Incivek should be available in pharmacies now

  • Tuesday, May 31, 2011
  • Posted by HCV New Drugs
  • File Under

Vertex Pharmaceuticals Incorporated
(VRTX) announced that the U.S. Food and Drug Administration (FDA) approved its Incivek (telaprevir) tablets for some patients with genotype 1 chronic hepatitis C with compensated liver disease and/or cirrhosis (liver scarring). Incivek (pronounced in-SEE-veck) was approved for people who are new to treatment and those treated previously without being cured. On May 13, the FDA also approved Victrelis (boceprevir) by Merck (MRK). These two are the first hepatitis C drugs in almost a decade to win FDA approval.

Vertex stated that Incivek should be available in pharmacies now. The company also introduced a comprehensive financial assistance and patient support program to help people who might not otherwise be able to afford the treatment get it and said that more information is available on its Website.

Vertex ran three Phase 3 studies on INCIVEK, indicating people who received it in combination treatment achieved significantly higher rates of sustained viral response (SVR) or cure compared with those who received pegylated-interferon and ribavirin alone, regardless of prior treatment experience. The Phase 3 comparison information from Vertex's release shows a striking improvement in SVR/Cure rates:
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Patient Assistance Program

Viruses and the heart

 

By Dr Michael Lim
Mon, May 30, 2011
MY first patient with inflammation of the heart as a result of a viral infection (viral myocarditis or VM) was a 15-year-old schoolgirl who had symptoms of fever, cough and runny nose. She continued to go to school and felt increasingly breathless. When her symptoms became unbearable, she was taken to the hospital by her parents and was found to have an enlarged heart on the chest X-ray.

Further investigations showed an enlarged heart with poor heart-pumping function. Fortunately for her, she was responsive to medical treatment and did not require a heart transplant.

Getting a fever, cough and runny nose as a result of a viral infection is very common. While most recover uneventfully, what is not commonly known is that the viruses can enter the blood stream in some cases. Once the virus enters the blood stream, it can infect the heart muscle cells causing cell death and activation of the body's immune response.

This may cause the body to develop antibodies to the virus and some heart cell proteins. As the immune response slows down, the damaged heart tissue is replaced by scar tissue. The heart chambers may dilate and the heart pump weaken resulting in a permanently swollen and damaged heart (dilated cardiomyopathy).

Viruses
While adenoviruses, enteroviruses and parvoviruses are the most common viruses associated with VM, other associated viruses include the human herpes virus, Epstein-Barr virus and even Hepatitis C virus.

While the exact incidence of VM is not certain, one study suggests that it is the cause of sudden death in close to 9 per cent and is also identified in 9 per cent of routine postmortem examinations. Most of those with VM may not have symptoms but if there is shortness of breath, chest pain or abnormal heart rhythm, the presence of VM must be considered. The common tests used for the diagnosis of VM has limitations.

Commonly available blood tests to detect damage of heart muscle such as troponin I or cardiac enzymes have a sensitivity of only about 50 per cent. Other commonly used tests include electrocardiography to look for changes in the electrical pattern of the heart and to detect abnormal heart rhythms , and echocardiography using ultrasound techniques to assess heart chamber dilatation and damaged pump function (dilated cardiomyopathy).

For many decades, the diagnosis of VM was dependent on taking a biopsy of the heart muscle. Unfortunately, in the real world, it is estimated that about 17 biopsies of the inner wall of the heart (endomyocardial biopsy) is required to diagnose VM with 80 per cent sensitivity. In real world practice, this is impractical and rarely done, and hence many experts have moved towards non-invasive methods to diagnose VM and to assess the damage to the heart muscle.

The current recommendations from an American College of Cardiology Foundation/American Heart Association/European Society of Cardiology (ACCF/AHA/ESC) scientific statement support a limited role for endomyocardial biopsy in the evaluation of patients with cardiomyopathy.

The most significant development in the diagnosis of VM is the use of magnetic resonance imaging (MRI) of the heart. Developments in Heart MRI technology in recent years has made this the investigation of choice for those suspected to have VM. What it means is that with the use of Heart MRI, for those with viral infections, the presence of VM can be determined more accurately in a safe and non-invasive manner.

http://health.asiaone.com/Health/Health%2BMatters/Story/A1Story20110530-281363.html


Autoantibodies against cardiac troponin I in patients presenting with myocarditis

Akira Matsumoria, Corresponding Author Contact Information, E-mail The Corresponding Author, E-mail The Corresponding Author, Toshio Shimadab, Hiroaki Hattoric, Miho Shimadaa and Jay W. Masond
a Department of Cardiology, Tokyo Medical University, Tokyo, Japan
b Shizuoka General Hospital, Shizuoka, Japan
c Department of Advanced Medical Technology and Development, BML Inc., Saitama, Japan
d University of Utah, Salt Lake City, USA
Received 19 August 2010; 
revised 22 November 2010; 
accepted 18 February 2011. 
Available online 22 March 2011.
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Summary
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Background
Autoantibodies against cardiac troponin I (cTnI) play an important role in the pathogenesis of experimental cardiomyopathy. We developed a new method to measure anti-cardiac troponin I autoantibody (Anti-cTnIAAB) in patients with myocarditis with or without HCV infection.

Methods
Patients with heart failure for up to 2 years, without a distinct cause, were enrolled in the Myocarditis Treatment Trial between 1986 and 1990. Frozen blood samples were available from 1315 to 2233 enrolled patients. Anti-cTnIAAB was determined by a two-step immunoassay.

Results
The mean (±SEM) value of serum Anti-cTnIAAB titer in the 1315 patients was 0.067 ± 0.003 arbitrary unit (AU), significantly higher than in 1115 healthy volunteers (0.053 ± 0.002 AU, P < 0.01). The mean Anti-cTnIAAB titer in 88 patients whose endomyocardial biopsies (EMB) satisfied the diagnostic Dallas criteria was 0.086 ± 0.010 AU, versus 0.066 ± 0.004 AU in 1227 patients whose EMB did not satisfy these criteria. The mean Anti-cTnIAAB in both groups was significantly higher than that measured in the healthy volunteers (P < 0.01). The mean Anti-cTnIAAB titer in the 88 patients with Dallas criteria-confirmed myocarditis tended to be higher than in the other 1227 patients. Among the 88 patients with Dallas criteria-confirmed myocarditis, the mean Anti-cTnIAAB titer in 5 patients infected with the hepatitis C virus infection (HCV) was significantly higher (0.146 ± 0.047 AU) than in 83 patients without HCV infection (0.082 ± 0.010 AU, P < 0.05).

Conclusions
Elevated autoantibody titers against cTnI were detected in patients with myocarditis, and were higher in HCV-infected patients. The presence of Anti-cTnIAAB might correlate with inflammation and viral infection of the heart.

Keywords: Myocarditis; Cardiac troponin I; Autoantibody; Hepatitis C virus
...
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2009
Myocarditis....

Other viruses implicated in myocarditis include influenza virus, echovirus, herpes simplex virus, varicella-zoster virus, hepatitis, Epstein-Barr virus, and cytomegalovirus. Hepatitis C, in particular, is becoming a major focus of research.


 

Stem Cells; Searching For A Cure

A few days ago I ran across an interesting article at Stanford Medicine Magazine entitled; "Peddling hope". The author Krista Conger wrote in detail about desperate and dying patients paying an exorbitant amount of money for injections of mysterious concoctions of "cells" which apparently cure just about every ailment known to man. These therapies are promoted by unscrupulous enterprising entrepreneurs through numerous websites online. The informative article sheds a light on the unfortunate patients who travel abroad to these facilities dubbed "stem cell clinics" searching courageously for a cure. The author writes;

“Harm is being done at a lot of levels,” agrees Loring. “But on the list of things that offend me, the false hope they offer to patients is at the top.”
But the hope is cleverly packaged. “These clinics never promise a patient will be healed,” says Sipp. “They’ll say things like, ‘most patients experience an improvement.’ And, when you’ve spent a lot of your own money, or money that was given to you by friends or relatives, the incentive to report that the treatment helped is very strong. There’s a lot of room for the placebo effect.”
“It’s a worldwide industry,” says Sipp, who estimates there are about 300 clinics that offer what they claim to be stem-cell-based treatments for everything from autism to diabetes, from ALS to cancer. “And recently we’ve been seeing a growing complement of places in the United States that either refer people to nearby international clinics in Mexico or the Dominican Republic for the treatment, or even perform procedures domestically.”

By tracking the number of patients some of the bigger clinics state they have treated, Sipp has concluded that tens of thousands of people may have received unproven stem cell treatments worldwide during the past decade, which indicates a market size approaching $1 billion.

Please do read the full article here.

In Germany a clinic offering experimental stem cell injections was shut down in August 2010 because of the death of an 18-month-old boy after a brain injection. The clinic "XCell" also has a clinic in Dusseldorf and one in Cologne,Germany although both clinics are now closed. Here is the article;
Europe's largest stem cell clinic, which is at the centre of a scandal over the death of a baby given an injection into the brain, has been shut down.

08 May 2011

The closure of the XCell-Center in Dusseldorf follows an undercover investigation by The Sunday Telegraph into its controversial practices, which attracted hundreds of patients from the UK. The clinic charged patients up to £20,000 for stem cell injections into the back and brain despite a lack of scientific proof that the treatments actually worked.

Experts in stem cell research had accused the clinic of preying on vulnerable patients, desperately seeking a cure for such illnesses and diseases as cerebral palsy, multiple sclerosis, autism, Parkinson's, Alzheimer's, heart disease, diabetes and spinal cord injuries.

While most other European countries - as well as the US, Canada and Australia - have banned stem cell treatments unless shown to be safe and effective, XCell had exploited a loophole in German law allowing it to charge for the experimental procedures.

But last week, the clinic suddenly announced it had ceased carrying out operations due to what it described as legal changes in Germany. In a posting on its website, XCell said last week: "Due to a new development in German law, stem cell therapy is currently not possible to perform at the XCell-Center. Regretfully for this reason, we must cancel your appointment until further notice. We will notify you for further updates about the matter."...full story here.

This "60 Minutes" show previewed in 2010, I remember watching the it with my friend, she passed from ALS six months after being diagnosed. You can view part two of the video here.
.
21st Century Snake Oil, Part 1

September 12, 2010 5:00 PM

"60 Minutes" hidden cameras expose medical con men who prey on dying victims by using pitches that capitalize on the promise of stem cells to cure almost any disease. Scott Pelley reports

 




Follow Up From U-M

Sean Morrison, director of the U-M Center for Stem Cell Biology


video


ANN ARBOR, Mich. — Patients should be wary of claims made by the operators of stem cell clinics outside the United States who offer unproven and potentially dangerous disease treatments, University of Michigan researcher Sean Morrison said during a segment of the CBS program “60 Minutes” that aired Sunday night.

“There are clinics that have been set up in countries with unregulated medical systems that are making claims that are not based on sound scientific and medical evidence,” said Morrison, director of the U-M Center for Stem Cell Biology.

“People who claim that they can cure diseases in the absence of strong scientific evidence are selling snake oil and preying on the hopes of desperate patients,” Morrison said during an interview conducted after the “60 Minutes” crew visited his Life Sciences Institute laboratory.
 
Clinics offering unproven stem cell therapies have arisen in countries such as China, Russia and Mexico. In many cases, there is little or no scientific evidence to support the effectiveness of treatments offered by these clinics, Morrison said. Yet patients are charged large amounts of money for the therapies, based on the promise that bone marrow or umbilical-cord-blood stem cells can cure their disease.
 
Political opponents of embryonic stem cell research in the United States have claimed that bone marrow or umbilical-cord-blood stem cells can cure more than 70 diseases. Morrison said this claim is inaccurate: To date, bone marrow and umbilical-cord-blood stem cells have only been proven effective for the treatment of blood and immune system diseases.
 
“If your doctor doesn’t have compelling reason to believe that your disease can be treated effectively with the therapy that is being offered, and if there’s no compelling evidence in the scientific literature that this treatment really is a cure, and if it hasn’t been the basis of sound clinical trials that are open to the light of day and replicated in independent clinics, then there is reason to be skeptical, and you should be very cautious about seeking treatment in those clinics,” Morrison said.
 
These clinics operate outside of the United States because the U.S. Food and Drug Administration would prevent them from making these claims or offering their therapies in the this country, due to the lack of evidence supporting the safety or efficacy of the therapies, Morrison said.
 
“The unproven therapies are not sold to patients in the United States because medical care, stem cell research, and human-subjects research are tightly regulated here,” he said.
 
Clinical trials are being launched now in this country to test whether various types of stem cells can reduce the symptoms of amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease.
 
Dr. Eva Feldman, director of the U-M’s A. Alfred Taubman Medical Research Institute, will test whether implantation of neural stem cells benefits ALS patients. These studies are promising. But until approved clinical trials like this one have been completed, it will remain unknown whether stem cell transplantation can help these patients, or what kind of stem cell is most effective.
 
“Stem cell research offers exciting new opportunities to cure disease, and promising research is being done in many countries throughout the world,” Morrison said. “However, years of additional research will be required to determine which diseases can be treated effectively, and how. Until that research is done, and the safety and effectiveness of new therapies are confirmed in clinical trials, there is no basis on which to represent potential new therapies as cures.”

Related;

If you want to learn more about Stem Cell Research; Click Here

These publications and references will provide a general understanding of stem cells and how they work..

Frequently Asked Questions (FAQ)

Answers to commonly asked questions on stem cell science.

Glossary

Refer to our glossary for definitions of scientific terms.

Stem Cell Facts

This downloadable brochure provides an introduction to stem cell research and contains a short glossary of commonly used terms.

Stem Cell Briefings

Read about advances in stem cell research.

Evaluation of three different hepatitis C virus typing methods for detection of mixed-genotype infections

Evaluation of three different hepatitis C virus typing methods for detection of mixed-genotype infections
  1. Muhammad IDREES, Irshad UR REHMAN, Sobia MANZOOR, Haji AKBAR,
  2. Sadia BUTT, Samia AFZAL, Muhammad Zubair YOUSAF, Abrar HUSSAIN
Article first published online: 26 MAY 2011
DOI: 10.1111/j.1751-2980.2011.00496.x

OBJECTIVE: 
To evaluate the clinical applicability of an eligible assay for the true prevalence of hepatitis C virus (HCV) mixed-genotype infections.
METHODS: 
A newly developed HCV genotyping method targeting all six major HCV genotypes and 12 subtypes, restriction fragment length polymorphism (RFLP) and a serotyping assay were utilized for the detection of HCV mixed-genotype infections using known HCV genotypes and unknown samples.
RESULTS: 
In a defined mix of HCV genotypes, a genotype present at levels as low as 8.3% was detected by our newly developed assay, showing a threefold increase in sensitivity over that of direct deoxyribonucleic (DNA) sequencing. A comparative study of the accuracy among the three genotyping methods was carried out on samples obtained from 50 thalassemic patients who received multiple blood transfusions. The results showed that viruses in approximately 42% of the samples from this group were determined to be infected with mixed genotypes by our newly developed method. A serotyping assay and RFLP analysis, performed with poor results, could identify only 18% and 10% of mixed-genotype infections, respectively.
CONCLUSION: 
The newly developed assay may be the method of choice when detection of genotypes present at low levels in mixed-genotype infections due to its higher level of sensitivity.

Two New Drugs To Treat Hepatitis C And My Doctor

Hello Folks,
Published today online is an article from the Detroit Free Press which mentions my hepatologist Dr. Stuart Gordon. The article written by PATRICIA ANSTETT  touches on both new FDA approved drugs to treat hepatitis c, victrelis and incivek. This blog has mentioned the importance of finding a physician who specialize in treating HCV patients and is familiar with these new FDA approved drugs. Adherence is essential and the treatment regimen is complex. If you're from this area (Detroit/Novi) and looking for a physician I highly recommend Dr. Gordon. This physician is remarkable, published, attentive, kind and compassionate. It has been ten years since I achieved  SVR, but  I still recall sitting in his office feeling pretty much shocked when we were discussing how long treatment would be and what it would consist of. Its funny what we really fear when it comes to this disease, it came in steps for me. The first hurdle would be the ever looming liver biopsy. When he suggested it, I agreed, but only if it wasn't performed by a resident, and I wanted drugs, I didn't want to feel a thing.

I was so scared, newly diagnosed, I thought I was going to die from HCV before my next birthday, my children just lost their father a year earlier to this disease. However, because we were divorced I wasn't told it was from HCV. When I found out (sadly after reading his death certificate, I was tested, positive for HCV.) my search began for a doctor, this all transpired two weeks prior to making this appointment with Dr. Gorden. I remember looking up HCV in a medical book in the library, it contained one sentence which only alluded to the fact HCV was the most serious of all the hepatitis viruses. Nothing more, nothing less. At the time I had no idea I was about to embark on the ride of my life, but safely under the care of Dr. Gorden.   
Three weeks later the day came for my liver biopsy and I wondered if he would remember " no resident", in walked Dr.Gordon. I was one fortunate patient. He administered my demerol, and I started to relax. Before the procedure I asked him if he was nervous, he laughed and said; "Not as nervous as you are.", I love this guy folks. This was a busy man, in fact at the time he was running a few clinical trials.  He published numerous papers on interferon back then, you can read a handful of his papers here , here, and here. In fact that's how I found him, I read his work online.

At the time I had a dear friend who needed a second opinion, I suggested Dr. Gorden and soon she made an appointment. The prognosis wasn't good, Dr. Gorden gently advised her to start the process of  putting together a transplant team, she needed a new liver. At the time she had no idea how sick she was, none of us knew. A family member told me later Dr. Gordon was concerned of the probability she would die from acute liver failure before an organ was available. She was listed and because of a rare blood type a liver did not come in time. Even with Dr. Gorden's intervention we lost her quickly . If any of you are familiar with ESLD its can be a long painful death, in my friends case it was acute. With these new drugs now FDA approved, this disease can now be treated successfully in individuals who failed prior therapy. Yes, sadly enough it comes too late for many of our friends, but hope is now alive for the many thousands waiting to treat again. These brave people have waited a decade for these new drugs. Now hope is within their reach.

Dr. Stuart Gordon
1-800-HENRYFORD
(1-800-436-7936)

2 new drug treatments have cured thousands of liver disease

Two newly approved hepatitis C drugs may bring a cure to thousands of Americans not helped by previous treatments. But the drugs are costly and can cause unwanted side effects.
The drugs --Victrelis and Incivek-- have generated excitement among many of the 170,000 Americans who are diagnosed each year with the liver disease because the treatments might help those who haven't responded to other drugs.

"There's going to be a great demand," said Dr. Stuart Gordon, chief of hepatology at Detroit's Henry Ford Hospital. "A lot of prior non-responders will give it a try again."
Some studies show the drugs can cure as many as four out of every five patients who take them along with two conventional medicines.

Gordon said research suggests people more recently diagnosed with hepatitis C may benefit most from the drugs.
An estimated 4 million Americans have hepatitis C, though many are unaware of it because the virus is slow-growing and can linger for years without symptoms.

The drugs recently were approved for genotype 1 hepatitis C, the most common strain of six types.
Merck, manufacturer of Victrelis, said the drug will cost $26,000 to $48,400 for a course of treatment, depending on how long a patient takes it.

Vertex Pharmaceuticals, manufacturer of Incivek, said its drug will cost $49,200 for a course of treatment. The manufacturers have programs to help many uninsured or low- to middle-income patients get the drugs for free or at reduced costs.

Blue Cross Blue Shield of Michigan, which, as the state's largest health insurer, often sets reimbursement trends in Michigan, is reviewing whether it will cover either drug, said spokeswoman Helen Stojic.
Still unclear, Gordon said, is whether patients who aren't helped by the new drugs will develop resistance to similar medicines............ Continue Reading.........

Bulgaria's black market in blood is flourishing

SOFIA, Bulgaria (AP) — Her 85-year-old husband needed immediate surgery but doctors told her to find blood for the operation herself. So Slavka Petrova swallowed her anguish and went to haggle on the black market outside the national blood clinic.

It's a grim reality for patients and families in Bulgaria, a struggling EU nation where donors are troublingly scarce, hospitals are strapped for funds and blood traders — mainly Gypsy, or Roma, men — are thriving.

Trading in blood and blood products is illegal in Bulgaria, punishable by a fine of up to €5,000 ($7,100). But lawyers say it's difficult to prove an illegal blood transaction because that requires an official complaint lodged by the person who pays the donor — and families are so desperate they consider the black market blood donors lifesavers.

In the streets around the blood clinic, a dozen men sit smoking on benches or in cafes, on the alert for people in need. They don't have to wait long.

"Even before I had decided what to do, three men stood in front of me and one asked me what blood group I was looking for," Petrova, an 82-year-old former government employee, told The Associated Press.

The price can be prohibitive.

"When they told me that this would cost me €250 ($355), I thought, my God, this is my whole pension," she said. "I went mute for a while and they decided to lower the price to €200 ($285)."

Once a deal is struck, a donor hanging out nearby — or at most a phone call away — is summoned, and turns up at the blood clinic masquerading as a relative. He gets a proof of donation certificate and sells it to the desperate family. The blood heads off to be checked, and if it is found to be disease-free it goes toward filling the clinic's reserves.

So, lifesavers or bloodsuckers? It depends on where you sit.

Mariana Shipkovenska favors the first description. The former journalist had to rely on paid blood donors when her 89-year-old mother had surgery for a fractured thigh bone. She said she would have given blood herself but after a medical check her doctor advised her not to.

"They are the ones that give you something priceless when you need it and you can't find it anywhere else," she told the AP.

Traders also claim they provide a good service.

"I don't think it is a crime to help people who are in need," one told an AP journalist, refusing to give his name for fear of prosecution. "I haven't been able to find a job for years now and selling blood is a way for me and my family to survive."

Health workers at the blood center are well aware of the illegal transactions but feel powerless to do anything. At most, they ask police to shoo the traders from the entrance door, but the men soon return.

The deputy director of the center, Natalia Masharova, admitted that there was no legal way to prevent the practice.

"Although it is not legal, everyone is free to come and donate blood," she said.

Often the center itself loses out in the transaction. Blood found to be infected with HIV or Hepatitis B or C is thrown out and the donor put on a blacklist, but that takes time and the donation certificates are issued immediately, Masharova said.

Her boss at the center, Andrei Andreev, told AP the national clinic has enough blood to help those in need and urged people not to turn to the black market. But Rumen Dimitrov, a surgeon at ISUL, one of the main hospitals in Sofia, the capital, says the lack of sufficient blood supplies is a problem he runs into every day.

"We often have to ask relatives of our patients for certificates for blood donations because we receive only one liter of blood for a surgery from the blood center. In some cases two or more liters are needed," Dimitrov said. "Due to lack of enough blood, some scheduled surgeries are being postponed by weeks."

Up until 1989, when the Balkan nation was under a communist government, Bulgarians were eager blood donors. Army conscripts were awarded a two-day home leave each time they donated blood.

But voluntary blood donation has been gradually shrinking here over the past two decades, leaving Bulgaria above only by Albania, Bosnia and Moldova in Europe in the percentage of voluntary donors — 23 per 1000 people. The average for the United States is 53 per thousand, according to the American Association of Blood Banks, a figure similar to most EU countries.

"Only few become voluntary blood donors, because most people donate blood only if a relative or a friend needs it," said Stavri Toshkov, a leading hematology expert. "It is difficult to overcome the crisis of blood donation. Economic hardships have led to a deficit of such important values in society as solidarity, compassion and the willingness to help."

Bulgarian authorities are now urging residents to show compassion with those in need by joining blood donor campaigns. The Red Cross and the Christian Orthodox Church launched a two-month campaign around Easter dubbed "Light a candle, donate blood," hoping to raise awareness about the country's chronic blood shortage.

"It is the only way to eliminate the illegal trade," said Evelina Dinkova, one of the campaign's main organizers.

Associated Press
Copyright 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Spontaneous loss of hepatitis C virus RNA from serum is associated with genotype 1 and younger age at exposure

Spontaneous loss of hepatitis C virus RNA from serum is associated with genotype 1 and younger age at exposure

K.J. Rolfe1,*, M.D. Curran1, G.J.M. Alexander2, T. Woodall2, N. Andrews3, H.E. Harris4

Article first published online: 26 MAY 2011

DOI: 10.1002/jmv.22115

Abstract

A variety of factors have been associated with spontaneous loss of hepatitis C virus (HCV)-RNA from serum, including infecting HCV type, although results are conflicting. This study aimed to investigate further whether infecting HCV type was linked to spontaneous loss of HCV-RNA. Serum samples from 321 untreated HCV antibody positive patients presenting at the Hepatology clinic at Addenbrooke's Hospital, Cambridge between 2004 and 2007 were tested. These individuals were classified either as HCV antibody and HCV-RNA positive (viremic, n = 219) or HCV antibody positive and repeatedly HCV-RNA negative (non-viremic, n = 102). Infecting HCV type was identified by genotyping (viremic) or serotyping (non-viremic). Binomial regression analysis investigated the independent effect of HCV type on spontaneous loss of HCV-RNA from serum by comparing the two groups. Ninety-one percent of patients were found to be either genotype 1 or genotype 3. The prevalence of type 1 infection was greater among non-viremic (64.5%) than viremic individuals (45%). After controlling for the effects of potential confounding factors, multivariable analyses showed that individuals with type 1 infections were more likely to be non-viremic than genotype 3 infections (RR = 2.07; 95% CI: 1.25, 3.43; P = 0.005). Individuals infected at an older age were also less likely to become HCV-RNA negative spontaneously (RR = 0.42 comparing those infected at ≥20 years of age against those infected at <20 years of age, 95% CI: 0.25, 0.72; P = 0.002). In conclusion, the results suggest that HCV genotype 1 infections are more likely than genotype 3 infections to become spontaneously non-viremic, as are infections acquired at younger age. J. Med. Virol. © 2011 Wiley-Liss,

Risk estimation for hepatocellular carcinoma in chronic hepatitis B

The Lancet Oncology, Volume 12, Issue 6, Pages 568 - 574, June 2011
doi:10.1016/S1470-2045(11)70077-8Cite or Link Using DOI
Published Online: 15 April 2011
/
Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score
/
Hwai-I Yang PhD a b, Prof Man-Fung Yuen MD c, Prof Henry Lik-Yuen Chan MD d, Prof Kwang-Hyub Han MD e, Prof Pei-Jer Chen MD f, Do-Young Kim MD e, Sang-Hoon Ahn MD e, Prof Chien-Jen Chen ScD a g Corresponding AuthorEmail Address, Vincent Wai-Sun Wong MD d, Wai-Kay Seto MBBS c, for the REACH-B Working Group
 
Summary
 
Background
Therapy for chronic hepatitis B reduces the risk of progressing to hepatocellular carcinoma (HCC); however, there is no suitable and accurate means to assess risk. This study aimed to develop and validate a simple scoring system to predict HCC risk in patients with chronic hepatitis B.
 
Methods
The development cohort consisted of 3584 patients without cirrhosis from the community-based Taiwanese REVEAL-HBV study (of whom 131 developed HCC during follow-up), and a validation cohort of 1505 patients from three hospitals in Hong Kong and South Korea (of whom 111 developed HCC during follow-up). We used Cox multivariate proportional hazards model to predict risk of HCC at 3, 5, and 10 years. Variables included in the risk score were sex, age, serum alanine aminotransferase concentration, HBeAg status, and serum HBV DNA level. We calculated the area under receiver operating curve (AUROC) and calibration of predicted and observed HCC risk.
 
Findings
A 17-point risk score was developed, with HCC risk ranging from 0·0% to 23·6% at 3 years, 0·0% to 47·4% at 5 years, and 0·0% to 81·6% at 10 years for patients with the lowest and highest HCC risk, respectively. AUROCs to predict risk were 0·811 (95% CI 0·790—0·831) at 3 years, 0·796 (0·775—0·816) at 5 years, and 0·769 (0·747—0·790) at 10 years in the validation cohort, and 0·902 (0·884—0·918), 0·783 (0·759—0·806), and 0·806 (0·783—0·828), respectively, after exclusion of 277 patients in the validation cohort with cirrhosis. Predicted risk was well calibrated with Kaplan-Meier observed HCC risk.
 
Interpretation
A simple-to-use risk score that uses baseline clinical variables was developed and validated. The score accurately estimates the risk of developing HCC at 3, 5, and 10 years in patients with chronic hepatitis B. Clinicians can use this score to assess risk of HCC in patients with chronic hepatitis B and subsequently make evidence-based decisions about their clinical management.
 
Funding
The Academia Sinica; the National Health Research Institute, Taiwan; and Bristol-Myers Squibb.
 

Hepatitis C Treatment; SVR is the goal, and humor is the rescue drug.

Happy Sunday folks,


Today is the second day of a nice long holiday weekend. For all of you getting ready to treat this serious disease, I thought I may offer up some advice from my own treatment experience, yuck. Hey, any seasoned patient who has treated will tell ya, you need to laugh, and laugh often!

10 Guideline's: Not In Any Particular Order, And Not Really Helpful





1-Before that first appointment take the time to print out the medication guide and prescribing information, ask the doc to read it to you. Then stand back and chuckle to yourself before saying; "Just kidding". 




2-Get prepared by getting your personal space ready, remove all family, sharp items, mirrors, and pets. I should mention my friend shot his dog during therapy, the dog was fine but his wife left him. We blamed it on the Riba Rage, she blamed it on his girlfriend.





3-Rash=Serious. If you develop a rash, move up your doctors appointment. Let the doc know he better take notice and then ask for your money back. Just kidding Vertex. Thank you for telaprevir !





4-Do not attempt to fix, manipulate, take apart, or re-wire anything in your household, unless its your teenager, and then do it just for fun.






5-If your hair is looking a little limp, thin, be grateful you still have your mind. If that starts to go, tell yourself its better then your limbo. If that's the next thing to go, then worry about your hair.






6-If you're working, ask the boss for a raise. When he looks surprised, blame it on treatment.  If you're not working- good- you won't miss work. If you're starting a new job, don't mention the high wage demands you made on the last job. Why make the same mistake twice ?





7-Hey, cooking during therapy is just silly and dangerous. STAND away from the kitchen. If you're the chosen one, the iron chef, a family of four can live on water and soup for around 24 to 48 weeks.







8-DO NOT look up your side effects on the Internet, I know you will, we all do. Warning; be prepared to ask the doc to test for yellow fever, chickenpox, hand-foot-and-mouth disease, chronic fatigue syndrome and intestinal parasites. An imagination is a terrible thing to waste on treatment.


  
9-Sorry, but no sun or tanning booths during therapy folks. Looking pale is the new tan, and who needs to walk around looking healthy all the time ?
Disclaimer typed in very small text so you can't read it.
<----The image is not a person on treatment, silly you,  its my doctor after I finished treatment. He still won't take my calls, just kidding.






10-Try to keep busy, move around, put up a birdhouse, get out, see friends, or talk on the phone; call your kids on the weekend, just to see if anyone answers. If the kids live at home, call their cell phone. If you have no kids, call a friend and tell them you're busy.

If you follow these ten guidelines, after treatment you'll either end up living alone, friendless or homeless.

Sending all my readers a huge smile, and a warm embrace. Wishing you all a safe and successful journey. SVR is the goal, and humor is the rescue drug.


Video/Vertex Incivek Patient Steve Goodwin On Telaprevir


At SFGate is a video interview with Steve Goodwin a patient who underwent HCV therapy with Incivek, better known as telaprevir. Steve is a genotype 1 null responder, see his video below.
You can read Mr. Goodwins paper on Incivek here.
   
 

Package Inserts for Peginterferon alfa and Ribavirin

Patient Assistance Program
INCIVEK/Telaprevir and VICTRELIS (Boceprevir) Patient Assistance Programs

FDA May 23, 2011 Teleconference Briefing on Direct Acting Antivirals, Victrelis (boceprevir) and Incivek (telaprevir) transcript
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New two part video from Melissa Palmer, M.D. on Telaprevir (Vertex Pharmaceuticals) & Boceprevir (Merck), the new protease inhibitor treatments for hepatitis C (HCV).
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From The AIDS Beacon
This article is first in a two-part series that will discuss the benefits and drawbacks of two drugs, boceprevir and telaprevir, which are being developed for hepatitis C. Part 1 discusses the efficacy of the two drugs in clinical trials. Part 2 discusses the complications and side effects for each drug


Organ Quality Varies According to Transplant Center

The quality of deceased-donor organs available for transplantation varies based on characteristics of the transplant center, according to a study published in the May issue of the American Journal of Transplantation.

MONDAY, May 16 (HealthDay News) --

The quality of deceased-donor organs available for transplantation varies based on characteristics of the transplant center, according to a study published in the May issue of the American Journal of Transplantation.

Michael L. Volk, M.D., from the University of Michigan in Ann Arbor, and colleagues evaluated whether the quality of donor livers used in transplants varies between transplant centers, and whether some centers systematically use lower-quality organs. A total of 23,810 adults who underwent deceased-donor liver transplantation between January 2005 and February 2009 were included in the analysis. Variations in the donor risk index (DRI) were measured by region, organ procurement organization (OPO), and transplant center.

The investigators found that the mean DRI for transplant centers ranged from 1.24 to 1.74, even after adjusting for geographic region and OPO. Centers with higher volume, and those with competing centers within their OPO, were more likely to use organs with high risk, particularly for recipients with lower model for end-stage liver disease scores. Waiting-list mortality rates were similar in centers that use high-risk organs, but they tended to have an increased post-transplant mortality (hazard ratio, 1.10 for a mean DRI increase of 0.1).

"These findings provide further evidence that decision making about organ quality is influenced by external forces, and emphasizes the importance of transparency in organ acceptance practices," the authors write.

Abstract
Full Text (subscription or payment may be required)

Natural substance may improve insulin sensitivity and limit fatty liver deposits in individuals with type 2 diabetes

  • Saturday, May 28, 2011
  • Posted by HCV New Drugs
  • File Under

A natural substance known as dilauroylphosphatidylcholine, or DLPC, has been shown by a recent study to reduce fatty deposits in the liver and improve insulin sensitivity, two major problems among individuals with type 2 diabetes.

Researchers from Baylor University began studying the substance because they thought it would stimulate the protein liver receptor homolog-1 (LRH-1). This protein is important because it regulates bile production, which is key to the body's ability to break down food.

While the results of the testing, which were published in the journal Nature, showed that DLPC led to modest gains in bile production, the compound's ability to eliminate fatty deposits in the liver and improve insulin sensitivity were much more encouraging.

In testing on laboratory mice bred to have impaired glucose control and insulin resistance, the team found that subjects treated with DLPC became much more sensitive to the effects of the hormone and had significantly lower blood sugar levels. Additionally, protein markers of fatty liver deposits were reduced.

However, these benefits were not evident in mice that were engineered to lack LRH-1, suggesting that the effects may be connected to bile production.

The researchers said that they were not completely sure how DLPC gets rid of fat in the liver but speculated that increased bile production may silence certain proteins that are involved in the production of fats.

The findings could have important implications for the treatment of individuals who may be likely to develop type 2 diabetes. Currently, the researchers are continuing their trial in humans who are overweight and at risk for the metabolic condition. The team is testing whether taking supplements containing DLPC for two months can improve insulin sensitivity.

If their trial is successful, it could mark a major advancement in the prevention of type 2 diabetes. DLPC is widely available in the form of lecithin supplements

The hepato-protective effect(s) of three cups of a coffee a day: Relevance for patients with chronic hepatitis C

Related; Caffeine and Liver Disease in People with Hepatitis C

The hepato-protective effect(s) of three cups of a coffee a day: relevance for patients with chronic hepatitis C

Volume 54, Issue 6, Pages 1085-1086 (June 2011)

Coffee intake has been reported to exert a number of beneficial effects on health including among others, reducing the risk of type 2 diabetes, reducing inflammatory activity and C reactive protein in various diseases and diminishing oxidative stress. The first observations regarding potential beneficial effects of coffee consumption on alanine aminotransferase and γ-glutamtyl transferase activities in patients with chronic liver disease (CLD) were already reported in the 1990s [1], [2]. Since then, evidence for this association gained significant support in several studies performed in Japan, Europe and the US. Recently Freedman and co-workers have conducted a large prospective study in 766 participants of the HALT-C study who had chronic hepatitis C (CHC) with bridging fibrosis and cirrhosis and who failed to achieve a sustained virologic response to pegylated interferon and ribavirin [3]. In this study coffee consumption at base line was shown to be associated with a number of factors including less severe steatosis and lower alanine aminotransferase levels. Furthermore, regular coffee consumption during the observation period (median follow-up 3.8years) was associated with lower rates of disease progression.

In this study, association of coffee intake with progression of liver disease was independent of alcohol intake and cigarette smoking. One year later, Modi and co-workers reported that caffeine consumption, mainly from regular coffee, at an equivalent of 2–3 cups a day, was associated with less severe fibrosis on liver biopsies, as observed in a cohort of 177 patients, of whom 68% had CHC [4]. Finally, two recent meta-analyses confirmed the protective effect of coffee intake on the development of hepatocellular carcinoma in patients with cirrhosis [5], [6].

In the present issue of the Journal, Costentin and co-workers assessed the impact of caffeine consumption on necroinflammatory disease activity and grade of fibrosis in a relatively homogenous cohort of 238 treatment naïve patients with histologically proven CHC, predominantly with genotype 1. Caffeine intake was established as the sum of mean consumption of coffee, tea and caffeine containing beverages and categorized into four levels according to the calculated daily dose. Multivariate analysis revealed that daily caffeine consumption of 408mg was associated with a lesser risk of necro-inflammatory activity as determined by the Metavir score. However, in contrast to previous observations, the investigators did not find a relationship between the degree of caffeine intake and fibrosis stage.

The results in the present study confirm a number of previous observations that caffeine intake has an indirect or direct effect on suppression of necroinflammtory activity as assessed by ALT measurements or by a liver biopsy in CLD in general and in CHC in particular. However, it stands in contrast to a number of previous studies including the recent report of Modi et al. who found a beneficial effect of caffeine on progression of fibrosis in CHC and most probably in CLD of other etiologies. How can these conflicting observations be reconciled? Costentin and co-workers try to provide a hypothesis to explain this difference which suggests that suppression of necroinflammatory liver injury by caffeine directly or indirectly slows down the progression of fibrosis.

Although this may be the case, such a hypothesis does not provide a clue to decipher the mechanism involved in the hepato-protective effect(s) of coffee and caffeine in CLD. In their study, Modi et al. could not establish a link between coffee consumption and hepatic inflammation and suggest that caffeine may have an independent anti-fibrogenic effect in the liver, possibly through inhibition of the transforming growth factor β pathway [4]. The impact of such a putative anti-fibrotic effect was not observed in the present study by Costentin et al. Last but not least, in addition to caffeine, coffee contains hundreds of other compounds which may act in concert with caffeine in suppressing the necro-inflammatory activity in patients with CHC and CLD. The lack of a control group of CHC patients consuming decaffeinated coffee in the present study does not enable assessment of the specific hepato-protective effect of caffeine on such activity.

In conclusion, many previous reports as well as the report discussed herewith, suggest that coffee consumption has a beneficial effect on disease progression in CHC and possibly also in CLD of other etiologies as reviewed in the articles by Freedman and Modi et al. [3], [4]. Thus, irrespective of the controversy regarding the mechanism involved and regardless of other potential confounding factors such as alcohol consumption and/or cigarette smoking, the already available evidence suggests that 2–3 cups of coffee a day are beneficial in patients with chronic liver disease in general and in CHC patients with advanced fibrosis in particular.

High Demand for New HCV Drugs Could Cause Ethical Problems

  • Posted by HCV New Drugs
  • File Under


High Demand for New HCV Drugs Could Cause Ethical Problems
Jim Kling

May 27, 2011 — Earlier this month, the US Food and Drug Administration approved the drugs boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex) for the treatment of hepatitis C virus (HCV) infection. The approvals are good news for patients with HCV, but high patient demand could lead to scarcity and ethical challenges for treatment providers, according to a viewpoint article published in the June issue of Hepatology.


HCV is responsible for 120 million infections worldwide and is a leading cause of liver failure mortality, explain authors Andrew Aronsohn, MD, and Donald Jensen, MD, from the Center for Liver Disease, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medical Center, Illinois. Pegylated interferon and ribavarin have had some effect, but less than half of patients with HCV achieve a sustained virologic response.
Clinical trial results suggest telaprevir and boceprevir will achieve marked improvement in sustained virologic responses in genotype 1 patients compared with current standard of care therapy.
Some patients who are at low risk for near-future progression have deferred therapy in anticipation of the arrival of these drugs. A recent Veterans' Administration study revealed that 50.3% of patients who refused treatment with interferon and ribavirin did so in anticipation of more effective drugs.
These patients will add to the demand for the drugs, complicating efforts to monitor and educate patients, which is already challenging because treatment regimens are complex. In addition, it could place undue demand on healthcare providers. The authors conducted a time analysis study at their own institution and found that the average healthcare provider could initiate treatment in 3 patients with HCV in a week. They anticipate receiving 500 new patients in the weeks after approval of the new drugs.
This situation, if widespread, could lead to scarcity and inequitable distribution of the drugs. Historically, as in the cases of penicillin, insulin, and other new medical developments that were initially scarce, this has led to inequitable and unjust distribution patterns.

Dr. Aronsohn and Dr. Jensen propose a needs-based solution to the dilemma. Highest priority would be given to the sickest patients, and the remaining patients could be prioritized based on need, starting with cirrhotic patients and ending with asymptomatic F0 to F2 patients. Patients could be educated about the need for providing therapy to the most ill patients and informed that waiting for therapy is safe for patients with early-stage disease.

The authors have disclosed no relevant financial relationships.
Hepatology. 2011;6:1789-1791.

Hepatitis C; Do I still need a liver biopsy? What Is A Noninvasive Test For Fibrosis ?

Picture
2013 - .....
In The News  - Related Updates

With the new drugs to treat hepatitis C now FDA approved some people are asking if a liver biopsy will be in the mix. Today on the blog we will discuss the newest guidelines presented at the 2011 EASL and the 2009 guidelines from the AASLD in regard to the latest  recommendations for undergoing a liver biopsy in  the HCV population .
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Alternative noninvasive tests will be covered with links to data that should help aid in a clear understanding of what is available, and how reliable these noninvasive tests are. The patient and their physician will determine if a liver biopsy may be useful, the information provided here today will also give you an update on the noninvasive tests available to monitor disease progression. 

Noninvasive measurements  (blood tests) of liver fibrosis biomarkers are an alternative to liver biopsy for diagnosing the degree of fibrosis due to HCV infection .The various biomarker tests included in this entry are as follows;
 Fibrotest, Fibrometer, Hepascore, AST: platelet ratio index (APRI), Forms, Fib-4, and SHASTA.

Also included is transient elastography (ultrasound-based scan) which is a non-invasive method for evaluating liver fibrosis by measurement of liver stiffness. Better known as FibroScan; the method has been shown to be reliable in the assessment of liver fibrosis in patients with chronic hepatitis C. 

According to a paper published in the Jan 2011 issue of  Liver International, combined use of transient elastography- TE, example "Fibroscan" and biomarkers (blood test) example "APRI and Fibrotest" could help most patients avoid a liver biopsy who have chronic hepatitis. As noted by the authors;

Numerous biomarkers have been proposed in hepatitis C (18, 19, 20) but the most widely used and validated with transient elastography-TE are the "aspartate-to-platelet ratio index (APRI) (a free non-patented index) and the FibroTest" (21, 22, 23).
The results of TE and serum biomarkers for the diagnosis of significant fibrosis have been shown to be equivalent in patients with chronic hepatitis C infection (24, 25). Indeed, in the largest study to date (n=1307) (25), comparing TE with several patented and non-patented biomarkers (FibroTest, Fibrometre, Hepascore and APRI) and using liver biopsy as a reference, the AUROCs of TE (0.76) did not differ from those of serum biomarkers (0.72–0.78).
In order to increase the diagnostic accuracy of these tests, the sequential combination of biomarkers (26, 27) or the concomitant combination of TE and biomarkers (24, 28, 29) has been proposed. The latter strategy may be more effective for diagnosing significant fibrosis, leading to a reduction in the use of liver biopsy in more than 70% of cases compared with 50% when using biomarkers (APRI and FibroTest) sequentially (30). Another advantage of combining two unrelated methods such as TE and biomarkers rather than two biomarkers is that TE provides a more direct measurement of liver structure than biomarkers and there is no relationship between the applicability of TE and biomarkers such as the FibroTest (28).
In the same paper entitled; How to assess liver fibrosis in chronic hepatitis C: serum markers or transient elastography vs. liver biopsy? the authors concluded that non-invasive tests can be used for the first-line staging of fibrosis in naive patients who will be treating HCV with antiviral therapy, .

Excerpted;

In naïve patients without comorbidities who are candidates for antiviral treatment, non-invasive tests can be used for the first-line staging of fibrosis. The use of either  transient elastography - TE or several patented biomarkers (FibroTest, Fibrometer and Hepascore) has recently been recommended, based on an independent systematic review by the French Health Authorities . However, this strategy should also take into account HCV genotype, local availability of non-invasive methods and any clinically relevant variable.
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For instance, when there is a strong clinical suspicion of cirrhosis, in most cases the use of TE is enough to confirm the diagnosis without a liver biopsy. Conversely, a liver biopsy may be necessary to differentiate between F1 "minimal scarring" and F2 "scarring has occurred and is inside the areas of in genotype 1-infected patients before making a decision on antiviral treatment. In the same way, a liver biopsy may be useful to differentiate between F3 "bridging fibrosis (the fibrosis is spreading and connecting to other areas that contain fibrosis" and F4 "cirrhosis" when cirrhosis is not clinically obvious and to decide when to start screening for hepatocellular carcinoma. However, with the availability of new antiviral treatments, differentiating between F1 and F2 may not be as important for treatment indications.
the liver including blood vessels" 

When deciding on retreatment, a liver biopsy may be indicated to investigate the presence of factors of impaired response such as non-alcoholic steatohepatitis or to obtain a prognosis especially if a liver biopsy has not been performed previously.
Finally, non-invasive methods can be of interest in the follow-up of untreated patients . Given the slow rate of the progression of fibrosis in chronic hepatitis C, a non-invasive evaluation can be performed on a yearly basis
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Using Noninvasive Tests To Evaluate Liver Disease Severity Earlier

From Medwire
These noninvasive tests - FibroTest (a liver biomarker test) and liver stiffness (measured by ultrasound scan example;FibroScan) - may help clinicians evaluate liver disease severity earlier in the disease process, and to decide if liver transplant, portosystemic shunts, or surgery will be required by the patient at a later date, say the authors.

Reported in the March 2011 issue of journal Gastroenterology an analysis showed that FibroTest and liver stiffness measurements had high predictive accuracies for 5-year chronic hepatitis C survival, with respective area under the receiver operating characteristic curve (AUC) values of 0.80 and 0.82.
In contrast, liver biopsy had a lower, albeit clinically acceptable, AUC value of 0.76.
The findings arise from a study involving 1457 patients with chronic hepatitis C who were followed-up for 5 years. You can view the abstract here.
Noninvasive Blood Tests (Biomarker Test)
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Fibrotest-FibroTest, known as FibroSure in the US, is a patented biomarker test that uses the results of  blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases.  The HCV-FibroSure Test includes the following five markers, as well as age and gender: alpha2-macroglobulin, haptoglobin, gamma-glutamyl transpeptidase (GGT), total bilirubin, apolipoprotein A1, plus alanine aminotransferase (ALT). 


APRI AST: platelet ratio index (APRI),
Abbreviation: (APRI), Definition: AST to platelet ratio index
APRI Score is an easy, low cost and practice alternative method which was described as an alternative for assessing structural changes in chronic hepatitis C .The APRI was designed to be a convenient marker of fibrosis because it incorporates laboratory data that are routinely obtained as the standard of care. Initial studies showed that it performed well in predicting fibrosis and cirrhosis in both a training and validation set of adults with chronic HCV infection. APRI, calculates only the AST to platelet ratio .

Fibrotest and APRI

Click On Table To Enlarge




Forns: A non-invasive method for monitoring liver disease . The Forns' score combines age, gGT, cholesterol, and platelet count.platelet count.
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Fib-4 A non-invasive method for monitoring liver disease. FIB-4 score, is based on a calculation of a person’s age, alanine transaminase (ALT) levels and the ratio of aspartate transaminase (AST) levels to platelet count.


SHASTA A non-invasive method for monitoring liver disease. The SHASTA index developed consists of serum hyaluronic acid, AST, and albumin

Fibrometer-FibroMeters are non-invasive blood tests for liver fibrosis . The score combines hyaluronate, prothrombin time, platelets, AST, a2 macroglobulin, urea, and age, and the formula is adjusted based on the cause of the liver disease.

EASL 2011- FibroMeter
This study, performed in several populations with C hepatitis, shows that the detailed classification in fibrosis stages of FibroMeter3G (1) is as performant as that of an expert pathologist and significantly superior to that of a first line pathologist or that of other non-invasive tests.

CirrhoMeter is the first validated and marketed test for cirrhosis diagnosis
EASL 2011-CirrhoMeter
This study, performed in 1710 C hepatitis, shows that the CirrhoMeter (5) offers an excellent cirrhosis diagnosis: accuracy superior to that of Fibroscan, on an intention to diagnose basis, with a higher precision

EASL 2011-During the last EASL meeting (Berlin), 5 communications on CirrhoMeter and FibroMeters were presented.


Hepascore- Hepascore is an Australian blood test combining the following clinical and laboratory variables: age, gender, bilirubin, GGT, hyaluronic acid, alpha 2 macroglobin to create a score.

Physical Non-invasive methods for the assessment of liver fibrosis

Transient elastography (TE)

Transient elastography that uses ultrasound and low frequency elastic waves to measure liver elasticity67 has improved the ability to define the extent of fibrosis without a liver biopsy, particularly when combined with other noninvasive markers (blood tests) .68 However, it is not yet ready to replace the liver biopsy since it is not FDA approved, the failure rate is higher in obese patients, and there is now evidence that the transient elastography score can be unexpectedly increased in persons with acute hepatitis who have high necroinflammatory activity but no or minimal fibrosis.

Video FibroScan


Excerpted From;

Assessment of liver disease severity

Assessment of the severity of hepatic fibrosis is important in decision making in chronic hepatitis C treatment and prognosis.

Liver biopsy is still regarded as the reference method to assess the grade of inflammation and the stage of fibrosis [22,23]. The shortcomings of biopsy have been highlighted in recent years and alternate non-invasive methods have been developed and extensively evaluated in patients with chronic HCV infection. They include serological markers and transient elastography [24,25]. Their performance,when used alone or together, has been reported to be comparable with liver biopsy [24,25]. Both non-invasive
methods have been shown to accurately identify patients with mild fibrosis or cirrhosis. They are less able to discriminate moderate and severe fibrosis.[22,23].

Assessment of liver disease severity is recommended prior to therapy. Identifying patients with cirrhosis is of particular importance, as their likelihood of responding to therapy and post-treatment prognosis are altered, and surveillance for HCC is required.

Assessment of the stage of fibrosis by biopsy is not required in patients with clinical evidence of cirrhosis. Since significant fibrosis may be present in patients with repeatedly normal ALT, evaluation of disease severity should be performed regardless of ALT patterns. Endoscopy to rule out esophageal varices and portal hypertension should be performed in patients with known cirrhosis.

Liver biopsy remains the reference method. The risk of severe complications is very low (1/4000–10,000), but biopsy remains an invasive procedure. Histological features (necroinflammation = grading; fibrosis = staging) should be reported using a structured, semi-quantitative method. Various scoring systems have been validated for use in chronic hepatitis C. The most widely used in Europe are METAVIR, Scheuer, Ishak, and Knodell’s HAI [63]. Metavir and Scheuer’s scores are more reproducible and less prone to observer variation, but less discriminant both for fibrosis and for necroinflammation than Ishak and Knodell [64].

Based on the abundant literature in chronic hepatitis C, alternative, non-invasive methods can now be used instead of liver biopsy in patients with chronic hepatitis C to assess liver disease severity prior to therapy at a safe level of predictability.


Transient elastography (TE), can be used to assess liver fibrosis in patients with chronic hepatitis C, provided that consideration is given to factors that may adversely affect its performance such as obesity, age, and biochemical necroinflammatory activity. TE results should be evaluated relative to interquartile range and to the success rate of measurements. TE performs better at detecting cirrhosis than lesser degrees of fibrosis [65,66].

The well established panels of biomarkers of fibrosis can be broadly categorized as those that include commonly performed biochemical and hematological tests, such as ALT, AST, prothrombin time, platelets (APRI, AST/ALT ratio, Forns Index); those that include specific indirect markers of liver fibrosis, such as a-2 macroglobulin; those that incorporate only direct markers of liver fibrosis (MP3), or combinations of direct and indirect markers (Hepascore, Fibrometer). Sufficient evidence exists to support the view that algorithms perform well in the detection of significant fibrosis (METAVIR score F2-F4). Thus, their use in patients
with chronic hepatitis C can be recommended for this purpose.

They all perform less well in the detection of lesser degrees of  fibrosis [66–69]. The combination of blood tests or the combination of TE and a blood test improve accuracy and reduce the necessity of using liver biopsy to resolve uncertainty. However, they increase the cost [70].[65,66].

Recommendations

(1) Liver disease severity should be assessed prior to therapy
(B1).

(2) Identifying patients with cirrhosis is of particular importance, as their prognosis and likelihood to respond to therapy are altered, and they require surveillance for HCC (A1).

(3) As liver disease can progress in patients with repeatedly normal ALT levels, disease severity evaluation should be performed regardless of ALT levels (B2).

(4) Assessment of the severity of liver fibrosis is important in decision making in patients with chronic hepatitis C (A1).

(5) Liver biopsy is still regarded as the reference method to assess the grade of inflammation and the stage of fibrosis (A2).

(6) Transient elastography (TE) can be used to assess liver fibrosis in patients with chronic hepatitis C (A2).

(7) Non-invasive serum makers can be recommended for the detection of significant fibrosis (METAVIR score F2–F4) (A2).

(8) The combination of blood tests or the combination of transient elastography and a blood test improve accuracy and reduce the necessity of using liver biopsy to resolve uncertainty

Excerpted From; AASLD

Utility of the Liver Biopsy and Noninvasive

Tests of Fibrosis
There are three primary reasons for performing a liver biopsy: it provides helpful information on the current status of the liver injury, it identifies features useful in the decision to embark on therapy, and it may reveal advanced fibrosis or cirrhosis that necessitates surveillance for hepatocellular carcinoma (HCC) and/or screening for varices. The biopsy is assessed for grade and stage of the liver injury, but also provides information on other histological features that might have a bearing on liver disease progression.49 The grade defines the extent of necroinflammatory activity, while the stage establishes the extent of fibrosis or the presence of cirrhosis. Several scoring systems have been conceived, the most common being the French METAVIR, the Batts-Ludwig, the International Association for the Study of the Liver (IASL) and the Ishak Scoring systems.50-54 (Table 7).

The two more common non-HCV conditions that might affect disease progression and possibly impede treatment response are steatosis 49,55,56 and excess hepatocellular iron.57 Identifying either of these two features does not preclude initiating treatment, but their presence provides additional information regarding the likelihood of response to treatment.

The liver biopsy has been widely regarded as the “gold standard” for defining the liver disease status, but it has drawbacks that have prompted questions about its value.

Click On Table To Enlarge
,
Table 7 Comparison of Scoring Systems for Histological Stage Stage




HEPATOLOGY, Vol. 49, No. 4, 2009 GHANY ET AL. 1339

The procedure is not without risks (including pain, bleeding and perforation of other organs),63,64 it is
subject to sampling error,65 it requires special expertise for interpreting the histopathology, it adds cost to medical care, and it is anxiety-provoking for the implicated person.

Thus, efforts are underway to seek alternative means of establishing information on the extent of fibrosis by focusing on noninvasive blood marker panels.66 These markers are useful for establishing the two ends of the fibrosis spectrum (minimal fibrosis and cirrhosis) but are less helpful in assessing the mid-ranges of fibrosis or for tracking fibrosis progression.66 The recently developed transient elastography that uses ultrasound and low frequency elastic waves to measure liver elasticity67 has improved the ability to define the extent of fibrosis without a liver biopsy, particularly when combined with other noninvasive markers.68 However, it is not yet ready to replace the liver biopsy since it is not FDA approved, the failure rate is higher in obese patients, and there is now evidence that the transient elastography score can be unexpectedly increased in persons with acute hepatitis who have high necroinflammatory activity but no or minimal fibrosis.69,70

Genotypes
A liver biopsy may be unnecessary in persons with genotypes 2 and 3 HCV infection, since more than 80% of them achieve a sustained virlogical response (SVR) to standard-of-care treatment. There is, however, an ongoing debate about whether a biopsy is warranted for persons infected with HCV, genotype 1, whose response to such treatment approximates 50% among Caucasians and 30% among African Americans.71-73 Even more uncertain is whether there is need for a liver biopsy in persons infected with the other less common genotypes (4 through 6).

Thus, although the liver biopsy was previously regarded as routine for defining the fibrosis stage in persons with genotype 1 infection,62 the issue is now in a state of flux and possible transition. Supporters of a biopsy cite the difficult nature and high cost of current antiviral therapy and are therefore willing to withhold or delay treatment if liver histology displays minimal to moderate fibrosis stage 2 (Table 7), especially if the infection is known to have been long-standing. These individuals are regarded as having slowly progressive liver disease that may not be responsible for their ultimate demise74-76

However, treatment is advised for those with more advanced fibrosis stage 3 (Table 7) It must be noted, however,that while information obtained from a biopsy is useful, the procedure is not mandatory for deciding on treatment. If performed and treatment is withheld, a common strategy is to repeat the liver biopsy 4 to 5 years later and to reconsider treatment should there be evidence of disease progression.77

The earlier views that persons with genotype 1 infection and persistently normal aminotransferase values did not require a liver biopsy because they were believed to have minimal liver disease, and that treatment may actually be harmful, are no longer valid.78 It is now apparent that as many as a quarter of such individuals have significant fibrosis,78-81 and that treatment response is similar to that of individuals with abnormal serum aminotransferase levels.82-84

Therefore, the decision to perform a liver biopsy should be based on whether treatment is being considered,taking into account the estimated duration of infection and other indices of advancing liver disease (e.g., the platelet count), the viral genotype, and the patient’s willingness to undergo a liver biopsy and motivation to be treated. If the biopsy is not performed and treatment not undertaken, the patient should continue to be monitored at least annually and a biopsy performed if the aminotransferase values become abnormal and other indicators of progressing liver disease become apparent.

Recommendations

7. A liver biopsy should be considered in patients with chronic hepatitis C infection if the patient and health care provider wish information regarding fibrosis stage for prognostic purposes or to make a decision regarding treatment (Class IIa, Level B)

8. Currently available noninvasive tests may be useful in defining the presence or absence of advanced fibrosis in persons with chronic hepatitis C infection, but should not replace the liver biopsy in routine
clinical practice (Class IIb, Level C).
.


Of interest published in the June 2011 issue of the Scandanavian Journal of Gastroenterology;
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Percutaneous liver biopsy is widely approved by patients and is also regarded as a useful procedure, reports June's issue of the Scandanavian Journal of Gastroenterology
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Hepatic fibrosis can be assessed through serum markers or by the implementation of new non-invasive techniques, such as elastography.
One must know patients' opinion on percutaneous liver biopsy when it comes to comparing it with other procedures.

Dr Luis Fernández-Salazar and colleagues from Spain investigated the point of view of patients undergoing a percutaneous liver biopsy with regard to information provided to them, as well as the procedures and biopsy consequences.

A questionnaire was sent by mail to 178 patients who underwent percutaneous liver biopsy from 2006 to 2010.

Results are expressed in percentages and compared based on gender and age.
The team reported that 90 patients of the group answered, of which 44 were females, with a mean age of 47 years.

The answers revealed that 93% of patients rated the information concerning the reasons for a percutaneous liver biopsy as adequate.

As for the information concerning the objective of the procedure, 88% of patients regarded it as adequate.
As for the information concerning the risks of a biopsy, 78% see it as sufficient.
About 12% of patients did not receive any information on the physician who asked for the percutaneous liver biopsy, or who performed it.

Percutaneous liver biopsy was considered very painful by 14% of patients, painful by 21%, bothersome by 41% and barely bothersome by 23% of patients.

The research team found that 35% of patients required analgesia after the puncture.
The team observed that even though 92% of patients regard percutaneous liver biopsy as a useful procedure, 46% of them have not received any treatment or a different nutritional regime.

The research team found that 80% of patients think that percutaneous liver biopsy has more benefits than drawbacks, although 87% would have opted for a less aggressive technique as long as it would have provided the same information.

However, 21% of patients would have also preferred a less aggressive technique, even though it provided fewer details.

Dr Fernández-Salazar's team concluded, "In general, percutaneous liver biopsy is widely approved by patients and is also regarded as a useful procedure."
"One out of 6 patients would rather choose a less-aggressive technique even if it provided less information."
"Percutaneous liver biopsy does not involve changes in the treatment in around a half of patients."
27 May 2011


Recommended Reading;
COMPARISON OF FIBROSIS DEGREE CLASSIFICATION ACCURACY BY LIVER BIOPSY AND NON-INVASIVE TESTS IN CHRONIC HEPATITIS C-Non-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been evaluated in comparison to liver biopsy, especially in clinical practice.