April 10, 2012

Organ donor's surgery death sparks questions

By Elizabeth Cohen , Senior Medical Correspondent

2012-04-08T15:33:15Z

CNN.com

120403034939-paul-lorraine-hawks-story-top

Lorraine Hawks and her husband Paul, who died during surgery after donating part of his liver to Lorraine's brother-in-law.

(CNN) -- Before dawn on her 57th birthday, Lorraine Hawks and her husband, Paul, piled into their brother-in-law Tim Wilson's Lexus in Pelham, New Hampshire, with Lorraine and her sister Susie in the back seat and the men up front. As the two couples drove to the Lahey Clinic in Burlington, Massachusetts, Lorraine and Paul teased Tim mercilessly.

"By 5 o'clock today, you're going to have a Republican liver!" they taunted Tim. "You're going to love Ann Coulter! You're going to love Glenn Beck!"

"No way!" protested Tim, a staunch Democrat. He swore that even with a chunk of his Republican brother-in-law's liver inside him, he'd never be conservative. The foursome joked and laughed during the 45-minute drive to Lahey. At the hospital, the sisters kissed their husbands goodbye, and the men were wheeled into operating rooms, where surgeons would remove 60% of Paul's liver and give it to Tim, who suffered from advanced liver disease.

As Lorraine sat in the waiting room with Susie that May morning two years ago, she prayed her husband's liver lobe would cure her brother-in-law. She prayed for her husband, too, but she was less worried about him, since she says the surgeons had reassured them while liver donation wasn't without risks, it was safe for Paul, a 56-year-old man in good health.

Neither of Lorraine's prayers came true. Tim died less than a year later, after receiving the transplanted part of Paul's liver. He was 58. Her husband died that very day on the operating room table.

"We walked into the hospital a married couple, and I left the hospital at the end of the day as they loaded my husband onto the coroner's truck," says Lorraine, who has hired a lawyer and plans to file a lawsuit against the hospital.

'He didn't hesitate to say yes'

Paul Hawks, an electrician for the Florida Department of Transportation, was one of more than 4,500 people in the United States in the past 25 years who have donated a section of their liver while still alive. Death is rare: Besides Paul, three other donors have died since 1999.

The relatives of the other donors -- they died in 1999, 2002 and 2010 -- have gone public, but this is the first time Lorraine has discussed her husband's death.

"I want everyone to know what a generous, wonderful man Paul was. When he found out Tim needed a liver, he didn't hesitate to say yes," said Lorraine, a school bus aide for children with special needs in Tampa, Florida. "They weren't blood relatives, but they were a perfect match, and he felt privileged that God was going to let him help Tim regain his health."

Living organ transplants are a miracle of modern medicine. In all, more than 100,000 people in the U.S. like Paul have donated a kidney, a liver lobe or another body part while still alive to save someone else's life. Most of the time, the surgeries go well. Not only are donor deaths rare, but major complications of any kind are the exception rather than the rule.

This makes it all the more difficult for Lorraine to understand why her husband was one of the few who didn't make it.

'We tried very hard to save Paul ...'

After her husband was wheeled into surgery, Lorraine, her father-in-law and Susie walked around the block a bit and got a bite to eat in the hospital cafeteria. Then shortly after 1 p.m., about four and a half hours after the surgery began, Lorraine says, the coordinator of the transplant team came out to talk to them.

Sitting next to Lorraine, their knees nearly touching and speaking in a near whisper, Lorraine says, the coordinator told her that they were having trouble getting Paul's blood to coagulate and that an expert had been called in. Then about an hour later, the coordinator came out again to say her husband was having "irregular heart rhythms."

"She was acting real strangely, and we were so frightened," Lorraine remembers.

The coordinator's cell phone rang, and she answered it. She hung up and rubbed Lorraine's arm, which Lorraine found strange, and told her she'd be back in five minutes.

When she returned, she asked the family to come into a small private waiting room. Lorraine remembers her father-in-law screaming, "Tell me what happened to my son!" But the coordinator wouldn't say anything. The family sat there for about 40 minutes. Then the coordinator asked the family to go into a conference room farther away from the waiting area.

"We're looking at each other and said 'this can't be good,' " Lorraine recalls. "We walked, crying, holding onto each other."

Suddenly the conference room filled with doctors, counselors and pastoral staff.

"We tried very hard to save Paul ..." Lorraine remembers one of the doctors saying. She was sobbing so hard she didn't hear the rest of his sentence. Then the surgeon who did Paul's operation, her eyes red and puffy, got down on her knees to speak with Lorraine eye-to-eye.

"I saw her mouth moving, but I couldn't hear what she was saying," Lorraine remembers. "My brain was on fire."

Lorraine stayed with her husband's body until the coroner came to take him away. She says the next day, people from the hospital called her six times, offering condolences and to pay for Paul's funeral. She didn't want to talk to them.

A few weeks later, back home in Tampa, Lorraine read a statement online from the Lahey Clinic's then-CEO, Dr. David Barrett.

"Lahey Clinic and its transplant team are extremely saddened by the loss of a gentleman who died while donating a portion of his liver to his relative," Barrett said. "Since the inception of its live donor liver transplantation program in 1999, Lahey Clinic has performed more than 200 of these complex life saving surgical procedures."

Reading the article made Lorraine feel worse, she says. It still didn't explain why her husband had died.

Then in July, about two months after her husband's death, Lorraine stopped by her post office after grocery shopping to pick up her mail. In her box was a thick envelope from the Massachusetts Department of Public Health. Inside was a nine-page report with the details of what happened during Paul's surgery.

Finally, she thought, her questions would be answered. Finally, she would find out why her husband died.

'Donor ... could not be resuscitated'

The Department of Public Health report gives a rare and gruesome picture of a surgical procedure gone horribly wrong.

The department's account is based on medical records, operating room communications and two days of interviews with the attending transplant surgeon and other doctors, nurses and administrators.

After Lorraine and Susie kissed their husbands goodbye, Paul and Tim were wheeled into separate operating rooms. Everything went fine until about four hours into the operation, when a vein that carries blood away from the liver partially tore off and started bleeding.

Paul's surgeons immediately called for assistance. More doctors and nurses arrived in his operating room. It was to be the beginning of a 2½-hour fight to save Paul.

The partially torn vein came all the way off, and doctors sewed up that tear, but then they noticed bleeding coming from somewhere else. As they searched for the source, a clamp on a vein got knocked off, injuring the vein. Repairing that injury, they noticed more tears. They fixed those tears, all the while giving Paul blood products and drugs to raise his blood pressure.

It seemed like Paul might be getting better, but then he started to bleed from several areas all at once. His heart started to beat very fast. Doctors performed CPR, and when that failed, they cut his chest open, massaged his heart directly and shot drugs into his heart to get it going again. But none of it worked.

"The patient had a cardiac arrest secondary to excessive bleeding & could not be resuscitated," the report states.

Paul Hawks was pronounced dead at 3:01 p.m. on May 24, 2010.

Pamela Johnston, a spokeswoman for the Lahey Clinic, one of the largest liver transplant centers in the country, declined to comment about the details in the state's report. Lahey voluntarily stopped operating on living liver donors for about four months.

The Massachusetts Department of Public Health did not cite the hospital for any deficiencies. The Lahey Clinic conducted its own internal investigation into Paul's death and hired outsiders to conduct an external investigation. Lahey declined CNN's request for copies of both these reports.

More red flags

Lorraine read the Department of Public Health report sitting in her car in the parking lot of the Tampa post office. As she read the details of her husband's failed surgery, she wondered whether all the tears and bleeding were anyone's fault, or were they just unavoidable consequences of surgery, inevitable events that statistically speaking happen sometimes, and Paul was just unlucky?

Three other items in the Department of Public Health report raised even more questions.

First, she found out Paul had been given a pre-operative EKG, and it was abnormal. It showed he might have had a past heart attack, but then follow-up testing showed no evidence of poor blood flow to his heart.

"I had no idea he'd had an abnormal EKG," she says now. "If I had known, I never would have let him have the surgery."

The report doesn't say whether Paul knew about his abnormal EKG or if a cardiologist was called in to evaluate whether his heart was strong enough to tolerate surgery. Johnston, the Lahey Clinic spokeswoman, declined to answer questions about the EKG or about any aspect of Paul's surgery or pre-operative care.

Second, the report pointed out that a special high-speed blood pump wasn't used to give Paul blood.

The $20,000 device pumps blood at least three times faster than other pumps. Called a Belmont Pump, it's saved soldiers' lives as they lay massively bleeding on battlefields in Afghanistan and Iraq.

Lahey owns a Belmont Pump. At the time of Paul's surgery, it was nearby in Tim Wilson's operating room. But as Paul lay bleeding to death for 2½ hours, no one brought it in to his operating room.

"It's portable," says George Herzlinger, president of Belmont Instrument, which makes the device. "It weighs 27 pounds. You just wheel it over."

Third, the report describes how Paul's surgeons never activated a set of procedures used when a patient is massively bleeding.

Called the "Massive Blood Transfusion Protocol," it directs surgeons to call the hospital's transfusion services and activate a set of procedures so a patient who's bleeding profusely can most efficiently get the blood products he needs.

The report notes that surgeons thought none of these things -- the abnormal EKG, the lack of the high-speed pump, the inactivated protocol -- contributed to his death.

Nonetheless, the report shows the hospital did think it could have done some things differently.

After Paul's death, staff members questioned whether there needed to be a "higher standard" when evaluating patients with abnormal EKGs. They said it would have been "nice" to have had a Belmont Pump in the room. They educated staff about activating the blood transfusion protocol.

A new type of surgery

In the end, the Department of Public Health report didn't answer Lorraine's questions as she'd hoped. She still didn't know what had killed her husband. Nearly two years after her husband's death, she still has no peace and no closure.

"DPH does not have a position on what caused the patient's death," Jennifer Manley, a DPH spokeswoman, explained in an e-mail to CNN. "Likewise, we don't look at who is to blame for the death."

Lorraine was emotionally spent. While she had the support of her sisters and her sons, she wanted something more.

"I wanted to talk to a widow, to someone else who'd gone through this," she said.

So Lorraine typed "donors that died" into Google. It didn't take her long to find Vickie Hurewitz, whose husband, Mike, was the donor who died in 2002. She found Hurewitz's e-mail address, and they set up a time to talk on the phone.

"I cried with her for two hours. Sometimes I couldn't even talk, I was crying so hard," Lorraine remembers. "Vickie said to me, 'Lorraine, I'm so sorry. I know your heart is broken.' "

At the end of the conversation, Vickie said, "Lorraine, I want you to meet a friend of mine."

That friend was Donna Luebke. A nurse in Ohio, Luebke donated a kidney to her sister in 1994. Now an associate at the Center for Biomedical Ethics at Metrohealth Medical Center and Case Western Reserve University in Cleveland, Luebke has developed an interest in the ethics of living organ donation.

Working with Luebke, Lorraine found out there was something else she didn't know about Paul's surgery.

Most liver donors in the United States have "open" surgeries with a long incision across the abdomen. According to medical records obtained by CNN, Paul had laparoscopically assisted surgery, a minimally invasive technique with three very small cuts.

The advantage of "lap-assisted" surgery is a much easier recovery for the patient. The downside, surgeons say, is if a patient starts bleeding, it can be harder to find the source, since they can look only through small incisions rather than a very large one.

"It's harder to see, especially if you're not used to doing this surgery," Luebke says.

Luebke told Lorraine she thought the Lahey surgeons might not have had much experience with "lap-assisted" surgeries on liver donors. The technique had only been used for a few years in the United States when Paul had his surgery, and some surgeons were trying it out for the first time.

"There's a steep learning curve," she says. "It's a different skill set than doing an open surgery."

Dr. Peter Pronovost, a patient safety expert at Johns Hopkins University School of Medicine in Baltimore, agrees.

"When a surgeon wants to try out a new surgical technique, they can just go ahead and do it," he says. "There's no rule saying you have to tell the patient you're taking out the liver in a different way and this will change the risk profile."

A spokeswoman for Lahey declined to say how many laparoscopic liver donor surgeries had been done at Lahey before Paul's operation.

A widow's regrets

Three months after Paul died, Ryan Arnold died after donating a liver lobe to his brother in Colorado. His death received a great deal of media attention, and the American Society of Transplant Surgeons released a statement.

"Living donor procedures are not without risk to the donor, even in experienced hands and programs," the statement read. "While attempts are always made to minimize donor risk, complications including death are always possible."

Now, nearly two years after her husband's death, after poring over the Department of Public Health report and her husband's medical records, Lorraine still wonders whether she could have done anything to keep from losing her husband on her 57th birthday.

She says there's one thing she knows she would have done differently. She had only enough time off work to fly from Florida to Boston for the surgery itself, so she wasn't there for Paul's pre-operative testing. He did that on his own.

"God, how I regret that," she says. "I would have asked a million questions."

Now she wonders whether Lahey gave Paul all the information he needed to make a smart decision about whether to go under the knife.

An inspection seven months after her husband's death by the federal Centers for Medicare & Medicaid Services (CMS) revealed that Lahey violated several federal rules for informing and protecting donors.

Under these regulations, each donor is supposed to be told about how other organ donors fared after their surgeries, both nationwide and at Lahey specifically. Studying the records for seven liver donors, CMS found Lahey failed to provide all of them with the most current surgical outcomes.

Dr. Roger Jenkins, the chairman of surgery at Lahey when Paul died, agrees that the data wasn't as up-to-date as it should have been.

"It got caught in the paper shuffle that's part of the hospital's record keeping," he said.

The CMS report noted that Lahey was out of compliance in another area.

Transplant centers are supposed to assign a staff person, such as a doctor or social worker, to be an independent advocate for the donor. The donor advocate is supposed to take into account only the donor's concerns -- for example, in Paul's case, the abnormal EKG findings -- and not the concerns of the recipient, since sometimes there can be a conflict of interest between the two.

To make sure the advocate is focused solely on the donor, there's supposed to be a "wall" between the donor advocate and the recipient's team, but federal inspectors observed Lahey's donor advocate going on medical rounds and participating in meetings run by the recipient's team.

"This goes against (federal) policy," the inspectors wrote in their report. "Their roles were not clearly defined to ensure protection of the rights of living donors."

Jenkins says he didn't know that the donor advocate wasn't supposed to attend meetings about the recipient.

"We interpreted the rules one way and the CMS reviewer interpreted them another way," Jenkins says. "There was certainly no intent not to comply with CMS regulations."

He added that it's not uncommon for hospitals to be out of compliance with CMS rules.

"If every center doesn't have at least one or two major out-of-compliance issues, that would be surprising to me," says Jenkins.

According to CMS, the hospital corrected the problems and was back in compliance with federal regulations about three months later.

'A very, very strong faith'

Lorraine knows she may never get all her questions answered about why her husband died that May afternoon.

She looks back on the day Paul made the decision to donate part of his liver with a mixture of sadness and pride. It was Thanksgiving Day, 2009, and they were at a Cracker Barrel in Tampa with their two grown sons.

During dinner, Lorraine's cell phone rang. When she answered the call and heard Susie crying, Lorraine excused herself to take the call outside.

When she returned to the table, Lorraine told Paul and their sons the bad news.

"Tim is ill, and if he doesn't get a liver donation, he'll die," she told them. Getting a liver from a cadaver was out of the question, she explained, since Tim was so sick, he'd never live long enough to get off the waiting list.

"My husband in 30 seconds -- no, less than that -- said 'I'll get tested,' " Lorraine remembers." And then our son Joseph said he'd get tested, too. Nobody ever asked them to do it. They just did it."

Before Joseph could protest, Paul told his son he'd fly to Boston first to get tested first, and if he wasn't a match, then Joseph could try. That turned out not to be necessary, as the tests showed Paul was a "perfect match," Lorraine says.

Before Paul flew to Boston for the transplant, the couple's other son, Gene, saw his father off at the Tampa airport.

"We had lunch together, and then right there in the middle of the airport I hugged him, even though he wasn't a touchy-feely guy," Gene remembers. "I prayed for good surgeons' hands to do the right thing."

In retrospect, Gene wishes he had advised his father to get a second opinion from another doctor about whether he was healthy enough to give away 60% of his liver -- from a doctor who didn't stand to financially gain from the transplant.

But his family says before the transplant, Paul Hawks wasn't looking for advice. He was looking to do good. Being a living donor was just an extension of the goodwill he did in his regular life, they say, like helping elderly people in his church with their home repairs for free.

"He wanted people to see Christ in him every day with every interaction," Gene says. "At lunch that day, he told me he wasn't going to die, because it was low risk, but if he did, he was prepared for it, because he was going to heaven."

CNN's Matt Sloane, Jennifer Bixler and John Bonifield contributed to this report.

Source

What Does The Liver Do: Liver Enzymes

What-Does-The-Liver-Do-300x300

Tuesday, April 10, 2012

The liver performs thousands of biochemical functions. In order to perform these functions, the liver contains thousands of enzymes. Enzymes are unique proteins that act as catalysts to speed the rate of particular chemical or metabolic reactions. Liver enzymes, therefore, help the liver to do its job. Enzymes utilized by the liver primarily exist in the cells of the liver. Under normal circumstances, these enzymes are also present in the bloodstream in low concentrations. However, when the liver is not working as it should, these enzymes spill over into the bloodstream. Liver function tests are blood tests that are used to detect the presence of enzymes in the bloodstream to determine liver disease.

Liver enzymes perform functions special for the liver though they are present in other organs of the human body. One category of liver enzymes is the aminotransferases or transaminases. These enzymes are used to detect the presence of liver damage or disease. Another category of enzymes include alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT). These enzymes are used to detect the presence of malfunction of the biliary tract.

The aminotransferase category includes the enzymes alanine aminotransferase (ALT), sometimes referred to as serum glutamic pyruvic transaminase (SGPT), and aspartate aminotransferase (AST), also known as serum glutamic oxaloacetic transaminase (SGOT). In particular, the aminotransferases act as a catalyst in the transference of amino group donor molecules to recipient molecules. In other words, these enzymes take out pieces from one structure to assist with production of another structure. The aminotransferases are the most sensitive and widely used of the liver enzymes and are normally present in the bloodstream in low concentrations. An increase in the bloodstream of either of these may indicate hepatocyte (liver cell) damage.

Although ALT is found primarily in the liver, lesser amounts can also be found in other organs, such as the kidneys, heart and muscles. When an increase of ALT levels has been detected in the bloodstream, it is usually due to liver damage, such as inflammation or cell death. An elevation in AST levels may be due to diseases of other organs, such as the heart. For this reason, clinicians determine the ratio of AST to ALT to determine if indeed the liver has been damaged.

ALP and GGT enzymes also participate in the movement of amino acids across the cellular membrane as well as metabolism. Like the aminotransferases, these enyzmes expand into the bloodstream when the biliary tract is obstructed, either within the liver or outside the liver in the bile channels. Since ALP is also found in organs other than the liver, such as bone, placenta and intestine, GGT levels are screened when there is an elevation in ALP levels. Since GGT does not increase in the presence of these other diseases, clinicians use the results from both tests to determine the cause of ALP elevation.

Clinicians use these tests together to determine the presence of liver disease or damage. Alone, these tests cannot allow a definite diagnosis but together they provide a better overall picture of liver function.

Source

Naloxone is a cheap, safe drug that could save countless people from overdosing on heroin and other opiates. So why isn't it in every first-aid kit?

storyimages_1329437011_naloxone

Photo Credit: PunchingJudy on Flickr

March 31, 2012 | When I was injecting drugs back in the mid-1980s, several sneaky killers were haunting addicts. We didn’t know it at the time, but half of all New Yorkers who shot drugs were already infected with HIV and many more were carrying the hepatitis C virus. There was no effective treatment for either disease. Thousands died. And unfortunately, many in the recovery community stayed silent.

The risk we knew about—overdose—seemed just as implacable. You could reduce the danger by limiting your doses and not mixing similar drugs, such as heroin, Valium and alcohol, say, or cocaine and amphetamines, and that remains good advice. Back then, we fatalistically assumed that this menace pretty much came with the territory.

In 2012, however, both HIV and hepatitis C are not only treatable but amenable to prevention campaigns. New HIV infections among drug users have been cut in half in the last decade, largely by clean-needle programs, which can also fight hepatitis C (though not as effectively).

But some 15,000 people still die annually from opioid overdoses—even though there’s a cheap, effective and safe remedy that could save most of these lives if it were more widely available. With prescription opioid misuse now the main cause of rising overdose fatalities and with the overwhelming failure of ongoing efforts to cut supply, it’s long past time to focus on the most direct way to prevent death by OD.

Since 1996, when Dan Bigg, of the Chicago Recovery Alliance, first began promoting the idea of distributing the opioid overdose antidote, naloxone, to drug users, overdose has been known to be a risk that can be dramatically reduced. As with needle exchange, however, drug-war politics has meant delays—and many needless deaths. The advocacy of the recovery community needs to be louder this time.

And more ambitious. We need not only to educate people about how to save lives with naloxone but to make it available over-the-counter and start a public-education campaign about why it’s essential for every first-aid kit.

Last month, the CDC reported that since Bigg started, more than 10,000 successful overdose reversals have been reported by the 188 programs in 15 states that currently provide naloxone and train users to administer it. Over 50,000 doses of the drug have been distributed.

Although some of the treated overdoses might not have been fatal without naloxone, the vast majority likely would have been because the drug is only used if the victim has stopped breathing.

Here are the facts about naloxone (brand name Narcan). It immediately reverses overdoses that involve an opioid, even if alcohol and benzodiazepines like Xanax are also involved, as is true in the vast majority of cases. It’s nonaddictive: in fact, about the only imaginable way to misuse it would be to torture people who are opioid addicted by using high doses to put them into withdrawal.

This property also means that addicted people won’t take extra opioids because they know a rescue drug is on hand: coming around from an overdose via naloxone is stressful, and anyway addicts tend to take the highest dose they have.

The story of Mark Kinzly, a recovering addict who now runs a harm-reduction program that distributes naloxone but who was himself saved by the drug during a relapse, illustrates why:

Kinzly was watching a Red Sox victory with a friend when he overdosed. “I am a Red Sox fan, but that's not what put me into an OD,” he jokes. He had injected two or three bags of heroin—a dose that he thought he could handle. Dangerously, he had misjudged his tolerance after years without heroin…

Fortunately, in Kinzly’s case, his friend had naloxone and knew how to help. “He said that he looked over and noticed I was turning gray and my lips were bluish. I had what he called a death gurgle. He loaded the Narcan into a syringe and injected it into my upper arm.”

Kinzly woke up, filled with shame over his relapse when he realized what had happened. Because naloxone reverses the effects of narcotics, it can cause withdrawal symptoms in addicted people. The symptoms are unpleasant but not dangerous.

“I certainly didn’t feel great, but I sure was grateful,” he says. “I was very embarrassed [but] I was incredibly grateful that I was going to have another opportunity to get clean again and watch my son grow up.”

Before his own overdose, he’d saved four people with naloxone and has since saved 10 others.

While doctors initially feared that naloxone carried the risk of causing seizures, this hasn’t been seen in the field. Naloxone distribution programs use lower doses than ER docs and EMTs typically do, finding that this saves lives without producing the intense withdrawal symptoms that might prompt users to seek and take more drugs. The drug is harmless if given in error for the wrong type of overdose. And because it's an opiate-receptor antagonist, or blocker (not to be confused with methadone and other opiate agonists, or substitutes), overdosing on naloxone itself is almost impossible.

Another fear has been that since naloxone is short-acting and some opioids have longer-lasting effects, people would be revived only temporarily and would need hospitalization for monitoring. While users are always advised to call 911 immediately—and many states are making “Good Samaritan” laws to exempt them from prosecution for drug possession if they call for help—at least one study found that refusing further medical care doesn’t increase the risk of death.

So what’s the catch? As with needle exchange, there’s moral discomfort among drug warriors who apparently feel that the wages of drug use should be death. Bertha Madras, the deputy drug czar under President George W. Bush, told NPR in 2008 that providing naloxone might sap users' motivation to get treatment because "sometimes having an overdose, being in an emergency room, having that contact with a healthcare professional, is enough to make a person snap into the reality of the situation and snap into having someone give them services."

Anything that reduces the risks of drugs, from this overdose-as-teachable-moment perspective, will keep addicts using longer and—why not?—even encourage children to start using. Yet in reality, of course, there’s no evidence that saving addicts’ lives prompts teens to take up drugs—and none that providing clean needles or naloxone deters recovery.

Indeed, Kinzly’s reaction to being revived—a recommitment to recovery—is common. And he might not have lived long enough to have it if he'd had to wait for an ambulance. Many people immediately seek treatment after surviving overdose. Also frequently reported by naloxone programs are people who kick addictions because the person who saved them was a sober example, showing them it was possible. In addition, the empowerment and self-esteem that comes from learning to help others and actually saving lives with naloxone can spur positive change.

So that’s why, just as I once called for recovery activism in support of needle exchange, I now believe we need it to push naloxone. People in recovery—simply by existing—show that addiction isn’t necessarily forever and that valuable, productive people can suffer from and beat back addiction. We need to stand with those who are not yet ready so they can survive long enough to hear that message of hope.

While more naloxone distribution programs at needle exchanges and other places frequented by active addicts are important, equally important is making naloxone available cheaply over-the-counter and educating the public that it’s a household essential. Here’s why. The riskiest periods of addiction are times when people have either just started using or recently quit, either in treatment or in prison. At those times, they are simply not likely to attend a needle-exchange program or to believe they have any need for naloxone.

Moreover, what parent—whether they find a teen blue on the couch or find a toddler (or even a pet) gobbling Grandma’s codeine—would not want to have the antidote on hand? Since parents typically believe, “Not my kid,” most would never visit a needle exchange or even think about overdose antidotes. Pain patients prescribed large doses of opioids are also at risk, not to mention addicted people who “doctor shop” and don’t associate with street drug users.

But if the Red Cross and similar organizations promoted naloxone as a first-aid measure that everyone should keep at home, this denial wouldn’t matter. There’d be no stigma to having it; it would just be something everyone stores in the bathroom or kitchen, like ace bandages or disinfectant. As pilots say about safety equipment, it’s better to have it and not need it than to need it and not have it.

At least half of all overdoses are witnessed, but if people don’t know the signs to look for or have the means to help, these lives can’t be saved. Key is recognizing erratic breathing, blue skin tone and strange snoring—and not letting someone “sleep it off,” which can be fatal.

Because people who have “been there” know what addiction is like and how helping others helps our own recovery, our voices are essential. Some of the key leaders in the fight for needle exchange, in fact, are or were recovering ex-addicts, and this is true for naloxone as well. But many, many more voices are needed—the fact that we’re still fighting with Congress over syringe exchange funding is only one illustration of why.

The FDA will hold a meeting April 12 to discuss making naloxone over-the-counter. Wouldn’t it be great if thousands of recovering people showed up or at least contacted the agency (where? click here) to make it know that our lives matter and we support OTC naloxone?

Maia Szalavitz is a columnist at The Fix. She is also a health reporter at Time magazine online, and co-author, with Bruce Perry, of "Born for Love: Why Empathy Is Essential—and Endangered" (Morrow, 2010), and author of "Help at Any Cost: How the Troubled-Teen Industry Cons Parents and Hurts Kids" (Riverhead, 2006).

Source

Review article | Published 24 February 2012, doi:10.4414/smw.2012.13516
Cite this as: Swiss Med Wkly. 2012;142:w13516

Swiss Association for the Study of the Liver1

1 Current Council Members of the Swiss Association for the Study of the Liver are listed in www.sasl.ch.

Abbreviations: AASLD, American Association for the Study of Liver Diseases; BOC, boceprevir; CHC, chronic hepatitis C; EASL, European Association for the Study of the Liver; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIV, human immunodeficiency virus; PEG-IFN-α, pegylated interferon-α; RBV, ribavirin; SVR, sustained virological response; SASL, Swiss Association for the Study of the Liver; TPV, telaprevir.

Summary

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. Two first-generation protease inhibitors, telaprevir and boceprevir, have recently been approved for the treatment of chronic hepatitis C genotype 1. Triple therapy comprising pegylated interferon-α, ribavirin and telaprevir or boceprevir increases sustained virological response rates to ~70% and allows to shorten treatment duration in ~½ of treatment-naïve patients with chronic hepatitis C genotype 1. Sustained virological response rates in treatment-experienced patients depend on the response to previous treatment, ranging from >80% in previous relapsers to ~30% in previous null responders. These advances come at the expense of new adverse effects and increased cost. In addition, treatment of chronic hepatitis C will become more complex. In these times of changing medical practice, the present expert opinion statement by the Swiss Association for the Study of the Liver shall provide guidance on the treatment of chronic hepatitis C with triple therapy comprising telaprevir or boceprevir.

Key words: boceprevir; chronic hepatitis C; HCV; hepatitis C virus; interferon; protease inhibitor; ribavirin; telaprevir

Introduction

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) [13]. An estimated 120–200 million individuals worldwide and about 1% of the general population in Switzerland are chronically infected with HCV. About 50% of the chronic HCV infections in Switzerland are due to genotype 1 [4]. While the incidence of acute hepatitis C has declined significantly since the introduction of anti-HCV screening of blood and blood products in 1990, the number of patients presenting with decompensated cirrhosis and HCC is expected to increase further, attaining a peak around 2020 [1, 5]. More than 50% of the individuals at risk may currently be unaware of their infection. Strategies to increase testing and detection rates are currently being explored (e.g., screening of populations at risk vs. birth cohort screening) [6, 7].

Fifty to 80% of acutely infected individuals develop persistent infection. Of these, 2–20% will develop liver cirrhosis within the first 20 years, and accumulating evidence suggests that disease progression may increase in a nonlinear fashion thereafter [8]. Once cirrhosis is established, the rate of HCC development is 1–6% per year. Factors associated with more frequent and rapid progression to cirrhosis are, among others, higher age at the time of infection, male sex, alcohol consumption, coinfections with the human immunodeficiency virus (HIV) or hepatitis B virus (HBV), nonalcoholic fatty liver disease and smoking. Comprehensive management of chronic hepatitis C (CHC) takes these factors into consideration and aims at improving the ones that can be modified (alcohol abstinence; weight loss, regular physical activity and other measures to control the metabolic syndrome; vaccination against HBV [and hepatitis A virus]; smoking cessation including cannabis) [9].

While non-invasive methods for fibrosis assessment are actively being pursued [10], liver biopsy remains the reference for grading and staging of CHC. The Metavir and Ishak scoring systems are most often applied. Fibrosis stages are classified from 0 (absence of fibrosis) to 4 (cirrhosis) in the Metavir system [11], and from 0 to 6 in the Ishak system [12].

The decision to treat CHC is based on the analysis of numerous variables and should take into account the specific situation of each patient. Treatment is clearly recommended for patients with Metavir fibrosis stage ≥2 who do not have any contraindications. For other patients, decisions will have to be made on an individual basis. Additional factors that come into consideration are, among others, the (biological) age and general condition of the patient, the patient’s personal and professional plans, the duration of HCV infection, the risk of developing cirrhosis, the likelihood of response to therapy, and comorbidity.

For the last 10 years, standard therapy of CHC consisted of pegylated interferon-α (PEG-IFN-α) combined with ribavirin (RBV) for (16-)24-48(-72) weeks, yielding sustained virological response (SVR) rates of 40–50% in patients infected with HCV genotype 1 and ~80% in patients infected with genotypes 2 and 3. Definitions of virological response patterns are provided in table 1.

Polymorphisms near the IL28B gene have recently been identified as strong predictors of the outcome of IFN-α-based antiviral therapy (reviewed in [13, 14]). A number of laboratories offer IL28B genetic testing, but its role in clinical practice and decision making, if any, remains to be defined.

A first generation of directly acting antivirals, the NS3-4A protease inhibitors telaprevir (TPV; Incivo®) and boceprevir (BOC; Victrelis®), has recently been approved for the treatment of CHC genotype 1. TPV and BOC have to be combined with PEG-IFN-α and RBV in order to avoid the rapid selection of HCV strains resistant to antiviral therapy [15, 16]. Triple therapy comprising TPV or BOC increases SVR rates to ~70% in treatment-naïve patients with CHC genotype 1 [1719]. In treatment-experienced patients, SVR rates depend on the virological response to previous therapy with PEG-IFN-α and RBV, ranging from >80% in patients with previous relapse to ~50% in patients with previous partial response and ~30% in patients with previous null response [2022]. Treatment schedules comprising TPV or BOC have more side effects than PEG-IFN-α and RBV, and should be managed carefully.

A significant increase in the number of patients with CHC to be treated is expected for 2012, with triple therapy regimens that are more complex, as discussed below [23]. These expected developments represent a significant challenge and will stretch current resources.

The present Swiss Association for the Study of the Liver (SASL) expert opinion statement is not intended as guideline but shall provide some guidance on the management of CHC genotype 1 and the use of TPV and BOC. It is based on the results of recently published phase III clinical trials performed in treatment-naïve and treatment-experienced patients (ADVANCE [17], ILLUMINATE [19] and REALIZE [20] for TPV as well as SPRINT-2 [18], RESPOND-2 [21] and PROVIDE [22] for BOC), and take into account the recently updated American Association for the Study of Liver Diseases (AASLD) Practice Guidelines [3] as well as the labels approved by the US Food and Drug Administration, the European Medicinal Agency, and Swissmedic. Current European Association for the Study of the Liver (EASL) Clinical Practice Guidelines [2] are expected to be updated shortly. In addition, different national guidelines are in preparation. Therefore, as recommendations are emerging and as real-life data and practical experience on the use of TPV and BOC are still limited, it is strongly recommended to initiate and pursue triple therapy comprising TPV or BOC only in close collaboration with an expert centre.

(Click on table to enlarge)

Capture

Practical use of telaprevir and boceprevir

TPV is available in the form of 375-mg film-coated tablets and has to be taken at a dose of 750 mg every 8 hours (i.e., two tablets every 8 hours), with a meal or a snack containing ~20 g of fat to increase bioavailability. BOC is available in the form of 200-mg capsules and has to be taken at a dose of 800 mg every 8 hours (i.e., 4 capsules every 8 hours), with a meal or a snack. Dosing every 8 ± 1 hour rather than 3 times per day is important to maintain inhibitory drug serum concentrations and to avoid antiviral resistance development. TPV and BOC should never be used alone, and doses should never be reduced. When used alone, these drugs will not be effective and will cause emergence of HCV strains with resistance to antiviral therapy that could be difficult to treat subsequently. RBV can be taken with the first dose of TPV or BOC in the morning and with the last dose of TPV or BOC in the evening.

TPV and BOC are only approved for use in patients with HCV genotype 1 infection. The development of antiviral resistance is more frequent in subtype 1a than 1b but this should not influence therapeutic decision making.

Both TPV and BOC have a strong potential for drug-drug interactions, as they affect the metabolism of other drugs metabolised through cytochrome P450 3A4 (CYP3A4) and other pathways [24]. See package inserts, continuously updated online databases (e.g., http://www.hep-druginteractions.org, Epocrates, Medscape) and Leise et al. [25] for known drug-drug interactions and contraindicated drugs. Commonly used drugs that are contraindicated in combination with TPV or BOC include, among others, atorvastatin, lovastatin, simvastatin, sildenafil, alfuzosin, carbamazepin, phenytoin, oral midazolam, and St. John’s wort. Among the drugs commonly used to manage adverse effects of therapy, paracetamol and metoclopramide (but not domperidone) are allowed. TPV and BOC may decrease citalopram levels and efficacy.

Main adverse effects of TPV include anemia, nausea and diarrhea, skin rashes and pruritus as well as anorectal disorders. Rash should be managed in collaboration with an experienced dermatologist and should follow recommendations that have recently been summarised [26]. TPV has to be discontinued if rash progresses and becomes severe. Rare cases of DRESS (drug-related eosinophilia with systemic symptoms) and Stevens Johnson syndrome/toxic epidermal necrolysis have been observed. If either one is suspected, all drugs have to be stopped immediately, followed by emergency dermatological consultation.

Main adverse effects of BOC include anemia, with a significant number of patients requiring concomitant erythropoietin treatment in phase II and III clinical trials, as well as dysgeusia.

Anemia can develop rapidly and become very pronounced with both TPV and BOC, especially in patients with cirrhosis. Therefore, close monitoring is recommended. Anemia should be managed by timely RBV dose reduction and, if needed, blood transfusions and/or erythropoetin.

Data on the safety and efficacy of TPV and BOC in patients with HIV coinfection are emerging. TPV and BOC should be used only in close collaboration with an expert in these patients.

There is no data in liver transplant recipients, hemodialysis patients and children, and the use of TPV and BOC in these situations is currently proscribed.

In registration trials, TPV was used with PEG-IFN-α2a 180 µg per week plus RBV 1000–1200 mg per day and BOC was used with PEG-IFN-α2b 1.5 µg/kg per week plus RBV 600–1400 mg per day. However, both forms of PEG-IFN-α may be used with RBV and either TPV or BOC.

PEG-IFN-α is contraindicated in decompensated cirrhosis.

Strict contraception must be followed during and for 6 months after the end of triple therapy because of the potential teratogenicity of RBV.

SMW-13516-Fig-01

Figure 1 Telaprevir-based triple therapy. (A) Treatment-naïve patients with CHC genotype 1 and treatment-experienced patients with previous relapse. (B) Treatment-experienced patients with CHC genotype 1 and previous partial or null response. eRVR, extended rapid virological response (see table 1 for definitions of virological response patterns); P, pegylated interferon-α; R, ribavirin; T, telaprevir; wks, weeks.

Who should be treated with triple therapy comprising TPV or BOC?

Triple therapy will represent a new standard for most treatment-naïve patients with CHC genotype 1 as well as treatment-experienced patients with a relapse or partial response to previous therapy with PEG-IFN-α and RBV (table 2).

Treatment of CHC is expected to change significantly within the next few years, with the arrival of better tolerated and even more efficacious new drugs as well as the advent of IFN-free/sparing regimens [2730]. These developments shall significantly improve the outlook for our patients. Therefore, deferring treatment may be considered in patients who’s treatment can be safely postponed.

Treatment-naïve patients with favourable baseline predictors (HCV RNA <4 x 105 IU/ml, absence of advanced fibrosis or cirrhosis) who achieve a rapid virological response (RVR; see table 1) have excellent chances to achieve SVR with 24 weeks of therapy with PEG-IFN-α and RBV alone [31]. Therefore, a 4-week lead-in with PEG-IFN-α and RBV may be considered in patients with the above-mentioned favourable baseline predictors and treatment continued without adding TPV or BOC for a total of 24 weeks in those who achieve RVR.

Lead-in with PEG-IFN-α and RBV may also be considered if there are doubts concerning the tolerance or adherence to PEG-IFN-α and RBV backbone therapy.

There is currently only limited data on the use of BOC in patients with previous null response. In general, retreatment of previous null responders has to be considered carefully, as SVR rates remain limited, especially in patients with cirrhosis. Inclusion of such patients into clinical trials involving quadruple therapy or IFN-sparing regimens may be considered. Lead-in with PEG-IFN-α and RBV may be considered in previous null responders, especially in cirrhotics, with the addition of TPV or BOC only in case of ≥1 log decline of HCV RNA at week 4. Subanalysis of the REALIZE trial revealed that 54% of the patients with ≥1 log decline after 4 weeks of lead-in with PEG-IFN-α and RBV achieved SVR with triple therapy comprising TPV, compared to only 15% of those with a decline of HCV RNA <1 log [32].

Careful monitoring and stopping rules, as detailed below, shall reduce the risk of selecting HCV strains resistant to antiviral therapy. While long-term consequences of the selection of such strains are presently unknown, antiviral resistance is likely to affect future treatment options [15, 16].

SMW-13516-Fig-02

Figure 2 Boceprevir-based triple therapy. (A) Treatment-naïve patients with CHC of genotype 1 without cirrhosis. (B) Treatment-experienced patients with CHC genotype 1 and previous relapse or partial response without cirrhosis. (C) All cirrhotic patients and prior null responders. B, boceprevir; BPR = B + P + R; P, pegylated interferon-α; R, ribavirin; RVR8, rapid virological response at week 8 (see table 1 for definitions of virological response patterns); wks, weeks.

(Click on table to enlarge)

Capture

Specific treatment algorithms

Telaprevir-based triple therapy

• Treatment-naïve patients and previous relapsers with CHC genotype 1 (fig. 1A)

Non-cirrhotic patients who achieve eRVR

12 weeks TPV + PEG-IFN-α + RBV

+ 12 weeks PEG-IFN-α + RBV

Non-cirrhotic patients who do not achieve eRVR and all cirrhotic patients

12 weeks TPV + PEG-IFN-α + RBV

+ 36 weeks PEG-IFN-α + RBV

• Previous partial and null responders with CHC genotype 1 (fig. 1B)

12 weeks TPV + PEG-IFN-α + RBV

+ 36 weeks PEG-IFN-α + RBV

Lead-in with PEG-IFN-α and RBV may be considered in previous null responders, especially in cirrhotics, with the addition of TPV only in case of ≥1 log decline of HCV RNA at week 4.

Stopping rules:

– Stop all therapy if HCV RNA >1000 IU/ml at either week 4 or 12 of triple therapy.

– Stop all therapy if HCV RNA detectable at wk 24.

– Stop all therapy if previously negative HCV RNA becomes confirmed positive again

Boceprevir-based triple therapy

• Treatment-naïve patients with CHC genotype 1 (fig. 2A and 2C)

Non-cirrhotic patients who achieve RVR8

4 weeks PEG-IFN-α + RBV lead-in

+ 24 weeks BOC + PEG-IFN-α + RBV

Non-cirrhotic patients who do not achieve RVR8

4 weeks PEG-IFN-α + RBV lead-in

+ 24 weeks BOC + PEG-IFN-α + RBV

+ 20 weeks PEG-IFN-α + RBV

Cirrhotic patients

4 weeks PEG-IFN-α + RBV lead-in

+ 44 weeks BOC + PEG-IFN-α + RBV

• Previous relapsers or partial responders with CHC genotype 1* (fig. 2B and 2C)

Non-cirrhotic patients who achieve RVR8

4 weeks PEG-IFN-α + RBV lead-in

+ 32 weeks BOC + PEG-IFN-α + RBV

Non-cirrhotic patients who do not achieve RVR8

4 weeks PEG-IFN-α + RBV lead-in

+ 32 weeks BOC + PEG-IFN-α + RBV

+ 12 weeks PEG-IFN-α + RBV*

Cirrhotic patients

4 weeks PEG-IFN-α + RBV lead-in

+ 44 weeks BOC + PEG-IFN-α + RBV

*For patients with prior null response, 4 weeks of lead-in with PEG-IFN-α + RBV, followed by 44 weeks of triple therapy with BOC + PEG-IFN-α + RBV is recommended.

Stopping rules:

– Consider stopping therapy in patients with cirrhosis and <1 log drop of HCV RNA after lead-in (chances of achieving SVR being 13–25% only [33]).

– Stop all therapy if HCV RNA ≥100 IU/ml at week 12.

– Stop all therapy if HCV RNA detectable at week 24.

– Stop all therapy if previously negative HCV RNA becomes confirmed positive again under treatment.

Conclusions

Key points are summarised in table 3.

Funding / potential competing interests: SASL or the SASL Council Members have not received any financial support in relation with the writing of this article. DM and BM as corresponding authors assume responsibility for the integrity of this article. Both have received research support from MSD and Roche and have acted as advisors to Janssen, MSD and Roche.

Correspondence: Professor Darius Moradpour, MD, Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Rue du Bugnon 44, CH-1011 Lausanne, Switzerland, darius.moradpour[at]chuv.ch
or
Professor Beat Müllhaupt, MD, Division of Gastroenterology and Hepatology, University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland, beat.muellhaupt[at]usz.ch

References

1 Nature Outlook: Hepatitis C. Nature. 2011;474:S1–S21.

2 EASL Clinical Practice Guideline: Management of hepatitis C virus infection. J Hepatol. 2011;55:245–64.

3 Ghany MG, Nelson DR, Strader DB, et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 Practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:1433–44.

4 Prasad L, Spicher VM, Zwahlen M, et al. Cohort Profile: the Swiss Hepatitis C Cohort Study. Int J Epidemiol. 2007;36:731–7.

5 Davis GL, Alter MJ, El-Serag H, et al. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513–21.

6 McGarry LJ, Pawar VS, Parekh HH, et al. Economic model of a birth cohort screening program for hepatitis C virus. Hepatology. 2012, in press.

7 Rein DB, Smith BD, Wittenborn JS, et al. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med. 2012, in press.

8 Thein HH, Yi Q, Dore GJ, et al. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression. Hepatology. 2008;48:418–31.

9 Missiha SB, Ostrowski M, Heathcote EJ. Disease progression in chronic hepatitis C: modifiable and nonmodifiable factors. Gastroenterology. 2008;134:1699–714.

10 Pinzani M, Vizzutti F, Arena U, et al. Noninvasive assessment of liver fibrosis by biochemical scores and elastography. Nat Clin Pract Gastroenterol Hepatol. 2008;5:95–106.

11 Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–93.

12 Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–9.

13 Rauch A, Rohrbach J, Bochud PY. The recent breakthroughs in the understanding of host genomics in hepatitis C. Eur J Clin Invest. 2010;40:950–9.

14 Lange CM, Zeuzem S. IL28B single nucleotide polymorphisms in the treatment of hepatitis C. J Hepatol. 2011;55:692–701.

15 Sarrazin C, Zeuzem S. Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology. 2010;138:447–62.

16 Halfon P, Locarnini S. Hepatitis C virus resistance to protease inhibitors. J Hepatol. 2011;55:192–206.

17 Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405–16.

18 Poordad F, McCone J, Jr., Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–206.

19 Sherman KE, Flamm SL, Afdhal NH, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med. 2011;365:1014–24.

20 Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417–28.

21 Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207–17.

22 Vierling JM, Flamm SL, Gordon SC, et al. Efficacy of boceprevir in prior null responders to peginterferon/ribavirin: the PROVIDE Study. Hepatology. 2011;54(Suppl 1):796A.

23 Deuffic-Burban S, Mathurin P, Pol S, et al. Impact of hepatitis C triple therapy availability upon the number of patients to be treated and associated costs in France: a model-based analysis. Gut. 2012;61:290–6.

24 Garg V, van Heeswijk R, Eun Lee J, et al. Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus. Hepatology. 2011;54:20–7.

25 Leise MD, Kim WR, Canterbury KM, et al. Drug therapy: Telaprevir. Hepatology 2011;54:1463-1469.

26 Cacoub P, Bourlière M, Lübbe J, et al. Dermatological side effects of hepatitis C and its treatment: patient management in the era of direct-acting antivirals. J. Hepatol. 2012;56:455–63.

27 Gane EJ, Roberts SK, Stedman CA, et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2010;376:1476–5.

28 Chayama K, Takahashi S, Toyota J, et al. Dual therapy with the NS5A inhibitor BMS-790052 and the NS3 protease inhibitor BMS-650032 in HCV genotype 1b-infected null responders. Hepatology. 2012, in press.

29 Gane EJ, Stedman CA, Hyland RH, et al. Once daily PSI-7977 plus RBV: pegylated interferon-alfa not required for complete rapid viral response in treatment-naïve patients with HCV gt 2 or gt 3. Hepatology. 2011;54(Suppl 1):377A.

30 Lok ASF, Gardiner D, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216–24.

31 Di Martino V, Richou C, Cervoni JP, et al. Response-guided peg-interferon plus ribavirin treatment duration in chronic hepatitis C: Meta-analyses of randomized, controlled trials and implications for the future. Hepatology. 2011;54:789–800.

32 Foster GR, Zeuzem S, Andreone P, et al. Subanalyses of the telaprevir lead-in arm in the REALIZE study: response at week 4 is not a substitute for prior null response categorization. J Hepatol. 2011;54(Suppl 1):S3.

33 Bruno S, Vierling JM, Esteban R, et al. Boceprevir in addition to standard of care enhanced SVR in hepatitis C virus genotype 1 with advanced fibrosis/cirrhosis: subgroup analysis of SPRINT-2 and RESPOND-2 studies. J Hepatol. 2011;54(Suppl 1):S4.

Source

7765_Roche-Elecsys-anti-HCV-II-(_jpg

10 Apr 2012

Due to the high rate of asymptomatic infections, clinical diagnosis of hepatitis C is difficult and screening assays are of major importance. An estimated 216,000 individuals are chronically infected with hepatitis C (HCV) in the UK, and HCV-related end stage liver disease and mortality continue to increase.

The new Roche Elecsys® anti-HCV II assay is used to demonstrate the presence of antibodies against HCV during acute and chronic stages of disease, and after a passed infection. The assay provides 100% clinical sensitivity for all known genotypes, leading to early detection of infection, and patient-oriented decision making.

With high specificity in blood donors (99.84%) and samples from clinical routine, pregnant women and dialysis patients, use of the Elecsys anti-HCV II assay increases laboratory testing efficiencies. To optimize workflows and provide operational cost savings, the ready-to-use liquid reagents have a long onboard stability of 31 days on all Roche immunoassay platforms.

The new assay complements the Roche serology assay menu that includes assays for Hepatitis A, Hepatitis B, Hepatitis C, HIV, TORCH, Herpes, Syphilis and other infectious diseases.

Source

HIV Treatment Guidelines for Adults and Adolescents Updated

From Medscape Medical News

Laurie Barclay, MD

April 10, 2012 — The Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents has updated recommendations for clinical practitioners caring for patients with HIV infection in the United States, based on current evidence.

"Antiretroviral therapy (ART) for the treatment of [HIV] infection has improved steadily since the advent of potent combination therapy in 1996," the guidelines authors write. "New drugs have been approved that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability."

Topics covered in the updated and in previous guidelines have included baseline evaluation, treatment goals, indications for starting ART, choosing initial therapy in ART-naive patients, drugs or combinations to be avoided, managing adverse effects and drug interactions, managing treatment failure, and ART-related considerations directed to specific patient populations.

A new section in the updated guidelines addresses HIV diagnosis and treatment considerations in older patients with HIV infection, who often have more comorbid conditions, which complicates treatment. A new table lists the monthly average wholesale price for US Food and Drug Administration–approved brand and generic antiretroviral (ARV) drugs, including fixed-dose combination products.

Key updates to existing sections of the guidelines include the following:

  • Starting ART in treatment-naive patients:
    • ART is recommended for all HIV-infected individuals, but the strength of this recommendation varies according to CD4 cell count before treatment.
    • Regardless of CD4 count, starting ART is strongly recommended for patients who are pregnant or who have a history of an AIDS-defining illness, HIV-associated nephropathy, or coinfection with hepatitis B virus.
    • ART should be offered to infected patients, particularly heterosexuals, who are at risk of transmitting HIV to sexual partners.
    • Patients starting ART should understand the benefits and risks and be willing and able to adhere to treatment. On a case-by-case basis, clinicians may decide to defer therapy because of specific clinical and/or psychosocial factors.
  • HIV-infected women: The update explains the use of hormonal contraception in HIV-infected women, including interactions between combined oral contraceptives and ARV drugs and a possible association between hormonal contraceptive use and HIV acquisition or transmission.
  • HIV/hepatitis C virus (HCV) coinfection: The update highlights the newly approved HCV NS3/4A protease inhibitors boceprevir and telaprevir, their interactions with ART, available evidence regarding ongoing research in HIV/HCV coinfected patients, and preliminary recommendations on administering these drugs with ART.
  • Mycobacterium tuberculosis disease with HIV coinfection: The update includes recommendations about when to start ART in HIV-infected patients diagnosed with tuberculosis but not yet receiving ART. Specific recommendations are based on CD4 counts and severity of major clinical disease.
  • Drug interaction tables: Based on recent pharmacokinetic data, key updates include:
    • a change in the recommendation on rifabutin dosing with HIV protease inhibitors;
    • a new recommendation not to use HIV protease inhibitors and nonnucleoside reverse transcriptase inhibitors with rifapentine;
    • additional information and recommendations on interactions of boceprevir and telaprevir with different ARV drugs; and
    • updated interactions between different ritonavir-boosted protease inhibitors and HMG-CoA reductase inhibitors.
  • Prevention of secondary HIV transmission: The update describes the role of effective ART in preventing HIV transmission and evidence-based interventions to facilitate identifying and counseling patients with high-risk behaviors.

Some of the study authors report various financial relationships with Bristol-Myers Squibb, Genentech/Roche, Janssen Therapeutics (formerly Tibotec Therapeutics), Merck, Abbott, Gilead, ViiV, GlaxoSmithKline, Hoffmann-La Roche, Tobira, Sanofi Pasteur, Abbott, RAPID Pharmaceuticals, Sangamo Biosciences, MedImmune, ViroStatics, Tai-Med, Medicines Dev Ltd, Pfizer, Virionyx Corp Ltd, Avexa, Human Genome Sciences, Oncolys, Roche, Vertex, VIRxSYS, Ardea Biosciences Avexa, Monogram Biosciences, Pain Therapeutics, Serono, Teva, Argos, BMS, and/or Boehringer Ingelheim.

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Source

PR-Logo-Newswire

PRESS RELEASE

April 9, 2012, 9:00 a.m. EDT

NEW YORK, April 9, 2012 /PRNewswire via COMTEX/ -- MTV Audience Encouraged to "GYT"

The fourth annual GYT: Get Yourself Tested campaign kicks off National STD Awareness Month (April) with new initiatives on-air, online, and on the ground at college campuses and in more than 5,000 health centers across the nation. GYT is an ongoing national campaign launched in 2009 as an extension of a longstanding public information partnership between MTV and the Kaiser Family Foundation to address the high rates of STDs among those under 25. It is supported by a broad range of organizations including the U.S. Centers for Disease Control and Prevention (CDC) and Planned Parenthood Federation of America, which reinforce the on-air campaign with on-the-ground promotions conducted with health centers and community organizations across the nation.

"MTV has made a sustained commitment to challenging the stigma that prevents countless young people from getting tested for STDs and HIV," said Jason Rzepka, Vice President of MTV Public Affairs. "We're proud that GYT has helped drive notable increases in STD testing, but there's no finish line in this race, and we will continue to do all we can to help our audience make responsible decisions about their sexual health."

GYT is a youthful, empowering campaign aimed at reducing the spread of STDs among young people through information; open communication with partners, health care providers, and peers; and testing and treatment as needed. GYT offers a short-hand reference for young people to open up dialogue about STDs and, in particular, the importance of testing. According to CDC, young people ages 15-24 represent nearly half of all new STDs occurring in the U.S., while representing just 25 percent of the population. Rates of chlamydia, a preventable and treatable STD, are particularly high. Chlamydia often has no symptoms, and when left undiagnosed and untreated can cause serious health consequences, including infertility in women. As a result, CDC recommends annual screening for all sexually active women aged 25 and younger.

"We're proud to be a part of GYT because of the positive difference it has made on the lives of so many young Americans," said Gail Bolan, M.D., director of CDC's Division of STD Prevention. "The facts are clear - STDs are common, and the life-long impact of an untreated STD is real. But, these don't have to be accepted parts of life. GYT provides the tools young people need to be proactive about their health."

GYT public service messages air throughout the year on MTV channels with cross promotions with health centers and community organizations. Extensive information resources - including a dedicated website ( www.gytnow.org ), which provides basic information about common STDs, talking tips and a zip code locator to find local testing locations - as well as mobile testing locator, GYTNOW (498669) - provide the audience with more information. During April, the campaign scales up its presence by introducing new messaging and outreach. Some elements of this year's national GYT campaign include:

"Team GYT" -- Celebrities recognizable to the GYT audience help carry the GYT message as part of "Team GYT." Coming from an array of backgrounds, these celebrities are hand-picked to offer a sense of inspiration and personal empowerment. This year, the campaign is pleased to welcome Litefoot, a Native American rap artist, actor and entrepreneur. Litefoot, a member of the Cherokee Nation of Oklahoma, also operates the "Reach the Rez Tour," an outreach program that promotes positive change among American Indian youth. Litefoot joins the ranks of the existing members of Team GYT including: The Jersey Shore's Vinny, rap visionary Talib Kweli, celebrity gossip blogger Perez Hilton, America's Best Dance Crew's Jungle Boogie, professional street skateboarder Stevie Williams, head of Thehundreds.com Bobby Hundreds, Paper Twins' artists Nica and Edgar A. English, aspiring fashion-conscious entrepreneur Allie Bashuk, surf-loving San Franpsycho, San Francisco designer/painter/artist Ube Urban, Levi Maestro of the online show "Maestro Knows," Buff Monster, designer Han Cholo, and DJ A-Trak. Team GYT will continue to grow throughout the year as new faces are added to the campaign. All will carry the GYT brand out into various aspects of youth culture, encouraging their fans and followers to know their status.

GYT "Party" -- GYT has created a new online interactive video experience to encourage conversations about STDs and testing with partners, peers, and health care providers. The video, a simulation of a party scene, includes five conversations among couples, peers and friends, about STDs and testing and is found at http://www.itsyoursexlife.com/gyt/talk/party . The GYT Party is filled with talking tips, an interactive quiz, key information for starting a conversation about STDs and testing and other bonus features.

GYT Nation -- GYT is also supported by an extensive on-the-ground outreach effort and is taking GYT to communities across the country. GYT promotional and informational materials, including T-shirts, posters, buttons, brochures, and stickers are being distributed to more than 5,000 health centers and organizations nationwide, including Planned Parenthood's network of nearly 800 health centers and additional public and private clinics identified by CDC. GYT is also working with state and local health departments the National Coalition of STD Directors, the American Academy of Pediatrics, the Society for Adolescent Health and Medicine and the National Assembly of School-Based Health Centers to provide young people with information about the campaign. And, the American College Health Association (ACHA) works with GYT to distribute materials through college health centers.

"When it comes to STDs, many of those at risk don't know it or assume they would know if they had one," said Tina Hoff, Senior Vice President and Director of the Kaiser Family Foundation's Health Communication & Media Partnerships Program. "Through a combination of on-air, online, and on-the-ground messages, GYT is working to increase knowledge and remove the stigma of STD testing."

During last year's GYT campaign, Planned Parenthood health centers tested almost 125,000 men and women in April, and Planned Parenthood affiliates held 240 events with 1,250 youth volunteers, reaching 67,000 people. Data collected from 10 Planned Parenthood affiliates show that STD testing has increased significantly since the launch of GYT in 2009. Among the 10 affiliates, there was a 51 percent increase in patients getting tested in April 2011 as compared to the same time in 2008, prior to the launch of the campaign - suggesting that the campaign helped drive an increase in STD tests. Nationally, Planned Parenthood reported significant increases in the populations most affected by STDs, including African Americans and people living at or below 150 percent of the federal poverty level. Data is not available for all 80 PPFA affiliates and more than 1000 clinics, colleges and universities, and other partners that also supported the campaign in 2011.

"At Planned Parenthood, we know that affordable testing and treatment, along with education, are the best ways to ensure that young people stay healthy and safe," said PPFA President Cecile Richards. "For almost a century, Planned Parenthood has been providing health care information and resources aimed at preventing STDs, and our doors are open to everyone. Getting tested is simply a basic part of staying healthy, and we're thrilled that the GYT campaign is getting that message out to teens and young people."

GYT launched in 2009 as an extension of a longstanding public information partnership between MTV and the Kaiser Family Foundation. It is supported by a broad range of organizations including Planned Parenthood Federation of America, the National Coalition of STD Directors (NCSD), American College Health Association (ACHA), American Social Health Association (ASHA), the National Chlamydia Coalition (NCC), CDC, and various state and local health departments, colleges and universities, and other community groups and non-profits. Gilead Sciences, Inc. provides support and resources for select elements of the campaign. CDC provided assistance to ensure scientific accuracy of GYT health information. Comprehensive informational resources -- designed for web and mobile applications -- provide facts and referrals to local health centers. For more information, visit www.GYTNOW.org .

MTV is the world's premier youth entertainment brand. With a global reach of more than a half-billion households, MTV is the cultural home of the millennial generation, music fans and artists, and a pioneer in creating innovative programming for young people. MTV reflects and creates pop culture with its Emmy®, Grammy® and Peabody® award-winning content built around compelling storytelling, music discovery and activism across TV, online and mobile. MTV's sibling networks MTV2 and mtvU each deliver unparalleled customized content for young males, music fans and college students, and its online hub MTV.com is the leading destination for music, news and pop culture. MTV is part of MTV Networks, a unit of Viacom, one of the world's leading creators of programming and content across all media platforms. For more information, go to www.mtvpress.com.The Kaiser Family Foundation, a leader in health policy analysis, health journalism and communication, is dedicated to filling the need for trusted, independent information on the major health issues facing our nation and its people. The Foundation is a non-profit private operating foundation, based in Menlo Park, California. www.kff.org Planned Parenthood Federation of America is the nation's leading sexual and reproductive health care provider and advocate. We believe that everyone has the right to choose when or whether to have a child, and that every child should be wanted and loved. Planned Parenthood affiliates operate more than 840 health centers nationwide, providing medical services and sexuality education for millions of women, men, and teenagers each year. We also work with allies worldwide to ensure that all women and men have the right and the means to meet their sexual and reproductive health care needs.CDC works 24/7 saving lives, protecting people from health threats, and saving money through prevention. Whether these threats are global or domestic, chronic or acute, curable or preventable, natural disaster or deliberate attack, CDC is the nation's health protection agency. For more information about CDC and its programs, visit http://www.cdc.gov .

SOURCE Kaiser Family Foundation

Source

Analysis: Lessons about HIV, STDs, Preventing Pregnancy Declining

By Sarah D. Sparks on April 9, 2012 9:36 AM

From guest blogger Nirvi Shah:

A new analysis from the Centers for Disease Control and Prevention finds that in 2010, the percentage of middle schools teaching about HIV, other sexually transmitted diseases, and pregnancy prevention was significantly lower in 11 states than in 2008.

The findings come from a CDC analysis of 2008 and 2010 School Health Profiles data for schools in 45 states.

The analysis also found that the percentage of secondary schools teaching several condom-related topics in a required course in grades 9, 10, 11, or 12 was significantly lower in eight states and significantly higher in three states.

Although a median of 90 percent of all public secondary schools across the 45 states in the report taught HIV prevention in a required course during 2010, the CDC said the findings indicate that little progress was made in increasing the number of specific topics covered as part of HIV, other STDs, and pregnancy prevention education during 2008-2010.

The agency said more research is needed to understand how schools decide the number of specific HIV, other STDs, and pregnancy prevention topics taught.

The CDC advocates for HIV, other STD, and pregnancy-prevention education in middle school because most students in those grades are not yet sexually active. HIV, other STD, and pregnancy-prevention education taught before most young people engage in risk behaviors, including information on the benefits of abstinence and delaying or limiting sexual activity, can prevent behavior that could lead to STDs and pregnancy.

And because many students become sexually active during high school—46 percent, the CDC says—education about STDs and pregnancy is "critically important."

The agency says education that includes information on condom efficacy, the importance of using condoms consistently and correctly, and how to obtain condoms taught to those who might decide to be or are sexually active can prevent behaviors STDs and pregnancy and address misconceptions about how HIV is transmitted. A 2011 public opinion poll showed that that 20 percent of of people age 18-29 believe incorrectly that a person can become infected with HIV by sharing a drinking glass, or are unsure whether the statement is true or false.

Earlier this year, several groups presented national standards about sexuality education that they hope will be widely adopted. The standards, about sexuality, sexual health, and relationships outline topics students should learn, starting in kindergarten, and that they can build on as they grow older.

Source

L.A. moves the needle

la-oe-scholar-hiv-needle-exchange-20120410-001

In 1992 in Los Angeles, where needle exchanges were already in effect, the rate of HIV among those who injected drugs was 8.4%. In 1993, the HIV rate in Miami for that population was the highest in the country: 48%. (Los Angeles Times / April 9, 2012)

The city's early action in AIDS/HIV prevention by providing a needle exchange program proved to be prescient. Now is no time to back off.

By Shoshanna Scholar

April 10, 2012

The first cases of HIV identified anywhere in the world are widely thought to have been in Los Angeles in 1981. Since then, 45,000 Angelenos have contracted HIV and nearly half have died due to the disease.

As terrible as that statistic is, we can look back over the last 30 years with considerable pride because Los Angeles' courageous response to the epidemic also saved many lives. We now know how much worse things would have been had local elected leaders not braved controversy to support one of the most effective HIV prevention tools we have: needle exchange.

How much worse? Consider some comparative data — needle exchange isn't solely responsible for the differences in these statistics, but it plays an important role.

In 1992 in Los Angeles, where needle exchanges were already in effect, the rate of HIV among those who injected drugs was 8.4%. In 1993, the HIV rate in Miami for that population was the highest in the country: 48%. Although Miami put into place HIV-prevention programs, there has never been a large-scale needle exchange program there. Today the rate of HIV among injection drug users in Miami is 16%. In Los Angeles, the rate stayed low, and as of 2009, the most recent data available, it was 5%.

These facts have important consequences. Extrapolating from county data, it's believed that about 34,000 Los Angeles residents are injection drug users. The California Department of Public Health calculates the lifetime costs of treating one person with HIV at $385,200. If those 34,000 Angelenos had an HIV rate of 16% rather than 5%, we'd be spending an additional $1.4 billion in treatment costs.

People affected by HIV/AIDS in the late 1980s and early 1990s faced all kinds of discrimination. Our civic leaders displayed wisdom and guts with a series of early actions in response to the epidemic, beginning with the country's first AIDS anti-discrimination law in 1985.

Four years later, L.A. put in place an AIDS coordinator, Fred Eggan, who provided a structure for the city to partner with community organizations to raise public awareness, prevent new HIV infections and support those affected by HIV/AIDS.

Needle exchange came next. It was highly controversial at first. Activists and volunteers, including the founder of my program, Renee Edgington, began the exchange underground in the late 1980s; it was formally established in 1992. They faced protesters, prosecution, conflicts with private security, law enforcement, even citizen's arrest.

Critics objected: Why give people who inject drugs the tools they need to break the law? It seemed to many observers that swapping sterile needles for used needles would only make things worse. But city leaders held firm, and decades of research have now vindicated decisions by the city and later county leaders who bet on needle exchange. In fact, more than 200 studies from the U.S. and abroad agree: Needle exchange programs not only prevent HIV, but people who use them are also more likely to enter drug treatment and get off drugs.

People who inject drugs will keep doing it with or without access to clean needles. Reusing old syringes greatly increases the risk of staph infection or the antibiotic resistant MRSA; sharing syringes leads to HIV and hepatitis C infection.

Ask anyone who's ever injected drugs how difficult it is to get sterile syringes without exchange. In California, some pharmacies sell syringes without a prescription, but they are few and far between. Most don't offer disposal or referrals to badly needed wraparound and referral services such as medical care and access to drug treatment. Outside of

the participating pharmacies and needle exchange programs, there are few options other than buying them on the street.

Earlier this year, Stephen Simon, the city's fifth AIDS coordinator, left the job for the private sector. Stephen was a tenacious champion of the city's exchange programs and syringe access in California.

"It's been a tough political challenge," Simon told the City Council as he left, but "we removed more than a million dirty needles from the streets of Los Angeles each year.... That's the kind of tough political decisions that you all have made here." Council members Bill Rosendahl, Eric Garcetti, Tom LaBonge, Paul Koretz, Dennis Zine and Ed Reyes all spoke with gratitude of Simon's tenacity and creativity in guiding the city's fight to reduce HIV and AIDS.

So far, however, Simon's job hasn't been filled. And yet the HIV epidemic is still with us, and we still need city and county help to protect the progress we've made so far. We still need local government to stand up against continuing and misguided opposition to needle exchange.

In a time of polarized political conversation and a distressed economy, it may be tough to remember how important L.A.'s pioneering prevention strategy has been. We can't afford to throw away people, or money, on treating those whose illnesses we could prevent. Not in times like these. L.A. needs to keep supporting needle exchange programs, and it needs to advocate for and coordinate with those programs.

Shoshanna Scholar has served as the executive director of Clean Needles Now/Harm Reduction Central in Los Angeles since 2003.

Source