Hepatitis C – von der individuellen Heilung zur weltweiten Elimination?

2019 ◽  
Vol 144 (08) ◽  
pp. 535-542 ◽  
Author(s):  
Tobias Boettler ◽  
Volker Lohmann ◽  
Ralf Bartenschlager
Keyword(s):  
Hepatitis C ◽  
Vaccine Development ◽  
Sustained Viral Response ◽  
Small Animal ◽  
Virus Elimination ◽  
To Come ◽  
Treat All ◽  
Direct Acting ◽  
Cure Rates ◽  
Similar Cure

AbstractWith the implementation of highly effective direct acting antivirals (DAAs), global control or even elimination of chronic hepatitis C virus (HCV) infection might have come into reach. In fact, DAA therapy leads to complete virus elimination, defined as sustained viral response (SVR), in the vast majority of patients. Moreover, in patients without cirrhosis, the risk of developing HCC after DAA therapy is significantly reduced. For viremic patients who have already received DAA therapy, a distinction must be made between relapse and reinfection. The rate of new infections remains high and many infected individuals are undiagnosed. In order to come closer to the WHO goal of eliminating HCV worldwide by 2030, programs are needed to identify and treat all HCV-infected individuals. Strategies are missing in most countries to achieve this goal. Generic DAA therapies are available in some countries and appear to have similar cure rates compared to those obtained with the original drugs. The high variability of HCV, the numerous strategies of the virus to escape the immune response, and the lack of a suitable small animal model are key hurdles for vaccine development. Currently, the efficacy of two vaccine candidates is being investigated in clinical trials. The development of a protective vaccine is important, despite available therapy, to sustainably reduce the rate of new infections both in developing countries and in people with risk behavior.

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-vírus-fertőzés és hepatocarcinogenesis

2019 ◽  
Vol 160 (22) ◽  
pp. 846-853
Author(s):  
Evelin Berta ◽  
Anna Egresi ◽  
Anna Bacsárdi ◽  
Zsófia Gáspár ◽  
Gabriella Lengyel ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Primary Liver Cancer ◽  
Antiviral Agents ◽  
Sustained Viral Response ◽  
Abdominal Ultrasound ◽  
Viral Response ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract: Hepatitis C virus infection causes approximately 4 million new infections worldwide, and 399 000 deaths due to its complications, cirrhosis and hepatocellular carcinoma (HCC). Microenvironmental changes, chronic inflammation, oxidative stress, endoplasmic reticulum stress caused by HCV infection, via genetic and epigenetic changes can result in primary liver cancer during decades. The direct oncogenic property of HCV is wellknown. The transforming effect of four HCV proteins (core, NS3, NS4B, NS5A) has been proven. Effective antiviral therapy, sustained viral response decreases the HCV-related general and liver-related mortality. Interferon-based therapy reduces the risk of HCC development. Shorter therapy with direct acting antiviral agents (DAA) has higher efficacy, fewer side-effects. Publications have reported the unexpected effects of DAA. The authors review the articles focusing on the occurrence of HCC in connection with DAA therapies. There is a need for prospective, multicentric studies with longer follow-up to examine the risk of HCC formation. After antiviral therapy, HCC surveillance is of high importance which means abdominal ultrasound every 3–6–12 months in sustained viral response patients as well. Orv Hetil. 2019; 160(22): 846–853.

scholarly journals A systematic review and meta-analysis of community and primary-care-based hepatitis C testing and treatment services that employ direct acting antiviral drug treatments

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Andrew Radley ◽  
Emma Robinson ◽  
Esther J. Aspinall ◽  
Kathryn Angus ◽  
Lex Tan ◽  
...  
Keyword(s):  
Primary Care ◽  
Hepatitis C ◽  
Meta Analysis ◽  
Antiviral Drug ◽  
Sustained Viral Response ◽  
Primary Care Providers ◽  
Care Providers ◽  
Hcv Treatment ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Background Direct Acting Antiviral (DAAs) drugs have a much lower burden of treatment and monitoring requirements than regimens containing interferon and ribavirin, and a much higher efficacy in treating hepatitis C (HCV). These characteristics mean that initiating treatment and obtaining a virological cure (Sustained Viral response, SVR) on completion of treatment, in non-specialist environments should be feasible. We investigated the English-language literature evaluating community and primary care-based pathways using DAAs to treat HCV infection. Methods Databases (Cinahl; Embase; Medline; PsycINFO; PubMed) were searched for studies of treatment with DAAs in non-specialist settings to achieve SVR. Relevant studies were identified including those containing a comparison between a community and specialist services where available. A narrative synthesis and linked meta-analysis were performed on suitable studies with a strength of evidence assessment (GRADE). Results Seventeen studies fulfilled the inclusion criteria: five from Australia; two from Canada; two from UK and eight from USA. Seven studies demonstrated use of DAAs in primary care environments; four studies evaluated integrated systems linking specialists with primary care providers; three studies evaluated services in locations providing care to people who inject drugs; two studies evaluated delivery in pharmacies; and one evaluated delivery through telemedicine. Sixteen studies recorded treatment uptake. Patient numbers varied from around 60 participants with pathway studies to several thousand in two large database studies. Most studies recruited less than 500 patients. Five studies reported reduced SVR rates from an intention-to-treat analysis perspective because of loss to follow-up before the final confirmatory SVR test. GRADE assessments were made for uptake of HCV treatment (medium); completion of HCV treatment (low) and achievement of SVR at 12 weeks (medium). Conclusion Services sited in community settings are feasible and can deliver increased uptake of treatment. Such clinics are able to demonstrate similar SVR rates to published studies and real-world clinics in secondary care. Stronger study designs are needed to confirm the precision of effect size seen in current studies. Prospero: CRD42017069873.

Impact of direct-acting antivirals and 12-week sustained viral response on clinical outcomes in patients with hepatitis C and hepatocellular carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 397-397
Author(s):  
William M Kamp ◽  
Cortlandt Sellers ◽  
Stacey Stein ◽  
Joseph K Lim ◽  
Hyun S. Kevin Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatitis C ◽  
Sustained Viral Response ◽  
Tumor Location ◽  
Care Hospital ◽  
Direct Acting Antivirals ◽  
Treatment Allocation ◽  
Viral Response ◽  
Direct Acting

397 Background: To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and hepatitis C viral infections (HCV). Methods: Retrospective analysis of HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Results: Nine hundred ninety-six patients met inclusion criteria (mean age 62.8±10.2 yrs, 79% male). Four hundred seventy-eight (50%) patients received interventional oncology (catheter-based therapies, ablation and combination locoregional therapies), 141 (15%) received supportive care (palliative or no treatment), 125 (13%) received a transplant, 112 (14%) had tumor resection and 94 (12%) received chemotherapy or radiation as their primary treatment. Median overall survival (OS) of the entire cohort was 24.2 months (95% CI: 20.9-27.9). Transplant patients were excluded from further analysis. Four hundred seventy patients had HCV (56%). One hundred twenty-three patients received one or more DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (68%). HCC occurrence and recurrence were reported in 29 (26%) and 38 (45%) patients, respectively, after DAA therapy. HCV-positive and HCV-negative patients had similar survival (OS 20.7 mo vs 17.4 mo, p=0.22). Patients receiving DAA therapy had a higher OS of 71.8 mo (CI: 39.5-not reached) vs 11.6 mo (CI: 9.8-14.5) for patients without DAA therapy (p<0.0001). DAA patients who achieved SVR12 had a higher OS of 75.6 mo (CI: 49.2-not reached) vs the non-SVR12 group (26.7 mo, CI: 13.7-31.1, p<0.0001). Multivariable analysis (MVA) showed that AJCC, Child-Pugh Score, MELD, tumor size, tumor location and treatment allocation had independent influence on survival for the cohort (p<0.05). In HCV patients, AJCC, MELD, tumor location, treatment allocation and DAA were significant (p<0.05). In patients receiving DAA, only MELD score and SVR12 remained significant factors (p<0.05). Conclusions: DAA therapy and achieving SVR12 is associated with increased overall survival in HCC patients with HCV. This analysis supports the importance of treating HCV to SVR12 as part of HCC management.

scholarly journals Diagnosis, treatment, and follow-up of hepatitis C virus related liver disease.National consensus guideline in Hungary

2015 ◽  
Vol 156 (9) ◽  
pp. 343-351 ◽  
Author(s):  
Béla Hunyady ◽  
Zsuzsanna Gerlei ◽  
Judit Gervain ◽  
Gábor Horváth ◽  
Gabriella Lengyel ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Liver Injury ◽  
Sustained Viral Response ◽  
Dual Therapy ◽  
Insurance Fund ◽  
Health Insurance Fund ◽  
Viral Response ◽  
Direct Acting

Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. Furthermore, these could from prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity, as a socioeconomic aspect. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40–45% of previously not treated (naïve), and in 5–21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63–75% and 59–66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antivirals and interferon-free combination therapies have been registered for the treatment of chronic hepatitis C with a potential efficacy over 90% and typically with a short duration of 8–12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained viral response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option. Orv. Hetil., 2015, 156(9), 343–351.

scholarly journals Sustained Viral Response in a Hepatitis C Virus-Infected Chimpanzee via a Combination of Direct-Acting Antiviral Agents

2010 ◽  
Vol 55 (2) ◽  
pp. 937-939 ◽  
Author(s):  
David B. Olsen ◽  
Mary-Ellen Davies ◽  
Larry Handt ◽  
Kenneth Koeplinger ◽  
Nanyan Rena Zhang ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Agents ◽  
Sustained Viral Response ◽  
Virologic Response ◽  
Proof Of Concept ◽  
Viral Response ◽  
Direct Acting Antiviral ◽  
Infected Chimpanzee ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

ABSTRACTEfforts to develop novel, interferon-sparing therapies for treatment of chronic hepatitis C (HCV) infection are contingent on the ability of combination therapies consisting of direct antiviral inhibitors to achieve a sustained virologic response. This work demonstrates a proof of concept that coadministration of the nucleoside analogue MK-0608 with the protease inhibitor MK-7009, both of which produced robust viral load declines as monotherapy, to an HCV-infected chimpanzee can achieve a cure of infection.

scholarly journals Diagnosis, treatment, and follow-up of hepatitis C virus related liver disease.Hungarian national consensus guideline

2015 ◽  
Vol 156 (Supplement 1) ◽  
pp. 3-23 ◽  
Author(s):  
Béla Hunyady ◽  
Zsuzsanna Gerlei ◽  
Judit Gervain ◽  
Gábor Horváth ◽  
Gabriella Lengyel ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Liver Injury ◽  
Sustained Viral Response ◽  
Dual Therapy ◽  
Insurance Fund ◽  
Health Insurance Fund ◽  
Viral Response ◽  
Direct Acting

Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. From a socioeconomic aspect, this could also prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40–45% of previously not treated (naïve), and in 5–21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63–75% and 59–66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antiviral interferon-free combination therapies have been registered for the treatment of chronic hepatitis C, with a potential efficacy over 90% and typical short duration of 8–12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and / or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment as well as for on-treatment decisions, accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained viral response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option. Orv. Hetil., 2015, 156(Suppl. 1), 3–23.

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