May 9, 2013

Hepatitis C Measures Open for Public Comment

May 02, 2013

The Hepatitis C Work Group, jointly convened by AGA Institute, AASLD and the Physician Consortium for Performance Improvement® (PCPI), has developed a proposed set of measures for improving outcomes for adult patients with hepatitis C. This work represents the formal periodic review and maintenance of an existing measure set. The proposed measures focus on appropriate evaluation and management of hepatitis C and associated symptoms, increasing patient awareness and participation in treatment decisions, care coordination, and promoting and enhancing patient safety. These measures can help guide treatment, decrease potentially preventable harmful events, lead to higher levels of personal functioning, and ease patient and caregiver burden through referrals to additional sources for support.

The public comment period began on April 30 and closes at 5 p.m. CDT on Thursday, May 30, 2013. View the measures and submit comments.


NIH Scientists Create New Tool for Identifying Powerful HIV Antibodies

National Institute of Allergy and
Infectious Diseases (NIAID)


Thursday, May 9, 2013


Advance Could Speed HIV Vaccine Research

A team of NIH scientists has developed a new tool to identify broadly neutralizing antibodies (bNAbs) capable of preventing infection by the majority of HIV strains found around the globe, an advance that could help speed HIV vaccine research. Scientists have long studied HIV-infected individuals whose blood shows powerful neutralization activity because understanding how HIV bNAbs develop and attack the virus can yield clues for HIV vaccine design. But until now, available methods for analyzing blood samples did not easily yield specific information about the HIV bNAbs present or the parts of the virus they targeted. In addition, determining where and how HIV bNAbs bind to the virus has been a laborious process involving several complicated techniques and relatively large quantities of blood from individual donors.

The new tool lets scientists determine precisely the HIV bNAbs present in a particular blood sample by analyzing the neutralized HIV strains there. Called neutralization fingerprinting, the tool is a mathematical algorithm (a problem-solving procedure) that exploits the large body of data on HIV bNAbs generated in recent years. The neutralization fingerprint of an HIV antibody is a measurement of which virus strains it can block and with what intensity. Antibodies that target the same portion of the virus tend to have similar fingerprints.

Blood samples contain mixtures of antibodies, so the new algorithm calculates the specific types of HIV bNAbs present and the proportion of each by comparing the blood’s neutralization data with the fingerprints of known HIV bNAbs. This approach is particularly useful when other methods of determining bNAbs targets in a blood sample are not feasible, such as when just a small amount of blood is available. Neutralization fingerprinting also is significantly faster than older analytic methods. According to the researchers who developed the assay, the underlying approach could be applied to the study of human responses to other pathogens, such as influenza and hepatitis C viruses, for which scientists have much information about neutralizing antibodies.

I. Georgiev et al. Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization. Science DOI: 10.1126/science.1233989 (2013).

Peter D. Kwong, Ph.D., chief of the Structural Biology and Structural Bioinformatics Core sections of the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases, part of NIH; and John R. Mascola, M.D., acting director of the VRC and chief of its Humoral Immunology section, are available for comment.

To schedule interviews, please contact Laura S. Leifman, (301) 402-1663,


Pressing Patients to Change Their Minds


Doctors May 9, 2013,10:56 am



When my patient Suzy took herself off the active liver transplant list, she was too embarrassed to tell me. I found out from her liver doctors.

When I confronted her, we discussed her reasoning. I told her I would continue to support and care for her. But as her longtime physician, I had to ask myself a question: Did I have some type of duty to get Suzy to change her mind?

Suzy was first found to have primary biliary cirrhosis, a severe liver disease, in the late 1990s. By 2005, when she became my patient, she had developed partial liver failure with a swollen abdomen. When the liver specialists told her she would eventually need a transplant, she agreed to go on the active list, which would put in her line to receive a donor organ. That would not occur, however, until she was much sicker.

Meanwhile, Suzy was gradually deteriorating. Fluid accumulated in her chest cavity, which caused shortness of breath and required frequent drainage. I was glad a transplant was in her future.

So Suzy’s decision to leave the active transplant list stunned me. The reason, she explained, was religious. Hailing from Mauritius, Suzy was raised a Catholic but had converted to the Pentecostal church, a branch of evangelical Protestantism that emphasizes personal experiences with God.

She had recently had a discussion with the pastor of her church, who told her how God had healed his own illness. He added that he would never submit to surgery.

Although the pastor never told Suzy to decline a transplant, she was moved by his story and concluded that if she showed the same type of faith, God would provide a “miracle of healing.” Suzy’s husband, also Pentecostal, supported her decision.

The liver specialists involved in Suzy’s case were upset. But they told her they would keep her on the “inactive list” in case she changed her mind.

Meanwhile, they made sure that Suzy understood the medical ramifications of her decision. Her liver would continue to worsen, and at some point she would die without a transplant. Moreover, even if Suzy eventually changed her mind, she might have become too sick by then to be saved by a transplant. The liver doctors were persistent, bringing Suzy back several times to remind her of her dire prognosis. They had her bring her children to an appointment, hoping that they would convince their mother to change her mind.

I wanted to do even more. Suzy had been my patient for years. I also took care of her mother, her husband and one of her best friends. As someone who teaches bioethics, I wanted to respect her choice and her religious beliefs — but if I was too understanding, I might actually be “doing harm,” something physicians must always avoid. Moreover, I was not convinced that Suzy’s decision reflected her actual wishes.

When I spoke to Dr. Eva Sotil, her liver doctor, she agreed. While Jehovah’s Witness patients consistently reject specific medical interventions, most notably blood transfusions, Pentecostal teachings stress “divine healing” but do not prohibit surgery or transplants, she pointed out.

I also kept thinking about a former patient of mine with severe liver disease who had come to my office one morning extremely ill with a blood infection. Another patient might have survived, but her liver was too diseased. She died in intensive care. I wanted to avoid a similar situation with Suzy.

So I decided to apply some pressure. A 2010 article in the journal Annals of Family Medicine argues for “beneficent persuasion” when patients make counterproductive decisions not in their long-term interest. In this spirit, I cajoled Suzy. I brought up the topic at each visit, continually asking why her religious beliefs precluded a transplant. I also asked to speak to her husband and children. I offered to attend her next liver clinic appointment, thinking that a larger group of physicians might be more persuasive.

I even told her at a December clinic visit that the best Christmas present she could give me would be to go back on the active transplant list.

Ultimately, as her medical condition worsened, Suzy changed her mind. Her children were now arguing for the transplant. And Suzy had asked God for a vision telling her to decline a new liver. When she did not receive one, she decided to return to active status.

One day the following summer, I got an e-mail from the liver transplant team telling me that Suzy had undergone a successful liver transplant. I was working at a different hospital, but called Suzy right away. She was elated. Her massively swollen body was returning to normal, and she was no longer short of breath.

I asked her how she reconciled her faith with having the transplant. She told me that she had prayed to God to get a good liver. “He healed me through surgery,” she explained.

She also had kind words for her doctors. Without us, she said, “I probably would not be here.”

It had been nagging me whether I might have crossed some line in Suzy’s case, applying undue pressure against her right to choose. Perhaps I had. But hearing the joy in her voice, I felt justified.


Elevated Cadmium Levels Linked to Liver Disease


Release Date: 05/09/2013

Men especially affected

People with higher levels of cadmium in their urine — evidence of chronic exposure to the heavy metal found in industrial emissions and tobacco smoke — appear to be nearly 3.5 times more likely to die of liver disease than those with lower levels, according to a study by Johns Hopkins scientists.

The research findings do not show that cadmium directly causes liver disease, the scientists caution, but do suggest an association that needs more investigation.

Reviewing information from a large population-based survey, the Johns Hopkins investigators say the cadmium-liver disease link disproportionately affects men. The gender differences could occur because of the protective effects of menopause chemistry, which may redistribute stored cadmium from liver and kidneys, where it can do more damage, and into bones where it remains more stable.

Cadmium levels in the body accumulate over time because of the metal’s long chemical half-life, according to the researchers, who reported their findings online in the Journal of Gastrointestinal Surgery.
“We already know about the health hazards of heavy metals like lead and mercury, but we don’t know much about what cadmium does to the body,” says study leader Omar Hyder, M.D., a postdoctoral fellow in the Department of Surgery at the Johns Hopkins University School of Medicine. “In mice, chronic cadmium exposure has been shown to cause liver failure, but we need to understand more about the factors that may cause liver disease in humans, and whether we can do anything to prevent it.”

Cadmium is found widely in the environment, with tobacco smoke the most important, single source of exposure in the general population. Other environmental sources of human exposure include fossil fuel combustion and the incineration of municipal waste. For many years, most of the batteries in the United States were made with cadmium, and it is also found in pigments and plastics.

Hyder says long-term exposure is known to cause kidney disease and has been linked to lung cancer. Studies have shown an increase in all-cause mortality and cancer mortality in populations exposed to low levels of cadmium for long periods of time.

For their study, Hyder and his colleagues analyzed data from 12,732 participants in the National Health and Nutrition Examination Survey (NHANES III), which also includes interviews, physical examinations, blood and urine tests and ultrasound scans. They looked at levels of cadmium in urine samples, as well as records of ultrasound results used to diagnose various liver diseases.

The researchers separated cadmium levels in the urine into four quartiles, finding that those in the highest quartile were nearly 3.5 times as likely to die of liver-related diseases than those in the lower three quartiles. The diseases included nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, both marked by fatty deposits in the liver that impede the liver’s efforts to filter toxins from the bloodstream, aid in digestion, produce hormones and store energy.

Hyder says that although occupational exposure to cadmium among factory workers has decreased, environmental exposure continues. If such exposure is ultimately found to cause liver disease, further efforts should be made to reduce it.

Medications are available that bind to heavy metals and remove them from organs, but such chelation therapies have not been used on those with chronic cadmium exposure because their value is unclear, Hyder says.

Other Johns Hopkins researchers involved in the study include Michael Chung, B.S., M.H.S.; David Cosgrove, M.D.; Joseph Herman, M.D., M.Sc.; Zhiping Li, M.D.; Amin Firoozmand, M.D.; Ahmet Gurakar, M.D.; Ayman Koteish, M.D.; and Timothy M. Pawlik, M.D., M.P.H., Ph.D.

Stephanie Desmon
Helen Jones


HCC risk persists 8 years after HCV eradication

Aleman S. Clin Infect Dis. 2013;doi:10.1093/cid/cit234.

May 9, 2013

The long-term risk for hepatocellular carcinoma among patients with hepatitis C remains up to 8 years after sustained virological response to antiviral therapy, researchers reported in Clinical Infectious Diseases.

“The number of patients with cancer was too low to draw any firm conclusion, but it was nevertheless somewhat surprising that the risk remained for such a prolonged time period,” Soo Aleman, MD, PhD, of the departments of gastroenterology and hepatology and infectious diseases at Karolinska Institutet in Stockholm, told Infectious Disease News.

“We need to know how long this risk persists and which subgroups of patients are at the highest risk after achieving sustained virological response (SVR). Future studies are needed to answer these questions.”

Aleman and colleagues conducted a prospective study that included patients who had HCV-related cirrhosis. Among the 351 patients, 110 reached SVR, 193 did not and 48 were untreated. The study was initiated in 2001 and the patients were followed for a mean of 5.3 years.

Six patients who achieved SVR developed hepatocellular carcinoma (HCC), for an incidence of 1 per 100 person-years. Two patients were diagnosed within a year after achieving SVR at 0.5 and 7.7 months, and the remaining four were diagnosed at 2.4, 7.4, 7.4 and 7.6 years. All of the patients were tested for HCV RNA at HCC diagnosis, and all were negative.

Among patients who did not achieve SVR or who were untreated, the risk for HCC was higher. The risk for any liver-related complication, liver-related death or overall death was lower among patients who achieved SVR. These differences were similar after controlling for alcohol use, age, sex and diabetes.

“Patients who have liver cirrhosis prior to the eradication of HCV should continue to undergo surveillance with ultrasound regularly for early detection of hepatocellular carcinoma,” Aleman said.

Soo Aleman, MD, PhD, can be reached at Department of Gastroenterology and Hepatology, and Infectious Diseases, Karolinska University Hospital at Karolinska Institute, 171 76 Stockholm, Sweden; email:

Disclosure: Aleman reports financial relationships with Gilead, Janssen, MSD and Roche.