This blog is all about current FDA approved drugs to treat the hepatitis C virus (HCV) with a focus on treating HCV according to genotype, using information extracted from peer-reviewed journals, liver meetings/conferences, and interactive learning activities.
Risk Of Developing Liver Cancer After HCV Treatment
World J Gastroenterol. Feb 7, 2018; 24(5): 613-622 Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.613
Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus: A retrospective cohort study Patrícia dos Santos Marcon, Cristiane Valle Tovo, Dimas Alexandre Kliemann, Patrícia Fisch, Angelo Alves de Mattos
To assess the incidence of hepatocellular carcinoma (HCC) in chronic liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfected with human immunodeficiency virus (HIV).
METHODS A retrospective cohort study was performed, including patients with chronic liver disease due to HBV or HCV, with and without HIV coinfection. Patients were selected in the largest tertiary public hospital complex in southern Brazil between January 2007 and June 2014. We assessed demographic and clinical data, including lifestyle habits such as illicit drug use or alcohol abuse, in addition to frequency and reasons for hospital admissions via medical records review.
RESULTS Of 804 patients were included (399 with HIV coinfection and 405 monoinfected with HBV or HCV). Coinfected patients were younger (36.7 ± 10 vs 46.3 ± 12.5, P < 0.001). Liver cirrhosis was observed in 31.3% of HIV-negative patients and in 16.5% of coinfected (P < 0.001). HCC was diagnosed in 36 patients (10 HIV coinfected and 26 monoinfected). The incidence density of HCC in coinfected and monoinfected patients was 0.25 and 0.72 cases per 100 patient-years (95%CI: 0.12-0.46 vs 0.47-1.05) (long-rank P = 0.002), respectively. The ratio for the HCC incidence rate was 2.98 for HIV-negative. However, when adjusting for age or when only cirrhotic are analyzed, the absence of HIV lost statistical significance for the development of HCC.
CONCLUSION In this study, the presence of HIV coinfection in chronic liver disease due to HBV or HCV showed no relation to the increase of HCC incidence.
Long-term consumption of sunflower and fish oils damages the liver
An international group of scientists led by the University of Granada (UGR) has demonstrated that the long-term intake of sunflower or fish oils damages the liver and can cause a series of alterations in it, giving rise to non-alcoholic steatohepatitis (NASH).
Of the three dietary fats studied (olive, sunflower and fish oil), virgin olive oil was ranked as the dietary fat source that best preserves the liver during the ageing process.
NASH, which causes inflammation of the liver that is not caused by alcohol abuse, is a very serious condition and can act as a catalyst for the onset of other diseases such as cirrhosis and liver cancer. Its prevalence in the general population increases with age: it affects 1% to 3% of children, 5% of teenagers, 18% of those aged between 20 and 40, 39% of those aged between 40 and 50, and more than 40% of those over 70.
The research, recently published in the prestigious Journal of Nutritional Biochemistry, analysed how the long-term consumption of different dietary fat sources such as olive, sunflower and fish oil affects the liver of rats. UGR researchers conducted a series of comprehensive analyses, including studies of pathological anatomy, ultrastructural analyses using electron microscopes, sophisticated bioenergy techniques, telomere length measurements, and oxidative stress. Most importantly, they conducted a comprehensive study of the liver genome in order to establish how it evolved in line with the consumption of the different oils.
As José Luis Quiles Morales, Full Professor of Physiology at the UGR explains: “[the research] demonstrates that fat accumulates in the liver with age, but the most striking finding is that the type of fat accumulated differs depending on the oils consumed and this means that, regardless of this accumulation, some livers age in a healthier way than others and with a greater or lesser predisposition to certain diseases.”
Three dietary fats (virgin olive oil, sunflower oil and fish oils) were studied and virgin olive oil was shown to the best of the three for preserving the liver throughout life. The research also revealed that sunflower oil induced fibrosis, ultrastructural alterations, gene expression blockades and high oxidation. Meanwhile, fish oil intensified oxidation associated with ageing, lowered mitochondrial electron transport chain activity and altered the relative telomere length. Telomeres are the ends of chromosomes, the shortening of which can cause cell ageing and the lengthening of which can cause cancer.
“The alterations caused by the long-term consumption of sunflower and fish oils make the liver susceptible to non-alcoholic steatohepatitis, a very serious disease that may act as a catalyst for other liver diseases such as cirrhosis and liver cancer”, Prof. Quiles notes. In light of the results, he also points out that: “virgin olive oil is the healthiest option, which has already been proven in relation to diverse aspects of health.”
According to Prof. Quiles, the most innovative aspect of this study is “how it reveals the mechanisms by which virgin olive oil provides these benefits and why the over-consumption of other dietary fats is dangerous. We believe that this study will be very useful in preventing and treating diverse liver diseases.”
Researchers from other institutions, such as the Hospital Complex of Jaen, the Marche Polytechnic University (UNIVPM) in Ancona, Italy, the Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research (GENYO) and the National Cancer Institute (NCI) of the United States, have also participated in this research project.
Bibliographical reference: Varela-Lopez A, Pérez-López MP, Ramirez-Tortosa CL, Battino M, Granados-Principal S, Ramirez-Tortosa MDC, Ochoa JJ, Vera-Ramirez L, Giampieri F, Quiles JL. Gene pathways associated with mitochondrial function, oxidative stress and telomere length are differentially expressed in the liver of rats fed lifelong on virgin olive, sunflower or fish oils. Journal of Nutritional Biochemistry. 2017 Sep 20; 52:36-44. doi: 10.1016/j.jnutbio.2017.09.007.
Accepted ManuscriptClinical predictors of liver fibrosis in patients with chronic hepatitis B virus infection from children to adults
Jia-Feng Wu Shih-Hsi Song Chee-Seng Lee Huey-Ling Chen Yen-Hsuan Ni Hong-Yuan Hsu Tzee-Chung Wu Mei-Hwei Chang
Background This study aimed to elucidate predictors of liver fibrosis in chronic hepatitis B virus (HBV)-infected subjects.
Methods Transient elastography was performed to define liver fibrosis in 533 chronic HBV-infected patients at 30.72 ± 0.57 years of age. Protein array was performed on serum samples and lysates of Huh7 cells transfected with HBV mutants; the results were confirmed by ELISA. Single nucleotide polymorphisms in the interleukin-1β gene were examined chronic HBV-infected patients with and without liver fibrosis.
Results Male gender, > 18 years old, and serum alpha-fetoprotein level > 3.6 ng/mL were independent predictors of a liver stiffness measurement of ≥ 7 kPa (P = 0.005, 0.019, and < 0.001, respectively). HBeAg-negative hepatitis is associated with increased liver stiffness (P<0.001). Elevation of serum interleukin-1β was demonstrated in subjects with liver fibrosis. Interleukin-1β was upregulated in Huh7 cells transfected with HBeAg-negative hepatitis-related mutants. The AA genotype at rs16944 and the CC genotype at rs1143627 of the interleukin-1β gene were associated with higher serum interleukin-1β levels and liver fibrosis.
Conclusions Male gender, beyond childhood, elevated alpha-fetoprotein level, and HBeAg-negative hepatitis are risk factors for liver fibrosis. Interleukin-1β is involved in the progression of liver fibrosis in subjects with HBeAg-negative hepatitis.
Evaluation of dried blood spot samples for screening of hepatitis C and human immunodeficiency virus in a real-world setting
Sonia Vázquez-Morón, Pablo Ryan, Beatriz Ardizone-Jiménez, Dolores Martín, Jesus Troya, Guillermo Cuevas, Jorge Valencia, María A. Jimenez-Sousa, Ana Avellón & Salvador Resino
Abstract
Both hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection are underdiagnosed, particularly in low-income countries and in difficult-to-access populations. Our aim was to develop and evaluate a methodology for the detection of HCV and HIV infection based on capillary dry blood spot (DBS) samples taken under real-world conditions. We carried out a cross-sectional study of 139 individuals (31 healthy controls, 68 HCV-monoinfected patients, and 40 HCV/HIV-coinfected patients). ELISA was used for anti-HCV and anti-HIV antibody detection; and SYBR Green RT-PCR was used for HCV-RNA detection. The HIV serological analysis revealed 100% sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The HCV serological analysis revealed a sensitivity of 92.6%, specificity of 100%, PPV of 100%, and NPV of 79.5%. Finally, the HCV-RNA detection test revealed a detection limit of 5 copies/µl with an efficiency of 100% and sensitivity of 99.1%, specificity of 100%, PPV of 100%, and NPV of 96.9%. In conclusion, our methodology was able to detect both HCV infection and HIV infection from the same DBS sample with good diagnostic performance. Screening for HCV and HIV using DBS might be a key strategy in the implementation of national programs for the control of both infections.
Report raises questions about long-term effects of DAAs for HCV The changing HCV treatment cascade Sharing injection paraphernalia does not lead to HCV transmission Women injecting drugs at higher risk for HCV than men IDSA, AASLD critical of Cochrane review of HCV drugs
Global cancer survival rates improve, but wide gaps remain Last Updated: 2018-01-31 By Kate Kelland
LONDON (Reuters) - Cancer patients' survival prospects are improving, even for some of the deadliest types such as lung cancer, but there are huge disparities between countries, particularly for children, according to a study published on Wednesday.
In the most up-to-date study of cancer survival trends - between 2010 and 2014 - covering countries that are home to two-thirds of the world's people, researchers found some significant progress, but also wide variations.
While brain tumor survival in children has improved in many countries, the study showed that for children diagnosed as recently as 2014, five-year survival is twice as high in Denmark and Sweden, at around 80%, as it is in Mexico and Brazil, at less than 40%.
This gap was most likely due to variations in the availability and quality of cancer diagnosis and treatment services, the researchers said.
Abstract
Non-invasive assessment of liver fibrosis has been one of the most rapidly advancing fields in hepatology in the last decade. Progressive liver fibrosis results in cirrhosis, hepatocellular carcinoma (HCC) and various liver-related complications in essentially all chronic liver diseases. Assessment of liver fibrosis allows clinicians to determine the prognosis, need of treatment, disease progression and response to treatment in patients with chronic liver disease. Liver biopsy has been the gold standard in last few decades and most adopted diagnostic tool in clinical trials. Nonetheless, it is impractical to apply the test in a large number of patients or to do it serially. Hence, various non-invasive assessments have been developed and adopted in some international management guidelines. Liver stiffness measurement (LSM) with transient elastography one of the most widely validated non-invasive assessments for liver fibrosis. It is an accurate and reproducible method to predict advanced fibrosis in chronic hepatitis B. Using transient elastography, it is possible to perform repeated liver fibrosis assessments on a large number of asymptomatic patients. The key challenge of his tool is the confounding effect of alanine aminotransferase (ALT) level, such that decrease in LSM may only reflect ALT normalization, hence not accurate enough to indicate regression of liver fibrosis. This may be partially handled by combining LSM with a serum-based formula which is independent of ALT such as the Forns index and Enhanced Liver Fibrosis test. A LSM-based HCC risk score (LSM-HCC score) is useful to prioritize patients for HCC surveillance.
Abstract
Novel direct-acting antivirals (DAAs) are now the standard of care for the management of Hepatitis C virus (HCV) infection. Branded DAAs are associated with high sustained virological response at 12 weeks post-completion of therapy (SVR12), but are costly. We aimed to assess the efficacy of generic oral DAAs in a real life clinical scenario. Consecutive patients with known HCV infection who were treated with generic-oral DAA regimens (May 2015 to January 2017) were included. Demographic details, prior therapy and SVR12 were documented. 490 patients (mean age: 38.9±12.7years) were treated with generic DAAs in the study time period. Their clinical presentations included chronic hepatitis (CHC) in 339 (69.2%) of cases, compensated cirrhosis in 120 (24.48%) cases, and decompensated cirrhosis in 31 (6.32%) cases. Genotype 3 was most common (n=372, 75.9%) followed by genotype 1 (n=97, 19.8%). Treatment naïve and treatment-experienced (defined as having previous treatment with peginterferon and ribavirin) were 432 (88.2%) and 58 (11.8%) respectively. Generic DAA treatment regimens included sofosbuvir in combination with ribavirin (n=175), daclatasvir alone (n=149), ribavirin and peginterferon (n=80), ledipasvir alone (n=43), daclatasvir and ribavirin (n=37), and ledipasvir and ribavirin (n=6). Overall SVR12 was 95.9% (470/490) for all treatment regimens. SVR12 for treatment-naïve and experienced patients was 97.0% (419/432) and 87.9% (51/58) respectively, P=0.005. High SVR12 was observed with various regimens, irrespective of genotype and underlying liver disease status. There were no differences in SVR12 with 12 weeks or 24 weeks therapy. No major adverse event occurred requiring treatment stoppage. Generic oral DAAs are associated with high SVR rates in patients with HCV infection in a real life clinical scenario.
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England could become first country to eradicate Hepatitis C in 2025
England could be the first country in the world to eliminate Hepatitis C, under ambitious plans announced by the NHS today.
NHS leaders today called on the pharmaceutical industry to work with them to provide best value for money for treatments so that in its 70th year, the NHS can commit to eliminating Hepatitis C in England at least five years earlier than the World Health Organisation goal of 2030.
Hepatitis C is currently a significant public health issue globally, accounting for around 400,000 deaths per year. Most recent figures show that Hepatitis C is affecting 160,000 people in England.
The NHS has invested in Hepatitis C treatment each year as new treatments became available to improve outcomes for people with the virus but doctors, patient groups and NHS leaders believe it is possible to go further and is encouraging pharma companies to work with them to meet this more ambitious target.
The next round of procurement, which launches in February, is the single largest medicines procurement ever done by the NHS, and NHS England expects to see more new treatments curing even more patients by October. Over 25,000 patients have already been treated to date and this number is expected to rise to 30,000 later this year, prioritising the sickest patients first.
Part of the new agreements between NHS England and drug companies will involve collaboration to identify more people who are living with Hepatitis C who need to be treated. Experts have predicted that this approach, combined with the NHS sustaining the same level of investment and the best new treatments being used could undoubtedly lead to Hepatitis C being eradicated as a major public health concern in the very near future.
England is one of few countries in Europe where numbers of patients receiving new oral treatments for Hepatitis C are already increasing year on year, enabled by deals previously agreed with industry. The deals, including ‘pay per cure’ where the NHS only pays when a patient is cured and a focus on prioritising the sickest patients, have led to a 10% reduction in the number of deaths and the numbers of patients needing a liver transplant have reduced by 50%.
Further progress to date in the treatment of Hepatitis C includes:
The creation of 22 ‘operational delivery networks’ in each area in England – driving improvements in treatment in local areas, ensuring all patients can access the treatment they need, regardless of where they live. This will enable improvements in areas with historically low service provision.
In 2017 a National Hepatitis C patient registry was established – making it possible to record and monitor treatment uptake, outcomes and increased diagnosis rates in real time.
Professor Graham Foster, National Clinical Chair for Hepatitis C, NHS England, said:
“The progress made in the treatment of Hepatitis C has transformed the lives of many of my patients and has been made possible by NHS England working closely with industry to bring prices down and expand treatment options. Yet we have the opportunity to do so much more. Over the last seven decades, the NHS has been at the forefront of medical innovation – to be able to commit to a world first in the year of the NHS’ 70th anniversary would be another remarkable and truly historic achievement.”
Peter Huskinson, National Commercial Director, NHS England, said:
“The NHS has made major headway in the last three years in the treatment of Hepatitis C, which has enabled a once in a generation opportunity to eliminate a major disease. With the right response from pharma companies in the coming months, we can strike the most competitive deal possible – improving the future for patients with Hep C alongside securing the best value for money for taxpayers.”
Charles Gore, CEO of The Hepatitis C Trust, the national Hepatitis C charity, said:
“This is wonderful news. It is exactly what is needed. The proposed deal will galvanise the action we must take to find all those living with Hepatitis C who have not yet been diagnosed so that we can cure them. It will prevent the liver cancer that Hepatitis C causes. It will save lives. In the current environment we applaud NHS England’s ambition to be a world leader.”
Judi Rhys, Chief Executive of the British Liver Trust, said:
“We are delighted that NHS England are playing a leading role in tackling Hepatitis C and eliminating this deadly virus. A key challenge will be the fact that hep C often has no symptoms in the early stages and it is thought that less than half of those living with the virus have been diagnosed. It is therefore vital that anyone who is at risk asks to be tested.”
ORIGINAL ARTICLE
Hepatitis C virus re-treatment in the era of direct-acting antivirals: projections in the USA
Authors
J. Chhatwal,
Q. Chen,
T. Ayer,
E. D. Bethea,
F. Kanwal,
K. V. Kowdley,
X. Wang,
M. S. Roberts,
S. C. Gordon
First published: 29 January 2018
Summary Background
The introduction of oral direct-acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment. However, a small percentage of patients fail to achieve sustained virologic response (SVR). Understanding the number of people who fail on DAAs and require re-treatment is important for budget impact and disease burden projections.
Aim
To quantify the number of HCV patients who fail to achieve SVR on oral DAAs (NS5A vs. non-NS5A) and require re-treatment.
Methods
We used a mathematical model to simulate clinical management of HCV in the USA, which included the implementation of HCV screening, treatment, and disease progression. We simulated different waves of DAA treatment and used real-world data to extract SVR rates and market shares of available therapies.
Results
Our model projected that the number of people living without viraemia (i.e. cured) would increase from 0.70 million in 2014 to 1.78 million by 2020. Between 2014 and 2020, 1.50 million people would receive treatment with DAAs, of whom 124 000 (8.3%) are projected to fail to achieve SVR. Among those treatment failures, 66 600 (53.7%) patients would fail treatment with NS5A inhibitors and 69 600 (56.1%) would have cirrhosis. During the same period, 34 200 people would progress to decompensated cirrhosis and 27 300 would develop hepatocellular carcinoma after failing to achieve SVR.
Conclusions
Even in the era of highly effective DAAs, a significant number of patients will fail to achieve SVR and will require re-treatment options. Timely and effective re-treatment is essential to prevent the long-term sequelae of HCV.
The availability of well-tolerated and highly effective DAAs offers a new hope to eliminate HCV as a public health threat. However, even with the newer generations of DAAs, a small proportion of patients will fail to achieve SVR and could develop advanced sequelae such as decompensated cirrhosis and HCC. In this study, we simulated the current clinical landscape of HCV treatment and projected the number of patients in the USA who would receive treatment, achieve SVR, or require re-treatment. We found that in the era of DAAs, a total of 1.50 million people would receive treatment between 2014 and 2020 and around 124 000 (8.3%) would fail to achieve SVR; the majority of those who fail treatment would have been exposed to NS5A inhibitors. Timely and effective retreatment of these patients could prevent the long-term sequelae of HCV.
Earlier studies have estimated the number of patients who would remain viraemic in the era of DAAs,[6] and projected disease burden under different screening and treatment scenarios.[5, 6, 25, 26] This study adds new information by estimating the number of patients who would fail to achieve SVR, especially with NS5A inhibitors, and require retreatment in the era of DAAs. Providing this data allows payers to assess the budget impact of HCV treatment and disease burden projections. Although the DAAs have been shown to be cost-effective/saving,[27, 28] budget needed to treat all HCV patients remains challenging in some settings.[29]
We observed that under current clinical practice, the number of patients receiving treatment would drop to 61 000 by 2020 in spite of the fact that around 844 000 patients would still be viraemic in that year. This is because the majority of viraemic patients aware of their status would have received treatment by this time, whereas, those unaware of their HCV status would not be able to avail the benefits of DAA therapy. This finding emphasises the need to update the current screening policies to diagnose patients who otherwise would remain unaware and untreated. In addition, there is a need to remove treatment barriers for patients who are already aware of their HCV status but not yet linked to care, such as many injection drug users and people in prisons.
National and global health policy initiatives have stressed the desirability of eliminating HCV as a public health threat by 2030. To achieve this goal, a comprehensive strategy of patient identification, linkage to care and treatment access is required.[30] In addition, the availability of effective treatment options for patients who fail to achieve SVR after initial therapy is necessary. Although the number of such patients is relatively small compared with the current burden of HCV, these patients could become a nonsignificant portion of the viraemic population in the future. Successful retreatment of these patients, who are already linked to care, could reduce the risk of long-term clinical sequelae. While viral clearance would prevent development of advanced sequelae from chronic HCV, other external factors such as abuse of alcohol or drugs would also need to be addressed via appropriate interventions to achieve the full benefits of viral clearance with DAA therapy.
Our study also shows a growing population of patients alive following HCV cure. As this patient population increases, disease management efforts focused on regular surveillance of persons with pre-treatment advanced fibrosis or cirrhosis is important, as they remain at risk of developing hepatocellular carcinoma.[31] In addition, the burden of management for these patients may also shift from specialists to general practitioners. If this transition does take place, future efforts should also focus on increasing the awareness among general practitioners and internists regarding appropriate medical care for patients cured of HCV.
This modelling-based study has some limitations. First, the analysis only included non-institutionalised HCV-infected persons as estimated by the NHANES studies. Therefore, our results likely underestimated the number of viraemic patients. Secondly, recent data suggest that the uptake of birth-cohort screening in practice remains low, therefore, our model may have over-estimated the number of patients who would become aware of their HCV status. Thirdly, we did not include in the model HIV-HCV co-infection, which is beyond the scope of the current work. Fourth, we did not consider the possibility of regression of fibrosis after SVR, which is unlikely to effect the results presented in this study. Finally, we made assumptions about future treatment capacity, which could vary over time.
In conclusion, we found that even in the era of highly effective DAAs, there are still going to be challenges. To achieve HCV elimination a national strategy will need to support the development of systems aimed at increasing the diagnosis of HCV and plans outlining the effective and timely retreatment of patients who have failed on DAAs.
BMJ Open. 2018 Jan 26;8(1):e017412. doi: 10.1136/bmjopen-2017-017412.
Impact of hepatitis C virus infection on long-term mortality after acute myocardial infarction: a nationwide population-based, propensity-matched cohort study in Taiwan. Kuo SH1, Hung WT1, Tang PL1, Huang WC1,2,3, Yang JS2, Lin HC1, Mar GY1, Chang HT1, Liu CP1,3.
Myocardial infarction , commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle.
Abstract INTRODUCTION: The influence of hepatitis C virus (HCV) infection on long-term outcomes of patients with acute myocardial infarction (AMI) is unclear. Therefore, this study aimed to analyse the impact of HCV infection on 12-year mortality rates after AMI using data from the Taiwan National Health Insurance Research Database (NHIRD).
METHODS: NHIRD data for approximately 23 000 000 patients between January 2000 and December 2012 were analysed. A total of 186 112 cases of first AMI admission were identified. A total of 4659 patients with HCV infection not receiving interferon therapy were enrolled and divided into those with (n=107) or without (n=4552) cirrhosis. Using one-to-one matching, 4552 matched controls were included in the final analysis.
RESULTS: The 12-year mortality rate was significantly higher in patients with AMI with HCV infection and cirrhosis than in those with HCV infection but without cirrhosis (P<0.0001) or controls (P<0.0001). Patients with HCV infection but without cirrhosis had significantly higher long-term mortality rates than the matched controls (P<0.0001). The HR for mortality was higher in patients with HCV infection (HR 1.12; 95% CI 1.06 to 1.18). HCV influenced outcomes among the subgroups of patients who were male (HR 1.15) and those who had hypertension (HR 1.14).
CONCLUSIONS: HCV infection influenced the 12-year mortality rates of patients with AMI, especially those who were male and those who had hypertension. Cirrhosis further increased the long-term mortality rates of patients with AMI with HCV infection.
World J Hepatol. Jan 27, 2018; 10(1): 88-94 Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.88
Efficacy of direct-acting antiviral treatment for chronic hepatitis C: A single hospital experience Rena Kaneko, Natsuko Nakazaki, Risa Omori, Yuichiro Yano, Masazumi Ogawa, Yuzuru Sato
Abstract
AIM To evaluate the efficacy of direct-acting antivirals (DAAs) in Kanto Rosai Hospital.
METHODS All patients with hepatitis C virus (HCV) who underwent DAA prescription were enrolled in this study. The present study was a single center retrospective analysis using patients infected with HCV genotype 1 or 2. Resistance analysis was performed by using direct sequencing and cycleave PCR in genotype 1 patients treated with interferon (IFN)-free DAA. The primary endpoint was sustained virologic response at 12 wk after therapy (SVR12).
RESULTS A total of 117 patients participated in the study, including 135 with genotype 1 and 42 with genotype 2. Of the 135 patients with genotype 1, 16 received protease inhibitor + IFN + ribavirin and all achieved SVR. Of the 119 patients who received IFN-free DAA (in different combinations), 102 achieved SVR and 9 failed (7/9 were on daclatasvir/asunaprevir and 2/9 on ledipasvir/sofosbuvir). Efficacy analysis was done only for 43 patients who received daclatasvir/asunaprevir. From this analysis, Y93 resistance-associated substitutions were significantly correlated with SVR.
CONCLUSION The SVR rate was 98% for genotype 1 and 100% for genotype 2. However, caution is needed for HCV NS5A resistance-associated substitutions that are selected by HCV NS5A inhibitors because cerebrovascular adverse events are induced by some DAA drugs.
Key Words: Resistance-associated substitutions, Direct-acting antivirals, Sustained viral response, Hepatitis C Core tip: Direct-acting antivirals have been approved for the treatment of hepatitis C virus (HCV) genotype 1 and 2 infections in Japan since 2011. In the new era of DAA therapy, predictors who fail to respond to DAA might be compromised by resistance-associated substitutions. There have been few reports of daclatasvir/asunaprevir failure because daclatasvir/asunaprevir is limited in Japan. Therefore, it might be important to report these cases for future research and treatment of HCV.
Vitamin D deficiency and hepatitis viruses-associated liver diseases: A literature review
Nghiem Xuan Hoan, Hoang Van Tong, Le Huu Song, Christian G Meyer, Thirumalaisamy P Velavan
Core tip: Vitamin D deficiency is common and associated with chronic liver diseases. Several studies have ascribed a strong association of vitamin D insufficiency with unfavorable clinical courses and progression of liver disease in hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. However, any causal relation is so far not fully understood. In addition, there are inconsistent results with regard to the impact of vitamin D supplementation on the virological response to IFN-based therapy; this applies particularly to HCV infections. The present review addresses general aspects of vitamin D deficiency and focuses on its association with HBV and HCV infection. Furthermore, the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients are reviewed.
Welcome, sit back and catch up on notable research articles and blog updates on the topic of viral hepatitis. However, we begin with updates on this year's flu season, with experts reporting it's the worst in nearly a decade.
A Look At The Most Intense Flu Season In Years
CDC
Keep up with the latest flu news as it is posted on the CDC's website.
We called this briefing to get you the latest FluView numbers and to provide advice on preventing the flu and information about what people can do to reduce the risk of flu or serious illness.
Listen here The American Council on Science and Health
This Year's Flu Is Different - It Kills In Two Ways Jan 29, 2018 It is the 100th anniversary of the 1918 Spanish flu (1,2) pandemic, and the date is not the only similarity between the two. While it is impossible that the morbidity and mortality that is being caused by this year's H3N2 strain (3) will even approach that of the monster that infected 5% of the world, killing 2% of it, there is one troubling feature that this year's strain shares with its centennial cousin. Flu typically kills because of secondary infections, usually pneumonia. While both "18s" do this, they also kill people directly. This is the scary part. The latter is mercifully rare but it dominates the news. Children seem to be more susceptible rapid deaths. Cases have been recently reported in Florida, California, and Connecticut. And it may be growing, especially as new strains emerge (4). The cause of fast deaths is very different from that normally seen in flu death. It is more insidious, harder to prevent and can nothing can be done about it. One hundred years ago there were reports of people dying within hours of becoming ill.
Patients who had a positive laboratory test for influenza were six times as likely to be hospitalized for acute myocardial infarction during the 7 days after specimen collection (the “risk interval”) as during the year before and the year after the risk interval.
Rob Stein
The flu is hitting the 65-and-over age group hardest, but the next-hardest hit is the 50-to-64 age group. Usually, children are the second-hardest hit. The reason is unclear. Jernigan says it may be because the strains of the flu to which baby boomers were exposed when they were young are different from the strains circulating this year, so they have less immunity.
“We often see different parts of the country light up at different times, but for the past three weeks the entire country has been experiencing lots of flu, all at the same time,” he said, adding: “We have several weeks to go.”
NBC News Virus looks like flu, acts like flu, but it's not influenza
by Maggie Fox
Jan.28.2018
There’s another virus out there that could be adding to the seasonal misery, but it’s not being identified. The virus is called adenovirus, and it can cause very severe flu-like symptoms. It’s so risky that the U.S. military vaccinates recruits against two major strains.
In The News England could become first country to eradicate Hepatitis C in 2025
Jan 29, 2018
NHS leaders today called on the pharmaceutical industry to work with them to provide best value for money for treatments so that in its 70th year, the NHS can commit to eliminating Hepatitis C in England at least five years earlier than the World Health Organisation goal of 2030.
HepCBC
Read today's news or check out the latest issue of Weekly Bull.
CDEC Recommends MAVIRET™ and VOSEVI™ for Reimbursement for Chronic HCV January 27, 2018
On January 25, 2018 the federal CADTH Canadian Drug Expert Committee (CDEC) released its extensive reviews of two new "pan-genotypic" hepatitis C treatments: Maviret™ (AbbVie) and Vosevi™ (Gilead). In both cases, the drugs were recommended for reimbursement by provincial PharmaCares for "adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection with or without compensated cirrhosis." And, for both, reimburseme...
Treating Genotype 1-6 HCV Treatment: Incorporating Glecaprevir/Pibrentasvir and sofosbuvir/Velpatasvir/Voxilaprevir Into Clinical Practice
This 15-minute activity features a brief video introduction by faculty expert Dr. Muir in which he discusses how the new combination therapies glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir have changed the treatment landscape. The activity then continues with a text-based review of the recent advances in direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) and the clinical trials that led to the approval of these new agents.
Free registration is required
Journal Updates Journal: Alimentary Pharmacology and Therapeutics Hepatitis C virus re-treatment in the era of direct-acting antivirals: projections in the USA
The introduction of oral direct-acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment. However, a small percentage of patients fail to achieve sustained virologic response (SVR). Understanding the number of people who fail on DAAs and require re-treatment is important for budget impact and disease burden projections.
This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBV- and HCV-related chronic liver diseases. Furthermore, current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.
Direct-acting antivirals have been approved for the treatment of hepatitis C virus (HCV) genotype 1 and 2 infections in Japan since 2011. In the new era of DAA therapy, predictors who fail to respond to DAA might be compromised by resistance-associated substitutions. There have been few reports of daclatasvir/asunaprevir failure because daclatasvir/asunaprevir is limited in Japan. Therefore, it might be important to report these cases for future research and treatment of HCV.
The following articles downloaded and shared by @HenryEChang via Twitter
NVHR and the Center for Health Law Policy and Innovation at Harvard Law co-hosted this webinar on highlights from the "Hepatitis C: State of Medicaid Access" report, including methodology and key findings.
The new report found that the number of inpatient hospital stays for patients seeking treatment solely for hepatitis C rose by nearly 49% from 2005 to 2014. In addition, hospital stays for hepatitis C patients also seeking treatment for hepatitis B, HIV, or alcoholic liver disease rose by about 11%. Overall, adults ages 52 to 72 years saw a more than 67% increase in hepatitis C-related hospitalizations –the most of any age group –while those ages 18 to 51 years saw a nearly 15% decrease in hospitalizations. Hospital stays involving hepatitis C were also longer, more expensive, and more likely to result in death than stays that did not involve hepatitis C.
By Kimberly Morgan Bossley - January 26, 2018
After curing hep C in 2014 many things changed in my life. I sold off half of my company and took the other with me and put in my home. After bringing the...
By Karen Hoyt - January 25, 2018
After years of living with hepatitis C, I was very sick. My husband gave up on my low-energy self. He was about done with having a brain foggy wife. Within months of...
By Daryl Luster - January 24, 2018
It has become evident to me that there are people who are treating their hep C with drugs that they purchase from countries where generic drugs are produced. These drugs are produced...
Growing up with Hep C colors the world very differently. Because I knew early, I avoided alcohol from the get-go. I’d like to think it allowed my liver to keep going to thirty. My biggest fear wasn’t dying, but accidentally infecting someone else. Over time I found my paranoia getting the better of me. I abhorred physical contact, because it added to the layered stress of social interaction. Having notified the school of my condition I was kept out of PE. I wasn’t shy about the topic, and the stigma merely fueled my rebellious teenage self. I clung to that rage, it felt justified, but often when we’re young we misidentify the real emotions at play.
So you heard the flu shot is 10 percent effective. With so many sources of information available, the primary care provider’s role increasingly becomes that of educator. It is important to me that the parents of my patients make informed decisions, so when I have a parent decline the influenza vaccine, I make an effort to ask why. The number one response I hear has been “What’s the point? The flu ...
Why herbal supplements taken with prescription drugs may be risky
Recommended Reading
Herbal Supplements May Be Dangerous When You Take Certain Prescription Drugs
By Amanda MacMillan
January 24, 2018
A number of common herbal supplements, including green tea and Ginkgo biloba, can interact with prescription medications, according to a new research review published in the British Journal of Clinical Pharmacology. These interactions can make drugs less effective—and may even be dangerous or deadly.
The new review analyzed 49 case reports of adverse drug reactions, along with two observational studies. Most people in the analysis were being treated for heart disease, cancer or kidney transplants, and were taking warfarin, statins, chemotherapy drugs or immunosuppressants. Some also had depression, anxiety or neurological disorders, and were being treated with antidepressant, antipsychotic or anticonvulsant medications.
Hepatitis C can damage the liver and lead to cirrhosis, or scarring of the liver. Damage to the liver may mean that a person needs to modify their diet.
Rob Stein The flu is hitting the 65-and-over age group hardest, but the next-hardest hit is the 50-to-64 age group. Usually, children are the second-hardest hit.
The reason is unclear. Jernigan says it may be because the strains of the flu to which baby boomers were exposed when they were young are different from the strains circulating this year, so they have less immunity.
Children are being affected, though. Seven more pediatric deaths from the flu were reported this week, bringing that total to 37.
Glecaprevir–Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection
Stefan Zeuzem, M.D., Graham R. Foster, Ph.D., Stanley Wang, M.D., Armen Asatryan, M.D., Edward Gane, M.D., Jordan J. Feld, M.D., M.P.H., Tarik Asselah, M.D., Ph.D., Marc Bourlière, M.D., Peter J. Ruane, M.D., Heiner Wedemeyer, M.D., Stanislas Pol, Ph.D., Robert Flisiak, M.D., Ph.D., Fred Poordad, M.D., Wan-Long Chuang, M.D., Ph.D., Catherine A. Stedman, M.B., Ch.B., Ph.D., Steven Flamm, M.D., Paul Kwo, M.D., Gregory J. Dore, Ph.D., M.P.H., Gladys Sepulveda-Arzola, M.D., Stuart K. Roberts, M.D., Ruth Soto-Malave, M.D., Kelly Kaita, M.D., Massimo Puoti, M.D., John Vierling, M.D., Edward Tam, M.D., Hugo E. Vargas, M.D., Rafi Bruck, M.D., Francisco Fuster, M.D., Seung-Woon Paik, M.D., Franco Felizarta, M.D., Jens Kort, M.D., Ph.D., Bo Fu, Ph.D., Ran Liu, Ph.D., Teresa I. Ng, Ph.D., Tami Pilot-Matias, Ph.D., Chih-Wei Lin, Ph.D., Roger Trinh, M.D., M.P.H, and Federico J. Mensa, M.D.et al.
Article shared and downloaded via Twitter by Henry E. Chang
Abstract
Background
Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection.
Methods
We conducted two phase 3, randomized, open-label, multicenter trials. Patients with genotype 1 infection were randomly assigned in a 1:1 ratio to receive once-daily glecaprevir–pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either glecaprevir–pibrentasvir or sofosbuvir–daclatasvir. Additional patients with genotype 3 infection were subsequently enrolled and nonrandomly assigned to receive 8 weeks of treatment with glecaprevir–pibrentasvir. The primary end point was the rate of sustained virologic response 12 weeks after the end of treatment.
Results
In total, 1208 patients were treated. The rate of sustained virologic response at 12 weeks among genotype 1–infected patients was 99.1% (95% confidence interval [CI], 98 to 100) in the 8-week group and 99.7% (95% CI, 99 to 100) in the 12-week group. Genotype 3–infected patients who were treated for 12 weeks had a rate of sustained virologic response at 12 weeks of 95% (95% CI, 93 to 98; 222 of 233 patients) with glecaprevir–pibrentasvir and 97% (95% CI, 93 to 99.9; 111 of 115) with sofosbuvir–daclatasvir; 8 weeks of treatment with glecaprevir–pibrentasvir yielded a rate of 95% (95% CI, 91 to 98; 149 of 157 patients). Adverse events led to discontinuation of treatment in no more than 1% of patients in any treatment group.
Conclusions
Once-daily treatment with glecaprevir–pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157.)
A number of common herbal supplements, including green tea and Ginkgo biloba, can interact with prescription medications, according to a new research review published in the British Journal of Clinical Pharmacology. These interactions can make drugs less effective—and may even be dangerous or deadly.
The new review analyzed 49 case reports of adverse drug reactions, along with two observational studies. Most people in the analysis were being treated for heart disease, cancer or kidney transplants, and were taking warfarin, statins, chemotherapy drugs or immunosuppressants. Some also had depression, anxiety or neurological disorders, and were being treated with antidepressant, antipsychotic or anticonvulsant medications.
Resources are required to support increased testing and treatment of hepatitis C in the community as significant numbers of patients are not presenting for hospital-based care, heard a recent seminar in Dublin organized by the Hepatitis C Partnership. Catherine Reilly reports.
Since 2015, DAAs have been accorded an annual budget of €30 million under the HSE National Hepatitis C Treatment Programme (NHCTP). But clinicians and community stakeholders are fervently calling for better-resourced outreach and support, as well as testing and care in community settings. They strongly believe there are significant numbers of unidentified progressive cases among the populations primarily affected by hepatitis C, ie, former and current injecting drug-users, which are hard-to-reach groups.
Abstract
Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.
Core tip: Optimal timing of antiviral therapy for hepatitis C virus (HCV) infection in liver transplant candidates using second generation direct-acting antivirals is debated. Available evidence lacks conviction if the viral eradication is beneficial in all HCV patients before liver transplantation. We aim to review the current literature to better delineate the appropriate timing of HCV treatment in the era of direct-acting antiviral agents.
Treating Insulin Resistance in Hepatitis C-Infected Patients With Diabetes
Elizabeth Kukielka, PharmD
Publish Date: Wednesday, January 24, 2018
Both insulin resistance (IR) and type 2 diabetes mellitus (T2DM) are more prevalent in patients with chronic hepatitis C virus (HCV) infection compared with the general population.
As this is one of the first studies to demonstrate the benefit of treating HCV-positive patients who also have IR with both standard HCV therapy and metformin to achieve SVR, more studies are needed to confirm the results and help determine a standard regimen for patients with HCV and IR, researchers noted.
Article in Press Hepatitis B Virus Infection and Hepatitis C Virus Treatment in a Large Cohort of Hepatitis C–Infected Patients in the United States
Anne C. Moorman, Jian Xing
ia
Loralee B. Rupp, Stuart C. Gordon
Philip R. Spradling
Joseph A. Boscarino
Mark A. Schmidt
Yihe G. Daida
Kaiser
Eyasu H. Teshale, Scott D. Holmberg
The rare emergence of hepatitis B virus (HBV) reactivation among hepatitis C virus (HCV)-infected patients receiving direct-acting antiviral (DAA) therapy raises questions about how many HCV-infected patients have active, past, or latent/occult HBV co-infection, and their DAA treatment experience1–3 We sought to characterize these factors, including possible post-DAA reactivation, among HCV patients in the Chronic Hepatitis Cohort Study (CHeCS), a “dynamic” observational study conducted at 4 large integrated U.S.
Abstract
Background
Hepatitis C virus (HCV) is the most burdensome infectious illness in Canada. Current screening strategies miss a significant proportion of cases, leaving many undiagnosed. Elevated HCV prevalence in those born between 1945 and 1965 has prompted calls for birth-cohort screening in this group. However, Canada lacks population-level data to support this recommendation. We performed a serosurvey to obtain population-based HCV prevalence estimates in Ontario residents born between 1945–1974, to generate evidence for birth-cohort screening recommendations.
Methods
We tested anonymized residual sera in five-year age-sex bands from Ontario for anti-HCV antibody. We performed descriptive epidemiological analysis and used a logistic regression model to determine HCV risk-factors.
Results
Of 10,006 sera analyzed, 155 (1.55%, 95% confidence interval (CI) 1.32, 1.81) were positive for HCV antibody. Individuals born between 1950–1964 had a significantly higher combined prevalence of 1.92% (95% CI 1.56, 2.34) compared to 1.14% (95% CI 0.69, 1.77) (p = 0.04) for those born between 1970–1974. For males, comprising 107/155 (69.03%) of positive samples, the highest prevalence was 3.00% (95% CI 1.95, 4.39) for the 1960–1964 birth-cohort. For females, the highest prevalence was 1.56% (95% CI 0.83, 2.65) for those born between 1955–1959. Male sex was significantly associated with positive HCV serostatus.
Interpretation
HCV prevalence in Ontario is highest among those in this birth cohort, and higher than previous estimates. The prevalence estimates presented in our study provide important data to underpin birth-cohort screening recommendations.
Diagnosing Frailty in Patients With Cirrhosis Frailty also increases the risk for morbidity and mortality in patients with chronic liver disease.[6,7] Sarcopenia (loss of muscle mass) and frailty may not directly correlate with the clinical severity of liver disease, and must be carefully sought to establish the diagnosis.[6]
Using observation alone to diagnose frailty in patients with end-stage liver disease is inadequate, because frailty may not be recognized by clinicians until late in the course of disease or simply be overlooked in well-groomed patients, some women, and those with obesity. Using body mass index as an indicator of malnutrition and frailty can be deceptive, because it fails to consider the functional issues of frailty. Multiple clinical measures of frailty have been published using a combination of findings, such as unintentional weight loss, reduced walking or gait speed, muscle weakness, and evidence of reduced physical activity.[1,2,7,8]
COMMENTARY
Co-managing HIV, Hepatitis C, and Opioid Abuse
Naveed Saleh, MD, MS
January 23, 2018
Infection and Opioids
Effective antiretroviral treatments for HIV and hepatitis C exist and are widely available. In fact, treatment for hepatitis C is curative, which hardly seemed imaginable only a few short years ago. But despite there being effective treatments for these diseases, barriers exist that make their treatment difficult. Chief among these barriers is intravenous use of opioids.
The stark reality is that people with hepatitis C or HIV, or both diseases, are much more likely to die of drug overdose than of chronic illness itself. Furthermore, according to the Centers for Disease Control and Prevention, in 2014 death from drug overdose was more common than death caused by motor vehicle accidents or firearms. Of note, 80% of people who inject drugs and are HIV-positive also have hepatitis C.
At IDWeek 2017, managing infectious disease in opioid users was an important topic of coverage. In a lecture titled "Co-management of Opioid Treatment, HIV, and Hepatitis C Treatment," Brianna Norton, DO, MPH, an assistant professor of infectious disease and internal medicine at the Albert Einstein College of Medicine, discussed evidence-based approaches to treating opioid use disorder in patients with HIV and hepatitis C.
