Wednesday, February 21, 2018

Similarities found in cancer initiation in kidney, liver, stomach, pancreas

Similarities found in cancer initiation in kidney, liver, stomach, pancreas

Potential for therapies that interfere with early cancer growth

by Jim Dryden
February 21, 2018

Recent research at Washington University School of Medicine in St. Louis demonstrated that mature cells in the stomach sometimes revert back to behaving like rapidly dividing stem cells. Now, the researchers have found that this process may be universal; no matter the organ, when tissue responds to certain types of injury, mature cells seem to get younger and begin dividing rapidly, creating scenarios that can lead to cancer.

Older cells may be dangerous because when they revert to stem cell-like behavior, they carry with them all of the potential cancer-causing mutations that have accumulated during their lifespans. However, because mature cells in the stomach, pancreas, liver and kidney all activate the same genes and go through the same process when they begin to divide again, the findings could mean that cancer initiation is much more similar across organs than scientists have thought. That could support using the same strategies to treat or prevent cancer in a variety of different organs.

The findings about how mature cells begin dividing again — a process the researchers have named paligenosis — are reported Feb. 15 in The EMBO Journal.

“When we began the war on cancer in the 1970s, scientists thought all cancers were similar,” said senior investigator Jason C. Mills, MD, PhD, a professor of medicine in the Division of Gastroenterology. “It turned out cancers are very different from one organ to another and from person to person. But if, as this study suggests, the way that cells become proliferative again is similar across many different organs, we can imagine therapies that interfere with cancer initiation in a more global way, regardless of where that cancer may appear in the body.”

Studying cells from the stomach and pancreas in humans and mice, as well as mouse kidney and liver cells, and cells from more than 800 tumor and precancerous lesions in people, the researchers found when tissue is injured by infections or trauma, mature cells can revert back to a stem-cell state in which they divide repeatedly. And along the way, those cells all activate the same genes to break down the mature cells and help them begin to divide again.

“First, we saw a massive increase in the activity of genes associated with cell degradation,” said first author Spencer G. Willet, PhD, a research associate in the Mills lab. “Then, the cell’s growth pathway senses that degradation and releases nutrients that then activate cell growth pathways and allow the mature cells we studied to proliferate.”

Paligenosis, Mills explained, appears similar to apoptosis — the programmed death of cells as a normal part of an organism’s growth and development — in that it seems to happen the same way in every cell, regardless of its location in the body.

“Nature has provided a way for mature cells to begin dividing again,” Mills said, “and that process is the same in every tissue we’ve studied.”

Willet, Mills and their colleagues believe the discovery that cells in different organs go through the same process to become proliferative could lead to new potential targets for cancer treatment because the factors that initiate tumors could be the same in multiple organs.

“If you were to compare this reprogramming of cells to tearing down a building and putting something new in its place, the slow way to go would be to remove and then replace each brick, one at a time,” Mills said. “What we’re seeing is that nature is smarter than just running the building program in reverse. Instead, there is a wrecking ball program: When an old cell begins to divide again, a program runs to clear things out and then rebuild, and the same program runs in every tissue we’ve analyzed.”

Significant Mortality Benefit Seen With Sustained HCV Virologic Response With DAAs

Significant Mortality Benefit Seen With Sustained HCV Virologic Response With DAAs
Hannah Dellabella
For patients infected with hepatitis C virus (HCV) without advanced liver disease, achieving sustained virologic response with direct-acting antivirals (DAAs) is associated with decreased mortality, according to results published in Hepatology.



Gilead’s pan-genotypic treatment for hepatitis C Vosevi has won the National Institute for Health and Care Excellence’s seal of approval for use on the NHS.

NICE nod for Gilead's pan-genotypic hepatitis C therapy
Gilead’s pan-genotypic treatment for hepatitis C Vosevi has won the National Institute for Health and Care Excellence’s seal of approval for use on the NHS.

Vosevi (sofosbuvir/velpatasvir/voxilaprevir; SOF/VEL/VOX) was cleared by European regulators in July last year as the first and only single tablet regimen for patients with any genotype of chronic hepatitis C virus infection.


NICE Guidance
Evidence-based recommendations on sofosbuvir–velpatasvir–voxilaprevir (Vosevi) for treating chronic hepatitis C in adults.

Opinion - It's criminal what Illinois is doing to Medicaid patients with hepatitis C

It's criminal what Illinois is doing to Medicaid patients with hepatitis C
By: OLUWATOYIN ADEYEMI, ANDREW ARONSOHN, BASMATTEE BOODRAM, DANIEL JOHNSON and MAI TUYET PHO 

Every day, Illinois Medicaid patients with hepatitis C are denied access to a simple cure to a disease that jeopardizes their life because of outdated and unconscionable restrictions on who can get this proven treatment.

Hepatitis C is a viral infection that causes inflammation and scarring of the liver. People who are infected with hepatitis C usually have no or few symptoms for decades until it reaches the end stages of disease, where patients are at risk of liver failure, liver cancer and death. Hepatitis C is a leading cause of liver-related death and need for liver transplantation in the United States. An estimated 150,000 people are affected by hepatitis C in this state alone, according to the Illinois Department of Public Health.

Hepatitis C Virus Clearance in Older Adults

Hepatitis C Virus Clearance in Older Adults
Does HCV clearance with direct-acting antiviral therapy improve outcomes in individuals aged 80 and older--even in the face of severe liver disease and multiple comorbidities?
February 21, 2018

Journal of the American Geriatrics Society
Hepatitis C Virus Clearance in Older Adults
Antonio Massimo Ippolito, MD; Angelo Iacobellis, MD; Michele Milella, MD; Fabio Conti, MD; Vincenzo Messina, MD; Maria Rosa Valvano, PhD; Grazia Anna Niro, MD; Filomena Morisco, MD; Michele Barone, MD; Antonio Patrizio Termite, MD; Giuseppina Brancaccio, MD; Angelo Andriulli, MD

Full Text

Abstract and Introduction
Abstract
Objectives To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy.

Participants Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis).

Measurements
We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs). Participants with cirrhosis were staged according to Child-Pugh-Turcotte class, Model for End-Stage Liver Disease score, and the D'Amico staging system. The type and number of comorbidities at baseline and hepatic and nonhepatic events during follow-up were registered.

Results
Ninety-five percent of participants with cirrhosis and 95% of those with advanced fibrosis attained SVR. The rate was independent of sex, HCV genotype, and treatment schedule. During a mean follow-up of 14 ± 4 months (range 5–23 months), 34 events occurred in 27 participants: 10 hepatocellular carcinomas, 12 hepatic decompensations, 9 nonhepatic events, 3 deaths. Multivariate analysis of risk factors for experiencing adverse events during follow up showed that participants in D'Amico Stages 4 and 5, with a baseline serum albumin level of 3.5 mg/dL or less, and 3 or more comorbidities were the most at risk.

Conclusion
In a real-world setting, DAAs are safe and effective in older adults with HCV-related advanced fibrosis or cirrhosis. Individuals with preserved albumin synthesis and fewer than 3 comorbidities at baseline have the most to gain from long-term DAA therapy.

Severe fibrosis improves in most patients after hepatitis C cure but persists in a quarter


Severe fibrosis improves in most patients after hepatitis C cure but persists in a quarter
Michael Carter
Published: 20 February 2018

Hepatitis C virus (HCV)-related liver fibrosis improves significantly in the majority of patients with pre-treatment advanced fibrosis or cirrhosis after treatment resulting in a sustained virological response, Swedish investigators report in the Journal of Viral Hepatitis.

However, advanced fibrosis persisted in a quarter of patients and worsened in a small subset of patients, showing the need for regular monitoring after successful HCV therapy. Pre-treatment cirrhosis, older age and high body mass index were risk factors for the persistence of advanced cirrhosis.

“Our study shows that the vast majority of our 269 patients with pre-treatment advanced fibrosis or cirrhosis improved their fibrosis during long-term follow-up after SVR,” comment the researchers. “A minority, however, continued to have advanced fibrosis even after more than 5-10 years follow-up. In this subset of patients, a point of no return for advanced liver fibrosis might have been reached, where improvement is not possible.”

Continue reading article: http://www.aidsmap.com/page/3217320/

Tuesday, February 13, 2018

High SVR Rates: Ombitasvir/Paritaprevir-ritonavir plus Ribavirin for 12 wks in HCV Geno 4 patients w-advanced fibrosis

12 WEEKS OMBITASVIR/PARITAPREVIR-RITONAVIR + RIBAVIRIN ACHIEVE HIGH SVR RATES IN HCV-4 PATIENTS WITH ADVANCED FIBROSIS
Elisabetta Degasperi, Alessio Aghemo, Stefania Paolucci, Roberta D’Ambrosio, Marta Borghi, Riccardo Perbellini, Federica Novazzi, Stella De Nicola, Giovanna Lunghi, Fausto Baldanti, Pietro Lampertico

DOI: https://doi.org/10.1016/j.dld.2018.02.003
Publication stage: In Press Accepted Manuscript
Published online: February 12, 2018

Abstract
Background
Ombitasvir/Paritaprevir-ritonavir (OBT/PTV-r) plus Ribavirin (RBV) for 12 weeks in hepatitis C virus (HCV) genotype 4 patients with advanced fibrosis has been only investigated in clinical trials.

Aims
To assess safety and efficacy of OBT/PTV-r + RBV for 12 weeks in real-life HCV-4 patients with advanced fibrosis.

Methods
HCV-4 patients with advanced fibrosis consecutively receiving OBT/PTV-r + RBV for 12 weeks in a single center were enrolled. Fibrosis was staged by transient elastography (TE) (F3: ≥10 kPa; F4 ≥11.9 kPa) or histologically. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks post-treatment.

Results
Between January 2016 and February 2017, 49 HCV-4 patients were included: median age 54 (39-72) years, 84% males, 59% Egyptians, 35% fibrosis F3 and 65% F4, all Child Pugh class A. Median RBV dose was 1,200 (200-1,200) mg/day. At ITT analysis, 47 (96%) patients achieved an SVR (100% at PP analysis). SVR was not affected by ancestry (Egyptian vs. Italian 97% vs. 95%, p = 1.0), fibrosis stage (F3 vs. F4 100% vs. 94%, p = 0.53), presence of baseline resistance associated substitutions (RASs) or RBV reduction.

Conclusions
We report 100% SVR with 12-weeks of OBT/PTV-r + RBV in HCV-4 patients with advanced liver disease, including compensated cirrhotics.


Understanding Spontaneous Hepatitis C Virus Clearance

MD Magazine

Understanding Spontaneous Hepatitis C Virus Clearance
FEBRUARY 13, 2018
Elizabeth Kukielka, PharmD

Among patients in the acute phase of hepatitis C virus (HCV) infection, a portion will spontaneously clear the infection without treatment, and HCV RNA will completely disappear from the serum. Estimates from various studies project that anywhere from 20% to 30% of patients will spontaneously clear HCV, with the biggest factors being sex, ethnicity, immune status, and genetics.

Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with HCV

Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with hepatitis C virus infection: A multi-centre observational study
Melissa Louise Kelly ,Stephen M. Riordan,Rohan Bopage,Andrew R. Lloyd,Jeffrey John Post

Published: February 13, 2018
https://doi.org/10.1371/journal.pone.0192763

View Full Text Online

Abstract
Introduction
Achievement of the 2030 World Health Organisation (WHO) global hepatitis C virus (HCV) elimination targets will be underpinned by scale-up of testing and use of direct-acting antiviral treatments. In Australia, despite publically-funded testing and treatment, less than 15% of patients were treated in the first year of treatment access, highlighting the need for greater efficiency of health service delivery. To this end, non-invasive fibrosis algorithms were examined to reduce reliance on transient elastography (TE) which is currently utilised for the assessment of cirrhosis in most Australian clinical settings.

Materials and methods
This retrospective and prospective study, with derivation and validation cohorts, examined consecutive patients in a tertiary referral centre, a sexual health clinic, and a prison-based hepatitis program. The negative predictive value (NPV) of seven non-invasive algorithms were measured using published and newly derived cut-offs. The number of TEs avoided for each algorithm, or combination of algorithms, was determined.

Results
The 850 patients included 780 (92%) with HCV mono-infection, and 70 (8%) co-infected with HIV or hepatitis B. The mono-infected cohort included 612 men (79%), with an overall prevalence of cirrhosis of 16% (125/780). An ‘APRI’ algorithm cut-off of 1.0 had a 94% NPV (95%CI: 91–96%). Newly derived cut-offs of ‘APRI’ (0.49), ‘FIB-4’ (0.93) and ‘GUCI’ (0.5) algorithms each had NPVs of 99% (95%CI: 97–100%), allowing avoidance of TE in 40% (315/780), 40% (310/780) and 40% (298/749) respectively. When used in combination, NPV was retained and TE avoidance reached 54% (405/749), regardless of gender or co-infection.

Conclusions
Non-invasive algorithms can reliably exclude cirrhosis in many patients, allowing improved efficiency of HCV assessment services in Australia and worldwide.

Monday, February 12, 2018

Liver International Special Issue: Treatment of HCV with direct-acting antiviral agents: 100% cure?

Liver International

Full text articles are open access, see index of review articles below. 

Special Issue:
Proceedings of the 11th Paris Hepatology Conference. International Conference on the Management of Liver Diseases  
Proceedings of the 11th Paris Hepatology Conference. International Conference on the Management of Liver Diseases: 15–16 January 2018, Paris, France. 

Review Article
Treatment of hepatitis C virus infection with direct-acting antiviral agents: 100% cure?
Tarik Asselah, Patrick Marcellin, Raymond F. Schinazi



Full Text
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Abstract
Around 71 million people are chronically infected with HCV worldwide. HCV antiviral drug development has been remarkable. The availability of pangenotypic direct-acting antivirals with excellent efficacy and good tolerability profiles offer a unique opportunity to achieve HCV elimination worldwide. IFN-free DAA combinations can now cure HCV in more than 95% of patients with HCV infection after 8-12 weeks of treatment. Programmes to eliminate HCV must include increased screening (risk-based and universal), linkage to care, as well as increased access to treatment worldwide. In this paper, we will review the available data on recently approved direct-acting antiviral agents, with sustained virological response that reaches almost 100%.

Continue to full text article

Index
REVIEW ARTICLES
Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening (pages 2–6)





Is global elimination of HCV realistic?

Liver International 
Is global elimination of HCV realistic?
Vincenza Calvaruso, Salvatore Petta, Craxì A
DOI: 10.1111/liv.13668

First published: 10 February 2018

Online:

Abstract
The elimination of hepatitis C virus (HCV) has been made possible through the availability of new antiviral drugs which may now be administered to all patients with HCV infection, even those with decompensated cirrhosis. The goal of the World Health Organization (WHO) is to reduce the incidence of chronic hepatitis infection from the current 6-10 million to 0.9 million cases of chronic infections by 2030, and annual deaths from 1.4 million to fewer than 0.5 million. Achieving these targets will require full implementation of epidemiological knowledge of HCV infection, screening and testing practices and strategies to link HCV patients to care. This review will focus on the current state of knowledge in the epidemiology of HCV and what can be done to increase patient awareness and reduce the barriers to treatment. Furthermore, we will discuss the role of HCV clearance on the control of HCV-related outcomes

For Viral Hepatitis Elimination One Size Does Not Fit All

A blog about Global Health. An open space for discussing equitable access to health for everyone, everywhere.

For Viral Hepatitis Elimination One Size Does Not Fit All
Jeffrey Lazarus
12 February 2018

“For elimination, one size does not fit all” was a refrain repeated in a number of different ways throughout the presentations and discussions at the European Association for the Study of the Liver (EASL) Monothematic conference on “Striving towards the elimination of HCV infection” that has just come to a close in Berlin.

Whether in discussions about prevention, interventions in drug users, improving linkage to care, or treatment itself, attendees agreed that there is no golden ticket for hepatitis C elimination. However, there are a number of evidence-based strategies for impact that were presented very effectively by over 30 speakers in the six thematic panel sessions.


Links

Shingles Vaccine Video, New Name for C. diff, Flu B Rising, and More — A Pre-Valentines Day ID Link-o-Rama


HIV and ID Observations

An ongoing dialogue on HIV/AIDS, infectious diseases, all matters medical, and some not so medical.

Paul E. Sax, MD

Highlights
The ACIP issued its official recommendations for herpes zoster (shingles) immunization.
Preferred: the new recombinant zoster vaccine, abbreviated RZV, for people 50 and older. They do not recommend it (yet) for immunocompromised individuals — stay tuned. Does the recommendation include our stable, on-therapy HIV patients, who in increasing numbers are over 50? I say yes.

In this terrible flu season, should we be choosing one type of flu vaccine over another?
In the absence of head-to-head trials, it’s difficult to make an official endorsement. But as this interesting piece notes, there are differences between the available vaccines, differences that may lead to different rates of protection. Credit to Helen Branswell, a local journalist who has done superb reporting on the flu this year.

FDA approves bictegravir/FTC/TAF for initial and switch HIV therapy.
Now come two inevitable questions: 1) When will my patient’s insurance/ADAP/etc. cover it? 2) Who came up with that brand name? Biktarvy, jeepers.

Elsulfavirine, an investigational NNRTI, is also approved for HIV therapy.
OK, ok, so it’s approved in Russia, not here. Here’s a clinical trial comparing it to efavirenz from last year’s CROI.

Mortality Benefit of Successful Anti-HCV DAA Therapy in Patients Without Advanced Liver Disease

NEJM Journal Watch
February 9, 2018
Mortality Benefit of Successful Anti-HCV DAA Therapy in Patients Without Advanced Liver Disease 
Atif Zaman, MD, MPH reviewing Backus LI et al. Hepatology 2018 Jan 29.

Compelling evidence supports elimination of insurers' restrictions on providing direct-acting antiviral therapy to these patients.

Although direct-acting antiviral (DAA) regimens are effective in eradicating hepatitis C virus (HCV), their effect on long-term survival is unclear. Early studies in the interferon-based treatment era noted improved survival among HCV patients with advanced fibrosis, but studies in those with milder fibrosis are lacking.

In an observational cohort analysis, researchers assessed mortality in over 40,000 patients of Veterans Affairs facilities who received all-oral DAA therapy for genotype 1, 2, or 3 HCV infection and did not have advanced liver disease (FIB-4 score ≤3.25 and no evidence of overt compensated or decompensated cirrhosis or hepatocellular carcinoma).

In patients who achieved sustained virologic response (SVR; rate, 97%), the mortality rate (1.2 deaths/100 patient-years) was significantly lower compared with nonresponders (2.8) and some 60,000 untreated patients (3.8). In subgroup analyses by FIB-4 score, responders with a FIB-4 score <1.45 had mortality reductions of 46% and 67% compared with nonresponders and untreated patients, respectively, and those with a FIB-4 score of 1.45 to <3.25 had mortality reductions of 63% and 71% compared with those respective groups. In multivariate analysis, SVR was independently associated with reduced risk for death.

Comment
This is the most direct and compelling evidence showing that DAA treatment in HCV-infected patients who have early fibrosis/nonadvanced liver disease improves overall survival. Strengths of this study include a large sample size, a well-defined population, and the fact that all patients were offered HCV treatment. These results should be enough evidence to lift restrictions imposed by public and private payers who base treatment candidacy on degree of liver fibrosis.

Citation(s):
Backus LI et al. Direct-acting antiviral sustained virologic response: Impact on mortality in patients without advanced liver disease. Hepatology 2018 Jan 29; [e-pub]. (https://doi.org/10.1002/hep.29811)

Medicaid Skimps on Hepatitis C Treatment in Many States

Medicaid Skimps on Hepatitis C Treatment in Many States
by Liz Highleyman
Contributing Writer, MedPage Today
"Hepatitis C: The State of Medicaid Access," issued by the National Viral Hepatitis Roundtable (NVHR) and the Center for Health Law and Policy Innovation (CHLPI) at Harvard Law School, evaluated hepatitis C treatment policies in all 50 states, the District of Columbia, and Puerto Rico.

The report shows that 12 states cover treatment only for people with advanced liver fibrosis, 20 states require at least 6 months of abstinence from drug or alcohol use, and nine require treatment to be prescribed by a liver disease specialist, NVHR executive director Ryan Clary reported at the American Association for the Study of Liver Diseases (AASLD) annual Liver Meeting in October.

Hepatitis C kills more Americans each year than all other infectious diseases combined, yet more than half of U.S. Medicaid programs continue to impose discriminatory and medically unfounded restrictions on hepatitis C cures," Clary told MedPage Today. "

Hepatitis C drugs not being accessed by thousands of Australians with the disease

Hepatitis C drugs not being accessed by thousands of Australians with the disease
By Lexi Metherell

The trend means the Government is at risk of missing its target to eradicate hepatitis C and of spending far more than necessary on the treatments.

Hepatitis Australia said fewer than half as many people were accessing the direct acting antivirals as they were immediately after they were first listed on the Pharmaceutical Benefits Scheme (PBS) in March 2016.

Eight-year survival in chronic HBV patients under long-term entecavir or tenofovir therapy is similar to the general population

The Journal of Hepatology
Eight-year survival in chronic HBV patients under long-term entecavir or tenofovir therapy is similar to the general population
George V. Papatheodoridis, Vana Sypsa, George Dalekos, Cihan Yurdaydin, Florian Van Boemmel, Maria Buti, John Goulis, Jose Luis Calleja, Heng Chi, Spilios Manolakopoulos, Alessandro Loglio, Spyros Siakavellas, Nikolaos Gatselis, Onur Keskın, Maria Lehretz, Savvoula Savvidou, Juan de la Revilla, Bettina E. Hansen, Anastasia Kourikou, Ioannis Vlachogiannakos, Kostantinos Galanis, Ramazan Idilman, Massimo Colombo, Rafael Esteban, Harry L.A. Janssen, Thomas Berg, Pietro Lampertico

Full-Text
Full-text article downloaded and shared by @HenryEChang via Twitter

Highlights
•Chronic hepatitis B patients under entecavir/tenofovir have excellent 8-year survival.
•Mortality of non-cirrhotics seems to be lower than that of the general population.
•Mortality of cirrhotics is similar to that of the general population.
•Hepatocellular carcinoma is the main factor affecting their mortality.

Abstract
Background/Aims
The effects of long-term antiviral therapy on survival have not been adequately assessed in chronic hepatitis B (CHB). In this 10-center, ongoing cohort study, we evaluated the probability of survival and factors affecting survival in Caucasian CHB patients treated with long-term entecavir/tenofovir therapy.

Methods
We included 1951 adult Caucasians with CHB with or without compensated cirrhosis and no hepatocellular carcinoma (HCC) at baseline who received entecavir/tenofovir for ≥12 months (median: 6 years). Kaplan-Meier estimates of cumulative survival over time were obtained. Standardized mortality ratios (SMR) were calculated by comparing death rates with the Human Mortality Databases.

Results
The 1-, 5- and 8-year cumulative probabilities were 99.7%, 95.9% and 94.1% for overall survival, 99.9%, 98.3% and 97.4% for liver related survival and 99.9%, 97.8% and 95.8% for transplantation free liver related survival. Overall mortality was independently associated with older age and HCC development, liver related mortality with HCC development only and transplantation free liver related mortality with HCC development and lower platelets at baseline. Baseline cirrhosis was not independently associated with any type of mortality. Compared to general population, mortality was not significantly different in all CHB patients (SMR: 0.82), while it was lower in patients without HCC regardless of baseline cirrhosis (SMR: 0.58) and higher in patients who developed HCC (SMR: 3.09).

Conclusion
Caucasian patients with CHB and compensated liver disease treated with long-term entecavir/tenofovir therapy have excellent overall and liver related 8-year survival, which is similar to that of the general population. HCC is the main factor affecting their overall mortality and the only factor affecting their liver related mortality.

Lay summary
Caucasian chronic hepatitis B patients with or without compensated cirrhosis treated with long-term entecavir or tenofovir therapy have an excellent overall 8-year survival which is similar to that of the general population.

Hepatocellular carcinoma is the main factor affecting their overall mortality and the only factor affecting liver related mortality in this setting.

https://jumpshare.com/v/2SEtriThRc5FnmTJYk1W

Friday, February 9, 2018

Salk researchers discover how liver responds so quickly to food

Salk researchers discover how liver responds so quickly to food

LA JOLLA--(February 9, 2018) Minutes after you eat a meal, as nutrients rush into your bloodstream, your body makes massive shifts in how it breaks down and stores fats and sugars. Within half an hour, your liver has made a complete switch, going from burning fat for energy to storing as much glucose, or sugar, as possible. But the speed at which this happens has flummoxed scientists--it's too short a time span for the liver's cells to activate genes and produce the RNA blueprints needed to assemble new proteins to guide metabolism.

Now, Salk researchers have uncovered how the liver can have such a speedy response to food; liver cells store up pre-RNA molecules involved in glucose and fat metabolism.

"The switch from fasting to feeding is a very quick switch and our physiology has to adapt to it in the right time frame," says  Satchidananda Panda, a professor in the Salk Institute's Regulatory Biology Laboratory and lead author of the paper, published February 6, 2018 in Cell Metabolism. "Now we know how our body quickly handles that extra rush of sugar."

It was known that a RNA-binding protein called NONO was implicated in regulating daily ("circadian") rhythms in the body. But Panda, along with first author Giorgia Benegiamo, a former graduate student in the Panda lab, and their collaborators wondered whether NONO had a specific role in the liver. They analyzed levels of NONO in response to feeding and fasting in mice. After the animals ate, speckled clumps of NONO suddenly appeared in their liver cells, newly attached to RNA molecules. Within half an hour, the levels of corresponding proteins--those encoded by the NONO-bound RNA--increased.

"After mice eat, it looks as if NONO brings all these RNAs together and processes them so they can be used to make proteins," says Panda.

When mice lacked NONO, it took more than three hours for levels of the same proteins, involved in processing glucose, to increase. During that time lag, blood glucose levels shot up to unhealthy levels. Since blood glucose levels are also heightened in diabetes, the researchers think that the mice without NONO may act as a model to study some forms of the disease.

"Understanding how glucose storage and fat burning are regulated at the molecular level will be important for the development of new therapies against obesity and diabetes," says Benegiamo.

Questions still remain about how exactly NONO is triggered to attach to the pre-RNA molecules after a meal. And Panda is hoping to assemble a more complete list of all the pre-RNAs that NONO binds to--in both the liver and other parts of the body. NONO has been found at high levels in the brain and muscle cells, so the researchers are planning studies to see whether is reacts similarly in those organs to food. 

https://www.salk.edu/news-release/salk-researchers-discover-liver-responds-quickly-food/

JOURNAL
Cell Metabolism
TITLE
The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding
AUTHORS
Giorgia Benegiamo, Ludovic S. Mure, Galina Erikson, Hiep D. Le, Ermanno Moriggi, Steven A. Brown and Satchidananda Panda

HCV infection and liver cirrhosis - Predictors of functional benefit of hepatitis C therapy in a ‘real-life’ cohort

World J Gastroenterol. Feb 21, 2018; 24(7): 852-861
Published online Feb 21, 2018. doi: 10.3748/wjg.v24.i7.852

Retrospective Study
Predictors of functional benefit of hepatitis C therapy in a ‘real-life’ cohort
Niels Steinebrunner, Kerstin Stein, Catharina Sandig, Thomas Bruckner, Wolfgang Stremmel, Anita Pathil

Therapeutic regimens for patients with chronic hepatitis C virus (HCV) infection have substantially improved over the last few years. However real-life data in patients with cirrhosis are still limited, and predictors of functional benefit of direct-acting antivirals are not well defined. We analysed data from patients with HCV infection and liver cirrhosis to evaluate predictors of functional benefit for identifying patients profiting most from antiviral therapy beyond HCV eradication.


Abstract
AIM
To define predictors of functional benefit of direct-acting antivirals (DAAs) in patients with chronic hepatitis C virus (HCV) infection and liver cirrhosis.

METHODS
We analysed a cohort of 199 patients with chronic HCV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated (76%) and decompensated (24%) liver cirrhosis at two tertiary centres in Germany. Patients were included with treatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression analysis.

RESULTS
Viral clearance was achieved in 88% (175/199) of patients. Sustained virological response (SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90% (n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57% (n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87% (n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67% (n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37% (65/179) of patients, no change of MELD score in 41% (74/179) of patients, and an aggravation was observed in 22% (40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the Child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional benefit.

CONCLUSION
Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HCV and with advanced liver disease.

Full Text

Herbal assault: liver toxicity of herbal and dietary supplements

DOI: https://doi.org/10.1016/S2468-1253(18)30011-6

Editorial
Herbal assault: liver toxicity of herbal and dietary supplements
The Lancet Gastroenterology & Hepatology
Published: March 2018

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The worldwide market for herbal and dietary supplements is booming. Even actress Gwyneth Paltrow's lifestyle company Goop has got in on the action, pedalling quirkily named supplements like “Balls in the air” and “The mother load”, targeted at those working at an “intense pace” and expectant mothers, respectively. These supplements promise to revitalise, replenish, and reinvigorate, in part via proprietary blends of herbal extracts. But the health benefits of such products are largely unsubstantiated by scientific data, and they are increasingly associated with harmful side-effects, including liver toxicity.

People on liver transplant waitlist may be no worse off if they have used marijuana

People on liver transplant waitlist may be no worse off if they have used marijuana
Last Updated: 2018-02-08
By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Candidates on the liver transplant (LT) waitlist who have used marijuana have no worse outcomes than their counterparts on the list who have not used it, a single-center study suggests.

"Unlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist. . . We found a high prevalence of historical marijuana use that did not have clear adverse effects on LT waitlist outcomes," lead author Prashant Kotwani of the University of California San Francisco School of Medicine and colleagues write in Transplantation, online January 10.

Continue reading: http://www.chronicliverdisease.org/reuters/article.cfm?article=20180208Other1065659537