October 10, 2012

Liver Health May Be Reflected in the Fingernails

October 10th, 2012

Learn why changes in the fingernails could be an indicator of a liver problem.

By Nicole Cutler, L.Ac.

Unless there is an obvious problem, many of us tend to take our physical bodies for granted. This is unfortunate because looking closely at the human body can divulge many clues about that person’s current state of health. Different kinds of alternative health practitioners are known to analyze a person’s eyes, gait and tongue, but these are not the only windows into a person’s well-being. If not covered up by acrylic nails or polish, fingernail anomalies can reveal several details about a person’s health – including the functionality of his or her liver.

Fingernails are not made of living tissue, but they reflect the health of living cells at the nail’s base. Composed of layers of the protein keratin and growing from beneath the base of the nail under the cuticle, fingernails are the accumulation of older cells becoming hard and compacted.

Continue reading this entire article …..

Pennsylvania General Assembly, Health Department Asked to Step Up Regulation of Tattoo Parlors

Provided by Infection Control Today

Pennsylvania auditor general Jack Wagner today called on the General Assembly and the state department of health to step up the state's role in regulating the tattoo parlor industry because of potential health risks to the general public, including hepatitis C.

Wagner said that requiring Pennsylvania's more than 750 known tattoo parlors and artists to obtain a state license would protect public health while helping state officials monitor one of the fastest-growing segments of the local economy.

"We license cosmetologists, hair salons and nail salons; it's time we join the growing number of states that also regulate tattoo parlors," Wagner says. "If we do not, the potential health risk to Pennsylvanians increases with every needle puncture."

In a letter sent today to the Pennsylvania Department of Health, Wagner pointed out that 21 percent of U.S. adults have at least one tattoo, according to a recent Harris poll. Reflecting the national popularity, Pennsylvania has upwards of 750 tattoo parlors or artists, including 84 in Philadelphia, 83 in Pittsburgh, 54 in Allentown, 51 in Scranton, 31 in Harrisburg and 15 in State College.

A tattoo is a permanent design created by using a needle to inject indelible ink under the skin, altering the skin's pigmentation. It is an invasive procedure which presents a risk of infection with bloodborne pathogens and other infections, especially if the tattoo equipment is not properly sterilized.

The Centers for Disease Control and Prevention (CDC) has cited the use of non-sterile equipment and suboptimal infection control as causes for skin infections in people receiving tattoos. It has also warned that the risk of contracting the hepatitis C virus is also possible with poor infection control practices. Hepatitis C primarily infects the liver, and is spread by blood-to-blood contact that may occur through the sharing of unsterilized needles or contaminated dyes. An estimated 130 million people are thought to be infected with the hepatitis C virus, according to the World Health Organization. The Pennsylvania Department of Health estimates that almost 4 million persons in the U.S., and 120,000 to 170,000 in Pennsylvania, are infected with the Hepatitis C virus.

The estimated 750 tattooists in Pennsylvania is based on known advertising and does not include those operating out of homes, mobile units or other non-sterile environments. These underground operators may employ dangerous practices such as reusing ink or using contaminated needles.

The only regulation now on the books in Pennsylvania makes it unlawful to tattoo a person under the age of 18 without parental consent. In 2009, the General Assembly considered regulating the tattooing industry, but legislation was not enacted.

Of the 10 most populous states, all but Pennsylvania have approved tattoo regulations or have legislation pending. California enacted one of the most comprehensive bills regulating its tattoo industry in July. Known as "The Safe Body Art Act," it requires consent forms signed by the client acknowledging that he or she understands the procedure and post-procedure instructions. It also requires tattoo owners to register with local health agencies and to obtain a permit certifying that it meets federal Occupational Safety and Health Administration health and safety guidelines.

Several local Pennsylvania communities have regulations in place for tattoo parlors, including Philadelphia, State College and Erie County.

Wagner's letter recommended several legislative and enforcement steps, including:
- The licensing of all tattoo parlors by the Department of Health, requiring regular safety and sanitation inspections.
- Requiring training for tattoo artists, which may include apprenticeships with a professional tattoo artist, certification of blood-borne pathogens, first aid and CPR training.
- Requiring tattoo establishment owners to purchase adequate liability insurance to cover clients and the premises.
- Imposing monetary fines for artists who operate illegally.

Wagner said that any approved legislation should help limit problem practitioners who operate under unsanitary conditions and also help to eliminate unqualified artists from applying tattoos.

Source: Pennsylvania Department of the Auditor General


HCV - Whats Coming

Provided by NATAP.org

from Jules of NATAP: Next month in November the big annual liver meeting AASLD will take place, where we will see the latest new data on new HCV therapies. We already know from the European EASL meeting held in April 2012 that interferon-free therapy regimens composed of 2-4 new oral drugs will be developed. There are 6 new HCV drugs in phase 3 now: 3 new once-daily protease inhibitors, a potent first-in-class NS5A inhibitor, a potent first-in-class nucleotide, and the new PegLambda. In addition right behind this in phase 2b & 2a are many new HCV oral drugs including potent protease inhibitors, NS5A inhibitors, non-nucleoside polymerase inhibitors, a nucleoside, as well as a newly developed 2nd nucleotide. At EASL we received the first new data reporting 90% to 100% cure rates with interferon-free regimens of 2-4 new oral drugs. But this was data from the initial regimens, much improved regimens will be developed so this year at AASLD we will see early developments of these newer & better regimens to be. But we will see in the future highly optimized regimens, which will provide as much as 100% cure rates. For patients who are the most difficult to treat and who have usually failed previous therapies, including patients with cirrhosis, it will be more challenging to find 100% cure regimens, but researchers are intent on accomplishing this & I predict we will be able to do this either with interferon or IFN-free. In fact research results already showed as much as 100% cure rates with QUAD in highly experienced patients with 2 new oral HCV drugs + pegIFN/RBV, so it is doable but I think we will find better regimens as well for these hardest to treat patients. The new peginterferon called PegLambda is in phase 3, and looked in phase 2 to be more tolerable than the current peginterferons on the market.

Here are links to tables & discussions of these new drugs, including links to all the data presented for each drug.

HCV Update Selected Highlights: key new HCV drugs, timelines & recent news developments

6 New HCV Drugs in Phase 3 Now

New HCV Drugs: non nucleoside polymerase inhibitors


HCV Screening/Baby Boomers, a misleading characterization

Provided by NATAP.org

From Jules Levin of NATAP: The anemic federal response to HCV is what the federal govt does, they don't respond to major issues =unless they are forced to, they don't respond unless it is politically necessary. They were forced to respond to HIV, not to HCV. The focus on baby boomers screening for HCV is misleading if you have come to think that screening baby boomers is the only or even the major focus. In NYC screening we are finding those testing HCV+ now using rapid HCV testing 40% are baby boomers BUT 53% ARE NOT. 53% are younger, born before 1965. The notion to screen for baby boomers is the latest in federal government tactics that are really focused on finding a way to save money in screening. Because its less expensive to focus on & recommend screening baby boomers and because the federal government refuses to spend the necessary money on screening everyone for HCV they developed a plan to provide what appears to be a good way to screen for HCV. Its all they can offer & support, but it mislead s the public. it makes it seem that they are doing something, but this baby boomer notion is misleading & a result of the fact that they only have a little amount to spend on HCV & are willing to spend only a little on HCV. Could you imagine if the federal government issued a study and a proclamation that in HIV most of those HIV+ fall within a certain age category. In fact in HIV the majority of those HIV do fall within a smaller age grouping. In reality we should test everyone in the USA for HCV. its a simple & easy matter to design a way that everyone gets screened for HCV. I have a solution to this. But if the federal government did that they would find at least 5 million people with HCV, I actually estimate we might have 8 million with HCV in the USA. And 80% of these people are & remain UNDIAGNOSED. If we identified all these individuals the federal government would have to explain why they don't have programs of care for all these individuals, and why they don't have any adequate funding programs dedicated to screening & care & awareness. these programs could cost $50 million & more to begin with going up to $300 mllion, I estimate. We can barely get $3-4 mill from the federal government. The federal government has not greatly been challenged on any of this, not like HIV activists did in the early 80s. There is a complete lack of loud in-your-face activism that is required to force the government to provide a serious response to the HCV problem, not this anemic baby boomer response. Calling them baby-boomers is a mis-characterization. Should we discuss the baby boomers having been infected YES, but only within the larger context that like we find in NYC 53% are NOT baby boomers. Can you imgine response back in the 198s to HIV by saying we should test baby boomers!. In NYC we are focused on screening IDUs in communities of color (African-Americans, Latinos) who are very disproportionately affected by HCV. The federal govt was forced to respond to HIV by loud in your-face activists in the 1980s, otherwise we may never have had the billions dedicated to the multitude of HIV programs, the $1 billion annual Ryan White Care Act.


HCV/HIV co-infection and the degree of liver fibrosis as risk factors of HAART-associated nephrotoxicity

Reported by Jules Levin
IAC Wash DC July 2012

M. del Palacio, A. Moreno, M. Martínez-Colubi, M.J. Pérez-Elías, P. Wikman, C. Quereda, P. Martí-Belda, S. Moreno, J.L. Casado

Dept of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain

Background: To investigate the effect of HCV coinfection, and liver fibrosis degree, on renal toxicity during HAART.

Methods: Prospective cohort study of 900 HIV/HCV co-infected patients with baseline and at least two determinations of serum creatinine (SCr) and estimated glomerular filtration rate (eGFR, MDRD). A transient elastometry measurement (TE) was performed at baseline. Nephrotoxicity was defined as a GFR decrease >50% from baseline and/or GFR < 60 ml/min/1.73m2 on two consecutive measurements.

Results: Mean age was 41 years, 76% male, 92% caucasian race, 26% on first HAART line. Overall, 372 (41%) were HCV positive. TE was available in 249 cases, showing fibrosis stage 1 in 43 %, fibrosis 2 in 16%, fibrosis 3 in 17% and fibrosis 4 in 24%. According to HCV, there was no difference in SCr and eGFR at inclusion, but eGFR decrease was significantly higher in HCV+ patients (-4.2 vs -1.3 ml/min at 24 w). Nephrotoxicity was greater in HCV+ patients (6% vs 3%; p=0.03), as well as a GFR decrease > 10% (47% vs 38%, p=0.01), >25% (15% vs 8%, p=0.01), and a isolated GFR decrease >50%(2.7% vs 0.6%, p< 0.01). In a Cox regression analysis, HCV coinfection (RR 1.96; p=0.03), CD4+ nadir (RR =1.01, p=0.01), hypertension (RR 5.88; p=0.001), tenofovir use (RR 3.06, p=0.02) and age (RR 1.06, p=0.003 for year) were associated with time to toxicity. Globally, GFR decrease was higher in fibrosis 4 than 1 (-7.24 vs -4.04 ml/min at 24 w), and this difference was statistically significant in not tenofovir-treated patients (-13.83 vs +1.18 ml/min for fibrosis 4 vs 1, p< 0.01).

Conclusions: HCV coinfection is an independent risk factor for nephrotoxicity in HIV infected patients. Of note, as liver fibrosis progress, risk of nephrotoxicity rises, especially evident for patients having advanced fibrosis and not receiving tenofovir.

From Jules: if you look at the last graph below it appears as though advanced fibrosis F4 is where there is the most significant risk for nephrotoxicity.

Click here to view slides ….

Santa Fe New Mexico Care center offers hepatitis C testing, support

Provided by NATAP.org

from Jules of NATAP: in this article several patients background stories are highlighted, they receive care at this HIV clinic whose medical director is the well known researcher Dr Trevor Hawkins. Individuals from the inner city are starkly different in large urban cities like NY, Miami, Dallas, Detroit, I could go on. Many of these highly marginalized underserved individuals are severely isolated from the healthcare system, they suffer from a multitude of both rational & irrational fears that are barriers to testing for HCV and prevent them from getting into a care system and from remaining in the care system. As well, the healthcare systems has itself many barriers to these individuals entering the system. These individuals are most often African-Americans & Latinos and IDUs in inner cities like NY, Los Angeles etc. It is simply totally inadequate to in general merely tell individuals in these communities they are at risk for having HCV & should be tested & receive care if they are HCV+. There are numerous ways in which they don't trust the healthcare system or the individuals who work in it, in some cases their reasons are justified and helps to explain why they are 'marginalized' & thus 'underserved, terms that are often not fully appreciated or understood if you don't work or live in these communities. These individuals often do not appreciate that a person needs access to healthcare & at the same time they do not know how to navigate the system. They live their lives on the margins of society, often without jobs, without contact with mainstream society, and live in communities of individuals just like themselves who provide a system that supports their thinking and behavior that does not serve them well. If services are available or offered to them they are very fearful & suspicious of them, and as I say with often rational or irrational justifications. These communities are ever-present & of significant numbers in cities throughout the USA and include in addition to those mentioned above Washington DC, Chicago, Houston, Seattle, Ft Lauderdale, West Palm Beach and on and on. These communities are the most disproportionately affected by HCV, suffer with the highest rates of HCV, have the most difficulties accessing care of any type particularly for HCV, the healthcare system does not welcome them, they respond to HIV & HCV treatment less favorably, they need much more services just to to interface with the healthcare system, and are the key to curing HCV. We will very soon have HCV treatment regimens that will be interferon-free consisting of 2-4 antiviral drugs, where 12-24 weeks duration of therapy will cure patients. In concept we will have the capacity to cure everyone with HCV, but if we do not provide a proper & adequate labor-intensive healthcare system for these communities we will not be able to do this. In NYC we are implementing the first 'Urban HCV Plan', a 'HCV Ryan white Care Act'. Unlike HIV there is no infrastructure for care & treatment for the poor & uninsured in HCV. Local, state & federal governments do not provide this for HCV. In our NY project called 'Check Hep C', we have a large-scale cutting edge awareness program, are implementing 5,000 rapid HCV tests, at 8 testing sites throughout the most hard-hit inner cities where HCV is most prevalent, we provide 7 patient navigators whose job is to stay with the client from the very moment they test & throughout the entire care scenario & to guide & navigate them, we provide 6 community based clinics in those same inner city communities where individuals prefer to receive their care, we provide access to treatment if warranted, and we provide weekly internet web-based education & case study review for the clinicians at the care centers by expert hepatologist researchers. This project was designed by me 4 years ago as a model that could be duplicated anywhere. In the US we estimate 80% of HCV+ individuals are undiagnosed. They are undiagnosed for good reasons, it will not be easy to identify everyone. There are reasons that 80% remain undiagnosed. There are as numerous different types of barriers as there are different types of patients, and there are many different types of patients, and this fact very often is unrecognized. We need diverse patient-oriented strategies & solutions to get people tested & into care, and this is & will be loaded with difficulties. The medical miracle that we are approaching is I think the top medical development of the last 50 years, that we will have the capacity to cure almost everyone suffering with a viral infection, HCV, with only 12-24 weeks of treatment. This goal will not be reached if we don't provide an adequate HCV care system. Who will step up to begin to implement such a large-scale national system? So far there has been a very small federal government response. I estimate we need $40 million to get a good start at such a project. Jules Levin


Care center offers hepatitis C testing, support

Santa Fe New Mexican.com

But the Santa Fe health care provider, which primarily treats HIV patients, recently began offering free testing for hepatitis C- the cause of most liver cancer and liver transplants - partially because New Mexico has a higher-than-usual prevalence

Oct 6, 2012.

In the year 2020, the hottest item for sale on eBay will be a healthy human liver. Not really; that's just a dark inside joke between staff members at Southwest Care Center.

But the Santa Fe health care provider, which primarily treats HIV patients, recently began offering free testing for hepatitis C - the cause of most liver cancer and liver transplants - partially because New Mexico has a higher-than-usual prevalence of the disease.

It's better to get tested for the disease early, center staff say, instead of waiting until you have symptoms - some of which include throwing up blood - because treatment is more effective the sooner it is provided.

Like its siblings, hepatitis A and B, hepatitis C is a virus that affects the liver and can lead to cirrhosis and cancer of the liver. But unlike A and B, there is not a vaccine for hepatitis C. It is curable, but not always, and catching the disease earlier gives patients a better chance of recovery.

The disease is transmitted via blood. So health care professionals who handle needles, intravenous drug users, people with tattoos and people who snorted cocaine or other drugs through a straw that was used by another person (who might have had a open sore in the nasal cavity) are at increased risk for getting the disease.

But a wild lifestyle isn't the only risk factor. The disease wasn't identified until 1986, and public blood supplies weren't screened for the virus until 1992. So anyone born between 1945 and 1965 has a greater likelihood of having been exposed to the virus.

Baby boomers are especially at risk, according to Stella Reed, director of outreach at the center, not only because they have a greater chance of having had a blood transfusion before 1992, but because they routinely lived communally, and the disease can be transmitted via a shared toothbrush or razor.

Treatment of the disease includes the drugs interferon and ribavirin, one of which needs to be injected daily and both of which come with significant side effects. A number of studies are being conducted with a goal of eliminating the need for injections and the number of pills patients must take.

Terry Bryant, program manager of the state Department of Health's HIV and hepatitis C epidemiology program, said data on hepatitis C is sparse. But, he said, in a 2009 U.S. Centers for Disease Control and Prevention study of five states - Connecticut, Minnesota, Oregon, Colorado and New Mexico - New Mexico had the second highest occurrence of disease. New Mexico's rate was about 147.4 people per 100,000 people, Bryant said, while New York state, the state with the highest rate of the disease, had a rate of 183.4 cases per 100,000 people. Nearby Colorado had a rate of just 68 cases per 100,000 people.

Bryant said New Mexico's high prevalence of intravenous drug use is one of the factors that could contribute to New Mexico's higher rates of the disease.

Southwest Care Center purchased 1,200 kits to test for exposure to the disease earlier this year. About a quarter of the tests were paid for by the Department of Health.

According to Reed, the center has administered about 200 tests since March and about 18 people, or 9 percent, tested positive for the disease - much higher than the national average of about 2.5 percent.

Some people can carry the virus for years before it becomes symptomatic, while others either clear the disease naturally, usually within six months of exposure, or become sick.

Mary Boudreau, a 62-year-old massage therapist and esthetician who tested positive for hepatitis C in 2007, admits she "partied" in her youth - including snorting cocaine - and got a $3 tattoo from a place called Sailor Jerry's in Hawaii in 1971. But she never felt sick.

It was a work-related pin prick - she does medical skin-care work for doctors sometimes - that prompted her to get tested in 2007.

When she found out she was positive, "the whole room turned a very bright white and it was kind of scary," Boudreau said.

She didn't have insurance, so she put her name on a waiting list for a clinical trial on hepatitis C. She began treatment in January 2010. She was in and out of treatment - taking up to nine pills per day for six months at a time - for about a year and a half. But in the end, she was cured. She now has undetectable amounts of the virus in her blood.

Sharon Ebert, 59, suspects she contracted the disease during a blood transfusion when she had her tonsils out at age 8. But she didn't see symptoms until decades later.

"I'm like the energizer bunny," Ebert said, "used to working 60 to 70 hour weeks, and all of sudden I couldn't do it. I kept getting more and more tired." She also had soreness on her right side where the liver is, but her doctor of 30 years told her the ailments were just "stress."

When she moved to Santa Fe in 2009, she had a panel of blood tests done and found out she had hepatitis C.

Finally, Ebert said, the fact that hard liquor and most pain medications make her violently sick made sense. Alcohol exacerbates the condition, and people with hepatitis C should not drink, Reed said.

Because the illness hadn't caused her any symptoms besides fatigue in 40 years and she doesn't like taking pharmaceutical drugs, Ebert waited and did research before deciding to seek treatment. The fact that she had recently become a grandmother, Ebert said, is what ultimately made her decide to accept treatment.

"It doesn't matter how you got it," Ebert said. "You got it. Deal with it. To me, the most important thing is attitude," she said. "You need to have a positive attitude and strong willpower. There are some days you don't want to get out of bed."

Both women said the care they received from Southwest Care Center was key in their recovery.
Ebert had insurance but couldn't cover the $400 monthly copay for the treatments. Southwest Care Center helped her gain access to copay assistance. The center helped Boudreau by connecting her to a pharmaceutical company that funded the clinical trial in which she participated.

"They treat you as an individual," Ebert said of the staff at the center. "They don't see you as a number who is coming in the door. From front desk to pharmacy, you always feel like you are their priority, not the money you bring in. They are there to make sure you are OK. At Southwest Care Center, you are not on your own. You have a team that supports you and helps you through the rough spots."

Southwest Care Center currently offers free hepatitis C tests as well as free confirmatory tests - more than one test is needed to confirm a diagnosis of the disease - for patients who test positive and meet certain criteria. The center also works with drug companies who are conducting clinic trials in hepatitis C treatment and in some cases provides free care to patients who are accepted into certain trials.

For more information or to make an appointment to be tested, call 989-8200.

Hepatitis C Can Be Successfully Treated in Injection Drugs Users with or without HIV

Published on Wednesday, 10 October 2012 00:00 Written by Liz Highleyman

HIV negative and HIV positive chronic hepatitis patients in Vancouver with a history of injection drug use -- most of whom were on methadone maintenance -- achieved sustained response rates with interferon-based therapy similar to those of non-users, researchers reported at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2012) last month in San Francisco.

Sharing syringes and other drug equipment is an efficient way to transmit hepatitis C virus (HCV) and HIV, and a large proportion of people with a history of injection drug use are infected with one or both viruses.

Although injection drug users (IDUs) are estimated to account for at least half of existing and more than 75% of new cases of hepatitis C in North America, only a minority have received treatment. Many clinicians are hesitant to treat current and past IDUs due to concerns about adherence, dealing with side effects, or simple prejudice. Current guidelines, however, state that this population should not be routinely denied treatment and should instead be evaluated on an individual basis.

Continue reading full article here …..

First Guideline on NAFLD Published

Gastroenterology & Endoscopy News


by Christina Frangou

Three leading American gastroenterology societies have published a new guideline on the diagnosis and management of non-alcoholic fatty liver disease (NAFLD). Prompted by the fact that physicians are seeing a growing number of patients with the disease, this is the first time that any of these professional societies have developed practice guidelines for NAFLD.

In the report, an expert panel representing the American Gastroenterological Association (AGA), the American Association for the Study of Liver Diseases (AASLD) and the American College of Gastroenterology (ACG) made 45 recommendations for clinicians who treat patients with this increasingly common disease.

The panel addressed many of the major questions in the field, including when patients should be screened and when they should undergo liver biopsy, and outlined the evidence supporting diagnostic techniques and interventions, as well as diagnosis and treatment of children with NAFLD.

The guidelines were published simultaneously in the June issues of the journals Gastroenterology, Hepatology and The American Journal of Gastroenterology.

Senior author Naga Chalasani, MD, professor of medicine and director of the Division of Gastroenterology and Hepatology at Indiana University, in Indianapolis, urged gastroenterologists and hepatologists to read the guideline and “apply it as they deem appropriate for their practice.”

Recommendations of the Report

The panel opposed routine screening for NAFLD in adults, even those at diabetes or obesity clinics, because of uncertainties surrounding diagnostic tests and treatment options, and a lack of knowledge about long-term benefits and cost-effectiveness. They also recommended against routine screening of family members of patients with known NAFLD.

The panel also stressed the importance of ruling out excessive daily alcohol consumption before making a NALFD diagnosis. However, they used a liberal definition of “significant alcohol consumption”—at more than 21 drinks, on average, per week for men and more than 14 drinks per week for women. This recommendation was made on a relatively low level of evidence (2C).

For patients with unsuspected hepatic steatosis detected on imaging, the panel made several recommendations backed by the highest level of evidence (1A). They called for patients with symptoms or signs of liver disease or abnormal liver biochemistries to be evaluated as though they have suspected NALFD. Patients with normal liver biochemistries and no symptoms should be assessed for metabolic risk factors and other causes for hepatic steatosis. The panel did not recommend liver biopsies for asymptomatic patients with normal liver biochemistries.

They confirmed liver biopsy as the gold standard for characterizing liver histology in patients with NAFLD. However, they said liver biopsy should be reserved for those who would benefit the most from the information gleaned by biopsy. Patients with metabolic syndrome or those with suspected NAFLD who are at increased risk for steatohepatitis and advanced fibrosis may be good candidates for liver biopsy, according to the panel.

When evaluating a patient with suspected NAFLD, the guidelines recommend that clinicians exclude all competing etiologies for steatosis and coexisting chronic liver disease. A liver biopsy should be considered, when necessary, to rule out competing etiologies.

Additionally, persistently high serum ferritin and increased iron saturation, especially in the context of homozygote or heterozygote C282Y HFE mutations, may warrant a liver biopsy.

It was premature to recommend serum/plasma CK18 as a biomarker for identifying steatohepatitis, the panel said and noted that patients with high serum titers of autoantibodies, and other features suggesting autoimmune liver disease, should undergo a more complete workup for this.

Several recommendations for treatment were presented that stressed weight loss and lifestyle interventions as key to the management of steatosis. Treatments aimed at improving liver disease should be limited to patients with nonalcoholic steatohepatitis (NASH), as NAFLD patients without steatohepatitis have an “excellent prognosis from a liver standpoint,” the panel said.

With regard to specific interventions, they found the following:

  • Weight loss generally reduces hepatic steatosis, and a weight loss of up to 10% may be needed to improve necroinflammation.
  • Metformin has no significant effect on liver histology and is not recommended as a specific treatment for liver disease in patients with NASH.
  • Pioglitazone can be used to treat steatohepatitis in patients with biopsy-proven NASH, but its long-term safety and efficacy in patients with NASH is not established.
  • Vitamin E administered at a daily dose of 800 IU per day should be considered a first-line pharmacotherapy in nondiabetic adults with biopsy-proven NASH; however, without more data supporting its effectiveness, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis or cryptogenic cirrhosis.
  • Ursodeoxycholic acid is not recommended for the treatment of NAFLD or NASH. Omega-3 fatty acids may be considered first-line therapy for hypertriglyceridemia in patients with NAFLD but it is premature to recommend Omega-3 for the specific treatment of NAFLD or NASH.
  • Statins can be used to treat dyslipidemia in patients with NALFD and NASH but should not be used to treat NASH specifically until randomized controlled trials (RCTs) are conducted.

The panel briefly addressed bariatric surgery, saying most patients who undergo weight loss surgery have associated fatty liver disease. They noted that foregut bariatric surgery is not contraindicated in otherwise eligible obese individuals with NALFD or NASH but without established cirrhosis. It is premature to consider foregut bariatric surgery as an established option to treat NASH, they said.

The small number of RCTs limits recommendations for treatment options in children, the panel noted. The treatment recommendations for children were similar to adults: Intensive lifestyle modification should be the first-line treatment, metformin offers no benefit and vitamin E offers histologic benefits but confirmatory studies are needed.

The guidelines offer a good summary of the published evidence for NAFLD but, unfortunately, the evidence is limited, said Eric Kallwitz, MD, assistant professor of medicine at Loyola University Medical College, Maywood, Ill.

“I think this guideline gives us clearer recommendations on what patients we should be aggressive in evaluating. Until now, there has been limited guidance on the necessity of procedures such as biopsy, given the high prevalence of NAFLD.”

He added that he would like to see more information on screening patients’ dietary intake and evidence supporting specific prescription for dietary modifications and exercise requirements.

Authors of the guidelines reported financial relationships involving Abbott Laboratories, Advanced Life Sciences, Amylin, Astellas Pharma, Biolex Therapeutics, Bristol-Myers Squibb, Celgene, Cumberland Pharmaceuticals, Daiichi Sankyo, Eli Lily, Genentech, Geneva Foundation, Gilead, GlaxoSmithKline, Ikaria, Immuron, Intercept, Johnson & Johnson, Karo Bio, Merck & Co., Mochida, Norgine, Pfizer, Quark Pharmaceuticals, Raptor Pharmaceuticals, Roche, Rottapharm, Salix Pharmaceuticals, Sanofi-Aventis, Schering-Plough, Synageva BioPharma, Takeda, Teva Pharmaceuticals, Tibotec and Vertex Pharmaceuticals.


Patients with diabetes, chronic HCV at elevated risk for malignancies

Arase Y. Hepatology. 2012;doi:10.1002/hep.26087.

October 8, 2012

Type 2 diabetes can increase the risk for hepatocellular carcinoma and other malignancies in patients with chronic HCV, according to recent results.

In a retrospective cohort study, researchers observed the incidence of malignancies during a mean follow-up of 8.1 years among 4,302 Japanese patients with chronic HCV who had undergone prior interferon [IFN] therapy. All participants had no malignancies, had received IFN therapy between 1 month and 1 year and were aged 30 to 80 years at enrollment.

Malignancy occurred in 606 patients, including 393 incidents of HCC, which had cumulative development rates of 4.3%, 10.5% ,19.7% and 28% after 5, 10, 15 and 20 years, respectively. Other malignancies — including stomach, colon, lung, pancreatic, prostate and breast cancers — had cumulative development rates of 2.4%, 5.1%, 9.8% and 18% for 5, 10, 15 and 20 years, respectively.

Factors associated with HCC development included the presence of cirrhosis (n=433 patients, HR=5.01; 95% CI, 3.92-6.40), a lack of sustained virological response during interferon therapy (n=2,402 patients; HR=4.93; 95% CI, 3.53-6.89) and type 2 diabetes (T2DM) (n=267 patients; HR=1.73; 95% CI, 1.30-2.30). Investigators noted that the risk for HCC decreased among patients with diabetes and mean HbA1c levels less than 7.0% (HR=0.56; 95% CI, 0.33-0.89).

The presence of non-HCC malignancies was associated with advanced age (HR=2.19, 1.84-2.62 for every 10-year increase), heavier smoking (20 or more pack-years) (HR=1.89, 1.41-2.53 compared to fewer than 20 pack-years) and T2DM (HR=1.70, 1.14-2.53). In particular, T2DM was significantly associated with pancreatic cancer (HR=3.75, 1.02-13.88), and also had a tendency to increase the risk for gastric cancer (HR=2.29, 0.95-5.52) (95% CI for all).

“The present study shows several findings with regard to the development incidence and predictive factors for total malignancies after IFN therapy for HCV patients,” the researchers wrote. “T2DM causes an approximately 1.7-fold enhancement in the development of HCC and malignancies other than HCC after IFN therapy. Additionally, in T2DM patients, maintaining mean HbA1c levels of [less than] 7.0% during follow-up reduced the development of HCC.”


Cirrhotic patients coinfected with HIV, HCV less responsive to peg-IFN/RBV

Mira JA. Clin Infect Dis. 2012;doi:10.1093/cid/cis779.

October 10, 2012

Treatment with pegylated interferon and ribavirin was less effective in patients with cirrhosis and coinfected with HIV and HCV than noncirrhotic patients in a recent study.

In a multicenter prospective cohort study, researchers evaluated 629 patients coinfected with HCV and HIV, including 175 with cirrhosis. All participants received treatment with pegylated interferon (peg-IFN) and ribavirin (RBV), and had undergone either a biopsy or liver stiffness measurement within 1 year of starting therapy. Follow-up included plasma HCV RNA measurement and assessment of adverse events, and occurred at least once every 4 weeks during the initial 24 weeks of treatment, then every 2 months until conclusion.

In intention-to-treat analysis, sustained virological response (SVR) occurred in 38.9% of noncirrhotic patients compared with 25.1% of those with cirrhosis (P=.001 for difference). Per-protocol analysis of 521 patients indicated significantly more incidence of SVR among those without cirrhosis (46% of patients compared with 33%, P=.007), and lack of cirrhosis was associated with SVR via multivariate analysis (adjusted OR=2.02; 95% CI, 1.1-3.4). Patients with cirrhosis also were significantly more likely to discontinue treatment due to adverse events than noncirrhotic patients (17% of patients vs. 8%, P=.001).

SVR was more common in cirrhotic patients with HCV genotype 2-3 (47% of patients) than those with genotype 1 (14%) or 4 (30%), and researchers observed a significant association between SVR and HCV genotype 1 or 4 (aOR=8.9, 2.7-29). Other factors predictive of SVR included baseline liver stiffness measurements of less than 30 kPa (aOR=4.1, 1.02-16.7) and a baseline HCV viral load of 600,000 IU/mL or less (aOR=6.0, 1.8-2.0) (95% CI for all).

“Although HIV-infected patients with compensated HCV-related cirrhosis are a hard-to-cure population, HCV therapy is a priority in these patients,” the researchers wrote. “Because of this, HCV therapy with peg-IFN plus RBV should be recommended to patients with genotype non-1 until more effective drugs are available. New drugs are needed to improve the efficacy of HCV therapy in HIV/HCV coinfected patients with compensated liver cirrhosis.”

Disclosure: See the study for a full list of relevant disclosures.


The 63rd Annual Meeting of the American Association for the Study of Liver Diseases in Boston, MA - Hynes Convention Center: November 10 - 13, 2012


ALEXANDRIA, Va. and BOSTON, Oct. 10, 2012 /PRNewswire/ -- The Liver Meeting® is the premier Annual Meeting in the science and practice of hepatology, including the latest findings on new drugs, novel treatments, and the results from pilot and multicenter studies.

Approximately 10 percent of Americans have some form of liver disease, but fortunately, the research community has made great strides in recent years in developing new treatments for patients.

At this year's meeting, 2107 abstracts addressing these issues that will be presented, including 258 abstracts that will be presented in oral sessions. Those abstracts are available to members of the press at our website (www.aasld.org).

Boston, MA: November 10 – 13, 2012

  • Poster Presentations: November 10 – 13
  • Oral Presentations: November 11 – 13

An AASLD President's press conference highlighting key abstracts and issues presented at The Liver Meeting® is scheduled for Saturday, November 10 at 4:00 pm.

Founded in 1950, AASLD is the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease. AASLD has grown into an international society responsible for all aspects of hepatology, and our annual meeting attracts more than 8,000 physicians, surgeons, researchers, and allied health professionals from around the world.

Please contact AASLD at 703-299-9766 begin_of_the_skype_highlighting 703-299-9766 end_of_the_skype_highlighting for information about the above presentations, or to receive any additional information about The Liver Meeting® – or visit our website at www.aasld.org.

Please visit our website to register as press for the meeting, or contact Ann Haran at aharan@aasld.org with any questions.

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.xpresspress.com.

SOURCE American Association for the Study of Liver Diseases (AASLD)



Update on the Diagnosis and Treatment of Hepatitis C

Infectious Disease Special Edition


by Arun B. Jesudian, MD and Ira M. Jacobson, MD

HCV infection is a national and global public health concern, affecting up to 4 million individuals in the United States and 200 million individuals worldwide. Despite a declining incidence of new HCV infections in the United States, the prevalence of advanced liver disease secondary to chronic HCV infection, including cirrhosis and hepatocellular carcinoma, is expected to rise in the coming years.

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-- Update on the Diagnosis and Treatment of Hepatitis C

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New hepatitis C initiative launched in the Bay (New Zealand)

the Hepatitis Foundation Wednesday 10 October 2012, 11:09AM

Media release from the Hepatitis Foundation

The Hepatitis Foundation (NZ), in partnership with the Ministry of Health and the Bay of Plenty DHB, have launched an innovative pilot targeting chronic hepatitis C in the Bay of Plenty. The pilot intends to significantly improve health outcomes and access to care for people living with this disease.

Chronic hepatitis C is the main cause of liver transplantation in New Zealand. Despite the serious nature of the disease, most people know very little about hepatitis C. "Hepatitis C has been ignored for too long," John Hornell, CEO of The Hepatitis Foundation (NZ) said. "Now is the time to confront this disease, to tackle it head on and to win the fight."

Hepatitis C is a global health issue, as recognised by the World Health Organisation. In New Zealand there are approximately 50,000 people living with chronic hepatitis C. Over 75% of these people are unaware they have the disease as many don't experience signs or symptoms for many decades after infection.

"Our integrated hepatitis C pilot aims to increase the number of people diagnosed, assessed and treated for hepatitis C", Kelly Barclay, Hepatitis C Project Manager said. "It will involve a hepatitis nurse delivering specialist care in the community. The goal is to provide those with hepatitis C with better access to testing, care and support where they live. This will help them make lifestyle changes to slow the progression of the disease before they consider treatment."

Over the coming months, The Hepatitis Foundation (NZ) will be working closely with General Practitioners, Specialists and other health providers to enrol those with hepatitis C onto a Community Assessment and Support Programme. The Community Hepatitis C Nurse will provide enrolled patients with an initial FibroScan®assessment (a non-invasive new ultrasound technique to assess the level of liver disease), blood tests, on-going support and education, and will liaise with health providers to centrally manage patients' needs. In the majority of cases, Fibroscan® takes away the need for liver biopsy altogether.

The Bay of Plenty DHB will be backing this pilot across the region. Phil Cammish, CEO for the BOPDHB said, "The innovative approach being introduced with this improved service should make a big difference to the lives of people with hepatitis C. This service will bring together all parts of the health service to address this health need."

Early 2013, a public campaign will be launched to identify people who are at risk or have been at risk of contracting hepatitis C and are currently undiagnosed. "We'll be actively encouraging people to get tested if they are or have been at risk of hepatitis C," Barclay said. "It's important people are diagnosed as early as possible."

Hepatitis C is spread through blood-to-blood contact. The virus causes inflammation of the liver, which can lead to cirrhosis or liver cancer if left undiagnosed. Current treatment provides 45-80% chance of cure (depending on the disease strain).

The Hepatitis Foundation (NZ) is a charitable trust promoting positive health outcomes for people living with chronic hepatitis.


Pilot to offer better support for Hep C patients in the sub‐region (New Zealand)

the Hepatitis Foundation Wednesday 10 October 2012, 11:43AM

Media release from the Hepatitis Foundation

People in the Wairarapa and greater Wellington regions will have better access to testing, assessment and treatment for hepatitis C thanks to a two‐year pilot programme being rolled out in the sub‐region.

Capital and Coast, Hutt Valley and Wairarapa DHBs are working with The Hepatitis Foundation (NZ) and community‐based health providers to improve access to support services for patients living with chronic hepatitis C and encourage people that may be at risk to get tested. Preparations are underway to launch the pilot at Capital and Coast, Hutt Valley and Wairarapa DHBs in early 2013.

According to the Foundation there are an estimated 5,800 people living with hepatitis C across the sub‐region. Chronic hepatitis C is the main cause of liver transplants in New Zealand and if left untreated can have serious health effects.

"This programme will be a terrific help to identify people that need treatment and offer them ongoing support," said Dr Richard Stein, supervising clinician for the Wairarapa pilot. "We have around 50 patients we hope to enrol in the Wairarapa and combined with the Hutt Valley and Wellington pilots will mean better service coverage and better outcomes for our populations," he said.

During the first stage of the pilot, people already diagnosed with hepatitis C will be enrolled into a Community Assessment and Support Programme. Patients' care is centrally managed by a community hepatitis nurse who is supported by a range of specialists including hospital staff, GPs and other community‐based health providers.

Patients will have improved access to services, including FibroScan. This ultrasound technique measures the amount of scar tissue (fibrosis) in the liver, which helps measure the progression of the disease. Patients will also receive ongoing follow‐up care which is important for managing their condition. During the second stage of the pilot, people will be encouraged to get tested if they are, or have been at risk of hepatitis C.

Those at risk of hepatitis C are people who have ever: injected drugs; received a blood transfusion before 1992; lived or received medical attention in high‐risk countries; been in prison; or used unsterile equipment for tattooing or body piercing. Children born to mothers with hepatitis C are also at risk.

Dr Nigel Stace, Wellington Hospital Gastroenterologist says, "the key to this pilot is to encourage and support people to come forward early to be tested and treated. It's easier to treat the disease in its early stages and there is a much better chance of a cure when patients complete their treatment."

"Before Fibroscan was available, patients had a biopsy and spent up to a day in hospital after the procedure to make sure they were fit to go home," says Dr Stace. "Results also took several days to come back from the lab. Now testing takes around 20 minutes and doesn't involve needles which can discourage people from being tested."

"The gastroenterology services at the three DHBs are looking for opportunities to work more closely together. We see the pilot as a great opportunity to get this started," says Dr Stace.
Gastroenterology involves providing care for people with diseases of the 'gut', liver and pancreas.

Dr Jeff Wong, Hutt Hospital gastroenterology specialist says, "we are delighted to participate in the Foundation's Hepatitis C Pilot Programme. We hope it will increase the number of people completing treatment and with the treatment currently available, two thirds of patients can be cured," he said.


FDA takes action against thousands of illegal Internet pharmacies


For Immediate Release: Oct. 4, 2012
Media Inquiries: Sarah Clark-Lynn, 301-796-9110, sarah.clark-lynn@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

En Español1

Agency participates in international Operation Pangea V to protect consumers from potentially dangerous, unapproved drugs

The U.S. Food and Drug Administration, in partnership with international regulatory and law enforcement agencies, took action this week against more than 4,100 Internet pharmacies that illegally sell potentially dangerous, unapproved drugs to consumers. Actions taken include civil and criminal charges, seizure of illegal products, and removal of offending websites.

The announcement takes place during the 5th annual International Internet Week of Action (IIWA), a global cooperative effort to combat the online sale and distribution of potentially counterfeit and illegal medical products. This year’s effort – Operation Pangea V – operated between Sept. 25 and Oct. 2 and resulted in the shutdown of more than 18,000 illegal pharmacy websites and the seizure of about $10.5 million worth of pharmaceuticals worldwide.

The goal of this annual effort, which involved law enforcement, customs and regulatory authorities from 100 countries, is to identify producers and distributors of illegal pharmaceutical products and medical devices and remove these products from the supply chain.

“Consumers in the United States and around the world face a real threat from Internet pharmacies that illegally sell potentially substandard, counterfeit, adulterated or otherwise unsafe medicines,” said FDA Commissioner Margaret A. Hamburg, M.D. “This week’s efforts show that strong international enforcement efforts are required to combat this global public health problem. The FDA is committed to joining forces to protect consumers from the risks these websites present.”

Last week, the FDA reinforced its online efforts with the launch of a national campaign to educate Americans about the risks of buying prescription medications over the Internet. BeSafeRx – Know Your Online Pharmacy2 seeks to raise public awareness about the health risks of using fraudulent Internet pharmacies and what consumers can do to protect themselves.

During Operation Pangea V, the FDA targeted websites selling unapproved and potentially dangerous medicines. In many cases, the medicines can be detrimental to public health because they contain active ingredients that are approved by FDA for use only under the supervision of a licensed health care practitioner or active ingredients that were previously withdrawn from U.S. market due to safety issues.

Among the illegal medicines identified through the operation were:

  • Domperidone: This medicine was removed from the United States market in 1998 because it may cause serious adverse effects, including irregular heartbeat, stopping of the heart, or sudden death. These dangers could convey to the nursing baby of breastfeeding women, who may be using domperidone to try increase milk production (which is not an approved use).
  • Isotretinoin (previously marketed as Accutane in the United States): This medicine is used to treat severe nodular acne and carries significant potential risks, including severe birth defects if pregnancy occurs while using this medicine. To minimize potential risks to consumers, FDA-approved isotretinoin capsules are only available through restricted distribution in the United States.
  • Tamiflu (oseltamivir phosphate): This medicine, which is used to treat the flu, is often sold online as “generic Tamiflu.” However, there is no FDA-approved generic version of Tamiflu. Previous FDA tests found that fraudulent versions of “generic Tamiflu” contained the wrong active ingredient, which would not be effective in treating flu. In these cases, the wrong active ingredient was similar to penicillin and may cause a severe allergic reaction, including a sudden, potentially life-threatening reaction called anaphylaxis, in consumers allergic to penicillin products.
  • Viagra (sildenafil citrate): This medicine is used to treat erectile dysfunction. Due to its vasodilation effects, sildenafil citrate should not be used by consumers with certain heart conditions. Consumers taking this medicine without the supervision of a health care professional may not learn about potential drug interactions, such as increased blood pressure lowering effects of organic nitrates when taken with sildenafil citrate.

The FDA sent Warning Letters to the operators of more than 4,100 identified websites. As a follow up, the agency sent notices to Registries, Internet Service Providers (ISPs), and domain Name Registrars (DNRs) informing them that these websites were selling products in violation of U.S. law. The FDA is working with its foreign counterparts to address the remaining websites that continue to offer unapproved or misbranded prescription medicines to U.S. consumers.

“Internet pharmacies that illegally sell unapproved, counterfeit, or potentially adulterated or substandard drugs are an inherently international crime problem,” said John Roth, director of the FDA’s Office of Criminal Investigation. “The FDA is pleased to work with INTERPOL, the international police agency, to fight this problem. Because these criminals do not respect international borders, the international coordinated law enforcement response represented by Operation Pangea demonstrates that international cooperation is the best way to protect the American public from the risk of unsafe drugs.”

The FDA coordinated the efforts of this year’s Operation Pangea V, including screening all drug products received through the international mail facilities during the IIWA. Preliminary findings showed that certain products from abroad, such as antibiotics, antidepressants, and other drugs to treat high cholesterol, diabetes, and high blood pressure, were on the way to U.S. consumers. Many of those products can pose health risks if taken without the supervision of a health care practitioner or if the products have been removed from the market for safety reasons.

The FDA encourages consumers to report suspected criminal activity at www.fda.gov/oci3.

The IIWA is a collaboration between FDA, INTERPOL4 5, the World Customs Organization, Permanent Forum of International Pharmaceutical Crime, Heads of Medicines Agencies Working Group of Enforcement Officers, the Medicines and Healthcare products Regulatory Agency of the United Kingdom, the Irish Medicines Board, the London Metropolitan Police, the U.S. Department of Homeland Security, the Center for Safe Internet Pharmacies, and national health and law enforcement agencies from 100 participating countries.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, and products that give off electronic radiation, and for regulating tobacco products.


Etanercept Recommended for RA Complicated by Hepatitis C

By: M. ALEXANDER OTTO, Family Practice News Digital Network

NEWPORT BEACH, CALIF. – Etanercept and a few other tumor necrosis factor inhibitors should be considered first-line therapy for treating rheumatoid arthritis in patients with active hepatitis C virus infection, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

A systematic literature review (Rheumatology (Oxford) 2011;50:1700-11) that included 153 patients – 91 with rheumatoid arthritis (RA) – "demonstrated quite clearly that there are no safety signals from this. TNF inhibitors work in the same general manner with the same predicted responses in hepatitis C patients as they do in patients who are uninfected," he said.

"Most of the data are on etanercept," and recent guidelines from the American College of Rheumatology recommend it in RA patients with hepatitis C based on observations and other level-C evidence, he noted.

For those and other reasons, "I consider TNF inhibitors first-lines of therapy. These drugs can [also] be used concomitantly" with hepatitis C treatments, including protease inhibitors, which seem to greatly improve cure rates when included with other antiviral therapies, he said at Perspectives in Rheumatic Diseases 2012, sponsored by Skin Disease Education Foundation (SDEF).

"When we find somebody with hepatitis C in our practice, we are doing them a huge favor because we can bring them into the circle of care and treat the thing that is more serious than their" RA, Dr. Calabrese said.

Meanwhile, the guidelines do not recommend methotrexate or leflunomide in the setting of hepatitis C virus infection because the drugs might cause additional liver damage.

Among others, Dr. Calabrese screens baby boomers – the largest reservoir of hepatitis C in the United States – and people going on to high-risk drugs, "which is basically anyone going onto a" disease-modifying antirheumatic drug, he said.

"Having antibody to hepatitis C does not prove you have chronic hepatitis C infection, only that you have immunologic memory to the virus. The confirmatory test [for active infection] is the presence of [hepatitis C virus] RNA in the serum, detected by" polymerase chain reaction. "When you find this, the most important part is to refer [the patient] to a hepatologist," he said.

Screening for hepatitis C based on liver enzymes "is a fallacy," he said. Patients with chronic infection can have normal levels, and persistently normal levels do not rule out significant disease.

Perhaps 5 million people in the United States have active, chronic infection. There’s been a slight uptick in cases among men who have sex with men and drug users in rural areas who inject prescription drugs, he noted.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. SDEF and this news organization are owned by Frontline Medical Communications.


HIV Mortality Falls but Some Gaps Persist


By Charles Bankhead, Staff Writer, MedPage Today

Published: October 09, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

HIV mortality has decreased significantly across racial and ethnic groups and in men and women but remains much higher in nonwhite than in white individuals, an analysis of vital statistics showed.

In absolute terms, the largest decreases occurred among black men with the most education (117.89 per 100,000 population during 1993 to 1995, and 15.35/100,000 in 2005 to 2007) and Hispanic men with the least education (61.60 versus 9.01/100,000), according to Edgar P. Simard, PhD, of the American Cancer Society in Atlanta, and co-authors.

Although mortality declined in both sexes and across all education levels, rates remained substantially higher in minority groups, owing to higher baseline rates, they reported online in Archives of Internal Medicine.

"There were strong declines for all groups except for non-Hispanic black women of low SES (socioeconomic status)," the authors wrote in conclusion. "Relative declines were generally greater for those with higher educational attainment and for non-Hispanic whites, and these trends resulted in widening gaps between these groups."

"The black-to-white mortality disparities were generally similar across educational levels in both periods ... , highlighting racial disparities in HIV prevalence, treatment, and prevention within each level of education, which may be due to a combination of societal and environmental factors," they added.

Total HIV mortality has declined substantially since the mid-1990s. Overall declines can obscure subgroups that have benefited more or less from earlier diagnosis and highly active antiretroviral therapy (HAART). Simard and colleagues sought to identify such subgroups by examining trends over time in HIV mortality by sex, race/ethnicity, and education level.

The authors searched the National Vital Statistics System for HIV-related deaths among men and women ages 25 to 64 in 26 states, covering the years 1993 to 2007, inclusive.

Investigators compared mortality during two periods: 1993 to 1995 (pre-HAART) and 2005 to 2007 (HAART era). The primary outcomes were age-standardized HIV mortality, mortality differences, and rate ratios by education and between the least- and most-educated individuals (≤12 versus ≥16 years).

The search of the database identified 91,307 HIV deaths during 1993 to 2007 (74,445 men and 16,862 women). White men accounted for 35,149 deaths, black men for 34,783, and Hispanic men for 4,513. Corresponding numbers for women were 4,147, 11,663, and 1,052, respectively.

Comparison of the pre-HAART and HAART eras showed little variation in death rates by education among white men (25.77 to 26.42/100,000 for least to most education) in the pre-HAART period. By 2005 to 2007, rates had declined to 5.04, 2.82, and 1.79/per 100,000 for white men with ≤12 years, 13 to 15 years, and ≥16 years of education, respectively.

Black men with the least education had the highest mortality in both periods: 122.02/100,000 during 1993 to 1995 and 52.71/100,000 in 2005 to 2007.

Among Hispanic men, those with the least education had an HIV mortality of 58.67/100,000 during 1993 to 1995, declining to 9.01/100,000 during 2005 to 2007. Hispanic men with the most education had HIV death rates of 49.84 and 3.13/100,000 for the early and later periods of years included in the study.

For both the pre-HAART and HAART eras, women of all races and education levels had lower HIV mortality compared with men. Nonetheless, HIV mortality declined across the board: 1.97 to 0.80/100,000 in white women; 22.50 to 16.97/100,000 in black women; and 12.24 to 2.32/100,000 in Hispanic women.

Despite declines in HIV mortality across all ethnic groups, disparities increased by level of education in two groups: most- and least-educated white men and black men.

During 1993 to 1995, the mortality disparity by education in white men was <1/100,000 but increased to >3/100,000 by 2005 to 2007. Among black men, the education-related disparity increased from ~4/100,000 during 1993 to 1995 to >37/100,000 during 2005 to 2007.

"HIV death rates remained markedly high among non-Hispanic black men of all SES levels and were unchanged for non-Hispanic black women in the lowest SES strata," the authors wrote in conclusion.

"These findings suggest the need for focused interventions and resources to facilitate the identification of high-risk individuals, as well as entry and retention into care for these most vulnerable groups affected by the HIV epidemic in the U.S."

The study was supported by the American Cancer Society.

The authors had no disclosures.

Primary source: Archives of Internal Medicine
Source reference:
Simard EP, et al "The influence of sex, race/ethnicity, and educational attainment on human immunodeficiency virus death rates among adults, 1993-2007" Arch Intern Med 2012; DOI: 10.1001/archinternmed.2012.4508.


‘Like this page’ to prevent sexually transmitted infections


Posted October 8, 2012 on ScienceBlog.com

Sexually transmitted infection (STI) prevention messages delivered by Facebook can be effective in promoting condom use among young adults in the short term, a new study has found. Few students and young adults receive comprehensive sexuality education or guidance on HIV and other STI risks. Social media may provide a viable alternative to promote safe sex using online networks of friends, the study published in the November issue of the American Journal of Preventive Medicine reports.

“The use of social media to influence sexual risk behavior in the short term is novel. It is a first step in considering how to reach the overwhelming numbers of youth online, and how to maximize approaches to technology-based interventions,” says lead investigator Sheana S. Bull, PhD, MPH, of the Department of Community and Behavioral Health at the Colorado School of Public Health at the University of Colorado Anschutz Medical Campus, Aurora, CO.

Researchers initially recruited study participants in community settings and through postings on popular blogs and websites, as well as advertisements in college and local papers in US cities with higher than average rates for STI and HIV. Recruitment focused on African-American and Latino youth given the disparity of infections between these groups and other young adults. Each recruit was given an incentive to recruit three friends to participate, and each new recruit was also incentivized to recruit three friends, for five recruitment waves.

Participants and those they recruited were randomly assigned as a network to either an intervention group or a control group. The intervention group signed up to “Like” and receive news from Just/Us, a Facebook community developed to promote sexual health. Each week a new topic such as communicating about sexual history, skills building for condom negotiation and use, and how to access STI testing was discussed on the site, with updates each day from youth facilitators in the form of video links, quizzes, blogs, and threaded discussions. The control page was called “18-24 News,” and shared news that happened during the hours of 6 pm to midnight on the 24 hour clock that was of interest to 18-24 year olds.

Demographic information and baseline information on condom use at last sexual encounter and the proportion of sex acts protected by condom use in the last 60 days were collected at the start of the study. 636 people were enrolled in the 18-24 News intervention and 942 in the Just/Us intervention. Surveyed two months after the intervention, 68% of the Just/Us group reported using a condom during the last sex act, versus 56% of the controls, and the proportion of sex acts protected by condom use in the last 60 days was 63% for the Just/Us group versus 57% for controls. The effects decreased over time and a survey six months after the intervention found no difference between the two groups. There was no evidence that any demographic characteristics influenced response to the intervention.

“The effect size from the short-term outcomes match or exceed those observed in other Internet interventions, suggesting Facebook for sexual health interventions is at least equally effective as other technology-based mechanisms, and these effects match those observed for more traditional HIV prevention programs delivered in real-world settings,” Dr. Bull observes.

Results also show success in recruitment of youth of color and youth living in geographic regions with high STI and HIV prevalence, and success in reaching large numbers of people with STI- and HIV-related content through Facebook. There is little evidence that youth actively seek out and engage with organizations on Facebook. Thus approaches like that of Just/Us to push messages out offer one way to get messages in front of a large number of youth.

Dr. Bull notes that the study relied on self-reporting, and condom use may have been over-reported. Another concern is that the number of active participants declined over time, as did the treatment effect. “Although this type of attrition has been documented in other online STI-related research, it underscores the need to redouble efforts to attract and engage higher-risk youth in prevention efforts using social media. Future work should explore approaches to keep audiences engaged in social media content related to sexual health,” she concludes.

In a commentary accompanying the article, Nathan K. Cobb, MD, from the Schroeder Institute for Tobacco Research and Policy Studies at the American Legacy Foundation, Washington, DC, says, “For health behavior change intervention designers, Facebook offers something unprecedented – direct access to an individual’s social network, in real time, and without the need for tedious network enumeration by participants. However, such approaches require multidisciplinary teams that include social media specialists, marketers, and software developers as equal partners in design and intervention development. Building such teams will undoubtedly require changes to traditional funding and development models, but the potential is too large to be ignored or minimized.”


Insulin Resistance Is Associated With Progression to Hepatic Fibrosis in a Cohort of HIV/Hepatitis C Virus-Coinfected Patients


Mark W. Hull; Kathleen Rollet; Erica E.M. Moodie; Sharon Walmsley; Joseph Cox; Martin Potter; Curtis Cooper; Neora Pick; Sahar Saeed; Marina B. Klein

Posted: 10/08/2012; AIDS. 2012;26(14):1789-1794. © 2012 Lippincott Williams & Wilkins

Abstract and Introduction

Objective: Hepatitis C virus (HCV) infection is associated with higher insulin levels and insulin resistance. We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the effect of insulin resistance on the development of hepatic fibrosis.
Methods: Data were analysed from 158 nondiabetic participants in a prospective Canadian cohort of HIV/HCV-coinfected patients. Patients were defined as having insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR) index. Factors associated with a high index (HOMA-IR ≥2) were identified using multivariate logistic regression. Incidence rates of liver fibrosis [aspartate aminotransferase-to-platelet ratio index (APRI) ≥1.5] were calculated, and multivariate time-dependent Cox regression models used to assess the effect of baseline insulin resistance on the risk of developing an APRI score of at least 1.5 during follow-up.
Results: Overall, 56% had baseline HOMA-IR of at least 2. In the adjusted multivariate logistic analysis, only baseline BMI of more than 25 kg/m2 remained associated with insulin resistance [adjusted odds ratio 3.66, 95% confidence interval (CI) 1.70–7.92]. Rates of progression to significant hepatic fibrosis (APRI ≥1.5) were higher in those with HOMA-IR of at least 2 (16.32 per 100 person-years, 95% CI 6.68–25.97) compared with those with HOMA-IR less than 2 (7.95 per 100 person-years, 95% CI 0.16–15.75). Baseline HOMA-IR of at least 2 was associated with the development of significant fibrosis (adjusted hazard ratio 7.71, 95% CI 2.55–23.36).
Conclusion: In this first longitudinal analysis, insulin resistance was very common among coinfected patients and was associated with modifiable risk factors such as elevated BMI. Insulin resistance was found to be strongly associated with progression to hepatic fibrosis over time.


Hepatitis C virus (HCV) infection has been associated with an increased risk for insulin resistance and diabetes[1] with 30–70% exhibiting some degree of insulin resistance.[2] Insulin resistance has been associated with a wide variety of adverse health outcomes such as cardiovascular disease and cancer and with decreased response to HCV therapy among HCV-monoinfected patients.[3–6] The homeostasis model for assessment of insulin resistance (HOMA-IR) index is a well validated noninvasive method to measure insulin sensitivity.[7] HCV-infected individuals have been shown to have higher HOMA-IR scores (compared with uninfected matched controls)[1] which have been associated with fibrosis and steatosis in cross-sectional analyses.[8] In HIV-infected patients, HCV has also been shown to be associated with the presence of insulin resistance,[9–11] but its association with progressive fibrosis is less clear.[12] We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the impact of insulin resistance on the development of liver fibrosis prospectively.

Materials and Methods
Study Design, Setting and Population

The Canadian Co-infection Cohort Study [CCC, CIHR Canadian HIV Trials Network (CTN222)] is a prospective multicentre study recruiting HIV/HCV-coinfected patients at 16 centres across Canada since 2003 with approval by participating research ethics boards and has been described in detail elsewhere.[13] As of October 2010, 955 patients were enrolled. To evaluate factors associated with insulin resistance, we included nondiabetic participants (based on recorded medical history and current prescription for insulin or oral hypoglycaemic medication) with at least one study visit between April 2003 and October 2010 and available baseline values of fasting insulin and glucose (n = 185). This sample was further restricted to assess the effect of insulin resistance on fibrosis progression. Only participants (n = 85) with virologic evidence of active HCV infection (HCV-RNA-positive, COBAS AMPLICOR HCV Test, version 2.0, Roche Diagnostics, Hoffmann-La Roche Ltd, Laval, Canada), an aspartate aminotransferase (AST)-to-platelet ratio index (APRI) less than 1.5 and absence of end-stage liver disease (ESLD) at study entry were studied. Patients were censored on their last clinic visit prior to October 2010, when an outcome occurred, at death or at initiation of HCV treatment.


Insulin resistance was determined at baseline for all eligible patients using the HOMA-IR [fasting insulin (mIU/l) × fasting glucose (mmol/l)/22.5].[7] APRI was used as a noninvasive surrogate marker for liver fibrosis defined as follows: 100 × (AST (U/l)/upper limit of normal)/platelet count (109 cells/l).[14] An APRI of at least 1.5 was considered significant fibrosis (corresponding to a biopsy score ≥F2).[14–16]

Statistical Analyses

Multiple logistic regression was used to identify factors independently associated with insulin resistance (HOMA-IR ≥2, a cut-point indicative of insulin resistance in other analyses.[5,17,18] The natural logarithm of the APRI [ln(APRI)], which nearly normalizes the distribution, was used in these analyses.[19]

We estimated incidence rates of liver fibrosis (APRI≥1.5) among those without fibrosis at baseline. Poisson count models were used to calculate confidence intervals (CIs) for incidence rates. Multivariate time-dependent Cox regression models were constructed to assess the effect of insulin resistance at baseline on the risk of developing an APRI of at least 1.5 during follow-up and included covariates that had statistically significant hazard ratios in univariate analyses along with those determined a priori to be clinically important. Insulin resistance was modelled either as a categorical variable (HOMA-IR<2 or ≥2) or as a continuous variable, using 2 log-base HOMA-IR to account for the skewed distribution of HOMA-IR values while allowing for straightforward clinical interpretation (e.g. risk for each doubling in HOMA-IR was estimated). Robust variance estimation was used in all Cox regression analyses to account for the correlation of data contributed by the same participant at multiple visits. Statistical analyses were performed using R program for Windows Release 2.11.1 (R cran, Auckland, New Zealand).


Overall, 158 individuals were included in the primary analysis. The major reason participants were excluded from the study was lack of fasting measures of insulin or glucose (n = 755). Included patients were similar in all regards to those excluded except there were fewer men (63 vs. 76%) and IDUs (74 vs. 82%) and more combination antiretroviral therapy (cART) users (88 vs. 80%). Notably, there was no difference in BMI, alcohol use, median CD4 cell count or types of ART (protease inhibitor vs. nonnucleoside reverse transcriptase inhibitor) used between those included and excluded. Overall, the median age was 45 years [interquartile range (IQR) 40–50], 63% were male, 23% had history of recent IDU and 89% received cART. At baseline, 70 (44%) had HOMA-IR less than 2; 45 (28%) had an index of 2.0–3.9; 22 (14%), had an index of 4.0–5.9, and 21 (13%) had HOMA-IR at least 6. There was no statistically significant association between baseline insulin resistance and baseline hepatic fibrosis (n = 32), although the median HOMA-IR was higher at 2.7 (IQR 1.8–4.5) compared with 0.8 (IQR 0.5–1.4, P = 0.35) for those with baseline APRI less than 1.5.

Factors Associated With Baseline Insulin Resistance

In adjusted multivariate analysis, only BMI of at least 25 was strongly associated with baseline insulin resistance (seeTable 1, HOMA-IR ≥2). Although receipt of protease inhibitor-based therapy was associated with insulin resistance in univariate analysis, this association was attenuated in multivariate analysis.

Factors Associated With the Development of Fibrosis

Fifteen individuals (18%) developed significant hepatic fibrosis (APRI ≥1.5) with median follow-up of 1.4 (IQR 1.0, 1.7) years. Rates of progression to significant fibrosis were higher in those with HOMA-IR of at least 2 (16.32 per 100 person-years, 95% CI 6.68–25.97, n = 11) compared with those with HOMA-IR less than 2 (7.95 per 100 person-years, 95% CI 0.16–15.75, n = 4).

In multivariate analyses, baseline HOMA-IR of at least 2 and HOMA-IR modelled as a continuous variable were both strongly associated with progression of hepatic fibrosis (Table 2). Among other covariates, only baseline APRI was also associated with fibrosis progression. Given the small number of events, we did not include more covariates in the final model. In sensitivity analyses, we examined cART use, triglycerides and ethnicity which were not associated with fibrosis nor did their inclusion in the multivariate model alter the main results (data not shown).


Insulin resistance was present in a majority of HIV/HCV-coinfected cohort participants with 56% having a baseline HOMA-IR of at least 2 and a significant proportion having very high levels of insulin resistance (27% having HOMA-IR score ≥4). As we excluded those receiving oral hypoglycaemics or insulin, this finding suggests that a substantial number of coinfected persons are not recognized as having impaired glucose tolerance and are, thus, at risk for common complications of insulin resistance.[3,4,20] Presence of insulin resistance was associated primarily with classic and potentially modifiable risk factors: elevated BMI and waist circumference. Although fasting glucose was higher among those having HOMA-IR of at least 2, all had values within the normal range; thus, fasting insulin levels are required to identify individuals with insulin resistance.

To understand whether insulin resistance contributes to the development of hepatic fibrosis, longitudinal studies in persons not having fibrosis or advanced liver disease are required. Ours is the first such longitudinal study to examine this question in coinfected patients. We found insulin resistance was strongly associated with development of hepatic fibrosis. In adjusted analyses, the risk of developing fibrosis was nearly eight times greater in the presence of insulin resistance and was independent of BMI. Furthermore, for each doubling in HOMA-IR score there was a 48% increase in risk for progression to fibrosis. This finding suggests that efforts to improve insulin sensitivity may potentially reduce rates of fibrosis progression among coinfected persons. Given the rise of ESLD morbidity and mortality among HIV/HCV-coinfected persons, the identification of this potentially modifiable risk factor for liver disease progression is of enormous relevance.

The prevalence of insulin resistance in our Canadian cohort is somewhat greater than that reported in other populations. Among 170 coinfected patients from France, the prevalence of insulin resistance was 37%.[17] In 1041 HIV-infected Spanish patients, the prevalence was 48% among 373 HIV/HCV-coinfected patients compared with 33% in those without HCV infection.[11]

We could not demonstrate an association of specific antiretroviral agents with the presence of insulin resistance at baseline. Particularly, certain protease inhibitors and cumulative exposure to nucleoside reverse transcriptase inhibitors, especially stavudine, have been implicated in previous studies.[21–24] In contrast, there has been no clear association of specific drug class or duration of ART exposure and insulin resistance in coinfected populations.[9,10] The lack of association between ART exposure and insulin resistance in our study and others may be due to a lack of power, given the relatively small numbers of individuals analysed to date, or may reflect more complex effects of ART on HCV-related disease.[25,26]

Prior cross-sectional studies in coinfected persons have not identified a clear relationship between insulin resistance and presence of hepatic fibrosis.[12,17] In contrast, in a cross-sectional study of 330 coinfected patients undergoing transient elastography, 64% of those with HOMA-IR of at least 4 had measures of at least 9 kPa compared with 39% of those with HOMA-IR less than 4 (P < 0.0001), and HOMA-IR of at least 4 was an independent predictor of elevated liver stiffness (adjusted odds ratio 5.33, 95% CI 2.70–10.49).[27] Insulin resistance has been associated with higher estimated fibrosis progression rates in monoinfected populations[1] but not in a small study of coinfected patients.[12] Finally, in HCV monoinfection, HOMA-IR more than 2 has been associated with decreased sustained virologic responses (SVRs) to HCV therapy. In coinfected patients, however, studies on the impact of insulin resistance on SVR have been contradictory.[18,28,29]

Mechanisms by which insulin resistance occur in HCV-infected patients have not been fully elucidated, but include effects of inflammatory cytokines such as tumour necrosis factor alpha,[30] other cytokine signalling pathways (e.g. upregulation of suppressor of cytokine signaling-3 protein)[31] and effects on insulin–receptor substrate which interferes with insulin signalling.[32] Whether HIV directly plays a role remains unclear.

Our study has some potential limitations. Overall, a significant proportion lacked fasting glucose and insulin values and, therefore, was excluded from analysis. This limited our power to determine associations between insulin resistance and such factors as specific antiretroviral drug classes or HCV genotype. The large number of excluded patients also potentially could have introduced a selection bias. Use of HOMA-IR in the evaluation of insulin resistance in HCV-infected patients is well established,[33] and we used a HOMA-IR score of at least 2 to define significant insulin resistance, as used in other North American and European coinfected populations,[5,17,18,34] although other cut-offs have been used.[12] We used the APRI score as a surrogate marker for hepatic fibrosis rather than liver biopsy. APRI has been validated against liver biopsy in our cohort as well as others and is widely accepted as a surrogate marker and is highly specific for fibrosis stages equal to or greater than F2 Metavir score (significant fibrosis, few septa).[14] A limitation of not using serial biopsies is the potential interplay between insulin resistance and hepatic steatosis, itself a consequence of insulin resistance, which may contribute to fibrosis progression.[17]


Given the very high prevalence of insulin resistance, its known association with important health outcomes and its associated high risk for liver disease progression observed in this study, routine screening for insulin resistance among coinfected persons may be warranted. Interventional studies to manage modifiable risk factors for insulin resistance and evaluate the role of pharmacotherapy in modifying the course of liver disease progression and improving HCV treatment outcomes among HIV/HCV-coinfected persons are needed.


The authors thank Alex Schnubb, Manon Desmarais, Curtis Sikora, Christine O'Reilly, Brenda Beckthold, Heather Haldane, Laura Puri, Nancy McFarland, Claude Gagne, Elizabeth Knight, Lesley Gallagher, Warmond Chan, Sandra Gordan, Judy Latendre-Paquette, Natalie Jahnke, Viviane Josewski, Evelyn Mann and Anja McNeil for their assistance with study coordination, participant recruitment and care.

The Canadian Co-infection cohort investigators (CTN222) are Jeff Cohen, Windsor Regional Hospital Metroplitan Campus, Windsor, Ontario, Canada; Brian Conway, Downtown IDC, Vancouver, British Columbia; C.C., Ottawa General Hospital, Ottawa, Ontario, Canada; Pierre Côté, Clinique du Quartier Latin, Montreal, Quebec, Canada; J.C., Montreal General Hospital, Montreal, Quebec, Canada; John Gill, Southern Alberta HIV Clinic, Calgary, Alberta, Canada; Mark Tyndall, Native Health Centre, Vancouver, British Columbia, Canada; Shariq Haider, McMaster University, Hamilton, Ontario, Canada; Marianne Harris, St Paul's Hospital, Vancouver, British Columbia, Canada; David Hasse, Capital District Health Authority, Halifax, Nova Scotia, Canada; Julio Montaner, St Paul's Hospital, Vancouver, British Columbia, Canada; E.E.M.M., McGill University, Montreal, Quebec, Canada; N.P., Oak Tree Clinic, Vancouver, British Columbia, Canada; Annita Rachlis, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada; Roger Sandre, HAVEN Program, Sudbury, Ontario, Canada; Danielle Rouleau, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; David Wong, University Health Network, Toronto, Ontario, Canada; M.W.H., British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada; and S.W., Toronto General Hospital, Toronto, Ontario, Canada.

This study was funded by the Fonds de recherche en santé du Québec, Réseau SIDA/maladies infectieuses (FRSQ), the Canadian Institutes of Health Research (CIHR MOP-79529) and the CIHR Canadian HIV Trials Network (CTN222). M.B.K. is supported by a 'Chercheur-boursiers cliniciens senior' career award from the FRSQ.

AIDS. 2012;26(14):1789-1794. © 2012 Lippincott Williams & Wilkins
Lippincott Williams & Wilkins

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