December 5, 2013

Docs won't rush to new Gilead HCV pill: poll

Provided by MM&M


DECEMBER 05, 2013


On the eve of the FDA's pending decision on Gilead's sofosbuvir, a MedLIVE PULSE survey—conducted by WorldOne Interactive for MM&M of 48 US hepatologists—suggests doctors may not be ready to embrace the drug for all their HCV patients.

When compared against the current HCV landscape, their choice looks clear. Findings show that 88% of the 48 docs polled have "warehoused" patients in anticipation of the drug's approval rather than use already available treatments like Vertex's Incivek or Merck's Victrelis.

However, the majority of hepatologists—83% (40 out of 48)—told researchers they would continue to warehouse their GT-1 patients in anticipation of an all-oral formulation, rather than immediately treat these patients with sofosbuvir and injected antivirals.

Barring any bombshells, approval seems highly likely this month. In an investor note, Leerink Swann analyst Alice Avanian pegged sofosbuvir's approval chances at 80% for its upcoming PDUFA date on December 8. That estimate comes one week after EU advisors also recommended the drug's approval, following in the footsteps of their US counterparts in October.

Sofosbuvir's initial application promises a treatment upgrade for patients with the genotype 2 and 3 forms of the virus. For those with the GT-1 form, the drug will initially require use with interferon (an injected antiviral that can produce flu-like symptoms). And GT-1 is the most prolific subset of HCV infections in the US.

An all-oral regimen for use in that patient subtype consisting of sofosbuvir and ledipasvir, an NS5A protease inhibitor, is not likely to come until later. Current estimates suggest an oral formulation from Gilead for GT-1 will be available by the end of 2014, and another option from Merck about 18 months further down the line.

The majority of liver specialists also said price could play a significant factor in the treatment's uptake. A total of 66% of polled doctors said sticker shock could dampen enthusiasm for a new therapy that could possibly cost between $60,000 to $100,000.

Janssen's simeprevir, approved last month, carries a price tag of roughly $66,360 for a three-month course.

Patients, too, appear ready to greet new treatments, although they may not know what they're embracing. When asked, only 11 of 42 doctors—or 26%—said that patients inquire specifically about sofosbuvir.

In the WorldOne survey, one doctor noted, “Most of my patients do not know sofosbuvir by name. My patients only know that there will soon be ‘better' drugs for hepatitis C and that perhaps in a couple of years, interferon will not be needed,” and that there are “frequent questions, but little facts.”

Another added, “My very knowledgeable patients know about sofosubivr and that it is likely to be approved within days. Those that know about it are very hopeful.”

That lack of name recognition suggest awareness and education around this new wave of treatments will be necessary, with other HCV treatments on the horizon.


The Faces of Hepatitis C

The Faces of Hepatitis C

You are a doctor or a nurse--You are a fifth grade grade teacher

Your skin is white or brown or black--you are Mecxican or Asian, Caucasian,or African American

You are very old, have grandchildren,near the end of your golden years

You are middle-aged--children grown and gone-ready to "enjoy" your life --

You are a young mother with a small child-a young father trying to provide for his family--

You are a teenager--waiting for proms,boy or girlfriends, your first kiss dreaming of college and a car of your own--

You are a newborn lying in your mother's arms

YOU are the Faces of Hepatitis C

I may not recognize you as you pass me on the street or in the store where I shop or the church where I worship, but you are there

The Faces of Hepatitis C

My heart cries out for you,for what fate has given you--it was not your fault--it was just meant to be

My heart swells with pride for you--your courage,your faith—you have been asked to keep going when others would have given up

You wait anxiously for another loving person to give you the "The Gift of Life"

The gift of their own liver at the end of THEIR life. I am filled with love for each of you--my brother--my sister and those I have met and those I will never know--

You see--I am one of those faces

The faces of Hepatitis

Given by God...written by Selles Dole

Selles lost her battle with HCV November 29, 2008

May You Always Sleep In The Arms Of Angels


I'm coming out ... A Poem by Nancy Burklin

By Nancy Burklin

If someone were to tell you
they had cancer to treat
would you hug them tight
or run away down the street?

There are so many chronic illnesses
that society doesn't blink
but if I tell you I have one
what would you think???

Would you run from or to me,
or talk behind my back?
ask me in a mean voice
"How did you get THAT???"

My friends will understand me,
others will fear my situation,
Others may walk away
others will show dedication...

Don't judge me or shun me
just try to understand
I have to find a way to beat it
will you help me if you can???

I can't keep this in the closet
I can't do this alone,
I need your love and support
not left out on my own.

I have Hepatitis C
my liver is fighting mad
my body is in turmoil
that's why I've been feeling bad.

Much like chemo to cancer
my treatment will be mean,
there will be good days
some days I'll want to scream.

My body will be under attack
from the meds that I will take
but I want to be well and live
of that make no mistake.

If you have questions, ask them
please just don't assume
that if you hang around me
you will get this too.

I don't have all the answers yet
I have to take it day to day
But I'm asking you my friends
please don't walk away.

If you think you can't handle it
that's ok too
I don't need negativity...move on
if that's what I'll get from you.

I don't need to be scolded
don't talk down to me please
I've done that to myself already
I'm down on my knees.

I can't change the past
or make this just disappear
but to fight this fight
I need my loved ones right here.

Peace of mind and love of life
that's what will get me through,
This is where I'm at,
I had to share it with you.

Nancy 12-04-13

I wrote this for my friends who are going through life changing battles...who are "afraid" of what people will think.  We HAVE to surround ourselves with "positive" and we don't need the stress of "hiding" to hinder our chances of beating this thing. The treatment has many side effects and if you read up on it you will see that it IS like chemo...mood changing, body aching, rashes, insomnia, not to mention what it will do to blood counts causing weakness, muscle spasms, weight loss, hair loss, etc... You cannot catch it just by being in the same room with a person infected, precautions are a must of course but an infected person doesn't have to live in seclusion or a hermit life. We are human beings and worthy of living like everyone else.  Society is not nice to people like us we shouldn't have to serve a life sentence for bad choices we made in the past (and many have NEVER done drugs...) You are told growing up that for every decision you make in life there are consequences...this is true. So, by me being open with you and sharing this with you maybe just maybe someone will be saved from this fate...and people will be educated about Hepatitis and not so quick to judge or push it under a rug. It's real and there are sooooo many people who have been fighting it for years and many who have won the battle. So if a friend or loved one opens up to you about this...please listen, love and support them WIN!!!!!!!!   Nancy Burklin

Living with Hepatitis C and Its’ Effects

December 05, 2013

Hi everyone, I'm 30 years old I'm from a beautiful small country where we have a big problem with HCV. We are two million people but is sad that statistics show 20% of population here have HCV and  I'm one of them. I have chronic HCV genotype 3 more then 13 years, last year had a biopsy and results were Cellular Fibrosis in early stage. Doctors put me on waiting list and I was waiting for one year tomorrow for the first meeting with my doctor. Now I have to take another test and if all is ok I will start with therapy with Interferon with ribivarin. I'm a little scared but with your support I'm sure gonna help me a lot thank you.

Now for my symptoms: For 10 years I did not have any symptoms but for the last three years I have been living in hell because of my illness so I decided to go in hospital. I see and realize that this virus is dangerous and if I not have the symptoms I'm sure that I would not ask for help? First start with alopecia, I lost a lot of my hair but am lucky for my hair again grew. Then my arms become swollen but this symptom was gone after a month. Then I started to itch, my skin on my legs and is like this is every day. For the whole year I felt like something eat me inside in my body. I fell pain in right side of abdomen energy is zero and nothing helps me.

For last two mounts I take silimarin, aronija, blueberry and other tea but symptoms is here they are not gone? Another symptom: my lymph nodes on my neck are swollen and I have white tongue and small bums on soft pilate in my mouth. I have red spots on my arms like spider webs on my skin when I  ask for help in hospital my doctor did some tests: the test of HIV, hepatitis B, syphilis, and immune test yet all was OK?

I don't have any virus only hepatitis C and doctors told me the most symptoms is not case by HCVhcv but is something else causing them? This answer confuses me and now I'm scared to start with standard therapy. Please tell me if somebody have similar symptoms like mine. That is my story and I wish all the best to all people I wish to we be healthy and happy. We are happy because have cure for hepatitis C and the new therapy is the best from God thank you.



Jerome Alex: Where to start? At my birth … Part 2

December 05, 2013

……. So the night before I'd been up all night with a friend, snortin, drinkin' smoking and then taking valium to level out. All was well until my friend who I'd known for years started getting very negative and was saying he may as well be dead and got into suicidal mode….it was extremely distressing to me: I loved hi m and was so messed up my self, just the thought of death was painful in my mind. Recently my boyfriend and band mate left me me due to the escalating drug and booze problem I knew I was in bad shape… I could see a tree with my name on it.

AS i mentioned when I awoke the next morning, I was soooooo hung over and sick but I had to work cleaning a house so I went.

The lady I worked for came home for lunch and told me she was going to AA so I asked could i go along.That was IT the turning point.

June 18th 1991. I have never looked back.

The hang over lasted for 6months and by then I decided I's best get a check-up. That's when I found out I had non-A/non-B hep, aka Hep C. At that time there was not treatment per-se and they told me to go home and get a check up every year. So there I went.

Meanwhile, so grateful that I had stopped my bad ways and was on my new path. It likely saved my life. I did not have insurance or a lot of family
so I muddled thru for the next  years until 2002, when I started looming into options again. At that time I started wondering about how to get cured.

I was a lucky one, and was not real sick from the virus but I could tell it was affecting me.

In 2004 at a gig I met someone who had just been thru a free treatment in Texas so I followed up and got some help thru a liver program and was
approved for tx. I had no idea what was in store. I had not been in AMA mode for yeas, being a musician who was poor. The good news was I cleared the virus super fast- the bad news? I started getting sick and sicker unto incapacitated. I ended up on the couch barely being able
to move.

Since I lived alone and was miles from town it was pretty rough- but I kept at it because I had cleared and I was gonna get thru!

I lost my ability to work and was really scared. Some how I made it thru the year and all the way was virus free-

After 6 months I went back for SVR test and was relapsed. The next day I started again: interferon + riba. It was pretty awful. sick sick sick lost 30 lbs. - couldn't eat. couldn't sleep couldn't just couldn't. it was at the time i got the idea to start a charity to help others in my condition get help.
(When ya can't work, something's gotta give). I again, had swift clearance- only to fail again. Round 2. Luckily on this round some friends took me and watched out for me.

So it I am one of the ones who is still waiting; but not to take SOC again- I must be allergic- and relish every day right now that I can function!

TO be cont'd.

Also See: Jerome Alex: Where to start? At my birth …

Soaring Hepatitis C Drug Prices Make Cures Costly

Provided by The Motley Fool

By Todd Campbell | More Articles
December 5, 2013 | Comments

The next wave of innovation is bringing new hope for better outcomes to hepatitis C patients. But it's also bringing higher costs.

Prices moved up substantially when Vertex (NASDAQ: VRTX ) and Merck (NYSE: MRK ) launched their highly anticipated Incivek and Victrelis in 2010, respectively. And those prices are likely to head even higher when Gilead (NASDAQ: GILD ) and Johnson & Johnson(NYSE: JNJ ) launch Sofosbuvir and Simeprevir.

Setting the stage for higher prices

Developing biologics isn't cheap. It takes considerable time and money to usher them through trials and commercialization. As a result, it wasn't surprising to see Vertex price its Incivek at $49,000 for the 12-week course of treatment when it reached market back in 2011. That price was well above the $15,000-$20,000 patients were paying for prior-generation treatments interferon and ribavirin. Merck's Victrelis carried a similarly higher price tag -- as much as $48,000 for the longest course of treatment.

Those high prices, coupled with pent-up demand from doctors warehousing patients, allowed Vertex's Incivek to become the fastest drug in history to reach $1 billion blockbuster status.

Rising tide of margin friendly drugs

Fast-forward to today, and Incivek and Victrelis are yesterday's news. If approved on its Dec. 8 PDUFA date, analysts estimate Gilead's Sofosbuvir could launch with a price of up to $100,000 for a twelve week treatment. 

Simeprevir, which will be sold as the branded drug Olysio, is expected to cost roughly $67,000 for a 12-week course of treatment.

Similar to the warehousing of patients ahead of Vertex's Incivek and Merck's Victrelis, doctors seem to have been holding off on treating patients this year, too.

Gilead hopes that's true, because the combination of a larger initial patient pool and its six-figure pricing will go a long way toward justifying the company's $11.2 billion purchase of Pharmasset, and its Sofosbuvir, back in early 2012.  It will also help offset costs tied to ongoing trials, which are evaluating Sofosbuvir in various combinations and as a stand-alone treatment.

Johnson is hoping the dynamic pays off for Olysio, too. But sales of Olysio may be more muted than for Sofosbuvir. Olysio, while a very good drug, appears to have a disadvantage against Sofosbuvir based on the FDA panel review in October. That review highlightedOlysio's less than compelling cure rate in patients with the Q80K polymorphism. Unfortunately for Johnson, Q80K is found in 48% of hepatitis C genotype 1a cases -- the most common genotype found in the United States.

Battling for market share

Gilead and Johnson will soon face a flurry of competition as other hepatitis therapies move through trials, suggesting the market could become very crowded over the coming two years.

Vertex is working on an oral drug follow-up to Incivek. However, Vertex is wrestling with delays tied to the FDA's partial halting of a mid stage trial of VX-135 in July. In that trial, the highest dose of 400 mg was deemed too toxic for patients.

Merck also hopes its MK-5172 can make its way to market as a successor to Victrelis. In a small patient population, MK-5172, when combined with fellow candidate MK-8742, produced between a 96% and 100% cure rate during a Phase 2 trial. That was good enough for the FDA to grant the combination coveted breakthrough status.

AbbVie (NYSE: ABBV ) , the drug company spun off by Abbott Labs earlier this year, is also in the hunt. AbbVie is in the final stages of Phase 3 trials for its oral hepatitis C challenger and the company hopes a successful launch can diversify it away from its mega blockbuster Humira, which generates more than 50% of AbbVie's sales. The company recently announced that it hopes to file for FDA approval of its three-drug combination therapy in Q2, 2014.

And Bristol Myers (NYSE: BMY ) shouldn't be counted out, either. Bristol made a splashthis fall when it announced it's likely to win approval for its oral hepatitis C drug in Japan. If so, Bristol will be the first of all of these competitors to tap into a very large and important market.

Seeking the grail

The goal of all these competitors remains a single-dose oral treatment that doesn't require being combined with ribavirin or interferon -- two drugs that cause discouraging side effects in patients.

Gilead, Johnson, and AbbVie have ongoing studies that eliminate the use of those drugs. But Bristol Myers is farthest along in erasing interferon and ribavirin from treatment. Bristol's combination therapy of daclatasvir and asunaprevir planned for Japan doesn't rely on either of them.

Regardless, the launch of Olysio and Sofosbuvir and potential launches from Bristol and AbbVie suggests you should pay a lot of attention to market share over the coming year, because these high-priced drugs are likely to generate billions in revenue.

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Significant differences in clinical outcomes between HIV-hepatitis C virus coinfected individuals with and without injection drug use history

2 January 2014 - Volume 28 - Issue 1 - p 121-127
doi: 10.1097/QAD.0000000000000020
Epidemiology and Social: Concise Communications

Cescon, Angelaa; Chan, Keitha; Raboud, Janet M.b,c; Burchell, Ann N.c,d; Forrest, Jamie I.a; Klein, Marina B.e; Loutfy, Mona R.c,f,g; Machouf, Nimah; Montaner, Julio S.G.a,i; Tsoukas, Chrise; Hogg, Robert S.a,j; Cooper, Curtisk


Objective: Studies focusing on HIV-hepatitis C virus (HCV) coinfected individuals without a history of IDU are limited. It is plausible that poorer clinical outcomes in HIV-HCV coinfection are due to factors associated with IDU, not from HCV itself. This study compares HIV treatment outcomes and survival between HIV-HCV coinfected individuals with and without IDU history.

Design: Observational cohort study.

Methods: We analyzed data from a multisite Canadian cohort study of HIV-positive individuals initiating combination antiretroviral therapy (ART) after 1 January 2000. This analysis was restricted to 1254 participants with HCV coinfection and known IDU history. Cox proportional hazards regression was used to evaluate time from ART initiation to virologic suppression (two consecutive measures <250 copies/ml) and CD4+ cell count recovery (+100 cells/μl). In order to account for loss to follow-up (LTFU), competing risk analysis was used to evaluate time to death.

Results: A total of 1254 participants (31% women) were included. During a median follow-up time of 3.8 years (interquartile range = 2.1–6.2), 217 deaths were reported and 148 participants were LTFU. In adjusted multivariable analysis, individuals with IDU history were significantly less likely to achieve virologic suppression [adjusted hazard ratio (AHR) = 0.78, 95% confidence interval (CI) = 0.64–0.95]; marginally less likely to have CD4+ cell count recovery (AHR = 0.82, 95% CI = 0.66–1.00); and had a significantly higher risk of death (AHR = 2.15, 95% CI = 1.25–3.70).

Conclusion: IDU history independently elevates risk for poorer clinical outcomes, separate from HCV coinfection. HIV-HCV coinfected persons are not homogeneous in characteristics or outcomes, suggesting care should be taken during statistical analyses if attributing poorer HIV-specific outcomes solely to HCV coinfection.


Liver Transplant Survival Rates Lower in Black than White Pediatric Patients

Liver Transplantation

More Press Releases in:
Medicine & Healthcare, Wiley-Blackwell

Press Release

December 02, 2013

Novel research reveals racial and socioeconomic disparities among pediatric liver transplant patients. Findings published in Liver Transplantation, a journal of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, indicate that graft and patient survival was higher in white children than minorities.

For patients with end-stage liver disease (ESLD) the only treatment option for survival is liver transplantation. Studies show that over the last 30 years pediatric patient survival, at one year following liver transplant, is 90% compared to 70% prior to 1980. Experts suggest that as survival rates improve, understanding racial and socioeconomic differences in pediatric populations are important factors to consider for overall health status.

“Little is known about the impact of race, ethnicity and socioeconomic status disparities on outcomes after liver transplantation among pediatric and adolescent recipients,” explains first author Rekha Thammana, MD of Emory University Department of Medicine in Atlanta, GA. “Our study is the first to investigation the impact of race and socioeconomic status on graft and patient survival among white and minority children.”

Researchers included 208 liver transplant recipients, aged 22 or younger, who were transplanted at Children’s Hospital of Atlanta between January 1998 and December 2008. Participants were followed through November 2011. Data from the United Network for Organ Sharing (UNOS) on transplant outcomes and donor characteristics was linked with Georgia Transplant Foundation financial aid data to examine the contribution of socioeconomic status to the observed racial disparities.

Results show that 51% of transplant recipients were white, 35% were black and 14% were other races or ethnicities. At 1, 3, 5, and 10 years following liver transplant the graft and patient survival was higher among white children compared to the minority children. The 10-year graft survival was 84% for white, 60% among black and 49% for the remaining minority patients. Patient survival at 10 years post-transplant was 92%, 65%, and 76% among whites, blacks, and other races, respectively.

Further analyses show that graft failure and mortality rates remained higher among minority groups compared to white children after accounting for differences in demographic, clinical, and socioeconomic factors. “While our study determined differences in post-transplant outcomes between minority and white pediatric liver transplant recipients, we were unable to fully explain the reason for these disparities,” concluded senior author Rachel Patzer, PhD, MPH with the Division of Transplantation at Emory University. “Further investigation of the reasons for racial and ethnic differences, particularly on a national level, is necessary to indentify interventions that may help reduce disparities in pediatric liver transplantation.”


High intensity focused ultrasound, liver disease and bridging therapy

World J Gastroenterol. 2013 November 21; 19(43): 7494–7499.

Published online 2013 November 21. doi:  10.3748/wjg.v19.i43.7494

PMCID: PMC3837248

Luigi Mearini


High-intensity focused ultrasound (HIFU) is a non-invasive modality that uses an extracorporeal source of focused ultrasound energy. This technique was introduced by Lynn et al and is able to induce coagulative necrosis in selected tissues without damaging adjacent structures. Although HIFU has been studied for 50 years, recent technological developments now allow its use for tumours of the liver, prostate and other sites. In liver disease, HIFU has been used to treat unresectable, advanced stages of hepatocellular carcinoma (HCC) and liver metastases. Hepatocellular carcinoma is a serious health problem worldwide and is endemic in some areas because of its association with hepatitis B and C viruses (in 20% of cases). Liver transplantation (LT) has become one of the best treatments available because it removes both the tumour and the underlying liver disease such as cirrhosis (which is present in approximately 80% of cases). The prerequisite for long-term transplant success depends on tumour load and strict selection criteria regarding the size and number of tumour nodules. The need to obtain the optimal benefit from the limited number of organs available has prompted strict selection criteria limited to only those patients with early HCC who have a better long-term outcome after LT. The so-called “bridging therapy” has the aim of controlling disease burden for patients who are on the organ transplant waiting list. Amongst various treatment options, transarterial chemoembolisation and radiofrequency ablation are the most popular treatment choices. Recently, Cheung et al demonstrated that HIFU ablation is a safe and effective method for the treatment of HCC patients with advanced cirrhosis as a bridging therapy and that it reduced the dropout rate from the liver transplant waiting list. In this commentary, we discuss the current value of HIFU in the treatment of liver disease, including its value as a bridging therapy, and examine the potential advantages of other therapeutic strategies.

Keywords: High-intensity focused ultrasound, Hepatocellular carcinoma, Liver transplantation, Bridging therapy, Waiting list

Core tip: High-intensity focused ultrasound (HIFU) is a non-invasive modality used to destroy tissue. It has been used to treat unresectable advanced stages of hepatocellular carcinoma (HCC) and liver metastases. In some HCC cases, liver transplantation has become one of the best treatments because it removes the tumour and the underlying liver disease such as cirrhosis. The so-called “bridging therapy” has the aim of controlling disease burden for patients who are on the organ transplant waiting list. Here, we discuss various treatment options including transarterial chemoembolisation and radiofrequency ablation, and we examine the utility of HIFU as a safe and effective method of bridging therapy that can reduce the dropout rate of patients who are on the liver transplant waiting list.


I have read with great interest the recent article by Cheung et al[1] reporting their experience in the use of high-intensity focused ultrasound (HIFU) in patients with hepatocellular carcinoma (HCC) and cirrhosis who are waiting for liver transplant. The study aim was to determine whether HIFU could reduce the patient dropout rate.

HIFU is a non-invasive modality that uses an extracorporeal source of focused ultrasound energy. The technique was introduced by Lynn et al[2], and it is able to induce coagulative necrosis in targeted tissues without damaging overlying and surrounding vital structures.

Although HIFU has been studied for 50 years, recent technological developments have allowed its use in treating tumours of the liver[3], prostate[4] and other sites[5].

HIFU is a highly precise medical procedure that applies high-intensity focused energy to “heat” and “destroy” diseased tissues. Its precision is under investigation for a possible application as “focal” therapy in case of prostate cancer, where whole gland therapy has a negative impact in terms of incontinence and impotence[6].

HIFU is a hyperthermia therapy, which is a class of clinical therapies [including radiofrequency ablation (RFA)] that use high temperature to treat diseases.

HIFU is also a modality of therapeutic ultrasound, involving minimally invasive or non-invasive methods to direct acoustic energy into the body. In addition to HIFU, other modalities include ultrasound-assisted drug delivery, ultrasound haemostasis, ultrasound lithotripsy and ultrasound-assisted thrombolysis.

A clinical HIFU procedure is typically performed in conjunction with an imaging procedure to enable treatment planning and targeting before applying any therapeutic or ablative levels of ultrasound energy. When diagnostic sonography is used, the technique is termed ultrasound-guided focused ultrasound (USgHIFU or USgFUS). Magnetic resonance imaging is also used for guidance; thus, the technique is sometimes called magnetic resonance-guided focused ultrasound, which is often shortened to MRgHIFU or MRgFUS.

Currently, USgHIFU is approved for use in Bulgaria, China, Hong Kong, Italy, Japan, Korea, Malaysia, Mexico, Russia, Romania, Spain and the United Kingdom. MRgHIFU is an approved therapeutic procedure to treat uterine fibroids in Asia, Australia, Canada, Europe, Israel and the United States (Food and Drug Administration, FDA approved). Research on other indications is actively underway, including clinical trials evaluating the effectiveness of HIFU for the treatment of cancers of the brain, breast, liver, bone, and prostate.

From a technical point of view, the ultrasound waves of high-intensity focused ultrasound are generated by high frequency (0.5 to 10 MHz) vibration of a piezoelectric or piezo-ceramic transducer. The ultrasound beams are then focused by spherical arrangement using an acoustic lens or parabolic reflectors into a small, discrete region that corresponds to the focal point. For clinical applications, and similar to ultrasound imaging, an ultrasound probe is usually coupled by degassed water between the source and patient surface (skin, rectal wall). Because of the comparable acoustic properties of water and tissue, the sound waves should penetrate the surface and the pre-target tissue with only slight absorption, reflection and heating. This phenomenon occurs because the power density of the converging ultrasound increases as it approaches the focal point. The focal region is a 3-dimensional zone, whose area depends on the frequency and the geometry of the source. Generally, the focal area is approximately 10 to 50 mm in length and 1 to 5 mm in diameter.

Based on target volume, the tissue can be ablated by sequentially shifting the focal zone with incremental movements of the transducer. This approach is combined with adjustments of the focal length and is coupled with an immobile organ or with the complex real-time tracking of a moving target (such as liver). The extent of tissue ablation is approximately that of the physical focal zone, although in practice cold spots (cause by blood perfusion in the tissue), beam distortion and beam mis-registration are impediments to finely controlled treatments. However, by scanning the target using multiple pulses and multiple focal points, large tissue areas can be ablated.

The effect of acoustic cavitation induced by the ultrasound beam is complex, and acoustic impedance is sometimes unpredictable. However, the result is cell necrosis induced through a combination of mechanical stress and thermal injury.

The mechanical effect is induced by cavitation, a process in which bubbles develop and increase in size to the point at which resonance is achieved. The bubble formation is a consequence of the negative pressure of the ultrasound wave. As the bubbles expand and collapse, high pressures ranging from 20000 to 30000 bars develop and damage nearby cells. The popcorn effect is the typical example of cavitation.

The thermal effect is directly induced by the ultrasound beams, and due to the significant energy deposition at the focus the temperature within the tissue can rise from 65 to 85 °C. The temperature increase destroys tissue by coagulative necrosis. Higher temperatures are typically avoided to prevent boiling of liquids inside the tissue.

Because ultrasound destroys the diseased tissue non-invasively, it is also known as a non-invasive surgery. In liver disease, HIFU has been used for the treatment of unresectable, advanced stages of hepatocellular carcinoma or for the treatment of liver metastases.

Previous studies have shown that HIFU is safe and effective for patients with hepatocellular carcinoma[7] and can improve the quality of life of patients with HCC. In a study involving 145 patients with HCC, symptoms improved or pain was relieved in 84.8% of the 145 patients. Additionally, the size of the target tumour shrank by various degrees. The 2-year survival rate was 80% in patients with stage Ib HCC, 51.4% in stage IIa, and 46.5% in stage IIIa.

Ng et al[8] involving 49 patients receiving HIFU for unresectable HCC showed that the technique was effective in 79.5% of cases. The study found that only tumour size (≥ 3.0 cm) was a significant risk factor affecting the complete ablation rate. The 1- and 3-year overall survival rates were 87.7% and 62.4%, respectively. Moreover, HIFU is safe for the treatment of disease adjacent to or surrounding a major liver vessel. The study by Zhang et al[9] enrolled 39 patients with HCC. All of the treated tumours had a distance between the tumour and main blood vessel (inferior vena cava, main hepatic vein branches, portal vein) of less than 1 cm, and no major blood vessel injury was observed in any subject.

HIFU has been used in combination with transarterial chemoembolisation (TACE) in prior studies. Jin et al[10] reported their experience of HIFU and transraterial chemoembolisation in 73 patients with unresectable HCC. That study demonstrated that 45.2% patients achieved complete tumour ablation. By multivariate analysis, ablation response (P = 0.001) and tumour size (P = 0.013) were major prognostic factors in predicting response to therapy. In an interesting randomised trial comparing TACE alone vs TACE + HIFU, Li et al[11] showed that the total effective rate for tumour response was 72.8% in the TACE + HIFU group. This response was significantly higher than in the TACE group alone (44.5%, P < 0.05). The corresponding 1-, 2-, 3- and 5-year overall survival rates for the TACE-HIFU group were 72.7%, 50.0%, 31.8% and 11.4%, respectively. These rates were higher than in the TACE alone group (47.2%, 16.7%, 2.8% and 0%, respectively , P < 0.01).

HIFU ablation is well tolerated in HCC patients with cirrhosis. According to Cheung et al[12], 13% of 100 patients developed 18 complications. Morbidity was mainly caused by skin and subcutaneous tissue injuries in nine cases. Based on the Clavien classification of surgical complications, only four complications were grade 3a, while the other 14 were below this grade. By univariate analysis, only age was found to be an independent factor for poor HIFU tolerance.

HCC is a serious health problem worldwide because of its association with hepatitis B and C viruses. Liver transplantation has become one of the best HCC treatments available because it removes both the tumour and the underlying liver disease.

A prerequisite for the long-term success of a transplantation program depends on tumour load and selection criteria regarding size and number of tumour nodules. The need to obtain the optimal benefit from the limited number of available organs has prompted the use of careful selection criteria to list only those patients with early HCC who have a prediction of superior long-term outcome after LT.

Patients who fulfil the so-called Milan criteria (single tumour ≤ 5 cm; two or three tumours, none > 3 cm; no vascular invasion) or the expanded University of California San Francisco criteria (UCSF criteria: single tumour ≤ 4.5 cm; two or three tumours, none > 4.5 cm; or total tumour diameter ≤ 8 cm; no vascular invasion) may have a 3-year survival of up to 88%. However, the expansion of these criteria for transplantation is still a topic of discussion.

Other problems arise from the differential between the number of patients on the liver transplant waiting list and the number of available donors. Additionally, there is a time lag between patient inclusion on a waiting list and the available organ. For example, in the United States, more than 2000 candidates die each year while awaiting transplantation.

Some therapies for HCC, called “bridge therapy”, have the capacity to “fix” or suspend tumour progression and to allow HCC patients to maintain active candidacy as long as necessary to obtain a liver. Several techniques are employed as bridge therapies for HCC patients awaiting liver transplantation. Treatment options such as TACE and radio frequency ablasion (RFA) are the most popular treatment choices as pre-transplant locoregional therapy.

Moreover, other goals of locoregional therapy, e.g., alcohol injection, radiofrequency ablation, transarterial chemoembolisation, transarterial radioembolization, and liver resection, are intended to decrease tumour size and number in patients who initially present with tumours that do not meet locally acceptable criteria for liver transplantation.

The TACE principle is intra-arterial injection of cytotoxic drug combinations (doxorubicin and/or cisplatin and/or mitomycin into the hepatic artery), followed by lipiodol injection, gelfoam for vessel occlusion and degradable microspheres. An aggressive ablation therapy in association with a short transplant waiting time has the potential to optimise the curative intent of liver transplantation in selected cirrhotic patients. Based on the local extension of the disease and the hepatic functional reserve, TACE may be performed as a ‘‘complete’’, selective or superselective procedure through a microcatheter. Contraindications for TACE include Child-Pugh C liver cirrhosis, presence of multifocal bilobar tumour spread, presence of extrahepatic metastases, portal vein thrombosis or arterio-portal fistula.

TACE has shown excellent outcomes as a bridging therapy. However, only patients with preserved liver function and asymptomatic multinodular tumours without vascular invasion or extrahepatic spread are eligible for TACE because it avoids hepatic failure and severe adverse events[13]. TACE has been used as a selective/superselective procedure and has shown excellent results that are superior to a simple lobar approach[14]. As a bridging (or down-staging) therapy, selective/superselective TACE induces a histological necrosis in 91.8% of cases and was maximal for tumours > 3 cm.

RFA represents a widely applied method to treat HCC in a palliative intent, or as a ‘‘bridging’’ to liver transplantation. RFA may be performed under ultrasonography, Computed tomography guidance, or during laparoscopic and open surgical procedures. This procedure has more limitations than TACE, including the number of nodules that may be treated (up to three in most cases) or the maximal tumour diameter of the nodules (up to 5 cm). Effective treatment has been achieved[15] when 100% tumour necrosis is present. However, it is difficult to reach this goal with tumours exceeding the above-mentioned diameter or number of tumour nodules. Mazzaferro et al[16] showed that although the complete response rate was high (55%), tumour size (> 3 cm) and time from treatment (> 1 year) predict a high risk of tumour persistence in the targeted nodule.

As a bridging therapy, RFA showed some limitations. Schroeder et al[17] demonstrated that although the majority of treated patients (62%) had a solitary tumour at the beginning of treatment, tumour progression was observed in a large proportion (38%) of patients. These results limit the role of RFA as a bridging treatment prior to LT.

Yttrium-90 (Y90) microsphere radio-embolisation is a recently FDA-approved, non-surgical procedure used to treat inoperable HCC. This innovative procedure delivers targeted, internal radiation therapy directly to the tumour[18]. Some promising results have been reported for this technique either as a “bridging” option before other treatment modalities (partial hepatectomy, liver transplantation) or as a main therapy for patients with diffuse intrahepatic tumour spread. Treatment with Y90 microspheres has the advantage of being able to treat all intrahepatic HCC lesions, including otherwise undetected tumours. This treatment may also be the alternative to TACE in selected patients with contraindications for TACE.

In conclusion, with increases in waiting times for liver transplantation, it has become common practice to monitor patients to ensure that they remain within the acceptable criteria for liver transplantation. Moreover, the dropout of patients on the waiting list is common because of cancer progression or other medical reasons. Locoregional therapy as a bridging strategy for patients on the waiting list aims to decrease tumour-related dropout rates and to reduce the incidence of recurrent diseases after liver transplantation. Current available techniques show a dropout rate up to 35% for transarterial embolisation and up to 15% for radiofrequency ablation.

Cheung et al[12] must be congratulated for testing the utility of high-intensity focused ultrasound in this particular setting. The study examined 49 consecutive HCC patients listed for liver transplant by UCSF criteria. Twenty-nine patients received TACE as a bridging therapy, 16 patients received no treatment before liver transplantation, and five patients received HIFU as bridging therapy. The control group of five patients received HIFU but were not on the transplant list. TACE was performed using cisplatin as the chemotherapeutic agent, and it was delivered with Lipiodol, followed by gelfoam particle embolisation. Selective cannulation and embolisation of the feeding arteries of the tumours were performed whenever possible. All of the HIFU treatments were conducted by an experienced hepatobiliary surgeon and radiologist using the JC HIFU system (Chongqing Haifu Technology, Chongqing, China). The system is composed of a real-time diagnostic imaging unit, a therapeutic unit, a degassed water circulation unit, and a computer system. The real-time diagnostic imaging unit provides direct visualisation of the tumour. The therapeutic unit consists of an ultrasound energy transducer that focuses the ultrasound energy at a 12-cm focal point. The degassed water circulation unit provides a medium for ultrasound transmission outside the body. The computer system controls these three units.

Cheung demonstrated that 90% of patients receiving HIFU had complete tumour response, while 10% had partial response. There was no complete or partial tumour response in the TACE group. Fourteen (46%) patients had progressive disease, and 14 (46%) patients had stable disease. The overall dropout rate was 24.1%.

HIFU was shown to be a safe treatment, and none of the patients receiving HIFU as a bridging therapy developed complications due to intolerance after the procedure. The complication rate was 8.2%, and the complications involved mild skin oedema and injury due to energy accumulation at the ultrasound beam pathway.

HIFU ablation is an entirely extracorporeal non-invasive ablative treatment method using focused ultrasound energy. It is capable of causing coagulative necrosis of the targeted HCC via intact skin, without the need for surgical incision.

HIFU has been well demonstrated to be an effective ablation modality that is non-invasive. It can effectively reduce the dropout rate from the liver transplant waiting list by providing effective tumour control. The histological proof from the liver explants provides evidence that the necrosis is effective in an in vivo model.

Despite the low number of enrolled subjects, the preliminary study by Cheung et al[1] is interesting and suggests the need for more extensive clinical trials that focus on the use of HIFU as a bridging therapy (Figure ​(Figure11).


Figure 1 Approach to the management of newly diagnosed hepatocellular cancer. Source from Parikh et al[19]. “Bridging therapy”: Surgical resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE). High-intensity focused ultrasound (HIFU) as proposal. PEI: Percutaneous ethanol injection; UNOS: United network for organ sharing.


P- Reviewers: Lin ZY, Maruyama H S- Editor: Gou SX L- Editor: A E- Editor: Wang CH


1. Cheung TT, Fan ST, Chan SC, Chok KS, Chu FS, Jenkins CR, Lo RC, Fung JY, Chan AC, Sharr WW, et al. High-intensity focused ultrasound ablation: an effective bridging therapy for hepatocellular carcinoma patients. World J Gastroenterol. 2013;19:3083–3089. [PMC free article][PubMed]

2. Lynn JG, Zwemer RL, Chick AJ, Miller AE. A new method for the generation and use of focused ultrasound in experimental biology. J Gen Physiol. 1942;26:179–193. [PMC free article] [PubMed]

3. Shen HP, Gong JP, Zuo GQ. Role of high-intensity focused ultrasound in treatment of hepatocellular carcinoma. Am Surg. 2011;77:1496–1501. [PubMed]

4. Mearini L, Porena M. Transrectal high-intensity focused ultrasound for the treatment of prostate cancer: past, present, and future. Indian J Urol. 2010;26:4–11. [PMC free article] [PubMed]

5. Kennedy JE, Ter Haar GR, Cranston D. High intensity focused ultrasound: surgery of the future? Br J Radiol. 2003;76:590–599. [PubMed]

6. Mearini L, Porena M. Pros and cons of focal therapy for localised prostate cancer. Prostate Cancer. 2011;2011:584784. [PMC free article] [PubMed]

7. Xu G, Luo G, He L, Li J, Shan H, Zhang R, Li Y, Gao X, Lin S, Wang G. Follow-up of high-intensity focused ultrasound treatment for patients with hepatocellular carcinoma. Ultrasound Med Biol. 2011;37:1993–1999. [PubMed]

8. Ng KK, Poon RT, Chan SC, Chok KS, Cheung TT, Tung H, Chu F, Tso WK, Yu WC, Lo CM, et al. High-intensity focused ultrasound for hepatocellular carcinoma: a single-center experience. Ann Surg. 2011;253:981–987. [PubMed]

9. Zhang L, Zhu H, Jin C, Zhou K, Li K, Su H, Chen W, Bai J, Wang Z. High-intensity focused ultrasound (HIFU): effective and safe therapy for hepatocellular carcinoma adjacent to major hepatic veins. Eur Radiol. 2009;19:437–445. [PubMed]

10. Jin C, Zhu H, Wang Z, Wu F, Chen W, Li K, Su H, Zhou K, Gong W. High-intensity focused ultrasound combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: long-term follow-up and clinical analysis. Eur J Radiol. 2011;80:662–669. [PubMed]

11. Li C, Zhang W, Zhang R, Zhang L, Wu P, Zhang F. Therapeutic effects and prognostic factors in high-intensity focused ultrasound combined with chemoembolisation for larger hepatocellular carcinoma. Eur J Cancer. 2010;46:2513–2521. [PubMed]

12. Cheung TT, Chu FS, Jenkins CR, Tsang DS, Chok KS, Chan AC, Yau TC, Chan SC, Poon RT, Lo CM, et al. Tolerance of high-intensity focused ultrasound ablation in patients with hepatocellular carcinoma. World J Surg. 2012;36:2420–2427. [PMC free article] [PubMed]

13. Vogl TJ, Naguib NN, Nour-Eldin NE, Rao P, Emami AH, Zangos S, Nabil M, Abdelkader A. Review on transarterial chemoembolization in hepatocellular carcinoma: palliative, combined, neoadjuvant, bridging, and symptomatic indications. Eur J Radiol. 2009;72:505–516. [PubMed]

14. Golfieri R, Cappelli A, Cucchetti A, Piscaglia F, Carpenzano M, Peri E, Ravaioli M, D’Errico-Grigioni A, Pinna AD, Bolondi L. Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (& lt; 5 cm) hepatocellular carcinomas. Hepatology. 2011;53:1580–1589.[PubMed]

15. Lu DS, Yu NC, Raman SS, Lassman C, Tong MJ, Britten C, Durazo F, Saab S, Han S, Finn R, et al. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Hepatology. 2005;41:1130–1137. [PubMed]

16. Mazzaferro V, Battiston C, Perrone S, Pulvirenti A, Regalia E, Romito R, Sarli D, Schiavo M, Garbagnati F, Marchianò A, et al. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study. Ann Surg. 2004;240:900–909. [PMC free article] [PubMed]

17. Schroeder T, Sotiropoulos GC, Molmenti EP, Kuehl H, Cicinnati VR, Schmitz KJ, Kóbori L, Paul A, Mathé Z. Changes in staging for hepatocellular carcinoma after radiofrequency ablation prior to liver transplantation as found in the explanted liver. Hepatogastroenterology. 2011;58:2029–2031.[PubMed]

18. Lau WY, Lai EC, Leung TW. Current role of selective internal irradiation with yttrium-90 microspheres in the management of hepatocellular carcinoma: a systematic review. Int J Radiat Oncol Biol Phys. 2011;81:460–467. [PubMed]

19. Parikh S, Hyman D. Hepatocellular cancer: a guide for the internist. Am J Med. 2007;120:194–202. [PubMed]


Consequences of Perceived Stigma Among Patients with Cirrhosis

Dig Dis Sci. 2013 Nov 19. [Epub ahead of print]

Vaughn-Sandler V, Sherman C, Aronsohn A, Volk ML.

Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.


BACKGROUND: Among patients with diseases such as HIV, cancer and mental illness, perceived stigma is common and is linked to quality of life (QOL), depression and healthcare-seeking behavior.

AIMS: We aimed to determine the prevalence and consequences of stigma in patients with cirrhosis.

METHODS: A survey was developed and mailed to 300 patients with cirrhosis from a variety of etiologies. Among the 149 respondents, stigma was measured using a composite of previously validated scales. Correlates of stigma were measured using an a priori theoretical construct in order to investigate hypothesized consequences such as impaired social support, depression and reduction in healthcare-seeking behavior.

RESULTS:  Eighty-nine percent of respondents chose "agree" or "strongly agree" for at least one of the 18 stigma-related questions, indicating they felt stigmatized in at least one aspect of their lives. Patient factors associated with more perceived stigma on multivariable linear regression included younger age (p = 0.008), and hepatitis C (p = 0.001) or alcohol (p = 0.01) as the etiology of liver disease. Patients with higher levels of perceived stigma had less social support (r 2 = 0.898, p < 0.001), were less likely to seek medical care (r 2 = 0.108, p < 0.001), suffered from more depression (r 2 = 0.17 p < 0.001) and had worse QOL (r 2 = 0.175, p < 0.001).

CONCLUSIONS: Perceived stigma is common among patients with cirrhosis, and is associated with adverse attitudes and behaviors such as decreased healthcare-seeking behavior. Healthcare providers need to be aware of these perceptions and their potential impact on patients' interaction with the medical system.

PMID: 24248421 [PubMed - as supplied by publisher]


Non-alcoholic fatty liver disease: Factors associated with its presence and onset

Journal of Gastroenterology and Hepatology

Special Issue: Third Asian-Pacific Topic Conference (APTC2012): Nutrition-related disorders and digestive system. Organized by Japanese Society of Gastroenterology (JSGE) and Asian-Pacific Association of Gastroenterology (APAGE), Tokyo, Japan, November 2–3, 2012. Guest Editor: Soichiro Miura

Volume 28, Issue Supplement S4, pages 71–78, December 2013

Nutrition-Related Liver Disorders: NAFLD

You have free access to this content

Teruki Miyake, Teru Kumagi*, Shinya Furukawa, Yoshio Tokumoto, Masashi Hirooka, Masanori Abe, Yoichi Hiasa,  Bunzo Matsuura, Morikazu Onji

Article first published online: 19 NOV 2013

DOI: 10.1111/jgh.12251

© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd

Keywords: blood tests;  non-alcoholic fatty liver disease;  risk factors;  physical measurements;  predictive factors


Non-alcoholic fatty liver disease (NAFLD) may progress to cirrhosis, liver failure, and complicated hepatocellular carcinoma. In addition, NAFLD is a risk factor for the development of other serious diseases, such as diabetes or cardiovascular disease. Therefore, the detection of early-stage NAFLD is important. Many studies have described the factors that predict the presence of NAFLD and its onset, and several markers have been identified. These markers have enabled the identification of high-risk patients and have improved routine medical practice. To prevent advanced disease, clinicians need to have simple markers that predict the onset of NAFLD so that interventions can be started at much earlier stages of disease. This review summarizes the current state of knowledge regarding independent factors, as reported in large studies, that predict the presence of NAFLD and its onset, especially markers that can be used in daily medical practice, such as physical measurements and blood tests.


Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and is a manifestation of metabolic syndrome in the liver.[1, 2] Pathologically, NAFLD represents a wide spectrum of liver conditions from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH may progress to cirrhosis, liver failure, or hepatocellular carcinoma[1-5] and thus requires periodic follow-up. NAFLD is also an independent risk factor for the onset of cardiovascular disease (CVD)[6] and diabetes,[7] making the prevention of NAFLD as important as the management of the condition.

In contrast, NAFLD has not been shown to be associated with an increased risk of death from all causes, CVD, cancer, or liver disease.[8]In large studies, approximately 5% of patients showing evidence of NAFLD are ultimately diagnosed with advanced NASH,[9] which is associated with a mortality rate similar to that of advanced liver fibrosis due to hepatitis C virus infection.[10] Considering the financial burden of the increasing number of individuals with metabolic syndrome, the identification of simple markers that can identify patients with NAFLD or those who might progress to NAFLD is desired. In this regard, this review provides an overview of the independent factors that predict NAFLD onset in individuals who do not have any other known liver disease, as previously reported in large studies.

Body mass index

A risk factor for the presence of NAFLD

Body mass index (BMI) is a simple marker that reveals an individual's degree of obesity. In Japan, a BMI of 22 is used to indicate the ideal body weight, and obesity-related diseases are associated with higher BMIs.[11] Previously, we reported a community-based, cross-sectional study involving the records of 6370 Japanese subjects, and confirmed that BMI was an independent marker for the presence of NAFLD (men: odds ratio [OR] 1.257; 95% confidence interval [CI] 1.20–1.319; P < 0.001; women: OR 1.291; 95% CI 1.245–1.340; P < 0.001)[12, 13] (Table 1). The BMI cut-off levels for identifying the presence of NAFLD were identified in men and women using the area under the receiver operating characteristic (ROC) curve (AUC) (95% CI). Using these techniques, the AUC (95% CI) (men, 0.809 [0.791–0.825]; women, 0.831 [0.82–0.843]), cut-off level (men, 24.1 kg/m2; women, 22.5 kg/m2), sensitivity (men, 71.6%; women, 77.9%), specificity (men, 76.5%; women, 75.4%), positive predictive value (PPV; men, 66.3%; women, 31.2%), negative predictive value (NPV; men, 80.6%; women, 96%), and diagnostic accuracy (men, 74.6%; women, 75.7%) for predicting NAFLD were identified (Table 1).[13] Eguchi et al. also carried out a large, multicenter, retrospective study examining 5075 subjects who underwent health checkups at three health centers, and identified BMI as a useful marker for determining the presence of NAFLD. They showed that BMI (> 25 kg/m2) was an independent risk factor for NAFLD (men: OR 3.81; 95% CI 3.11–4.67; P < 0.01; women: OR 7.23; 95% CI 5.5–9.5; P < 0.01) by multiple regression analysis, and the prevalence of NAFLD showed a linear increase with increasing BMI (BMI < 23 kg/m2, 10.5%; 23 ≤ BMI < 25 kg/m2, 37.9%; 25 ≤ BMI < 28 kg/m2, 58.4%; BMI ≥ 28 kg/m2, 84.2%)[14] (Table 1).

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Vitamin D deficiency is associated with mortality in patients with advanced liver cirrhosis

Eur J Clin Invest. 2013 Nov 15. doi: 10.1111/eci.12205. [Epub ahead of print]

Stokes CS, Krawczyk M, Reichel C, Lammert F, Grünhage F.

Department of Medicine II, Saarland University Medical Center, Homburg, Germany.


BACKGROUND: Chronic liver disease is the fifth most common cause of mortality in Europe. Recently, vitamin D deficiency has been associated with an increased risk of mortality in the general population. Since patients with advanced liver disease frequently exhibit vitamin D deficiency, we assessed for a possible association of vitamin D deficiency with survival in a cohort of patients with advanced liver disease.

METHODS:  Sixty-five patients with liver cirrhosis (median age, 58 years; range, 19-76 years; 66% male; Child-Pugh stage C, 46%) were included in our prospective single-center survival study. Serum 25-hydroxyvitamin D concentrations were measured by chemiluminescence immunoassay. The optimal cut-off was determined using area under the curve (AUC) and Kaplan-Meier analysis. Chi-square statistics and multivariate binary logistic regression analysis were also conducted.

RESULTS: Median serum vitamin D levels were 8.2 ng/ml (range < 4.0-95.8 ng/ml). Overall, 48% of patients (31/65) died during a 24-month follow-up period. AUC analysis determined a vitamin D level of 6.0 ng/ml as optimal cut-off for discriminating survivors from non-survivors. Kaplan-Meier analysis of survival confirmed low vitamin D levels as significant predictor of death (P = 0.012). Finally, multivariate analysis identified low vitamin D levels (OR = 6.3; 95% CI, 1.2-31.2; P = 0.012) and MELD scores (OR = 1.4; 95% CI, 1.2-1.7; P < 0.001) as independent predictors of survival.

CONCLUSION: Low vitamin D levels are associated with increased mortality in patients with advanced liver disease. Thus, serum levels of vitamin D might represent a critical marker of survival in advanced liver cirrhosis. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: 25-hydroxyvitamin D, cholecalciferol, chronic liver disease, survival analysis

PMID: 24236541 [PubMed - as supplied by publisher]


FDA Expected To Approve New, Gentler Cure For Hepatitis C

Provided by NPR

December 05, 2013 4:00 AM



The Food and Drug Administration is expected any day now to approve the first in a new class of drugs that can cure the leading cause of liver failure and liver cancer.

The disease is hepatitis C, a slow-moving but deadly virus that infects more than 3 million Americans. The new treatment is a once-a-day pill that can cure at least 85 percent of victims without the need for injections of interferon, an immune stimulant that causes severe side effects.

The advent of interferon-free treatments for hepatitis C is an advance that's "about as hot as I've ever seen," says Dr. David Thomas, a liver specialist at Johns Hopkins University.

He says the new drugs are almost like curing lung cancer with only three months of once-a-day pills.

"That's kind of an exaggeration because lung cancer treatment is worse than what we used to do (to treat hepatitis C)," Thomas says. "But it's that kind of thing — where we did something that didn't work that much and hurt people a lot. And then we go from that to something that's ... really an amazing transformation."

The first of the new hepatitis C drugs is Gilead Science's sofosbuvir. It interferes with the virus' replication without much affecting cell metabolism. The drug won a unanimous recommendation for approval from of an FDA advisory committee last October for interferon-free treatment of two strains of the virus, in combination with the oral drug ribavirin. Agency approval is expected by Dec. 8.

The advisory panel also recommended approval of sofosbuvir for treatment of the most common and difficult-to-treat strain of hepatitis C, called genotype-1. But in that case, it needs to be used with interferon.

But other new hep-C drugs are in the pipeline, with approvals expected in late 2014 or early 2015. Some regimens may enable treatment of genotype-1 without interferon too.

"This is really a landmark shift in the treatment of hepatitis C," says Dr. Eric Lawitz of the Texas Liver Institute. "It's going to lead to a new generation of all-oral pills for all patients without the use of interferon, which is very tough for patients to take."

One of Lawitz's patients illustrates the potential. Over the past eight years, Henry Alameda, a 54-year-old carpenter who lives in San Antonio, endured two grueling six-month treatment regimens that failed to clear the virus from his blood. He thinks he was infected 20 years ago from the contaminated needle of an amateur tattoo artist.

The interferon side effects were hard to take. It's "like waking up with a bad cold," he says. "You would have to get under the blanket and you would start shaking. You would get real bad chills." Interferon, which is intended to get patients' immune systems to attack the virus, also commonly causes fatigue, nausea, diarrhea, anemia and depression.

Two years ago Alameda got into a study of sofosbuvir in combination with ribavirin. "It was like a miracle pill," he says. "It was just like taking an aspirin. I had no side effects at all." Some study patients have had headaches, fatigue, nausea, itching and weakness, but few have had to stop taking the pills because of side effects.

The new regimen worked for Alameda. Fifteen months after he finished taking the pills, there's no trace of the virus in his blood. Doctors have pronounced him cured.

The safety, effectiveness and low rate of side effects from the new regimens are expected to increase the number of hepatitis C patients who get treatment, although many doctors may hold off until other drugs are approved and combinations are tested in different types of patients.

The potential impact is huge. Hepatitis C infects up to five times as many people as HIV – another insidious virus that takes years to cause life-threatening disease. The U.S. Preventive Services Task Force says all Americans born between 1945 and 1965 should get tested for the infection – a population that includes 79 million baby boomers.

Thomas says the new treatments are coming at just the right time. Many baby boomers got infected decades ago – by experimenting with drug use, from blood transfusions or medical treatments that exposed them to contaminated blood, from things like tattoos and piercings. The virus can be transmitted sexually as well, although the evidence is controversial.

Now an increasing number of infected people are beginning to show signs of liver damage. Untreated, the virus causes progressive liver scarring and eventually cirrhosis that can require liver transplants. It's also the reason that liver cancer rates are increasing. Alcohol use greatly accelerates the damage.

But the new drugs won't come cheap. The price of sofosbuvir hasn't been set, but it's expected to cost around $90,000 for a course of treatment.

That's going to spark a lot of debate about who should be treated at what stage of infection.

But Johns Hopkins' Thomas says society should consider the cost of forgoing treatment. "If we fail to provide treatment to an expanding population of persons at risk of cirrhosis and liver cancer, then we'll have even greater costs," he says. "And they won't all be economic."


Age and gender differences in the relationship between hepatitis C infection and all stages of Chronic kidney disease

Journal of Viral Hepatitis

Early View (Online Version of Record published before inclusion in an issue)

Original Article

W.-C. Li1,*, Y.-Y. Lee2,3, I.-C. Chen4,5, S.-H. Wang6,7,8,9, C.-T. Hsiao4,5, S.-S. Loke10

Article first published online: 5 DEC 2013

DOI: 10.1111/jvh.12199

© 2013 John Wiley & Sons Ltd


Keywords: Chronic kidney disease;  creatinine;  eGFR;  hepatitis C virus;  proteinuria


Chronic kidney disease (CKD) is a worldwide health issue with heavy economic burden. Chronic hepatitis C virus (HCV) infection is a common cause of CKD, which can significantly impact the progression and mortality among patients with CKD. The prevalence of both illnesses is high in Taiwan. A multicentre and population-based cross-sectional study including 24 642 subjects was conducted to explore the association of HCV infection with the prevalence and severity of CKD. The measurements of metabolic parameters, eGFR and CKD stages were compared between subjects with HCV seropositivity and seronegativity. The analyses of association between HCV infection with CKD stages and evaluation of potential risk factors of CKD were performed by gender and age (≤ and >45 years). HCV-seropositive subjects accounted for 6.9% and had a significantly older age. The prevalence of CKD increased in those with HCV seropositivity (16.5%). Significantly higher prevalence of CKD stages ≥3 in HCV-seropositive subjects was noticed (7.8%). Age (>45 year), male gender, alcohol drinking, hypertension, creatinine and HCV infection were the significant factors associated with the presence of CKD. HCV seropositivity was an independent risk factor of developing CKD and associated with an increased risk of having CKD of all stages. The higher prevalence of earlier stage of CKD warrants longitudinal studies with frequent testing on renal function and sufficient duration to determine the changes of eGFR over time. Implementation of effective treatment intervention is also required for these subjects to prevent the progression of CKD to late stages.


Military Fights HIV Infection & Discrimination

by Conswella Bennett
Thursday Dec 5, 2013


(Source:Thinkstock by Getty Images)

Despite what opponents thought would happen, the repeal two years ago of "Don’t Ask Don’t Tell," the law that kept gay men and lesbians from openly serving in the military, has not resulted in HIV infection increasing.

"No statistically significant rise in HIV infection rates can be noted since DADT was repealed," John Gillespie, co-chair of OutServe, told EDGE. "In some services, such as the Air Force, there has been a steady decline." OutServe-SLDN, the association of actively serving LGBT military personnel, provides legal services, and acts as a watchdog and policy organization dedicated to bringing about full LGBT equality to America’s military.

Although there has not been a significant increase in HIV infections in the Armed Forces, Gillespie noted that the military continues to do surveillance for HIV among military members "to ensure their health and maintain force readiness." The periodic testing helps assist in early detection of HIV infection.

Service members on active duty or reserve duty in all branches of the military services are currently screened every two years. Testing is also performed within 24 months after a permanent change of station orders, as well as during selected pre- and post-deployment periods.

Just such testing uncovered a number of HIV cases in the military. Earlier this year, Fort Bliss in El Paso, Texas, led Army installations with the most HIV infections in the past two years. Former Air Force Sgt. David Gutierrez was charged with aggravated assault for exposing multiple sex partners to HIV at swinger parties in Wichita, Kansas. Two years ago, Gutierrez was sentenced to eight years in prison.

Such situations come to no surprise to Gillespie. He observed that the military is made up of younger males who typically engage in risk-taking behaviors and may not be up to date on safer sex. The repeal of "Don’t Ask Don’t Tell," however, has actually provided additional opportunities for prevention messages targeted to men who have sex with men.

According to data collected by Dr. Wesley D. Reynolds of the US Air Forces, the years from 1990 to 2011 saw 7,423 cases of HIV in the military. Of those numbers, 1,485 are still currently serving in the military. (This data excludes the Air Force Reserve.)

The U.S. Department of Defense works to minimize the risk of HIV transmission through aggressive disease surveillance and health education programs. Its education and prevention programs are often targeted to military service members who engage in high-risk sexual behavior, Gillespie noted.


(Source:Thinkstock by Getty Images)

Progress on Women Still Lags

While there are policies in place that reduce sexual interactions among service members, they are difficult to enforce. Gillespie pointed out that recent results of surveys of members of the military have revealed that safe-sex messaging, particularly on the importance of condom use, remains "unheeded by many."

If there are safe sex education programs in place, they are often more geared to men, Chantell D. Leak, who had served in the Navy, told EDGE. Leak, who served during DADT, said that for the most part her sexuality didn’t matter.

"The military is an organization with a very heteronormal, male-dominated perception on how it should operate," Leak complained. "When it comes to sex education, it is almost non-existent. If you are lucky to have a command which puts emphasis on safe sex practices, they are geared solely towards male protection and not on both-sex protection."

Leak witnessed this bias firsthand when a group of concerned females in her command brought up a request for female condoms to be provided for free in their medical unit -- as male condoms were. It took forever for their request to be fulfilled, Leak recalled: "When we asked why there weren’t any in stock for females, one woman was told there was simply not a great demand for them onboard."
That said, she added that "with the exclusion of HIV/AIDS and other incurable STD’s/STI’s -- which is not accepted in any branch of services -- they provide good medical treatment for sexually transmitted diseases."

Leak believes that the male-dominated thinking prevalent in the military needs to be changed, especially when it comes to issues to surrounding sex. "Females make up a significant percentage of sailors in the Navy," Leak pointed out. The total number of active and reserve females enlisted is 56,214, or 18 percent of enlistees.

SHARP, which stands for the Sexual Health and Responsibility Program, was established in the Navy and Marine Corps in 1999 as a public health center that converted an HIV train-the-trainer program into a broader effort aimed at preventing, not only HIV, but all sexually transmitted infections (STIs) as well as unplanned pregnancies.

STD’s and HIV have been on the military’s radar for years. In 1994, prevention of STD transmission has become a much higher priority in the military because of HIV.

The Armed Forces work to make sure that they have a population of combat-ready men and women. If a service member becomes diagnosed with HIV, they may remain in service as long as they are able to perform their military duties, according to Gillespie.

Some services, like the Air Force an Army, do limit deployments and mobility based on infection. But the Navy has begun to open up more assignments overseas and at-sea duty to HIV positive sailors.

Fighting HIV in the military is an ongoing project. For now, there appears to be progress on all fronts, from education to HIV-related discrimation.


Hepatitis C spreading among drug users


05 Dec 2013


The emergency room at the Meilahti hospital in Helsinki.
Over 20,000 hepatitis C infections remain untreated in Finland.

Only a fraction of people infected with the liver disease are treated.

A MAJORITY of hepatitis C infections go untreated. More than 20,000 people are estimated to be living with the virus leading to liver disease but only 400 of them receive treatment each year. Kaarlo Simojoki, the chief physician of A Clinic Foundation and Kalle Jokelainen, a specialist from the Meilahti hospital, point a finger at the medical professionals, who may not have the latest information on treatment options.

Treatment is often also regarded as expensive even though prescribing antiviral medication at early stages of hepatitis C infection is a more cost-effective alternative than treating a patient with advanced disease.

“With the price of treating 300 patients with cirrhosis of the liver in an intensive care unit or giving a liver transplant to 30 patients, we could treat 2,000 patients with medicines,” explains Jokelainen.

Simojoki is in favour of treating hepatitis C while the patient is participating in a drug rehabilitation programme as this is the time when the treatment is most likely to be successful.

“If the patient’s state is likely to vary, a course of treatment that is started some months later will not usually work out. The disease is then left untreated,” says Simojoki.

In several European countries, patients receive treatment for hepatitis C within a drug rehabilitation programme, which can also serve as an incentive for the patients to stick with the hepatitis C therapy, according to Jokelainen.

“There is a stigma attached to hepatitis C and people are keen to get rid of it. Patients in rehabilitation are very motivated to receive treatment for the disease,” Jokelainen stresses.

Drug users aware of testing

The number of new infections has been on the increase since 2009, with 1,175 people testing positive for the disease last year. In the vast majority of the cases the disease had been transmitted through the shared use of syringes among injecting drug users.

A Clinic Foundation’s Vinkki Health Advice Centre in Helsinki tests users of intravenous drugs anonymously for hepatitis C. According to Tanja Sorsa, a nurse at the advice centre, clients are aware of the disease risk and the screening services offered by the centre, with requests for testing coming in every day when the service is open.

If a test is positive, the client is advised to make an appointment with a doctor.

“We explain to the client what having the infection means and how to cope with it in everyday life. We also hand out brochures on hepatitis C as the news on the infection comes as a great shock to many people,” says Sorsa.



EASL Chooses App Studio for Digital Journal Publishing

December 5, 2013

EASL Creates Journal of Hepatology App with App Studio Using XML-based Content

LONDON - Quark Software Inc. announced today that EASL (European Association for the Study of the Liver) has selected App StudioTM to create the Journal of Hepatology iPad app. The app is available through iTunes and is free to subscribers.

EASL has an impressive track record in promoting research into liver disease, supporting wider education and promoting changes in European liver policy. The associations primary publication, the Journal of Hepatology, was already available in print and online. To reach an audience that increasingly relies on mobile devices for research and data collection, EASL needed a digital publishing solution that could fit seamlessly into its workflow and render XML-based content and InDesign files as compelling iPad experiences.

With an interactive app for the iPad, EASL has increased the value of content for subscribers by making it more relevant, discoverable and usable. As App Studio creates real, selectable and searchable text, readers can easily search for specific articles, link to related content, bookmark articles, add notes and more. This interactivity improves the relevance of the content and encourages increased user engagement.

After evaluating a number of digital publishing solutions used by medical journal publishers, EASL selectedApp Studio. The New England Journal of Medicine, British Medical Journal, Health Affairs, Wiley Cochrane Library and others choose App Studio because it provides easy ingestion of NLMXML content and an app experience optimised for journal reading. The XML content is transformed into paginated HTML5 that is responsive to support the iPad in both portrait and landscape orientations. It also supports a wide range of interactive enrichments, digital ad serving infrastructure, analytics, CRM integration and social media.

We are proud to offer our subscribers the iPad edition of the Journal of Hepatology, said Gregoire Pavillon, Executive Director of EASL. The ability to automate digital journal publishing using the XML content and InDesign files we already create set App Studio apart from other solutions that either cant support XML or only allow for digital PDF output. It was clear to us that the App Studio team understands journal publishing.

The Journal of Hepatology iPad app allows readers to: Quickly navigate through articles View figures and tables in full screen Bookmark and share articles Download and store supplementary materials and PowerPoint slides Watch videos related to specific articles Store monthly issues in a personal library Shaun Barriball, Vice President of Mobile Products at Quark said, It is a pleasure to partner with EASL to create the Journal of Hepatology app. At Quark we have a strong pedigree in producing tablet apps for medical journals and have developed an approach to designing and building apps in the most efficient way possible.

About EASL
EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy. EASLs main focus on education and research is delivered through numerous events and initiatives, including: The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology Journal of Hepatology published monthly Participation in a number of policy initiatives at European level

About App Studio for Digital Journals
App Studio ( is the leading digital publishing platform for journal apps and is used by journal publishers around the world including the New England Journal of Medicine, British Medical Journal, and Health Affairs. Content can be automatically repurposed from content management systems using industry XML standards such as NLMXML and Atom+MRSS. By leveraging HTML5 for content presentation, journal publishers can create apps for iPad, iPhone, Kindle Fire and Android tablets and smartphones. It is also possible to create Web apps, giving subscribers an engaging digital, interactive experience that includes audio and video on desktop and laptop computers. Real text search, interactive charts and support for citations, cross-referencing, bookmarking, tracking and sharing are just some of the features that make App Studio a compelling solution for digital journals.

App Studio is a trademark or registered trademark of Quark Software Inc. and its affiliates in the U.S. and/or other countries.

Contact: Sarah Rector, Quark Software Inc., 303-894-3753,
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