Showing posts with label probiotics. Show all posts
Showing posts with label probiotics. Show all posts

Wednesday, August 8, 2018

Hep C and B August Newsletters - Liver Wellness Tips & Generic Direct Acting Antivirals

News updated Aug 8, 2018

August Newsletters
Welcome folks! Read the latest hep B or C news in this months collection of newsletters, published monthly by a small group of kind people devoted to educating us all about liver disease. In addition, access new blog posts with information about major issues surrounding viral hepatitis, as well as tips for maintaining a healthy liver, again, provided by a handful of inspirational writers who blog just for you. Finally read today's news updated as the day progresses, check back for updates. 

Liver Wellness Tips
In honor of World Hepatitis Day, start with:10 TERRIFIC WAYS TO LOVE YOUR LIVER THIS SUMMER, a must read series covering everything from foods containing anti-inflammatory agents to liver-friendly yoga poses! Recently launched by Al D. Rodriguez Liver Foundation.

Today's News
GIS – 08 August 2018: The Ministry of Health and Quality of Life will organise a Conference on Hepatitis C in October 2018. 
The Conference will involve the participation of experts from the United Kingdom, Australia, Egypt and South Africa so as to guide the health care professionals on treatment and elimination of hepatitis C in Mauritius.

Its main objectives will be to educate the local doctors in the new treatments of hepatitis C and to develop a large scale treatment strategy for those who have been diagnosed. The Conference also aims at sourcing affordable tests for hepatitis C and developing a strategy for eliminating hepatitis C in Mauritius by 2025.

New PHE data shows a decrease in deaths from hepatitis C but diagnoses of advanced liver disease and related cancers remain stable.

Researchers have found that a group of viruses that cause severe stomach illness — including the one famous for widespread outbreaks on cruise ships — get transmitted to humans through membrane-cloaked “virus clusters” that exacerbate the spread and severity of disease.

The World and Everything in It: hospice for the homeless.
Death with dignity - WORLD Radio Blog
At age 50, Linda is dying of Hepatitis C that she contracted from needles while she was a heroin addict. Now the disease is causing her liver to fail. She's in a lot …

August 7
Express Scripts Holding Co. said it will drop 48 drugs next year from its closely watched lineup of covered therapies, including Gilead Sciences Inc.’s HIV treatment Atripla and AbbVie Inc.’s hot-selling Mavyret medicine for hepatitis C. Express Scripts said that next year it will cover Symfi, a new HIV combo pill from Mylan NV that the benefit manager said has a 40 percent lower list price than Atripla. Express Scripts will also cover Merck & Co.’s lower-cost hepatitis C medicine Zepatier. In July, Merck said that it was cutting its list price for the drug by 60 percent.

Seeking your help to end the HIV and hepatitis C epidemics and significantly reduce the incidence of STDs in California!
Aug 7, 2018
It is time for California to develop its own Ending the Epidemic plan! The California HIV/AIDS Policy Research Centers, together with viral hepatitis and STD organizations (including Project Inform), have launched a community-driven effort to inform development of a statewide plan to end the HIV and hepatitis C epidemics and significantly reduce the incidence of STDs.

"This is a lifesaver": Patients who accepted infected kidney transplants cured of hepatitis C
Some patients in desperate need of a kidney transplant participated in a bold experiment where they received organs infected with hepatitis C. The gamble paid off.

7, 2018 (HealthDay News) -- Dialysis patients waiting for kidney transplants might safely accept an organ from a donor infected with hepatitis C virus (HCV), …

Publish date: August 7, 2018
By Mark S. Lesney ID Practitioner
Marked differences were seen in the composition of hepatitis C virus hypervariable region 1 (HVR1) when comparing HIV-coinfected (CIP) with HCV-monoinfected (MIP) individuals, according to the results of a genetic analysis of nearly 300 patients.

Study: Alcohol Abuse Increases Risks in Patients with Hepatitis C
Aug 7, 2018
The interaction between alcohol abuse and hepatitis C virus (HCV) can ... The study noted that approximately 20% of patients with alcoholic hepatitis have HCV.

August 6
Healio - Aug 6, 2018
Patients with chronic hepatitis B virus infection died an average of 14 years ... evidence of diabetes (27.2%), a history of alcohol abuse (17.7%), hepatitis C or …

FDA gives drugmakers new ways to prove opioid disorder treatments work
By Steven Ross Johnson | August 6, 2018
Under the new draft guidance, drug developers can look beyond whether medication-assisted treatments reduce patients' opioid use. They can prove efficacy through drops in mortality, emergency department visits, or transmission of hepatitis C. Other measurable outcomes could include improvements in patients' ability to resume work or school, or by the share of patients with moderate to severe forms of opioid use disorder who go into remission while using the experimental MAT therapies.

Entecavir Associated With Later Virological Relapse Than Tenofovir
Aug 6, 2018
A comparison of the nucleos(t)ide analogues tenofovir and entecavir revealed that virological relapse occurred much later for people with a chronic hepatitis B virus (HBV) infection who were e antigen negative after stopping entecavir, according to findings published in The Journal of Infectious Diseases.

Ascletis Pharma Inc. (1672.HK) announced today Ravidasvir is recommended by the World Health Organization (WHO) Guidelines for the Care and Treatment of Persons Diagnosed with Chronic Hepatitis C Virus Infection (July 2018) as a future pan-genotypic direct-acting antivirals agent (DAA). Ascletis received the acceptance letter for Ravidasvir new drug application (NDA) from the China Food and Drug Administration (CFDA) on August 1.

Related: April 12, 2018
The results indicate that the sofosbuvir/ravidasvir combination is comparable to the very best hepatitis C therapies available today, but it is priced affordably and could allow an alternative option in countries excluded from pharmaceutical company access programmes,” said Dr Bernard Pécoul, Executive Director, DNDi.

Integrating Treatments for Opioid Use Disorder and Infectious Diseases
Aug 6, 2018
All healthcare providers have a role in combating the opioid use disorder (OUD) epidemic and its infectious disease (ID) consequences, according to an article published in Annals of Internal Medicine

Britain plans for opt-out organ donation scheme to save lives
LONDON Britain plans to increase the number of organ donors by changing the rules of consent and presuming that people have agreed to transplants unless they have specifically opted out.

Read The Latest News
For a quick review of news, stroll over to the good people at HepCBC to read the latest issue of the Weekly Bull.

Journal Updates
Managing Neurologic Complications of Chronic HCV Infection
Chronic hepatitis C virus (HCV) infection can cause a multitude of extrahepatic complications, including neurologic manifestations. These complications can lead to substantial neuropsychiatric deficits, such as fatigue, cognitive impairment, restless legs syndrome, Parkinson's disease, and peripheral neuropathy. In addition to detecting and managing these neurologic complications, pharmacists in community settings can promote HCV screening, improve medication access and adherence, and recommend preventive strategies patients can use to avoid transmission of this widespread infection.

International Journal of Infectious Diseases
2 August 2018
Download: High Efficacy of Generic and Brand Direct Acting Antivirals in Treatment of Chronic Hepatitis C.

August Updates On This Blog
New Articles Under: Other Conditions Related To HCV 
- Hepatitis C-Diabetes associated w-advanced fibrosis and progression in HCV non-genotype 3 patients
- Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings 

New Articles Under: HCC during and after direct-acting antiviral therapy in patients with hepatitis C
- Direct Antiviral Therapy of Hep C May Not Boost Hepatocellular Carcinoma Risk

New Articles Under: HCV-Statins 
- Statins: old drugs as new therapy for liver diseases?

New Articles Under: HCV-Education
- Long–term effect of liver fibrosis after SVR in patients with HCV 

July News
Spotlight on mortality trends in liver disease
One study looked at 10-year U.S. mortality trends related to chronic liver diseases, while another assessed mortality from cirrhosis and liver cancer in the U.S. from 1999 to 2016.
“It is clear that the introduction of oral, highly efficacious and well-tolerated antiviral agents has improved outcomes in patients with viral hepatitis,” they wrote. “However, future challenges with [alcoholic liver disease] and NAFLD will pose a different set of problems and will necessitate a multidisciplinary approach with a dedicated focus on minorities.”

Disparities in Access to Direct Acting Antiviral Regimens for Hepatitis C Virus (HCV): The Impact of Race and Insurance Status 
Despite highly effective and well-tolerated regimens for treating hepatitis C virus (HCV), patients face barriers in accessing treatment. In addition to suboptimal HCV screening programs and lack of effective linkage-to-care, other barriers include strict requirements from some payers to cover treatment. This study reports insurance status and Hispanic ethnicity as predictors of not receiving treatment. 

“Coordinated care has the potential to improve access to treatment for individuals with hepatitis C who are naive to direct-acting antivirals; however, having Medicaid could hamper access, according to a recent study published in PLoSONE.”

People born between 1945 and 1975 are the group of people who are most likely to suffer from chronic hepatitis C in Canada, and Greg Powell is a Canadian who is part of those people. Greg contacted the hepatitis C in the 1980s, but the diagnosis came ten years later. Greg was already suffering from hemophilia B which is a hereditary bleeding disorder, so he needed to benefit from a series of blood transfusions.

Wayne Kuznar, for MDLinx
Nearly three fourths of patients who present with acetaminophen-induced acute liver injury (ALI) or failure (ALF) are women, according to findings from a North American registry. Women with acetaminophen overdose leading to ALI/ALF were more likely than men to present with high-grade hepatic encephalopathy and have critical care needs, and more likely to have psychiatric disease and to co-ingest sedating agents with acetaminophen.

HCV Advocate
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education.
Newsletter Highlights
August Issue
HealthWise – Hepatitis C and Sugar by Lucinda Porter, RN – Lucinda discusses effects of sugar on the body, hepatitis C, and fatty liver. 
(1) State Prisons Fail to Offer Cure to 144,000 Inmates with Deadly Hepatitis C
(2) What’s Being Done to Stop the Spread of Hepatitis A in the Midwest? 
SnapShots by Alan Franciscus: 
-Efficacy of sofosbuvir and velpatasvir, with and without ribavirin, in patients with HCV genotype 3 infection and cirrhosis
-Incidence and spontaneous clearance of hepatitis C (HCV) in PWID at the Stockholm needle exchange – importance for HCV elimination
-Microenvironment eradication of hepatitis C: A novel treatment paradigm
-All‐oral direct‐acting antiviral therapy against hepatitis C virus (HCV) in human immunodeficiency virus/HCV–coinfected subjects in real‐world practice: Madrid coinfection registry findings
Abstract:  Use of ribavirin in viruses other than hepatitis C. A review of the evidence,
Genotype from Punjab, India: Expanding classification of hepatitis C virus into 8 genotypes

The National Viral Hepatitis Roundtable
The National Viral Hepatitis Roundtable (NVHR) is national coalition working together to eliminate hepatitis B and C in the United States.
Save the date: Webinar August 8th on Engaging Drug Users to Fight Stigma and Access HCV
On Wednesday, August 8, 2018
National Viral Hepatitis Roundtable, the Urban Survivor's Union, the People’s Harm Reduction Alliance, and the Atlanta Harm Reduction Coalition will be hosting a webinar; Engaging Drug Users to Fight Stigma and Access HCV. These groups are working collaboratively on the "More than Tested, Empowered" project which addresses barriers to hepatitis C care faced by individuals who use drugs. The webinar will include findings from surveys delivered to healthcare providers and suggested educational messaging to improve access to hepatitis C care. In addition, each partner will discuss their methods for integrating participants into their work. After the presentation, there will be time for questions and discussion. 

Need To Talk To Someone?
If you need information and resources about finding financial help to pay for low cost testing, or finding a free or low cost clinic, or financial help with payment for treatments, please call us. We know how to find doctors and support groups. We know how to help you find resources where you live. We have experienced hepatitis C ourselves or have supported patients living with hep C. We are peer counselors. Help-4-Hep is a trusted source of information, support and referrals—all free of charge to you.
Learn more about Help-4-Hep
View all NVHR newsletters

The New York City Hepatitis C Task Force
The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community.
July 27, 2018 - NY Governor Announces First-In-Nation Task Force To Eliminate Hepatitis C 
View: Hep Free NYC Newsletters
Review all news updates.

HCV Action
HCV Action brings together hepatitis C health professionals from across the patient pathway with the pharmaceutical industry and patient representatives to share expertise and good practice.
Aug 3, 2018
HCV Action e-update: July 2018

World Hepatitis Alliance
We run global campaigns, convene high-level policy events, build capacity and pioneer global movements, ensuring people living with viral hepatitis guide every aspect of our work.
View Recent Newsletters 
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.

GI & Hepatology News
Over 17,000 gastroenterologists and hepatologists rely on GI & Hepatology News every month to cover the world of medicine with breaking news, on-site medical meeting coverage, and expert perspectives both in print and online. 
Hot topics
Lin Chang, MD
Publish date: August 1, 2018
Hepatitis B virus reactivation, endoscopic bariatric therapy, and more.
View all updates here....

Hep-Your Guide to Hepatitis
Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and are the go-to source for educational and social support for people living with hepatitis.
View - all issues
Check out the talented people who blog at Hep.

Hepatitis Victoria
Hepatitis Victoria is the peak not-for-profit community organisation working across the state for people affected by or at risk of viral hepatitis.
Check out this new Liver Health app: 'Top app for liver health is LiverWELL' says influential U.S. health blogger.
View the Latest Newsletter, or relax and listen to a short podcasts interviewing health experts and practioners on topics related to viral hepatitis - come have a listen!

British Liver Trust
The British Liver Trust is the leading UK liver disease charity for adults – we provide information and support; increase awareness of how liver disease can be prevented and promote early diagnosis; fund and champion research and campaign for better services. 
News: Almost half of people with Hepatitis C in the UK are unaware
On Saturday 28th July, World Hepatitis Day, the British Liver Trust unites with organisations, health professionals and supporters across the world to push for urgent …
View Recent Newsletters, here.

National Institutes of Health
A monthly newsletter from the National Institutes of Health, part of the U.S. Department of Health and Human Services
August Newsletter
Loneliness Affects All Ages
Health Capsule - Preventing Shingles

Harvard Health
Ask the doctors

Inspirational Bloggers
Karen Hoyt is devoted to offering support and accurate information to people coping with the effects of hepatitis C.
Latest blog entry: Tired with Liver Disease: There’s a Nap for That

Lucinda K. Porter
Lucinda Porter is a nurse, speaker, advocate and patient devoted to increasing awareness about hepatitis C.
Latest blog entry: Wading Through Medicare

Hep is an award-winning print and online brand for people living with and affected by viral hepatitis.
Latest blog entry: A World Without Hepatitis Advocates
Healing Your Fatty Liver

Hepatitis NSW 
We provide information, support, referral and advocacy for people affected by viral hepatitis in NSW. We also provide workforce development and education services both to prevent the transmission of viral hepatitis and to improve services for those affected by it.
Latest blog entry: Govt intervenes to keep hep C elimination on track

Life Beyond Hepatitis C
Life Beyond Hep C is where faith, medical resources and patient support meet, helping Hep C patients and their families navigate through the entire journey of Hep C.
Latest blog entry: Newly Diagnosed with Hepatitis C, What Do I Do Next?

A comprehensive website for HIV and hepatitis C information
Latest blog entry: Eliminating hepatitis C among Canadian immigrants and newcomers: how
CanHepC’s blueprint will impact my work.

Canadian Liver Foundation 
We strive to improve prevention and the quality of life of those living with liver disease by advocating for better screening, access to treatment, and patient care.
Latest blog entry: Life After Hepatitis C: A New Chapter

Pacific Hepatitis C Network
The Pacific Hepatitis C Network works with people living with hepatitis C, with community based organizations and with government to address concerns about hepatitis C prevention, care, treatment access and support.
Latest blog entry: A few words from PHCN’s President on World Hepatitis Day 2018

The Hepatitis B Foundation is a national nonprofit organization dedicated to finding a cure and improving the quality of life for those affected by hepatitis B worldwide.
Latest blog entry: - Newly Diagnosed with Hepatitis B? How Did I Get this? Learning the HBV Transmission Basics.
At we empower patients and caregivers to take control of Hepatitis C by providing a platform to learn, educate, and connect with peers and healthcare professionals.
Latest blog entry: Should I Be Screened for Liver Cancer?

HIV and ID Observations  
An ongoing dialogue on HIV/AIDS, infectious diseases, all matters medical, and some not so medical.
Latest blog entry: Really Rapid Review — International AIDS Conference 2018, Amsterdam

From The Archives 
SVR leads to significant improvement of liver fibrosis.
Research has shown people who are cured of their HCV infection experience a reduction in the rate of liver fibrosis progression, as well as improved liver function. For instance published in Antiviral Therapy/Aug 2017, evidence suggest HCV eradication or response to treatment (cure) is associated with regression of fibrosis and recovery of liver function which can be detected as early as end of treatment, check out the article: SVR in HCV leads to an early and significant improvement of liver fibrosis. In this more recent study presented at the 2018 Liver Congress researchers reported; Sustained & continued improvement in hepatic fibrosis beyond the first-year (& in the subsequent 3 years) following HCV treatment. Finally, published in Alimentary Pharmacology & Therapeutics/May 29, 2018 researchers reported: anti-viral therapy reduced liver fibrosis and steatosis in patients with chronic hepatitis C virus.

Healthy You
Simple swaps to eat less salt
The top 10 sources of sodium in the American diet include processed foods that contain several high-sodium ingredients, such as cheese and cured meats

Diet Heavy in Meat Boosts NAFLD Risk
Large study shows 40% increased risk in overweight, elderly patients

Probiotic use is a link between brain fogginess, severe bloating
Medical College of Georgia at Augusta University
While probiotics can be beneficial in some scenarios, like helping a patient restore his gut bacteria after taking antibiotics, the investigators advised caution against its excessive and indiscriminate use.

"Probiotics should be treated as a drug, not as a food supplement," Rao says, noting that many individuals self-prescribe the live bacteria, which are considered good for digestion and overall health.... 

August 6, 20184:58 AM ET
Heard on Morning Edition 
New research suggests the mix of microbes in our guts can either help — or hinder — weight-loss efforts.

Watch: Liver Function Tests
The ACG now suggests that "liver function tests" be referred to as "liver chemistries" or "liver tests.
The reasoning behind the name change is "Liver Function Tests" are not true measures of hepatic function. Listen to this 2017 short podcast hosted by Arefa Cassoobhoy, MD, MPH to learn more about test guidelines.

Recently, Lab Tests Online AU uploaded the following video explaining commonly used tests to check liver function such as; alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and bilirubin tests. The ALT and AST tests measure enzymes that your liver releases in response to damage or disease.

Thanks for stopping by!

Sunday, December 31, 2017

Problems and potential with probiotics

ACP InternistConference Coverage | January 2018
Problems and potential with probiotics
By Mollie Durkin
Probiotics are becoming more prevalent in both consumer and health care settings, but the excitement is tempered by problems, including how to define what is and what isn't one.

Researchers also face regulatory challenges to studying probiotics, Dr. Hibberd said. The FDA's current approach to probiotics is that, when they are intended to prevent, mitigate, or cure any disease, they are considered a drug or biologic, subject to approval and regulation.

On the other hand, if the purported health benefit is structure or function (e.g., digestive health), the products do not need regulatory approval. “Consequently, this is why we hear mostly about what's called structure/function claims that really are unhelpful in terms of thinking about when and which [probiotics] to use,” she said.

Another issue is that some probiotic products in grocery stores may list unheard-of organisms. “Some of the ‘strains' in these products are actually not real bacteria at all; they are commercial names,” Dr. Hibberd said. “So that also makes things a lot more complicated.”

Sunday, February 26, 2017

Probiotics for people with hepatic encephalopathy

Cochrane Database Of Systematic Reviews

Probiotics for people with hepatic encephalopathy
Rohan Dalal, Richard G McGee, Stephen M Riordan, Angela C Webster
First published: 23 February 2017 Editorial Group: Cochrane Hepato-Biliary Group
DOI: 10.1002/14651858.CD008716.pub3

Plain language summary

Why the review is important
Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient’s quality of life and daily functioning and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts may confer a health benefit on the host. We searched and summarised randomised trials about the benefits and harms of any probiotic in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy.

Main findings
The evidence is current to June 2016. Of the 21 included trials including 1420 participants, 14 trials compared a probiotic with placebo or no treatment and seven trials compared a probiotic with lactulose. The treatment duration of the trials ranged from 10 days to 180 days.

Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but may lead to little or no difference in mortality. Probiotics may slightly improve quality of life when compared with no intervention; however, this conclusion is based on three trials with low-quality evidence. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence was very low. There were no reports of septicaemia attributable to probiotic in any trial. There was no evidence of more adverse events with probiotics when compared to placebo or lactulose.

Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source.

Limitations of the review
Many of the included trials suffered from a high risk of systematic error (‘bias’) and a high risk of random error (‘play of chance’). Accordingly, we consider the evidence to be of low quality.

Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but probiotics may lead to little or no difference in mortality. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence was very low. High-quality randomised clinical trials with standardised outcome collection and data reporting are needed to further clarify the true efficacy of probiotics.

*Purchase required to access this article

Wednesday, February 1, 2017

2017 February Hepatitis Newsletters - AbbVie's Glecaprevir/Pibrentasvir

2017 February Hepatitis Newsletters
Hello everyone, welcome to this months index of newsletters, with links pointing you to the latest headlines, journal articles, and recent posts by your favorite HCV bloggers.

Quick Links
Check out an article all about Probiotics, over at MD Whistleblower, written by Michael Kirsch, M.D. Or sit back and watch Karen Hoyt from I Help C discuss Hepatic Encephalopathy. Jump over to HCV Advocate and read; Is It Really ‘FDA Approved? updated recently by the FDA. Finally, don't forget to mark your calendar for an upcoming Treatment Access Webinar; Strategies to address reimbursement restrictions for Hep C treatment: Lessons from Australia, presented by CATIE, CanHep C and The Kirby Institute.

In The News - AbbVie's Glecaprevir/Pibrentasvir (G/P)
In December AbbVie submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration for Glecaprevir/Pibrentasvir (G/P), last month AbbVie's G/P regimen was granted accelerated assessment by the EMA, on Feb 1, AbbVie submitted a New Drug Submission (NDS), and received priority review from Health Canada. Today, Feb 2, Glecaprevir/Pibrentasvir G/P received accelerated review; U.S. FDA Grants Priority Review to AbbVie’s Investigational HCV Regimen of Glecaprevir/Pibrentasvir (G/P) for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT1-6).

AbbVie's Glecaprevir/Pibrentasvir (G/P) is an investigational regimen for the treatment of all hepatitis C genotypes (GT1-6).  According to AbbVie's press release Glecaprevir/Pibrentasvir may provide a shorter, eight week treatment option for hepatitis C patients without cirrhosis and who are new to treatment. AbbVie is also studying G/P in patients with specific treatment challenges, such as genotype 3, patients who were not cured with previous DAA treatment and those with Chronic kidney disease (CKD), including patients on dialysis. The following journal updates discuss the above mentioned patient population; Glecaprevir/Pibrentasvir (G/P) in HCV genotype 1-infected patients who failed previous DAA containing therapy (Hepatology), patients with chronic genotype 3 HCV infection (Medscape) and patients with chronic kidney disease (MD Magazine). AbbVie press release: SVR12 Rates in Genotype 1 Japanese Patients.

HIV and Hepatitis - Glecaprevir/Pibrentasvir  
The Liver Meeting (AASLD 2016)
Studies presented at the Liver Meeting showed that glecaprevir/pibrentasvir taken for 8 or 12 weeks cured 98%-99% of non-cirrhotic treatment-naive and treatment-experienced people with HCV genotypes 1, 2, 4, 5, and 6 in the Phase 3 ENDURANCE trials. In the Phase 2 SURVEYOR-2 study the combo taken for 12 or 16 weeks cured at least 96% of treatment-naive and treatment-experienced people with HCV genotype 3 and cirrhosis. Glecaprevir/pibrentasvir also cured almost all hepatitis C patients with advanced kidney disease in the EXPEDITION-4 trial.

In The News
BLACK HISTORY MONTH: Pioneer turns sights to hepatitis C
Researched by SANDRA SEALEY
02 February 2017
WAYNE LAMAR GREAVES, originally from Church Hill, St Lucy, was always interested in science and why things worked the way they did. As a student at Harrison College he was fond of catching frogs and dissecting them in biology class.

Trump immigration ban upends international work on disease     
February 1, 2017
The bodies of patients infected with both hepatitis B virus (HBV) and hepatitis C virus (HCV) respond to the diseases differently than those infected with only one of the two. A recent study conducted by Fei Chen, PhD, of the University of South China, and colleagues compared the virological and immunological features of patients with dual and single infections and found significant differences.

Risk of liver cancer low in patients with cirrhosis, study finds
February 1, 2017
The results of a study by researchers at The University of Nottingham suggest that the risk of liver cancer in patients with cirrhosis may be much lower than previously thought.
The study found that only 1.2 per cent of patients with alcoholic cirrhosis and 1.1 per cent of patients with cirrhosis of unknown cause will develop HCC within a decade. The highest 10-year incidence of HCC was among those with cirrhosis due to chronic viral hepatitis (four per cent).

Of Interest
January 31, 2017
Regulus Announces Continuation of RG-101 Clinical Hold - FDA requests longer-term follow-up data from ongoing studies

Report Cites Liver Failure Risk With New Hepatitis C Drugs
January 26, 2017
Researchers find 524 cases of liver failure in people taking some of the drugs. Experts say the findings are inconclusive, the fatality rate is low, and the report should not influence prescribing.

HCV Advocate
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education

February Newsletter

HealthWise – Connecting the Heart and the Liver – Lucinda K. Porter, RN. Lucinda talks about the health of these important organs. The number of people who die from heart disease annually is staggering.

Under The Umbrella – Harm Reduction and Hepatitis C – Matthew Zielske. Matthew discusses aspects of harm reduction geared towards hepatitis C transmission. He is also working on many new Harm Reduction fact sheets for the HCV Advocate Website. Three new fact sheets are listed below.

SnapShots – Alan Franciscus. In this month’s column I cover three studies—deaths caused by hepatitis C among Mexican Americans, non-Hispanics Whites and non-Hispanic Blacks, the changes in the most common indications for liver transplants and transplant waitlists and finally, a study that looked at the best practice to screen people at risk (including Baby Boomers) for hepatitis C in an effort to increase screening. All three studies are very illuminating.

Drug Pipeline — no changes in this month’s Drug Pipeline

Coming Mid-February: Hepatitis C Drug Pipeline and Conference Coverage – The new feature will be populated by our conference coverage from 2016, from EASL and AASLD, and future conferences as well as current and future articles about drugs in development.

The Hepatitis C Mentor and Support Group (HCMSG)
The Hepatitis C Mentor and Support Group (HCMSG) was founded to address the lack of awareness, support, and services for people living with Hepatitis C (including patients co-infected with other conditions such as HIV/AIDS and Hepatitis B), and patients in need of or living with liver transplants. To address these needs, we provide resources and services to foster the development and operation of successful support groups for Hepatitis C and co-infected patients. These services are provided to prospective and current support group facilitators FREE OF CHARGE. In the future, we will also provide one-on-one mentoring services to Hepatitis C and liver transplant patients.

New 2017 Patient Newsletter
All Newsletters
Visit - HCMSG Blog

The New York City Hepatitis C Task Force
The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community.

January 2017 Hep Free NYC Newsletter
All Newsletters - Archives

HCV Action
HCV Action brings together hepatitis C health professionals from across the patient pathway with the pharmaceutical industry and patient representatives to share expertise and good practice.

HCV Action e-update: January 2017
31 Jan 2017

Pacific Hepatitis C Network (PHCN)
Welcome to the Pacific Hepatitis C Network (PHCN) newsletter. This is where we review all of the major current issues and events around hepatitis C and hep C treatments. It is an email that includes links to our recent blog posts—including links to blog posts about Public Health Agency of Canada funding.

Subscribers to our mailing list will receive a bi-weekly newsletter, via email, highlighting all of the blog posts written by PHCN and published for PHCN's Newsletter and Hep C TIP News. Current subscribers of either blog will begin receiving this one bi-weekly newsletter. Open them for information and links to blog posts that interest you.
Sign up here.

What’s Been Recently Published About Hep C

Save The Date - February 6th at 12-1:30pm
Treatment Access Webinar
Click here for more information and to register for the webinar on February 6th at 12-1:30pm PST.

In collaboration with CanHepC, CTAC, and the Kirby Institute in Australia, CATIE is organizing a webinar looking at strategies to address Canada’s current restrictive and inconsistent approach to direct-acting antiviral (DAA) access and lessons we can learn from the Australian model.

Register now and learn from experts such as Alison Marshall and Greg Dore of Australia’s The Kirby Institute; and Helen Tyrell of Hepatitis Australia. Engage in discussion with Adam Cook of CTAC and Action Hepatitis Canada; Community Organizer Zoe Dodd.

GI & Hepatology News
Over 17,000 gastroenterologists and hepatologists rely on GI & Hepatology News every month to cover the world of medicine with breaking news, on-site medical meeting coverage, and expert perspectives both in print and online. The official newspaper of the AGA Institute was launched in partnership with IMNG in January 2007.

Newsletter - February 2017
Review all newsletters - Past Issues

Weekly Bull
For over a decade HepCBC a Canadian non-profit organization has published an incredible monthly newsletter offering awareness, personal stories and basic information about HCV.

Recently the highly successful newsletter has been retired, however without fail a new publication "The Weekly.Bull" will continue to serve us well, here is the latest issue.

Latest Issue: Weekly Bull

British Liver Trust
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If Hepatitis B Is Sexually Transmitted, How Come My Partner Isn’t Infected?
February 1, 2017
By Christine Kukka
I thought hepatitis B was sexually transmitted? I just tested positive, but my partner tested negative, we’ve been together for years, what gives?
This question is a common one. Hepatitis B is indeed easily transmitted sexually, so why do some people — who were not vaccinated — never get hepatitis B from their sexual partners?

January 11, 2017
It’s Flu Season: When You Have Hepatitis B, Too Much Tylenol Can Damage Your Liver
Cold season is here and sometimes getting a flu shot and consistently washing our hands aren’t enough to keep colds at bay. If you do get sick, make sure the over-the-counter medication you take doesn’t damage your liver while it’s relieving your aches and pains.

I Help C
Your Best Friends Guide To Hepatitis C and Cirrhosis
Karen Hoyt
This site is dedicated to helping those who have Hepatitis C or Cirrhosis. I'm not a doctor, but I'll be your Best Friend.

Hepatic Encephalopathy
Video - Help for Hepatic Encephalopathy
Help for Hepatic Encephalopathy is usually medications like Xifaxan or Lactulose. I made some Youtube Video blogs for you about how diet and exercise can help.
View latest video, view all videos here

At we empower patients and caregivers to take control of Hepatitis C by providing a platform to learn, educate, and connect with peers and healthcare professionals.

Victim or Victor
By Daryl Luster - January 31, 2017
Over the years I have spoken to some people in the community who feel victimized because of their diagnosis of hepatitis C. It doesn’t sound the same with everyone and this is...

Practicing Self-Care on a Budget
By Editorial Team - January 30, 2017
We’ve previously defined and described the importance of self-care, and have given examples of how you can practice it in your daily life. While some tasks are easier than others, it isn’t...

Hepatitis C Researchers Eye Pre-Exposure Prophylaxis
By Jenelle Marie Davis - January 29, 2017
What Is It? Pre-exposure prophylaxis (often written out in the abbreviated word “PrEP”) is a medical treatment decision in which antiviral hepatitis C drugs are given to an individual who has definitely...

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MD Whistleblower
Michael Kirsch, M.D.
I am a full time practicing physician and writer. I write about the joys and challenges of medical practice including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When I'm not writing, I'm performing colonoscopies.

Probiotics Promote Digestive Health - Is There a Germ of Truth
January 29, 2017
Several times each week, I am asked about the value of probiotics. Many of my patients are already on them, based on a personal recommendation or an advertisement. As a gastroenterologist, I routinely treat patients with all varieties of diarrhea conditions, such as irritable bowel disease, ulcerative colitis, Crohn’s disease, lactose intolerance, celiac disease and the highly feared gluten sensitivity. Many of them arrive in the office with a probiotic in hand waiting for me to pass judgment. These patients look to me as a Digestive Supreme Court Justice as they sit on the edge of their chairs waiting for my ruling in the case of Probiotics vs Disease.

Hep BOOMers
Hep BOOMers is dedicated to the millions of Baby Boomers who contracted hepatitis C and to the boom in medical research that could cure them.

Phony Harvoni spurs new packaging in Japan
Posted on January 20, 2017 by Elizabeth
Gilead Sciences in Japan has decided to change the packaging of Sovaldi and Harvoni in that country. The direct-acting antivirals will now be sold in blister packs rather than bottles, which would make it harder for counterfeiters to scam patients who have hepatitis C.

Creating a World Free of Hepatitis C
By Lucinda K. Porter
Welcome to my website and blog. My name is Lucinda Porter and I am a nurse committed to raising awareness about hepatitis C. I believe that we can create a world free of hepatitis C. We do this together, one step at a time.

Important Information That Everyone Needs
by Lucinda Porter on February 2, 2017
Lately we hear a lot about fake news and alternative facts. Leading news organizations bypass reporting the news and publish opinion pieces about what is truth and what is a lie. It can all get quite fuzzy.

Take with a Grain of Salt
on January 26, 2017
Last year, I had a lot of medical problems. Nothing life-threatening, all of them treatable. I don’t want to write a litany of woes, but I will discuss one of my issues in this post – Meniere’s Disease. If you’ve never heard of it, and want to know more, look it up. Vertigo, loss of balance, and hearing loss are the common symptoms. Tinnitus is a constant companion.
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HEP - Blog Updates
Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and Hep Magazine are the go-to source for educational and social support for people living with hepatitis.

Hepatitis C Treatment in the USA
By Greg Jefferys
Greg Jefferys shares his opinion and concerns about the problems some people in the US have accessing treatment.

Hepatitis C in the News: Reading Between the Lines
By Lucinda K. Porter, RN
Is the news you are reading about hepatitis accurate? Sometimes you need to read between the lines.

What a New Year Can Mean to You
By Karen Hoyt
The new year can be a time of new beginnings , especially for people with health issues such as liver disease.

Misleading Hep-C Article
By Carleen McGuffey
I wonder how many people considering treatment for hepatitis c will read this and decide its too risky?

Conquering Hep C Patients; Where Are They Now?
By Connie M. Welch
A look at one person with cirrhosis who was cured of hepatitis C, and how she is doing years later.

Healthy You
‘Geriatric tsunami’ carries elderly obesity
From the February ACP Internist, copyright © 2017 by the American College of Physicians
By Mollie Durkin
By 2030, more than 20% of the U.S. population is expected to be over the age of 65, according to the U.S. Census Bureau. As John A. Batsis, MD, FACP, sees it, “We're in the midst of a geriatric tsunami.” And the wave may carry with it patients with obesity and poor eating habits.

Happy Valentines Day!

Monday, December 1, 2014

Probiotics for Cirrhosis?

bacteria in the intestinal microbiota
Probiotics for Cirrhosis?

A probiotic solution significantly reduced the risk of hospitalization for hepatic encephalopathy and markers of liver disease severity in patients with cirrhosis, researchers report in the December issue of Gastroenterology.

Hepatic encephalopathy develops in 50%–70% of patients with cirrhosis; fewer than 50% of these patients survive for 1 year. Rifaximin and lactulose are commonly used to try to prevent hepatic encephalopathy, but there are concerns about their cost and side effects. Many patients develop breakthrough episodes of hepatic encephalopathy despite prophylactic treatment with these agents.

Hepatic encephalopathy has been linked to alterations in the intestinal microbiota, increased production of gut-derived toxins such as ammonia and indoles, and endotoxemia, which lead to systemic and cerebral inflammation.

Probiotics can alter numbers, composition, and functions of bacteria in the intestinal microbiome and reduce levels of ammonia. Radha K. Dhiman et al therefore performed a randomized controlled trial to determine whether probiotics could prevent recurrence of hepatic encephalopathy and improve liver function in patients with cirrhosis.

At a hospital in India, 130 patients with cirrhosis who had recovered from an episode of hepatic encephalopathy in the previous month were randomly assigned to groups given a probiotic preparation (VSL#3, 9 × 1011 colony-forming units per sachet) or placebo (controls) each day for 6 months.

VSL#3 contains 4 Lactobacillus species (L paracasei, L plantarum, L acidophilus, and L delbrueckii subspecies bulgaricus), 3 Bifidobacterium species (B longum, B infantis, and B breve), and Streptococcus thermophiles.

After the 6 month period ended, only 34.8% of subjects in the probiotic group had developed hepatic encephalopathy, compared with 51.6% in the control group, although this difference was not significant.

However, significantly fewer patients in the probiotic group were hospitalized for hepatic encephalopathy (19.7% vs 42.2% of controls) or for complications of cirrhosis (24.2% vs 45.3% of controls). The mean time to hospitalization for any reason was 136 days in the probiotic group and 109 days in the placebo group.

Child–Turcotte–Pugh and model for end-stage liver disease scores (indicators of liver disease) improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group.

There were no adverse events related to VSL#3. Thirty patients died during the study: 14 in the probiotic group and 16 in the placebo group.

Fasting blood ammonia levels decreased among patients in the probiotic group and increased among patients in the placebo group, although these were not statistically significant. Plasma indole levels decreased significantly only in the probiotic group.

Although plasma levels of the inflammatory cytokines tumor necrosis factor (TNF), IL1B, and IL6 decreased significantly in the probiotic group, there was no significant change in the placebo group. Plasma levels of renin and brain-type natriuretic peptide (BNP) also decreased significantly in the probiotic group but not the placebo group.

How could a probiotic reduce markers of liver disease, complications of cirrhosis, and even risk of hospitalization? Dhiman et al explain that bacterial overgrowth and impaired intestinal barrier integrity in patients with cirrhosis leads to endotoxemia. Endotoxemia initiates liver damage through its interaction with Toll-like receptors, which activate immune and inflammatory responses. Systemic inflammation and infection exacerbate the symptoms of hepatic encephalopathy in patients with all grades of cirrhosis. Production of inflammatory cytokines such as TNFa, IL1b, and IL6 can the increase the cerebral effects of ammonia.

Probiotics have been shown to improve the integrity of the gut epithelium, promote innate immunity in the gut, and reduce local and systemic inflammation.

Dhiman et al propose that in the patients receiving the probiotics, significant reductions in renin, aldosterone, and BNP probably resulted from improved cardiac function, systemic hemodynamics, and increased renal blood flow following reductions in inflammatory cytokines. However, further studies of hemodynamic parameters are needed to confirm model.

The authors conclude that probiotic use significantly reduces the risk of hospitalization, related primarily to the development of fewer complications and episodes of breakthrough hepatic encephalopathy in patients with cirrhosis. They say that this could translate into significant cost savings.

In an editorial that accompanies the article, David W. Victor, III and Eamonn M.M. Quigley state that additional studies, to demonstrate a clinically meaningful reduction in recurrence of hepatic encephalopathy, are required before this or any other probiotic can be recommended for treatment of patients.

They say it is also important to identify the bacterial populations whose presence, or absence, affect risk for hepatic encephalopathy. This would facilitate development of probiotic formulations best suited for therapy or prevention.

Source -

Friday, September 13, 2013

Considering Probiotics?

Considering Probiotics?

You might have noticed “probiotics” listed on the label of your yogurt. Maybe you’ve seen probiotic pills on store shelves next to vitamins or other supplements.

Probiotics are live microbes, such as bacteria, similar to those found naturally in the human body. We tend to think of microbes as harmful, but certain kinds are good for us and help the body to function properly.

Probiotics are found in some foods or are taken by mouth as dietary supplements. Probiotics also come in other products, such as creams.

The U.S. Food and Drug Administration hasn’t approved any health claims for probiotics. Although some products have shown promise, there’s little evidence to support specific uses of probiotics for most conditions.

Some evidence suggests that probiotics may relieve diarrhea, ease irritable bowel syndrome and reduce symptoms of atopic eczema, an itchy skin condition usually seen in infants. Probiotics generally have few side effects, but there’s little data about their long-term safety.

Talk with your health care provider before taking probiotics for a health condition. These products contain different types of bacteria, and their effects on the body can vary from person to person. Probiotics might cause serious side effects in people with underlying health conditions. To learn more, visit NIH’s Probiotics Web page.

  • Oral Probiotics: An Introduction
  • 5 Things To Know About Probiotics

  • Friday, May 13, 2011

    Effects of Gut Flora Modulation using Prebiotics, Probiotics and Synbiotics on Minimal Hepatic Encephalopathy

    From Alimentary Pharmacology & Therapeutics

    The Effects of Gut Flora Modulation using Prebiotics, Probiotics and Synbiotics on Minimal Hepatic Encephalopathy

    S. Shukla; A. Shukla; S. Mehboob; S. Guha
    Authors and Disclosures

    Posted: 05/11/2011; Alimentary Pharmacology & Therapeutics. 2011;33(6):662-671. © 2011 Blackwell Publishing



    Minimal hepatic encephalopathy (MHE) is characterised by subtle neurocognitive deficits without overt clinical manifestations. Although several trials have individually evaluated the role of prebiotics, probiotics and synbiotics, there is yet no consensus on the management of MHE.

    To estimate the efficacy of prebiotics, probiotics and synbiotics in MHE in randomised controlled trials.

    MEDLINE, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews were searched for published studies in all languages. Inclusion and exclusion criteria were defined a priori. Pooled relative risk and heterogeneity were estimated as the measures of association.

    Nine studies met our inclusion criteria. Use of prebiotics, probiotics and synbiotics significantly reduced the pooled relative risk (RR) of no improvement of MHE (RR 0.40, 95% CI 0.32–0.50; P < 0.001). Upon subgroup analysis, five studies with lactulose showed significant reduction of risk of no improvement of MHE (RR 0.34, 95% CI 0.24–0.47; P < 0.0001) with no inter-trial heterogeneity. In two trials each of probiotics and synbiotics, their use was associated with significant beneficial effects (RR 0.41, 95% CI 0.26–0.65; P < 0.0001 and RR of 0.51, 95% CI 0.32–0.80; P = 0.004 respectively). There were no major adverse events though probiotics and synbiotics were better tolerated than lactulose.
    Conclusions The use of prebiotics, probiotics and synbiotics was associated with significant improvement in minimal hepatic encephalopathy. Among individual agents, lactulose appears to have the most beneficial effect, followed closely by probiotics and synbiotics.


    Rikkers et al. first described subclinical hepatic encephalopathy in cirrhotic patients who by conventional neurological and mental status examination appeared normal but had abnormalities in psychometric tests.[1] Now recognised as Minimal Hepatic Encephalopathy (MHE),[2] it is a part of spectrum along hepatic encephalopathy characterised by abnormalities in psychometric and neurophysiological tests without overt clinical symptoms.[3–5] Incidence of MHE ranges from 30 to 84% in patients with chronic liver disease.[3] MHE is an under diagnosed problem, but its effect on daily activities could be profound as it impairs attention span and reaction time.[6] Wein et al. showed that MHE impairs fitness to drive.[2] Similar observations by Bajaj et al. in this subpopulation of cirrhotics confirm that MHE is a strong predictor for traffic violations and accidents.[3,7] Cirrhotics with MHE have poor health related quality of life[5] and impaired daily functioning as confirmed by lower scores on the sickness impact profile (SIP).[8] MHE impairs employability; up to 60% of blue collar workers and 23% of white collar workers maybe unfit for working.[9]

    The major treatment modalities for MHE have been similar to that of overt hepatic encephalopathy (OHE): targeting ammonia production and absorption. As the gut microbiota play an important role in the generation of ammonia, its modulation using prebiotics, probiotics and synbiotics have been evaluated by several small studies as a therapeutic option for MHE. Prebiotics are defined as a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health.[10] Probiotics are 'live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance'.[11] The combination of prebiotics and probiotics is known as a synbiotic.
    The studies using these agents (prebiotics probiotics and synbiotics) have been conducted in a small number of patients with short treatment duration. As a result of seemingly inadequate data, patients with MHE often go untreated, thus potentially subjecting them to all its complications. Pooled results of the available trials would give more conclusive and stronger evidence about the role of gut based therapy. Hence, we conducted a meta-analysis of available randomised controlled trials (RCT) to further ascertain the effect of prebiotics probiotics and synbiotics and resulting gut flora modulation on course of MHE. As MHE remains undertreated, evaluating the efficacy of the available treatment options is of critical importance.


    Literature Search

    Two independent reviewers (SS, AS) searched MEDLINE, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews and Cochrane Controlled Trials Register. The search was restricted to human studies in adult subjects from January 1966 to June 2010. The search terms used were 'minimal hepatic encephalopathy', 'subclinical hepatic encephalopathy', 'latent hepatic encephalopathy''probiotics', 'prebiotics', 'synbiotics', 'lactulose', 'lactitol', 'fibre''gut flora' and 'cirrhosis'. The abstracts of all the studies were reviewed and most of the times full text reports were evaluated. The search was extended by review of bibliography of the pertinent retrieved clinical trials and other papers on the subject without language restriction. The authors were contacted when the methodology of the clinical trial or the result was not clear or relevant data not reported.

    Inclusion criteria were: (i) studies involving patients with MHE or subclinical hepatic encephalopathy (SHE), (ii) study had to be a RCT comparing use of prebiotics, probiotics or synbiotics with a placebo, (iii) patients 18 years or older with established cirrhosis irrespective of the aetiology, and (iv) the study should have reported clinical outcome with regard to reversal, maintenance of MHE or worsening to OHE. The exclusion criteria were: (i) studies involving patients with OHE at the onset of clinical trial, (ii) nonrandomised controlled trial, (iii) any coexistent psychiatric illness, (iv) use of psychotropic drugs or presence of active alcoholism in patients, and (v) use of antibiotics including rifaximin or neomycin. The primary outcome evaluated was any change in the course of MHE with treatment as reported by individual clinical trials. The secondary outcome was the effect of treatment on changes in venous ammonia levels and adverse events specific to use of the drugs.

    Data Abstraction

    The review process was carried out as per the guidelines laid by the QUOROM statement.[12] The reviewers independently assessed the eligibility of each study for inclusion. Non-English studies that fit the inclusion criteria were translated. Any discrepancy in the selection of studies or data retrieved by the reviewers was resolved by discussion with a third reviewer. The following data from the included trials was recorded: inclusion and exclusion criteria, aetiology and method of diagnosis of cirrhosis, method used to diagnose MHE, agent and duration of treatment, side effect profile, and changes in serum ammonia levels when available. We recorded the course of MHE as reported by individual studies, based on their own criteria of diagnosing and following up MHE. The methodological quality of the included trials was assessed using the Jadad 5 point scoring system. This scale evaluates an RCT via three itemised scoring system: randomisation (0–2 points), masking (0–2 points) and dropouts and withdrawals (0–1 point), with a score of 3 considered acceptable and a higher score indicating better reporting.[13] Each study was given a total score with a maximum of five.

    Data Analysis

    The effect of gut flora altering regimens on the neuropsychological changes of MHE was evaluated in three different ways. The primary analysis focused on evaluating the effect of combined medical therapy involving prebiotics probiotics and synbiotics on the course of MHE. Further subgroup analysis was performed to evaluate the effect of these agents individually. Next, effect of treatment regimen on serum ammonia levels and any adverse effect were evaluated. We measured weighted κ to assess interrater variability for study inclusion and assessment of the methodological quality. From each study outcome, the risk ratio (RR) with 95% CI was derived. The results were pooled using the Mantel-Haenszel (M-H) fixed effects model and the random effects model was to be used for outcomes if heterogeneity was present. With the M-H model, based on number of patients that had no worsening of MHE, weighting for each study was calculated to form an average overall outcome statistic and 95% CI. Both χ2 and I 2 statistics were analysed to assess heterogeneity between the studies. Using the χ2, a P value less than 0.1 was considered significant heterogeneity and using the I 2 statistics, 0% to 40% unimportant, 30% to 60% moderate, 50% to 90% substantial and 75% to 100% considerable heterogeneity.[14] All statistical analysis was performed using stata software version 10.0 (StataCorp, College Station, TX, USA)


    Our search yielded a total of 174 potential articles, of which 165 were excluded (Figure 1). Nine RCT's with a total of 349 patients met our specified criteria.[15–23] Of these, five evaluated the effect of lactulose,[19–23] two of synbiotics[15,16] and two of probiotics[17,18] on MHE. Eight potentially relevant trials were identified which used lactitol, however, they were excluded either because comparison was not with a placebo, but with an antibiotic[24,25] or different doses of lactitol,[26] or lactulose[27–31] or included patients with OHE.[31] Four controlled trials with lactulose were excluded because either they did not report the outcome of interest (number of patients that improved or worsened with treatment[32] but only mean change in the psychometric tests) or involved patients with OHE[33] or were not placebo controlled (compared with fructo-oligosaccharides[34]) or was not an RCT.[35] Similarly, search with fibre yielded a study with acarbose[36] in low grade hepatic encephalopathy that was excluded from our review as it did not report the outcomes of interest.

    Figure 1. Flowchart of selection of trials.

    The term latent hepatic encephalopathy yielded several studies none of which met our inclusion criteria i.e. either were not a RCT or did not study the agents of interest in the treatment. We contacted two primary authors[16,18] and received the information about the results of trial outcomes from both the authors. While five studies used the term MHE,[15–18,21] four reported their patient population to have SHE.[19,20,22,23] As the patients in the group with SHE did not have overt hepatic encephalopathy and SHE is now synonymous with MHE, they were included in our analysis. The interrater agreement between the study reviewers for study inclusion was excellent with κ = 0.92.

    Table 1 shows the design and the characteristics of the trials. Briefly, the trials were similar with respect to the patient population studied. The age group of patients included was homogeneous ranging from 44 to 62 in the treatment group and 45 to 65 in the placebo group. Males formed the predominant patient population in four studies.[15,21–23] All the studies enrolled patients diagnosed with cirrhosis of different aetiology including alcohol, viral, autoimmune, except one[17] which described its patient population as non-alcoholic cirrhotics. The method of diagnosis of cirrhosis in the patients was described by all the studies except one.[17] Furthermore, all but one study[19] reported CPT scoring of the patients at the onset of the trial. The trial durations ranged from 15 days to 6 months.

    All studies used abnormality in neuropsychometric tests (outside the mean ± 2 s.d.) for the diagnosis (except for the study by Horsmans et al. [19]) and response to treatment of MHE (Table 2). The neuropsychometric tests used in the studies were different (Table 2). Three studies used abnormality in one test,[15–18] while others used two or more abnormal tests to diagnose and report outcomes of MHE.[20–23] In the study by Horsmans et al.,[19] the patients involved cirrhotics with documented portosystemic shunting without overt encephalopathy. These patients had abnormalities in neuropsychometric tests at baseline, although these tests were not formally used to divide the patients into MHE and non-MHE groups. Table 2 shows the type and doses of the agents used in respective trials. The studies differed in terms of the treatment regimen utilised to alter the gut flora. While two studies used synbiotic preparation,[15,16] two used probiotics[17,18] and five studies used lactulose (a prebiotic).[19–23]

    The quality of the studies included in our analysis was good except for one[18] which had a Jadad score of 2. Six of the studies[15,17,20–23] had a score of three, while the remaining two had a score four[19] and five.[16] The mean Jadad score of all the trials included in our study was 3.22.

    The alteration of gut flora using pre, pro and synbiotic significantly reduced the risk of no improvement of MHE compared with placebo (RR 0.40, 95% CI 0.32–0.50; P < 0.001; Figure 2, nine trials). There was no significant heterogeneity between the trials (χ2 = 10.22, P = 0.250, I 2 = 22%). A post hoc subgroup analysis of this data excluding the study with a low Jadad score[18] revealed similar results (RR 0.39, 95% CI 0.31–0.50; P < 0.001; Figure S1, eight trials) with no significant intertrial heterogeneity (χ2 = 10.36, P = 0.169, I 2 = 32%).

    Click Figure To Enlarge;

    Figure 2.
    Number of patients without improvement of MHE in trials with prebiotics, probiotics and synbiotics compared with control (fixed effects analysis). CI, confidence interval; RR, relative risk

    Five studies provided data on change in course of MHE with lactulose. Using the Mantel-Haenszel model, the use of lactulose significantly reduced the risk of no improvement of MHE in comparison with placebo (RR of 0.34, 95% CI 0.24–0.47; P < 0.0001; Figure 3). There was no significant heterogeneity between the studies (χ2 = 6.11, P = 0.191, I 2 = 35%). Furthermore, two studies with synbiotics too showed that their use reduced the risk of no improvement of MHE (RR 0.51, 95% CI 0.32–0.80, P = 0.004; Figure 4) with no significant intertrial heterogeneity (χ2 = 0.74, P = 0.390, I 2 = 0%). Similar results were obtained with two studies using probiotics i.e. reduced risk of no improvement of MHE with RR 0.41 (95% CI 0.26–0.65, P < 0.0001; Figure 4) without heterogeneity with χ2 = 0.65, P = 0.421, I 2 = 0%. Venous ammonia levels were evaluated by four studies, two of which used synbiotics,[15,16] one probiotic[17] and another with lactulose.[23] The pooled results showed that therapy led to lowering of serum ammonia in these patients (WMD −19.85, 95% CI −22.94 to −16.77, P < 0.0001 with some heterogeneity among the studies with χ2 = 5.73, P < 0.125, I 2 = 48%.

    Figure 3.

    Number of patients without improvement of MHE in trials with Lactulose compared with control (fixed effects analysis). CI, confidence interval; RR, relative risk.

    Figure 4
    Number of patients without improvement of MHE in trials with synbiotics and probiotics compared with control (fixed effects analysis). CI, confidence interval; RR, relative risk.

    Of the four studies that evaluated the use of probiotics and synbiotics, three[15–17] contained information about adverse effects. These were mainly confined to gastrointestinal system and the study by Malaguarnera et al. included abdominal pain, nausea in the treatment group and diarrhea, headache in the placebo group. In the study by Bajaj et al. two patients dropped out because they did not like the taste of the probiotic. The study by Liu et al. reported good tolerance of the agents in all patients with no adverse effects. Overall, none of these studies reported any serious adverse effects in the patients. In the five studies evaluating the effect of lactulose, two studies[19,20] reported adverse effects. In the study by Horsman et al. three patients reported diarrhoea with the use of lactulose that required dose reduction. In the study by Watanabe et al. eight patients (19%) reported diarrhoea, one reported soft stools, one anorexia, one abdominal pain, one vomiting, one glycosuria (out of the total 43 patients who received lactulose in this study). None reported any serious adverse effect that required withdrawal from the study. As most of the studies did not reliably give information about the adverse effects in the respective treatment and the placebo group, we were unable to perform a meta-analysis of this outcome.

    The result of our meta-analysis provides substantial evidence for the efficacy of prebiotics, probiotics and synbiotics in the treatment of MHE. Upon sensitivity analysis with exclusion of the study with low Jadad score, the outcome remained unchanged, corroborating the strength of evidence of the gut based therapy. Moreover, as seen on subgroup analysis, lactulose, synbiotics and probiotics individually have significant beneficial effect on MHE. On further comparison, use of synbiotics and probiotics was associated with a 50% and 60% decrease in the risk of no improvement of MHE respectively, while use of lactulose was associated with a 67% risk in comparison with placebo. Because the prevalence of MHE is common in chronic liver disease, these findings have important clinical implications.

    While the natural history of MHE remains to be completely elucidated, it is known that it may progress to OHE[4,37,38] and may have a fluctuating course. As the neurocognitive deficits seen in MHE impair driving skills and other important aspects such as ability to work, early recognition and treatment of this condition is warranted. Once MHE has been diagnosed it can be challenging for the physician to decide which agent would be the most effective in reversing the neurocognitive deficits. Several different treatment options exist but there is yet no definite standard of care mainly because of the variable efficacy and side effect profile of the available options. A recently published editorial underscored the importance of studies that elucidate the effect of changing gut flora composition (using pre and probiotics) for the treatment of hepatic encephalopathy.[39] The results of our pooled analysis provide significant evidence that bridges the knowledge gap of MHE, thus providing an impetus for treatment.

    Modulation of gut flora presumably works by several mechanisms in cirrhosis to exert a favourable effect on neurological dysfunction.[40] As reported by Liu et al. [15] and Lata et al. [18] the reduction in potential pathogenic bacteria such as Escherichia coli and Staphylococcal species in stool at the end of treatment period with increase in non-urease producing Lactobacillus limits ammonia production. Moreover, lactulose is converted to lactic and acetic acid which results in acidification of colonic contents. The low pH decreases passive non-ionic diffusion of ammonia thus lowering its systemic concentration. Furthermore, with its prebiotic potential, lactulose also encourages growth of probiotic bacteria such as Bifidobacterium species that are known to have health-promoting effects. While this potential therapeutic target of modifying the gut microbiota using pre–pro or synbiotics has been evaluated in other conditions such as inflammatory bowel disease,[41] irritable bowel syndrome,[42,43] antibiotic-associated diarrhoea,[44,45] to our knowledge this is the first meta-analysis to assess the beneficial effect of these agents in MHE.

    The results in our study are reported using the fixed-effects model and showed a lack of any inter-trial heterogeneity, thus strengthening the outcomes. Moreover, all studies were conducted in patients with documented cirrhosis and not a reversible hepatic dysfunction such as alcoholic or viral hepatitis. Furthermore, the studies had a mixture of patients with CPT scoring in all categories (except one study[17]) with consistent relative risk reduction among all, pointing towards the usefulness of treatment irrespective of the initial CPT scoring of the patients. The presence of MHE in the study subjects or worsening to OHE during follow-up was not resulting from any confounding insult to the liver such as intercurrent infections, concomitant alcohol use or any other illness that could worsen hepatic function. This along with the short duration of the study periods and with a consistent beneficial effect in each trial further strengthen the evidence that the therapeutic action in MHE can be ascribed to the use of the individual agents themselves and not to a chance finding.
    Although patients in the studies with lactulose did report problems related to palatability, diarrhoea and flatulence, overall it was well tolerated as all studies titrated the dose to two to three bowel movements per day. The patient acceptability of probiotics or synbiotics seemed better with no reported adverse effect except for issue with palatability of the probiotic in the study by Bajaj et al. which again could be ascribed to the specific manufacturer of the probiotic (flavoured vs. unflavoured). As the agent in this study was not strictly a probiotic but yogurt, any beneficial as well as adverse effect could also be ascribed to its other constituents including lactose and milk protein. Although the trials individually showed significant reduction in venous ammonia levels, the results of our pooled analysis showed some heterogeneity. A wide variance in the mean serum ammonia levels in the studies along with small population size could be possible contributors to this effect. Based on this we conclude that the reduction in venous ammonia levels should be interpreted with caution.

    Our meta-analysis has several limitations, related both to our study and to the inherent nature of meta-analyses. The result of any meta-analysis depends upon the quality of the RCT's included. Hence the result of our study is limited because of the nature of the trials included. Firstly, the duration of all the included trials is short. While this could be appropriate in patients with OHE who may have a dramatic clinical presentation which changes with treatment or sometimes spontaneously after the precipitating event is corrected, patients with MHE have a more subtle course. A trial over a longer duration would give a better picture of the extent of benefit effect. Second, the number of patients included in each trial is small. While a meta-analysis mathematically combines these patients to develop overall picture, a small number of included patients do increase the alpha error that would be associated with the study. Next, the difficulty with any study with hepatic encephalopathy and especially with MHE is a lack of a standard diagnostic test. The International Society for Hepatic Encephalopathy and Nitrogen metabolism (ISHEN committee) itself acknowledges the current lack of consensus on how best to detect MHE.[46] To the extent that neuropsychological tests have more face validity as they directly measure cognitive functions, the PSE-Syndrome test is a battery recommended for assessment for MHE by the committee. Most of the studies included in this meta-analysis used tests which are components of the PSE-Syndrome-test. Meta-analyses tend to have shortcoming of their own. In general, data retrieved from a well conducted, adequately powered randomised controlled trial cannot be replaced by a meta-analysis. However, to design a study in MHE addressing the limitations cited above and appropriately evaluate the effect of treatment would require a large, well conducted trial over a more prolonged period. Until that is done, the results from a well conducted meta-analysis would be of considerable importance to shed some light on this newly evolving area of considerable importance. Furthermore, we attempted to minimise publication bias in our study by conducting a comprehensive literature search. Additionally, as the studies included in our analysis also contained negative and nonsignificant end results, our study is less likely to be affected by negative publication bias. Evaluation for heterogeneity in outcomes is another factor that requires consideration while interpreting meta-analyses. The results of our study, however, showed that there was a very minor heterogeneity across the studies.
    Our findings have important implications for the clinical practice as well as research in relation to MHE. The results of our study provide the strongest yet available evidence for the use of prebiotics, probiotics and synbiotics in management of MHE. Furthermore, we conclude that while each of the agents individually have a role, lactulose appears to be the most studied and beneficial followed closely by probiotics and synbiotics. Probiotics may be particularly useful in scenarios of noncompliance or intolerance to lactulose. Moreover, the beneficial effect of these agents with a relatively low side effect profile further necessitates the need for recognising and treating MHE. Whether or not treatment of MHE has any mortality benefits over a longer period of time needs to be addressed in large-scale clinical trials.