Thursday, August 30, 2018

Current status of imaging in nonalcoholic fatty liver disease

Patients with non-alcoholic fatty liver disease (NAFLD) are at risk of steatohepatitis and progressive liver fibrosis culminating in cirrhosis, typically over a period of decades. Early diagnosis and risk stratification are essential for effective management. Current imaging methods such as ultrasound, computed tomography, and magnetic resonance elastography have demonstrated their values to serve as noninvasive imaging biomarkers to evaluate NAFLD progression, but they are still relatively limited in the detection of inflammation, which is more important than steatosis in terms of its high risk for fibrosis, cirrhosis, and hepatocellular carcinoma.

Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2018; 10(8): 530-542
Published online Aug 27, 2018. doi: 10.4254/wjh.v10.i8.530 

Current status of imaging in nonalcoholic fatty liver disease
Qian Li, Manish Dhyani, Joseph R Grajo, Claude Sirlin, Anthony E Samir 

Non-alcoholic fatty liver disease (NAFLD) is the most common diffuse liver disease, with a worldwide prevalence of 20% to 46%. NAFLD can be subdivided into simple steatosis and nonalcoholic steatohepatitis. Most cases of simple steatosis are non-progressive, whereas nonalcoholic steatohepatitis may result in chronic liver injury and progressive fibrosis in a significant minority. Effective risk stratification and management of NAFLD requires evaluation of hepatic parenchymal fat, fibrosis, and inflammation. Liver biopsy remains the current gold standard; however, non-invasive imaging methods are rapidly evolving and may replace biopsy in some circumstances. These methods include well-established techniques, such as conventional ultrasonography, computed tomography, and magnetic resonance imaging and newer imaging technologies, such as ultrasound elastography, quantitative ultrasound techniques, magnetic resonance elastography, and magnetic resonance-based fat quantitation techniques. The aim of this article is to review the current status of imaging methods for NAFLD risk stratification and management, including their diagnostic accuracy, limitations, and practical applicability.

Coffee and marijuana may sharply reduce the risk for early death from Hep C?

In the News
AUGUST 30, 2018

Coffee, Pot Linked to Lower Mortality From Hepatitis C
Increased consumption of coffee and marijuana may sharply reduce the risk for early death from hepatitis C infection, researchers have found.

The study of more than 1,200 patients with HCV and HIV found that those who drank the most coffee and used marijuana regularly or daily had more than a 60% lower risk for death from the infection over a five-year period.

How cannabis in particular might reduce mortality is unclear, but the researchers, led by Maria-Patrizia Carrieri, PhD, of the Université Aix Marseille, in France, noted that the substance has been previously associated with a reduced risk for insulin resistance and steatosis, two conditions that could increase mortality in patients with HCV.
Read the article:

Wednesday, August 29, 2018

Blog Updates: Nutrition in Cirrhosis, Living With Cirrhosis, Alzheimer’s and Liver Health

Welcome folks, start by downloading a comprehensive guide about nutrition written for people with cirrhosis, or check out an interview featuring a courageous individual battling cirrhosis who bravely treated the hepatitis C virus. Finally, review a study from the University of Pennsylvania investigating possible links between the gut, liver and Alzheimer’s disease.
*links are provided below

Hepatology - Top Story From Healio 
Healio features the industry’s best news reporting, dynamic multimedia, question-and-answer columns, educational activities in a variety of formats, blogs, and peer-reviewed journals.
Latest News: August 29, 2018 
Results of a recent mortality profile of New York City residents with hepatitis C and hepatitis B showed that patients with HCV were significantly more likely to have HIV coinfection, hepatocellular carcinoma, and lower survival rates compared with HBV.

Thank you CLF, Healio and the following awesome bloggers who continue to share their experience with liver disease, viral hepatitis, liver cancer and more... 

Canadian Liver Foundation
At CLF we strive to improve prevention and the quality of life of those living with liver disease by advocating for better screening, access to treatment, and patient care.
Latest blog entry: The Nutrition in Cirrhosis Guide
Filled with practical tips and healthy recipes, this guide will help patients with cirrhosis and their caregivers navigate more effectively through daily life.

Hep is an award-winning print and online brand for people living with and affected by viral hepatitis.
Latest blog updates: Aug 29, 2018
Patient Experience Living With Cirrhosis with John M., Part 1
By Connie M. Welch
Connie Welch’s interview of John M, who was successfully treated and cured from hepatitis C in 2014 with Harvoni.

Aug 23, 2018
By Karen Hoyt
After being sick with cirrhosis, treatment for Hepatitis C, liver cancer, and transplant, Karen wonders about PTSD from liver disease.

ADRLF (Al D. Rodriguez Liver Foundation)
Al D. Rodriguez Liver Foundation is a non-profit organization that provides resources, education and information related to screening, the prevention of and treatment for the Hepatitis Virus and Liver Cancer. 
Latest blog entry: Aug 28, 2018
It is safe to assume that many people do not know, nor would even suspect that there is a connection between liver health and Alzheimer’s disease. Last month, at the annual Alzheimer’s Association International Conference held in July in Chicago, researchers from the University of Pennsylvania presented interesting findings which identify the liver as a ‘new player’ in the study of Alzheimer’s disease.

Lucinda K. Porter
Lucinda Porter is a nurse, speaker, advocate and patient devoted to increasing awareness about hepatitis C.
Latest blog entry: August 23, 2018
Healing and the Power of Support Groups
I am a huge fan of support groups, especially for those who are going through HCV treatment. In this era of short medical appointments, support groups provide an opportunity for participants to share tips with each other. Further, patients who have personal experience with treatment bring perspective and a streetwise expertise that is highly valuable to those who are newly diagnosed or in treatment.

Hepatitis NSW
At NSW we provide information, support, referral and advocacy for people affected by viral hepatitis in NSW. We also provide workforce development and education services both to prevent the transmission of viral hepatitis and to improve services for those affected by it.
Latest blog entry: August 15, 2018
DAAs decrease hep C deaths but double GPs needed
Hepatitis C deaths have declined by 20% in the two years since direct-acting antivirals were added to the PBS, infectious diseases physicians say. Professor Greg Dore, from the Kirby Institute,…

Life Beyond Hepatitis C
Life Beyond Hep C is where faith, medical resources and patient support meet, helping Hep C patients and their families navigate through the entire journey of Hep C.
Latest blog entry: August 29, 2018
Dealing with liver disease or any chronic illness can be challenging enough and can bring an out of control feeling. Your diet is something you can control. It gives you a sense of being behind the wheel with your health.
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.
Latest blog updates: August 29, 2018
It’s Not Easy Being Yellow: Thoughts on Jaundice
By Karen Hoyt
For me, jaundice was the symptom that sent me to the emergency room. There, they pronounced that I had hepatitis.

August 24, 2018
Summer Heat & Hep C
By Kimberly Morgan Bossley
It’s the heat of the summer. The temperatures are soaring, with record heat across the country. News stations are reminding people to stay hydrated, to stay inside during peak hours, and to check on the elderly and those with health conditions. But what does all this heat mean for people with hep C?

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.
Latest blog entry: August 29, 2018
Journey to the Cure: What Does Liver Cancer Research Look Like?
Aejaz Sayeed, PhD
Welcome to “Journey to the Cure.” This is a web series that chronicles the progress at the Hepatitis B Foundation and Baruch S. Blumberg Institute towards finding the cure for hepatitis B.

Healthy You
Harvard Health Blog
10 superfoods to boost a healthy diet
August 29, 2018
Katherine D. McManus, MS, RD, LDN
Over the years, research has shown that healthy dietary patterns can reduce risk of high blood pressure, heart disease, diabetes, and certain cancers.

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How response to HCV treatment impacts the incidence of type 2 diabetes

Impact of Sustained Virologic Response on Risk of Type 2 Diabetes Among Hepatitis C Patients in the United States 
J. Li; T. Zhang; S. C. Gordon; L. B. Rupp; S. Trudeau; S. D. Holmberg; A. C. Moorman; P. R. Spradling; E. H. Teshale; J. A. Boscarino; M. A. Schmidt; Y. G. Daida; M. Lu

J Viral Hepat. 2018 Aug;25(8):952-958. 

Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used the data from the longitudinal Chronic Hepatitis Cohort Study-drawn from four large US health systems-to investigate how response to HCV treatment impacts the risk of subsequent diabetes. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated the incidence of type 2 diabetes from 12 weeks post-HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virologic response [SVR] or treatment failure) and baseline risk factors on the development of diabetes, considering any possible risk factor-by-SVR interactions, and death as a competing risk. Among 5127 patients with an average follow-up of 3.7 years, diabetes incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR] = 0.79; 95% CI: 0.65-0.96). Risk of diabetes was higher among African American and Asian American patients than White patients (aHR = 1.82 and 1.75, respectively; P < .05), and among Hispanic patients than non-Hispanics (aHR = 1.86). Patients with BMI ≥ 30 and 25-30 (demonstrated higher risk of diabetes aHR = 3.62 and 1.72, respectively; P < .05) than those with BMI < 25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR = 1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for the development of type 2 diabetes mellitus than patients with treatment failure.

Discussion Only 
Full text available online @ Medscape 
In a large US cohort of patients treated for HCV, we found that the achievement of SVR independently reduced the risk of T2D. There were no SVR-by-covariate interactions detected, meaning the SVR effect was consistent across patient demographic characteristics and clinical conditions at the time of treatment, including serum alanine aminotransferase (ALT) levels.

We observed an independent effect of HCV-related cirrhosis on increasing T2D incidence after adjusting for other covariates as well as SVR status. This effect has been reported previously; univariate analyses in a smaller European study (n = 365) showed that increasing fibrosis score was a risk factor for the development of T2D.[2] We did not observe a significant effect of ALT in either univariate or multivariate analyses. It is possible, however, that the lack of a significant finding was a consequence of a relatively large proportion (20%) of missing ALT data and/or the strong correlation between ALT and cirrhosis, which may have diminished the observed effect of ALT.

Race has been previously identified as a factor associated with increased the risk of T2D in the general US population and among patients with HCV in Europe.[9,10] Our results are consistent with these findings, although the effects we observed were larger than those reported in other studies; the risk of T2D was 92% higher among African American patients and 75% higher among ASINPI patients compared with Whites, after adjusting for BMI and other covariates.

Some studies have suggested that sex and HCV genotype are associated with the risk of T2D, but these results have not been consistent.[9] In our study, sex was a significant risk factor in univariate analysis, but was not significant after adjusting for other covariates. HCV genotype was not significantly associated with T2D incidence in either univariate or multivariate analyses.

Our study has some limitations. Data available to calculate baseline BMI and to impute FIB4 score were incomplete, given our reliance on electronically collected observational data as well as the inclusion of some patients treated beginning in the early 1990s. Additionally, our study was largely limited to the interferon era of HCV treatment. However, the CHeCS "dynamic" sampling design, which adds new patients to the cohort at regular intervals while continuing to follow the existing patients, has allowed us to begin the preliminary analyses of the impact of DAA regimens on the incidence of T2D.

Debate remains regarding whether and how HCV infection might increase the risk of T2D.[11,12] Although some studies have found that T2D occurs more frequently among subsets of HCV-infected versus uninfected individuals,[13–15] other studies suggest that observed increases in the risk of T2D may be a consequence of HCV-related elevation in ALT,[16,17] perhaps further confounded by high BMI and/or cirrhosis.[18] We found that cirrhosis, but not baseline ALT, independently increased the risk of T2D in all treatment groups. Although we observed that successful HCV treatment reduced the risk of future diabetes, our analysis could not evaluate whether this risk reduction resulted from viral eradication, from subsequent reductions in inflammation or fibrosis, or through some other mechanism. Future analyses may help elucidate these mechanisms.

Additionally, although we observed that the absence of successful antiviral therapy increases HCV patients' risk of T2D, a number of studies have suggested that T2D and insulin resistance reduce response to antiviral therapy, particularly interferon-based treatments.[19–22] This two-way association illustrates the complex relationship between T2D, HCV and SVR, and may have introduced bias into the observed effect of SVR on the risk of T2D. We excluded patients previously diagnosed with T2D from our analysis, but due to the observational nature of our study, comprehensive identification of each patient with potentially elevated glucose and insulin resistance was not feasible. To address this issue, we performed a sensitivity analysis of patients with available glucose assessments, excluding those with fasting or random glucose levels greater than 110 mg/dl. Exclusion of these patients produced results similar to our main analysis.

Another limitation is that our assessment of the association between independent baseline covariates and the risk of T2D incidence was restricted to treated patients. Given the absence of variable-by-SVR interactions and the increasing uptake of DAA treatment in the HCV patient population, we expect that our observations regarding the impact of race and cirrhosis on the development of T2D may be generalizable to a broader population of patients with HCV.

In conclusion, among a geographically and racially diverse cohort of more than 5000 patients from US healthcare systems, successful HCV treatment was associated with significant reductions in the incidence of T2D. African American and ASINPI race as well as the presence of cirrhosis appear to increase the risk of developing T2D among those without SVR. Therefore, patients with these risk factors should be monitored closely for T2D prevention and care.

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FDA statement on the agency’s ongoing work to address the opioid crisis

FDA Statement 

Statement by FDA Commissioner Scott Gottlieb, M.D., on the agency’s ongoing work to forcefully address the opioid crisis
August 29, 2018
Over the past 17 months, we’ve set out to address the opioid crisis forcefully, using all the agency’s tools and authorities. These steps have been part of a comprehensive approach that the Secretary of Health and Human Services has outlined. Our efforts at the U.S. Food and Drug Administration are part of these broader efforts and cut across three broad areas.

First, we set out to cut the rate of new addiction. We did this in part by taking new steps to rationalize the prescribing of opioids, and amounts dispensed, as a way to reduce exposure to the drugs in the medical setting.

Second, we’ve stepped up enforcement of the marketing and sale of illicit opioids. One way that we’re doing this is by targeting online sites that enable the illegal sale of these drugs and their shipment through the mail.

Finally, we’ve undertaken new efforts to support novel product innovation. This includes innovation in treatments for opioid addiction, and efforts to promote their more widespread use. And it also includes steps to advance the development of non-addictive treatments for pain. We have great concern for the millions of Americans who live with chronic pain and for whom traditional treatment options have been exhausted.

I want to take this opportunity to provide an update on some of the work we are doing across each of these three areas and some of the new efforts we’re going to pursue. To pursue these goals, and many other commitments, in the last 17 months, we’ve taken a range of new steps.

We set out to extend our risk evaluation and mitigation strategy program to cover the immediate release formulations of opioid drugs, and we’ve updated our educational content for providers to include information on non-opioid alternatives. We also, for the first time, extended this training to non-physician prescribers.

And we’ve advanced a broad effort to develop evidence-based guidelines for opioid prescribing. We want to make sure that when opioids are used, the amount dispensed comports with the clinical reasons why these drugs are being used in the first place. No more 30-day prescriptions for a tooth extraction or an appendectomy.

We’ve also taken steps to protect children from unnecessary exposure to certain opioids in some common prescription cough and cold medicines.

We committed to look closely at the risks associated with the illicit use of these drugs as a factor in how we evaluate their pre- and post-market safety. We requested the market withdrawal of one drug – Opana ER – based on a consideration of risks that were manifest only when this drug was being misused and abused. We’ll soon release new guidance outlining how we make these considerations of risks associated with illicit use a clear factor in our pre- and post-market regulatory decisions.

We also took enforcement actions, including work in collaboration with the Federal Trade Commission targeting the proliferation of products on websites that marketed unapproved treatments for pain and addiction. With additional actions that we took yesterday, we’ve brought to 70 the number of web sites that we’ve targeted this summer for marketing unapproved opioid drugs. More enforcement actions are on the way. We also formed a broad collaboration with legitimate internet sites – including leading social media platforms – to target the sale of opioids in ways that are visible to the public, and in some ways that are not apparent.

We sharply expanded our oversight of drugs being shipped illegally through international mail facilities, growing by nearly a factor of 10 the number of packages that the FDA is able to open and inspect. We have also increased our special agents doing criminal work at the ports of entry as well as cybercrime, strategic intelligence and strategic analysis units – all of whom are critical to effective enforcement. And we launched major operations with other federal partners to target these shipments and get an accurate estimate of how many opioids are coming in illegally through the mail. We’ll soon announce the findings from this operation.

We expanded new pathways for the development of safe and effective treatments for addiction, lowering the barriers to innovation for treatments that meet our gold standard. New guidance we issued will expand the range of clinical endpoints that treatments for addiction can pursue, creating more opportunities for more efficient product development. And we undertook a broad campaign to promote Medication-Assisted Treatment (MAT), and address the inappropriate stigma that’s sometimes associated with replacement therapy.

We developed new regulatory guidance to promote abuse-deterrent formulations of opioid drugs, including a new path for the development of generic versions of drugs with these features. And we’ve launched an effort to evaluate whether the nomenclature that we use to describe these drugs inappropriately promotes a view that these formulations are somehow less addictive.

We launched an innovation challenge to spur the development of medical devices and mobile applications that can ultimately serve as alternatives to oral opioids to help combat the opioid crisis and prevent and treat opioid addiction. We also held two public meetings this year focused entirely on patients – one for Opioid Use Disorder and one for Chronic Pain. And we did many of these things under the direction of a new Opioid Policy Steering Committee that I formed when I arrived at the FDA, that brings together senior leaders from our programs. That Steering Committee has helped generate and oversee some of the new ideas that drive our strategy.

We appreciate the support that Congress has given us in the pursuit of these goals, with new resources as well as the new authorities that have passed the House and that the Senate is now considering that will help us in this fight. Along the way, as we’ve embraced these challenges, we’ve learned some hard lessons. I’ve learned some hard lessons. And one sticks with me above others. It’s this.

The reason that we find ourselves with a crisis of such proportion is that as a medical profession, we’ve been one step behind its sinister advance. Collectively, we didn’t take all the steps we could, when we could, to stop the advance of this crisis. We shunned hard decisions. As a profession, providers were too liberal in our use of these drugs well past the point where there were signs of trouble, and the beginning of a crisis of addiction.

I’m committed to making sure that we don’t perpetuate these mistakes of the past. And so, when we see this crisis taking new twists and turns, we’ve acted swiftly. For example, we’ve taken steps to address what we believe may be abuse of substances that contribute to the opioid crisis, like gabapentinoids and loperamide or kratom. And we’re increasing our vigilance around the risk of addiction, and acting more quickly to warn the public when we identify harmful trends and emerging risks.

I don’t want to look back ten years from now and wish there were more policies we had pursued, or more steps we had taken, to stop the advance of this crisis. We must all be able to say we did everything we could. That we acted as aggressively as needed. And that we succeeded.

So at the FDA, we’ve done all these things, and taken many other actions, with this promise in mind. We’re going to be taking many additional steps to continue to pursue these goals. That includes additional steps to foster innovation. Part of our approach is focused on developing non-opioid, and non-addictive alternatives for the treatment of pain. We know that many Americans suffer from chronic and episodic acute pain. For these people, sometimes opioids are the only drugs that work. To address these medical needs, we’re taking new steps to foster development of treatments for pain that don’t rely on opioids and don’t have their addictive features.

First, we intend to withdraw our existing, 2014 analgesic guidance document on developing new pain drugs. That guidance typically called for a large number of studies to get a general chronic pain indication and may have been difficult to implement because it was so broad. Instead, we’ve determined that a more focused approach would streamline drug development in specific areas.

To that end, we plan to issue at least four new guidance documents in place of this 2014 analgesic guidance document. We’ll issue these guidances in a series over the next six to twelve months. These new policies will create a more efficient path for new product innovation.

The new guidance documents will recommend the study of one or two populations for innovators who wish to pursue a more limited indication for the treatment of specific kinds of pain. This will broaden the range of new drug development opportunities that are available. Our new approach should also help more novel products for the treatment of pain come to market more efficiently.

Among the forthcoming guidance documents that we plan to issue is a guidance, which will be out soon, and will address drugs that can spare the use of opioids in the treatment of acute pain. This guidance document will set forth the FDA’s current thinking on how sponsors can demonstrate a clinically meaningful reduction in the use of opioid pain medications when used for acute pain.

In addition to this guidance, we also plan to issue a guidance to outline the information that the FDA will ask drug makers to provide to help assess the benefits and risks when new opioid pain drugs are put into development. This will include an updated framework for evaluating the risks associated with intentional or illicit misuse or abuse of drugs. As I noted, we’re explicitly considering the risks associated with illicit use as a factor in how we assess risks and benefits.

In a third guidance, we’ll outline a path for developing extended-release local anesthetics, which can serve as an alternative to the systemic use of oral opioid drugs. This guidance will address the clinical pharmacology, the proper evaluation of safety and efficacy, and the types of studies that may support approval of these products.

Finally, we also plan to issue a guidance document to assist sponsors with the development of new non-opioid pain medications for chronic pain that can provide therapeutic alternatives to the use of opioids.

These are just some of the new steps we’re taking to promote innovation for alternatives to opioid drugs for those who need treatment for acute and chronic pain. And today, I outlined just some of the overall steps we’re taking to address the crisis of addiction to opioids. We have many other actions underway. This is an all-of-the-above approach. Everything is on the table.

We needed to broaden our approach as this crisis continues to evolve. The epidemic is turning from one that was largely dominated by addiction formed in the medical setting, involving prescription drugs, to one that increasingly implicates the use of illicit drugs, including highly potent fentanyls. These drugs are obtained illegally, often through purchases made on-line, and in many cases shipped through the international mail.

A recent FDA analysis of commercially available data showed steep drops in dispensing of opioid analgesics in retail outpatient settings. In the first six months of 2018, the volume of opioid analgesics dispensed was 74.1 metric tons of oral morphine equivalent, down more than 16 percent from the first half of 2017, when the volume dispensed was 88.8 metric tons. Earlier declines were there, but smaller. The volumes of opioid analgesics dispensed in the first half of 2017 and 2016 were about 10.4 percent and 3.4 percent less than comparable values 12 months earlier. These trends seem to suggest that the policy efforts that we’ve taken are working as providers, payers and patients are collectively reducing some of their use of prescription opioid analgesic drugs.

But the public health impact from these reductions in prescription opioid use could be offset by the rising availability of illicit opioids, and principally fentanyl, that’s coming into America. The growing use of fentanyl is contributing to a rise in overdose deaths. It isn’t necessarily the case that more people are suddenly switching from prescription opioids to these illicit drugs. The idea of people switching to illicit drugs isn’t new as an addiction expands, and some people have a harder time maintaining a supply of prescription drugs from doctors. Many heroin users switched from prescription drugs. What’s new is that more people are now switching to highly potent drugs that are far deadlier. That’s driven largely by the growing availability of the illicit fentanyls.

At the FDA, we’re taking steps right now to accurately estimate the flow of these illicit drugs. But our current estimates are largely based on the fentanyl seized by our colleagues and partners at Customs and Border Protection (CBP). Based off of publicly available information, seizures of fentanyl by our CBP colleagues were reported as two pounds in fiscal year 2013, rising to 440 pounds in FY16, and 1,377 pounds in FY17. CBP reported 1,640 pounds seized during the first 10 months of fiscal year 2018. During these same periods, reported heroin seizures also increased, from 4,790 pounds in 2016, to 4,878 pounds in fiscal year 2017 and an estimated 5,472 pounds in fiscal year 2018 if we were to extrapolate seizures through July to the full fiscal year.

If we assume that the seizures effected by our colleagues at CBP represent some fraction of the overall illegal flows that are being smuggled into the U.S. through different routes and despite our best efforts; then we should worry that the public health impact of a decline in prescription opioid use in the medical setting could be offset by the rise in highly potent, illicit opioids like fentanyl. The FDA has garnered a strong partner with CBP in our efforts to combat these trends, whether it be our joint scientific or operational work. Our two teams are collaborating closely on solutions to this problem. We’re taking new steps to confront this dangerous turn.

We have additional enforcement operations underway. We’re taking new steps to promote innovation in the development of alternative treatments for pain that may not be as addictive as opioids. At the same time, we’re advancing new policies to rationalize the legal use of prescription opioid drugs in the medical setting. To address this goal we are also developing an approach on the use of blister packs for opioid drugs as a way to better control prescription dispensing and reduce exposure.

And we’re actively considering other new policy options, like novel steps to better manage the use of high-dose opioid formulations. More FDA action is on the way.

I made a commitment 17 months ago, when I first joined the FDA as the agency’s Commissioner, that we’d do everything in our scope to address this crisis. I’ve made this promise a cornerstone of my efforts at the agency, and a foundation of my obligation to Americans.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by 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.

FDA warned more online networks illegally marketing unapproved opioids; including tramadol

FDA News Release 

FDA takes action against 21 websites marketing unapproved opioids as part of agency’s effort to target illegal online sales

The U.S. Food and Drug Administration today announced it has warned four more online networks, operating a total of 21 websites, illegally marketing potentially dangerous, unapproved, and misbranded versions of opioid medications, including tramadol. The warning letters issued by the FDA to each of the networks state that they must immediately stop illegally selling these products to American consumers.

“The illegal online sale of opioids represents a serious risk to Americans and is helping to fuel the opioid crisis. Cutting off this flow of illicit internet traffic in opioids is critical, and we’ll continue to pursue all means of enforcement to hinder online drug dealers and curb this dangerous practice,” said FDA Commissioner Scott Gottlieb, M.D. “Today’s effort builds on previous actions against the illegal online sale of opioids, for a total of 13 warning letters to more than 70 websites just this summer. The FDA remains resolute in our promise to continue cracking down on these networks to protect the public health. We have more operations underway, and additional actions planned. We are also working closely with legitimate Internet stakeholders, including leading social media sites, in these public health efforts.”

Patients who buy prescription medicines, including opioids, from illegal online pharmacies may be putting their health at risk because the products, while being marketed as authentic, may be counterfeit, contaminated, expired, or otherwise unsafe. As noted in the warning letters, these websites offer for sale opioids that are misbranded and unapproved new drugs, including unapproved tramadol, in violation of the Federal Food, Drug, and Cosmetic Act. In addition to health risks, illegal online pharmacies can pose other risks to consumers, including credit card fraud, identity theft, and computer viruses.

The illegal sale of these products is particularly concerning considering that FDA-approved tramadol carries a boxed warning, the FDA’s most prominent warning, indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. The boxed warning for tramadol addresses risks including addiction, abuse, misuse, life-threatening respiratory depression (breathing problems), and neonatal opioid withdrawal syndrome (withdrawal symptoms in newborn babies). In addition, when taken with other central nervous system depressants, including alcohol, tramadol’s use may result in coma or death.

The networks receiving warning letters include:

The FDA requested responses from each of the companies within 10 working days. The companies are directed to inform the agency of the specific actions taken to address the agency’s concerns. Companies who fail to correct the violations, as outlined in the warning letters, may be subject to legal enforcement action.

Opioid addiction is an immense public health crisis. Addressing it is one of the FDA’s highest priorities and supports the U.S. Department of Health and Human Services’ 5-Point Strategy To Combat the Opioid Crisis. One critical step to addressing this public health emergency is the adoption of a more proactive approach by internet stakeholders to crack down on internet traffic in illicit drugs. Illegal online pharmacies, drug dealers, and others continue to use the internet to further their illicit distribution of opioids, where the risk of detection and repercussions is significantly reduced.

The FDA has been active in combating the illegal online sales of opioids. In June, the agency announced a similar series of warning letters, and on June 27 the FDA hosted internet stakeholders and thought-leaders, government entities, academic researchers, and advocacy groups at an Online Opioid Summit to discuss ways to collaboratively take stronger action in combatting the opioid crisis by reducing the availability of illicit opioids online. Topics that were addressed during the summit included: research into the ease with which illicit opioids can be purchased online and industry approaches to addressing opioids marketed online, followed by a roundtable discussion to identify gaps and new solutions. The FDA continues to be engaged with the companies that participated in the Summit and will share more in the coming months.

The FDA remains committed to addressing the national crisis of opioid addiction on all fronts, with a significant focus on decreasing exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies and opioids more resistant to abuse and misuse; and taking action against those who contribute to the illegal importation and sale of opioids. The agency will also continue to evaluate how opioids currently on the market are used, in both medical and illicit settings, and take regulatory action where needed.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by 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.

Perinatal Transmission of Hepatitis C Virus: Defining the Cascade of Care

Perinatal Transmission of Hepatitis C Virus: Defining the Cascade of Care
Rachel L. Epstein, MD, Vishakha Sabharwal, MBBS, Elisha M. Wachman, MD,
Kelley A. Saia, MD, Claudia Vellozzi, MD, MPH, Susan Hariri, PhD, Benjamin P. Linas, MD, MPH


Complete article shared by @HenryEChang via twitter

The US National Viral Hepatitis Action Plan calls for major efforts to expand hepatitis C virus (HCV) diagnosis and treatment; prenatal care settings are potential venues for expanding HCV testing. We aimed to characterize the HCV diagnostic cascade for women and infants and investigate factors associated with linkage and follow-up.

Study design
We used electronic health records for a 10-year cohort of 879 women with opioid use disorder from an obstetric clinic serving women with substance use disorders.

Altogether, 744 women (85%) were screened for HCV; 510 (68%) were seropositive, of whom 369 (72%) had nucleic acid testing performed and of these 261 (71%) were viremic. Of 404 infants born to HCV-seropositive women, 273 (68%) were tested at least once for HCV, 180 (45%) completed the American Academy of Pediatrics-recommended perinatal HCV screening, and 5 (2.8%) were diagnosed with HCV infection and linked to care. More recent delivery date (2014-2015) was associated with maternal linkage to care (aOR, 2.5; 95% CI, 1.4-4.7). Maternal coinfection with HIV (aOR, 9.0; 95% CI, 1.1-72.8) and methadone maintenance therapy, compared with buprenorphine (aOR, 1.5; 95% CI, 0.9-2.5), were associated with higher rates of infant HCV testing.

HCV prevalence among pregnant women with opioid use is high and infant HCV screening is imperfect. Programmatic changes to improve both mother and infant follow-up may help to bridge identified gaps in the cascade to cure.

Monday, August 27, 2018

New target could prevent progression of liver damage to cancer

Journal of Clinical Investigation

New target could prevent progression of liver damage to cancer 
AUGUSTA, Ga. (Aug. 27, 2018) - Problems like obesity and alcoholism appear to chronically trigger in the liver a receptor known to amplify inflammation in response to invaders like bacteria, scientists report.

The relentless, increased activity of TREM-1 in turn accelerates injury and scarring of the liver, a first step toward cirrhosis and liver cancer, says Dr. Anatolij Horuzsko, reproductive immunologist in the Georgia Cancer Center and Department of Medicine at the Medical College of Georgia at Augusta University.

TREM-1, or triggering receptor expressed on myeloid cells-1, is known to help turn up inflammation short-term to help us deal with external invaders. It has increased activity immediately after an injury as well, when increased inflammation, damage cleanup and collagen production aid healing.

But Georgia Cancer Center scientists report in the Journal of Clinical Investigation the first evidence that when activated by chronic offending agents, like obesity and hepatitis, TREM-1 instead contributes to a destructive level of inflammation that results in liver damage and possibly cancer.

The unhealthy transformation can occur in five to 50 years, depending on factors like the level of insult, and may be largely reversible up to the point of cirrhosis, if the offending agent is stopped, and the liver's natural ability to regenerate takes over.

Horuzsko and his colleagues think TREM-1 could one day be another point of intervention, possibly with a drug that could return TREM-1 activation to normal levels on resident, garbage-eating, watchdog immune cells called Kupffer cells.

"Right now we have treatment for hepatitis C, for example, which is very efficient, if we treat it before too much damage is done. But we don't have treatment for alcohol- or obesity-related damage," Horuzsko says.

They already are doing experiments with a drug that, because of its structure, should enable tamping down of TREM-1, but long-term goals include a drug that would target this receptor on Kupffer cells.

It's known that inflammation is a key process in the thickening and scarring of the liver called fibrosis, and that tamping down inflammation can help prevent fibrosis progression. But just how inflammation and fibrosis happen at the cellular and molecular level is largely unknown, say Horuzsko, the study's corresponding author.

Their work in both animal models and human tissue indicate TREM-1 is essential to both.

In the liver, TREM-1 is found primarily on Kupffer cells, the liver's resident macrophages, as well as monocytes, a type of white blood cell that can also become garbage-eating macrophages.

TREM-1's expression is limited in a healthy human liver but its activation goes up short-term following an insult, like a laceration.

To look at what happens in the face of a chronic problem, the scientists created a model of chronic liver disease - like obesity or high alcohol consumption might - using carbon tetrachloride, a poisonous solvent found in oils, varnishes and resin. They found TREM-1 activation went up and stayed up on a larger number of Kupffer cells in the liver as well as other immune cells circulating in the body.

When they deleted TREM-1 from the model, it reduced inflammation, injury and subsequent fibrosis. When they gave TREM-1 back to the mice, inflammation and related damage came back with a vengeance, leading them to dub TREM-1 the main target that drives fibrogenesis.

They found TREM-1 even recruits other pro-inflammatory cells from the bone marrow to the liver, many of which could become macrophages as well, which further multiplies the inflammation, liver cell damage and death.

"This creates a loop," says Horuzsko, of increased activity on many fronts. "This creates chronic inflammation - with no bacterium or virus involved - which is important to the development of liver disease."

As liver cells die in the face of chronic inflammation, they release their innards, called damage associated molecular patterns, or DAMPs, when they get outside the cells. DAMPs further activate TREM-1 on the macrophages and the damaging momentum builds, he says.

That's where collagen and fibrosis set in. Stellate cells in the liver are normally quiescent and mainly store vitamin A. When TREM-1 gets activated on the macrophages, it also activates the macrophages themselves which, in turn, activate stellate cells.

Stellate cells literally change their shape, release vitamin A and start to make collagen. Collagen is a component of connective tissue that typically helps hold tissues and blood vessels together and aids wound healing. The liver already has some collagen, but in this scenario too much gets deposited and liver function suffers.

"Efficiency goes down and it causes additional damage to liver cells that already have been damaged by something like hepatitis or obesity," Horuzsko says. The liver of a patient with cirrhosis, for example, is overrun with collagen, he notes.

Blood levels of the enzymes alanine aminotransferase, or ALT, and aspartate aminotransferase, or AST, are indicators of liver injury and both went up and remained high in their models. However, in mice where TREM-1 was knocked out, rates went up only short- term before returning to pre-injury levels, another indicator of TREM-1's role in persistent inflammation and resulting damage, Horuzsko says.

They also found that while mice with and without TREM-1 both recruited additional immune cells, such as more macrophages and monocytes, from their bone marrow immediately after the injury, 72 hours later the levels were much higher both in the blood and livers of the mice that also still had TREM-1.

To look further at the role of Kupffer cells when TREM-1 is out of the picture, they first removed the cells from both mice models, then gave Kupffer cells that contained TREM-1 back to both, and both were able to cause localized damage and recruit immune cells from the marrow to further bolster inflammation. But when they put TREM-1-deficient Kupffer cells back in normal mice, the exaggerated inflammation and liver damage did not happen.

Likewise, they found markedly increased infiltration of TREM-1 expressing cells in patients with liver fibrosis.

"TREM-1 is a molecule that can be very dangerous and is normally very controlled in the body," Horuzsko says. In fact, one of the diagnostic criteria for body-wide infection, or sepsis, is the level of TREM-1 protein in the fluid portion of a patient's blood. And, in hepatitis B related liver cancer in humans, high levels of TREM-1 expression on stellate cells is considered an indicator of poor prognosis.

"The balance in our body is very, very tightly regulated and important. Alcohol, obesity, hepatitis viruses all change the balance," Horuzsko says.

The scientists suspect their findings of TREM-1 gone wild will hold true in other organs including the lungs, heart and kidneys, which also have TREM-1 on their macrophages.

Liver cancer rates have risen dramatically in the United States, 43 percent in men and 40 percent in women, from 2000-16, according to a report released this summer by the Centers for Disease Control and Prevention. In May 2017, the CDC reported that newly reported cases of hepatitis C tripled between 2010-15 and the American Cancer Society says liver cancer rose from ninth to the sixth leading cause of cancer death from 2000-16.

The most common causes of liver cancer include infection with the hepatitis B or C virus, heavy alcohol use, obesity and diabetes, according to the CDC.

The liver is part of the gastrointestinal tract and filters blood coming from the GI tract before the blood circulates to the rest of the body. Its myriad of functions include secreting bile, which helps us absorb fats and eliminate waste; producing cholesterol, triglycerides and blood clotting factors; and detoxifying chemicals. The liver is the heaviest solid organ in the body and sits on the right sight of the body behind the lower ribs. 

The research was funded by the National Institutes of Health.

Saturday, August 25, 2018

No Amount Of Alcohol Is Good For Your Health

NPR - Heard on All Things Considered
The Latest Scientific Advice On Drinking Alcohol: Don't
A new study published in The Lancet finds alcohol is associated with 2.8 million deaths each year worldwide. Researchers conclude that there is no safe level of alcohol and say the risks outweigh the potential benefits

No Amount Of Alcohol Is Good For Your Health, Global Study Says
August 24, 20183:42 PM ET
Samantha Raphelson
No amount of alcohol is safe, according to The Global Burden of Diseases study, which analyzed levels of alcohol use and its health effects in 195 countries from 1990 to 2016.

The Lancet
Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
Open Access
Published: August 23, 2018

Linked Article
No level of alcohol consumption improves health

Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.

Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.

Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5–3·0) of age-standardised female deaths and 6·8% (5·8–8·0) of age-standardised male deaths. Among the population aged 15–49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2–4·3) of female deaths and 12·2% (10·8–13·6) of male deaths attributable to alcohol use. For the population aged 15–49 years, female attributable DALYs were 2·3% (95% UI 2·0–2·6) and male attributable DALYs were 8·9% (7·8–9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0–1·7] of total deaths), road injuries (1·2% [0·7–1·9]), and self-harm (1·1% [0·6–1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2–33·3) of total alcohol-attributable female deaths and 18·9% (15·3–22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0–0·8) standard drinks per week.

Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.

Funding Bill & Melinda Gates Foundation.

Observational Data: Drinking coffee can be part of a healthy diet

Cleveland Clinic Reports
New research says you can drink as much as eight cups a day.
Cleveland Clinic’s Julia Zumpano, RD, did not take part in the research, but says the study showed that regular ground coffee had the most benefit. The researchers noted their results were based on observational data and should be interpreted with caution. “Nevertheless, these results provide further evidence that coffee drinking can be part of a healthy diet and may provide reassurance to those who drink coffee and enjoy it,” the authors concluded. Complete results of the study can be found in JAMA Internal Medicine.
July 2017
Observational evidence published in Annals of Internal Medicine
Journal Review - Richard Lehman
Coffee: wake up and smell the confounding
Two big observational studies suggest that coffee drinking is associated with longevity. You drink coffee, and would like to believe good things about coffee. So your first instinct, as you sip the aromatic liquid and feel the caffeine buzz, is to rejoice. But you are a scientist: look closer. The first study is of the EPIC cohort, where E stands for European. Over half a million Europeans recorded their coffee consumption on one occasion. Those who claimed to drink the most had a slightly higher rate of survival at 16.4 years than those who said they did not drink coffee. There was a markedly lower rate of death from gastrointestinal causes. Epidemiologically, it’s quite intriguing, but I defy anyone to conduct a randomised trial for a sufficient length of time. So at best we can say that coffee drinking is unlikely to be harmful. The same message emerges from a study of 185 855 Americans of mixed ethnicity, after adjustment for confounders. The coffee drinkers were a bit less likely to die over a period of 16 years, compared with non-coffee-drinkers. Don’t let your coffee get cold while you muse on these matters. Observational evidence is observational evidence and will never be anything more.

Friday, August 24, 2018

Treatment in HCV genotype 1b patients with advanced fibrosis and cirrhosis

PLoS One. 2018 Aug 23;13(8):e0202777. doi: 10.1371/journal.pone.0202777. 

Hepatic decompensation during paritaprevir/ritonavir/ombitasvir/dasabuvir treatment for genotype 1b chronic hepatitis C patients with advanced fibrosis and compensated cirrhosis.
Hsieh YC1, Jeng WJ1,2,3, Huang CH1,2, Teng W1, Chen WT1, Chen YC1,2, Lin SM1,2,3, Tai DI1,2, Lin CY1,2, Sheen IS1,2.

Full Text

Hepatic decompensation is a severe on-treatment adverse event for chronic hepatitis C treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Till now, few papers regarding on-treatment hepatic decompensation have been reported. The study aims to analyze the general feature and predictive factors of on-treatment hepatic decompensation in hepatitis C virus (HCV) genotype 1b-infected patients with advanced fibrosis and compensated cirrhosis who receive treatment with PrOD.

METHODS: A real-word cohort enrolled 189 HCV genotype 1b patients with advanced fibrosis and compensated cirrhosis treated with 12-week PrOD. Clinical and laboratory data were analyzed between patients with and without on-treatment hepatic decompensation.

RESULTS: The sustained virologic response rate at 12 weeks after treatment was 97.3% in HCV subtype 1b patients with advanced fibrosis and cirrhosis. On-treatment hyperbilirubinemia (total bilirubin >2 mg/dL) occurred in 27 (14.3%) patients, and the incidence of the increase of total and direct form bilirubin was significantly different during treatment between patients with Child-Turcotte-Pugh score 5 and score 6. Five (18.5%) hyperbilirubinemia patients progressed to hepatic decompensation. Older age (adjusted OR: 1.2, 95% CI: 1.0-1.4) and albumin ≤3.6 g/dL (adjusted OR: 10.4, 95% CI: 1.3-81.2) may be two predictors for on-treatment hepatic decompensation by multivariate analysis.

CONCLUSIONS: PrOD is an effective direct-acting antiviral agent for antiviral therapy in HCV genotype 1b patients with advanced fibrosis and cirrhosis. Hyperbilirubinemia is possibly the early warning feature of on-treatment hepatic decompensation. This serious adverse event of on-treatment hepatic decompensation is not common. Older age and low baseline albumin level may be predictive factors.

PMID: 30138456 DOI: 10.1371/journal.pone.0202777

Frequent antiviral treatment failures in patients infected with hepatitis C virus genotype 4

Hepatology. 2018 Aug 19. doi: 10.1002/hep.30225. [Epub ahead of print]

Frequent antiviral treatment failures in patients infected with hepatitis C virus genotype 4, subtype 4r.
Fourati S1,2, Rodriguez C1,2, Hézode C2,3, Soulier A1,2, Ruiz I2,3, Poiteau L1,2, Chevaliez S1,2, Pawlotsky JM1,2.

Full Text
Downloaded and shared via twitter by @HenryEChang 

Hepatitis C virus (HCV) genotype 4 is highly heterogeneous. HCV subtype 4r has been suggested to be less responsive to direct-acting antiviral (DAA) drug treatment than other genotype 4 subtypes. Among 537 DAA-treated patients who experienced a virological failure in France between 2015 and 2018, 121 (22.5%) were infected with genotype 4 and 27 of them (22.3%) with subtype 4r; subtype 4r was thus over-represented as compared to its prevalence in the French general population. Population sequencing of the NS3, NS5A and NS5B genes was performed in all subtype 4r patients at treatment failure and in 6 of them at baseline, while full-length HCV genome sequencing was performed in 2 baseline and 3 treatment failure samples by means of an original shotgun metagenomics method based on deep sequencing. At treatment failure, all subtype 4r patients harbored 2 to 3 dominant NS5A resistance-associated substitutions (RASs), including at least L28A/C/I/M/V and L30R. Among 13 patients exposed to sofosbuvir and an NS5A inhibitor (daclatasvir, ledipasvir or velpatasvir), 5 (38.5%) also harbored NS5B S282C/T RASs at treatment failure. An additional patient harbored S282C/T RASs at treatment failure by deep sequencing. The prevalence of S282C/T RASs at treatment failure was significantly higher in patients infected with genotype 4r than with other genotypes, including other subtypes of genotype 4.

The lower rates of SVR in patients infected with subtype 4r are related to the frequent preexistence at treatment baseline and subsequent selection by DAA treatment of both NS5A and NS5B S282 RASs. Our study suggests that these patients should be identified and receive a triple DAA combination regimen as first-line treatment. 

This article is protected by copyright. All rights reserved.

Full text 

PMID: 30125371 DOI: 10.1002/hep.30225

Thursday, August 23, 2018

CLD Updates: Hepatitis B Diagnosis, Treatment, HBV in Pregnancy And Guidelines

CLD Updates
Review the following hepatitis B articles in the latest issue of Clinical Liver Disease (CLD) available on Wiley Online Library. CLD is an official digital educational learning resource from the American Association for the Study of Liver Diseases. Visitors are able to watch author interviews, access full-text articles, and download files in either HTML or PDF formats.

Hepatitis B
Tram Tran, MD 
Bo Hyun Kim , M.D., W. Ray Kim , M.D.
Pages: 1-4 | First Published: 22 August 2018
Watch a video presentation of this article

Kathy Jackson , B.App.Sci., Stephen Locarnini , M.B.B.S, Ph.D., B.Sc. (Hons), F.R.C. (Path), Robert Gish , M.D. 
Pages: 5-11 | First Published: 22 August 2018
Watch a video presentation of this article
Watch the interview with the author

Marc G. Ghany , M.D., M.HSc., Timothy M. Block , Ph.D. 
Pages: 12-18 | First Published: 22 August 2018
Watch a video presentation of this article

Joseph C. Ahn M.D., Joseph Ahn M.D., M.S., F.A.A.S.L.D., F.A.C.G., A.G.A.F.
Pages: 19-23 | First Published: 22 August 2018
Watch a video presentation of this article
Watch the interview with the author 

Tatyana Kushner M.D., M.S.C.E., Monika Sarkar M.D., M.A.S.
Pages: 24-28 | First Published: 22 August 2018
Watch a video presentation of this article 

Brian J. McMahon M.D. 
Pages: 29-32 | First Published: 22 August 2018
Watch a video presentation of this article 

Norah A. Terrault, Anna S. F. Lok, Brian J. McMahon, Kyong‐Mi Chang, Jessica P. Hwang, Maureen M. Jonas, Robert S. Brown Jr, Natalie H. Bzowej, John B. Wong 
Pages: 33-34 | First Published: 22 August 2018
Watch a video presentation of this article
Watch the interview with the author

Wednesday, August 22, 2018

Drop in Aussies seeking hepatitis C cure

More than 170,000 Australians are able to access subsidised medication to cure Hepatitis C but the number of people choosing to do so is declining.

Chief investigator Margaret Hellard told AAP she hopes to see 15,000 people a year accessing treatment to reduce the number of people dying and the rate of transmission.

Ensuring health practitioners are aware of the treatment, who is eligible and how to treat patients with hepatitis C is also part of the plan, being launched by Health Minister Greg Hunt in Canberra on Wednesday night.

It's hoped the partnership will result in a 65 per cent reduction in hepatitis C related deaths and an 80 per cent reduction in new infections....

Source: AAP

Toxin at heart of drug recall shows holes in medical safety net

August 22, 2018

Toxin at heart of drug recall shows holes in medical safety net 
Alexandra Harney, Ben Hirschler
SHANGHAI/LONDON (Reuters) - A toxin inadvertently produced in the manufacture of a widely prescribed medicine but not spotted for years raises questions about regulators’ ability to detect risks in a sprawling global drug supply chain increasingly reliant on factories in China.

China’s Zhejiang Huahai Pharmaceutical (600521.SS), which produces bulk ingredients for drugmakers, told its customers in late June it had found NDMA in its valsartan, an off-patent blood pressure drug originally developed by Novartis (NOVN.S). The discovery means that some of the 10 billion pills containing valsartan sold worldwide last year to prevent heart attacks and strokes had traces of N-nitrosodimethylamine (NDMA), classified as a probable human carcinogen. No one has been reported as sickened by the toxin, once used in the production of liquid rocket fuel... 

Tuesday, August 21, 2018

Hepatitis C - Adverse events from DAAs can persist for months after treatment

Of Interest
March 14, 2018
March 24, 2018
May 30, 2018

Adverse events from DAAs can persist for months after treatment, study finds
Liz Meszaros, MDLinx | August 21, 2018
Adverse events (AEs) related to treatment with direct-acting antivirals (DAAs) may persist after treatment in a significant number of patients with chronic hepatitis C, according to results from a study published in the European Journal of Gastroenterology and Hepatology. Clinicians and patients should be aware of this possibility.

Abstract: Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals: a clinical randomized study

“This real-life study is to the best of our knowledge the first to examine the rate of AEs in patients with hepatitis C virus (HCV) genotype (GT) 1 infection, randomized to one of two different DAA regimens in a real-world setting,” noted these authors, led by Christina Sølund, MD, PhD, Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.

Recently, the development of DAA agents has revolutionized the treatment of chronic hepatitis C, which is estimated to affect more than 70 million people worldwide. Before the advent of DAAs, the standard of care for these patients consisted of treatment with pegylated-interferon and ribavirin (RBV), lasting for 24 to 48 weeks, which not only had significantly lower cure rates and tolerability, but also carried a high incidence of severe AEs.

Now in their second iteration, DAAs have changed the playing field in the treatment of chronic hepatitis C by directly targeting the proteins responsible for viral replication. Improved sustained virologic responses (SVR) of 90% or more and good tolerability and efficacy in patients who have historically been difficult to treat—such as those with liver cirrhosis, liver transplantation, or previous treatment failures—have characterized the second-generation DAAs.

Few studies, however, have compared different DAA regimens. For this reason, Dr. Sølund and colleagues conducted their investigation. They included 96 patients with chronic hepatitis C with either GT1 or GT3, who were randomized to two different treatment arms. The first was comprised of 72 patients infected with GT1, who were treated for 12 weeks with ledipasvir/sofosbuvir/RBV vs paritaprevir/ombitasvir/ritonavir/dasabuvir/RBV. The second group consisted of 24 patients infected with GT3, who were treated with daclatasvir/sofosbuvir/RBV for 12 weeks vs a 24-week course of sofosbuvir/RBV.

Unfortunately, due to a change in national treatment guidelines, the GT3 treatment arm was prematurely terminated. Therefore, efficacy data are available from both GT3 and GT1 patients, but the incidence of AEs is available only for GT1 patients.

Cure was achieved by 97% of GT1 patients and 83% of GT3 patients, with SVR at 12 months. Virologic failure occurred in only one G3 patient.

Adverse events occurred in 97% of GT1 patients with the most common being anemia, fatigue, and headache.

“We found no statistically significant difference in AEs, neither between treatment groups nor in relation to anemia or cirrhosis. The overall rate of AEs was comparable to other real-world studies, but the frequency of the most common AEs, such as anemia (78%), fatigue (74%), headache (74%), pruritus/eczema (46%), and heartburn/abdominal discomfort (38%), was higher in our study,” they added.

Only 3% of GT1 patients discontinued treatment due to AEs. Notably, 45% of patients with AEs thought to be related to a DAA regimen still manifested the AEs at 4 weeks after treatment. At 12 weeks this was still the case in 11% of patients.

“We consider this an important finding that can be used when informing the patient about AEs that might be caused by the DAA regimen, despite the number of patients included in our study being relatively small,” noted the authors. “The low discontinuation rate reflects that AEs possibly induced by DAA treatment are rarely treatment limiting, even when DAA treatment is given in combination with RBV,” they concluded.

This study received support from the Faculty of Health and Medical Sciences, University of Copenhagen and from Hvidovre Hospital Research Foundation, the Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, the Capital Region of Denmark’s Research Foundation, the Innovation Fund Denmark project 060-2009-3, the Novo Nordisk Foundation, and the Danish Research Council.