Alcohol and the Liver: The Return of the Prodigal Son

Annals Of Hepatology

January - February, 2019 issue
Vol. 18 Issue 1

OPINIONS 

Alcohol and the Liver: The Return of the Prodigal Son
Octavio Campollo

Full-text article
Download Pdf

Abstract

With the discovery of direct-acting antivirals and the prospective of viral hepatitis becoming curable, alcohol liver disease (ALD) is back to primetime. In the last 20 years, there have been many advances in the understanding of the biology, the psychology and the social and environmental factors associated with this long-known medical problem. Recent information about regional, ethnic, cultural and genetic factors seem to be relevant for the Latin American (LA) population. New approaches based on the new concepts and current information will render better results in the overall management of patients with this problem. Considering alcohol use disorder and ALD as part of the same entity managing it in a multidisciplinary approach seems to be best way to deal with this disease.

Continue reading: http://annalsofhepatology.com/revista/numeros/2019/HP191-02-Alcohol%20(Opinion)%20(F_191218M)_LIBRE.pdf

Related Articles On This Blog
Alcohol Consumption

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

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

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

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

Full-Text Article Available Online

ABSTRACT

AIM

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

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

RESULTS

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

CONCLUSION

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

Full-Text Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871858/
World J Hepatol. 2018 Mar 27; 10(3): 379–387.
Published online 2018 Mar 27. doi: 10.4254/wjh.v10.i3.379

New at Healio - Virtual touch quantification accurately measures fibrosis stage

New at Healio

Virtual touch quantification accurately measures fibrosis stage
January 3, 2018
Virtual touch quantification provided a noninvasive method for fibrosis staging and was more accurate than Fibrosis-4 index and aminotransferase-to-platelet ratio index…

HepCom score detects high mortality risk during HCV treatment
January 2, 2018
The HepCom score — which combines Charlson Comorbidity Index, age, international normalized ratio, albumin and bilirubin — accurately detected patients with…

Early warning score accurately predicts mortality risk in liver disease
January 2, 2018
The National Early Warning Score accurately identified patients with chronic liver diseases at risk for death, admission to the intensive care unit or cardiac arrest…

2017 saw record number of FDA approvals for drugs
January 1, 2018
The FDA approved 46 drugs in 2017, tying a record set for approvals in 2015. Cancer medications led the way, with 16 oncology and 11 hematology drugs approved. There…

New liver disease atlas points to significant variation across England

Liver Disease Atlas - News Release      

New liver disease atlas points to significant variation across England

The rate of people dying early from liver disease in some parts of England is almost 8 times higher than others, according to new data published by Public Health England (PHE) today. 

Liver disease is almost entirely preventable with the major risk factors: alcohol, obesity and Hepatitis B and C accounting for up to 90% of cases. The atlas will help health professionals to allocate their resources to improve patient outcomes. 

The Atlas shows premature mortality rates – dying before the age of 75 – ranged from 3.9 per 100,000 in South Norfolk CCG to 30.1 per 100,000 in Blackpool CCG, a 7.7-fold difference. 

The Atlas paints a mixed picture, with 10 indicators showing improvements including; a reduction of premature deaths and fewer hospital alcohol specific admissions for under 18s.

Nine of the indicators have become worse over time, including a doubling of hospital admission rates for cirrhosis from 54.8 per 100,000 to 108.4 per 100,000 people over the past decade. This indicator also varies significantly across the country with an 8.5 fold variation across CCGs and this gap has widened over the past decade.  

Liver disease is responsible for almost 12% of deaths in men aged 40 to 49 years and is now the 4th most common cause of Years of Life Lost in people aged under 75 after heart disease and lung cancer. 

Professor Julia Verne, head of clinical epidemiology at Public Health England said:
“Chronic liver disease is a silent killer of young adults, creeping up and showing itself when it’s often too late. However, around 90% of liver disease is preventable. 

“We hope local health professionals will make the most of this rich data source to inform how they reduce the burden of liver disease in their areas.”

The Atlas also lays bare the impact of the stark health inequalities in England. Inequality plays a role in the significant variation in risk factors of liver disease – excessive alcohol consumption, obesity, and hepatitis B and C. 

For example, there is a 7.4-fold difference in the rate of alcohol-specific hospital admissions across the country, with the majority of the higher rates being clustered in the more deprived areas. Also, in the most deprived fifth of the country, people with liver disease die 9 years earlier than those in the most affluent fifth.

These data will underline the importance of developing a strategy to tackle the rising burden of liver disease, especially in younger adults and even children. Liver disease can take 20 years to show up as symptoms.

The Atlas is made up of 39 indicators, 19 of which show trend data over time. It shows the degree of variation across the country, a national figure for comparison and commentary providing options for action and a list of evidence based resources for local health systems to improve.

The 2nd Atlas of Variation in risk factors and healthcare for liver disease in England will be published on the PHE fingertips website here: https://fingertips.phe.org.uk/profile/atlas-of-variation

LINK
Full Press Release
________________________________________________________

The Financial Case for Action on Liver Disease - Escalating costs of alcohol misuse, obesity and viral hepatitis JULY 2017

The Foundation for Liver Research

Monday 17th July 2017
The Lancet Commission into Liver Disease in the UK has today published 'The Financial Case for Action on Liver Disease'

In this paper the Foundation for Liver Research seeks to make the financial case for concerted preventative action through public health measures to tackle the 3 main causes of liver disease: alcohol misuse, obesity and viral hepatitis. The paper summarises the escalating financial costs to the health and care system as well as the wider societal costs related to the 3 lifestyle-related factors.

Download Report

Liver diseases exhibit differing patterns in ethnic minorities

Liver diseases exhibit differing patterns in ethnic minorities

Chronic liver disease (CLD) and cirrhosis are serious liver conditions but little is known about how they affect ethnic minority populations in the United States. When researchers examined CLD and cirrhosis among different groups, they found that the prevalence of CLD ranged from 3.9 percent in African Americans and Native Hawaiians to 4.1 percent in whites, 6.7 percent in Latinos, and 6.9 percent in Japanese.

Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52 percent), followed by alcoholic liver disease (ALD) (21 percent).
NAFLD was the most common cause of cirrhosis in the entire study, and by ethnicity, it was also the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32 percent of cases. ALD was the most common cause of cirrhosis in whites (38.2 percent), while hepatitis C virus was the most common cause in African Americans (29.8 percent).

"This is the first study of its kind to include Native Hawaiians and Japanese Americans, and it revealed the important discovery that NAFLD is the most common cause of CLD and cirrhosis in Japanese Americans, Latinos, and Native Hawaiians and that NALFD prevalence in Japanese is higher than in Latinos and other ethnic groups," said Dr. Veronica Wendy Setiawan, lead author of the Hepatology study. "This paper addresses the gap in knowledge for understudied populations with respect to CLD's underlying etiology and underscores NAFLD as the most important cause of CLD. It also highlights the need to implement improved screening, diagnostic, and management approaches to face this growing epidemic."

http://dx.doi.org/10.1002/hep.28677

Helping Patients with Liver Disease Choose Wisely

Helping Patients with Liver Disease Choose Wisely

As in every field of medicine, there are certain tests and procedures that patients with liver disease and their physicians should discuss to ensure they are truly necessary and will improve care. The AASLD is proud to partner with the ABIM Foundation's Choosing Wisely® campaign to identify specific tests, procedures, and treatments that may be unnecessary and may even cause harm.

AASLD has made recommendations on a wide range of liver conditions that affect patients with:
Cirrhosis and small varices
Hepatitis encephalopathy
Hepatitis C virus
Benign focal liver lesions

View the specific recommendations [PDF]

AASLD's list was developed by a group of experts to broadly represent varying practice settings and subspecialty expertise within the field of hepatology after soliciting the input of the entire AASLD membership. The recommendations that AASLD made are based on the most current evidence found in scientific literature.

Health care in America often includes practices that may provide little, if any, benefit to patients. Some estimate that up to 30 percent of health care spending goes toward duplicative or unnecessary interventions. The Choosing Wisely® campaign of the ABIM Foundation is one way of encouraging conversations between physicians and patients to avoid these unnecessary tests or procedures and improving overall health.

Since launching in April 2012, nearly 100 national, regional and state medical specialty societies, health collaboratives and consumer groups have become Choosing Wisely partners. The campaign has released 54 lists covering more than 250 tests and procedures that the specialty society partners say are overused or inappropriate.

“AASLD is pleased to be working with the ABIM Foundation to help streamline the care of our patients with liver disease and spark conversations with their physicians about the care that is best for them,” said Adrian M. Di Bisceglie, AASLD president.

To view the specific recommendations, click here. [PDF]To learn more about Choosing Wisely and to view the complete lists and additional detail about the recommendations and evidence supporting them, visit www.ChoosingWisely.org.

###

About the ABIM Foundation
The mission of the ABIM Foundation is to advance medical professionalism to improve the health care system. We achieve this by collaborating with physicians and physician leaders, medical trainees, health care delivery systems, payers, policy makers, consumer organizations and patients to foster a shared understanding of professionalism and how they can adopt the tenets of professionalism in practice. To learn more about the ABIM Foundation, visit www.abimfoundation.org, read our blog blog.abimfoundation.org, connect with us on Facebook or follow us on Twitter.

About Choosing Wisely®
First announced in December 2011, Choosing Wisely® is part of a multi-year effort led by the ABIM Foundation to support and engage physicians in being better stewards of finite health care resources. Participating specialty societies are working with the ABIM Foundation and Consumer Reports to share the lists widely with their members and convene discussions about the physician's role in helping patients make wise choices. Learn more at www.ChoosingWisely.org.

http://www.aasld.org/PATIENTS/Pages/choosewisely.aspx

Scientists at the UA make critical end-stage liver disease discovery

Scientists at the UA make critical end-stage liver disease discovery

The discovery of an unknown cellular pathway has helped scientists and physicians better understand end-stage liver disease and offers a potential target for new therapeutics 

IMAGE: Zhang's research group studies the molecular mechanisms cells use to protect themselves from damage caused by toxicants and carcinogens.

A team of researchers in the University of Arizona's College of Pharmacy has discovered a molecular pathway that could be key to creating new therapeutics that would slow or even reverse the progression of end-stage liver disease.

Although cirrhosis of the liver is most commonly associated with alcohol or drug abuse, the condition – marked by scar tissue replacing healthy liver tissue – also can result from viral hepatitis, obesity and diabetes, as well as certain inherited diseases. According to the National Institutes of Health, cirrhosis is the 12th leading cause of death by disease in the U.S. As with many other human pathologic conditions, end-stage liver disease goes hand in hand with oxidative stress, which refers to damage inflicted to biological tissues by reactive oxygen molecules. Such molecules, also called free radicals, occur naturally as a byproduct of metabolic processes in the body and are associated with many chronic diseases including cancer, diabetes, neurodegenerative and cardiovascular diseases.

"Cells keep oxidative stress under control through various mechanisms," said Donna Zhang, a professor in the UA Department of Pharmacology and Toxicology, explaining that most of these mechanisms involve Nrf2, a protein present in virtually every cell that acts as a molecular switch. Nrf2 activates various biochemical mechanisms inside the cell that capture reactive oxygen molecules or dispose of damaged cellular components before they can cause more trouble. The antioxidants found in many fruits and vegetables exert their healthful benefits by capturing reactive oxygen molecules.

Under normal, healthy conditions, when no oxidative stress response is needed, an enzyme called Keap1 constantly chews up Nrf2, keeping its level low.

"Then, under stress from reactive oxygen molecules, or when you eat antioxidants from certain plants like broccoli sprouts, it prevents Keap1 from eating up Nrf2, allowing it to accumulate in the cell," explained Zhang, who is also a member of the UA BIO5 Institute. "Nrf2 then activates the cellular antioxidant response. That is how antioxidants work." According to conventional wisdom, our bodies turn on their Nrf2-mediated protection pathway when subjected to high oxidative stress to limit the damage from the destructive oxygen compounds. During liver cirrhosis, Nrf2 should be induced by oxidative stress, but for reasons unclear until this study, this does not happen.

"This was a puzzle before we did our study," she said. "Somehow the protective mechanism mediated by Nrf2 is compromised by another factor, other than Keap1, in liver cirrhosis." Adding to the mystery is the fact that drugs aimed at inhibiting Keap1 from chewing up Nrf2 have proven ineffective in a cirrhotic liver.

When Zhang and her colleagues studied tissue samples from a human cirrhotic liver, they discovered the reason behind the inexplicably low Nrf2 levels in the face of rampant oxidative stress.

It turned out that another enzyme chews up Nrf2 and prevents the much-needed antioxidant response, exacerbating the disease process. That protein, Hrd1, is part of the cells' garbage disposal – it specializes in destroying misfolded proteins before they can accumulate and damage cell components.

Under normal conditions, Hrd1 levels are low, so it does not interfere much with Nrf2, explained Zhang. As liver cirrhosis progresses, excessive inflammation triggers the garbage-mediated stress response and Hrd1 becomes very abundant and begins chewing up Nrf2.

The study is published in the April 1 issue of the journal Genes and Development. The first author of the report is Tongde Wu, a graduate of the UA Department of Pharmacology and Toxicology, who developed the project as part of her dissertation research. Fei Zhao and Eli Chapman, in the same department, also contributed to the research. The work resulted from a collaboration between Zhang's research group and Deyu Fang, Beixue Gao and Can Tan at Northwestern University Feinberg School of Medicine in Chicago. Other contributors are Naoko Yagishita and Toshihiro Nakajima of St. Marianna University School of Medicine in Kawasaki, Japan, and Pak K. Wong of the UA College of Engineering.

The discovery could change the way scientists develop therapeutics, as it provides a new target for future drugs. In laboratory experiments, Zhang and her colleagues were able to restore Nrf2 levels in cirrhotic liver tissue by inactivating Hrd1, effectively reversing liver cirrhosis in mice.

"Previous efforts only focused on the Keap1 protein and tried to prevent it from breaking down Nrf2," Zhang said. "Now we know there is a second player in the game – Hrd1 – that we need to inhibit in order to restore Nrf2 levels.

"Boosting Nrf2 is good for protection in general, which is why you should always eat your broccoli," she stressed.

http://www.eurekalert.org/pub_releases/2014-04/uoa-sat042514.php

Monday Hepatitis C News: Sofosbuvir, Faldaprevir, Liver Disease and Second Opinions

Hello Folks,
Welcome to a new week of HCV news and research. If you missed it over the weekend an editorial on several new DAA agents currently in late stages of development was posted on the website, simeprevir and sofosbuvir were included.

Dr. Galati a leading authority on liver transplantation, liver disease and gastroenterology last week launched an interesting concept for patients with HCV or liver disease seeking a second opinion. Liver Specialists of Texas, Dr. Galati’s practice located in Huston, Texas is offering a 30 minute consultation via the Internet using an innovative software program.

Through Videoconferencing liver patients who can not travel to Huston are able to review and ask questions about past consultations, including abnormal liver tests, fatty liver, or biopsies.

Liver Specialists of Texas is one of America’s largest private liver services. Galati also produces and hosts Your Health First, a weekly one-hour radio program.

Videoconferencing - Huston, Texas

Second Opinion in Hepatitis: Videoconferencing Between Houston and the World
by Dr. Joe Galati on 10/07/2013

Each week, I receive dozens of e-mails from followers of our social media sites (Twitter, YouTube, FaceBook, Your Health First, and Liver Specialists of Texas) seeking assistance regarding some form of liver disease they are suffering from, or one of their relatives. I usually respond back with some direction they should head in, or ask if they are available to travel to Houston for a face-to-face evaluation.

As technology improves, the availability of videoconferencing has never been easier. Working with Houston based software developers, there is now the opportunity to participate in a second opinion program with experts in liver disease in our practice. Because there is such variability in everyone’s home or work connectivity to the internet, we plan on supplying you with the needed technology to connect.

The savings of not having to travel to Houston, hotel and food charges, lost wages, and time, makes this an economically sensible alternative.

Second opinions in all aspects of liver disease will be available, including abnormal liver tests, fatty liver disease, hepatitis C, hepatitis B, cirrhosis, liver cancer, alcohol related liver disease, liver transplant, hemochromatosis, and autoimmune disease of the liver. The cost for this service will be based on a minimum of a 30 minute consultation, allowing for additional time at 15 minute increments. Medical records, x-ray reports and films, biopsies, and past consultations will be reviewed.

Feedback on this program is important to us. Please let us know what you think.

For additional information, contact Dee at (713) 634-5103.

Here we go with today's news and headlines, enjoy your day! 

New HCV Drugs 

Effectiveness of New Hepatitis C Treatments Featured at ACG Annual Scientific Meeting Rapid Evolution of Medical Research Advancing Hepatitis C Treatment

San Diego, CA (October 14, 2013) – Data on new treatment options and combinations of therapies to treat chronic viral hepatitis C infection were presented at the 78th Annual Scientific Meeting of the American College of Gastroenterology in San Diego in a scientific session dedicated to liver disease. Three research teams reported on trials of several experimental treatments, including interferon-free drug combinations and direct acting antiviral agents effective against genotypes 2 and 3 of the Hepatitis C virus, as well as new agents which have the potential to shorten the duration of therapy.

“These studies highlight how rapidly medical research is advancing in hepatitis C,” said Kris V. Kowdley, M.D., FACG, director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center, and Clinical Professor of Medicine at the University of Washington in Seattle. “The new wave of direct-acting oral agents has the potential to transform therapy for patients living with hepatitis C, both in terms of their safety and efficacy profiles, but also in terms of the possibility of reducing the duration of, or completely eliminating the need for, interferon injections.”

Faldaprevir STARTVerso1 Trial: Up to 89 Percent of Patients Eligible to Stop Treatment at 24 Weeks

Final results of the STARTVerso1 Phase 3 trial of faldaprevir plus pegylated interferon and ribavirin in chronic hepatitis C infection in treatment-naïve patients infected with genotype1 were presented by Christophe Moreno, M.D., Ph.D. of the Hôpital Universitaire Erasme in Brussels, Belgium and colleagues. This randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of faldaprevir, an investigational protease inhibitor.

Treatment-naïve patients with chronic hepatitis C genotype 1 were randomized to receive 24 weeks of pegylated interferon and ribavirin with faldaprevir placebo (arm 1); or faldaprevir 120 mg for 12 or 24 weeks (response guided; arm 2); or faldaprevir 240 mgs for 12 weeks (arm 3). Patients in arms 2 and 3 also received pegylated interferon and ribavirin for 24 weeks. Patients with early treatment success (ETS) at week 8 in Arms 2 and 3 stopped all treatment at week 24. Early treatment success was defined in the protocol as virus at week 4 below limit of quantification [BLQ] and at week 8 below limit of detection.

The investigators reported that in previously untreated patients with genotype-1 hepatitis C virus (HCV) who received once-daily faldaprevir plus PegIFN/RBV, 79 percent and 80 percent in the 120mg and 240mg arms, respectively, achieved viral cure when measured 12 weeks after treatment was completed (SVR12). This is compared with 52 percent of patients receiving PegIFN/RBV plus placebo (p<0.0001).

Anemia, rash and gastrointestinal issues were the most common Grade 2-4 adverse events in placebo, faldaprevir 120mg and faldaprevir 240mg arms, respectively. In total, up to 89 percent of patients treated with faldaprevir were eligible to stop all treatment at week 24. The study was supported by a grant from Boehringer Ingelheim.

“In the STARTVerso™1 study, faldaprevir has shown efficacy in achieving viral cure for treatment-naïve patients with HCV, with the potential for a shorter treatment duration. These results are particularly promising, as the study evaluated genotype 1a and 1b HCV patients, including difficult to treat patients such as those with liver cirrhosis,” commented Dr. Moreno.

Sofosbuvir with Ribavirin and Pegylated Interferon Shortens Treatment for HCV Genotype 1

Kris V. Kowdley, M.D., FACG reported results of four multi-center randomized trials of combination therapies of sofosbuvir for patients with chronic hepatitis C.

“Among genotype 1 patients receiving sofosbuvir plus ribavirin and pegylated interferon, the sustained viral response rate was 91 percent at 12 weeks after end of treatment,” commented Dr. Kowdley, highlighting findings from the NEUTRINO study, one of four trials of sofosbuvir reported by Dr. Kowdley and his colleagues.

The four studies reported included the NEUTRINO trial, in which treatment- naïve patients with genotype 1,4, 5 and 6 received 12 weeks of sofosbuvir and pegylated interferon plus ribavirin; FISSION in which treatment-naïve patients with genotype 2 or 3 were randomized to receive either 12 weeks of sofosbuvir plus ribavirin or 24 weeks of pegylated interferon plus ribavirin; POSITRON in which interferon-ineligble, -intolerant or –unwilling genotype 2 or 3 patients were randomized to receive 12 weeks of sofosbuvir plus ribavirin or placebo; and FUSION in which treatment-experienced genotype 2 or 3 patients were randomized to receive 12 or 16 weeks of sofosbuvir and ribavirin.

In the FISSION, POSITRON and FUSION trials, patients with genotype 2 infection had rates of sustained viral response at 12 weeks after the end of treatment (97 percent VR-12 FISSION; 93 percent SVR-12 POSITRON and 86 percent SVR-12 FUSION) that were higher than those patients with genotype 3 (56 percent SVR-12 FISSION; 61 percent SVR-12 POSITRON; and 30 percent SVR-12 FUSION).

Researchers concluded that previously treated patients with genotype 3 hepatitis C infection may benefit from extending treatment to 16 weeks. Currently, no direct-acting antiviral agents have yet been approved for patients with genotype 2 or 3 Hepatitis C infection. This work was supported by a grant from Gilead Sciences Inc.

“The sofosbuvir results seen in these four pivotal studies represent a significant advance in hepatitis C treatment,” said Dr. Kowdley. “First, they indicate that we should be able to shorten therapy for many patients to just 12 weeks. Second, for the first time we have Phase 3 evidence that we can do away with debilitating interferon injections for some patients. Sofosbuvir has the potential to usher in a new era of simple, tablet-based treatment for hepatitis C that boosts cure rates and is much easier for patients to take and to tolerate.”

Results of the Aviator Study of an Interferon-Free Regimen for Hepatitis C

Dr. Kowdley was also the lead author on a study on the safety and efficacy of interferon-free regimens for hepatitis C patients with genotype 1 using a combination of three experimental direct-acting anti-viral agents (DAA) ABT-450/r, ABT-267, and ABT-333 with or without ribavirin. This trial, known as Aviator, treated 247 subjects in the 12 and 24 week arms of three DAA plus ribavirin.

Overall, the sustained viral response at 12 weeks post treatment was 98.7 percent in treatment naïve patients and 93.3 percent in null responders (those patients with hepatitis C virus who failed to respond to prior therapy with other drugs). “Comparable responses were seen with 12 and 24 weeks of treatment, supporting selection of a 12-week duration of therapy in these populations. Consistently high SVR rates were achieved in naïve and prior null responder patients with a three direct acting anti-viral agent regimen, across HCV subtype, IL28B genotype baseline HCV-RNA or severity of fibrosis,” concluded Dr. Kowdley. The design, study conduct, analysis and financial support of this clinical trial were provided by Abbvie.

According to Dr. Kowdley, "The high sustained viral response rates across patient types in the Aviator study were very encouraging. This study, one of the largest phase 2 trials of interferon-free therapy for HCV, was designed to identify the most effective regimens for treating HCV genotype 1 infection. It is noteworthy that the trial included a large number of prior interferon null responders, a population that typically has a poorer response to treatment than treatment-naïve patients. Aviator was the first trial to show that a highly active interferon-free regimen could achieve high SVR rates in null responders. The fact that a well-tolerated 12-week regimen of 3 DAA+ribavirin showed consistently high SVR rates regardless of baseline predictors of poor response suggest that it could be an effective treatment even in difficult-to-treat patients."

About Hepatitis C Virus
Hepatitis C is a liver disease affecting as many as 170 million people worldwide. The virus is primarily spread through direct contact with the blood of an infected person. Hepatitis C infection increases the risk of chronic liver disease, cirrhosis, liver cancer and death. Of the six main genotypes of hepatitis C, genotypes 1, 2 and 3 are the most widespread. Genotype 1 is the most common genotype in the United States and the most difficult to treat with interferon-based therapies. Patients with genotypes 2 and 3 are more likely than individuals with genotype 1 to respond to therapy with pegylated interferon or the combination of pegylated interferon and ribavirin. To learn more, visit the ACG Patient Resource Center on Hepatitis C.

About the American College of Gastroenterology
Founded in 1932, the American College of Gastroenterology (ACG) is an organization with an international membership of more than 12,000 individuals from 80 countries. The College's vision is to be the pre-eminent professional organization that champions the evolving needs of clinicians in the delivery of high quality, evidence-based, and compassionate health care to gastroenterology patients. The mission of the College is to advance world-class care for patients with gastrointestinal disorders through excellence, innovation and advocacy in the areas of scientific investigation, education, prevention and treatment. www.gi.org. View releases on research breaking at the ACG meeting and follow ACG on Twitter and share your live updates #acg2013. 

Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed treatment comparison of fixed-length and response-guided treatment regimens in treatment-naive and --experienced patients

Armin D Goralczyk, Silke Cameron and Ahmad Amanzada

BMC Gastroenterology 2013, 13:148 doi:10.1186/1471-230X-13-148 Published: 14 October 2013

Abstract (provisional)
Background
Telaprevir (TVR) has been approved for response-guided-therapy (RGT) of chronic hepatitis C (HCV) genotype-1-infection in treatment-naive and --experienced patients. In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4--12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR.

Methods
This systematic review and Bayesian mixed-treatment-comparison (MTC) aimed to compare the efficacy and safety of standard-therapy with pegylated-interferon-alpha/ribavirin (Peg-IFN-alpha/RBV (48 weeks), group A), FLT with TVR, Peg-IFN-alpha/RBV for 12 weeks with a long (+36 weeks, group B) or short (+12 weeks, group C) tail of Peg-IFN-alpha/RBV treatment, and RGT with 12 weeks of TVR, Peg-IFN-alpha/RBV followed by 12 weeks of Peg-IFN-alpha/RBV (group D) or no therapy (group E).

Results
We identified seven randomized controlled trials including 3505 patients. Compared to standard-treatment (group A), treatment-naive patients allocated to groups B, C, and D were significantly more likely to achieve sustained-virological-response (SVR, odds ratios (OR): B vs. A 3.5 (credibility interval [CrI] 2.2-5.4), C vs. A 3.0 (CrI 1.8-4.9), D vs. A 3.4 (CrI 2.5-4.6)). Treatment-experienced patients achieved increased SVR rates when they were treated in group B (OR: 8.2 (CrI 5.0-13.5)), C (OR 7.0 (CrI 3.9-12.8)), or simulated group D (OR 8.2 (CrI 4.3-15.3)). Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naive patients (OR E vs. A 1.6 (CrI 0.9-2.7)).

Conclusion
Long FLT and RGT regimens are useful treatment options for HCV-genotype-1 in both treatment-naive and -experienced patients. A short 24-weeks FLT regimen does not seem to be inferior and should further be evaluated in clinical trials to reduce side effects and costs of treatment.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production. 

Support

If You Are Newly Diagnosed with Hepatitis C or Feeling Afraid Because of It
by Lucinda Porter on October 14, 2013
You are not alone. You may feel alone, scared, confused, angry, numb, or shattered. A hepatitis C diagnosis changes everything, at least at first. You may wonder how you got hepatitis C. Perhaps you know how you got it, and if it is because of choices you made earlier in your life, you may be kicking yourself right now. Please don’t do that. The past is past, and kicking yourself when you are down is cruel, unnecessary, and it won’t help anything........

Awareness

Hepatitis C Trust says strategy urgent as related liver disease on the rise

Only 3% of people with hepatitis C are treated each year, yet government is dragging its heels on strategy, says trust

There are 160,000 people living with the hepatitis C virus in England and yet half of those do not know it, said the Hepatitis C Trust. They are at risk of developing a disease which could destroy their liver and cause their death. Only 3% of people receive treatment each year......

Liver Cancer 

World J Gastroenterol. 2013 Oct 7;19(37):6127-6130.

Strategy for improving survival and reducing recurrence of HCV-related hepatocellular carcinoma.

Source

Toru Ishikawa, Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan.

View - Free full text

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death in the world. With advances in imaging diagnostics, accompanied by better understanding of high-risk patients, HCC is now frequently detected at an early stage; however, the prognosis remains poor. The recurrence rate after treatment of HCC is higher than that associated with cancers of other organs. This may be because of the high incidence of intrahepatic distant recurrence and multicentric recurrence, especially with hepatitis C virus (HCV)-related hepatocellular carcinoma. The Barcelona Clinic Liver Cancer (BCLC) classification has recently emerged as the standard classification system for the clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, transcatheter arterial chemoembolization, percutaneous ethanol injection therapy, percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation) can improve survival in HCC patients diagnosed at an early stage and offer a potential long-term cure. However, treatment strategies for recurrent disease are not mentioned in the BCLC classsification. The strategy for recurrence may differ according to the recurrence pattern, i.e., intrahepatic distant recurrence vs multicentric recurrence. In this article, we review recurrent HCC and the therapeutic strategies for reducing recurrent HCC, especially HCV-related HCC.

KEYWORDS:

Arterial chemotherapy, Hepatitis C virus, Hepatocellular carcinoma, Interferon, Intrahepatic distant recurrence, Multicentric recurrence 
Free full text 

Transmission

 Scars! Some people will pay for scarification as an alternative to tattoos
 

SCARS

Blair McLean shows off his scarification which is similar to tattooing but instead you burn your skin to create scar tissue as a work of art in Toronto on Thursday, Oct. 3, 2013. The procedure, known as scarification, is a form of extreme and permanent body modification that is offered in many tattoo and piercing stores across the country and is gaining popularity.

ByErica Lenti 

TORONTO - When Holly Mosienko decided to cover up an unsightly scar on her leg, she strayed away from typical solutions, like plastic surgery or makeup. Instead, she opted for more scarring — this time, in the shape of a tribal dragon. 

The procedure, known as scarification, is a form of extreme and permanent body modification that is offered in many tattoo and piercing stores across the country and is gaining popularity.

It involves a process in which one's skin is cut, etched, burned or branded into a design to create a inkless tattoo-like scar. Though it is not as widely practised as tattooing or piercing, it has been around for just as long. 

"Branding and cutting is not all that different from tattooing," said Mosienko, 51, who runs a piercing store in Peterborough, Ont. 

"It's popular. I'd say it's even more interesting than getting a tattoo." 

Mosienko says she chose scarification for practical reasons. A lover of body art, she knew covering up her scar — caused by surgery — with a tattoo would be too painful, the constant pressure of a needle over scar tissue would be unbearable. Rather, she chose to have the design etched into her skin. 

The entire process — from sketching the design on her leg to the actual cutting — took about an hour. 

Mosienko's artist, 45-year-old Blair McLean of New Tribe Tattoos and Piercings in Toronto, says there are many misconceptions about the practice. 

He says scarification often hurts less than a tattoo; in fact, all forms of scarification occur on the same level of the skin as tattoos: on the dermis, far above fatty tissues and muscle matter. 

The practice is illegal in some countries such as the United Kingdom and several U.S. states. Most recently, the practice was banned in Arkansas, though that bill was overturned after public outcry against the decision. Winnipeg declared the practice illegal in 2008. 

A spokesman for the Ontario Ministry of Health and Long-Term Care says there can be severe health risks that result from having these procedures. 

"Because certain body modification practices break intact skin and mucus membranes through cutting, burning and piercing, there is an increase in the risk of scarring, hemorrhaging and psychological trauma as well as exposure and infection with blood borne pathogens, such as hepatitis B, hepatitis C and HIV," David Jensen said. 

In Toronto, the public health board monitors tattoo and piercing parlours through regular inspections, though officials say they have yet to come across the practice of scarification, which is considered a "personal service." 

"We inspect (the practice) as part of the Personal Service Settings program. We would follow the same Infectious Prevention and Control principles as any other invasive service," said agency spokesman Kris Scheuer. 

"Toronto Public Health does inspect a number of places for control and to stop the spread of infection," she added. 

McLean, who has practised scarification for decades in Canada and around the world, including Tokyo, London and New York, says prohibition poses more health risks to the public.

"It sends people into the underground to practice on their friends," he says. "That increases the risk for infection or problems." 

Scarification was not always an alternative practice: It has roots in tribal culture, in which members would brand themselves as a rite of passage to either their tribes or the gods. But with the body modification movement of the '80s came a resurgence in scarification, during which fraternity brothers would brand their house letters on their body to symbolize eternal membership.

While it is historically a symbolic practice, McLean says those opting for scarification today typically do it for aesthetic reasons or to gain status. 

"In the past, fraternity brothers didn't care what the scar looked like," McLean said. "It was about brotherhood." 

"Today, (clients) seem to be vainer." 

For clients who are "in it for the right reasons," McLean says the decision to be scarified runs deeper than plain aesthetics. 

"Some people don't want ink or foreign pigments in their body, like from tattoos," he said. "With scarification, the design is from your body only." 

Others, he adds, want an intense, euphoric experience, making the body art all the more important.

"At the end of the day, it's not just about me getting paid," McLean said. "I want it to be mean a lot, to be special."

The Canadian Press    

Health Tip: Stay Safe at the Nail Salon
Published: October 14, 2013 7:21 AM @ HealthDay
 -- Nancyann Rella

Whether you live in a big city or small town, you'll probably find no shortage of nail salons. But before you treat yourself to a manicure or pedicure, find out if health and sanitation guidelines are being met.

Dirty instruments and poor sanitation at some nail salons can put women at risk for diseases such as athlete's foot and hepatitis B and C.

St. Mary's Hospital Medical Center in Green Bay, Wisc., advises taking these precautions:

• Make sure your salon has an up-to-date operating license.
• Don't shave your legs the night before or the day of a salon footbath. Scrapes and nicks can make you more susceptible to infection.
• Check that nail instruments are properly sanitized. Heat sterilization is best. Even better: Bring your own nail tools.
• Wash your hands before a manicure and ask your manicurist to do the same.
• Insist on fresh soapy water for hand or foot soaking.
• Ask the manicurist to push back cuticles instead of cutting them.

Copyright © 2013 HealthDay. All rights reserved. 

Celebrity Diagnosis 

Did Yo-Yo Dieting Cause Tom Hanks' Diabetes?
10/11/2013

By Michele R. Berman, MD

Just "like a box of chocolates. You never know what you're gonna get" when you have Tom Hanks as a guest on your show.

So David Letterman found out when he was talking to Hanks about his upcoming movie, Captain Phillips.When complementing Hanks on his svelter figure, Hanks said:

I went to the doctor, and he said, 'You know those high blood sugar numbers you've been dealing with since you were 36? Well, you've graduated! You've got Type 2 diabetes, young man.'

Hanks went on to say that it is a "controllable" condition and that he is working to "maintain the temple."

Tom Hanks is one of those actors who is well known for the dramatic, voluntary weight gains and losses he has undergone for a number of his film roles:

• Hanks gained 30 pounds to play baseball coach Jimmy Dugan in 1992's "A League of Their Own." 
• He lost 55 pounds playing a FedEx employee on an abandoned island after a plane crash in "Castaway."
• He won his first Academy Award for Best Actor in the 1993 film  "Philadelphia" for which he lost 26 pounds to play a lawyer with AIDS.

A number of media outlets are questioning whether Hanks' diabetes was caused by this degree of weight fluctuation. But Hanks doesn't think that's the main reason. Speaking at a press conference for Captain Phillips on Wednesday, he said:

"Gaining and losing of weight may have had something to do with this because you eat so much bad food and you don't get any exercise when you're heavy."

"But I think I was genetically inclined to get it and I think it actually and goes back to a lifestyle I've been leading ever since I was 7 years old, as opposed to 36."

Weight cycling, also known as yo-yo dieting, is a term  coined by Kelly D. Brownell at Yale University to describe a process whereby the dieter is initially successful in the pursuit of weight loss but is unsuccessful in maintaining the loss long-term and begins to gain the weight back. The dieter then seeks to lose the regained weight, and the cycle begins again.

What is the evidence regarding weight fluctuation and Type 2 diabetes?

As is often the case in topics such as this, the evidence is mixed.

A study by Waringet.al in the American Journal of Epidemiology looked at the association between weight patterns during middle age and the incidence of type 2 diabetes using a subset (n = 1,476) of the Framingham Heart Study original cohort. They conclude that although being overweight or obese was associated with higher rates of diabetes, weight cycling was not associated with a higher incidence of diabetes.  In other words, weight itself was a more important factor than changes in weight.

Furthermore, Stevens et. al, concluded, based on epidemiological evidence, that weight cycling does not lead to an increased risk of mortality.

It has been shown that accumulation of proinflammatory immune cells in adipose tissue contributes to the development of obesity-associated disorders.Emily Anderson, Alyssa Hasty, and their colleagues at Vanderbilt University alternated mice between high- and low-fat diets. They were trying to determine whether weight cycling altered the numbers of immune cells, inflammation, and insulin resistance in adipose tissue. They found that adipose tissue in mice who had been weight cycled do show an amplified T-cell response compared with mice that lost weight without cycling. Weight cycling also impaired systemic glucose tolerance and AT insulin sensitivity.

But there is some good news:Anne McTiernan,et.al. at the Fred Hutchinson Cancer Research Center, found that "a history of weight cycling does not impede successful participation in lifestyle interventions or alter the benefits of diet and/or exercise on body composition and metabolic outcomes."

Cancer biggest killer of Hispanic Texans

Cancers more common among Hispanics were stomach and liver cancer in men and stomach, liver and cervical cancer in women. Such cancers can arise from untreated infections.

Overall mortality from all cancer was lower among Hispanics with the exception of stomach and liver cancer


Cancer biggest killer of Hispanic Texans

More Hispanic Texans die from cancer than any other cause, according to a new report by the Comparative Effectiveness Research on Cancer in Texas research group.

The report documents cancer as the leading cause of death among Hispanic Texans under the age of 76. Only three percent of Hispanic Texans are older than 75.

Texas's Hispanic population has more than doubled since 1990. Texans of Hispanic ethnicity now comprise 38 percent of the state's population.

The findings are published in a September 2013 special issue of the Texas Public Health Journal, available online at http://txcercit.org/.

Based on data from the Texas Cancer Registry, Medicare claims records and state vital statistics, researchers compared rates and trends for cancer in Hispanics to those for non-Hispanic whites in Texas.

Key findings include:

Hispanic Texans are less likely to be screened for breast or colon cancer.

Hispanics have lower rates of new cancer diagnoses for breast, colon and lung cancer.

Of the cancers diagnosed in Hispanics, fewer were in the earliest, most treatable stages – those typically detected through screening. Breast cancer at the most advanced stage was diagnosed at a 12 percent higher rate.

Cancers more common among Hispanics were stomach and liver cancer in men and stomach, liver and cervical cancer in women. Such cancers can arise from untreated infections.

Overall mortality from all cancer was lower among Hispanics with the exception of stomach and liver cancer.

Survival after a diagnosis of cancer is superior for Hispanics compared to non-Hispanic whites.

These findings were based on 10 years of data about the diagnoses of new cancer cases and 21 years of data about cancer deaths.

The CERCIT researchers noted one puzzling contradiction. Even though cancers tend to be more advanced when diagnosed in Hispanics, death rates were lower than in the white population. This phenomenon, known as the Hispanic Paradox, has been noted before by other researchers looking at disease and survival rates across the spectrum. Hispanic Americans tend to survive illness and live longer than white Americans with the same diseases even though the Hispanics have less education, income and access to health care.

Foreign-born Hispanics had lower mortality rates than those born in the United States, according to analyses of regional differences within the state.

The multidisciplinary consortium of CERCIT investigators works on issues related to cancer screening, cancer treatment, post-treatment surveillance and supportive care for cancer patients and survivors. CERCIT is funded by the Cancer Prevention and Research Institute of Texas.

The CERCIT project is led by principal investigator Dr. James S. Goodwin of University of Texas Medical Branch at Galveston and co-principal investigator Dr. Linda S. Elting of the University of Texas MD Anderson Cancer Center. Other project and core lead investigators include Drs. Catherine D. Cooksley, Anthony DiNuzzo, Karl Eschbach, Jean Freeman and Taylor S. Riall of UTMB; Dr. Sharon H. Giordano of MDA; Dr. Vivian Ho of Rice University and Dr. Melanie Williams of the Texas Cancer Registry.

###

The University of Texas Medical Branch
Office of Marketing and Communications
301 University Boulevard
Galveston, Texas 77555-0144
http://www.utmb.edu

ABOUT UTMB HEALTH: Texas' first academic health center opened its doors in 1891 and today comprises four health sciences schools, three institutes for advanced study, a research enterprise that includes one of only two national laboratories dedicated to the safe study of infectious threats to human health, and a health system offering a full range of primary and specialized medical services throughout Galveston County and the Texas Gulf Coast region. UTMB Health is a component of the University of Texas System and a member of the Texas Medical Center.

A New Drug for Diabetes and Fatty Liver Disease?

 A New Drug for Diabetes and Fatty Liver Disease?

Posted on September 3, 2013 by Kristine Novak, PhD, Science Editor

Obeticholic acid (OCA)—an agonist of the farnesoid X receptor (FXR)— increases insulin sensitivity and reduces markers of liver inflammation and fibrosis in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), according to a study published in the September issue of Gastroenterology.

Type 2 diabetes mellitus and NAFLD are components of the metabolic syndrome—a complex disorder characterized by insulin resistance, dyslipidemia, hypertension, and visceral obesity. Although several drugs are available to improve insulin resistance in patients with diabetes, none are currently approved for NAFLD or nonalcoholic steatohepatitis.

FXR is a bile acid receptor expressed in liver, intestine, kidney, and adipose tissue. It regulates many genes involved in bile acid synthesis and transport, lipid metabolism, and glucose homeostasis. FXR also controls glucose metabolism and glycogenolysis in the liver, and peripheral insulin sensitivity in striated muscle adipose tissue. Factors that activate FXR might therefore be used to control diabetes and fatty liver disease.

OCA is a selective agonist of FXR agonist with anti-cholestatic and hepato-protective properties. In preclinical studies, OCA was found to increase insulin sensitivity, regulate glucose homeostasis, modulate lipid metabolism, and have anti-inflammatory and anti-fibrotic effects in the liver, kidney, and intestine.

Sunder Mudaliar et al. tested the effects of OCA in a Phase 2 study of 64 patients with type 2 diabetes mellitus and NAFLD. Patients were given 25 or 50 mg OCA or placebo, once daily for 6 weeks. The hyperinsulinemic-euglycemic clamp technique was used to assess insulin sensitivity. Various markers of tolerance and safety, and markers of FXR activation (increased plasma levels of FGF19 and reduced bile acid synthesis), were assessed.

Mudaliar et al. found that OCA increased hepatic and peripheral insulin sensitivity (by about 25%), whereas insulin sensitivity decreased by about 5% in subjects given placebo. OCA produced a significant decrease in levels of γ-glutamyltransferase—a marker of fatty liver disease that is a risk factor for development of diabetes in patients with NAFLD.

OCA also caused patients to lose weight (see below figure).

 

 

 

Weight loss among patients given 25 mg or 50 mg OCA, compared with placebo.

 

Serum levels of FGF19 increased, whereas levels of C4 and endogenous bile acids decreased, indicating FXR activation in patients given OCA. The authors state that this was the first phase 2 clinical trial of an FXR agonist.

In an editorial that accompanies the article, Saul Karpen says that these findings herald a new era, in which bile-acid–based strategies are used to control metabolic signaling and treat liver and other types of diseases.

However, Karpen points out that the observed increases in low-density lipoprotein, reductions in high-density lipoprotein, and lack of change in alanine aminotransferase or liver fibrosis scores in subjects receiving OCA were notable and require further analysis. Mudaliar et al. did not perform liver biopsies, so they were not able to determine the degree and effect of OCA on liver histology.
Karpen says that studies with a larger sample sizes and more analyses are needed before conclusions can be made.

More Information on Fatty Liver Disease:

• The American Liver Foundation
• The Mayo Clinic Website on NAFLD
• The NIDDK Website on Nonalcoholic Steatohepatitis

Read the article online.
Mudaliar S, Henry RR, Sanyal AJ, et al. Efficacy and safety of the farnesoid x receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013;145:574–582.e1.

Read the accompanying editorial.
Karpen SJ. Do therapeutic bile acids hit the sweet spot of glucose metabolism in NAFLD? Gastroenterology 2013;145:508–510.

http://agajournals.wordpress.com/





Coffee May Offer Real Benefits to the Liver

Source: Clinical Care Options - ClinicalThought

 

Coffee May Offer Real Benefits to the Liver

 

Mark S. Sulkowski, MD

8/13/2013  More from this author

 

 

Mixed Realities of Alternative Therapies for Hepatitis
Approximately 50% of patients who have failed initial therapy for hepatitis C take some form of alternative or complementary therapy. In my practice, I’m frequently asked by these and other patients: “What can I do to help my liver?” Most have heard of, have taken, or are taking milk thistle, licorice root, ginseng, schisandra, and/or thymus extract—with milk thistle being the most common. Not all alternative therapies are created equal and there are few randomized controlled trials to guide clinicians seeking answers. For instance, the active ingredient in milk thistle, silymarin, has been evaluated and generally found to provide little or no clinical benefit to the liver. In fact, a recent study found that even at higher-than-usual doses, silymarin failed to reduce HCV RNA or ALT levels more than placebo.

There is, however, a growing body of research supporting a beverage I’d wager a majority of you have enjoyed today: coffee.

The Coffee Alternative
Curiously, patients who will spend up to $30 a day or more for milk thistle and its extracts or ingest unproven therapies of varying quality are skeptical about the idea that drinking coffee can actually be good for you. Real and perceived cardiovascular and other effects of coffee have led many patients to view coffee as “unhealthy.” But the reality is that coffee consumption has been linked to a number of potential benefits – lower risk of diabetes, dementia and, yes, liver disease. Coffee contains more than 1000 compounds; one or more of which is responsible for the benefit that has been linked to coffee intake on liver disease in patients with alcoholic and viral hepatitis. Benefits include decreases in markers of liver disease progression and reductions in the risk for fibrosis and hepatocellular carcinoma.

Epidemiologic studies have suggested that there is a cause and effect associated with coffee intake and its benefits on the liver. These findings are supported by the few randomized controlled trials available. In one study comparing patients infected with hepatitis C, those who drank 3 cups of coffee per day or more received the greatest benefit. In order to maximize the effects of the coffee some (but not all) studies suggest that caffeinated coffee may be better for the liver than decaffeinated coffee. However, it seems that caffeine itself does not appear to have a beneficial effect.

There is also an interesting conundrum. Not just any caffeinated beverage will do. For instance, studies evaluating the effect of green tea – popularly considered a “healthier” source of caffeine – have not shown the benefits associated with filtered, caffeinated coffee. This lack of benefit appears to be true for sources of caffeine other than green tea as well.

Lastly, coffee should ideally be prepared by filtration because filtering removes cafestol and kahweol, two substances found in coffee that may increase serum cholesterol.

So, What Do We Tell Our Patients?
Simply put: moderation and common sense are my watchwords. Investigate what you are taking. What’s in it, by whom and how is it manufactured? Is there any literature supporting its use, or recommending against it? Natural, alternative, and complementary substances may provide benefits, but there are far too many tragic stories in the scientific popular press to proceed without caution. For example, in the late 1990s, several cases were reported of previously healthy patients who presented with a toxic serum digoxin level after the ingestion of botanical dietary supplements due to contamination of the natural product.

I support my hepatitis patients’ interests in adding natural products to a “liver healthy” lifestyle which include no alcohol, daily exercise and maintaining a normal body mass index. So, I discuss the data supporting moderate coffee intake of 2-3 cups per day in addition to abstaining from alcohol use, achieving or maintaining a normal BMI by eating a low fat, low cholesterol diet, and taking a curative hepatitis therapy. Of course, when patients are taking antiviral therapy, I recommend that patients limit their intake of all complementary and alternative therapies to avoid the potential for drug-drug interaction that can undermine the efficacy of treatment or increase the risk of toxicity. Despite this pragmatism, many of my patients are surprised by my willingness to accept a nontraditional adjunct to care, but my acceptance is based on data from respected sources. What could be more traditional than that?

Your Thoughts?
I am interested to hear your own experiences with patients’ use of alternative or complementary therapies for hepatitis. How do you approach their use by patients and how many of your patients use them? Do you recommend any in particular or, conversely, do you recommend against them altogether?

Topics: HBV - Treatment, HCV - Treatment

 

Related: Impact of Coffee on Liver Diseases: A Systematic Review
In this August 2013 systematic review offered online at Liver International, researchers investigated several studies assessing the effect of coffee on liver disease.
The abstract, introduction and discussion "only" are provided on the blog, here,  The complete review article is available in a PDF format published in Liver International found in Accepted Articles. In addition, posted over at Healio is an easy to read summary of the article:Studies indicate protective effects of coffee for liver disease  

 

Coffee and Tea May Contribute to a Healthy Liver 
Surprise! Your morning cup of tea or coffee may be doing more than just perking you up before work.

Behind the Headlines - Can excess coffee intake lead to an 'early grave'?
“More than four cups of coffee a day increases the risk of an early death,” The Daily Telegraph warns, on the basis of a large, long-term – but rather flawed – study.

Caffeinated drinks may be good for the liver
The study's researchers show that caffeine reduces fat content within the liver and "stimulates β-oxidation in hepatic cells and liver via an autophagy-lysosomal pathway."
Paul Yen, associate professor at Duke NUS, says: This is the first detailed study of the mechanism for caffeine action on lipids in liver and the results are very interesting. Coffee and tea are so commonly consumed and the notion that they may be therapeutic, especially since they have a reputation for being 'bad' for health, is especially enlightening."


 

Impact of Coffee on Liver Diseases: A Systematic Review

Impact of Coffee on Liver Diseases: A Systematic Review

In this recent systematic review offered online at Liver International, researchers investigated several studies assessing the effect of coffee on liver disease.

The abstract, introduction and discussion "only" are provided below, the complete review article is available online in Liver International found in Accepted Articles. Download the PDF here.  

 

In addition, posted today over at Healio is an easy to read summary of the article: Studies indicate protective effects of coffee for liver disease

 

Impact of Coffee on Liver Diseases: A Systematic Review

 

Liver International

Accepted Article
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record.

Please cite this article as doi: 10.1111/liv.12303
This article is protected by copyright.
All rights reserved.

Received Date : 03-Jun-2013
Revised Date : 05-Aug-2013
Accepted Date : 05-Aug-2013

Article type:
Reviews Impact of Coffee on Liver Diseases: A Systematic Review

Sammy Saab, MD, MPH, AGAF, 1,2 Divya Mallam, MD, 3 Gerald A. Cox II, BA, 2 Myron Tong, PhD, MD 1,2,4 Departments of Medicine 1 and Surgery 2 , David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California, The Department of Medicine, Harbor-UCLA Medical Center 3 , Torrance, California, and the Huntington Medical Research Institutes, Pasadena, California

Accepted manuscript online: 12 AUG 2013

Abstract
Coffee is one of the most commonly consumed beverages in the world. Its health benefits including improved overall survival have been demonstrated in a variety of disease states. To examine the association of coffee consumption with liver disease, a systematic review of studies on the effects of coffee on liver associated laboratory tests, viral hepatitis, nonalcoholic fatty liver disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed.

Coffee consumption was associated with improved serum gamma glutamyltransferase, aspartate aminotransferase and alanine aminotransferase values in a dose dependent manner in individuals at risk for liver disease. In chronic liver disease patients who consume coffee, a decreased risk of progression to cirrhosis, a lowered mortality rate in cirrhosis patients, and a lowered rate of HCC development were observed. In chronic hepatitis C patients, coffee was associated with improved virologic responses to antiviral therapy. More over, coffee consumption was inversely related to the severity of steatohepatitis in patients with non-alcoholic fatty liver disease. Therefore, in patients with chronic liver disease, daily coffee consumption should be encouraged.

Introduction Only

Coffee is a commonly consumed beverage worldwide. In the United States, over 50% of Americans consume coffee on a daily basis. 1 The commonly cited reasons for coffee consumption are its stimulatory effects, taste and aroma. 2, 3 Recent data suggests that coffee consumption may have health benefits in a number of medical ailments. Long-term coffee drinkers may be at a decrease risk for type II diabetes, symptomatic gallstone disease, Parkinson’s disease, heart disease and stroke. 2, 4-7 Moreover, coffee consumption is associated with decreased all-cause mortality. 8, 9 In a recent analysis of the NIH- AARP Diet and Health Study data, a dose-dependent inverse association between coffee consumption and total mortality was described. 9 Men and women who drank 6 or more cups daily had a 10% and 15% decreased risk of death, respectively.

Chronic liver disease is major health burden in the United States, ranking 12 th amongst the leading causes of death and accounting for over 30,000 deaths in 2009 alone. 10 Chronic liver disease affects approximately 15% of the U.S. population and is a major economic strain through direct healthcare expenditures as well by indirect costs related to lost income due to premature death or disability. 11, 12 Treatments for liver disease is often viewed with suspicion, and many patients often seek alternative therapies for their liver disorders. 13-1

Given the potential health benefits in a variety of medical conditions and its impact on survival, we explored the impact of coffee consumption on patients with liver ailments. A systematic, comprehensive review on the interaction between coffee consumption and liver associated tests, viral hepatitis, nonalcoholic Fatty Liver Disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed and is presented herein.

Discussion Only

Coffee is one of the most commonly consumed beverages in the world. 2 There is increasing evidence that daily consumption of 2-3 cups of coffee has significant health benefits. Not only has coffee been associated with a decrease in a number of liver diseases, but its consumption may also decrease mortality. 9 Thus, coffee appears to have ‘hepatoprotective” health benefits. 64 Coffee is composed of over one hundred compounds, any of which could be responsible for its beneficial effects. 46 It is possible not one compound in particular, but the synergistic effect of multiple compounds, which provides the health benefits described.

Not all types of coffee may be beneficial in liver disease. Numerous studies have shown a hepatoprotective role for filtered coffee, and a potentially deleterious effect for unfiltered coffee. 24, 65 It was postulated that this difference is due to the presence of kahweol and cafestol, which are caffeine diterpenes that are released from ground coffee beans but removed by paper filters. 65, 66 Moreover, another study found that espresso coffee had no beneficial effect on liver disease, particularly in NAFLD. 46 In the U.S, filtered coffee is one of the main types of coffee consumed, whereas in Europe, espresso coffee is more commonly consumed. 46 Anty et  al postulated that perhaps espresso coffee was not found to be beneficial in NAFLD because of the sucrose added to the coffee. 46 Sucrose is composed of glucose and fructose, and fructose has been associated with increased severity of hepatic fibrosis in NASH. 7

There are a number of proposed mechanisms for the hepatoprotective effects of caffeine (Table 6). In rat studies, methylxanthine caffeine has been implicated in the hepatic fibrinogenesis pathway by (1) downregulating transforming growth factor beta-1 (TGFB-1)-induced connective tissue growth factor (CTGF) production in hepatocytes via promotion of breakdown of SMAD2 (a TGF-B effector protein), (2) inhibition of SMAD3 phosphorylation, and (3), by upregulation of the PPAR-gamma receptor. 67 The antioxidant hepatoprotective effects of coffee may also be induced by UDP glucoronosyltransferases (UGT1A). 68 Caffeine has also been implicated to have antifibrotic effects via its influence on hepatic stellate cells (HSC) through inhibition of focal adhesion kinase (FAK) and actin synthesis, stimulation of HSC apoptosis, induction of intracellular F-actin and cAMP expression, and via inhibition of procollagen type 1C and alpha-smooth muscle actin (SMA) expression. 69

Caffeine as well as cafestol and kahweol may have anticarcinogenic effects by upregulation of (ARE)-regulating signaling (Table 6). 70, 71 The antioxidant-responsive element (ARE) sequence plays a key role in carcinogenesis as it has been found on the promoter of numerous genes involved in detoxification processes. Furthermore, animal models and in-vitro studies indicate that kahweol and cafestol may deregulate enzymes involv ed in detoxification of carcinogens. 72, 73 These compounds also induce glutathione-S-transferase (GST) and gamma-glutamylcysteine synthetase (GCS), leading to protection against mutagenesis, and inhibit N-acetyltransferase. 75

Although caffeine is a major component of coffee, studies evaluating non-coffee caffeinated sources have revealed inconsistent evidence of hepatoprotective effects. 29, 26 With regards to tea consumption, studies have found no statistically significant association between tea intake and risk of cirrhosis, 30, 29 death from cirrhosis, 32 chronic liver disease, 28 HCC, 54 or death due to HCC. 77, 60, 52 Most studies did not specify which type of tea participants consumed. However, Inoue et al studied green tea and Kurozawa et al studied green, black, and oolong tea. 56, 60

Coffee preparation methods include filtered, unfiltered, and espresso, and can also vary in its roast profile (medium vs. dark). Differences in prep aration method (filtered, unfiltered, espresso) as well as type of roast play a role in the composition of coffee. Filtered coffee does not contain cafestol and kahweol; however, filtration of coffee better preserves chlorogenic acids than the barista method of espresso preparation. 46 The various degrees of roast refer to the internal bean temperatures found during roasting. Darker roasts have had higher roasting temperatures. Caffeine content also varies between types of coffee [generic brewed coffee (95-200 mg per 8 oz), espresso (40-75 mg per 1 oz), generic instant coffee (27-173 per 8 oz)].

There are numerous limitations when interpreting the studies regarding the health benefits of coffee. Many of the larger studies, including those by Freedman et al, Modi et al, Hu et al, and Molloy et al, did not necessarily account for differences in socioeconomic status or other dietary factors. 38, 27, 57, 45 Although one would argue that perhaps patients who had greater coffee intake were likely healthier, Freedman et al found that coffee drinkers tended to have poorer overall health (p= 0.29) and vitality scores (p=0.018) compared to non-coffee drinkers. In addition, participants who drank coffee may have had higher cigarette use and alcohol consumption. 38 Also, many studies collected data on coffee intake at only one time point, thus, the coffee intake noted may not have accurately reflected participants’ intake over time. 26, 30, 32- 34 If it is assumed that caffeine is indeed responsible for the hepatoprotective effects of coffee, then another potential limitation is the variation of caffeine content of coffee within and among coffee shops. 77 Furthermore, many studies failed to define coffee cup size. 22, 26, 29,32 Although it is clear that coffee intake has hepatoprotective effects, the lack of standardization of coffee cup size amongst various studies leads to ambiguity regarding how much coffee intake is necessary for these effects.

Our study is limited in that it is based mostly upon observational studies with inherent biases, including recall bias in retrospective studies, as well as selection bias and unmeasurable confounding factors amongst all non-randomized controlled studies. 79 Cross-sectional studies, such as NHANES III, are limited in that they cannot establish a temporal association between coffee intake and study findings. 26,79

Numerous epidemiological studies suggest that consumption of approximately 3 or more cups of coffee daily will reduce the risk for and severity of hepatotoxicity due to a variety of underlying pathologic processes. While the aforementioned studies provide comp elling evidence to suggest that coffee is useful as an alternative medicine in the treatment of the most common types of liver disease, blinded randomized controlled trials must be performed to provide evidence for causation, and to eliminate confounding variables and various types of bias inherent in cross-sectional, cohort, and case- control studies. Additional animal and cell culture studies are also warranted to further elucidate the biochemical basis for the potential beneficial effects of coffee in liver disease patients.

WHAT IS CURRENT KNOWLEDGE
• Coffee is one of the most commonly consumed beverage.
• The beneficial impact of coffee consumption on liver related complications are not well understood or appreciated.

WHAT IS NEW HERE
• Liver enzymes are lower in patients who regularly consume coffee
• Coffee consumption associated with decreased hepatitis C fibrosis progression.
• The risk of hepatocellular carcinoma is decreased in consumers of coffee.

Full text available online in Liver International
Download PDF here....