Saturday, March 31, 2018

Mediterranean Diet - Reduces Liver Fat & May Impact Healthy Aging

About Fatty Liver, NAFLD, NASH & Cirrhosis
Start by learning more about Fatty Liver Disease, watch the following videos available online @ Fatty Liver Foundation.

Eating better tied to lower risk of liver disease
April 27, 2018
(Reuters Health) - People who make an effort to improve their diet may be more likely to have less fat in their livers and a lower risk of liver disease than individuals who stick to unhealthy eating habits, a U.S. study suggests.
Continue reading @ Reuters Health

Mediterranean diet reduces liver fat, risk for NAFLD
Ma J, et al. Gastroenterol. 2018;doi:10.1053/j.gastro.2018.03.038.
March 30, 2018
Improved diet quality based on the Mediterranean-style diet score and Alternative Healthy Eating Index score correlated with less liver fat accumulation and a reduced risk for new-onset nonalcoholic fatty liver, according to a recently published study.
Continue reading @ Healio

NASH Education Program launches, initiates first international NASH day
March 29, 2018
The NASH Education Program, an independent legal entity and nonpartisan initiative designed to increase education and awareness of nonalcoholic steatohepatitis, recently launched in the U.S., according to a press release.
Continue reading @ Healio

Of Interest
Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR
This particular study may be of interest to people with HCV, according to data published Mar 21, 2018 in the online journal World J Gastroenterology, evidence of steatosis was reported to be found in close to half of patients who achieve a sustained virologic response after treating with direct-acting antivirals.
Full-text, here....

Public Release: 30-Mar-2018
Can a Mediterranean diet pattern slow aging?
The Gerontological Society of America
A series of six articles appearing in the March issue of The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences finds new correlations between a Mediterranean diet and healthy aging outcomes -- while also underscoring the need for careful approaches to the use of data in order to measure the diet's potential benefits.

Among their findings, the new articles report on underlying mechanisms of the diet; the positive relationship between the diet and physical and cognitive function; the value of taking a coenzyme Q10 supplement while adhering to the diet; and the role of the diet in reducing inflammation. But in several of the studies, the level of benefit was dependent on how adherence to the diet was measured.

"Greater clarity on how this diet is defined, in both interventions and observational studies, will be critical in the aim of achieving a consensus on how to optimally apply this dietary pattern towards maximizing healthy aging," state Michelle A. Mendez, PhD, and Journals of Gerontology: Medical Sciences Editor-in-Chief Anne B. Newman, MD, FGSA, in an opening editorial.

Hallmarks of the Mediterranean diet include: a variety of minimally processed whole grains and legumes as the staple food; plenty of a huge diversity of fresh vegetables consumed on a daily basis; fresh fruits as the typical daily dessert; cold pressed extra-virgin olive oil, nuts, and seeds as the principal source of fat; moderate consumption of fish; dairy products consumed in low amounts; red and processed meat consumed in very low frequency and amounts; and wine consumed in low to moderate amounts only with meals.

There are a number of scales used to measure adherence to the diet. One of the journal's studies, conducted by researchers at the University of Paris 13, found that among test subjects, higher numbers on the Literature-based Adherence Score to the Mediterranean Diet were associated with higher odds of meeting certain healthy aging criteria. Similar results were found with another index, the Mediterranean Diet Score; however, use of the Mediterranean Diet Scale yielded a weaker correlation. In another study by researchers at the Autonomous University of Madrid, closer adherence to the diet was associated with a lower likelihood of physical function impairment in older adults, although in this case using the Mediterranean Diet Adherence Screener provided more significant results than the Mediterranean Diet Score.

The exact mechanism by which an increased adherence to the diet exerts its favorable effects is still unknown to scientists. However, writing in one of the new articles, researchers from Washington University in St. Louis state there is accumulating evidence of five important adaptations induced by the Mediterranean dietary pattern. These include lipid lowering; protection from oxidative stress and inflammation; modification of growth factors that can promote cancer; inhibition of nutrient sensing pathways by amino acid restriction and gut microbiota-mediated production of metabolites.

Editor's Choice - The Journals of Gerontology
Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms
Valeria Tosti, MD; Beatrice Bertozzi, PhD; Luigi Fontana, MD, PhD
Consuming a Mediterranean diet rich in minimally processed plant foods has been associated with a reduced risk of developing multiple chronic diseases and increased life expectancy. Data from several randomized clinic trials have demonstrated a beneficial effect in the primary and secondary prevention of cardiovascular disease, type 2 diabetes, atrial fibrillation, and breast cancer. The exact mechanism by which an increased adherence to the traditional Mediterranean diet exerts its favorable effects is not known. However, accumulating evidence indicates that the five most important adaptations induced by the Mediterranean dietary pattern are: (a) lipid-lowering effect, (b) protection against oxidative stress, inflammation and platelet aggregation, (c) modification of hormones and growth factors involved in the pathogenesis of cancer, (d) inhibition of nutrient sensing pathways by specific amino acid restriction, and (e) gut microbiota-mediated production of metabolites influencing metabolic health. More studies are needed to understand how single modifications of nutrients typical of the Mediterranean diet interact with energy intake, energy expenditure, and the microbiome in modulating the key mechanisms that promote cellular, tissue, and organ health during aging.
The Journals of Gerontology: Series A, Volume 73, Issue 3, 2 March 2018, Pages 318–326,
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View all articles:

Recommended Reading
In January of this year, AASLD updated practice guidelines for the "Diagnosis and Management of NAFLD"

Fatty Liver Disease articles available on this blog:

Strategies for the elimination of HCV infection as a public health threat in the United States

Strategies for the elimination of HCV infection as a public health threat in the United States
Charitha Gowda & Vincent Lo Re III

Full-text shared via Twitter by Henry E. Chang
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Charitha Gowda
Vincent Lo Re III

Purpose of Review Direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection became available in 2014, and these highly curative therapies have the potential to reduce HCV-associated morbidity and mortality, decrease HCV transmission, and eliminate HCV infection as a public health problem. This review summarizes the recommendations by the National Academies of Sciences, Engineering, and Medicine for a US strategy for HCV elimination.

Recent Findings
To achieve proposed targets of reducing HCV incidence by 90% and decreasing HCV-related mortality by 60% by 2030, there is a critical need to improve HCV diagnosis and linkage to care, reduce HCV-related disease by antiviral treatment scale-up, reduce HCV incidence, and strengthen HCV surveillance to determine achievement of HCV elimination targets over time.

While HCV elimination is feasible, success of this national effort will require ongoing collaboration and critical resource investment by key stakeholders, including medical and public health communities, legislators, community organizers, and patient advocates

View complete article:

Current Hepatology Reports

Management of restless legs syndrome in chronic liver disease: A challenge for the correct diagnosis and therapy

Management of restless legs syndrome in chronic liver disease: A challenge for the correct diagnosis and therapy
Rita Moretti, Paola Caruso, Marzia Tecchiolli, Silvia Gazzin, and Claudio Tiribelli

World J Hepatol. 2018 Mar 27; 10(3): 379–387.

The diagnosis of restless legs syndrome (RLS) relies on the presence of unpleasant sensation in the legs associated with the urge to move. Symptoms mostly begin during periods of rest or inactivity and worsen in the evening or night. Partial or total relief is related to movement. Chronic hepatic failure was recently described in association with RLS, but there are very limited studies, with no mention to treatment. We describe RLS syndrome associated with well-defined chronic liver disease along with therapeutic options, discussing risks, benefits and potential side effects, with a particular look at the augmentation phenomenon in hepatic failure.

Full-Text Article Available Online

To investigate the association between restless legs syndrome (RLS) and well-defined chronic liver disease, and the possible therapeutic options.

Two hundred and eleven patients with chronic liver disease, complaining of sleep disturbances, painful leg sensation and daily sleepiness, were included. Patients with persistent alcohol intake, recent worsening of clinical conditions, or hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns Hopkins questionnaire and verified by fulfilling the diagnostic criteria by Allen. All patients were tested, both at baseline and during follow-up, with the Hamilton rating scale for depression, sleep quality assessment (PSQI), Epworth sleepiness scale (ESS), International Restless Legs Syndrome Study Group evaluation, and international RLS severity (IRLS) scoring system. Iron-free level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological examinations and blood test occurred at the beginning of the therapy, after 2 wk, and at the 28th, 75th, 105th, 135th, 165th and 205th day. Regarding therapy, pramipexole or gabapentin were used.

Patients were moderately depressed, with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep problems and involuntary leg movements had been underestimated, and RLS syndrome had not been considered before the neurological visit. All (211/211) patients fulfilled the RLS diagnostic criteria. Twenty-two patients considered their symptoms as mild, according to IRSL, but 189 found them moderate to very severe. No correlation was found between ammonium level and ESS or PSQI. Augmentation was rather precocious in our patients (135th day), and more frequent (35%) than previous data (8.3%-9.1%). The dosage of dopamine agonists was found to be associated with augmentation and appears in range with the literature. Previous intake of alcohol and lower levels of vitamins have been related to the phenomenon in our study.

RLS is a common disorder, requiring rapid diagnosis and treatment. Further research is therefore fundamental.

Full-Text Article:
World J Hepatol. 2018 Mar 27; 10(3): 379–387.
Published online 2018 Mar 27. doi: 10.4254/wjh.v10.i3.379

Friday, March 30, 2018

Staying Alive: How To Fight An Opioid Addiction

Staying Alive: How To Fight An Opioid Addiction
By Emily Bazar March 30, 2018

Rule No. 1: Stay alive.
If you or a loved one wants to beat an opioid addiction, first make sure you have a handy supply of naloxone, a medication that can reverse an overdose and save your life.

“Friends and families need to keep naloxone with them,” says Dr. David Kan, an addiction medicine specialist in Walnut Creek who is president of the California Society of Addiction Medicine. “People using opioids should keep it with them, too.”

More than 42,200 Americans died from opioid overdoses in 2016, victims of a crisis that’s being fueled by the rise of a powerful synthetic opioid called fentanyl, which is 30 to 50 times more potent than heroin. Rock stars Prince and Tom Petty had fentanyl in their systems when they died.

People can become addicted to opioids through long-term use, or misuse, of prescription painkillers. In most cases, that leads to heroin use, according to the National Institute on Drug Abuse.

If you’re ready to address your own addiction, or that of a loved one, know that you may not succeed — at first. You probably won’t be able to do it without outside help or medications. And you’ll probably have to take those medications for years — or the rest of your life.

“Getting over a drug addiction is a process. There are going to be ups and downs,” says Patt Denning, director of clinical services and training at the Center for Harm Reduction Therapy in San Francisco and Oakland. “We need to hang with people while they’re struggling. It might take awhile.”

That’s why Denning and others suggest you start with having naloxone on hand, which can help you stay alive through the process.

Last year in San Francisco, about 1,200 potentially fatal overdoses were reversed by regular folks administering naloxone, not doctors, police or paramedics, Kan says.

Naloxone, which can be administered as a nasal spray or injection, is available without a prescription in more than 40 states, including California. Ask your pharmacy if it stocks the drug. Needle exchange programs also offer the medication at no charge, Denning says, as do some public health clinics.

Rehab Doesn’t Work
People addicted to opioids face staggering relapse rates of 80 to 90 percent within 90 days if they try short-term rehab or detox programs that wean them off the drugs without assistance from medications, says Richard Rawson, a UCLA psychiatry professor emeritus.

Rawson warns that rehab can also increase the risk of an overdose, because your body’s tolerance to opioids is lower after you withdraw from them.

“If you leave rehab and take the same dose you used to take, you’re not just going to get high, you’re going to be dead,” he says.

Instead of treating opioid addiction like a curable illness, he and other experts liken it to lifelong, chronic conditions such as diabetes that require ongoing management.

“This isn’t going to be one visit. If you have an addictive disorder, this is going to be the rest of your life,” says Dr. Stuart Gitlow, an addiction specialist in New York City who is past president of the American Society of Addiction Medicine.

Chronic illnesses often require medication. Rawson and others point to two drugs in particular that may help break your addiction: buprenorphine and methadone.

There is some unwarranted stigma attached to these drugs, along with a belief that “you’re just exchanging one addiction for another,” Kan says.

While these medications are actually opioids themselves, they control craving and withdrawal — and help prevent the compulsive and dangerous behavior often associated with addiction.

They also reduce your chances of an overdose, Rawson says. And they protect you from other risks that come with opioid addiction, such as exposure to blood-borne infections from sharing needles, including HIV and hepatitis C.

Essentially, the medications make you “comfortable enough physically” to confront the issues behind your addiction, from anxiety and depression to post-traumatic stress disorder, Denning says.

The federal government agrees.
“Abundant scientific data show that long-term use of maintenance medications successfully reduces substance use, risk of relapse and overdose, associated criminal behavior, and transmission of infectious disease, as well as helps patients return to a healthy, functional life,” according to the Surgeon General’s 2016 report on addiction in America.

To obtain methadone, you must visit a clinic governed by state and federal rules.

“These clinics are not particularly patient-friendly. You have to go every day. You can’t travel,” Denning says. “It takes over your life.”

Buprenorphine, on the other hand, can be obtained from doctors, including primary care physicians, who have undergone training and received federal approval.

“The beauty of buprenorphine is it can be prescribed like any medication out of a doctor’s office,” Denning says.

To find a doctor who prescribes buprenorphine, go to the Substance Abuse and Mental Health Services Administration website at and click on the “Find Help & Treatment” link from the home page. You can search by state and ZIP code.

Though you can receive care from your primary care physician, Gitlow recommends that you also consult with an addiction specialist.

In California, find one by visiting the California Society of Addiction Medicine’s website at and clicking on the “Physician Locator” tab.

If you do not live in California, check the American Academy of Addiction Psychiatry’s website at and click on the “Patient Resources” tab on the home page.

After You Start The Medication …
Once patients start one of the medications, it’s not clear how long they should stay on — a question that deserves further research, Rawson says.

“The longer people stay on treatment, the lower the death rate is and the more they’re able to function,” he says.

Often patients face pressure from family members, who badger them to get off the medications even though it would be better for them to stay on them, Kan says.

“We don’t say to patients who suffer from diabetes … ‘Have you changed your diet enough so you can get off insulin?’” he says.

Kan and other addiction specialists generally don’t encourage medication treatment alone, no matter how long you stay on it. Pairing the medication with therapy or other support, including 12-step programs such as Narcotics Anonymous, can reduce relapse rates further, they say.

Al-Anon and Nar-Anon groups also can be helpful resources for families, Kan adds.

“12-step is something I encourage for everybody. I don’t consider it a treatment, per se. It’s like mutual support,” he says.

Questions for Emily:

Click here to read previous Ask Emily columns. 

This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation.

CDC MMWR - Opioids were involved in 66.4% of all drug overdose deaths in 2016

Morbidity and Mortality Weekly Report (MMWR)
Weekly / March 30, 2018 / 67(12);349–358

Opioids were involved in 66.4% of all drug overdose deaths in 2016. The rate of opioid overdose deaths increased nearly 28% from the previous year.

Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants — United States, 2015–2016 
Puja Seth, PhD1; Lawrence Scholl, PhD1,2; Rose A. Rudd, MSPH1; Sarah Bacon, PhD

What is already known about this topic?
From 1999 to 2015, the drug overdose epidemic resulted in approximately 568,699 deaths. In 2015, 52,404 drug overdose deaths occurred; 63.1% (33,091) involved an opioid. From 2014 to 2015, the age-adjusted opioid-involved death rate increased by 15.6%; the rapid increase in deaths was driven in large part by synthetic opioids other than methadone (e.g., fentanyl).

What is added by this report?

In 2016, there were 63,632 drug overdose deaths in the United States. Opioids accounted for 66.4% (42,249) of deaths, with increases across age groups, racial/ethnic groups, urbanization levels, and multiple states. Age-adjusted death rates for overdoses involving synthetic opioids other than methadone doubled from 2015 to 2016, and death rates from prescription opioids, heroin, cocaine, and psychostimulants also increased.

What are the implications for public health practice?

There is an urgent need to implement a multifaceted, collaborative public health and public safety approach. Building on existing resources, more rapidly available and comprehensive surveillance data are needed to track emerging drug threats to guide public action to prevent and respond to the epidemic through increased naloxone availability, harm reduction services, linkage into treatment (including medication-assisted treatment), safe prescribing practices, and supporting law enforcement strategies to reduce the illicit drug supply.
Read the full report:

Recommended Reading
Epidemic worsened dramatically in 2016 across most demographics
by Judy George, Contributing Writer, MedPage Today March 29, 2018
Death rates for overdoses involving highly potent synthetic opioids other than methadone -- including illicitly manufactured fentanyl as well as the prescription kind -- more than doubled from 2015 to 2016, propelling an overall increase in opioid deaths of 27.9% in that one-year period, according to the CDC.

Synthetic opioids were present in 19,413 overdose deaths in 2016, up from 9,580 deaths in 2015, reported Puja Seth, PhD, of the CDC in Atlanta and colleagues in Morbidity and Mortality Weekly Report. They accounted for 30.5% of all drug overdose deaths and 45.9% of all opioid-involved deaths in 2016.
Continue reading @ MedPage Today

Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US

Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US
D. C. Des Jarlais , H. L. F. Cooper, K. Arasteh, J. Feelemyer, C. McKnight, Z. Ross

For HIV, the lack of potential hotspots is further validation of widespread effectiveness of efforts to reduce injecting-related HIV transmission. Injecting-related HIV transmission is likely to be a rare, random event. HCV prevention efforts should include focus on potential hotspots for transmission and on hotspots for initiation into injecting drug use. We consider application of methods for the current opioid epidemic in the US.
Published: March 29, 2018

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We identified potential geographic “hotspots” for drug-injecting transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs (PWID) in New York City. The HIV epidemic among PWID is currently in an “end of the epidemic” stage, while HCV is in a continuing, high prevalence (> 50%) stage.

We recruited 910 PWID entering Mount Sinai Beth Israel substance use treatment programs from 2011–2015. Structured interviews and HIV/ HCV testing were conducted. Residential ZIP codes were used as geographic units of analysis. Potential “hotspots” for HIV and HCV transmission were defined as 1) having relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive PWID reporting transmission risk—passing on used syringes to others, and 3) having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk—injecting with previously used needles/syringes. Hotspots for injecting drug use initiation were defined as ZIP codes with 5 or more persons who began injecting within the previous 6 years.

Among PWID, 96% injected heroin, 81% male, 34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP codes were identified as potential hotspots due to small numbers of HIV seropositive PWID reporting transmission risk. Four ZIP codes were identified as potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for injecting drug use initiation.

Thursday, March 29, 2018

Pearls collections: What we can learn about infectious disease and cancer

Pearls collections: What we can learn about infectious disease and cancer
Laura J. Knoll, Deborah A. Hogan, John M. Leong, Joseph Heitman , Richard C. Condit

Published: March 29, 2018


Viruses and cancer
Viruses account for an estimated 10% to 15% of human cancers [2]. Currently, the known cancer-causing viruses in humans include seven viruses comprising five virus families [2, 3]. Epstein–Barr virus (EBV)—a herpesvirus—is associated with a variety of malignancies, including for Burkitt lymphoma, diffuse large B cell lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric adenocarcinoma, leiomyosarcoma, and posttransplant lymphoproliferative disease. Kaposi sarcoma herpesvirus is the causative agent in Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman disease. Hepatitis B virus, a hepadnavirus, and hepatitis C virus, a flavivirus, both cause hepatocellular carcinoma. Human T-lymphotropic virus-1, a retrovirus, is responsible for adult T-cell leukemia. Human genital papillomavirus is the causative agent for cervical carcinoma, vulvar cancer, anal cancer, and a number of head and neck cancers. Finally, Merkel cell polyomavirus is responsible for a specific skin cancer called Merkel cell carcinoma. The mechanisms by which viruses cause cancer are under intense investigation and are varied but generally fall into two broad categories: direct and indirect. Direct causation represents the action of viral genes, known in this context as oncogenes, on cellular processes. Indirect causation represents the outcome of chronic inflammation resulting from a persistent viral infection. In no case is cancer the normal outcome of a virus infection. Rather, it is an incidental side effect of the action of viral gene products evolved for the normal process of infection, as in direct causation, or the circumstances of the immune response to infection, as in indirect causation. The identification of viruses as the etiological agent of a number of common cancers provides a unique opportunity to prevent cancer through the use of either vaccination or antiviral drug therapy. Ironically, due to their unique ability to target and kill cells selectively and stimulate a robust immune response, viruses are being developed as “oncolytic” agents to treat cancer.

This compendium of PLOS Pearls includes eight articles that together comprise a survey of the role of viruses in cancer, including mechanism, prevention, and oncolytic agents. Four articles address the mechanism or viral oncogenesis. Moore and Chang explore mechanisms in general and focus on the role of common commensal viruses in cancer [4]. Cavallin et al. discuss the complex mechanisms involved in the induction of Kaposi sarcoma by Kaposi sarcoma herpesvirus [5], and Price and Luftig describe the complexity of EBV latency and its implications for EBV oncogenesis [6]. McBride and Warburton examine the unique role that viral DNA integration into the cellular genome plays in papillomavirus oncogenesis [7]. Three articles address prevention of cancer using antiviral vaccines or drugs. DiMaio provides a succinct history of vaccination, culminating in the development of vaccines for hepatitis B virus and human papillomavirus [8]. Pogoda et al. explore in more depth the development of vaccines for human papillomavirus [9]. Horner and Naggie present an analysis of the successes and challenges surrounding the development of antiviral drugs to treat hepatitis C infections [10]. Lastly, a contribution by Cattaneo and Russell probes the use and potential of viruses to treat cancer, using as an example a remarkable success story on the use of the measles vaccine to treat multiple myeloma [11]. Together, these articles provide insight into the role of viruses in cancer and the hope for cancer therapy that this knowledge brings. The role of viruses in the cause and treatment of cancer is an exciting and expanding area of research, and we can expect significant advances in the future that provide both basic insights into cancer and promise for cancer therapy.
Continue reading this editorial @ PLOS Pathogens 

Harm reduction, screening and treatment would save money and lives in Eastern European, Central Asian countries where injecting drug use drives rising rates of HIV, HCV

Science Speaks: Global ID News
Harm reduction, screening and treatment would save money and lives in Eastern European, Central Asian countries where injecting drug use drives rising rates of HIV, HCV
By Antigone Barton on March 28, 2018
Increasing access to sterile needles and syringes and to opioid substitution therapy, as well as to HIV and hepatitis C screening services and effective treatment would lower new infection rates by double digit percentages, save money and lives, and contain the spread of the viruses in Eastern European and Central Asian countries where people who inject drugs currently have limited access to proven interventions, a study reported in the March Open Forum Infectious Diseases says.

Intervention Packages to Reduce the Impact of HIV and HCV Infections Among People Who Inject Drugs in Eastern Europe and Central Asia: A Modeling and Cost-effectiveness Study

Liver Congress™ 2018 - Enanta to present data on EP-027367 for HBV

Enanta Pharmaceuticals Announces Data Presentations at The International Liver Congress™ 2018

Oral presentation to feature preclinical data on novel core inhibitor EP-027367 targeting hepatitis B virus

March 28, 2018 07:30 AM Eastern Daylight Time
WATERTOWN, Mass.--(BUSINESS WIRE)--Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, today announced that data from Enanta’s wholly-owned development programs, including EP-027367, one of Enanta’s novel core inhibitors in preclinical testing for hepatitis B virus (HBV), and EDP-305, an FXR agonist in development for non-alcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC), have been accepted for presentation at The International Liver Congress™ (ILC) 2018, April 11-15, in Paris, France.

EP-027367, one of several core inhibitors Enanta is evaluating, has been selected for an oral presentation. There will also be three posters on EDP-305, which is currently in a Phase 2 study for NASH and a Phase 2 study for PBC. The U.S. Food and Drug Administration has granted EDP-305 Fast Track designation for the treatment of NASH patients with liver fibrosis and Fast Track designation for the treatment of patients with PBC.

In addition, several abstracts from AbbVie will be presented on their HCV regimens containing glecaprevir/pibrentasvir and marketed under the tradenames MAVYRET™ (U.S.) and MAVIRET™ (ex-U.S.). Glecaprevir is Enanta’s second protease inhibitor discovered and commercialized through its protease inhibitor collaboration with AbbVie.

The full ILC 2018 scientific program as well as the abstracts can be found at Further details will be available at the time of these presentations.

Oral Presentation:
Thursday, April 12, 17:45 - 18:00 CET
PS-032 - “Discovery of a novel HBV core inhibitor EP-027367 with potent antiviral activity both in vitro and in a humanized mouse model” (M.Vaine, S.Clugston, J.Kass, X. Gao, H. Cao, W. Li, X. Peng, L.J. Jiang, K. Daniels, Y. Qiu, Y.S. Or, K. Lin)

Poster Presentations
Thursday, April 12, 09:00 - 17:00 CET

THU-469 - “EDP-305 modulates lipoprotein metabolism via distinct chromatin and microRNA regulatory mechanisms” (M. Roqueta-Rivera, M.D. Chau, K. Garlick, Y. Li, G. Wang, Y.S. Or, and L.J. Jiang) 

Friday, April 13, 09:00 - 17:00 CET
FRI-084 - “EDP-305, a highly selective and potent farnesoid X receptor agonist, favorably regulates the expression of key fibrogenic genes in vitro and in vivo” (Y. Li, J.Y. Shang, M.D. Chau, M. Roqueta-Rivera, K. Garlick, P. An, K. Vaid, G. Wang, Y. Popov, Y. S. Or, and L. J. Jiang)
FRI-489 - “Pharmacokinetics, pharmacodynamics, and safety of EDP-305, in healthy and presumptive NAFLD subjects” (A. Ahmad, K. Sanderson, D. Dickerson, N. Adda) 

Hepatitis C genotype 3 - 12 weeks of SOF/VEL safe and highly efficient across a diverse patient population

In conclusion, we confirm an overall very high efficacy and safety of 12 weeks of SOF/VEL in patients with HCV GT3 infection in a real-world setting. While the prevalence of clinically relevant NS5A RASs was low, our data indicate that their impact may be of less importance than previously expected. Thus, addition of RBV may only be required in certain subgroups, including patients with previous DAA-experience and/or decompensated cirrhosis.

Alimentary Pharmacology and Therapeutics
High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance‐associated substitutions in hepatitis C genotype 3 infection
J. von Felden J. Vermehren P. Ingiliz S. Mauss T. Lutz K. G. Simon H. W. Busch A. Baumgarten K. Schewe D. Hueppe C. Boesecke J. K. Rockstroh M. Daeumer N. Luebke ...

First published: 14 March 2018

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Summary Background
Twelve weeks of the pangenotypic direct‐acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL‐3 approval study. However, presence of resistance‐associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response.

To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real‐world setting.

In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end‐of‐treatment (SVR12) in modified intention‐to‐treat (mITT) and per‐protocol analysis (PP). NS5A RASs were tested by population‐based sequencing.

A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co‐infected and 21.8% were treatment‐experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment‐related major adverse events occurred.

Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.

Full article:

Hepatitis C in Injection-Drug Users — A Hidden Danger of the Opioid Epidemic

New England Journal of Medicine
Interview with Dr. Jake Liang on the increasing spread of hepatitis C virus associated with injection-drug use.

Hepatitis C in Injection-Drug Users — A Hidden Danger of the Opioid Epidemic
T. Jake Liang, M.D.,
and John W. Ward, M.D.
Much has been written about the escalating crisis of opioid-overdose deaths in the United States and its mounting social and economic costs. Although political and public health leaders have begun to confront this urgent problem, hidden beneath it lies another danger: the increasing spread of hepatitis C virus (HCV) associated with injection-opioid use
Related article

Wednesday, March 28, 2018

Liver cancer caused by alcohol consumption may have worse prognosis than other forms

Liver cancer caused by alcohol consumption may have worse prognosis than other forms

A new study indicates that patients with alcohol-related liver cancer often do not live as long as patients with liver cancer that is not associated with alcohol consumption, mainly due to diagnoses at later stages. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings indicate that efforts should be made to improve both screening for early signs of liver cancer and the management of alcohol abuse.

Liver cancer is the second leading cause of cancer-related deaths worldwide, with hepatitis B and C infections being the main causes. Alcohol abuse and non-alcoholic fatty liver disease are other dominant risk factors. Due to improvements in the treatment of hepatitis infections and increased alcohol consumption in some regions, it is likely that alcohol will become a leading cause of liver cancer in the near future. Indeed, alcohol is already the first cause of liver cancer in France and involved in 25 percent to 30 percent of diagnoses in the United States. The real US figure is likely higher as alcohol consumption is often underreported when another risk factor is present.

To compare aspects of alcohol-related and non-alcohol-related liver cancer, Charlotte Costentin, MD, of Hôpital Henri-Mondor in France, and her colleagues examined 894 patients with newly diagnosed liver cancer who were followed for 5 years; 582 patients (65 percent) had a history of chronic alcohol abuse and 312 (35 percent) did not. Investigators also recorded whether patients with alcohol-related liver cancer were abstinent or not at the time of cancer diagnosis.

A total of 601 patients had died by the time of the investigators' final analyses. Alcohol-related liver cancers were more likely to be diffuse and were detected in patients with worse liver function. Median overall survival was 9.7 versus 5.7 months in the non-alcohol-related and alcohol-related groups respectively. When investigators looked at each stage of cancer individually, however, survival was similar in patients with non-alcohol-related and alcohol-related cancer. The findings suggest that patients with alcohol-related liver cancer have a reduced overall survival mainly due to worse liver function and tumor characteristics at diagnosis.

The analysis also examined whether patients were participating in cirrhosis follow-up programs before their cancers were diagnosed. (Most people who develop liver cancer show signs of scarring, or cirrhosis, in the liver, and international guidelines recommend ultrasound every six months to detect early liver cancer in patients with cirrhosis.) Patients whose liver cancer was detected during a cirrhosis follow-up program had improved survival compared with patients whose cancer was diagnosed incidentally. This was especially pronounced in patients with non-alcohol-related liver disease or those with alcohol-related liver disease who are no longer drinking alcohol compared with non-abstinent patients. Also, non-abstinent alcoholic patients had the lowest survival in the study, even when restricting the analysis to patients involved in cirrhosis follow-up programs.

"To improve prognosis of liver cancer in the alcoholic population, efforts should be made to implement effective screening programs for both cirrhosis and liver cancer, and to improve access to alcoholism treatment services," said Dr. Costentin. "A smaller tumor burden and a better liver function at diagnosis should translate into higher rates of patients with alcohol-related liver cancer amenable to curative treatment such as tumor resection or ablation and liver transplantation."

Full Citation: "Hepatocellular carcinoma is diagnosed at a later stage in alcoholic patients: results of a prospective nationwide study." Charlotte E. Costentin, Abbas Mourad, Pierre Lahmek, Xavier Causse, Alexandre Pariente, Hervé Hagège, Anca Stela Dobrin, Claire Becker, Bérangère Marks, Robert Bader, Bertrand Condat, Frédéric Héluwaert, Jean François Seitz, Bruno Lesgourgues, Jacques Denis, Sylvie Deuffic-Burban, Isabelle Rosa, and Thomas Decaens on behalf of CHANGH study group. CANCER; Published Online: March 28, 2018 (DOI: 10.1002/31215).

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Tuesday, March 27, 2018

Hepatitis C Virus Screening Rates Remain Low Among Baby Boomers

Hepatitis C virus screening rates remain low among baby boomers

Nearly half of all cases of US liver cancer are caused by HCV
American Association for Cancer Research

Bottom Line: Despite the steady increase of liver cancer incidence in the United States in recent decades, data from 2015 indicates that less than 13 percent of individuals born between 1945 and 1965 are estimated to have undergone screening for hepatitis C virus (HCV).

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Authors: Susan Vadaparampil, PhD, MPH, senior author, senior member and professor, Health Outcomes and Behavior Program, Moffitt Cancer Center, Tampa, Florida; Monica Kasting, PhD, lead author, postdoctoral fellow, Division of Population Science, Moffitt Cancer Center; Anna Giuliano, PhD, founding director of the Center for Infection Research in Cancer, Moffitt Cancer Center.

Background: "In the United States, approximately one in 30 baby boomers are chronically infected with HCV," said Vadaparampil. "Almost half of all cases of liver cancer in the United States are caused by HCV. Therefore, it is important to identify and treat people who have the virus in order to prevent cancer."

"Hepatitis C is an interesting virus because people who develop a chronic infection remain asymptomatic for decades and don't know they're infected," explained Kasting. "Most of the baby boomers who screen positive for HCV infection were infected over 30 years ago, before the virus was identified."

Because over 75 percent of HCV-positive individuals were born between 1945 and 1965, both the Centers for Disease Control and Prevention (CDC) and the U.S. Preventive Services Task Force (USPSTF) now recommend that baby boomers get screened for the virus. However, data from the 2013 National Health Interview Survey (NHIS) indicated that only 12 percent of baby boomers had been screened for HCV, Kasting explained. The researchers wanted to study if HCV screening rates had increased following the FDA approval of several well-tolerated and effective treatments for HCV infection.

How the Study Was Conducted: Using NHIS data from 2013-2015, Kasting and colleagues analyzed HCV screening prevalence among four different age cohorts (born before 1945, born 1945-1965, born 1966-1985, and born after 1985). Participants were asked if they had ever had a blood test for hepatitis C. As the researchers were interested in assessing HCV screening in the general population, they excluded certain populations who were more likely to be screened for the virus, resulting in a total sample size of 85,210 participants.

Results: After multivariable analysis, Kasting and colleagues found that females were screened less often than males in every age cohort. Additionally, among baby boomers and those born between 1966-1985, HCV screening rates were lower among Hispanics and non-Hispanic Blacks. "This is concerning because these groups have higher rates of HCV infection and higher rates of advanced liver disease," noted Kasting. "This may reflect a potential health disparity in access to screening, and therefore treatment, for a highly curable infection."

Among baby boomers, HCV screening rates ranged from 11.9 percent in 2013 to 12.8 percent in 2015. Regardless of the federal screening recommendations, less than 20 percent of baby boomers reported that the reason for their screening was due to their age.

Author's Comments: "Our most important finding is that the HCV screening rate isn't increasing in a meaningful way," said Giuliano. "Between 2013 and 2015, HCV screening only increased by 0.9 percent in the baby boomer population. Given rising rates of liver cancer and high HCV infection rates in this population, this is a critically important finding. It shows that we have substantial room for improvement and we need additional efforts to get this population screened and treated as a strategy to reduce rising rates of liver cancer in the United States."

Study Limitations: Limitations of the study include a reliance on self-reported data. "Another limitation is that this is secondary data and we didn't collect it ourselves," noted Kasting. "There are several questions we would have liked to ask about behavioral risk factors, such as drug use, that weren't utilized on this survey."

Funding & Disclosures: This study was supported by the Biostatistics Core and the H. Lee Moffitt Cancer Center & Research Institute. Kasting is supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH).

As a member of Merck Scientific Advisory Boards, Giuliano and her institution have received funds from Merck. An additional author on the study, David Nelson, MD, has received grant support from Abbvie, Gilead, and Merck. All other authors declare no conflicts of interest.

NVHR Urges Congress to Pass the Eliminating Opioid-Related Infectious Diseases Act

NVHR Urges Congress to Pass the Eliminating Opioid-Related Infectious Diseases Act

Bill Would Increase Funding to Fight infectious Diseases Like Hepatitis B and C

Washington, DC (March 27, 2018) - The National Viral Hepatitis Roundtable (NVHR) today called for immediate passage of the Eliminating Opioid-Related Infectious Diseases Act, a bill that would increase funding for fighting infectious diseases like hepatitis B and C.

Congressman Leonard Lance (R-NJ) and Joseph P. Kennedy III (D-MA) introduced the bipartisan legislation (H.R. 5353) on March 20, 2018. A Senate companion bill (S. 2579) has been introduced by Senators Todd Young (R-IN) and Edward J. Markey (D-MA). The Eliminating Opioid-Related Infectious Diseases Act would expand surveillance and education about infections associated with injection drug use. The bill would appropriate $40 million for the Centers of Disease Control and Prevention to implement programs that address the high rates of infectious diseases such as hepatitis B and C, which have been dangerously on the rise because of the opioid crisis.

Skyrocketing rates of infection with hepatitis C and hepatitis B are among the devastating public health consequences of the opioid crisis in the United States. Hepatitis C is the deadliest infectious disease in America, killing nearly 20,000 people in 2014 alone,1 and injection drug use is the cause of most new infections.2 From 2010 to 2015, the number of new hepatitis C infections jumped by 294 percent, with particularly sharp increases among states hardest hit by the opioid crisis.3 Reported cases of hepatitis B, which can also be transmitted via injection drug use, increased 20.7 percent in 2015.4

The underfunding of surveillance and testing programs for hepatitis B and C has contributed in part to the explosion of these epidemics. “Even a modest increase in funding would help
1 Centers for Disease Control and Prevention, “Hepatitis C Kills More Americans than Any Other Infectious Disease” (May 2016), available at 2 Campbell, Canary, Smith, et al. State HCV Incidence and Policies Related to HCV Preventive and Treatment Services for Persons Who Inject Drugs — United States, 2015–2016. MMWR MORB MORTAL WKLY REP 2017;66:12. 3 Id. 4 Centers for Disease Control and Prevention, “Surveillance for Viral Hepatitis – United States, 2015” (June 2017), available at
communities hard-hit by the opioid crisis and suffering from high rates of hepatitis B and C,” said Elizabeth Paukstis, NVHR’s Public Policy Director. “The Eliminating Opioid-Related Infectious Diseases Act would take a step in the right direction by allocating desperately needed funding toward the prevention of these devastating diseases.”

“Because of the direct link between injectable opioid use and hepatitis C and B, any initiative to tackle the opioid crisis in America must include a robust effort to screen, provide hepatitis B vaccination, and treat people for hepatitis B and C,” said Dr. Stacey Trooskin, Director of Viral Hepatitis Programs at Philadelphia FIGHT Community Health Centers. “We cannot afford to ignore the tragic public health consequence of this crisis any longer. The Eliminating OpioidRelated Infectious Diseases Act is commonsense legislation that should be passed and enacted without delay.”

About NVHR: The National Viral Hepatitis Roundtable (NVHR) is a national coalition working together to eliminate hepatitis B and C in the United States. NVHR’s vision is a healthier world without hepatitis B and C.

Hepatitis B Foundation Presents - Journey to the Cure: How Do I Know if I Have Hepatitis B?

Journey to the Cure: How Do I Know if I Have Hepatitis B?

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.

In the first episode (part 1), Kristine Alarcon, MPH sits down with Timothy Block, PhD, President and Co-Founder of the Hepatitis B Foundation, to talk about the basics of hepatitis B.
In the second episode, Kristine Alarcon, MPH sits down with Chari Cohen, DrPH, MPH, Vice President of Public Health of the Hepatitis B Foundation, to talk about hepatitis B symptoms and testing.
View all videos: Hepatitis B Foundation

Hepatitis B Foundation Blog Updates In March
Hepatitis B Precautions for People Living with Diabetes
StigmaStops: Can We End Hepatitis B Discrimination

For any questions about hepatitis B, please email

The Hepatitis B Foundation is a national nonprofit organization dedicated to finding a cure and improving the lives of those affected by hepatitis B worldwide through research, education and patient advocacy. Visit us at, on Facebook at, on Twitter at twitter@hepbfoundation, and our Blog at

Disclaimer: The information provided in this video is not intended to serve as medical advice or endorsement of any product. The Hepatitis B Foundation strongly recommends each person discuss this information and their questions with a qualified health care provider.

Only 5% of hepatitis B patients received antiviral therapy in 2016

In The News

HBV Treatment Fails to Meet Global Targets

by Molly Walker, Staff Writer
MedPage Today March 26, 2018

Only 5% of hepatitis B patients received antiviral therapy in 2016

Only an estimated one in 20 patients with hepatitis B worldwide received antiviral therapy for their illness in 2016, a modeling study found.

Of the estimated 292 million people living with hepatitis B virus (HBV), there were 94 million individuals eligible for treatment, but only 4.8 million (5%) actually received it, reported The Polaris Observatory Collaborators. Moreover, less than half of infants received timely birth dose vaccination, and less than 1% of mothers with a high viral load received antiviral therapy in 2016, the authors wrote in the Lancet Gastroenterology & Hepatology.

MedPage Today Full Article:

Lancet Study:
Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study
The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment.

Methadone maintenance therapy and having access to regular physician care regarding HCV among people who inject drugs

The impact of methadone maintenance therapy on access to regular physician care regarding hepatitis C among people who inject drugs
Lianping Ti, María Eugenia Socías, Evan Wood, M-J Milloy, Ekaterina Nosova, Kora DeBeck, Thomas Kerr, Kanna Hayashi

Published: March 26, 2018

Background & aims
People who inject drugs (PWID) living with hepatitis C virus (HCV) infection often experience barriers to accessing HCV treatment and care. New, safer and more effective direct-acting antiviral-based therapies offer an opportunity to scale-up HCV-related services. Methadone maintenance therapy (MMT) programs have been shown to be effective in linking PWID to health and support services, largely in the context of HIV. The objective of the study was to examine the relationship between being enrolled in MMT and having access to regular physician care regarding HCV among HCV antibody-positive PWID in Vancouver, Canada.

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Monday, March 26, 2018

Editorial: diabetes, obesity and clinical inertia—the recipe for advanced NASH

We should screen patients with diabetes for “diabetic hepatopathy” (NAFLD), in the same way, we do today for diabetic retinopathy or nephropathy, considering NASH as the “new” complication of T2DM. Earlier treatment will likely benefit patients as evidence shows that the majority of patients that lose ≥8%‐10% of body weight,1 or about two‐thirds of prediabetics/diabetics treated with pioglitazone,8 experience resolution of NASH. Breaking clinical inertia by targeting obese patients with T2DM is a reasonable first step to curb the looming epidemic of NASH‐cirrhosis among us.

Editorial: diabetes, obesity and clinical inertia—the recipe for advanced NASH

J. Leey K. Cusi
First published: 25 March 2018

Linked content
This article is linked to Patel et al and Patel and Hunt papers. To view these article visit and

The prevalence of NAFLD continues to rise, with T2DM and obesity being major risk factors for advanced NASH, cirrhosis and HCC.1 The prevalence of diabetes in adults ≥18 years in the USA is 12.2%, but doubles to 25.2% in those aged ≥65 (CDC, July 2017). This epidemic is particularly concerning at the Veterans Health Administration (VHA) that looks after an ageing population. At our Veterans Administration Medical Center (Gainesville, Florida), the prevalence of diabetes in 2016 among primary care clinics was 29%. Obesity is also a problem: 41% of all veterans are obese.2 Calls to systematically screen obese patients with T2DM are gaining traction.3 Despite veterans being a high‐risk population, and NAFLD being identified as a significant problem,4 a cohesive early screening/treatment strategy is still lacking within the VHA and at a national level.

In a recent issue, Patel5 makes an even stronger case for action. They examine risk factors for advanced NASH in 399 patients identified with a liver biopsy between 2005 and 2015. The strength of the study was the large sample size with patients divided into well‐defined categories across the spectrum of NAFLD. Shortcomings were the lack of centralised pathology reading and inclusion of few females. However, the study had two important take home messages: the relevance of T2DM as the major risk factor for advanced NASH and the need to reverse clinical inertia. Both diabetes and clinical inertia, combined with obesity, appeared to be the perfect mix for disease progression, cirrhosis and even HCC. For instance, while 37% of patients with NAFL steatosis had T2DM, this climbed to 66% and 80% with NASH‐fibrosis and NASH‐cirrhosis respectively. Relative to controls, diabetics had a 4‐fold increase in the odds of being in the group of NASH‐without‐fibrosis, but eightfold in the NASH‐fibrosis and 12‐fold in the NASH‐cirrhosis groups. No other risk factor was as significant as diabetes; although most patients were obese and obesity‐related metabolic defects and “lipotoxicity”6 contributed to advanced NASH. Of note, 68% of women and 56% of men with T2DM in the VHA are obese.2 The study5 also highlights the need to educate healthcare providers about NAFLD. Even for a study between 2005 and 2015, lifestyle or pharmacological interventions were unacceptably low. The value of weight loss for NASH is well‐established,1 but only 12.3%‐19.5% of patients were offered diet/exercise and ≤2.6% had bariatric surgery. Considering ~30%‐40% of veterans have obesity/T2DM, still today few are offered the VHA behavioural modification programme and weight loss medications remain restricted. Medications proven to be effective for NASH, such as pioglitazone or vitamin E,1 were rarely prescribed (≤10%) in the study.5 The thiazolidinedione has been reported to be safe and effective in RCTs in NASH since 2006,7 including patients with7, 8 and without T2DM.1, 4 Pioglitazone may benefit even patients with advanced NASH‐fibrosis.9

In summary, Patel's work5 makes the case for screening obese patients with T2DM. It is ill‐advised to wait on long‐term outcome studies before supporting such a strategy as ~70% of obese patients with T2DM have NAFLD, and ~20% moderate‐to‐severe NASH‐fibrosis.4 We should screen patients with diabetes for “diabetic hepatopathy” (NAFLD), in the same way, we do today for diabetic retinopathy or nephropathy, considering NASH as the “new” complication of T2DM.10 Earlier treatment will likely benefit patients as evidence shows that the majority of patients that lose ≥8%‐10% of body weight,1 or about two‐thirds of prediabetics/diabetics treated with pioglitazone,8 experience resolution of NASH. Breaking clinical inertia by targeting obese patients with T2DM is a reasonable first step to curb the looming epidemic of NASH‐cirrhosis among us.

Alimentary Pharmacology & Therapeutics

Chemoembolization plus radiotherapy improve liver cancer survival

Chemoembolization plus radiotherapy improve liver cancer survival

Last Updated: 2018-03-26
By David Douglas

NEW YORK (Reuters Health) - In patients with hepatocellular carcinoma with macroscopic vascular invasion, treatment with transarterial chemoembolization (TACE) plus external beam radiotherapy (RT) improves survival compared with sorafenib therapy, according to South Korean researchers.

"Our study may have significance as a first-ever randomized trial that demonstrates a treatment strategy showing a significant improvement in overall survival over sorafenib," Dr. Young-Suk Lim, told Reuters Health by email.

"During the last 10 years," he added, "all phase 3 trials assessing first-line therapies in advanced hepatocellular carcinoma have failed to improve overall patient survival over sorafenib."

In a paper online March 15 in JAMA Oncology, Dr. Lim and colleagues at the University of Ulsan College of Medicine in Seoul note that sorafenib, the current standard systemic treatment, has considerable limitations. However, observational studies have suggested more benefit with TACE plus RT.

To investigate, the team randomized 90 patients to sorafenib 400 mg twice daily or TACE every six weeks plus RT within three weeks of the first TACE. The patients' median age was 55 years and 77 were men. Their median maximal tumor diameter was 9.7 cm and most patients (78.9%) had multiple lesions.

At 12 weeks, progression-free survival was much higher in the TACE-RT group than in those given sorafenib (86.7% vs. 34.3%, P<0.001). Overall survival TACE-RT group was 55 weeks, compared to 43 weeks with sorafenib (P=0.04).

There was also a significantly higher radiologic response rate at 24 weeks (33.3% vs. 2.2%).

The researchers conclude, "Further studies are needed to confirm our findings and, given the poor overall patient survival even with TACE plus RT, to further improve patient outcome."

Dr. Khashayar Farsad, co-author of an accompanying editorial, told Reuters Health by email that the study "provides valuable prospective data supporting a role for targeted liver-directed therapy in advanced hepatocellular carcinoma."

"Moreover," said Dr. Farsad of Oregon Health and Science University in Portland, "the study highlights an evolving trend toward multimodality therapy to best treat this challenging disease."


JAMA Oncol 2018.

No Extra Liver Cancer Risk with Interferon-Free HCV Regimens

No Extra Liver Cancer Risk with Interferon-Free HCV Regimens

by Diana Swift, March 25, 2018

Earlier suggestions not supported in retrospective study of 857 patients

Successful treatment of cirrhotic patients with hepatitis C virus (HCV) with direct-acting interferon (IFN)-free antiviral therapy did not increase the risk of incident hepatocellular carcinoma (HCC), researchers said, nor was it associated with increased nodule size or number in those diagnosed with HCC.

According to a Scottish study published in the Journal of Hepatology, the elevated risk suggested by previous research was attenuated after accounting for differing characteristics between patients given regimens with or without interferon.
Continue reading:

Resource Link
Liver Cancer After Treatment For Hepatitis C​
This page offers an index of links to current data investigating the possible risk of developing liver cancer (hepatocellular carcinoma, or HCC) during and after direct-acting antiviral therapy in patients with hepatitis C.

Oxycodone use shifts in Australia after tamper-resistant versions introduced

Study -  CMAJ (Canadian Medical Association Journal
Tamper-resistant formulations of higher-strength oxycodone decrease use
March 26, 2018 Dispensing rates for higher-strength oxycodone formulations among Australians younger than 65 years decreased when tamper-resistant versions were implemented, according to findings recently published in the Canadian Medical Association Journal.

Oxycodone use shifts in Australia after tamper-resistant versions introduced
Canadian Medical Association Journal
After the introduction of tamper-resistant oxycodone in Australia, dispensing rates for higher-strength formulations decreased for people younger than 65 years, but there was no change in older adults, according to new research in CMAJ (Canadian Medical Association Journal).

Canada, the United States and Australia are the highest per capita consumers of opioids worldwide. Opioid use has increased 15-fold in Australia over 20 years (1992 to 2012), making it the country with the second highest per capita consumption of oxycodone. In 2014, the country introduced tamper-resistant controlled-release oxycodone.

The study looked at whether reformulation changed use of controlled-release oxycodone and opioid-related harms in a sample cohort of 36 528 adults who had at least one filled prescription for oxycodone during the study period (July 2012 to November 2016). After reformulation, dispensing of oxycodone in both 10-30 mg and 40-80 mg strengths gradually decreased for people under age 65 years, for total decreases of 11% and 31.5%, respectively. People younger than 65 years, especially those younger than 45 years, were more likely to switch to morphine after reformulation, and there was an increase in participants of all ages switching to oxycodone/naloxone.

"The observed decline in dispensing of higher-strength oxycodone controlled-release in participants less than 65 years of age may be due to an increase in switching to other strong opioids, chiefly morphine, rather than an increase in ending use," writes Dr. Andrea Schaffer, University of New South Wales, Sydney, Australia, with coauthors. "This is of concern because it suggests that people may be seeking out opioids without tamper-resistant properties."

The authors note that as the study was observational, the results do not indicate causation between reformulation and changes in behaviour, but rather an association.

Despite reductions in dispensing of stronger oxycodone, poisonings from injected oxycodone did not decrease, as measured by calls to the New South Wales Poison Information Centre, which receives about 50% of all poisoning calls yearly in Australia.

"We did not find an increase in ending use of strong opioids in parallel with an increase in switching to other non-tamper-resistant strong opioids," write the authors.

They note that people under age 65 who were using higher-strength opioids and switched to different types of opioids had been identified as having a higher risk of opioid use problems and should be closely monitored by their physicians.

The study was funded by Australia's National Health and Medical Research Council Centre of Research Excellence in Medicines and Ageing.

"Person-level changes in oxycodone use after the introduction of a tamper-resistant formulation in Australia" is published March 26, 2018.

Saturday, March 24, 2018

Fatty Liver Disease May Be Easier to Prevent than Treat

In The Media
MedPage Today published on March 22, 2018

NAFLD May Be Easier to Prevent than Treat
by Liz Highleyman
Contributing Writer, MedPage Today
Several new agents in the pipeline for non-alcoholic fatty liver disease, but weight loss remains key

Fatty liver disease is typically asymptomatic in its early stages and may go undiagnosed for years or decades. Over time, however, steatosis can result in hepatocyte damage (known as ballooning), and the associated inflammation and fibrosis can interfere with normal liver function and lead to hepatocellular carcinoma. People with NAFLD have a shorter life expectancy compared with the general population, and they often die of cardiovascular disease rather than liver-related causes.

The prevalence of fatty liver disease is increasing along with the epidemic of obesity in the U.S. and worldwide. It is expected to account for a growing proportion of advanced liver disease, liver cancer, and liver transplantation as vaccination reduces the incidence of hepatitis B virus infection and new direct-acting antivirals cure hepatitis C before it can cause serious liver damage.

An estimated 65 million Americans have NAFLD, and nearly 17 million have NASH, Scott Friedman, MD, of the Icahn School of Medicine at Mount Sinai in New York City, said during a press briefing on the topic at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting this past November. He predicted that these numbers could reach 100 million and 27 million, respectively, by 2030.
Continue reading...

MDedge News March 20, 2018
Red meat intake linked to NAFLD risk
Publish date: March 20, 2018
By Bianca Nogrady 
Higher dietary intake of red meat and processed meats such as salami may increase the risk of nonalcoholic fatty liver disease and insulin resistance, new research suggests.

In a cross-sectional study, published in the March 20 edition of the Journal of Hepatology, researchers used food-frequency questionnaires to examine red and processed meat consumption in 789 adults aged 40-70 years, including information on cooking methods.
Continue reading...

Of Interest
World J Gastroenterology published March 21, 2018
In people with HCV evidence of steatosis is found in close to half of patients who achieve a sustained virologic response after treating with direct-acting antivirals, according to data published Mar 21, 2018 in the online journal World J Gastroenterology.

An overview of the article: This is the first prospective study to assess the prevalence of fatty liver in hepatitis C patients who have achieved a sustained virological response with direct-acting antivirals. The study’s findings that fatty liver is present in 47.5% of these patients and that some steatotic patients have clinically significant fibrosis despite normal liver enzymes should raise awareness of the post-sustained virological response (SVR) prevalence of fatty liver and the importance of post-SVR assessment of steatosis and fibrosis and long-term follow up with these patients.

Patient-Reported Outcomes After HCV Treatment With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir

This is an extensive evaluation of Patient-Reported Outcomes (PROs) during and after treatment with 2 pangenotypic regimens for HCV. Our data clearly show that both regimens improve several PRO scores shortly after initiation of treatment. This improvement in PROs persisted throughout treatment and was even more considerable after achieving SVR-12. Moreover, the gains in PROs were not only sustained 12 weeks post-treatment but continued to further improve by Week 24 of follow-up.

Clinical Gastroenterology and Hepatology
April 2018 Volume 16, Issue 4, Pages 567–574.e6

Patient-Reported Outcomes Following Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir
Young-A HeoEmail authorEmma D. Deeks

Background & Aims
Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12).

We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placebo to 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period.

There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P = .0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0–100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05).

In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR.

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This is an extensive evaluation of Patient-Reported Outcomes (PROs) during and after treatment with 2 pangenotypic regimens for HCV. Our data clearly show that both regimens improve several PRO scores shortly after initiation of treatment. This improvement in PROs persisted throughout treatment and was even more considerable after achieving SVR-12. Moreover, the gains in PROs were not only sustained 12 weeks post-treatment but continued to further improve by Week 24 of follow-up.

We believe that initial gains in PROs are related to viral suppression that can occur with both regimens. Indeed, no similar improvement was seen in subjects who received placebo in a blinded fashion. In addition, unlike previously studied interferon + ribavirin-containing and interferon-free ribavirin-containing regimens, which resulted in decrements in PROs during treatment and weeks after treatment cessation,18, 22 no treatment-emergent PRO decrements were observed in actively treated patients in this study. Furthermore, presented PRO gains were similar to those reported for other all-oral interferon- and ribavirin-free regimens regardless of their duration.8, 15, 16, 20, 21, 23 This suggests that patients’ experience was not adversely affected by the side effects of the studied regimens and supports excellent tolerability of these regimens for HCV treatment.

In addition to the PRO benefit during treatment, the data clearly show that achieving SVR leads to sustainable gains in PROs, again consistent with previous reports for other DAA-based regimens.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 The magnitudes of post-SVR PRO improvements suggest their clinical relevance because most PROs increased by more than 3%–5% of a PRO range size, which is believed to be the minimal clinically important difference in PROs.38, 39

Furthermore, such improvements are comparable with long-term improvements in PRO scores observed in patients who had cardiac bypass surgery for their coronary artery disease or patients with rheumatoid arthritis after 24 weeks of treatment with methotrexate.40, 41 Accompanied by high efficacy of SOF/VEL ± VOX regimens, these PRO data provide support to the comprehensive benefit (to include clinical, or SVR, and patients’ experience, or PROs) of these new regimens for HCV-infected patients.

Finally, we have confirmed that the presence of cirrhosis, fatigue, and psychiatric comorbidities contributes to impaired PROs in patients with HCV; this is consistent with similar findings from prior studies.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 Although the exact causes of the observed association of location with baseline PROs are unclear, this is also consistent with prior reports on the contribution of cultural and ethnic factors to various PRO measures.42, 43 Nevertheless, the sociodemographic reasons for this difference requires future investigation. Furthermore, our multivariate analysis clearly shows that receiving active treatment with SOF/VEL or SOF/VEL/VOX is independently and similarly associated with improvement of PROs during treatment and in post-treatment follow-up. It is important to note, however, that other major predictors of greater on-treatment and post-treatment PRO gains were factors associated with lower baseline scores, such as history of depression, anxiety, and clinically overt fatigue, suggesting that these conditions, potentially associated with the extrahepatic manifestations of HCV, may also potentially resolve with virologic clearance; further prospectively designed studies are needed to confirm this hypothesis.

The main limitation of this study is the setting where PRO data were collected. Given that the PRO improvements were documented in the clinical trials setting, similar data from real-world clinical practices are needed; this issue applies both to clinical outcomes and PROs. Other limitations include open-label design of POLARIS-4, which might have affected PROs in participants; limited follow-up duration; and the lack of data on other potentially important PRO predictors, such as patients’ education, family status, and other socioeconomic parameters.

In summary, our study assessed the effect of 2 anti-HCV regimens, SOF/VEL and SOF/VEL/VOX, on PRO scores. The data are supportive of the comprehensive benefit of the new all-oral pangenotypic regimens for patients infected with HCV who had failed another DAA-based regimen and might have been left with no treatment options otherwise.
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