factors respondents identified as crucial to the success of future scale-up. Accounting for such perspectives matters because of the influence expert discourse has in shaping implementation. Methods Semi-structured interviews were conducted with nineteen HCV experts working across key policy, advocacy, research and clinical dimensions of the Australian HCV response. Data were coded using qualitative data management software (NVivo 11). Analysis proceeded via a hybrid deductive and inductive approach. Results Notwithstanding concerns regarding the lack of primary prevention in Australian prisons, stakeholders reported broad levels of support for the intervention and for the future scale-up of HCV treatment. A number of considerations, both external and internal to the prison system, were identified as key. The principal external factor was an enabling political-cum-policy environment; internal factors included: obtaining support from prisons’ executive and custodial staff; promoting health within a security-first institutional culture; allocating time for treatment within prisoners’ tightly regulated schedules; ensuring institutional stability during treatment given the routine movement of prisoners between prisons; prioritizing the availability of retreatment given the paucity of primary prevention; and securing sufficient clinical space for treatment. Conclusion The challenges to implementation are considerable, ranging from macrolevel concerns to in-prison logistical matters. Nonetheless, we argue that prisons remain an obvious setting for treatment scale-up, not only for prevention and potential elimination benefit, but for the treatment opportunities they afford a socially disadvantaged and underserved population. While noting widespread concerns among respondents regarding the paucity of primary prevention in Australian prisons, results indicate broad levels of support among expert stakeholders for HCV treatment scale-up in prison.

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Oncogenic transcriptomic profile is sustained in the liver after the eradication of the hepatitis C virus

Carcinogenesis ◽

10.1093/carcin/bgab014 ◽

2021 ◽

Author(s):

Haruhiko Takeda ◽

Atsushi Takai ◽

Eriko Iguchi ◽

Masako Mishima ◽

Soichi Arasawa ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Molecular Basis ◽

Elevated Serum ◽

Gene Clusters ◽

Viral Clearance ◽

Hcv Infection ◽

Transcriptomic Profile ◽

Direct Acting ◽

Liver Tissues

Abstract Hepatocellular carcinoma (HCC) developing after hepatitis C virus (HCV) eradication is a serious clinical concern. However, molecular basis for the hepatocarcinogenesis after sustained virologic response (SVR) remains unclear. In this study, we aimed to unveil the transcriptomic profile of post-SVR liver tissues and explore the molecules associated with post-SVR carcinogenesis. We analysed 90 RNA-sequencing datasets, consisting of noncancerous liver tissues including 20 post-SVR, 40 HCV-positive and 7 normal livers, along with Huh7 cell line specimens before and after HCV infection and eradication. Comparative analysis demonstrated that cell cycle- and mitochondrial function-associated pathways were altered only in HCV-positive noncancerous liver tissues, while some cancer-related pathways were upregulated in the noncancerous liver tissues of both post-SVR and HCV-positive cases. The persistent upregulation of carcinogenesis-associated gene clusters after viral clearance was reconfirmed through in vitro experiments, of which, CYR61, associated with liver fibrosis and carcinogenesis in several cancer types, was the top enriched gene and co-expressed with cell proliferation-associated gene modules. To evaluate whether this molecule could be a predictor of hepatocarcinogenesis after cure of HCV infection, we also examined 127 sera from independent HCV-positive cohorts treated with direct-acting antivirals, including 60 post-SVR-HCC patients, and found that the elevated serum Cyr61 was significantly associated with early carcinogenesis after receiving direct-acting antiviral therapy. In conclusion, some oncogenic transcriptomic profiles are sustained in liver tissues after HCV eradication, which might be a molecular basis for the liver cancer development even after viral clearance. Among them, upregulated CYR61 could be a possible biomarker for post-SVR HCC.

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Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents

F1000Research ◽

10.12688/f1000research.7970.2 ◽

2016 ◽

Vol 5 ◽

pp. 223 ◽

Cited By ~ 1

Author(s):

Sara Sobhy Kishta ◽

Reem El-Shenawy ◽

Sobhy Ahmed Kishta

Keyword(s):

Clinical Trials ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Agents ◽

Antiviral Agent ◽

Viral Clearance ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Direct Acting Antiviral Agents

Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs (e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

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French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

BMC Infectious Diseases ◽

10.1186/s12879-020-05478-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Cécile Brouard ◽

Josiane Pillonel ◽

Marjorie Boussac ◽

Victor de Lédinghen ◽

Antoine Rachas ◽

...

Keyword(s):

Hepatitis C ◽

Antiviral Treatment ◽

Hcv Infection ◽

World Health ◽

Direct Acting Antivirals ◽

Substantial Impact ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting ◽

The Impact

Abstract Background Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.

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An Investigation of the Side Effects, Patient Feedback, and Physiological Changes Associated with Direct-Acting Antiviral Therapy for Hepatitis C

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16244981 ◽

2019 ◽

Vol 16 (24) ◽

pp. 4981

Author(s):

Pin-Sheng Wu ◽

Te-Sheng Chang ◽

Sheng-Nan Lu ◽

Hsiang-Jou Su ◽

Shu-Zhi Chang ◽

...

Keyword(s):

Hepatitis C ◽

Side Effects ◽

Rural Areas ◽

Virologic Response ◽

Hcv Infection ◽

Physiological Changes ◽

High Cure ◽

Patient Feedback ◽

Direct Acting ◽

Physiological Markers

Background: Hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and hepatocellular carcinoma globally. The advent of direct-acting antivirals (DAAs) with high cure rates provides an opportunity to reduce the rising HCV disease burden. However, few studies have explored the side effects and physiological benefits of DAA therapy in rural areas. The aim of this study was to investigate the subjective reports of discomfort, patient feedback about the course of treatment, and physiological changes after DAA treatment in HCV patients. Methods: A descriptive, prospective, comparative cohort study was conducted from January to August 2019 in western coastal Yunlin County, Taiwan. Data regarding demographic characteristics, subjective discomfort levels, and physiological responses were collected through face to face interviews and from medical records by a cooperating hospital. Results: Six-hundred-and-twenty-three participants with an active HCV infection were identified; 555 (89.1%) had completed treatment, and sustained virologic response was achieved in 99.6% (n = 553). The mean age was 64.9 (standard deviation = 13.1) years, and 35% of patients experienced discomfort during DAA treatment, including fatigue, itching, and dizziness. After three months of treatment, physiological markers, including body weight (p < 0.001), waist circumference (p < 0.05), blood pressure (p < 0.001), alanine aminotransferase (p < 0.001), and aspartate aminotransferase (p < 0.001), had significantly improved. Almost all participants provided positive feedback about the treatment experience and reported manageable side effects. Conclusions: The findings showed that, in an endemic rural area, DAA treatment had a high cure rate and improved physiological markers with few discomforts. These results can be used to reduce the barriers HCV patients face in adopting new medications.

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Hepatitis C and HIV Co-Infection

10.1093/med/9780199392742.003.0043 ◽

2017 ◽

Author(s):

Jennifer Cohen Price ◽

Priyanka Amin ◽

Antoine Douaihy

Keyword(s):

Hepatitis C ◽

Natural History ◽

The United States ◽

Hcv Infection ◽

Hepatic Decompensation ◽

History Of ◽

Chronic Hcv ◽

Direct Acting ◽

End Stage ◽

Shared Risk

Chronic infection with hepatitis C virus (HCV) is a leading cause of end-stage liver disease and is the most common indication for liver transplantation in the United States. Because of shared risk factors, individuals living with HIV infection are disproportionately affected by HCV. Moreover, co-infection with HIV accelerates the natural history of chronic HCV infection, increasing the risk of cirrhosis, hepatocellular carcinoma, hepatic decompensation, and death. Highly effective medications such as direct-acting antivirals (DAA) to cure HCV are now available and have the potential to profoundly improve the health of HIV-HCV-co-infected individuals. However, addressing the many gaps in the HCV care cascade is necessary to fully achieve the benefits of these drugs. This chapter reviews the natural history of HIV-HCV co-infection, the psychiatric comorbidities associated with HCV infection, the evolution of HCV treatment, and the barriers to care that HIV-HCV-co-infected individuals continue to face.

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