October 15, 2012

A Hep C Hip Check

By Brian Orelli, The Motley Fool

Posted 6:53PM 10/15/12

Posted under: Investing

On its cakewalk to hepatitis C supremacy, Gilead Sciences (NAS: GILD) just got a hip check from Abbott Labs (NYS: ABT) .

Nearly all of the hepatitis C patients taking a combination of three Abbott drugs -- ABT-450, ABT-267, and ABT-333 -- and a generic called ribavirin were free of virus 12 weeks after finishing the drug regimen, which itself lasted 12 weeks. Just one of the 77 patients who have gotten that far in the trial had a relapse. There were also two patients with missing data, so those patients could bring down the 99% cure rate a little.

What's truly amazing is that 93% of patients who failed to respond to previous treatments were free of virus 12 weeks after treatment ended. That number might come down a little when we get data for longer sustained virological response, but it still towers over the current treatments. Vertex Pharmaceuticals' (NAS: VRTX) Incivek cured 32 % of null responders. Patients who had a partial response to previous treatment, which tend to have better response the next time, achieved only a 52 % cure rate for Merck's (NYS: MRK) Victrelis.

Abbott's four-drug regimen isn't exactly simple, especially compared with Gilead's combination of GS-7977 and GS-5885. Gilead might also include ribavirin in the combination, but three drugs are still less than four.

Abbott might be able to combine the drugs to reduce the number of pills taken, but under the current treatment regimen, there won't be a single pill because two of the drugs are taken once daily while another has to be taken twice daily.

Pill burden is a big issue for HIV patients and has helped Gilead make a lot of money with its combination pills, but I'm not sure it'll be as big of an issue for hepatitis C patients. HIV patients have to take the drugs for the rest of their lives; hepatitis C drugs will be taken for only a few months.

This is only phase 2 data; we need to wait for the phase 3 data to declare a winner. I think doctors will prescribe the drug with the best efficacy assuming it has a tolerable safety profile. If the two drug combinations are fairly equal on both those fronts, then the one with the best convenience will certainly win.

Of course, cure rates can't get higher than 100%, so safety and convenience will become an increasingly important aspect of hepatitis C drug characteristics. Investors in hepatitis C drugmakers, such as Achillion Pharmaceuticals (NAS: ACHN) and Idenix Pharmaceuticals (NAS: IDIX) , with drugs further back in the clinic had better take notice if they don't want to get stomped on.


Related Article: Abbott's Investigational Interferon-Free Hepatitis C Treatment Regimen Achieved SVR12 (Observed Data) Rates in 99 Percent of Treatment-Naïve and 93 Percent in Prior Null Responders for Genotype 1 Patients in Phase 2b Study

DOH survey shows public has liver disease misconceptions

Updated Sunday, October 14, 2012 0:03 am TWN, The China Post

By Wen Shin Kuo--A survey conducted by the Department of Health (DOH, 衛生署) from July 20 to 27 of 3,668 participants aged from 25 to 64 showed worrying results, with the majority of participants having misconceptions on liver-related diseases such as Hepatitis B and C.

In a multiple-choice question on what were the main causes of liver diseases, the most popular answer was “staying up late” (93.3 percent), with “alcohol consumption” (91.9 percent), “Hepatitis B” (81.3 percent), “working overtime” (70 percent), “liver-related diseases” (69.8 percent), “overdosing on medication” (65.4 percent), “Hepatitis C” (64.3 percent), “family history” (64.1 percent) and so on as the more popular answers.

Of the 3,668 participants, 16.4 percent answered that they have Hepatitis B, and only 0.9 percent said they have Hepatitis C. Almost 80 percent of the participants were liver-disease free.

When those with Hepatitis B were asked if they had consulted a doctor after learning that they had the disease, 29.9 percent replied that they did not think it necessary to consult a doctor. When further questioned as to why they did not deem it necessary to seek medical help, 73.8 percent of that group replied that they did not develop any symptoms, and therefore did not seek medical help. Other answers were that they “did not know where to seek help” (20 percent), “did not think they needed to seek medical help” (16.9 percent), “had no time” (13.1 percent) and finally “forgot” (2.3 percent).

According to the Bureau of Health Promotion (健康局), Hepatitis B and C make up 80 percent of the main causes of liver cancer. Every year there are 13,175 deaths due to chronic liver diseases, liver sclerosis and liver cancer, according to the DOH. The DOH is urging the public to raise its awareness of preventative measures against contracting Hepatitis B and C in order to prevent further risks of liver diseases. The DOH encourages the public to seek medical help if they test positive for Hepatitis B and C. If the disease is closely monitored, liver disease treatment and liver cancer prevention can be better addressed.



Studies provide data on BARACLUDE in special populations


Oct. 15, 2012, 3:47 p.m. EDT

PRINCETON, N.J., Oct 15, 2012 (BUSINESS WIRE) -- Bristol-Myers Squibb Company today announced that the U.S. Food and Drug Administration (FDA) has approved an update to the labeling for BARACLUDE(R) (entecavir) to include data on African Americans and liver transplant recipients with chronic hepatitis B infection. BARACLUDE, a nucleoside analogue discovered at Bristol-Myers Squibb, was first approved by the U.S. Food and Drug Administration in March 2005 for use in adult chronic hepatitis B patients with compensated liver disease. BARACLUDE is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. The following points should be considered when initiating BARACLUDE: This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naive and lamivudine-resistant adult patients with HBeAg-positive or HBeAg-negative chronic HBV infection and compensated liver disease; virologic, biochemical, serologic, and safety data are available from a controlled study in adult patients with chronic HBV infection and decompensated liver disease; virologic, biochemical, serologic, and safety data are available for a limited number of adult subjects with HIV/HBV co-infection who have received prior lamivudine therapy. The current labeling update was accepted based on one study in African-American patients and one study in post-liver transplant recipients, each investigating BARACLUDE in these populations.

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted. Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE (entecavir) is used to treat chronic HBV infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART). Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, alone or in combination with antiretrovirals. Please see the Important Safety Information section of this press release for additional risk information, including Boxed WARNINGS.

BARACLUDE in Racial/Ethnic Groups (Study ETV-085 Results)

There are no significant racial differences in entecavir pharmacokinetics. The safety and efficacy of BARACLUDE 0.5 mg once daily were assessed in a single-arm, open-label trial in hepatitis B e antigen (HBeAg) positive or negative, nucleoside-naive, African American (n=40) and Hispanic (n=6) patients with chronic HBV infection.In this trial, 76% of patients were male, the mean age was 42 years, 57% were HBeAg-positive. The mean baseline HBV DNA was 7.0 log10 IU/mL, and the mean baseline ALT was 162 U/L.At 48 weeks of treatment, 32 of 46 (70%) patients had HBV DNA <50 IU/mL (approximately 300 copies/mL), 31 of 46 (67%) patients had aminotransferase (ALT) normalization (less-than or equal to 1 times ULN), and 12 of 26 (46%) HBeAg-positive patients had HBe seroconversion. Safety data were similar to those observed in the larger, controlled BARACLUDE clinical trials. Due to low enrollment, safety and efficacy were not established in Hispanic patients.

BARACLUDE in Liver Transplant Recipients (Study ETV-109 Results)

The safety and efficacy of BARACLUDE were assessed in a single-arm, open-label trial in 65 patients who received a liver transplant for complications from chronic HBV infection. Eligible patients who had HBV DNA less than 172 IU/mL (approximately 1000 copies per mL) at the time of transplant were treated with BARACLUDE 1 mg once daily in addition to post-transplantation management consistent with the standard practice at a site, including hepatitis B immune globulin. The trial population was 82% male, 39% Caucasian, and 37% Asian, with a mean age of 49 years; 89% of patients had HBeAg-negative disease at the time of transplant.

Four of the 65 patients received 4 weeks or less of BARACLUDE (entecavir) (2 deaths, 1 retransplantation, and 1 protocol violation) and were not considered evaluable. Of the 61 patients who received more than 4 weeks of BARACLUDE, 60 received hepatitis B immune globulin post-transplant. Fifty-three patients (82% of all 65 patients treated) completed the trial and had HBV DNA measurements at or after 72 weeks treatment post transplant. All 53 patients had HBV DNA <50 IU/mL (approximately 300 copies/mL). Eight evaluable patients did not have HBV DNA data available at 72 weeks, including 3 patients who died prior to study completion. No patients had HBV DNA values greater-than or equal to 50 IU/mL while receiving BARACLUDE (plus hepatitis B immune globulin). All 61 evaluable patients lost HBsAg post-transplant; 2 of these subjects experienced recurrence of measurable HBsAg without recurrence of HBV viremia. This trial was not designed to determine whether addition of BARACLUDE to hepatitis B immune globulin decreased proportion of patients with measurable HBV DNA post-transplant compared to hepatitis B immune globulin alone. If BARACLUDE treatment is determined to be necessary for a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus, renal function must be carefully monitored both before and during treatment with BARACLUDE.

Chronic hepatitis B infection remains an area of concern among African Americans. In the United States, approximately 1.4 to 2.0 million individuals are chronically infected with chronic hepatitis B.

Patients with chronic hepatitis B and end-stage liver disease may undergo a liver transplantation as a treatment option. However, recurrence of a disease that caused the need for a liver transplant, such as chronic hepatitis B, can damage the new liver.

"Treating patients with chronic hepatitis B who have undergone a liver transplant can be complicated," said Dr. Michael Charlton, MBBS, FACP, Hepatology Director and Liver Transplant Director, Mayo Clinic. "These data included in the BARACLUDE label will help healthcare providers prescribe treatment among chronic hepatitis B patients, including liver transplant recipients."



BARACLUDE (entecavir) is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

The following points should be considered when initiating BARACLUDE:

-- This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naive and lamivudine-resistant adult subjects with HBeAg-positive or HBeAg-negative chronic HBV infection and compensated liver disease.

-- Virologic, biochemical, serologic, and safety data are available from a controlled study in adult subjects with chronic HBV infection and decompensated liver disease.

-- Virologic, biochemical, serologic, and safety data are available for a limited number of adult subjects with HIV/HBV co-infection who have received prior lamivudine therapy.



-- Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

-- Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE (entecavir) is used to treat chronic HBV infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART).

-- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, alone or in combination with antiretrovirals.

Warnings and Precautions

-- Before initiating BARACLUDE therapy, HIV antibody testing should be offered to all patients. BARACLUDE has not been studied as a treatment for HIV infection and is not recommended for this use.

-- Lactic acidosis with BARACLUDE use has been reported, often in association with hepatic decompensation, other serious medical conditions, or drug exposures. Patients with decompensated liver disease may be at higher risk for lactic acidosis. BARACLUDE should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.

Adverse Reactions

-- In clinical trials in patients with compensated liver disease, the most common (greater-than or equal to 3%) adverse reactions of any severity with at least a possible relation to study drug for BARACLUDE-treated subjects were headache, fatigue, dizziness, and nausea. In these trials, the most common adverse reactions of moderate to severe intensity (grades 2-4) were diarrhea, dyspepsia, nausea, vomiting, fatigue, headache, dizziness, somnolence, and insomnia.

-- In the decompensated liver disease trial, the most common adverse reactions of any severity among patients treated with BARACLUDE (entecavir), regardless of causality, included: peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic encephalopathy (10%), and upper respiratory infection (10%). In this trial, 18% (18/102) of BARACLUDE patients and 20% (18/89) of adefovir patients died during the first 48 weeks of therapy. The majority of those deaths were due to liver related causes.

Drug Interactions

BARACLUDE is primarily eliminated by the kidneys, therefore coadministration of BARACLUDE with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug. Patients should be monitored closely when receiving BARACLUDE with other renally-eliminated drugs.

Pregnancy and Nursing Mothers

-- There are no adequate and well-controlled studies of BARACLUDE in pregnant women. BARACLUDE should be used during pregnancy only if clearly needed and after careful consideration of the risks and benefits.

-- There are no studies on the effect of BARACLUDE on transmission of HBV from mother to infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV.

-- It is not known whether BARACLUDE is excreted into human milk; however, many drugs are excreted into breast milk. Due to the potential for serious adverse reactions in nursing infants from BARACLUDE, risks and benefits should be considered when deciding whether to discontinue breast-feeding or discontinue BARACLUDE in nursing women.

Pediatric Use

-- Safety and effectiveness of BARACLUDE in pediatric patients below the age of 16 years have not been established.

Renal Impairment

-- Dosage adjustment of BARACLUDE (entecavir) is recommended for patients with a creatinine clearance <50 mL/min, including those on hemodialysis or continuous ambulatory peritoneal dialysis.

Liver Transplant Recipients

-- Renal function must be carefully monitored both before and during treatment with BARACLUDE in a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function, such as cyclosporine or tacrolimus.

Dosage and Administration

BARACLUDE should be administered on an empty stomach (at least 2 hours after a meal and at least 2 hours before the next meal).

The recommended dose of BARACLUDE:

-- in nucleoside-naive adults and adolescents (16+ yrs) with compensated liver disease is 0.5 mg once daily

-- in adults and adolescents (16+ yrs) with compensated liver disease, and refractory to lamivudine or with known lamivudine or telbivudine resistance mutations (rtM204I/V with or without rtL180M, rtL80I/V, or rtV173L) is 1 mg once daily

-- in adults with decompensated liver disease is 1 mg once daily

The optimal duration of treatment with BARACLUDE for patients with chronic HBV infection and the relationship between treatment and long-term outcomes such as cirrhosis and hepatocellular carcinoma are unknown.

Additional Information

BARACLUDE (entecavir) is not a cure for HBV. Patients should be advised that treatment with BARACLUDE has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination.

Please see accompanying Full Prescribing Information, including Boxed WARNINGS, or visit www.BARACLUDE.com or click here.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews .

SOURCE: Bristol-Myers Squibb Company


What your eyes say about your health



10/15/2012 2:09 PM

By Deborah Kotz, Globe Staff

I was intrigued to hear about an experimental test that could detect signs of Alzheimer’s disease by imaging the retina at the back of the eye. Researchers have found, at least in mice, that beta amyloid plaques can be detected in the retina before they gunk up the brain and interfere with memory and other mental functions.

They’ve also found amyloid plaques in the retinas during autopsies of eight Alzheimer’s disease patients and in five living patients who had dementia and other symptoms indicative of the disease -- but not in five healthy individuals of the same age who also participated in a 2010 study published in the journal NeuroImage. Dr. Keith L. Black, chair of neurosurgery at Cedars-Sinai Hospital in Los Angeles, who helped conduct the initial studies, told me he and his colleagues are now gearing up for larger studies in humans to see if the imaging technique -- which uses curcumin, a compound in the spice turmeric which binds to the amyloid and makes it visible on the imaging test -- really does hold promise for the early detection of Alzheimer’s disease.

But using the eyes as a window to detect our overall health is nothing new. Ophthalmologists can detect everything from clogged arteries to diabetes to liver disease when they conduct routine eye exams since the body’s organ systems are all linked. Changes in blood vessels, hormonal systems, and the vast network of nerves all can be seen by examining the internal structures of the eye during an exam.

In addition to eye diseases like glaucoma and macular degeneration, here are some other health issues that can be revealed during an eye exam.

1. Diabetes. Small blood vessels in the back of the retina that leak blood can be a sign of diabetes. “I’d say about 5 percent of the exams I conduct detect small hemorrhages in the blood vessels in the retina,” said Dr. Sherleen Chen, director of the comprehensive ophthalmology service at Mass Eye and Ear. The problem itself requires treatment to prevent permanent vision loss as well as the underlying conditions causing the hemorrhages.

2. Clogged arteries. A blockage in smaller veins in the retina can occur when larger retinal arteries have been clogged by artery plaque. This shows up as retinal occlusion on an eye exam. Atherosclerosis in the retina can signal clogged arteries elsewhere in the body as well as uncontrolled hypertension, said Chen, and may require a cardiology workup.

3. Allergies. Dark under-eye circles can be a sign of aging, but sometimes they’re the mark of an allergy known as allergic shiners. They result from clogged sinuses that cause blocked blood flow in the nasal passages surrounding the eye and -- along with persistent nasal congestion -- may be a sign that you need to see an allergy specialist.

4. Liver disease. Yellowing in the whites of the eye can indicate a buildup of bile or jaundice, which could indicate liver disease. Some people, though, make excess bile -- and have slightly yellowish eyes -- due to mild benign jaundice known as Gilbert’s disease. A routine blood panel can distinguish one from the other.

5. Autoimmune diseases. Bulging protruding eyes are a sign of overactive thyroid, an autoimmune condition called Grave’s disease.

6. Cancer. Sometimes the first signs of cancer metastases can be picked up on an eye exam, said Chen. And lesions on the retina can signal Gardner syndrome, a genetic disorder that causes numerous colon polyps, raising the risk of colon cancer.

7. High cholesterol. A thin white or gray ring around the edge of the eye’s cornea indicates a deposit of fat and cholesterol, which is common in older folks. When found in those under age 65, a blood test is probably warranted to measure cholesterol levels.

Deborah Kotz can be reached at dkotz@globe.com . Follow her on Twitter @debkotz2.


Rapid Tests Accurate in First-Line HCV Screening


Courtesy US. Dept of Veterans Affairs

By: JENNIE SMITH, Family Practice News Digital Network



Major Finding: Blood-based point-of-care tests for hepatitis C virus have the highest sensitivity for screening at 98.9%, with specificity ranging from 99.5% for whole blood and 99.7% for serum or plasma.

Data Source: A meta-analysis of 18 studies that evaluated the accuracy of one or more tests.

Disclosures: Ms. Shivkumar and colleagues’ study was supported by grants from the Canadian Institutes of Health Research. None of the authors declared conflicts of interest.

Rapid diagnostic and point-of-care tests for hepatitis C virus are accurate enough to be used in first-line HCV screening worldwide, according to results from the first systematic review of evidence on such tests.

Blood-based point-of-care tests (POCTs) had better sensitivity and specificity overall than did blood-based rapid diagnostic tests (RDTs), Sushmita Shivkumar of McGill University, Montreal, Quebec, and her colleagues reported Oct. 15 in Annals of Internal Medicine.

POCTs do not require sample processing or refrigeration, and have a shelf life of 6 months or more. Rapid diagnostic tests, or RDTs, require refrigeration and sample processing. Manufactured by a variety of firms under various marketing names, all the tests can detect HCV infection in under 30 minutes, with many taking less than 5 minutes, according to the investigators, who conducted a meta-analysis of 18 studies evaluating the accuracy of one or more RDT or POCT, compared with standard assays (Ann. Intern. Med. 2012;157:558-566).

Ms. Shivkumar and her colleagues found blood-based POCTs (using serum, plasma, or whole blood) to be the most accurate of the tests evaluated in the included studies, showing 98.9% sensitivity with a 95% confidence interval [CI] of 94.5% to 99.8% for whole blood and 96.8% to 99.6% for serum or plasma). RDTs of serum or plasma had 98.4% sensitivity (95% CI 88.9% to 99.8%). Specificity was highest in POCTs of serum or plasma at 99.7% (95% CI, 99.3% to 99.9%), followed by POCTs of whole blood at 99.5% (95% CI, 97.5% to 99.9%), RDTs of serum or plasma at 98.6% (95% CI, 94.9% to 99.6%). POCTs for oral fluids had a sensitivity of 97.1% (95% CI, 94.7% to 98.4%) and specificity of 98.2% (95% CI, 92.2% to 99.6%).

POCTs and RDTs cannot distinguish between acute and chronic HCV infections, which is one of the reasons that public health organizations continue to favor conventional assays. The Food and Drug Administration currently approves the use of a single POCT for HCV, and for use only in nontraditional settings; in the United Kingdom and Canada such tests have not yet been approved.

However, by being fast, accurate, and cheaper than conventional tests, the rapid diagnostic and point-of-care tests offer "great potential for expanded first-line screening for hepatitis C infection and demonstrate the utility of blood-based singleton POCTs and of multiplex POCTs designed to provide integrated HIV and HCV screening of at-risk populations," Ms. Shivkumar and her associates wrote in their analysis. "Their rapid turnaround time limits loss to follow-up and facilitates early linkages."

The authors also concluded that their findings showed that the rapid and point-of-care tests could play a "substantial role" in expanded global screening initiatives for HCV.

The blood-based POCTs, besides being the most accurate, have the advantage of not requiring refrigeration, the investigators wrote. This feature is key in developing countries in Africa and Asia, where prevalence of HCV infection is highest.

Ms. Shivkumar and her colleagues noted several weaknesses in their meta-analysis, mostly related to the quality of studies included. Only three of the studies they evaluated were blinded, while four received industry funding; the conventional assays used as reference varied in the studies, and HCV genotype information was not collected in most.

The study was supported by grants from the Canadian Institutes of Health Research. None of the authors declared conflicts of interest.

View on The News

Tests Can Get More Into Treatment

Chronic hepatitis C virus (HCV) infection is a common worldwide problem. It is estimated that 170 million people are afflicted. Unfortunately, the majority of infected people remain undiagnosed. In many parts of the world, patients do not have access to medical personnel or diagnostic testing so that the diagnosis of HCV can be made. For patients that do have access, standard testing for HCV is cumbersome and expensive, adding to the diagnostic burden and diminishing the opportunity for diagnosis. Even in the United States, it is estimated that the majority of people infected with HCV have not been diagnosed. These factors have provided the impetus to develop less cumbersome and inexpensive tests for HCV, with the hope that they could be implemented throughout the world to increase the number of patients diagnosed with HCV.

Although there have been numerous studies examining individual diagnostic tests for HCV, there has not been an exhaustive review of both rapid and point-of-care screening tests for HCV. Ms. Shivkumar and her associates performed a literature review and meta-analysis of 18 studies worldwide that use the tests to screen for HCV in adults. They assessed the studies for diagnostic accuracy variables including sensitivity, specificity, likelihood rates (LRs) and diagnostic odds ratios (DORs) for available rapid and point-of-care diagnostic tests.

The assessment indicates that point-of-care tests of blood (serum, plasma, or whole blood) have the highest accuracy, followed by rapid diagnostic tests of serum or plasma and then by point-of-care diagnostic tests of oral fluids. However, all tests showed excellent sensitivity, specificity, likelihood rates and diagnostic odds ratios.

Strategies to improve the identification of patients infected with HCV are changing. In fact, the Centers for Disease Control and Prevention recently updated screening guidelines, recommending that screening change from ineffective risk-factor based screening to age-based screening. Testing strategies are also a source of potential improvement. This comprehensive global review suggests that rapid diagnostic and point-of-care tests are useful as initial screening tests for HCV. Although potential biases inherent in retrospective meta-analysis reviews are discussed, the quality of the analysis is excellent and the conclusions are valid.

These diagnostic test results are available rapidly in the field, and thus are available at the point of care. The tests are also relatively inexpensive and are easy to perform. With more effective therapies for HCV in development, broadening the ability to diagnose HCV worldwide is increasingly important. Integration of these tests into the diagnostic algorithm for HCV offers a more effective screening strategy with subsequent diagnosis of more people infected with HCV worldwide.

Dr. Steven L. Flamm is a professor of gastroenterology, hepatology, and surgery at Northwestern University, Chicago. He has no disclosures.



October 15, 2012

Abbott Park, Illinois (NYSE: ABT) — Abbott today announced initial results from "Aviator," a phase 2b study of its interferon-free, investigational regimen for the treatment of hepatitis C (HCV). Initial results show sustained virological response at 12 weeks post treatment (SVR12) in 99 percent of treatment-naïve (n=77) and 93 percent of null responders (n=41) for genotype 1 (GT1) HCV patients taking a combination of ABT-450/r, ABT-267, ABT-333 and ribavirin for 12 weeks, based on an observed data analysis.

Full results from the study will be presented at the Latebreaker Session of The Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston, November 9-13. Abstracts are available at www.aasld.org.

The observed data analysis used in this abstract does not include six patients who had not yet reached post-treatment week 12 or had missing values (data points) at the time of the abstract submission. All virologic failures and safety discontinuations were included in the analysis.

"There is a significant unmet medical need for genotype 1, the most common form of HCV in the U.S. and Europe," said Kris Kowdley, M.D., director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center, and Clinical Professor of Medicine at the University of Washington in Seattle. "Results from this phase 2b study suggest that sustained virological response can be achieved without interferon in a high proportion of genotype-1 patients, including patients who have not responded to previous treatment. This is exciting news as we continue to study treatment options for patients."

"Based on the promising results we've seen, Abbott has selected a triple direct acting antiviral regimen, with and without ribavirin for phase 3 development," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott. "The ability to show sustained virological response in these patient populations, without the use of interferon, is extremely encouraging."

Study M11-652 (Aviator)

  • Kris Kowdley, et al.; Monday, November 12 (3:00-3:15 p.m. ET)
    "A 12-Week Interferon-free Treatment Regimen with ABT-450/r, ABT-267, ABT-333 and Ribavirin Achieves SVR12 Rates (Observed Data) of 99% in Treatment-Naïve Patients and 93% in Prior Null Responders with HCV Genotype1 Infection"

The objective of this phase 2b study was to assess the safety, and efficacy of ABT-450/r (dosed 100/100 to 200/100mg QD), ABT-267 (25mg QD), ABT-333 (400mg BID) and ribavirin in non-cirrhotic treatment-naïve patients and prior peg-interferon/ribavirin null responders for 8, 12 or 24 weeks.

Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based.

The 12-week regimen of three direct acting antivirals plus ribavirin had the highest SVR12 rates among the 8 and 12 week arms. Results from the 12 week treatment groups containing three direct acting antivirals plus ribavirin are summarized in the chart below.


  Treatment-naïve (N=79) Null responders(N=45)
BL HCV RNA (log10 IU/mL) 6.5±0.6 6.6±0.5
BL IL28B non-CC genotype 72% 96%
SVR4 78/79 (99%) 42/45 (93%)
OD SVR12 76/77 (99%) 38/41 (93%)
PTW12 data missing* 2 4
Breakthrough 0 3
Relapse 1 0
OD SVR12 (GT1a) 52/53 (98%) 24/27 (89%)
OD SVR12 (GT1b) 24/24 (100%) 14/14 (100%)
OD SVR12 (IL28B non-CC) 54/55 (98%) 36/39 (92%)
* Did not follow up (2 treatment-naïve patients and 1 null responder) or have not yet reached PTW12 (3 null responders)

Additional data presented in the abstract represent all 8- and 12-week arms (n=448) of this 14-arm study (571 patients enrolled: 438 treatment-naïve and 133 prior null responders). SVR12 rates for other 8- and 12-week regimens ranged from 89-92 percent. Complete SVR12 data for 8- and 12-week arms will be presented at the Liver Meeting.

Four of 448 patients (one percent) in the 8- and 12-week arms discontinued due to adverse events. Of five serious AEs (1 percent), 1 (arthralgia or joint pain) was possibly study drug-related. In the trial, the most common adverse events were fatigue (28 and 27 percent) and headache (28 and 31 percent) for treatment naïve and null responders respectively.

Abbott Data at AASLD

In addition to Aviator, there are four poster presentations on Abbott's investigational medicines for the treatment of HCV:

  • Tami Pilot-Matias et al.; Sunday, November 11 (8:00 a.m.-5:30 p.m. ET)
    "Characterization of Resistant Variants in NS3 and NS5B Detected in Subjects Treated with ABT-450/r, Ribavirin, and Either ABT-072 or ABT-333 in the Pilot and Co-Pilot Studies Who Experienced Virologic Breakthrough or Relapse"
  • Preethi Krishnan et al.; Tuesday, November 13 (8:00 a.m.-12:00 p.m. ET)
    "Antiviral Activity and Resistance Profiles for ABT-267, a Novel HCV NS5A Inhibitor, In Vitro and During 3-Day Monotherapy in HCV Genotype-1 (GT1)-Infected Treatment-Naïve Subjects"
  • Lane Kirbach et al.; Tuesday, November 13 (8:00 a.m.-12:00 p.m. ET)
    "Evaluation of Patient Preferences for Treatment Outcomes in Hepatitis C Virus (HCV)"
  • Amit Khatri et al.; Sunday, November 11 (8:00 a.m.-5:30 p.m. ET)
    "Pharmacokinetics and Safety of Co-administered ABT-450 plus Ritonavir (ABT-450/r), ABT-267 and ABT-333 as a Single Dose in Subjects with Normal Hepatic Function and in Subjects with Mild, Moderate and Severe Hepatic Impairment"

About the Hepatitis C Virus

Hepatitis C is a liver disease affecting as many as 170 million people worldwide. The virus is primarily spread through direct contact with the blood of an infected person. HCV increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death; and liver disease associated with HCV infection is growing rapidly.

About Abbott's HCV Development Programs

Abbott's HCV portfolio includes investigational medicines with three different mechanisms of action, including protease (ABT-450/r), polymerase (ABT-333) and NS5A (ABT-267) inhibitors, currently being studied in clinical trials. ABT-450 is being developed with low dose ritonavir which enhances the pharmacokinetic properties of ABT-450. The use of ritonavir 100 mg with ABT-450 for the treatment of HCV is investigational. ABT-450 was discovered during the course of a collaboration between Abbott and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors.

ABT-450 is being developed by Abbott for use in combination with Abbott's other investigational medicines for the treatment of HCV. Abbott is well-positioned to explore combinations and co-formulations of these medicines.

Ritonavir Use in Treatment of HIV

Ritonavir is in a class of medicines called the HIV protease inhibitors. Ritonavir is used in combination with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. Ritonavir is for adults and for children greater than 1 month in age and older.

Ritonavir does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. People taking ritonavir may still get opportunistic infections or other conditions that happen with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.

Ritonavir Safety in Treatment of HIV

Patients should not take ritonavir with certain medicines, as these can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties, or excessive sleepiness. Patients should not take ritonavir if they have had a serious allergic reaction to any of its ingredients. Some patients taking ritonavir may develop liver and pancreas problems, which can cause death.

Patients may develop large increases in triglycerides and cholesterol, diabetes, high blood sugar, changes in body fat, increased bleeding in people with hemophilia, allergic reactions, and/or changes in heart rhythm. Patients may develop signs and symptoms of infections that they already have after starting anti-HIV medicines.

For more information, please see the Important Safety Information and full Prescribing Information for ritonavir.

About Abbott

Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacturing and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs approximately 91,000 people and markets its products in more than 130 countries.

Tracy Sorrentino
Roseanne Durril
(847) 937-8712
(847) 938-6114

Larry Peepo
Liz Shea
(847) 935-6722
(847) 935-2211



Exceptions are patients without rapid viral response to boceprevir or the IL28B genotype, for whom dual therapy is still best.

The new triple therapy regimens with peginterferon alfa, ribavirin, and boceprevir or telaprevir lead to high rates of sustained virologic response (SVR) in patients with hepatitis C virus (HCV) infection (JW Gastroenterol Mar 30 2011 and JW Gastroenterol Sep 16 2011). But, given their adverse effects, drug interactions, potential viral mutations, and expense, it is unclear whether these regimens are more cost-effective than dual therapy.

Now, European investigators have created a Markov decision model — using data from untreated patients with genotype 1 HCV infection and stage 2 liver fibrosis — to evaluate the cost-effectiveness of the following five strategies over a 20-year horizon:

  • Boceprevir response-guided therapy (RGT)
  • Boceprevir IL28B genotype-guided therapy (IL28B)
  • Boceprevir rapid virologic response–guided therapy (RVRT)
  • Telaprevir RGT
  • Telaprevir IL28B

In the IL28B strategies, if the IL28B CC genotype was identified, patients underwent dual therapy. In the boceprevir RVRT strategy, if rapid viral response was achieved during boceprevir lead-in, patients received dual therapy. Outcomes included costs (in 2011 euros), years of life gained, and incremental cost-effectiveness ratio (ICER).

The telaprevir IL28B and boceprevir RVRT strategies were the most clinically effective (survival improvement, 4.42 years and 4.04 years, respectively) and the most cost-effective. For both of these strategies, the quality-adjusted life year (QALY) estimate was improved by about 7 years, thanks to a 25% improvement in SVR rate, compared with dual therapy. This gain in SVR came at a relatively low cost of ICER per QALY of <10,000.

Comment: These results show that HCV triple therapy regimens are more cost-effective than previous dual therapy, especially if RVRT and IL28B data are used. Furthermore, the ICER per QALY was lower than the accepted societal threshold for willingness to pay. As with many modeling studies, the results are highly sensitive to certain assumptions and variables, including the cost of the regimens.

Source: Journal Watch Gastroenterology

13 of VA’s Top Links for Vet Services

You Can Help Get Information Out to Our Vets

The Veterans Health Administration wants to let Veterans know about the health support services available to them. Check out 13 of VA’s top links for Veteran services below.

We can use your help in getting information about these services out to Veterans.

Here is a quick list of links to the many programs available to our Vets.

If you know a Veteran, we hope you will print out this list (pdf) and give it to them.

  • It may be a homeless Vet you pass on the street every day — you can suggest they take the list to a public library computer to learn what VA has to help them.
  • It may be a young Vet recently returning from a combat zone, who is not aware of the benefits he or she is entitled to.

There are many potential opportunities for you to help Veterans make the connection to the services VA has for them, benefits they have earned!

In addition to the doctors and nurses who provide our Vets with high-quality health care, VHA has many programs to help Vets reach their optimal health.

Vets! Here are 13 of the top links for VA services. Use these health support services to maintain your physical and mental wellness:

Health Benefits
Start here to learn what VA health benefits you are elligible for and apply for care.
Helpful Phone Numbers
Health Benefits: 877-222-VETS  (8387)
Other VA Benefits: 800-827-1000
Homeless Services: 877-424-3838 
Compensated Work Therapy
A vocational rehabilitation program to match and support work ready veterans in competitive jobs.
Disease Prevention
Advocating for health promotion, disease prevention, and health education for our nation’s Veterans.
Geriatrics & Extended Care
Geriatric and extended care services for Veterans including non-institutional and institutional options.
Homeless Services
To end Veteran homelessness within the next five years, VA offers a variety of resources, programs and benefits to assist Veterans who are homeless.
Mental Health
Maintaining and improving the health and well-being of Veterans through excellence in health care, social services, education, and research.
Anywhere, anytime Internet access to VA health care information and services.
National Center for Post-Traumatic Stress Disorder
VA’s center of excellence for research and education on the prevention, understanding and treatment of posttraumatic stress disorder.
Readjustment Counseling (Vet Centers)
Offers services to Veterans and their families to aid their successful transition from military to civilian life.
Rural Health
Improving access and quality of care for Veterans living in rural areas.
Substance Abuse Programs
Treatments addressing problems related to substance use, from unhealthy use of alcohol to life-threatening addictions.
Veterans Crisis Line
The Veterans Crisis Line (Dial 1-800-273-8255 and press 1) is a toll-free, confidential phone support line that connects Veterans in crisis and their families and friends with qualified, caring VA responders.
Women Veterans Health Care
Implementing positive changes in providing care for all women Veterans.


New study to combat the most common form of liver cancer


12 October 2012 Southampton, University of

    Scientists at the University of Southampton are to investigate the best way to use natural killer cells (NK) to target the most common form of liver cancer.

    NK cells are able to directly kill cancer in the body and stimulate other cells in the immune system to help attack cancer.

    At the moment, NK cells, and the chemicals that manipulate them, are being used to treat a variety of different cancers, mainly cancers of the blood.

    However there is growing evidence that these cells could be used to create an immune response to hepatocellular cancer (HCC) cells and be used to kill them.

    HCC is the most common form of liver cancer and is mainly caused by cirrhosis of the liver - where the liver has become scarred as a result of damage over a long period of time.

    Funded by the British Liver Trust, researchers at the University of Southampton will investigate how to manipulate NK cells to attack HCC cells.

    The University's Salim Khakoo, Professor of Hepatology and Aymen Al-Shamkhani, Professor in Immunology will be leading the study.

    Professor Khakoo explains: "Hepatocellular cancer accounts for 90 per cent of all primary liver cancers and is an extremely difficult condition to treat. At this early stage of the study we aim to create a method to form the basis for a clinical trial to use NK cells to treat HCC.

    "To do this we will study patients with HCC and then use three different stimuli to activate NK cells. These different stimuli include a chemical stimulant of NK cells and antibodies that target molecules on the surface of the NK cells. By trying different combinations of these chemicals and antibodies together, we will be able to develop an optimal method to use them for immunotherapy."

    When the team has developed a successful method for stimulating the NK cells, tests will be carried out to determine the best way to use them for an anti-cancer effect.

    Andrew Langford, Chief Executive of the British Liver Trust commented "The British Liver Trust is delighted to fund what we hope will be invaluable research for new treatment of liver cancer.

    Unfortunately, of the big five killer diseases, deaths from liver cancer is the only one that continues to increase and the average age at which people die of a liver disease is now 59 and this gets lower each year; consequently, any research into new treatments offers hope that we can treat those that have liver cancer more effectively."


    NIH launches free database of drugs associated with liver injury

    Friday, October 12, 2012

    A free source of evidence-based information for health care professionals and for researchers studying liver injury associated with prescription and over-the-counter drugs, herbals, and dietary supplements is now available from the National Institutes of Health. Researchers and health care professionals can use the LiverTox database to identify basic and clinical research questions to be answered and to chart optimal ways to diagnose and control drug-induced liver injury.

    Drug-induced liver injury is the leading cause of acute liver failure in the United States, accounting for at least half of cases. It occurs at all ages, in men and women, and in all races and ethnic groups. Drug-induced liver disease is more likely to occur among older adults because they tend to take more medications than younger people. Some drugs directly damage the liver, while others cause damage indirectly or by an allergic reaction. The most important element to managing drug-induced liver injury is to identify the drug that's causing the problem and appropriate steps to eliminate or reduce damage to the liver.

    "Because drug-induced liver disease is not a single, common disease, it is very difficult to diagnose, with each drug causing a somewhat different pattern of liver damage," said Jay H. Hoofnagle, M.D., the major creator of LiverTox and director of the Liver Disease Research Branch at NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). "Doctors have to rule out all other causes of liver disease before saying that a patient has drug-induced injury liver."

    LiverTox has a searchable database of about 700 medications available in the United States by prescription or over the counter. Over the next few years, another 300 drugs will be added. The database offers these features:

    • An overview of drug-induced liver injury, including diagnostic criteria, the role of liver biopsy, descriptions of different clinical patterns and standard definitions.
    • A detailed report of each drug, including background, case study, product package insert, chemical makeup and structure, dose recommendations and references with links.
    • An interactive section, allowing users to report cases of drug-induced liver injury to the LiverTox website. Reports will be automatically forwarded to the Food and Drug Administration's (FDA) MedWatch program. MedWatch allows the public and health care professionals to report adverse events, product defects, or product use errors. The FDA uses the information to monitor product safety.

    "LiverTox is the result of a significant scientific collaboration between the national and international clinical and research communities, the NIDDK and the National Library of Medicine (NLM)," said Steven Phillips, M.D., co-sponsor of LiverTox and director of NLM's Division of Specialized Information Services. "LiverTox demonstrates the importance of using informatics to provide easy access to evidenced-based information to clinicians and researchers that will improve the health and well-being of all and help prevent unnecessary morbidity and mortality, worldwide. I hope the dynamic LiverTox model can be used to create a new suite of databases that can identify drug-induced injury to other organs such as the heart, kidney, and lung. The National Library of Medicine is honored to be part of this significant scientific endeavor."

    The developers of LiverTox worked with outside experts in drug-induced liver disease as well as specialists in arthritis, cancer, diabetes, infectious diseases, and other conditions. The content of each section of the database has been reviewed by an outside expert. The finished website has also been reviewed by FDA and pharmaceutical industry experts on liver-related complications.

    "By integrating data that tends to be scattered across the published literature into a single, readily accessible place, we hope to bring greater focus and interest to the study of drug-induced liver injury, and to guide doctors involved with patient care and ultimately, reduce liver injury and improve the health of people," said Hoofnagle.

    The database will be updated regularly with information about drug-induced liver injury as well as new drugs and new concepts. LiverTox welcomes input and comments from users through the website, at www.livertox.nih.gov .

    The NIDDK, part of the NIH, conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The Institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases. For more information, visit www.niddk.nih.gov.

    The National Library of Medicine (NLM) is the world's largest library of the health sciences and collects, organizes and makes available biomedical science information to scientists, health professionals and the public. For more information, visit http://www.nlm.nih.gov.


    NASH Spikes as Reason For Liver Transplant


    General Surgery News

    ISSUE: OCTOBER 2012 | VOLUME: 39:10

    Obesity Faulted; Study Shows Transplant Helps Nonalcoholic Steatohepatitis Patients

    By Christina Frangou


    Population-based studies suggest about 12% of Americans may have fat and inflammation present in the liver.

    The epidemic of hepatitis C, which currently accounts for about half of liver transplants in the United States, appears to have peaked and the numbers are expected to slide downward.

    Analysis showed that NASH patients required more resources during their surgery and postoperatively, but that long-term survival of NASH patients matches those of other transplant patients.

    Researchers identified two predictors of lower survival in NASH patients: obesity and pretransplant hemodialysis

    America’s stretched donor pool and limited resources for transplant will come under further stress in the next decade as nonalcoholic steatohepatitis (NASH) supplants hepatitis C as the primary indication for liver transplant, experts say.

    According to a study presented at the American Surgical Association’s annual meeting, NASH is now the fastest-growing indicator for liver transplant at the University of California, Los Angeles (UCLA), which has one of the country’s largest transplant programs.

    In 2002, NASH was the primary indication for liver transplant in about 3% of all liver transplants at UCLA. By 2011, it accounted for 19% of all liver transplants and was the second most common indication for liver transplant at the center, representing a fivefold increase over nine years.

    “NASH will soon become the leading indication for liver transplantation in the United States,” said Vatche Agopian, MD, a transplant surgeon at the David Geffen School of Medicine at UCLA.

    The situation in Los Angeles is similar to that at transplant centers across the country, said John P. Roberts, MD, professor of surgery and chief of transplantation at the University of California, San Francisco.

    NASH is rising dramatically in the United States, yet another consequence of the sky-high obesity rate. Population-based studies suggest about 12% of Americans may have fat and inflammation present in the liver. At the same time, the epidemic of hepatitis C, which currently accounts for about half of liver transplants in the United States, appears to have peaked and the numbers are expected to slide downward.

    Even at its peak, hepatitis C affected about 1% of the U.S. population. The growing prevalence of NASH suggests that a much larger proportion of the population could one day be candidates for liver transplant, said Dr. Roberts.

    “It’s changing very fast. My sense is that you are going to see a big switch in indication for liver transplant from hepatitis C to NASH within the next decades,” said Dr. Roberts. “This is where the future is going and it has the potential to overwhelm the system. We’re already short of organs now.”

    A study presented at the American Association for the Study of Liver Diseases meeting this fall showed that NASH accounts for an increasing proportion of liver transplants nationally and liver transplant recipients with NASH have poorer survival compared with non-NASH recipients without hepatitis C (Brandman D et al. Temporal trends in liver transplantation [LT] for nonalcoholic steatohepatitis [NASH]; abstract).

    The UCLA study is the largest single- institution experience of liver transplant for NASH. Unlike previous research, it demonstrates that NASH patients can have outcomes that are comparable to other patients undergoing liver transplants. Even so, NASH patients place increased demand on hospital resources, the study showed.

    Between 1997 and 2011, 144 patients underwent liver transplant for NASH, representing 12% of all liver transplants at UCLA during that time. Before 2002, only eight patients in total underwent liver transplantation for NASH. Since then, the number has leaped upward annually.

    Patients with NASH had more pretransplant comorbidities and higher pretransplant acuity than patients who underwent liver transplants for other causes. Two-thirds of NASH patients had a body mass index (BMI) of 30 kg/m2 or greater and/or diabetes; 50% of patients had hypertension and 30% had metabolic syndrome—all significantly higher than in other transplant patients. NASH patients had an average Model for End-Stage Liver Disease score of 33, 45% were on hemodialysis and 17% were receiving vasopressors.

    Analysis showed that patients with NASH required more resources during their surgery and postoperatively. They had significantly longer operative times, reaching a median of 6.9 hours compared with 5.3 hours for other patients (P<0.001); they had greater operative blood loss (18 vs. 14 units of packed red blood cells; P=0.004) and a longer total hospital length of stay (35 vs 29 days; P=0.046).

    But long-term, the survival of patients with NASH matches those of other transplant patients. One- and three-year graft survival reached 80% and 70%, respectively, and one- and three-year patient survival was 84% and 75%, respectively. The survival rates were similar to those for all other patients undergoing liver transplant except for patients with hepatitis C. Patients with hepatitis C who received liver transplants had much poorer outcomes: a 62% survival and 57% graft survival after three years.

    Two factors appear to be important predictors of survival in patients with NASH: namely, patients who had a BMI greater than 35 kg/m2 and patients requiring pretransplant hemodialysis had worse outcomes after transplant. The authors said these factors might help guide the selection of patients who may benefit most from liver transplant.