Monday, April 30, 2018

Battling an Epidemic - Part Three: What Iowa's parents, doctors and others are doing to overcome opioids' fatal effects

Battling an Epidemic - Part Three: What Iowa's parents, doctors and others are doing to overcome opioids' fatal effects
Michaela Ramm and Lee Hermiston, The Gazette April 30, 2018 | 9:43 am

Its staff and volunteers work in Cedar Rapids, Iowa City and Des Moines to address the impacts of the national opioid crisis that has caused the death of more individuals in 2016 than the number of Americans who were killed during the Vietnam War, according to the Police Executive Research Forum.

And they are not alone. The organization is among several others across the state — including public agencies, law enforcement, private insurance company officials and elected state leaders — working toward the same goal to address the effects of the opioid crisis within the state’s borders.

Iowa Harm Reduction Coalition Founder Sarah Ziegenhorn said the nonprofit operates under the assumption substance abuse and addiction cannot be totally eradicated in the population, so the main priority is to prevent the spread of disease and infection associated with injectable drug use, such as HIV or hepatitis C....

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Journal Of Hepatology
May 2018 Volume 68, Issue 5, Pages 1063–1075

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease
Thomas Jensen , Manal F. Abdelmalek, Shelby Sullivan, Kristen J. Nadeau, Melanie Green, Carlos Roncal, Takahiko Nakagawa, Masanari Kuwabara, Yuka Sato, Duk-Hee Kang, Dean R. Tolan, Laura G. Sanchez-Lozada, Hugo R. Rosen, Miguel A. Lanaspa, Anna Mae Diehl, Richard J. Johnson

Full-Text

TAKE-HOME MESSAGE
While we have known for many years that fructose and beverages sweetened with high fructose corn syrup can contribute to nonalcoholic fatty liver disease, this is an excellent review of the literature to date on this topic. In addition, it postulates the potential mechanisms that could be contributing to fructose's contribution to the development of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. It also highlights the factors that can potentiate the effect that fructose has on the liver, including genetic mechanisms, the role of fructokinase, high-fat diets, and alcohol.

While certainly more research is needed, this review is beneficial when speaking to our patients and providing guidance on dietary changes that may improve their disease.

– Natasha VonRoenn, MD

Summary
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome; its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and a sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high-fructose corn syrup [HFCS]) not only increase the risk of NAFLD, but also non-alcoholic steatohepatitis (NASH). Herein, we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked to the metabolism of fructose by fructokinase C, which results in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations to gut permeability, the microbiome, and associated endotoxemia contribute to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

Sunday, April 29, 2018

Cochrane Review Flawed For Discounting SVR As A Marker Of Viral Cure & Endpoint For Measuring Treatment Impact.

One Step Forward, Two Steps Back
Is it just me, or does it seem like each emerging milestone we make on the war against hepatitis C is eventually somewhat derailed? Either in the media, or worse yet, by failed and highly disputed research. Let me explain, over the years it went something like this; awareness (test all baby boomers, not everyone agreed), stigma (still working on it), cost (great drugs, too expensive), access & coverage (restrictions, you're not sick enough), and finally we cure the virus (Cochrane Review, cure, no proof of benefit).

Cochrane Review - Controversial Paper On HCV Therapy
Patients, advocates, and experts agree stigma and discrimination remains a barrier to testing and treatment, however, the benefit of curing hepatitis C with astounding cure rates is not all that controversial. Reason enough for experts to get caught up in a 2017 systematic review published by the Cochrane Collaboration on the benefit of achieving a cure using hepatitis C direct-acting antivirals (DAAs). The review concluded patients who were cured with DAA-based regimens did not reduce their risk for HCV-related morbidity or all-cause mortality. Within days, an outcry emerged from experts urging patients not to be influenced by the misleading and harmful conclusion, or be confused by any media coverage that followed.

*In case you missed the backstory, click here to review each expert rebuttal.

Cochrane Research Flawed 
Published April 10, 2018, online in Critical Public Health, patients can further explore the most recent rebuttal; Evidence-making controversies: the case of hepatitis C treatment and the promise of viral elimination.

*Thank you Henry E Chang, for downloading and sharing the full-text report on Twitter.

Here is an excerpt to get you started:
The EASL claims the Cochrane research has a ‘flawed methodological approach’, and that this is linked to its lack of hepatology expertise, including an ‘ignorance of the natural history of hepatitis C’. This ‘ignorance’ centres on the truth most troubled by the Cochrane review; that it ‘fails to accept that DAA treatment to attain an SVR is a pivotal outcome of treatment’, and that it ‘does not accept the likelihood that an SVR will reduce the risks of long-term outcomes of hepatitis C’. All the published responses we analysed (see above) present as ‘unanimous’ in characterising the Cochrane review as flawed for its discounting of SVR as a marker of viral cure and as an appropriate endpoint for measuring treatment impact.
Begin here.....

EASL's 2018 International Liver Congress - The Evidence Is In
Although this months "infohep bulletin" is not an official rebuttal over the failed Cochrane group's review, it does offer us an overview of EASL's 2018 International Liver Congress, and highlighted two studies at the meeting that "provided clear evidence that curing hepatitis C infection results in a reduction in the risk of dying from a liver-related cause."

Begin here....

Until next time,
Tina

Saturday, April 28, 2018

April "infohep bulletin" - Overview of EASL's 2018 International Liver Congress

Patients looking for an overview of EASL's 2018 International Liver Congress can find it in this month's "infohep bulletin"

Effectiveness of hepatitis C treatment
Direct-acting antiviral (DAA) treatment for hepatitis C is highly effective in curing hepatitis C infection but the long-term objective of treatment is to prevent liver disease and death. The long-term effects of curing hepatitis C virus (HCV) infection with DAAs was called into question by a Cochrane Collaboration systematic review in 2017. The review concluded that there was not yet sufficient evidence to show that curing HCV infection reduced illness and death. This conclusion was strongly questioned by liver experts.

At The International Liver Congress in Paris, a large prospective study carried out in Italy provided clear evidence that curing hepatitis C infection results in a reduction in the risk of dying from a liver-related cause. People with Child-Pugh A cirrhosis (compensated cirrhosis) were 15 times more likely to die of a liver-related cause if they did not achieve a sustained virologic response to DAA treatment, the study found. They were also at higher risk of dying from cardiovascular disease.

A study which followed everyone treated for hepatitis C in Scotland found that liver decompensation due to cirrhosis in people previously diagnosed with chronic hepatitis C declined by 29% between 2013 and 2016. During the same period 94% of people treated for hepatitis C in Scotland achieved a sustained virologic response.

Similarly, a Europe-wide study of liver transplants found that while the number of transplants carried out in Europe remained stable between 2007 and 2017, the proportion that were carried out as a consequence of hepatitis C fell from 23% to 11%. The decline in HCV-related transplants became evident after 2014 and was especially evident in people with HCV-related decompensated cirrhosis. The survival of liver transplant recipients with HCV also improved.

April Bulletin
This edition of the infohep bulletin covers news from the annual meeting of the European Association for the Study of the Liver (EASL), The International Liver Congress. The meeting took place in Paris from 11 to 15 April 2018. 

Friday, April 27, 2018

Harvoni effective for HCV genotype 4, including cirrhotic cases

In The Journal
Original article Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt
gamal Shiha,1,2 gamal esmat,3 Mohamed Hassany,4 reham Soliman,2,5 Mohamed elbasiony,1,2 rabab Fouad,3 aisha elsharkawy,3 radi Hammad,4 Wael abdel-razek,6 talaat Zakareya,6 Kathryn Kersey,7 Benedetta Massetto,7 anu Osinusi,7 Sophia lu,7 Diana M Brainard,7 John g McHutchison,7 imam Waked,6 Wahid Doss4

Full Text
Download PDF

Significance of this study
What is already known about this subject?
► In Egypt, which has one of the highest prevalences of hepatitis C virus (HCV) infection in the world (6.3%), >90% of patients are infected with HCV genotype 4.
► At the time of study design, sofosbuvir was the only direct-acting antiviral (DAA) drug available in Egypt. As such, the only DAA treatment options were sofosbuvir plus ribavirin plus pegylated interferon for 12 weeks, or sofosbuvir plus ribavirin for 24 weeks; there were no treatment options for patients who had failed direct-acting antiviral agent therapy.
► We sought to find the optimal regimen for ledipasvir–sofosbuvir in Egypt. Shorter treatment durations and/or the removal of ribavirin and pegylated interferon and their associated toxicities would be of benefit to patients. What are the new findings?
► Treatment-naive patients without cirrhosis were effectively and safely treated with the fixeddose combination of ledipasvir/sofosbuvir for 8 weeks.
► Rates of sustained virological response 12 weeks post-treatment (SVR12) of ≥94% were observed with 12 weeks of ledipasvir/ sofosbuvir±ribavirin treatment in interferonexperienced patients with or without cirrhosis. All sofosbuvir or ledipasvir–sofosbuvirexperienced patients in this study achieved SVR12 with 12 weeks of ledipasvir–sofosbuvir plus ribavirin for 12 weeks.
► Overall, the addition of ribavirin did not appear to increase rates of SVR observed with ledipasvir–sofosbuvir, but it was associated with an increase in the incidence of adverse  events.
Continue to article: http://gut.bmj.com/content/gutjnl/early/2018/04/21/gutjnl-2017-315906.full.pdf

Commentary @ Healio
Harvoni effective for HCV genotype 4, including cirrhotic cases
April 27, 2018 
Patients with hepatitis C genotype 4 had high sustained virologic response rates with Harvoni over 8 weeks in treatment-naive cases without cirrhosis and over 12 weeks with ribavirin regardless of cirrhosis or treatment experience, according to recently published data from a phase 3 study in Egypt.

“Given the high prevalence of HCV in Egypt and the heterogeneity of the HCV-infected population with respect to age, comorbidities and prior HCV therapy, there is a need in Egypt for a highly efficacious, well-tolerated, single-tablet regimen with simple monitoring,” Gamal Shiha, MD, PhD, from the Liver Research Institute and Hospital in Egypt, and colleagues wrote. “With the widespread use of sofosbuvir, an efficacious treatment for those who have failed treatment with a sofosbuvir-based regimen would also be highly desirable.”

Full Article: https://www.healio.com/hepatology/hepatitis-c/news/online/%7B30747e3b-aaf2-4095-ab47-fb6278189b95%7D/harvoni-effective-for-hcv-genotype-4-including-cirrhotic-cases

Opioid epidemic: More funding needed

In The Journals 
Increases in Acute HCV Infection, Injection Drug Use, and the Opioid Epidemic
April 27, 2018
It appears that the increase in acute hepatitis C virus (HCV) infection in the United States is related to the country's opioid epidemic and increase in injection drug use, according to a study in the American Journal of Public Health.

Published: 25 April 2018
For over a decade, the vast majority of new hepatitis C virus (HCV) infections have been among young people who inject drugs (PWID). Well-characterized gaps in chronic HCV diagnosis, evaluation, and treatment have resulted in fewer than 5% of PWID receiving HCV treatment. While interferon-based treatment may have intentionally been foregone during part of this time in anticipation of improved oral therapies, the overall pattern points to deficiencies and treatment exclusions in the health care system. Treatment for HCV with all-oral, highly effective direct-acting antiviral medication for 12 weeks or less is now the standard of care, putting renewed focus on effective delivery of care. We describe here both the need for and process of chronic HCV care under the roof of addiction medicine.

Opioid epidemic: More funding needed
Nardy Baeza Bickel

ANN ARBOR—More funding is needed to address the opioid epidemic that is projected to cost the U.S. economy $200 billion by 2020, says a University of Michigan researcher.

In an article published in JAMA Psychiatry, Rebecca Haffajee, assistant professor of health management and policy at the U-M School of Public Health, says funding has been insufficient to face the epidemic that in 2016 took the lives of 116 people per day.

"Recent estimates have suggested that the crisis is costing the country tens of billions, perhaps hundreds of billions, per year, but our allocations are not catching up to those costs," Haffajee said. "Congress is starting to have an appreciation of the magnitude of the epidemic and what it's going to cost to really get us over this, but we're not nearly there yet.

"We're hearing from the states that they are overwhelmed. They do not have the resources to actually address this crisis, and they need the federal government to lend resources to help them address it."

Haffajee and co-author Richard Frank of the Department of Health Care Policy at Harvard Medical School propose focusing on four areas to deal with the acute, emergency aspects of the opioid crisis. They say that putting federal funding—on the order of hundreds of millions—into specific programs could help save lives and mitigate other immediate harms in the short-term.

The researchers suggest:
Congressional appropriation of money into an emergency fund to purchase naloxone hydrochloride, a drug that when used correctly and promptly can reverse opioid overdose.
Provision of funds for clean syringe programs that facilitate substance use treatment and access to naloxone, and could also help reduce transmission of infectious diseases such as HIV and Hepatitis C. Outbreaks of these diseases have been linked to the opioid epidemic.
Increased funding for state foster care systems. Opioid-related overdoses have been blamed for a recent peak in the number of children in foster care—a 7-percent increase between 2012 and 2016.
Provision of funds and relaxed regulations to help deal with severe shortages of medication-assisted therapy in rural communities.

Haffajee and Frank say that opioid-related overdose deaths increased 80 percent between 2012 and 2016. Synthetic opioid-related overdose deaths, in particular, have skyrocketed—a 675-percent increase during that time.

"That's just an astronomical increase and actually shows no signs of slowing down," Haffajee said. "We propose that the most direct mean of averting these deaths is to expand access to and training on administering naloxone hydrochloride, a drug that when used correctly and promptly can reverse opioid overdose. But the deaths are just the tip of the iceberg.

"For every death, you have multiple hospitalizations and emergency department visits and other adverse health outcomes that precede or surround death."

Haffajee said there is good evidence that medication-assisted treatment can improve outcomes for those with opioid use disorders, especially those in rural communities.

"We know that the provider shortages are very acute in rural areas, with over 90 percent of rural counties lacking an opioid treatment program and 70 percent lacking a buprenorphine provider," she said. "So there are a lot of counties where people would not even be able to actually access this treatment. And we know that the rates of overdoses and the increases in those places are particularly high as well."

Haffajee said it's important to know that these measures would provide temporary emergency relief, but a long-term plan is needed as well.

"There is some misconception that we're going to be able to cure the addiction suddenly and immediately and that's not what the clinical evidence tells us," she said. "We should be thinking about it as a chronic health condition much like diabetes.

"Many people will need to be treated for years, not just for a short amount of time or a couple of months. But we need people to get started on treatment and then continue to provide support."

More information:
Article in JAMA Psychiatry: Making the Opioid Public Health Emergency Effective
Rebecca Haffajee

There’s A Cure For Hepatitis C, But Oregon Limits Access

There’s A Cure For Hepatitis C, But Oregon Limits Access
By Amelia Templeton / OPB
Oregon’s decision to continue to limit treatment based on a patient’s fibrosis score conflicts with guidelines set by health professional groups.

The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recommend that all patients with chronic hepatitis C should be treated.

The groups note that treating patients early, before significant fibrosis has developed in the liver, appears to be a particularly effective way of reducing deaths associated with hepatitis C.

Thursday, April 26, 2018

World Hepatitis Alliance - April Issue "Hep Voice"

Out of the 325 million people living with viral hepatitis globally, upward of 300 million (that’s 9 in 10!) are living with the hepatitis B or hepatitis C without knowing. Without a massive scale-up in diagnosis, treatment rates will fall, infection rates will rise and our opportunity to eliminate viral hepatitis by 2030 will be lost.

On World Hepatitis Alliance (WHA), we are launching the Find the Missing Millions global campaign to raise awareness of viral hepatitis, increase testing both at individual and policy level and improve linkage to care.

World Hepatitis Day (WHD) takes places every year on 28 July bringing the world together under a single theme to raise awareness of the global burden of viral hepatitis and to influence real change.

Join us on World Hepatitis Day 2018 in the quest to Find the Missing Millions. Sign up here.

World Hepatitis Alliance (WHA) presents hepVoice, a monthly magazine with updates on the latest projects, news from WHA members and key developments in the field of hepatitis.

Contents
This month in numbers NOhep
Visionaries, access to treatment, WHA members in Nigeria

Hep headlines
Hepatitis B among pregnant women, hepatitis C in PWIDs, new reports from WHO

World Hepatitis Day 2018 - Find the Missing Millions
WHD 2018 campaign launches with focus on diagnosis

Universal Health Coverage
#HealthForAll Community steps up efforts towards UHC

Wall of Stories snapshots: “Late diagnosis left me with cirrhosis”
Rosario from Uruguay shares her story

Reports
PROGRESS REPORT ON ACCESS TO HEPATITIS C TREATMENT FOCUS ON OVERCOMING BARRIERS  IN LOW- AND MIDDLE-INCOME COUNTRIES MARCH 2018

The World Hepatitis Alliance is an ambitious patient-led and patient-driven not-for-profit organisation who works with governments, national members and other key partners to raise awareness of viral hepatitis and influence global change – transforming the lives of the 325 million people living with viral hepatitis and the future we share.

A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6‐ to 12‐ year old children

A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6‐ to 12‐ year old children
M. H. F. El‐Shabrawi N. M. Kamal H. R. El‐Khayat E. M. Kamal M. M. A. H. AbdElgawad M. Yakoot

First published: 25 April 2018 https://doi.org/10.1111/apt.14677

Full-Text
View Online

Summary
Background
No available data on the use of sofosbuvir/ledipasvir combination in treatment of hepatitis C virus (HCV) infection in children 6‐ to 12‐ year old.

Aim
To assess the safety and efficacy of sofosbuvir plus ledipasvir in children 6‐ to 12‐ year old with chronic HCV genotype 4 infection.

Methods
This is a pilot prospective single arm observational open‐label multicentre study. A total of 20 consecutive eligible chronic HCV infected children, aged from 6‐ to 12‐ years were included in this study and treated with a fixed sofosbuvir/ledipasvir combination in half the adult dose (200/45 mg) once daily for 12 weeks. Laboratory tests including virological markers were measured at baseline, 2, 4, 8 and 12 weeks (end of treatment [EOT]), and 12 weeks after end of treatment for sustained virological response 12 (SVR12).

Results
The intention‐to‐treat (ITT) SVR12 rate was 19/20 (95%; 95% CI: 76.4%‐99.1%). SVR12 was not assessed in one patient who was lost to follow‐up after showing viral negativity at the EOT12. All the remaining 19 patients (100%, 95% CI: 83.18%‐100%) who completed the full protocol and follow‐up visits achieved SVR12 with normal liver, haematological, and renal function tests and no side effects or fatalities.

Conclusions
This pilot study demonstrated that the fixed dose sofosbuvir/ledipasvir combination could be safe and effective treatment in children 6‐ to 12‐ years with chronic hepatitis C genotype 4 infection. Our pilot results might encourage larger and multicentre studies in this age group.

Strategies for Reducing Opioid-Overdose Deaths — Lessons from Canada

April 26, 2018
N Engl J Med 2018; 378:1565-1567
DOI: 10.1056/NEJMp1800216

Perspective
Strategies for Reducing Opioid-Overdose Deaths — Lessons from Canada
Evan Wood, M.D., Ph.D.

Audio Interview with Dr. Evan Wood on actions taken by Canada to reduce opioid-overdose deaths.
Listen Here.....

As the United States faces this unprecedented epidemic, there are lessons to be learned from Canada, which has taken bold action on a number of fronts with the aim of reducing deaths related to fentanyl, fentanyl analogues, and other opioids. For instance, in March 2016, the Canadian government made the overdose-reversal drug naloxone available without a prescription. Although naloxone is also increasingly available in many regions of the United States, laws in 14 states provide no immunity from criminal prosecution for health care providers who prescribe or distribute it to laypersons. Furthermore, in 36 states, existing laws make possession of naloxone without a prescription illegal.

The Canadian government has also passed legislation aimed at facilitating the development of medically supervised injection facilities, where people who use drugs can inject opioids they buy on the street under the supervision of health care staff. Although research has found that supervised injection facilities can reduce rates of fatal overdoses by more than 30% in communities with high rates of drug use1 and can help facilitate greater uptake of addiction treatment, there are few, if any, such programs in the United States. In recent months, however, public health officials in several U.S. cities, including San Francisco, Seattle, and Philadelphia, have endorsed plans to open pilot supervised injection programs to address increasing rates of overdose deaths.

Wednesday, April 25, 2018

Liver disease burden and required treatment expenditures for hepatitis C virus (HCV) infection in Thailand

Liver disease burden and required treatment expenditures for hepatitis C virus (HCV) infection in Thailand: Implications for HCV elimination in the new therapeutic era, a population-based study
Rujipat Wasitthankasem, Preeyaporn Vichaiwattana, Nipaporn Siripon, Nawarat Posuwan, Chompoonut Auphimai, Sirapa Klinfueng, Napha Thanetkongtong, Viboonsak Vuthitanachot, Supapith Saiyatha, Chaiwat Thongmai, Saowakon Sochoo, Natnada Pongsuwan, Kittiyod Poovorawan, Pisit Tangkijvanich, Yong Poovorawan

Published: April 24, 2018
https://doi.org/10.1371/journal.pone.0196301

Full-Text
Available Online

Abstract
The prevalence of hepatitis C virus (HCV) infection has been decreasing globally, but the growing effects of HCV-related morbidity and mortality remain of concern. Advances in curative medicine, involving direct-acting antivirals (DAAs), have led many countries to aim to eradicate HCV. Information on epidemiology and disease burden is essential for national policy development. Thus, this study aimed to determine the HCV-related hepatic disease burden in areas of Thailand with high and average HCV prevalence in order to extrapolate the viral burden across Thailand. Patients previously diagnosed as positive for anti-HCV antibodies were recruited to assess chronic HCV infection (CHC) status, liver function, HCV-RNA level and hepatic fibrosis. The number of patients eligible for Universal Health Coverage (UC) scheme and the approximately required expenditure on interferon (IFN)-based treatment were estimated. In areas of both high (12%) and average (2%) HCV viremic prevalence, over half of the patients (52.2% to 62.5%) had advanced liver fibrosis (F3 and F4). A striking percentage of patients with F4 (38.9%) were found in the high-prevalence area, while comparable proportions of advanced liver fibrosis presented in the two areas and disease burden peaked at 50–59 years. Under the current UC program treatment scenario, 78–83% of CHC patients with stage F2–F4 fibrosis were eligible for treatment. The estimated expenditure required for overall CHC treatment across the whole country was 1,240 million USD at this current status, but the declining cost of generic DAA-based therapy may reduce the requirement to <90 million USD. This study provides information on the estimated number of CHC patients, liver disease burden and expenditure requirements for Thailand. To eliminate HCV by 2030, proactive government strategies raising public health to minimize transmission and emphasizing targeted screen-and-treatment programs, novel therapeutic guideline development for decentralizing treatment, and effective budget allocation are urgently needed.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196301

Medicare to require hospitals to post prices online

Medicare to require hospitals to post prices online
Nation
Apr 24, 2018 6:27 PM EDT

WASHINGTON — Medicare will require hospitals to post their standard prices online and make electronic medical records more readily available to patients, officials said Tuesday.

The program is also starting a comprehensive review of how it will pay for costly new forms of immunotherapy to battle cancer.

Tuesday, April 24, 2018

Radiotherapy offers new treatment option for liver cancer

Radiotherapy offers new treatment option for liver cancer

Radiological Society of North America

OAK BROOK, Ill. - A novel technique that delivers high doses of radiation to tumors while sparing the surrounding normal tissue shows promise as a curative treatment option for patients with early-stage liver cancer, according to a study published online in the journal Radiology.

Curative treatment options for early-stage hepatocellular carcinoma (HCC), the most common type of liver cancer, include surgery, liver transplantation and radiofrequency ablation. However, many patients are not candidates for these therapies due to the presence of other conditions. In addition, these treatments carry significant costs and potential complications.

Radiation segmentectomy (RS) is a minimally invasive option that uses the radioisotope yttrium-90 (Y90) to destroy tumors. The isotope is embedded into tiny beads that are delivered through a catheter into a blood vessel in the liver. They then travel to the site of the tumor, where they come to rest and deliver their radioactive effect while sparing much of the surrounding healthy tissue.

The procedure's name derives from the fact that surgeons divide the liver into a number of segments. Using an imaging approach called cone beam CT, interventional radiologists gain a detailed view of the complex liver vasculature and can focus delivery of the Y90 to the relevant segment.

"Cone beam CT has revolutionized our ability to perform segmental injections isolated to very small tumors, sparing the majority of normal tissue," said study senior author Riad Salem, M.D., chief of vascular interventional radiology in the Department of Radiology at the Northwestern University Feinberg School of Medicine in Chicago. "Before cone beam CT, we had the ability to focus radiation, but not with this level of accuracy."

Dr. Salem and colleagues studied long-term outcomes in 70 early-stage HCC patients who had undergone RS between 2003 and 2016. They analyzed the patients' responses to treatment based on two commonly used sets of criteria.

Based on one criteria, 90 percent of patients showed positive response to the therapy, of which 59 percent showed complete response. Based on a second criteria, 71 percent achieved positive response, of which 16 percent achieved complete response.

RS controlled the target tumor, slowed the time to disease progression and improved survival outcomes at rates comparable to radiofrequency ablation, surgery and transplantation for early-stage HCC patients.

Almost three-quarters of patients had no progression of cancer in the target tumor five years after treatment. Median overall survival was 6.7 years, and one-, three-, and five-year survival probabilities were 98 percent, 66 percent and 57 percent, respectively. One-, three-, and five-year overall survival probability was 100 percent, 82 percent and 75 percent in patients with a baseline tumor size of 3 centimeters or less.

"The results show that we are able to impart curative outcomes to these patients," Dr. Salem said. "Our numbers with radiation segmentectomy match or outperform those of other curative treatments in terms of tumor control, survival rate and recurrence."

RS is performed on an outpatient basis, is minimally invasive and has a low toxicity profile, Dr. Salem said. Given the potency of the radiation, RS outperforms transarterial chemoembolization, another minimally invasive procedure in which cancer-killing drugs are injected into the liver's main artery under imaging guidance and travel to the tumor microvasculature. Transarterial chemoembolization has the additional disadvantage of requiring hospitalization.

The researchers continue to follow the patients from the study group as they work on ways to optimize the treatment.

"We want to see these outcomes validated in patients over the longer term," Dr. Salem said. "We also want to minimize the time from clinic visit to treatment, and fine-tune dosimetry so that we can find the optimal dose that will kill the tumor. In the right patient setting, RS can be considered curative."
https://www.eurekalert.org/pub_releases/2018-04/rson-ron041718.php

Implementation of hepatitis C cure in Australia: one year on

J Virus Erad. 2018 Apr 1;4(2):115-117.
Implementation of hepatitis C cure in Australia: one year on.
Richmond JA, Wallace J1.

Full Article
View Online

Abstract
Objectives:
Direct-acting antivirals (DAAs) for the treatment of hepatitis C (HCV) became universally available in Australia in March 2016, with an aim to achieve HCV elimination. Fourteen per cent of Australians with HCV have initiated treatment. The objective of this study was to explore and identify challenges and enablers that have emerged during this initial phase of HCV cure implementation.

Methods:
Key stakeholders (KS) in primary care, non-government and government sectors were recruited to participate in a telephone-based semi-structured interview to describe challenges and enablers facing individuals with HCV and the healthcare system in implementing HCV cure. Data were thematically analysed.

Results:
Eleven KS participants were interviewed with each commending the significantly increased numbers of people accessing HCV treatment since March 2016. There was concern that this momentum was waning and that targeted interventions to normalise HCV treatment within primary care were needed. Furthermore, workforce development activities needed to acknowledge the priority of HCV elimination, and develop training and resources for clinicians, most of whom had limited HCV experience. The role of professional champions and multidisciplinary teams of both clinical and non-clinical workers was identified as critical for services that had cured a significant number of people with HCV.

Conclusions:
Australia has many of the essential elements necessary to eliminate HCV, including universally funded DAA access and multiple treatment access points through primary care. Additional systematic activity is needed to ensure that the DAA-access momentum is maintained and HCV elimination achieved.

Monday, April 23, 2018

HCV, type 2 diabetes & fatty liver disease - Importance of diet and exercise

Importance of diet and exercise 

This Michigander is announcing winter might just be over. I am so done walking on my ugly, hated, overrated treadmill, looking forward to moving my morning routine outside.

If you too are feeling a bit of spring fever, or preparing for a lifestyle change, check out the links provided below and learn about the importance of diet and exercise for people with HCV, type 2 diabetes or fatty liver disease.

On The Radio
To get you started we begin with Dr Norman Swan, the host of Health Report, along with his guest Professor Mike Lean, lead author in a study investigating the impact of weight loss on type 2 diabetes, published in the Lancet 10 February 2018; Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The study found after a year, participants who lost weight (around 30 pounds) on a 800 calorie diet, no longer had type 2 diabetes. The diet may be too difficult or not recommended for some people, in the trial patients were followed closely, however, the outcome is amazing. The interview starts at 8:29, listen to the program, here, read the transcript below or visit Health Report.

Transcript
Norman Swan: There's good news, for once, from the west of Scotland where a trial in general practice of an extremely low calorie diet has reversed type 2 diabetes in a large percentage of participants. Mike Lean is Professor of Human Nutrition at the University of Glasgow and is on the line. Welcome to the Health Report.

Mike Lean: Hello, how are you?

Norman Swan: Fine. You say in the paper that this is the first trial of its kind in type 2 diabetes, which is extraordinary.

Mike Lean: We've known about type 2 diabetes and thought of it as a distinct disease growing enormously in numbers and costing perhaps more than any other single disease for about 100 years, and it has been noted in a number of studies that some people if they lose enough weight will get rid of their diabetes. But no study has previously gone out to actually try and do that, to actually get as many people as possible to become non-diabetic, to get rid of their diabetes completely.

Norman Swan: So what did you do in this study?

Mike Lean: Well, this is not rocket science. What we did was we recruited people in primary care, in general practice, who were overweight, BMI over 27, so not enormously overweight but overweight, with type 2 diabetes. And we ask them to follow a formula diet, not a very low calorie but and 800-odd calorie diet for as long as it took, and it took quite a long time in some cases, to lose enough weight to become non-diabetic. And we aimed to get 15 kg weight loss because we knew from other observations that that was likely to do it. And of course not everybody managed, sadly, a lot of people found it really hard. A lot of people did manage. In the end we got about a quarter of our patients to lose that amount of weight. And those who lost 15 kg, almost 90% were no longer diabetic after a year, they were off all their medication, they were off all their diabetic medication and their antihypertensive medication, and they felt a lot better, their quality of life went up.

The remainder who didn't lose 15 kg, none of them got worse. Of those who lost over 10 kg, over half of them were non-diabetic. So you don't need to lose 15 kg but it's much better if you do. And I think what we've learnt from this is what we've regarded as a distinct disease, type 2 diabetes, is actually all part and parcel of obesity when you think about obesity as a disease process…

Norman Swan: We'll come back to the diet in a minute. And what was the recidivism rate, if you want to call it that, in terms of people gaining weight again and returning to diabetes?

Mike Lean: Yes, so that is of course…we've only published the one-year results and there's a lot more to find out. What we did find out was that the proportion of people with diabetes who wanted to have a go at this was very high. It was probably no great surprise because being diabetic is a penalty and it carries terrible medical risks as well as financial. The number within a year who put on any weight was really quite small, but we know very well from earlier studies that it's hard to maintain…the biggest problem is not losing the weight, it's actually maintaining it long term, and that's where our big research effort needs to go.

Norman Swan: So the diet itself…an 800 calorie diet is not something you try yourself at home because you can go into nutritional deficiency. This was a shakes and bars diet, wasn't it, it was a meal plan diet.

Mike Lean: That's correct, it was a formula diet which made sure it had all the vitamins and minerals, everything that was necessary, provided the patients actually followed this. And they didn't have to pay for it, they were given it for the study. And so they did that, so it was perfectly safe, there was no…

Norman Swan: That's my point, so it's one of these things you can buy in the chemist and it comes in various boxes, but we won't talk about the branding.

Mike Lean: The branding doesn't matter, all these things are pretty much the same. What matters is not what comes in the box or out of the packet, it's the support that is given with it, because people who go and get these type of diets from the chemist or from a supermarket generally do it for two or three or four weeks and then they peel off. If you are going to get rid of your diabetes you've got to stick in for probably 12 weeks if you do it full time. There are plenty of people who do it off and on for 12 weeks and need to carry on doing it off and on for a bit longer to lose their 10 or 15 kg. So there are different routes to getting there, you don't half to lose it all in one go but it works better if you do.

Norman Swan: What about complications, like if you lose weight fast when you are overweight you can get gallbladder disease…

Mike Lean: Ah, you're well informed!

Norman Swan: You can low blood sugar if you're on insulin, or diabetes complications. What sort of complications did people get?

Mike Lean: Well, the first thing was for this particular study we didn't include people who were already on insulin, partly because their likelihood of getting a remission is much lower. It had probably done damage to their pancreas by that stage. And what we did on day one was that we stopped all our anti-diabetes medication, so there's no risk of hypoglycaemia at all, and nobody had hypoglycaemia. And the same thing went for the blood pressure tablets, we stopped all their blood pressure tablets on day one because otherwise if you lose weight there is a risk of possible hypotension, and just to pick up your other point, there was one patient amongst the 150 who started, one who developed abdominal pains and we think that was probably by gallstones. That's a common complication of obesity, very common in people with diabetes anyway, and it can be made worse during weight loss.

Norman Swan: These are similar findings to bariatric surgery.

Mike Lean: Oddly the remission rate was actually a tiny bit better than bariatric surgery if you can lose 15 kg. If you lose 15 kg you will almost certainly get rid of your diabetes, whether or not it's done with surgery. There are of course many fewer hazards doing it without surgery. They produce very similar results, yes.

Norman Swan: Mike, thanks very much for joining us, a fascinating study.

Mike Lean: Thank you very much.

Norman Swan: Mike Lean is Professor of Human Nutrition at the University of Glasgow.

Fatty Liver Disease & Type 2 Diabetes 
"Given the increasing worldwide incidence of obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. Recent developments in the field have shown that NAFLD not only is a “liver disease” but also is the underlying cause of an increasing number of extrahepatic manifestations; thus, it should be treated as a multisystem disease. NAFLD is most prominently linked to chronic kidney disease, mellitus type 2 and cardiovascular disease, as well as a number of other severe chronic diseases. These findings demonstrate that NAFLD ranks amongst the most serious public health problems of our time."

Also noted in the article; The prevalence of Nonalcoholic Steatohepatitis (NASH), in people who are obese and have type 2 diabetes may be as high as 40%, whereas it is less than 5% in people without type 2 diabetes.
Read the article, here.

Presented at Liver Congress 2018
Alcoholic liver disease replaces hepatitis C infection as leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA
Two independent studies presented at the conference reported; that alcoholic liver disease has now replaced hepatitis C virus (HCV) infection as the leading cause of liver transplantation in the USA in patients without HCC. Non-alcoholic steatohepatitis (NASH) is also on the increase, now ranking second as a cause of liver transplantation due to chronic liver disease.
Read the article, here.

Hepatitis C & Diabetes
Several studies have demonstrated the risk for development of diabetes is increased in people with chronic hepatitis C infection (HCV), for instance people with HCV have a 2.3 fold increased chance of having type 2 diabetes. According to a 2013 study published in Alimentary Pharmacology Therapeutics; Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes mellitus and hypertension) and congestive heart failure.

HCV Treatment & Type 2 Diabetes
The good news is with today's high sustained viral response rates using direct antiviral medications to treat HCV, people who successfully reach SVR, or achieve a cure, lower their risk for the development of type 2 diabetes, the recent study was published in the Journal of Viral Hepatitis [published online February 25, 2018]. A quick overview of the study can be found online, here.

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....

Tips - Eating Right
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.

The Liver Loving Diet
"The Liver Loving Diet" is a book that will help you learn to eat well during all phases of liver disease. Karen Hoyt, the author, also blogs about living with and treating hepatitis C, cirrhosis, liver cancer and liver failure.

Mediterranean diet reduces liver fat, risk for NAFLD
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

Bottom Line
Spring is a great time to start again, experts agree two key elements in the prevention and management of type 2 diabetes and fatty liver disease is weight loss and exercise. In the end, its all good for your liver!

See you soon,
Tina

Saturday, April 21, 2018

Albumin predicts cirrhosis improvement after SVR with DAAs

Albumin predicts cirrhosis improvement after SVR with DAAs
April 20, 2018

PARIS — Rapid improvement in albumin levels after 4 weeks of treatment with direct-acting antivirals for hepatitis C significantly predicted long-term clinical and biochemical improvements among patients with advanced liver disease, according to a presentation at the International Liver Congress 2018.

“The introduction of DAAs has completely changed the HCV setting in clinical practice,” Chiara Mazzarelli, MD, from King’s College Hospital, United Kingdom, said in her presentation. “As hepatologists, we know that HCV clearance ... is associated with improvement and normalization of liver function.”

On This Blog

Hepatocellular carcinoma as a consequence of hepatitis C direct-acting anti-virals-the great urban myth of hepatology

Aliment Pharmacol Ther. 2018 May;47(10):1418-1419. doi: 10.1111/apt.14634.

Linked Content
This editorial is linked to Singer et al paper; Direct‐acting antiviral treatment for hepatitis C virus infection and risk of incident liver cancer: a retrospective cohort study, published 7 March 2018  https://doi.org/10.1111/apt.14593.

Editorial: hepatocellular carcinoma as a consequence of hepatitis C direct‐acting anti‐virals—the great urban myth of hepatology
Hussaini T1,2, Zhu J2,3, Yoshida EM2,3.

Achieving sustained virologic response (SVR), the surrogate marker for the cure of chronic hepatitis C virus (HCV) infection, has long been associated with decreased all‐cause and liver‐related mortality including progression to end stage liver disease or development of hepatocellular carcinoma.1 During the interferon (IFN) era, many studies demonstrated decreased incidence of HCC after HCV eradication, although the risk was not eliminated, especially in patients with advanced hepatic fibrosis or cirrhosis.2-4 With the availability of direct acting antiviral agents (DAAs), offering high SVR rates of greater than 90%, a dramatic decrease in HCC incidence was expected. Single‐center observational studies, however, reported an unexpected increase in both HCC occurrence and recurrence following DAA associated SVR.5-8 The majority of these studies were limited by methodological flaws: small sample size, lack of control groups and short follow‐up time, resulting in a suspicion of selection bias and other potential confounders. Nonetheless, these reports raised concern that DAA therapy may promote HCC recurrence by altering immune surveillance after HCV eradication.

Recently, the results of a large retrospective cohort trial studying 62 352 HCV infected patients treated with IFN, DAAs, or a combination of both, challenged the findings of the earlier studies.9 Based on HCV treatment regimens, patients were divided into three groups; IFN only (N = 35 871), DAAs + IFN (N = 4535), and DAA only (N = 21 948). Although the HCC incidence was higher with DAA only therapy, after adjusting for important baseline confounders, there was no difference in HCC incidence between the groups. In fact, SVR was associated with significantly lower incidence of HCC regardless of regimen utilised.

In a recent issue of Alimentary Pharmacology & Therapeutics, Singer and colleagues, report the results of another large population based study that further dispels the myth of increased HCC occurrence after DAA associated SVR. They studied 30 183 patients treated with DAAs, 12 948 patients treated with IFN‐based therapy and 137 502 treatment‐naïve patients.10 The unadjusted incidence rate of HCC was higher in DAA treated group as compared to both IFN treated (unadjusted HR = 1.22, 95% CI: 1.04‐1.42) and treatment naïve patients (unadjusted HR of 1.84 (95% CI: 1.65‐2.05). However, after adjusting for known baseline risk factors for HCC such as older age, male gender and advanced liver disease, DAA therapy was associated with reduced incidence of HCC as compared to untreated (adjusted HR = 0.84, 95% CI: 0.73‐0.96) and IFN treated individuals (adjusted HR = 0.84, 95% CI: 0.73‐0.96).

The introductions of DAA regimens have revolutionised HCV therapy, both in terms of outstanding SVR rates and excellent tolerability profiles. They offer a chance for virological cure in those with few treatment options due to age or advanced liver disease. Therefore, it is not surprising that the unadjusted incident rate of HCC is higher in cohorts treated with DAAs as compared to IFN based therapy. The results of the recent large studies that were designed to control for known HCC risk factors such as older age and advanced liver disease have again demonstrated that HCV eradication reduces the risk of HCC regardless of anti‐viral regimen. We are therefore confident that DAAs do not increase the risk of HCC.

ACKNOWLEDGEMENTS
Declaration of personal: Drs. Hussaini and Zhu have no conflict of interest to declare Dr. Eric Yoshida has been an investigator of clinical trials sponsored by Gilead, Merck, Abbvie, Janssen, Intercept, Genfit, Springbank. He has received honoraria for CM/ad board lectures from Gilead Canada, Abbvie Canada, Merck Canada, Celgene Canada, Intercept Canada.

FUNDING INFORMATION
None.

References
1Van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all‐cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584‐2593.
Google Scholar
2Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck‐Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta‐analysis of observational studies. Ann Intern Med. 2013;158:329‐337.
Google Scholar
3Singal AK, Singh A, Jaganmohan S, et al. Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis. Clin Gastroenterol Hepatol. 2010;8:192‐199.
Google Scholar
4Van der Meer AJ, Feld JJ, Hofer H, et al. Risk of cirrhosis‐related complications in patients with advanced fibrosis following hepatitis C virus eradication. J Hepatol. 2017;66:485‐493.
Google Scholar
5Reig M, Marino Z, Perello C, et al. Unexpected high rate of early tumor recurrence in patients with HCV‐ related HCC undergoing interferon‐free therapy. J Hepatol. 2016;65:719‐726.
Google Scholar
6Kozbial K, Moser S, Schwarzer R, et al. Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon‐free direct‐acting antiviral treatment. J Hepatol. 2016;65:856‐858.
Google Scholar
7Cardoso H, Vale AM, Rodrigues S, et al. High incidence of hepatocellular carcinoma following successful interferon‐free antiviral therapy for hepatitis C associated cirrhosis. J Hepatol. 2016;65:1070‐1071.
Google Scholar
8Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV‐ related cirrhosis treated with direct‐acting antivirals. J Hepatol. 2016;65:727‐733.
Google Scholar
9Ioannou GN, Green PK, Berry K. HCV eradication induced by direct‐acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2018;68:25‐32.
Google Scholar
10Singer AW, Reddy KR, Telep LE, et al. Direct‐acting antiviral treatment for hepatitis C virus infection and risk of incident liver cancer: a retrospective cohort study. Aliment Pharmacol Ther. 2018;47:1278‐1287.
Google Scholar

Clinical Insights in NAFLD and NASH for 2018

Clinical Liver Disease (CLD) is a digital educational resource published on behalf of the American Association for the Study of Liver Diseases (AASLD). CLD publishes easy to read reviews on relevant topics for clinicians diagnosing and managing patients with liver disease.

LATEST ISSUE > Volume 11, Issue 4
Pages: 81-104
April 2018

Clinical Insights in NAFLD and NASH for 2018
Guest Edited by Arun Sanyal, MD

An update on the pharmacological treatment of nonalcoholic fatty liver disease: Beyond lifestyle modifications
Naim Alkhouri M.D.
Andrea Scott B.S.
Pages: 82-86
First Published:20 April 2018
Watch a video presentation of this article
Abstract
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References

Kara Wegermann M.D.
Anna Mae Diehl M.D.
Cynthia A. Moylan MD, MHS
Pages: 87-91
First Published:20 April 2018

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Abstract
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References

Free Access
The epidemiology of nonalcoholic steatohepatitis

Zobair M. Younossi M.D., M.P.H., F.A.A.S.L.D.
Pages: 92-94
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Abstract
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References

Pediatric nonalcoholic fatty liver disease

Tania Mitsinikos M.D.
Rohit Kohli M.B.B.S., M.S.
Pages: 95-97
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Abstract
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References

Diagnostic challenges of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Erin Cleveland M.D.
Andrew Bandy M.D.
Lisa B. VanWagner M.D., M.Sc.
Pages: 98-104
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Abstract
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References 

Friday, April 20, 2018

International Liver Congress 2018 - Webinars covering critical studies on viral hepatitis and NAFLD/NASH

Clinical Care Options 
Program Overview
2018 Annual Meeting of the European Association for the Study of the Liver*
April 11-15, 2018 | Paris, France

Review Capsules Summaries, download slides, and listen to audio commentary from expert-led Webinars covering critical studies on viral hepatitis and NAFLD/NASH from Paris.
Link: https://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/Paris%202018.aspx

Free registration required

Viral Hepatitis
Listen to downloadable audio from a live Webinar in which Stefan Zeuzem, MD, assessed the clinical impact of new data reported at the Paris meeting and answered case questions from participants.

Addition of RBV Associated With Increased Efficacy of 12 Weeks Sofosbuvir/Velpatasvir in Patients With Genotype 3 HCV Infection and Compensated Cirrhosis

Retreatment of Patients Who Failed Glecaprevir/Pibrentasvir Treatment for Hepatitis C Virus Infection

A Phase 3b, Open-Label, Randomized, Pragmatic Study of Glecaprevir/Pibrentasvir +/- Ribavirin (RBV) for HCV Genotype 1 Subjects Who Previously Failed an NS5A Inhibitor + Sofosbuvir (SOF) Therapy

8 Weeks Sofosbuvir/Velpatasvir in Genotype 3 Patients With Significant Fibrosis: Highly Effective Amongst an OST Cohort

Safety and Efficacy at 1 Year After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Chronic HBV Patients With Risk Factors for TDF Use

High Efficacy and Safety of Grazoprevir and Elbasvir for 8 Weeks in Treatment-Naive, Nonsevere Fibrosis HCV GT1B-Infected Patients: Interim Results of the STREAGER Study


NAFLD/NASH
Capsule Summaries (4) 
Low-Moderate Alcohol Use Is Associated With a Lower Prevalence of Nonalcoholic Fatty Liver Disease in Hispanics/Latinos Living in the US: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Substantial Comorbidities and Rising Economic Burden In Real-World Nonalcoholic Fatty Liver Disease (NAFLD)/Nonalcoholic Steatohepatitis (NASH) Patients With Compensated Cirrhosis (CC): A Large German Claims Database Study

Nonalcoholic Fatty Liver Disease and Relative Risk of Incident Steatohepatitis, Cirrhosis and Hepatocellular Carcinoma Events in 4 European Primary Care Databases

Prevalence and Stratification of NAFLD/NASH in a UK and US Cohort Using Noninvasive Multiparametric MRI

Begin here.......

Thursday, April 19, 2018

Life of a liver awaiting transplantation - Machine that preserves livers might offer a way forward


NEWS AND VIEWS
18 April 2018

Life of a liver awaiting transplantation
Stefan Schneeberger
People waiting for a liver transplant can die before an organ is found, or, if one is available but of poor quality, there is a risk of transplant failure. A machine that preserves livers might offer a way forward.

The concept of machine perfusion of an organ awaiting transplantation is not new. Indeed, machine-assisted perfusion was in use before cold storage became the method of choice owing to its simplicity and reproducibility2. However, interest in revisiting perfusion as a transplant approach has been gaining momentum.

The main outcome monitored in the latest trial was the post-transplantation level of the enzyme aspartate transaminase in patients’ blood. This measurement is commonly used to assess liver damage and to estimate the risk of transplant failure. The authors found that the use of NMP was associated with less liver damage than that found in livers preserved on ice. Moreover, preservation by NMP reduced the number of organs that were discarded as unsuitable for transplantation compared with livers preserved on ice, and was associated with a better blood-flow profile in the recipient.

Scientific guidelines for using cannabis to treat stress, anxiety and depression

Scientific guidelines for using cannabis to treat stress, anxiety and depression

Washington State University

PULLMAN, Wash.--In a first-of-a-kind study, Washington State University scientists examined how peoples' self-reported levels of stress, anxiety and depression were affected by smoking different strains and quantities of cannabis at home.

Their work, published this month in the Journal of Affective Disorders, suggests smoking cannabis can significantly reduce short-term levels of depression, anxiety, and stress but may contribute to worse overall feelings of depression over time.

It marks one of the first attempts by U.S. scientists to assess how cannabis with varying concentrations of the chemical compounds tetrahydrocannabinol (THC) and cannabidiol (CBD) affect medicinal cannabis users' feelings of wellbeing when smoked outside of a laboratory.

"Existing research on the effects of cannabis on depression, anxiety and stress are very rare and have almost exclusively been done with orally administered THC pills in a laboratory," said Carrie Cuttler, clinical assistant professor of psychology at WSU and lead author of the study. "What is unique about our study is that we looked at actual inhaled cannabis by medical marijuana patients who were using it in the comfort of their own homes as opposed to a laboratory."

For example, the WSU research team found that one puff of cannabis high in CBD and low in THC was optimal for reducing symptoms of depression, two puffs of any type of cannabis was sufficient to reduce symptoms of anxiety, while 10 or more puffs of cannabis high in CBD and high in THC produced the largest reductions in stress.

"A lot of consumers seem to be under the false assumption that more THC is always better," Cuttler said. "Our study shows that CBD is also a very important ingredient in cannabis and may augment some of the positive effects of THC."

The researchers also found that while both sexes reported decreases in all three symptoms after using cannabis, women reported a significantly greater reduction in anxiety following cannabis use.

Data for the study were taken from the trademarked app Strainprint, which provides medical cannabis users a means of tracking how different doses and types of cannabis affect a wide variety of symptoms of wellbeing.

Strainprint users rate the symptoms they are experiencing before using cannabis on a scale of 1-10 and then input information about the type of cannabis they are using. Twenty minutes after smoking, they are prompted to report how many puffs they took and to rerate the severity of their symptoms.

Cuttler and WSU colleagues Alexander Spradlin and Ryan McLaughlin used a form of statistical analysis called multilevel modeling to analyze around 12,000 anonymous Strainprint entries for depression, anxiety and stress. The researchers did not receive any of the Strainprint users personally identifying information for their work.

"This is to my knowledge one of the first scientific studies to provide guidance on the strains and quantities of cannabis people should be seeking out for reducing stress, anxiety and depression," Cuttler said. "Currently, medical and recreational cannabis users rely on the advice of bud tenders whose recommendations are based off of anecdotal not scientific evidence."

The study is among several cannabis-related research projects currently underway at WSU, all of which are consistent with federal law and many of which are funded with Washington state cannabis taxes and liquor license fees.

Photo Credit
WSU

Hepatic Steatosis and its Effects on Fibrosis in Patients With Chronic Hepatitis B Virus Infection

Clinical Gastroenterology and Hepatology (CGH)
April 2018 Volume 16, Issue 4, Pages 491–494

Hepatic Steatosis and its Effects on Fibrosis in Patients With Chronic Hepatitis B Virus Infection
Mauricio Garcia-Saenz-de-Sicilia, MD, Andres Duarte-Rojo, MD, MS, DSC

Full-Text
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Obesity rising prevalence has reawakened interest in the potential interactions between chronic viral hepatitis and hepatic steatosis. The metabolic syndrome and its components are independent risk factors associated with fibrosis progression, development of cirrhosis,1 and potentially with lack of fibrosis reversal following antiviral therapy in chronic viral hepatitis.2 However, the particular role of hepatic steatosis, the hallmark of nonalcoholic fatty liver (NAFLD), has been less of a focus of attention in chronic hepatitis B virus (HBV) infection when compared with chronic hepatitis C, in part because of the lack of proper evaluation tools.3

Liver biopsy is considered to be the gold standard for steatosis grading. However, it is invasive, has potential life-threatening complications, can result in sampling errors particularly when fatty infiltration is unevenly distributed (typical biopsy represents 1/50,000 of liver), and interpretation reaches only moderate interobserver or intraobserver agreement.4 Furthermore, repeated monitoring following a therapeutic intervention is hard to justify because of the invasive nature of the procedure and cost, and the fact that noninvasive options are now available. Imaging techniques provide reliable noninvasive alternatives to assess steatosis. Proton density fat fraction from magnetic resonance is perhaps the most accurate method for steatosis quantification; however, it is not a point-of-care method, and has associated high costs and limited availability, making it impractical for routine clinical care at most institutions. All of these limitations are at least partially overcome by the controlled attenuated parameter (CAP) feature from FibroScan (Echosens, Paris, France). This technique, based on the principle that fat affects ultrasound propagation, quantifies variations in M-mode (unidimensional) ultrasound attenuation during liver stiffness measurement (LSM) with vibration-controlled transient elastography, to yield a steatosis estimate. When testing CAP against steatosis grading by liver biopsy, fair to excellent performance has been reported across studies, and discrepancies are likely explained by variations in liver disease etiology, population body composition, and spectrum bias (Table 1). Although CAP interpretation has been limited by uncertainty as to the optimal cutoff values between grades of steatosis, Karlas et al5 have recently brought some certainty to this issue. In a meta-analysis including 2735 cases with histology and CAP analysis, the authors defined cutoff values and variables influencing the output, such as body mass index (BMI), diabetes, and etiology.