Thursday, November 30, 2017

Drug-drug interactions in hepatitis C virus treatment: Do they really matter?

Clinical Liver Disease
Clinical Liver Disease is an official digital educational learning resource from the American Association for the Study of Liver Diseases. Visitors are able to view videos, access full text articles, and download files in either HTML or PDF formats.

November 2017 Volume 10, Issue 5 Pages 107–133

Controversies in HCV Management
Drug-drug interactions in hepatitis C virus treatment: Do they really matter? (pages 111–115)
Aijaz Ahmed, Glen A. Lutchman and Paul Y. Kwo
Version of Record online: 30 NOV 2017 | DOI: 10.1002/cld.668

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Clinical Liver Disease

Wednesday, November 29, 2017

Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt

Alimentary Pharmacology and Therapeutics - November 29, 2017

Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt
H. Omar, W. El Akel, T. Elbaz, M. El Kassas, K. Elsaeed, H. El Shazly, M. Said, M. Yousif, A. A. Gomaa, A. Nasr, M. AbdAllah, M. Korany, S. A. Ismail, M. K. Shaker, W. Doss, G. Esmat, I. Waked, Y. El Shazly

Treatment of chronic hepatitis C using combination of sofosbuvir (SOF) and daclatasvir (DCV) was used in several clinical trials and multicentre studies, which were somewhat limited to genotypes 1-3. The national program in Egypt is using SOF-DCV combination for large scale treatment.

To assess the efficacy and safety of combined SOF-DCV in treating patients with HCV-G4 in a real-world setting.

Data and outcome of chronic HCV patients who were treated for 12 weeks with generic medications: DCV 60 mg plus SOF 400 mg ± ribavirin (RBV) within the national hepatitis C treatment program in Egypt are presented. Treatment-naïve patients without cirrhosis were treated without RBV, and those who had cirrhosis or were treatment-experienced (interferon experienced or SOF experienced) received RBV. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored.

During the first 2 months of the programme, 18 378 patients with HCV-G4 started treatment with SOF-DCV with or without RBV. Overall, 95.1% achieved SVR12 (95.4% among patients treated without RBV and 94.7% for patients treated with RBV, P = .32). Treatment was prematurely discontinued in only 1.5% of patients. The most common events leading to discontinuation were patient withdrawal (n = 76) and pregnancy (n = 5). Five deaths occurred within this group.

Real-world experience of generic SOF-DCV in patients with chronic HCV-G4 proved to be safe and associated with a high SVR12 rate, in patients with different stages of fibrosis.

HCC in Chronic HBV vs Chronic HCV After Virologic Response

Does the achievement of virologic response modify the risk of hepatocellular carcinoma differently in patients with chronic hepatitis B as compared to those with chronic hepatitis C?

J Viral Hepat. 2017;24(11):990-997. 
Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis B vs Chronic Hepatitis C After Achievement of Virologic Response
G.-A. Kim

Full Text

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg-interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow-up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30–3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg-interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.

Tuesday, November 28, 2017

Critical link between obesity and diabetes has been identified

Critical link between obesity and diabetes has been identified

DALLAS - Nov. 28, 2017 - UT Southwestern researchers have identified a major mechanism by which obesity causes type 2 diabetes, which is a common complication of being overweight that afflicts more than 30 million Americans and over 400 million people worldwide.

Researchers found that in obesity, insulin released into the blood by the pancreas is unable to pass through the cells that form the inner lining of blood vessels. As a result, insulin is not delivered to the muscles, where it usually stimulates most of the body's glucose to be metabolized. Blood glucose levels rise, leading to diabetes and its related cardiovascular, kidney and vision problems, said Dr. Philip Shaul, Director of the Center for Pulmonary and Vascular Biology in the Department of Pediatrics at UT Southwestern.

"It was totally unpredicted that a major problem in obesity is the delivery of circulating insulin to your muscle. It was even more surprising that this problem involves immunoglobulins, which are the proteins that make up circulating antibodies," said Dr. Chieko Mineo, Associate Professor of Pediatrics, who is a co-senior author on the report with Dr. Shaul.

The researchers found that obese mice have an unexpected chemical change in their immunoglobulins. "The abnormal immunoglobulins then act on cells lining blood vessels to inhibit an enzyme needed to transfer insulin from the bloodstream into the muscle," said Dr. Shaul, who holds the Associates First Capital Corporation Distinguished Chair in Pediatrics. "Type 2 diabetes patients have the same chemical change, and if we give a mouse immunoglobulins from a type 2 diabetic individual, the mouse becomes diabetic."

The findings reported in The Journal of Clinical Investigation may lead to new tools for diabetes risk screening and new avenues for diabetes prevention or treatment. The researchers identified an agent that they could administer to mice that prevents the chemical change in immunoglobulins that occurs with obesity and preserves healthy glucose status. The researchers plan to test this strategy in humans in the near future.

Funding for the study came from the American Diabetes Association, the American Heart Association, The Hartwell Foundation, the Cancer Prevention and Research Institute of Texas (CPRIT) and the National Institutes of Health (NIH). Further research on both adults and children is under way with support from The Hartwell Foundation and the National Institutes of Health.

Other researchers involved were Dr. Keiji Tanigaki, senior research scientist and first author; Dr. Wanpen Vongpatanasin, Director of the Hypertension Section and holder of the Norman and Audrey Kaplan Chair in Hypertension Research at UT Southwestern; Dr. Jennifer Kohler, Associate Professor of Biochemistry; Dr. William Holland, Assistant Professor of Internal Medicine in the Touchstone Diabetes Center at UT Southwestern; and collaborators from the University of Texas at Dallas, University of Alabama, University of Georgia, and Imperial College London.

Monday, November 27, 2017

Listen To The Health Report - Non-alcoholic fatty liver disease & the brain

Today on Health Report, a radio program based in Australia, host Norman Swan interviews Sudha Seshadri, lead author of a study investigating an association between non-alcoholic fatty liver disease with total brain size. The program clearly points out what you need to know about fatty liver disease, very interesting.
Listen here...

Program Summary
November 27, 2017
Fatty liver disease and your overall brain volume
When fat's deposited in the liver, it triggers metabolic changes — and the brain's not immune from those changes, as a new study indicates.

In the research, non-alcoholic fatty liver disease was associated with a reduction in total brain volume. That could have implications for your risk of stroke or dementia.
Listen here...

Related On This Blog
"Fatty liver can be prevented by conducting appropriate lifestyle and diet," Weinstein added. "In turn, if one retains a healthy liver, his/her risk for other diseases, such as diabetes and heart diseases, is also reduced. In this study, we show that keeping a healthy liver may also be linked with a healthier brain."

Dramatic response of HCV patients with genotype 3 to sofosbuvir-based therapies in Punjab, Pakistan: A prospective study

World J Gastroenterol. Nov 28, 2017; 23(44): 7899-7905
Published online Nov 28, 2017. doi: 10.3748/wjg.v23.i44.7899

Dramatic response of hepatitis C patients chronically infected with hepatitis C virus genotype 3 to sofosbuvir-based therapies in Punjab, Pakistan: A prospective study
Sajjad Iqbal, Muhammad Haroon Yousuf, Muhammad Iftikhar Yousaf

Received: June 12, 2017
Peer-review started: July 12, 2017
First decision: August 10, 2017
Revised: September 6, 2017
Accepted: September 13, 2017
Article in press: September 13, 2017
Published online: November 28, 2017

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Core tip: Previously, hepatitis C was treated with interferon-based therapies. Intolerable side effects, prolonged treatment duration and unsatisfactory response rates were the major droughts of those therapies. The introduction of sofobuvir (SOF) was claimed as a highly responding oral drug for hepatitis C patients, with minimal side effects in different trials; thus, it was important to assess its efficacy in our population. We found an outstanding response rate of SOF in hepatitis C patients infected with genotype 3 of hepatitis C virus. These findings revealed that with SOF we may eliminate hepatitis C from our population.

To prospectively evaluate the efficacy of sofobuvir (SOF) in hepatitis C patients infected with hepatitis C virus (HCV) genotype 3 in Pakistan.

The present study was performed with the coordination of gastroenterology and pathology departments of Shalamar Hospital Lahore from August 2014 to May 2016. The total number of patients included in this study was 1375 and all of them were infected with HCV genotype 3. On the basis of drug combinations, all the patients were separated into two groups. The first group of patients was treated for 24 wk with SOF (Sovaldi® by Gilead Sciences) plus ribavirin (RBV) [Ribazol® by Getz Pharma Pakistan (PVT) Ltd], while the patients of the second group were treated with SOF + RBV + pegylated-interferon (pegIFN) alfa-2a (Ropegra by Roach) for 12 wk. HCV genotyping and viral load measurement were performed on fully automated Abbott Real-Time PCR system (Abbott m24sp automated nucleic acid extraction system and Abbott m2000rt amplification system; abbott Molecular, Des Plaines, IL, United States). For the assessment of sustained virological response (SVR), all HCV RNA negative patients were followed for 12 weeks after the treatment completion. Any patient with less than 12 IU/mL viral load after 12 wk of treatment completion was considered as a sustained virological responder (SVR-12).

A total of 1375 patients chronically infected with HCV genotype 3 were treated with two drug combinations SOF + RBV and SOF + RBV + pegIFN alfa-2a. On the basis of these drug combinations, patients were divided into two groups (first and second). Overall SVR-12 was excellent in both groups (99.17% and 97.91%). Older patients (> 40 years) of second group showed lower SVR-12 (93.46%) compared to first group older patients (98.79%), while in the younger patients of both groups, the SVR-12 rate was almost the same (99.54% in first group and 99.05% in second group). No such difference regarding SVR-12 rate was seen in males and females of first group patients (99.68% and 98.88%, respectively), while in second group the males were found to be better responders compared to females (98.96% and 95%). The SVR-12 rate in previously treated patients of first group was better (99.34%) than second group (93.70%), while naïve patients of second group were marginally better responders (99.25%) than first group (97.80%). Rapid viral response at week-4 was found to be a very effective predictor for assessing the SVR rate at this stage of therapy in both groups. Headache, anemia and fatigue were common side effects in both groups either treated with SOF + RBV or SOF + RBV + pegIFN alfa-2a, while the overall percentage of the side effects was higher in second group.

The remarkable SVR response rate of HCV genotype 3 infected patients to SOF provided a new way to look forward to eliminate hepatitis C from our region.

Key Words: Sofosbuvir, Sustained virological response, Pakistan

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Sunday, November 26, 2017

Hepatitis C - Impact of SVR on cognitive performance

BMC Gastroenterology
Hepatitis C virus eradication improves immediate and delayed episodic memory in patients treated with interferon and ribavirin
Mary Ellen Dias Barbosa, Ana Luiza Zaninotto, Daniel Ferraz de Campos Mazo, Mario Guimarães Pessoa, Cláudia Pinto Marques Souza de Oliveira, Flair José Carrilho and Alberto Queiroz Farias
Received: 26 June 2017 Accepted: 15 November 2017 Published: 25 November 2017

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Chronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders.

A prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment.


Thirty six patients were enrolled and 21 completed HCV treatment (n = 16 with SVR and n = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective attention (p < 0.001) and phonemic fluency (p = 0.043). Patients with SVR displayed significant improvement in immediate (p = 0.045) and delayed verbal episodic memory (p = 0.040) compared to baseline. The baseline frequency of depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6 months after the end of treatment, without significant difference between patients with and without SVR. Depressive symptoms were observed in 19.1% before treatment, 62% during (p = 0.016) and 28.6% 6 months after the end of treatment (p = 0.719).

Eradication of HCV infection improved cognitive performance but did not affect the frequency of depressive symptoms at least in the short range.

Cognition Memory Attention Neuropsychology Hepatitis C Depression

Saturday, November 25, 2017

Drug resistance-associated substitutions identified in HCV genes

Gastroenterology 2017
View Abstract

Drug resistance-associated substitutions identified in HCV genes
Last Updated: 2017-11-24
By Marilynn Larkin
NEW YORK (Reuters Health) - In patients who fail direct-acting antiviral therapy for hepatitis C virus (HCV) infection, resistance-associated substitutions (RASs) vary by HCV genotype and subtype and with different classes of drugs - a finding that might be used to select salvage therapies, researchers suggest.

"Little is known about (genetic) substitutions that mediate resistance of HCV to direct-acting antivirals, due to the small number of patients with treatment failure in approval studies," note Dr. Christoph Sarrazin of the University of Frankfurt, in Germany, and colleagues.
To investigate, the team analyzed samples from patients who had HCV infection with genotypes 1 to 6 for RASs in HCV genes (NS3, NS5A, NS5B) that are targeted by direct-acting antivirals.
Continue to article -

Friday, November 24, 2017

FDA scientists provide rationale behind Vosevi indications

Accepted manuscript online:

FDA scientists provide rationale behind Vosevi indications
Last Updated: 2017-11-23
By Reuters Staff
NEW YORK (Reuters Health) - Food and Drug Administration (FDA) scientists explain why the indication for Vosevi is narrower for NS5A inhibitor-naive hepatitis C virus (HCV) patients in a new report.

The FDA approved sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in July 2017, stating that the fixed-dose combination (FDC) was indicated for patients with genotype 1, 2, 3, 4, 5, or 6 HCV infection treated previously with NS5A inhibitor-containing regimens. But in patients not exposed to NS5A inhibitors who had taken sofosbuvir previously, SOF/VEL/VOX was only indicated for patients with genotype 1a or 3 HCV, the authors explain in Hepatology, online October 23.
Continue to article -

Nonalcoholic Fatty Liver Disease - Liver fat may have a direct association with brain aging

Original Investigation
JAMA Neurol. Published online November 20, 2017. doi:10.1001/jamaneurol.2017.3229
View Abstract - Association of Nonalcoholic Fatty Liver Disease With Lower Brain Volume in Healthy Middle-Aged Adults in the Framingham Study

Reuters Health Reports
Fatty liver linked to a shrinking brain
By Will Boggs MD
Last Updated: 2017-11-23

"Liver fat may have a direct association with brain aging," lead author Galit Weinstein from School of Public Health at the University of Haifa in Israel said in an email.

Reuters Health - Fatty liver disease that is not related to excess drinking is associated with greater brain shrinkage than normally happens with age, researchers say.

The reduced brain volume linked to non-alcoholic fatty liver disease (NAFLD) is equivalent to an extra 4.2 years of aging for people in their 60s and early 70s, or an extra 7.3 years of aging for people under age 60, researchers report in JAMA Neurology November 20.
Continue to article -

Thursday, November 23, 2017

Happy Thanksgiving

Happy Thanksgiving

"Poultry Yard," Melchior de Hondecoeter, c. 1668, oil on canvas.
Detroit Institute of Arts

Wednesday, November 22, 2017

HCV Advocate – Direct-Acting Antiviral Treatment & Decrease a Incidence of Liver Cancer

In Case You Missed It

SnapShots – Direct-Acting Antiviral Treatment & Decrease a Incidence of Liver Cancer
Alan Franciscus

Did you know that people who were treated with direct-acting antiviral (DAA) medications….
  • Were significantly less likely to die than the people who were untreated.
  • Had at least a 20% decrease in liver fibrosis after 24-weeks of the completion of DAA therapy
  • Experienced a 71% reduction in liver cancer risk after being cured with a DAA medication.
 The studies on this blog looked at treatment with DAAs to find out if curing hepatitis C (HCV) with DAAs improved HCV disease progression and reduced the risk of liver cancer.

Continue reading........

FDA issues guidance on developing generic abuse-deterrent opioids

FDA issues guidance on developing generic abuse-deterrent opioids
Today, the FDA revealed its newest action to reduce the span of the opioid abuse and addiction crisis — guidance to assist the development of generic versions of approved opioids formulated to deter abuse. The FDA plans to decrease unnecessary exposure to opioids by promoting the development of improved alternatives that are harder to manipulate and abuse for patients who need pain medications. It is critical to also encourage the use of opioids with abuse-deterrent formulations over opioids without such properties until a new nonopioid drug for pain management is available, according to Scott Gottlieb, MD, commissioner of the FDA.
Commentary available online @ Healio

FDA Press Release
Statement from FDA Commissioner Scott Gottlieb, M.D., on steps to promote development of generic versions of opioids formulated to deter abuse
As we continue to confront the staggering human and economic toll created by opioid abuse and addiction, we’re focused on taking actions that reduce the scope of new addiction by decreasing unnecessary exposure to opioids. At the same time, we also must take steps to help those with acute and chronic pain who need access to medicines, including opioids, get access to improved alternatives. Until we’re able to find new non-opioid forms of pain management for those who need treatment for pain, it’s critical that we also continue to promote the development of opioids that are harder to manipulate and abuse, and take steps to encourage their use over opioids that don’t offer any form of abuse deterrence.

Opioids with abuse-deterrent formulations (ADFs) are intended to make certain types of abuse, such as crushing a tablet to snort or dissolving a capsule to inject, more difficult or less rewarding. To date, the U.S. Food and Drug Administration has approved 10 opioid drugs with these properties. But their uptake has been slow among doctors who are treating patients in pain. The reason for their more limited use is likely multifold. We know there can be a learning curve that comes with new technologies. Some prescribers may not be aware of the existence of these drugs, or may be uncertain of when to prescribe the abuse-deterrent versions. But we also know a significant barrier to use can be price. Because these new formulations are currently only available as brand-name products, they’re inherently more expensive than the numerous non-abuse deterrent formulations that are also available in generic formulations.

Transitioning from the current market, dominated by conventional opioids, to one in which most opioids have abuse-deterrent properties, holds significant promise for a meaningful public health benefit. But to transition this market more quickly to the ADFs, and consider permanently withdrawing the older formulations that lack abuse-deterrent features in the event these products were judged to be less safe ‒ there are a number of factors we must consider. One of the factors that the FDA would consider relates to generic access. We must have the potential to improve access to the newer formulations, for appropriately selected and monitored patients, through the introduction of generic competitors.

In order to support this transition and encourage advancements in this area, today the FDA issued a final guidance to assist industry in their development of generic versions of approved ADF opioids. This guidance includes new recommendations about the type of studies companies should conduct to demonstrate that the generic drug is no less abuse-deterrent than its brand-name counterpart. We’re also taking additional steps beyond the new guidance to help developers of generic ADFs navigate the regulatory path to market as quickly as possible and make the review process more efficient and predictable. For example, we’re developing appropriate, improved testing methodologies for evaluating complex features like abuse deterrence for both brand name (innovator) and generic opioid drug products. In addition, we’re also taking a flexible, adaptive approach to the evaluation and labeling of ADF opioids.

These efforts also include the development of new tools for expediting the generic development of complex products. The same features that make drugs hard to manipulate and abuse also make these formulations more complex, and therefore harder to develop generic versions of. To provide a more efficient pathway for the generic entry of these and other complex formulations, the FDA is advancing new review policies. For example, the new guidance will now assist generic drug developers who meet with the agency to discuss scientific and regulatory issues before submitting their applications. These meetings will enable the FDA to clarify the agency’s expectations early in the development process with the goal of reducing the time it takes to obtain approval. We’ll be taking additional steps to facilitate the efficient entry of complex generic drugs in the near future.

Together, all of these efforts are aimed at creating a more robust path for applicants who plan to develop and seek approval of generic ADF opioids. Our goal is, when the use of any opioid drug product is appropriate, to make prescribing of these new formulations more commonplace. But let us be clear on one point. While these innovative formulations are designed to make it harder for people to manipulate the opioid drug so they can’t be abused, it’s important that prescribers and patients understand that these drugs are not “abuse-proof,” and they do not prevent addiction, overdose, or death. To address these issues, among other steps, we’re currently conducting a study to evaluate whether the nomenclature we use to describe these drugs, by labeling them “abuse deterrent,” is accurately conveying their benefits.

We also recognize that the science of abuse deterrence is relatively new. Both the formulation technologies and the analytical, clinical, and statistical methods for evaluating those technologies are rapidly evolving. That’s why we’re also focusing our efforts on determining how effective the current abuse-deterrent products are in the real-world setting and better understanding the attitudes and beliefs of health care professionals and those who are prescribed these products.

Further, all of these steps shouldn’t be mistaken as an effort that will encourage more opioid use. Our goal is to decrease the rate of new addiction, and thus any unnecessary legitimate and especially illicit use of opioids. Rather, this is an effort designed to encourage the shift – only when opioids are clinically appropriate ‒ from existing, easily abused products to those that are harder to manipulate.

This final guidance is one piece of the FDA’s ongoing work aimed at finding solutions to combat the opioid crisis. This effort must include treatments for those who are already addicted. That’s why we are also focusing new efforts on the development and promotion of medication-assisted treatments for addiction. As we balance the need to effectively treat pain with the public health emergency related to opioid addiction, we must find creative ways to prevent new cases of abuse and addiction.

The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Intrapatient viral diversity & treatment outcomes in patients with genotype 3a HCV infection on SOF-containing regimens

Journal of viral hepatitis
Intrapatient viral diversity & treatment outcomes in patients with genotype 3a HCV infection on SOF-containing regimens
Neeru Bhardwaj, Manon Ragonnet-Cronin, Ben Murrell, Krishna Chodavarapu,  Ross Martin, Silvia Chang, Michael D. Miller, Jordan J. Feld, Mark Sulkowski, Alessandra Mangia, Joel O. Wertheim, Anu Osinusi, John McNally, Diana Brainard, Hongmei Mo, Evguenia S. Svarovskaia

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Shared By Henry E. Chang 

Treatment with the direct-acting antiviral agent (DAA) sofosbuvir (SOF), an NS5B inhibitor, and velpatasvir (VEL), an NS5A inhibitor, demonstrates viral cure rates of ≥95% in hepatitis C virus (HCV) genotypes (GT) 1-6. Here we investigated intrapatient HCV diversity in NS5A and NS5B using Shannon entropy to examine the relationship between viral diversity and treatment outcome. At baseline, HCV diversity was lowest in patients infected with HCV GT3 as compared to the other GTs, and viral diversity was greater in NS5A than NS5B (p<0.0001). Treatment outcome with SOF/VEL or the comparator regimen of SOF with ribavirin (RBV) was not correlated with baseline diversity. However, among persons treated with SOF/VEL, a decrease in diversity from baseline was observed at relapse in the majority virologic failures, consistent with a viral bottleneck event at relapse. In contrast, an increase in diversity was observed in 27% of SOF+RBV virologic failures. We investigated whether the increase in diversity was due to an increase in the transition rate, one mode of potential RBV-mediated mutagenesis; however, we found no evidence of this mechanism. Overall, we did not observe that viral diversity at baseline influenced treatment outcome, but the diversity changes observed at relapse can improve our understanding of RBV viral suppression in vivo.

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Tuesday, November 21, 2017

Value and innovation of direct-acting antivirals: long-term health outcomes of the strategic plan for the management of hepatitis C in Spain

Rev Esp Enferm Dig. 2017 Nov 20. doi: 10.17235/reed.2017.5063/2017. [Epub ahead of print]

Value and innovation of direct-acting antivirals: long-term health outcomes of the strategic plan for the management of hepatitis C in Spain.
Turnes J1, Domínguez-Hernández R2, Casado MÁ3.

Full Text

To assess the long-term healthcare costs and health outcome in association with the access to new direct-acting antivirals (DAAs), during the first year of the National Strategic Plan for Chronic Hepatitis C (SPCHC) in patients with chronic hepatitis C (CHC) in Spain.

A decision tree and a lifetime Markov model were developed to simulate the natural history, morbidity, and mortality of a cohort of 51,900 patients with CHC before (pre-DAA strategy) and after (post-DAA strategy) access to DAA, following SPCHC approval. The percentage of patients treated, transition probabilities, disease management costs, health state utility values, sustained virologic response rates and treatment costs were obtained from the literature and published data from Spain. The results were expressed in terms of costs (€, 2016), quality-adjusted life years (QALYs) and prevention of clinical events, with an annual discount rate of 3%.

The post-DAA strategy would prevent 8,667 cases of decompensated cirrhosis, 5,471 cases of hepatocellular carcinoma, 1,137 liver transplants and 9,608 liver-related deaths. The cohort of 51,900 patients would require investments of 1,606 and 1,230 million euros with the post-DAA and pre-DAA strategies, respectively. This would produce 819,674 and 665,703 QALYs.

The use of new DAA-based treatments in CHC patients during the first year after the implementation of the SPCHC significantly reduced long-term morbidity and mortality and increased quality of life; demonstrating that this plan is an efficient use of public health resources.

PMID: 29152988 DOI: 10.17235/reed.2017.5063/2017 

Saturday, November 18, 2017

Clinical improvement after successful antiviral DAA therapy for hepatitis C

Follow-up of sustained virologic responders with hepatitis C and advanced liver disease after interferon/ribavirin - free treatment
Karin Kozbial 1 , Stephan Moser 2 , Ramona Al - Zoairy 3 , Remy Schwarzer 4 , Christian Datz 5 , Rudolf Stauber 6 , Hermann Laferl 7 , Michael Strasser 8 , S andra Beinhardt 1 , Albert Friedrich Stättermayer 1 , Michael Gschwantler 2 , H einz Zoller 3 , Andreas Maieron 4 ,9 , Ivo Graziadei 10 , Michael Trauner 1 , P etra Steindl - Munda 1 , Harald Hofer 1, 11 , P eter Ferenci

doi: 10.1111/liv.13629

Link To Article:
*Article downloaded and shared by Henry E. Chang‏ today on Twitter.

Key points
SVR is durable irrespective of the interferon - free DAA regimen used. 
Survival was excellent for patients with F3 and Child - Pugh A cirrhosis. 
Decompensation before or at baseline was significantly associated with decompensation and with death during follow-up . 
Despite successful therapy a risk of hepatocellular carcinoma remains among patients with cirrhosis, necessitating a regular follow-up

Vosevi & Mavyret: The Impact of New Options for DAA-Experienced Patients With HCV

Latest ClinicalThought commentaries from Clinical Care Options (CCO).

Over at Clinical Care Options, using an easy to follow patient case scenario experts discuss treatment options with newly approved drugs: Mavyret (glecaprevir/pibrentasvir) GLE/PIB and Vosevi (Sofosbuvir/Velpatasvir/Voxilaprevir) SOF/VEL/VOX.

The Impact of New Options for DAA-Experienced Patients With HCV
Jordan J. Feld MD, MPH - 11/16/2017
With the approvals of SOF/VEL/VOX and GLE/PIB, what is the new management approach for DAA-experienced patients with HCV infection?

In this viral hepatitis case series, we highlight common patient case scenarios and the critical decision making that informs selection of optimal patient management strategies. This commentary features a woman with cirrhosis who is seeking retreatment after failure of first-line direct-acting antiviral (DAA) therapy. The impact of the recent approvals of sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) and glecaprevir (GLE)/pibrentasvir (PIB) on treatment for this class of patient is discussed.

Case Details
A 59-year-old white woman with compensated cirrhosis (elastography 24 kPa) and genotype 1a HCV infection was previously treated with SOF/ledipasvir (LDV) for 12 weeks, but she experienced a relapse at posttreatment Week 6. She reports strict adherence to her previous regimen and is seeking advice on retreatment options.
Continue reading @ CCO

How Recent Drug Approvals Have Affected First-line HCV Treatment
Nancy Reau MD, FAASLD, AGAF - 11/15/2017
What parameters now qualify a patient infected with HCV for shortened first-line therapy?

In this viral hepatitis case series, we highlight common patient case scenarios and the critical decision making that informs selection of optimal patient management strategies. This commentary features a treatment-naive, noncirrhotic patient who is infected with HCV and ready to begin therapy. The candidacy of this patient for 8-week vs 12-week therapy is discussed, with a focus on the latest treatment options and guidelines.

Case Details
A 56-year-old white man newly diagnosed with genotype 1a HCV infection presents for initiation of treatment. His baseline HCV RNA is 8,500,000 IU/mL and he has F2 fibrosis. He expresses a desire to take as short a course of HCV treatment as possible.
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Friday, November 17, 2017

Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without SVR after interferon-based therapy

Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without sustained virological response after interferon-based therapy: Prioritize who needs urgent direct-acting antiviral agents
Huang, Chao-Min PhDa; Hu, Tsung-Hui MD, PhDb; Chang, Kuo-Chin MDb; Tseng, Po-Lin MDb; Lu, Sheng-Nan MD, PhDb; Chen, Chien-Hung MD, PhDb; Wang, Jing-Houng MD, PhDb; Lee, Chuan-Mo MD, PhDb; Tsai, Ming-Chao MDb; Lin, Ming-Tsung MDb; Yen, Yi-Hao MDb; Hung, Chao-Hung MD, PhDb; Cho, Chung-Lung PhDa; Wu, Cheng-Kun MDb,* Section Editor(s): Gao., Chun

Medicine: November 2017 - Volume 96 - Issue 46 - p e8696
doi: 10.1097/MD.0000000000008696
Research Article: Observational Study

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Article as PDF (513 KB)

Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).

A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period.

HCC developed in 93 patients. The risk factors for HCC were pre-existing liver cirrhosis, low hemoglobin level at baseline, low pretreatment platelet count, high post-treatment alpha-fetoprotein (AFP) level (≥15 ng/mL), and high post-treatment Fibrosis 4 (FIB4) index (>3.25). For patients without pre-existing cirrhosis, those with high post-treatment AFP level and FIB4 index had the highest risk of HCC (1 year: 6.7%; 3 years: 10.9%; 5 years: 29.7%), followed by those with high post-treatment AFP level and low post-treatment FIB4 index (5 years: 25%), and those with low post-treatment AFP level and high post-treatment FIB4 index (1 year: 3.7%; 3 years: 5.2%; 5 years: 10.6%). The risk was even lower for patients with low post-treatment AFP level and FIB4 index (1 year: 0%; 3 years: 0.4%; 5 years: 2.5%). None of the patients with FIB4 indexes consistently below 1.45 developed HCC.

The combined use of post-treatment AFP level and FIB4 index was useful for risk stratification of HCV-infected patients with non-SVR status after IFN therapy. These data may help clinicians to identify patients who most urgently need DAA treatment.

Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review

Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review
Hosnieh Fathi, Andrew Clark, Nathan R. Hill and Geoffrey Dusheiko

BMC Infectious Diseases BMC series – open, inclusive and trusted 201717:722©

View Full Text Article Online

Received: 24 May 2017
Accepted: 6 November 2017
Published: 16 November 2017

Six distinct genetic variants (genotypes 1 − 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN). GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development.

According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis) of data in the public domain from relevant clinical trial or observational (real-world) study publications within a 5-year period (February 2011 to May 2016) identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016).

Of the all-oral regimens, the efficacy (SVR12 ≥ 90%) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir), offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect corresponding clinical trial data in terms of treatments most likely to achieve good responses.

On the basis of SVR12, we established that for treating GT3 infections (i) regimens incorporating newer DAAs are more effective than those comprising older DAAs, and (ii) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens. The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection.

Hepatitis C virus Genotype 3 Direct-acting antiviral Cirrhosis Co-infection Systematic literature review

For Patients
HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C
This version of the guidance has been updated to reflect several important developments, including the recent approvals of glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir. Updated recommendations reflecting these approvals are provided throughout the guidance

New Treatment-Naïve & Treatment-Experienced
The following pages include guidance for management of treatment-naive patients.
The following pages include guidance for management of treatment-experienced patients.
Stay current with all guideline updates, "click here."

Of Interest
September 29,2017
Merck Discontinues MK-3682B and MK-3682C Development Programs
Merck announced its strategic decision to discontinue the development of the investigational combination regimens MK-3682B (grazoprevir/ruzasvir/ uprifosbuvir) and MK-3682C (ruzasvir/uprifosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection. This decision was made based on a review of available Phase 2 efficacy data and in consideration of the evolving marketplace and the growing number of treatment options available for patients with chronic HCV infection

Potential impact of coffee consumption on chronic liver disease, liver cancer and cirrhosis

Moderate coffee intake reduces risk for liver cancer, cirrhosis, fibrosis
November 16, 2017
In a roundtable format, experts gathered to discuss the latest research on coffee and liver disease, which indicate that drinking approximately three to five cups per day is associated with a reduced risk for hepatocellular carcinoma, cirrhosis and fibrosis.
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Report suggests association between coffee and up to 70 percent reduced risk of liver disease
New report on coffee and liver health discusses potential impact of coffee consumption on chronic liver disease, liver cancer and cirrhosis

Institute for Scientific Information on Coffee
17th November 2017 - A new roundtable report from the Institute for Scientific Information on Coffee (ISIC) on 'Looking after the liver: coffee, caffeine and lifestyle factors' highlights the potential role of coffee consumption in reducing the risk of liver diseases such as liver cancer and cirrhosis.

Roundtable delegates including academics, media medics and representatives from national liver associations from across seven European countries, met to discuss the most recent research into coffee and liver health, and the potential mechanisms behind a suggested reduced risk of liver disease.

The roundtable, held at the Royal Society of Medicine in London, was chaired by Professor Graeme Alexander (University College London and senior advisor to the British Liver Trust) who also presented on the prevalence of liver disease in Europe and the role of lifestyle. Dr. Carlo La Vecchia (Professor of Medical Statistics and Epidemiology, Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano) discussed the latest research on coffee and liver health and potential mechanisms. Group discussion focussed on how best to disseminate the latest findings and challenges for both liver associations and healthcare professionals.

Liver disease is a significant concern across Europe, where chronic liver disease is the fifth most common cause of death1 and approximately 29 million people in the European Union suffer from a chronic liver condition2.

Key research findings highlighted in the report include:
  • Meta-analyses have suggested that coffee consumption versus no coffee consumption is associated with up to a 40% risk reduction of liver cancer, although this appears to be a dose-dependent relationship3-5.
  • Research from the US6 and Italy7,8 suggests that coffee consumption is consistently associated with a reduced risk of cirrhosis, with a potential risk reduction of 25-70%.
  • Research suggests an inverse association between coffee consumption and risk of chronic liver disease, with an average risk reduction of 25-30% in low coffee consumers, and up to 65% in high coffee consumers9.*.
During the roundtable, Professor Alexander suggested that it is likely that liver cancer develops from an existing liver disease, and proposed that the association between coffee consumption and a reduced risk of liver cancer may in fact link back to an effect of coffee drinking on liver disease.

One of the main issues discussed at the roundtable was the diagnosis of liver disease, and the fact that a majority of sufferers are unaware of their condition. Even though the liver is a vital organ, the perception in some European countries is that liver health is not considered as high a priority as other conditions, such as heart disease.

Professor Graeme Alexander, senior advisor to the British Liver Trust, commented: "Liver disease is on the rise across Europe and it is important that we understand how coffee, one of the most popular drinks in the world, and diet affects the disease. Research suggests that coffee may reduce the risk of liver diseases and it is important patients have access to dietary information and advice from health care professionals in a manner that is easy for them to understand and act upon."

Judi Rhys, Chief Executive, British Liver Trust said: "Liver disease is a silent killer as often there are no symptoms until it's too late. Coffee is something that is easily accessible to everyone and regularly drinking it - filtered, instant or espresso - may make a difference in preventing and, in some cases, slowing down the progression of liver disease- it is an easy lifestyle choice to make."

To read the report, titled 'Looking after the Liver: Lifestyle, Coffee and Caffeine' click here.

Readers interested in finding out more about coffee and health can visit:

* Definitions of low and high coffee consumption from the studies within the meta-analysis vary and tend to be study specific dependent on levels of coffee consumed by participants.
* Moderate coffee consumption can be defined as 3-5 cups per day, based on the European Food Safety Authority's review of caffeine safety.
* To read a full overview of coffee and liver function, click here.

Roundtable delegates
  • Professor Graeme Alexander University College London and senior advisor to the British Liver Trust, United Kingdom.
  • Dr. Carlo La Vecchia, Professor of Medical Statistics and Epidemiology, Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy.
  • HIlje Logtenberg-van der Grient, Physician Educator, Scientific Committee ELPA/Dutch Liver Patient Association, The Netherlands.
  • Andreas Röhrenbacher, Steering Committee Member, Die Hepatitis Hilfe Osterreich, Plattform Gesunde Leber (HHO), Austria.
  • Raquel Peck, CEO, World Hepatitis Alliance, United Kingdom.
  • Dr David Semela, Council Member, Swiss Association for the Study of the Liver, Switzerland.
  • Dr Trisha Macnair, Speciality Doctor/Medical Journalist, NHS, United Kingdom.
  • Dr Ellie Cannon, NHS GP, Abbey Medical Centre, London, United Kingdom.
  • Dr JW Langer, medical doctor, author, lecturer and medical journalist, Denmark.
  • Dr Luca Miele, MD, PhD, Consultant Internist and Hepatologist, University Hospital Policlinico A. Gemelli Foundation, Italy.
  • Dr Beatrice Alfonso PhD, Fondazione Italiana Fegato, ONLUS- Italian Liver Foundation, Italy.
  • Gerardo Reyna, Federación Nacional de Enfermos y Trasplantados Hepáticos, Spain.
1. European Association for the Study of the Liver (2013) 'The burden of Liver Disease in Europe: A Review of Available Epidemiological Data' Available at:
2. Eurostat (2007) 'Europe in Figures: Eurostat yearbook 2006-07' Available at:
3. Bravi F. et al. (2007) Coffee drinking and hepatocellular carcinoma risk: a meta-analysis. Hepatol, 46:430-435.
4. Larsson S.C. et al. (2007) Coffee consumption and liver cancer: a meta-analysis. Gastroenterol, 132:1740-1745.
5. Bravi F. et al. (2013) Coffee reduces risk for hepatocellular carcinoma: An updated meta-analysis. Clin Gastro and Hepatol, 11:1413-1421.
6. Klatsky A.L. et al. (1993) Coffee, tea, and mortality. Ann Epidemiol. 3(4):375-81.
7. Corrao G. et al. (1994) The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption - A case-control study. Europ J Epidemiol, 10 (6): 657-664.
8. Gallus S. et al. (2002) Does coffee protect against liver cirrhosis? Ann Epidemiol, 12(3):202-5.
9. Bravi F. et al. (2016) Coffee and the risk of hepatocellular carcinoma and chronic liver disease: a systematic review and meta-analysis of prospective studies. Eur J Cancer Prev, 26(5):368-377.
10. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2015) Scientific Opinion on the safety of caffeine. EFSA Journal, 13(5):4102.

Efficacy/prognosis of antiviral therapy on hepatitis C following treatment of lymphoma in HCV-positive diffuse large-cell lymphoma

Annals of HematologyDecember 2017, Volume 96, Issue 12, pp 2057–2061 |

Efficacy and prognosis of antiviral therapy on hepatitis C following treatment of lymphoma in HCV-positive diffuse large-cell lymphoma
Yutaka Tsutsumi, Chie Nakayama, Koki Kamada, Ryo Kikuchi, Daiki Kudo, Shinichi Ito, Satomi Matsuoka, Souichi Shiratori, Yoshiya Yamamoto, Hirohito Naruse, Takanori Teshima

Full Text

It was recently reported that performing antiviral therapy against HCV in the treatment of HCV-positive lymphoma has had positive effects including improvement of the lymphoma, and that antiviral therapy including interferon against low-grade lymphoma may be able to improve the prognosis when performed following chemotherapy for low-grade lymphoma [9, 10]. In our report, since HCV is often stained in tissue samples, and since cases where there is a drop in HCV viral RNA are less likely to recur [7], it is suggested that HCV is directly or indirectly associated with the occurrence and progression of lymphoma. However, the main causes of the transition to lymphoma are still unclear. Furthermore, it has been reported that improvements can be obtained with antiviral therapy alone (e.g., in cases of splenic marginal zone lymphoma), and it is expected that the use of antiviral therapy against HCV-positive lymphoma yields an improved prognosis [11, 12, 13].

On the other hand, studies of whether treatment of HCV with antiviral drugs after treatment for diffuse large-cell lymphoma contributes to the prognosis are being conducted either retrospectively or through a combination of retrospective and prospective methods [14, 15]. It has been reported that the 5-year OS and PFS can both be improved [14, 15]. Also, a report by Michot et al. pointed out the possibility of including cases where diffuse large B cell lymphoma is thought to have transformed from splenic marginal zone lymphoma [14], but in this case, cases that have transformed from splenic marginal zone lymphoma are not included. In Europe and the USA, there are many cases where splenic marginal zone lymphoma is associated with HCV. These cases are highly responsive to HCV antiviral therapy, suggesting the possibility of an improved prognosis. On the other hand, in a report by Michot et al., there were cases in which SVR could not be obtained in the antiviral therapy group, while in a report by Hosry et al., there were many cirrhosis cases among the analysis subjects, and it is thought that these factors may have acted on OS and PFS in a negative direction [14, 15]. In our analysis, genotype 2 was more common in the DAA group, while genotype 1 was more common in the control 1 group, and the difference in genotype may also have affected the outcome of treatment. It is thought that this affected the OS and PFS analysis of this report and earlier reports [14, 15].

Since DAA was used after obtaining confirmation of chronic HCV-positive hepatitis by liver biopsy in the cases analyzed here, DAA therapy was performed about 6 weeks after treatment with anticancer drugs. However, there are no clear guidelines on the appropriate timing for DAA treatment, such as whether antiviral therapy should be performed after or during lymphoma treatment, or before anticancer treatment of the lymphoma. A recent report investigated the interactions of DAA administered simultaneously with various anticancer drugs in cancer cases complicated by HCV infection. In this report, although blood toxicity and gastrointestinal toxicity were found, the change brought about by DAA therapy was only 10%, and the SVR was also 95%, and it was reported that it may be possible to use DAA therapy simultaneously with anticancer treatment [16, 17]. On the other hand, in this analysis, there were no problems arising from the continued use of DAA therapy, or complications requiring a change of medication regime, but this could be because there were no cases where DAA therapy was performed at the same time as the anticancer treatment.

In this study, we are conducting a prospective examination of five cases, and so far, 2 years has elapsed since the start of treatment, but in all five cases, the patients have survived without any recurrence, and it seems that following chemotherapy with antiviral therapy may contribute to the prognosis in cases of HCV-positive diffuse large-cell lymphoma. Furthermore, although analysis has only been performed in a few cases, it seems that HCV-RNA-positive cases may have a poorer prognosis than non-HCV-infected diffuse large-cell lymphoma cases, and although there are signs that the prognosis is improved for DAA treatment cases, it may be recommended that DAA treatment is performed after remission in HCV-RNA-positive diffuse large-cell lymphoma. However, since we have only examined a few cases for a short period of time, we are hopeful that the usefulness of antiHCV therapy will be demonstrated more clearly by a prospective study involving a larger number of people.

The Impact of Hepatitis B Virus Infection and Vaccination on the Development of Non-hodgkin Lymphoma

Perspective > Journal of Viral Hepatitis

The Impact of Hepatitis B Virus Infection and Vaccination on the Development of Non-hodgkin Lymphoma

This study investigated the association of HBV infection and risk of non-Hodgkin's lymphoma. Might HBV vaccination reduce the risk in certain populations?

The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing

BMC Infectious Diseases
The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing
Joseph D. Tucker, Kathrine Meyers, John Best, Karyn Kaplan, Razia Pendse, Kevin A. Fenton, Isabelle Andrieux-Meyer, Carmen Figueroa, Pedro Goicochea, Charles Gore, Azumi Ishizaki, Giten Khwairakpam, Veronica Miller, Antons Mozalevskis, Michael Ninburg, Ponsiano Ocama, Rosanna Peeling, Nick Walsh, Massimo G. Colombo and Philippa Easterbrook
Published: 1 November 2017

Map of countries with contributions to the hepatitis testing innovation contest

Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines.

This contest involved four steps: 1) establishment of a multisectoral steering committee to coordinate a call for contest entries; 2) dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals); 3) independent ranking of submissions by a panel of judges according to pre-specified criteria (clarity of testing model, innovation, effectiveness, next steps) using a 1-10 scale; 4) recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines.

The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5), people who inject drugs (PWID) (n = 4), pregnant women (n = 4), general populations (n = 4), high-risk groups (n = 3), relatives of people living with hepatitis B and C (n = 2), migrants (n = 2), incarcerated individuals (n = 2), workers (n = 2), and emergency department patients (n = 2). A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12); integrated testing with harm reduction and addiction services (n = 9); use of electronic medical records to support targeted testing (n = 8); decentralization (n = 8); and task shifting (n = 7).

The global innovation contest identified a range of local hepatitis testing approaches that can be used to inform the development of testing strategies in different settings and populations. Further implementation and evaluation of different testing approaches is needed.

Wednesday, November 15, 2017

Blog Updates Around The Web: Does an SVR to Therapy for HCV-associated Cirrhosis Reduce Portal Pressure?

Viral Hepatitis Updates
With Thanksgiving just around the corner, and Christmas on the way, it's a busy time of the year, hopefully you'll save some time online with this quick summary of blog and journal updates. 
AGA Journals BLOG
Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology. She has worked as an editor at biomedical research journals and as a science writer for 15 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.

Does an SVR to Therapy for HCV-associated Cirrhosis Reduce Portal Pressure?
A sustained virologic response (SVR) to all-oral therapy in patients with hepatitis C virus (HCV)-associated cirrhosis significantly reduces the hepatic venous pressure gradient (HVPG), researchers report in the November issue of Gastroenterology. Nevertheless, almost 80% of patients maintain significant portal hypertension and have a continued risk of decompensation.
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Clinical Care Options CCO
Mission Statement - To optimize clinicians’ competence with the goal of improving patient care through the development of educational solutions that address the explosion of new medical information and the overwhelming task of its assimilation by clinicians, with easy-to-use, innovative, interactive educational and decision support models that can be used at the point of care and provide the latest evidence-based information whenever, wherever, and however it is needed.

Hepatology Meeting Shed Light on the Clinical Benefits of HCV DAAs
Jordan J. Feld, MD, MPH - 11/14/2017 Clinical Thought 
For the first time in several years, we did not see the presentation of dramatic data from phase III trials of emerging investigational HCV therapies at the American Association for the Study of Liver Diseases (AASLD) meeting. What we learned is that we likely now have the full complement of direct-acting antivirals (DAAs) and—unfortunately—that some relatively promising regimens that were in clinical development are unlikely to come to clinical use.

What did emerge at the meeting were several studies that provided critical evidence that treatment with DAAs leads to important clinical benefits for patients with HCV infection. Although these types of studies can feel like something of a foregone conclusion, they are actually critical for payers, policymakers, and clinicians to be confident that contemporary HCV therapies are associated with the intended benefits.

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On Twitter
The Cochrane Review Conclusion for Hepatitis C DAA Therapies Is Wrong

*Article shared by Henry E. Chang‏ today on Twitter.

Full Text Articles
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

On The Blog
HepCBC is a non-profit organization run by and for people infected and affected by hepatitis C. Our mission is to provide education, prevention and support to those living with HCV.

Read today's news or check out the latest issue of: Weekly Bull
The CATIE Blog is a unique opportunity for individuals to express a wide latitude of opinion on a range of issues. The views expressed in the blog are solely those of the authors and do not necessarily reflect the policies or opinions of CATIE nor the views of its funders

Eliminating viral hepatitis is possible: Four lessons from the World Hepatitis Summit
By Melisa Dickie
As deaths from many communicable diseases continue to decline globally, deaths caused by viral hepatitis have now surpassed all other chronic infectious diseases, including HIV/AIDS, malaria and tuberculosis. Yet it is one of the few global health threats with easy solutions. Highly effective vaccines exist for hepatitis A and B. We now have a cure for hepatitis C. With these tools at our disposal, why aren’t we seeing an impact on the epidemic?
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National Viral Hepatitis Roundtable
The National Viral Hepatitis Roundtable is a broad coalition working to fight, and ultimately end, the hepatitis B and hepatitis C epidemics. We seek an aggressive response from policymakers, public health officials, medical and health care providers, the media, and the general public through our advocacy, education, and technical assistance.

Why We Need a Movement for Racial Justice and Health Equity in Order to Eliminate Hepatitis B and Hepatitis C
by the National Viral Hepatitis Roundtable’s Steering Committee
Recently, some people have questioned why the National Viral Hepatitis Roundtable’s staff and members of its Steering Committee have made statements in words and action standing up for racial justice. We hope this statement provides additional context for why speaking out about the need for racial justice and health equity is critical to the hepatitis B and hepatitis C response.

NVHR Welcomes New Hepatitis B Vaccine
NVHR today welcomed the U.S. Food and Drug Administration’s (FDA) approval of HEPLISAV-B for prevention of hepatitis B virus infection in adults ages 18 and older.
Médecins Sans Frontières/ Doctors Without Borders (MSF)
Médecins Sans Frontières (MSF) is an international, independent, medical humanitarian organisation. We offer assistance to people based on need, irrespective of race, religion, gender or political affiliation. Our actions are guided by medical ethics and the principles of neutrality and impartiality.

Fighting Hepatitis in Cambodia: Medical Week

"The best part of Medical Week was the opportunity to meet MSF colleagues from all over the world, most of whom had more experience than I have and who had lots of advice for me, such as..."
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POZ is an award-winning print and online brand for people living with and affected by HIV/AIDS. Offering unparalleled editorial excellence since 1994, POZ magazine and are identified by our readers as their most trusted sources of information about the disease.

Finding Folks Who Have HIV or Hep C in an Opioid-Ravaged Region
West Virginia has been hit hard by the opioid epidemic, so it is important to identify people living with HIV and hepatitis C virus (HCV), which can be spread by injection drug use. A four-year $1.375 million grant aims to do exactly that. Funding goes to the West Virginia University (WVU) School of Medicine’s Department of Emergency Medicine and arrives from Frontlines of Communities in the United States (FOCUS), an initiative of pharma giant Gilead Sciences.
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At we empower patients and caregivers to take control of Hepatitis C by providing a platform to learn, educate, and connect with peers and healthcare professionals.

Elimination: What Does It Look Like?
By Daryl Luster—November 14, 2017
Elimination. There’s a kind of ominous ring this word, but this is what we hear a lot in the world of viral hepatitis, including HBV and HCV. The meaning here is meant to describe a global effort to eliminate hep C as a health threat. With estimates of worldwide infection ranging wildly, suffice to say it is well over 100 million people now living with hep C. Some peg it at around 150-170 million, and no matter which is accurate it is a huge number.
Hepatitis B Foundation
The Hepatitis B Foundation is a national nonprofit organization dedicated to finding a cure and improving the quality of life for those affected by hepatitis B worldwide. Our commitment includes funding focused research, promoting disease awareness, supporting immunization and treatment initiatives, and serving as the primary source of information for patients and their families, the medical and scientific community, and the general public.

Diagnosing Hepatitis Delta in the U.S.
November 15, 2017 hepbtalk
Hepatitis D, or hepatitis delta, is the most severe form of viral hepatitis known to humans. The hepatitis D virus infects the liver and is dependent on the hepatitis B virus to reproduce. This means that people who are already infected with hepatitis B are at risk of contracting hepatitis D as well.
MD Magazine
MD Magazine is a comprehensive clinical news and information portal that provides physicians with up-to-date specialty and disease-specific resources designed to help them provide better care to patients.

Aspirin Could Reduce HBV Patients' Liver Cancer Risk
Patients with chronic hepatitis B virus (HBV) who take an aspirin a day may reduce their risk of hepatocellular carcinoma (HCC), the most common form of adult liver cancer, a new study suggests.
Medscape is the leading online global destination for physicians and healthcare professionals worldwide, offering the latest medical news and expert perspectives; essential point-of-care drug and disease information; and relevant professional education and CME.

Preventing Perinatal Transmission of Hepatitis B
November 14, 2017
 Dr William Balistreri surveys the latest guidelines and studies aiming to improve maternal and neonatal outcomes.
Kaiser Family Foundation
Kaiser Health News (KHN) is a nonprofit news service committed to in-depth coverage of health care policy and politics. And we report on how the health care system — hospitals, doctors, nurses, insurers, governments, consumers — works.

Vaccine Shortage Complicates Efforts To Quell Hepatitis A Outbreaks
By Stephanie O'Neill
San Diego County, battling a deadly outbreak of hepatitis A, is postponing an outreach campaign to provide the second of two inoculations against the contagious liver disease until a national shortage of the vaccine is resolved, the county’s chief public health officer said. “Our goal is to get that vaccine in as many arms as possible for that first dose,” said Dr. Wilma Wooten, who is leading the fight against an epidemic that has ravaged unsanitary homeless encampments in San Diego County for the past year, sickening 544 people and killing 20 of them as of Nov. 6.
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Harvard Health Blog
Harvard Health Publishing is the media and publishing division of the Harvard Medical School of Harvard University, under the direction of Dr. Gregory Curfman, Editor in Chief. The goal of our publications is to bring people around the world the most current health information that is authoritative, trustworthy, and accessible, drawing on the expertise of the 10,000+ faculty physicians at Harvard Medical School.

Seasonal Influenza
What’s new with the flu shot?
Posted November 13, 2017, 10:30 am
Dominic Wu, MD, Contributing Editor
Should you get the influenza (flu) vaccine this year? The short, quick answer (barring any medical reasons you shouldn’t, such as severe allergies), is yes! But recent research raises another important question: When should you get the shot?
Healio features the industry’s best news reporting, dynamic multimedia, question-and-answer columns, CME and other educational activities in a variety of formats, quick reference content, blogs, peer-reviewed journals and a full line of popular book titles.

Welcome to the New World Order A Competitive HCV Drug Marketplace
November/December print edition of HCV NEXT, available online at Healio.
Monthly Prescribing Reference (MPR) is a multispecialty drug information resource for healthcare professionals offering concise prescribing information, point-of-care tools, as well as news and features on hot topics in pharmacotherapy.

Labeling for Several HCV Drugs Updated With New Drug Interactions
Specifically, the prescribing information for Viekira Pak (ombitasvir, paritaprevir, ritonavir, with dasabuvir; AbbVie), Viekira XR (dasabuvir, ombitasvir, paritaprevir, ritonavir; AbbVie), Technivie (ombitasvir, paritaprevir, ritonavir; AbbVie), Sovaldi (sofosbuvir; Gilead), Harvoni (ledipasvir, sofosbuvir; Gilead), Epclusa (sofosbuvir, velpatasvir; Gilead), Vosevi (sofosbuvir, velpatasvir, voxilaprevir; Gilead), Olysio (simeprevir; Janssen), Daklinza (daclatasvir; Bristol-Myers Squibb), and Zepatier (elbasvir, grazoprevir; Merck) has been updated to include information pertaining to changes in International Normalized Ratio (INR) values in patients receiving warfarin. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment.
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Journal Updates
The world’s first multidisciplinary Open Access journal, PLOS ONE accepts scientifically rigorous research, regardless of novelty. PLOS ONE’s broad scope provides a platform to publish primary research, including interdisciplinary and replication studies as well as negative results. The journal’s publication criteria are based on high ethical standards and the rigor of the methodology and conclusions reported.

Evolution of acute hepatitis C virus infection in a large European city: Trends and new patterns
The aims of this study were to describe the evolution of acute hepatitis C virus (HCV) infections since 2004 and to determine its associated factors. Acute HCV infections diagnosed in Barcelona from 2004 to 2015 were included. Incidence ratios (IR) were then estimated for sex and age groups. Cases were grouped between 2004–2005, 2006–2011 and 2012–2015, and their incidence rate ratios (IRR) were calculated. In addition, risk factors for acute HCV infection were identified using multinomial logistic regression for complete, available and multiple imputed data. 204 new HCV cases were identified. Two peaks of higher IR of acute HCV infection in 2005 and 2013 were observed. Men and those aged 35–54 had higher IR. IRR for men was 2.9 times greater than in women (95% confidence intervals (CI): 1.8 ‒ 4.7). Factors related to the period 2012–2015 (versus 2006–2011) were: a) sexual risk factor for transmission versus nosocomial (relative-risk ratio (RRR): 13.0; 95% CI: 2.3 ‒ 72.1), b) higher educated versus lower (RRR: 5.4; 95% CI: 1.6 ‒ 18.7), and c) HIV co-infected versus not HIV-infected (RRR: 53.1; 95% CI: 5.7 ‒ 492.6). This is one of the few studies showing IR and RRRs of acute HCV infections and the first focused on a large city in Spain. Sexual risk for transmission between men, higher educational level and HIV co-infection are important factors for understanding current HCV epidemic. There has been a partial shift in the pattern of the risk factor for transmission from nosocomial to sexual.
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Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis.
Stroffolini T, et al. PLoS One. 2017
BACKGROUND: The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation.

OBJECTIVE: Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis.
DESIGN: We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis.
RESULTS: Females were older than males (p<0.01) and less frequently showed HBV and alcoholic aetiology (p<0.01). In both sexes, an overtime increasing age and an increasing proportion of subjects with liver cirrhosis was observed, reflecting a better survival (0.01). An additive interaction is observed in females: the O.R. generated by the simultaneous presence of HBV, HCV, and alcohol (5.09; 95% C.I. 1.06-24.56) exceeds the sum (4.14) of the O.R. generated by a single exposure (O.R. = 0.72 for HBsAg positivity, OR = 1.34 for anti-HCV positivity, and O.R. = 2.08 for alcohol intake). No interaction is observed in male sex.
CONCLUSIONS: The observed gender difference suggests that the simultaneous presence of HBV/HCV coinfection and risky alcohol intake enhances the mechanism of liver damage to a greater extent in females than in males.
The Lancet
The Lancet began as an independent, international weekly general medical journal founded in 1823 by Thomas Wakley. Since its first issue (October 5, 1823), the journal has strived to make science widely available so that medicine can serve, and transform society, and positively impact the lives of people.

Eliminating viral hepatitis: time to match visions with action

Of Interest
AMI Podcast - November 13, 2017 episode
2017 World Hepatitis Summit

Hepatitis C in Canada

Dr. Jordan Feld from the Toronto Centre for Liver Disease discuss what it will take for hepatitis C to be cured in Canada.

Of all infectious disease in Canada the one disease that causes most years of life lost is hepatitis C. 
Listen here......