September 30, 2010

WASHINGTON, Sept. 30 /PRNewswire-USNewswire/ -- In response to the Centers for Disease Control (CDC) Director Dr. Thomas Frieden's release of "six winnable battles" in health care, Ms. Lorren Sandt, Chair of the National Viral Hepatitis Roundtable (NVHR) and Executive Director of Caring Ambassadors Program, based in Portland, Oregon, released the following statement:

"The CDC's newly released 'six winnable battles' strategy makes a mockery of the broad-based, comprehensive, and integrated public-health strategy that our nation so desperately needs. In seeking to win six narrowly defined health care battles, the CDC may well lose the overall public-health war.

"Chronic viral hepatitis B and C are among dozens of conditions that are shortchanged by this PR-driven public-health approach from CDC. We can and must do better. How can a vaccine preventable virus, hepatitis B, and the only virus we can cure, hepatitis C, fail to make this list?

"Chronic viral hepatitis afflicts more than 5 million Americans directly and, by extension, tens of millions more of their loved ones. Most Americans are not aware they are infected until they present with serious related illnesses. Without adequate screening and treatment, chronic viral hepatitis often progresses to cirrhosis, liver cancer, and liver failure.

"Over the past year, experts from the Institute of Medicine, the American Association for the Study of Liver Diseases, and the Trust for America's Health have all identified how best to address the viral hepatitis epidemic with common-sense action plans. Regrettably, the Administration is lacking the political will to implement them.

"The CDC's omission of viral hepatitis from its list of 'winnable battles' is not simply an oversight – it's an abdication of duty to many Americans who may well lose their battle with chronic viral hepatitis in the decades to come."

NVHR is a coalition of more than 170 public, private, and voluntary organizations dedicated to reducing the incidence of infection, morbidity, and mortality from chronic viral hepatitis that afflicts more than 5 million Americans. http://www.nvhr.org/

SOURCE National Viral Hepatitis Roundtable

RELATED LINKS
http://www.nvhr.org/

Source

Also See: CDC chief picks 6 'winnable battles' in health
Sept. 30, 2010, 4:00 p.m. EDT

NEW HAVEN, Conn., Sep 30, 2010 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. /quotes/comstock/15*!achn/quotes/nls/achn (ACHN 3.02, -0.03, -0.98%) , a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today announced that the Company has initiated patient dosing in a Phase II clinical trial of ACH-1625 for the treatment of hepatitis C virus (HCV) infection. ACH-1625 is a potent small molecule inhibitor of HCV protease, an enzyme necessary for viral replication. The drug candidate was discovered and is being advanced by Achillion.

The clinical trial is a Phase IIa, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability and antiviral activity of oral ACH-1625 in combination with pegylated interferon alfa-2a and ribavirin after 28 days of dosing and after 12 weeks of dosing in subjects with chronic hepatitis C virus genotype 1. The trial will take place in the United States and Europe and is designed to enroll approximately 120 HCV-infected patients. The 28-day and 12-week trial data are anticipated to be announced in the first and fourth quarters of 2011, respectively.

"This Phase II clinical trial will allow us to establish the most appropriate once-daily dose to use in longer-term trials, and will augment our existing safety database for ACH-1625 in humans," stated Elizabeth A. Olek, D.O., Vice President and Chief Medical Officer of Achillion. "The results will also provide important combination data for use of ACH-1625 with standard of care. We anticipate that the 28-day segment of the trial will provide us with rapid viral response (RVR) data early next year, and that the 12-week segment will provide extended viral response (cEVR) data by the end of next year."

"The initiation of Phase II dosing for ACH-1625 is a very important step in further solidifying this compound's profile as a potentially best-in-class protease inhibitor for HCV treatment," said Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "We believe ACH-1625 has the potential to provide an improved safety and tolerability profile, a more convenient dosing schedule and an extended period of viral suppression compared to currently available treatments for HCV-infected patients."

About ACH-1625

ACH-1625 is an HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. With its rapid and extensive partitioning to the liver, as well as high liver/plasma ratios demonstrated in preclinical studies, Achillion believes that ACH-1625 has the potential for once daily dosing. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50~1nM.

In clinical studies completed to date, subjects receiving both single and multiple ascending doses ranging from 50 mg to 2000 mg for periods up to 5 days demonstrated that ACH-1625 was well tolerated at all doses and there were no serious adverse events, and no clinically significant changes in vital signs, electrocardiograms (ECGs) or laboratory evaluations. HCV-infected patients receiving doses ranging from 200 to 600 mg twice daily, and 400 to 600 mg once daily, showed mean maximal reductions in viral load ranging from of 3.07 log10 to 4.25 log10. Furthermore, all patients had viral loads that remained suppressed for at least 7 days after dosing was completed, maintaining a mean reduction of more than 1log10 from baseline through day 12, the last day of viral load measurement in the study.

About HCV

The hepatitis C virus (HCV) is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80% of individuals become chronically infected following exposure. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, injectable route of administration and high cost.

About Achillion

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease --hepatitis C, resistant bacterial infections and HIV. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including statements with respect to the potency, safety and other characteristics of ACH-1625, which may not be duplicated in future cohorts at different doses or in future clinical studies of longer duration; Achillion's expectations regarding timing and duration of other clinical trials, including additional dosing cohorts. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are uncertainties relating to results of clinical trials and unexpected regulatory actions or delays. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2009.

All forward-looking statements reflect Achillion's expectations only as of the date of this release and should not be relied upon as reflecting Achillion's views, expectations or beliefs at any date subsequent to the date of this release. Achillion anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Achillion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.

ACHN-G

This news release was distributed by GlobeNewswire, http://www.globenewswire.com/

SOURCE: Achillion Pharmaceuticals, Inc.

CONTACT: Achillion Pharmaceuticals, Inc.

Mary Kay Fenton
(203) 624-7000
mfenton@achillion.com

Lippert/Heilshorn & Associates, Inc.
Anne Marie Fields
(212) 838-3777
afields@lhai.com

Bruce Voss
(310) 691-7100
bvoss@lhai.com
 
Source

CDC chief picks 6 'winnable battles' in health

By MIKE STOBBE (AP) – 37 minutes ago

ATLANTA — Where would you start if you were charged with keeping the nation healthy? Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention, has chosen six priorities — winnable battles, he calls them.

They are smoking, AIDS, obesity/nutrition, teen pregnancy, auto injuries and health care infections. These are long-standing, major challenges that get a lot of attention already.

But elevating a handful of problems above dozens of others is a bold move for a public health official. So far, it's been received like a bucket of cold water — invigorating some, infuriating others.

Many advocates, legislators and others in public health have devoted their lives to problems that did not make Frieden's short list. So there are complaints.

A CDC employee blog is peppered with postings like, "I guess climate change is not a battle worth winning," and "Don't we still owe the patients of tomorrow an investment in things that may not pay off immediately?"

Some advocates wonder aloud just how targeted federal public health dollars are going to be. A particular point of concern is hepatitis C, a long under-recognized liver-destroying virus which has infected more than 3 million Americans. Some experts consider the issue a ticking time bomb and have called for the government to step up efforts to prevent it and better diagnose and treat people who already are infected.

Hepatitis B and C already are "badly neglected" by the CDC, and their omission from Frieden's winnable battles list is more bad news, said Bruce Burkett, past president of the National Hepatitis C Advocacy Council.

"I was very disappointed that it wasn't on there. This is going to affect millions by not being on there," he said.

Frieden, who took over CDC in June last year, already had a reputation as something of a public health maverick. When he started his previous job as New York City's health commissioner in 2002, he began by identifying the city's most pressing health issues. He led campaigns to ban smoking in the workplace, tax soda, cut salt in processed foods, and ban artificial trans fats in restaurants.

It's no surprise that he is boldly painting targets at the CDC, said Dr. Jo Ivey Boufford, president of the New York Academy of Medicine. She's a fan of Frieden's who worked with him as a member of an advisory council to the city health department.

Frieden's CDC job, ironically, does not provide the same kind of power he had in New York City to engineer bans or tax increases. But Frieden calls his new short list "winnable battles" because, he says, proven programs can save lives and reduce harm from each of these health problems. He believes government can make dramatic improvements if available money and manpower are focused.

"In each of these areas we know what to do to make a difference and we need to do it to a much greater extent," he said in an interview.

Frieden, with a low-key demeanor, has said relatively little about this to the public, though he seems to be building support within the public health community.

There is some nervousness about how far Frieden's going to take this.

"I think everyone is going to be cautious in how the focus on winnable battles is balanced against other areas" that are also deemed important but may not be as easy to dent, said Jeff Levi, who heads Trust for America's Health, a research group.

Top CDC officials have been quick to say they have no intention of walking away from other public health missions. They couldn't even if they wanted to, because much of the agency's funding is directed to certain causes by Congress. According to one estimate, less than one-tenth of 1 percent of CDC's $6.6 billion budget is discretionary money that can be channeled into the winnable battles campaign. Indeed, the agency has been asking for more flexibility.

But there's power in perception, especially concerning CDC's grant money to states. Nearly a quarter of that is targeted at the six battle areas, which already were major areas of interest. State health officers say they're acutely aware of Frieden's priorities and want him to know it when they apply for CDC money.

"We're in the position of focusing pretty much on what we can get federal funds for," said Will Humble, director of the Arizona Department of Health Services.

Humble and several other public health leaders applaud Frieden's priorities as an overdue attempt to narrow the public health message and better market health improvement to Americans.

"You can't market if your message is too diffuse," Humble said. "If we're all on the same page and working in the same direction, we can get a lot more momentum."

This isn't how many public health officials traditionally operate, partly because they tend to worry about alienating employees, legislators and advocates, observed Stanton Glantz, a University of California-San Francisco expert on the health effects of smoking.

Other top federal health officials have not been as specific. U.S. Surgeon General Dr. Regina Benjamin, the government's chief health educator, has made the broader themes of prevention and wellness her focus.

But Frieden clearly has the blessing of his Obama administration bosses to set clear targets.

"Getting focused, and getting some quick wins under your belt, is terribly important," said Victor Strecher, a University of Michigan health behavior expert.

Progress in these areas has long been measured by health statistics. What exactly will constitute a win? Frieden hasn't said yet.
___

Online:
CDC Web page describing winnable battles: http://bit.ly/bCd8Lr

Source

Bleeding Complication With Liver Biopsy: Is It Predictable?

Clinical Gastroenterology and Hepatology
Volume 8, Issue 10 , Pages 826-829, October 2010

Stephen Caldwell, MD, Patrick G. Northup, MD
published online 28 June 2010.

Liver biopsy remains a cornerstone of diagnosis and disease staging and an important measure of natural history and therapeutic outcomes in many forms of liver disease. The major limitations of biopsy are the risk of procedure-related complications especially bleeding and adequacy of the sample to ensure accurate histologic interpretation. In the current issue of Clinical Gastroenterology and Hepatology, Seeff et al report liver biopsy complication rates in 1 of the largest cohorts of patients with histologically advanced disease.1

The study involved 2740 percutaneous biopsies performed over 7 years at 10 centers as part of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. The study assessed the efficacy of low dose maintenance peginterferon alfa-2a therapy in patients with histologically advanced hepatitis C—related fibrosis undergoing biopsy at baseline (n = 1187), 1.5 years (n = 852), and 3.5 years (n = 701) of treatment. Eighty percent of the biopsies were performed with ultrasound guidance, 40% used an aspiration needle, and 60% used a cutting needle. Single passes were reported in 40% and 2 passes in 60%. Complication rates were determined prospectively with no difference between baseline and follow-up biopsies.

Overall, serious adverse events (AE) occurred in 29 of the biopsies with no deaths. Severe bleeding was the most common cause seen in 16 (0.6%) of the biopsies including hemoperitoneum in 8, subcapsular hematoma in 4, hemobilia in 3, and hemothorax in 1. About one fourth of the adverse events were due to severe pain and one fourth were due to other causes including punctured gallbladder in 2, pneumothorax in 1, syncope in 1, and hypotension in 2. Because of its higher frequency and potential severity, the authors focused on bleeding risk assessment. No difference in those who bled versus those who did not was seen between 2 passes versus a single pass, use of a cutting needle versus an aspiration needle, or performance by a fellow as opposed to an attending physician. Factors that were statistically different between those with bleeding and those without were lower albumin, presence of varices, platelets less than 60,000 and INR ≥ 1.3 although it should be noted that among the 8 patients with international normalized ratio (INR) > 1.5, none had bleeding. Moreover, while these variables were statistically significant, the clinical differences were not clinically dramatic as is evident in Tables 6 and 7 of the report. The relationship to varices and albumin levels suggests that the variation in risk may be due to changes in hepatic vasculature in more advanced disease rather than changes in hemostatic mechanisms.

Although several other factors limit interpretation of the data including preset study inclusion criteria (based in part on conventional coagulation parameters) and the retrospective acquisition of procedure details by questionnaire as discussed by the authors, the study raises the interesting and challenging issue of bleeding risk assessment with percutaneous liver biopsy. Reassuringly, the mortality was zero although the incidence of nonfatal severe bleeding was higher in this cohort of advanced fibrosis stage patients, 1 in 200, compared with about 1 in 500 biopsies from a compilation of past reports of patients of all stages.2

Is the INR useful to predict bleeding in a cirrhosis patient? Despite the implications of the current study, the answer to this is clearly no. Although this test unfortunately continues to hold on to some adherents as a valid indicator of bleeding risk in cirrhosis patients, the practice is unfounded both physiologically (see below) and methodologically as the conventional INR in cirrhosis patients is not normalized to the various thromboplastin reagents used in the test.3 This problem is very evident by the marked interlaboratory variation consistently reported now in a number of studies represented in Figure 1.4, 5, 6, 7, 8 Thus an INR of 1.2 in 1 clinical reference laboratory can be an INR of 2 on the identical sample in another clinical reference laboratory. The problem lies with variation in activity of the thromboplastin and normalization of the test to warfarin-treated patients (international sensitivity index; ISI) rather than to liver disease patients.9 In the present study, liver disease—corrected INR (termed INRLiver) was not utilized so the degree of variation between the 10 involved centers is unknown. Even ignoring this, it is noteworthy that 6 of the patients who had bleeding had INR <1 while none of the 8 patients with INR >1.5 had bleeding.


Figure 1.
Variation between different clinical reference laboratories in INR values on identical samples from patients with cirrhosis. High and low values for identical sample sets are shown. The variation is thought to result from differences in thromboplastin reagents. The values straddle the 1.5 cutoff in 8 of 19 cases. Aside from the substantial physiological limitations of this test (based on abnormalities of the hemostatic system in cirrhosis; see text), this degree of interlaboratory variation renders nonsensical the application of a universal clinical cutoff value as a measure of bleeding risk in cirrhosis patients although it remains a valid indicator in warfarin therapy for which the test was developed..

Clearly, the problem with INR as an index of bleeding risk in cirrhosis is more profound than simply marked interlaboratory variation. Because the test is derived from the prothrombin time, it is a reflection only of procoagulant factor activity and fails to account for the full breadth of both anti- and pro-hemostatic disturbances which are now known to exist in cirrhotic patients. It is especially notable that in stable cirrhosis patients the magnitude of procoagulant thrombin generation can be on the order of congenital protein C deficiency.10 This results from a relative resistance to endothelial-derived thrombomodulin (a protein C cofactor) due itself to decreased protein C levels and increased factor VIII activity. Hypercoagulability in cirrhosis is also supported by increased von Willebrand factor and decreased antithrombin III the latter of which can also lead to heparin resistance in this group of patients.11 Clinically, the presence of a hypercoagulable state is evident in the prevalence of deep vein thrombosis in this group.12, 13
 
On the other hand, bleeding is clearly a problem in these patients especially during episodes of decompensation requiring hospitalization. In a recent survey from our inpatient service, we observed 34 bleeding events (12 variceal and 22 nonvariceal) over a 42-day period about three fourths of which warranted transfusion of human blood products (Shah N, unpublished survey). Nonvariceal sources included mucosal bleeding, puncture wound bleeding, severe epistaxis, severe limb hematomas, and contusions and severe bleeding after dental extractions. Thus the issue is not an absence of bleeding risk but rather it is how to measure the risk and how to respond to a poorly balanced pro- and anti-hemostatic system. Other more discrete variables also contribute significantly to impaired hemostasis in this setting. These include hyperfibrinolysis seen in about 10% of cirrhosis patients and which should be suspected with delayed bleeding following a procedure,14, 15 renal insufficiency with uremic changes in platelets, and associated volume expansion which engorges the portal system,16 infection and associated release of endogenous heparinoids, and the very poorly characterized condition of dysfibrinogenemia which occurs in cirrhosis.16, 17 These complicated interactions are not measured by conventional coagulation indices such as INR. On the other hand, although INR clearly is limited as a bleeding risk measure, it remains unknown whether or not it is useful as a marker of dose effect of hemostatic agents used when cirrhosis patients bleed and it remains as a useful indicator of prognosis albeit with some unresolved problems arising from interlaboratory variation.

Are platelet levels useful to predict bleeding? The data are clearer with regard to platelet levels. While qualitative platelet changes which may be either pro- or anti-coagulant are largely unmeasured, convincing data have been published that show platelet levels of around 56,000/mL are associated with adequate in vitro thrombin production.18 Similar to the conclusions in the present study, a prior report also indicated a greater bleeding risk in liver biopsy when platelet levels were <60,000/mL.19 On the other hand it should be recalled that laparoscopically measured liver biopsy bleeding was unrelated to conventional coagulation parameters including platelet count in another study.20 Similarly, in the present study, 11 of the bleeding episodes occurred in patients with platelet levels >60,000/mL and 3 of them had platelet levels >150,000/mL.

Postbiopsy bleeding occurs in several forms ranging from arterial spurting to portal venous oozing to internalized hemobilia. Of these, arterial spurting is the most dramatic and usually becomes evident early in the postbiopsy period with associated hemodynamic changes. Although the timing of the bleeding episode after the biopsy and details of the management were not available, a number of the patients underwent interventional vascular imaging and embolization consistent with inadvertent small arterial puncture and bleeding. Such small vessels are not easily seen by conventional ultrasound and the incidence of arterial bleeding may well represent roughly the same frequency of incidental transgression of these structures. Histologic analysis of the specimens was not available to determine the presence or absence of these structures in those who bled versus those who did not bleed but it is our experience (thankfully infrequent) that such structures are evident on the histopathology slides when arterial bleeding is encountered (Figure 2). Because of changes in the hepatic vascular bed as early cirrhosis transitions to advanced cirrhosis with atrophy, it is possible that the likelihood of such an event increases with more advanced disease. Such a relationship is suggested by the association of bleeding with varices and lower albumin in the present study. As the authors likely have these biopsies in repository, it would be helpful to review these with attention to the presence or absence of vascular structures vis-à-vis the history of bleeding.


Figure 2.
(A) A 48-year-old male with human immunodeficiency virus (HIV) in remission and possible drug-induced liver disease underwent ultrasound-guided biopsy with 16-gauge automated needle with a single pass. Prebiopsy INR = 0.9 and platelets 71,000/mL. Developed pain and decreased blood pressure postbiopsy. Computerized tomography (CT) showed site of bleeding (arrow). (B) Same patient underwent arteriography showing arterial extravasation (arrow). (C) Same patient status post coiling of the bleeding site. (D) Biopsy sample shows vessel wall of very small artery which likely represents the site of bleeding (H&E 200×). (E) Closer view of (D) (H&E 400×)..

The role of ultrasound (US) guidance either as real time imaging or prebiopsy site marking was not directly addressed as a potential risk modifier in the present study. This is probably because the majority (80%) of the biopsies were described as ultrasound-guided which likely limited the comparison. Whether or not the patients with bleeding were equally distributed in the US-guided group versus those without image guidance would be interesting but is not reported. However, given the size of the small arteriolar vessels that may be the source of severe hemorrhage (Figure 2) and the limitations of ultrasound resolution, it seems very unlikely that ultrasound guidance will have an effect on the risk of severe hemorrhage. This assessment is supported by several prior observational studies and a controlled trial of US-guided versus nonguided biopsy.21, 22, 23 In the latter study, a substantial difference in the complication rate (including bleeding) between US-guided and non-US-guided biopsy was only reported as a difference which included both severe pain and significant bleeding combined. Based on these studies, the use of US guidance is likely to have its greatest impact on the incidence of postbiopsy pain and more significantly on organ puncture including gall bladder puncture (seen in 2 patients in the present study) and pneumothorax (seen in 1) which is more likely to be reduced with US guidance. In the present study, it would be helpful to know the relative incidence of these events in those with US guidance versus those without.

Although other parameters may eventually supplant biopsy as a measure of the natural history of liver diseases and/or as an indicator of treatment response, at this time biopsy remains a key part of the evaluation in these patients. Acquisition of an adequate sample while ensuring safe performance remains paramount in this situation. Current data supports aiming for platelet levels in the range of at least 55,000/mL–60,000/mL and taking into account the possibility of coexisting conditions such as hyperfibrinolysis which might be evident from a history of easy bleeding for example. For the reasons discussed above, the INR warrants much less emphasis and certainly no data exist to support a specific cutoff. Transvenous biopsy may at first appear to offer a safer approach but a close review of the literature reveals a complication rate similar to that of percutaneous biopsy albeit the patient population may be selected with higher inherent risk.2 Most clearly, better measures of the hemostatic system balance in cirrhosis and the possible role of other prophylactic measures such as emerging procoagulants need clinical investigation to complement recent laboratory advances in this field.

References
 
1.Seeff LB, Everson GT, Morgan TR, et al. HALT-C TRIAL GROUP Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C Trial. Clin Gastroenterol Hepatol. 2010;8:877–883 

2.Rockey DC, Caldwell SH, Goodman ZD, et al. Liver biopsy. Hepatology. 2009;49:1017–1044

3.Malloy PC, Grassi CJ, Kundu S, et al. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol. 2009;20:S240–S249

4.Tripodi A, Chantarangkul V, Primignani M, et al. The international normalized ratio calibrated for cirrhosis (INR(liver)) normalizes prothrombin time results for model for end-stage liver disease calculation. Hepatology. 2007;46:520–527

5.Bellest L, Eschwege V, Poupon R, et al. A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology. Hepatology. 2007;46:528–534

6.Lisman T, van Leeuwen Y, Adelmeijer J, et al. Interlaboratory variability in assessment of the model of end-stage liver disease score. Liver Int. 2008;28:1344–1351

7.Trotter JF, Brimhall B, Arjal R, et al. Specific laboratory methodologies achieve higher model for endstage liver disease (MELD) scores for patients listed for liver transplantation. Liver Transpl. 2004;10:995–1000

8.Trotter JF, Olson J, Lefkowitz J, et al. Changes in international normalized ratio (INR) and model for endstage liver disease (MELD) based on selection of clinical laboratory. Am J Transplant. 2007;7:1624–1628

9.Porte RJ, Lisman T, Tripodi A, et al. The International Normalized Ratio (INR) in the MELD score: problems and solutions. Am J Transplant. 2010;10:1349–1353

10.Tripodi A, Primignani M, Chantarangkul V, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009;137:2105–2111

11.Lisman T, Bongers TN, Adelmeijer J, et al. Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology. 2006;44:53–61

12.Northup PG, McMahon MM, Ruhl AP, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol. 2006;101:1524–1528quiz 1680

13.Sogaard KK, Horvath-Puho E, Gronbaek H, et al. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol. 2009;104:96–101

14.Ferguson JW, Helmy A, Ludlam C, et al. Hyperfibrinolysis in alcoholic cirrhosis: relative plasminogen activator inhibitor type 1 deficiency. Thromb Res. 2008;121:675–680

15.Gunawan B, Runyon B. The efficacy and safety of epsilon-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis. Aliment Pharmacol Ther. 2006;23:115–120

16.Smalberg JH, Leebeek FW. Superimposed coagulopathic conditions in cirrhosis: infection and endogenous heparinoids, renal failure, and endothelial dysfunction. Clin Liver Dis. 2009;13:33–42

17.Cunningham MT, Brandt JT, Laposata M, et al. Laboratory diagnosis of dysfibrinogenemia. Arch Pathol Lab Med. 2002;126:499–505

18.Tripodi A, Primignani M, Chantarangkul V, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006;44:440–445

19.Sharma P, McDonald GB, Banaji M. The risk of bleeding after percutaneous liver biopsy: relation to platelet count. J Clin Gastroenterol. 1982;4:451–453

20.Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci. 1981;26:388–393

21.Lindor KD, Bru C, Jorgensen RA, et al. The role of ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy. Hepatology. 1996;23:1079–1083

22.Manolakopoulos S, Triantos C, Bethanis S, et al. Ultrasound-guided liver biopsy in real life: comparison of same-day prebiopsy versus real-time ultrasound approach. J Gastroenterol Hepatol. 2007;22:1490–1493

23.Stone MA, Mayberry JF. An audit of ultrasound guided liver biopsies: a need for evidence-based practice. Hepatogastroenterology. 1996;43:432–434

Conflicts of interest The authors disclose the following: Dr Caldwell consults for and has research support from CL Behring and consults for Bioengineering Inc, Charlottesville, VA. Dr Northup discloses no conflicts.

PII: S1542-3565(10)00607-5
doi:10.1016/j.cgh.2010.06.010
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Source

Use of Statins in Patients with Chronic Hepatitis C

Southern Medical Journal:

October 2010 - Volume 103 - Issue 10 - pp 1018-1024
doi: 10.1097/SMJ.0b013e3181f0c6b4
CME Topics, Questions, Submission Forms

Andrus, Miranda R. PharmD, BCPS, FCCP; East, Jessica PharmD
 
Author Information
 
From the Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Huntsville, AL.
 
Reprint requests to Miranda R. Andrus, PharmD, BCPS, FCCP, Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, 301 Governors Drive, Suite 385B, Huntsville, AL 35801. Email: andrumr@auburn.edu

Dr. Andrus and Dr. East have no financial disclosures to declare and no conflicts of interest to report.

Accepted February 12, 2010.

Abstract
 
Hepatitis C is a leading cause of liver failure and transplantation in the United States and a major public health issue. Studies have shown that patients with hepatitis C are at an increased risk of cardiovascular disease, which make statins of particular benefit in this patient population. However, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) lists active or chronic liver disease as an absolute contraindication to statin therapy. The available literature regarding the safety of statins in this patient population is limited, but has not shown clinically significant differences in aminotransferase elevations or evidence of hepatotoxicity in patients with hepatitis C who have received statins versus those who have not. Statins should continue to be avoided in advanced end-stage liver disease, as there is a lack of safety data in these patients and drug metabolism would be severely compromised. Treatment with statins can be used in those with chronic, stable hepatitis C with elevated cardiac risk or a previous cardiac event.
 
Key Points
 
* Patients with chronic hepatitis C often have elevated cardiac risk and could benefit from statin therapy.

* The National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) lists active or chronic liver disease as an absolute contraindication to statins.

* Studies of statins in patients with chronic hepatitis C have not shown a clinically significant risk for hepatotoxicity.

* Statins should be considered in patients with chronic hepatitis C with elevated cardiac risk.

Hepatitis C is a major public health issue and a leading cause of liver failure and transplantation in the United States.1 The most recent data estimate that 1.6% of the United States population (about 4.1 million people) is infected with hepatitis C.2 Of these, over three-fourths (about 3.2 million) have chronic hepatitis C infection.

Two studies have shown that patients with hepatitis C are at an increased risk for cardiovascular disease based on an increased carotid intima-media thickness. In a Japanese study, a higher percentage of patients with persistent hepatitis C infection were found to have carotid plaque (P < 0.0001) and carotid intima-media thickening (P < 0.05) compared to a control group.3 Multivariate logistic regression analysis also showed persistent hepatitis C infection to be an independent predictor of carotid plaque, with an odds ratio of 5.61 (95% confidence interval [CI] 2.06–15.26, P < 0.001). A second study also demonstrated that patients with hepatitis C had greater carotid intima-media thickness compared to control (P < 0.001).4

These increases in markers of early atherosclerosis in chronic hepatitis C may make 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) of particular benefit in this patient population. However, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) lists active or chronic liver disease as an absolute contraindication to statin therapy.5 The guideline authors state that it is not known if statins worsen outcomes in patients with chronically elevated aminotransferase levels (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) due to hepatitis C. They do recognize that it is unknown if elevated aminotransferase levels due to statin therapy represents true hepatotoxicity, and that progression to liver failure is rare. Clinical trials of statins have generally excluded patients with a history of chronic liver disease, so safety data in this patient population are limited. However, patients with hepatitis C may actually have increased cardiovascular risk, and could greatly benefit from the lipid lowering and pleiotropic effects of statins.

The Liver Expert Panel of the National Lipid Association has affirmed that there is a relationship between statin therapy and elevations in aminotransferase levels.6 However, these experts acknowledge that liver failure associated with statins is extremely rare. Although there are reports of liver failure requiring transplantation, there are no reported deaths due to liver failure associated with statins.6 Elevations in aminotransferase levels of greater than 3 times the upper limit of normal (ULN) have been seen in less than 1% of patients receiving starting or intermediate doses of statins, and up to 2–3% of those receiving maximal doses.7 Most of these elevations are asymptomatic, and usually return to baseline if the statin is discontinued.7 Often, these elevations are transient and resolve spontaneously, even if the statin is continued.7 The elevations also appear to be dose-related, with higher doses of statins more likely to cause enzyme elevations.7–9 Single, unconfirmed enzyme elevations may not be related to statin therapy at all, and these elevations generally do not indicate liver damage or failure.6,7

The exact mechanism by which statins cause increased aminotransferase levels is not clearly understood; however, the mechanism appears to be hepatocellular injury.7 The adverse effect is thought to be more related to the dose and concentration of the statin in tissues, rather than the degree of low density lipoprotein (LDL) reduction.7 Conditions that can increase statin concentrations—and therefore increase the risk of adverse effects—include advanced age, small body frame, declining renal function, infection, untreated hypothyroidism, drugs which inhibit the metabolism of statins, and alcohol abuse.7 The Liver Expert Panel has concluded that all marketed statins can cause elevations in aminotransferase levels, and that no particular statin causes these adverse effects more frequently than the others.6

Several review articles recommend that statins be considered, with careful monitoring, in chronic hepatitis C patients.7–9 The potential benefits of statins in patients with coexisting chronic hepatitis C and elevated cardiovascular risk led us to review the primary literature for specific evidence regarding the safety of statins in this population.

Literature Review
 
A literature search was conducted using Ovid Medline (1950 to January, Week 1, 2010), combining the medical subject heading search terms “hydroxymethylglutaryl-CoA reductase inhibitors” and “hepatitis C.” References of relevant articles were also reviewed. Studies examining the safety of using statins in patients with hepatitis C are limited to 1 prospective study, 3 retrospective studies in the Veterans Affairs (VA) population (1 of which only included 17 patients), and 1 retrospective study in patients with human immunodeficiency virus (HIV). A summary of these trials is provided in the Table.

A prospective, randomized, double-blind, placebo-controlled, parallel-group trial was designed to determine the efficacy and safety of high-dose pravastatin (80 mg daily) in hypercholesterolemic subjects with well-compensated liver disease.10 The study enrolled 326 patients, of which 62% had nonalcoholic fatty liver (NAFL)/nonalcoholic fatty liver disease (NAFLD), 27% had chronic hepatitis C, and the remainder had other liver diseases.
 
Inclusion criteria were a LDL cholesterol ≥100 mg/dL after a 4-week lead-in phase of lifestyle modifications, triglycerides <400 mg/dL, age ≥18 years old, and chronic, well-compensated liver disease. Patients were excluded if they were pregnant or breastfeeding, had AST or ALT levels >5 times the upper limit of normal (ULN), total bilirubin level above normal, serum creatinine >1.5 mg/dL, creatinine kinase >3 times the ULN, albumin less than the lower limit of normal, prothrombin time >2 seconds, or platelet count less than the lower limit of normal. Patients were also excluded if they had ascites, jaundice, or cirrhosis with a Child-Pugh score >5, had a disorder affecting serum bilirubin, were taking antiviral therapy for hepatitis B or C, had lipid lowering therapy in the previous 8 weeks or more, had cancer or cancer chemotherapy, or had significant cardiovascular, cerebrovascular, renal or thyroid disease, or uncontrolled diabetes mellitus within 6 months prior to randomization.

The safety objective was to determine the number of patients who had an increase in the ALT ≥2 times the ULN for those with a normal ALT at baseline, or a doubling of the baseline ALT in those who had an elevated ALT at baseline. By these definitions, fewer patients in the pravastatin group experienced ALT elevations compared to the placebo group. The proportion of subjects who had sustained elevations in ALT was comparable, with 8/160 (5%) in the pravastatin group, and 11/160 (7%) in the placebo group. Side effects were experienced in 26.4% of pravastatin patients and 25.2% of placebo patients. Six patients receiving pravastatin and 4 patients receiving placebo experienced treatment-emergent adverse effects associated with aminotransferase elevations, and no clinically apparent hepatotoxicity was experienced in either group. The terminology “treatment-emergent adverse effects” and “clinically apparent hepatotoxicity” was not clearly defined by the study. No patients experienced an acute exacerbation of their underlying liver disease. The study was not specifically powered for the safety endpoint; however, the authors calculated that a sample size of 150 per treatment group would provide approximately 20% power for this endpoint.

A retrospective, multicenter study in the VA population was conducted to determine whether statin therapy increased the risk for developing hepatotoxicity in patients with hepatitis C.11 Eight hundred and thirty patients were divided into 3 cohorts, and the antibody to hepatitis C virus (anti-HCV) was used as a surrogate marker for hepatitis C virus (HCV) infection. Cohort 1 included 166 patients positive for anti-HCV on statin therapy, Cohort 2 included 332 patients anti-HCV positive without statin therapy, and Cohort 3 included 332 patients who were anti-HCV negative and on statin therapy. Patients were excluded from Cohorts 1 and 3 if they did not have liver function tests checked within 1 year before and after initiation of statin therapy. Patients were excluded from Cohort 2 if they did not have liver function tests checked within 1 year before and after hepatitis C diagnosis. The majority of patients were taking simvastatin or lovastatin.

Patients in Cohort 1 (anti-HCV positive + statin) had a lower percentage change in median aminotransferase levels compared with those in Cohort 2 (anti-HCV positive + no statin; AST: 1% versus 5%, respectively, P = 0.032, ALT: 7.3% versus 6.0%, respectively, P < 0.01), and Cohort 3 (anti-HCV negative + statin; AST 5%, P = 0.004; ALT 4.8%, P = 0.002). However, none of the median changes were clinically significant, as all were less than 8%. A higher percentage of patients in Cohort 1 developed mild to moderate increases in aminotransferase levels (defined as AST or ALT ≤10 times the ULN or from baseline) compared to Cohort 2 (22.9% vs. 13.3%, P = 0.009). However, Cohort 2 had a higher percentage of patients with severe increases in liver function tests (defined as serum bilirubin value >3 mg/dL, or AST or ALT >10 times the ULN or baseline) compared to Cohort 1 (6.6% versus 1.2%, P = 0.015). There was no statistically significant difference in the percentage of patients with increased aminotransferase levels who discontinued statin therapy between Cohort 1 (21.6%) and Cohort 3 (9.2%; P = 0.147). The study was not adequately powered to detect idiosyncratic drug reactions.

In another retrospective study conducted in the VA system, 146 males who were seropositive for hepatitis C and received a statin between January 1, 1995, and September 9, 2003 were evaluated.12 Patients were excluded if there were no documented baseline lipid and aminotransferase levels before the start of statin therapy, or no documented follow-up levels. Patients were also excluded if triglyceride levels were ≥400 mg/dL. Hepatotoxicity was defined as an increase in ALT >3 times the ULN.

More than 90% of patients were taking simvastatin (the formulary agent), and statins were taken for a mean of 2.5 years in the study. At baseline, 66% had ALT levels greater than the ULN, and 8% had ALT levels >3 times the ULN. There was no significant increase in ALT at short-term follow up (3–6 months), or long-term follow up (mean 22 months). One patient discontinued statin therapy due to ALT levels >3 times the ULN.

A post hoc analysis did not show a statistically significant increase in the frequency of patients with ALT levels >3 times the ULN at any point in time. When patients who had ALT levels >3 times the ULN at baseline or after statin discontinuation were excluded, only 10 patients had ALT levels >3 times the ULN while receiving statin therapy during the study period. In 3 of these patients, levels later returned to normal. Statin therapy was discontinued in 1 of the 10 patients due to excessive alcohol intake. Of the remaining 6 patients, 3 continued receiving the statin and had subsequent ALT levels between 1 and 3 times the ULN, 1 had subsequent ALT levels 4 to 5 times the ULN, 1 had therapy discontinued, and 1 was lost to follow up.

In another very small retrospective VA study, 17 male patients with a diagnosis of chronic hepatitis C taking statins were reviewed.13 Only 5 patients had elevations of aminotransferase levels while taking statins, and the greatest increase was 1.5 times the ULN.

In a retrospective Italian study reported as a letter to the editor, the safety of statin therapy in patients infected with both HIV and hepatitis C was examined.14 Patients with HIV who had taken statins were divided into 2 groups. Group A included 38 patients with HIV and hepatitis C co-infection who started statin therapy at least 6 months after diagnosis of hepatitis C. Group B included 42 patients with HIV who were hepatitis C and hepatitis B negative who were on statin therapy. Patients were excluded if they had a history of alcohol abuse, concomitant hepatotoxic medications other than antiretrovirals, or were on treatment for hepatitis C. The median age was 45.5 years, and 76.2% of patients were male.

No significant difference was found between the groups in aminotransferase levels. The percentage of patients with an increase of ≥1.5 times the baseline level of AST was 7.9% in Group A and 4.8% in Group B, and for ALT was 7.9% in Group A and 14.3% in Group B. No patients had an increase of aminotransferase levels ≥3 times the ULN, and no patients discontinued a statin due to liver toxicity. About 40% of patients actually experienced a decrease in their aminotransferase levels while on statin therapy. A positive correlation was found between patients who had a decrease in ALT and those who had higher baseline levels of ALT.

All of these studies had weaknesses, limiting their clinical applicability. Almost all patients in the studies were male, and though hepatitis C is more common in males, this may limit the applicability to female patients. Only 1 study was prospective, and it had extensive exclusion criteria, which limits the applicability to the general hepatitis C population (which often has numerous comorbidities). The other 4 studies were retrospective, and therefore not blinded or controlled. Some of the studies used positive anti-HCV as a marker for chronic HCV, which could have included patients without the disease. Other studies did not state how chronic hepatitis C was defined. The safety endpoints and definitions were not consistent between studies, and were not always the most appropriate endpoints. For example, one of the VA studies used the outcome percentage change in aminotransferase levels. If the enzymes were already increased at baseline, a percentage change would not be as significant as it would if the enzymes were normal at baseline. In general, the studies were probably not powered with a large enough sample size to detect a statistically significant difference in safety outcomes.

Potential Benefits of Statins
 
Interestingly, there is literature to support the theory that statins actually have anti-HCV activity that might be beneficial, in addition to lowering cholesterol. Statins have been identified to have antiviral properties by inhibiting hepatitis C replication.15 Lipid metabolism is part of the life cycle of many viruses, and the resulting metabolites are incorporated into a lipid raft membrane, which is enriched with cholesterols and sphingolipids.16 The hepatitis C virus also forms a replication complex on the lipid raft membrane; therefore, a reduction in cholesterol from the lipid raft structure could theoretically decrease hepatitis C viral replication.15,16 The authors of 1 in vitro study have suggested that the antiviral effect of statins might be useful in treating hepatitis C in combination with interferon alpha.17 In vivo studies have been small and inconclusive at this time.18,19

Conclusion
 
In summary, the available literature has not shown clinically significant differences in aminotransferase levels or evidence of hepatotoxicity in patients with hepatitis C who have received statins versus those who have not. Statins should continue to be avoided in advanced end-stage liver disease, as there is a lack of safety data in these patients, and drug metabolism would be severely compromised. Treatment with statins should be considered in those with chronic, stable hepatitis C with elevated cardiac risk or a previous cardiac event. If baseline AST or ALT levels are >3 times the ULN statins should be used cautiously, but can be considered if the disease is stable, as the benefit is likely to outweigh the risk of treatment.

When used in patients with hepatitis C, statins should be started at low doses, and the AST and ALT should be monitored more closely than in patients without underlying liver disease, especially at drug initiation. If elevations of >3 times the ULN do occur with statin therapy, these should be repeated and confirmed before discontinuing the drug. After enzymes return to baseline, another statin can be tried if there are no other signs of hepatitis. Alcohol use should be avoided.

We feel that, with careful monitoring of the AST and ALT, statins can be used to reduce cardiovascular risk in patients with chronic, stable hepatitis C.

References
 
1.Ghany MG, Strader DB, Thomas DL, et al; American Association for the Study of Liver Diseases. Diagnosis, management and treatment of hepatitis C: an update. Hepatology 2009;49:1335–1374.

2.Armstrong GL, Waley A, Simard EP, et al. The prevalence of hepatitis C infection in the United States, 1999 through 2002. Ann Intern Med 2006;144:705–714.

3.Ishizaka Y, Ishizaka N, Takahashi E, et al. Association between hepatitis C virus core protein and carotid atherosclerosis. Circ J 2003;67:26–30.

4.Targher G, Bertolini L, Padovani R, et al. Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C. J Hepatol 2007;46:1126–1132.

5.National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–3421.

6.Cohen DE, Anania FA, Chalasani N; National Lipid Association Statin Safety Task Force Liver Expert Panel. An assessment of statin safety by hepatologists. Am J Cardiol 2006;97:77C–81C.

7.McKenney JM, Davidson MH, Jacobson TA, et al; National Lipid Association Statin Safety Assessment Task Force. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006;97:89C–94C.

8.Anfossi G, Massucco P, Bonoma K, et al. Prescription of statins to dyslipidemic patients affected by liver disease: a subtle balance between risk and benefits. Nutr Metab Cardiovasc Dis 2004;14:215–224.

9.Russo MW, Jacobson IM. How to use statins in patients with chronic liver disease. Cleve Clin J Med 2004;71:58–62.

10.Lewis JH, Mortensen ME, Zweig S, et al. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology 2007;46:1453–1463.

11.Khorashadi S, Hasson NK, Cheung RC. Incidence of statin hepatotoxicity in patients with hepatitis C. Clin Gastroenterol Hepatol 2006;4:902–907.

12.Segarra-Newnham M, Parra D, Martin-Cooper EM. Effectiveness and hepatotoxicity of statins in men seropositive for hepatitis C virus. Pharmacotherapy 2007;27:845–851.

13.Gibson K, Rindone JP. Experience with statin use in patients with chronic hepatitis C infection. Am J Cardiol 2005;96:1278–1279.

14.Milazzo L, Menzaghi B, Corvasce S, et al. Safety of statin therapy in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr 2007;46:258–260.

15.Kim SS, Peng LF, Lin W, et al. A cell-based, high-throughput screen for small molecule regulators of hepatitis C virus replication. Gastroenterology 2007;132:311–320.

16.Ikeda M, Kato N. Life style-related diseases of the digestive system: cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: suppression of HCV replication by statins and synergistic action with interferon. J Pharmacol Sci 2007;105:145–150.

17.Ikeda M, Abe K, Yamada M, et al. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology 2006;44:117–125.

18.O'Leary JG, Chan JL, McMahon CM, et al. Atorvastatin does not exhibit antiviral activity against HVC at conventional doses: a pilot clinical trial. Hepatology 2007;45:895–898.

19.Bader T, Fazili J, Madhoun M, et al. Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol 2008;103:1383–1389.

Source

September 29, 2010

Hepatitis C Virus Faces New Weapon From Scientists

Released: 9/29/2010 12:00 PM EDT Source: Florida State University

Newswise — In recent human trials for a promising new class of drug designed to target the hepatitis C virus (HCV) without shutting down the immune system, some of the HCV strains being treated exhibited signs of drug resistance.

In response, an interdisciplinary team of Florida State University biologists, chemists and biomedical researchers devised a novel genetic screening method that can identify the drug-resistant HCV strains and the molecular-level mechanisms that make them that way –– helping drug developers to tailor specific therapies to circumvent them.

The potentially life-saving technology also works when screening other viruses with drug-resistance issues, notably human immunodeficiency virus (HIV) and influenza.

More than 170 million people worldwide are infected with HCV, which leads to both acute and chronic liver diseases.

“In collaboration with pharmaceutical firm Gilead Sciences and researchers from the University of Heidelberg (Germany), what our research team discovered was how the latest drug for HCV works and what changes in the virus that makes it resistant to this unique therapy,” said Hengli Tang, a Florida State University molecular biologist.

“This is knowledge that is essential to drug developers focused on HCV,” said Tang, “but equally important is that our method, which we call ‘CoFIM’ (Cofactor-independent mutant) screening, can also be applied to other drug targets and other viruses.

“And, since we now understand how this latest class of drug works and what causes resistance to it, we can better select other classes of drugs with distinct mechanisms –– in other words, those that target other parts of the virus –– in order to craft a combination therapy, which is the future of HCV therapy and the key to overcoming drug resistance.”

The groundbreaking research is described in a paper published online in the September 2010 issue of the journal PLoS Pathogens.

Florida State biology doctoral student Feng Yang led the research team. The award-winning scholar earned her Ph.D. in August 2010 and is now a postdoctoral associate at Yale University. Yang designed the CoFIM screening methodology with fellow FSU graduate students, postdoctoral associates and distinguished faculty colleagues –– including Associate Professor Tang; chemistry/biochemistry Professor Timothy M. Logan, director of FSU’s Institute of Molecular Biophysics; and Research Assistant Professor Ewa A. Bienkiewicz, of the FSU College of Medicine, where she directs the Biomedical Proteomics Laboratory.

Driving the team’s development of CoFIM screening was the need to identify key “cellular cofactors” and their mechanisms of action –– a fundamental aspect of virus-host interaction research.

“’Cellular cofactors’ are proteins that normally exist in host cells that have been hijacked by viruses to facilitate viral replication.” Tang said. “They became accomplices to the invading viruses.

“Our research team was the first to show that ‘cyclophilin A’ (CyPA) is an essential cellular cofactor for hepatitis C virus infection and the direct target of a new class of clinical anti-HCV compounds, which include cyclosporine A (CsA)-based drugs that are devoid of immunosuppressive function,” Tang said.

“In addition, we went a step further than other research teams by employing our newly developed CoFIM screening method, which we used to demonstrate not only HCV’s dependence on cellular cofactor cyclophilin A and susceptibility to cyclosporine A drugs but also to uncover the molecular-level regulators that determine those two traits in the virus.”

Those molecular-level regulators are known as “small interfering RNA libraries” –– collections of molecules so named for their size and ability to suppress gene expression. They act to individually suppress every gene in the cell, resulting in different consequences depending upon which gene is suppressed by a given member in the library.

The CoFIM screening method involves inducing or “coaxing” the HCV virus to mutate by itself, in vitro, absent the replication assistance it normally receives from a particular cellular cofactor. Then, CoFIM tracks the changes in the virus’s response both to CsA-based drugs and any other drug designed to inhibit the cofactor.

Funding for the research conducted at Florida State University came in largest part from a $1.4 million grant awarded by the National Institutes of Health (NIH). And, because chronic liver disease caused by HCV can lead to liver cancer, a grant from the American Cancer Society provided additional support.

In addition to now-doctoral alumna Feng Yang and faculty members Hengli Tang, Timothy M. Logan and Ewa A. Bienkiewicz, the Florida State University co-authors of the PLoS Pathogen paper (“A Major Determinant of Cyclophilin Dependence and Cyclosporine Susceptibility of Hepatitis C Virus Identified by a Genetic Approach”) are current biology doctoral students Henry Grise and Stephen Frausto and postdoctoral associates Anita Nag and Jason M. Robotham. Co-authors from the University of Heidelberg Department of Infectious Diseases are Vanesa Madan, Margarita Zayas and Ralf Bartenschlager, and from Gilead Sciences (Foster City, Calif.), Andrew E. Greenstein and Margaret Robinson.

Source

Hep C may benefit from genetic fingerprinting, research says

September 28, 2010 Genetic fingerprinting may predict who will benefit from early hepatitis C treatment and who will clear the virus spontaneously, new research shows.

The way doctors think about hepatitis C treatment is changing, with researchers saying it is now possible to use genotyping to predict which patients are likely to clear the infection spontaneously and which will benefit from early therapy.

A team of UNSW researchers, led by Professor Gregory Dore and Dr. Jason Grebely, has determined that genetic changes near the human IL28B gene - identified recently as linked to the ability to control hepatitis C infection - may also be used to identify those patients with recent infection whose own immune system is likely to clear the virus without therapy.

“The use of human genotyping may change the landscape of how we treat patients with recent HCV infection,” said Dr. Grebely, a lecturer in the Viral Hepatitis and Clinical Research Program at UNSW’s National Centre in HIV Epidemiology and Clinical Research (NCHECR).

It’s the first time that patients with early hepatitis C infection, who are likely to clear the virus on their own, might be identified and spared treatment, which is expensive and has side effects, Dr. Grebely said.

“IL28B genetic testing, prior to treatment for HCV infection, is likely to be incorporated into clinical care to identify those most likely to respond,” Dr. Grebely said. “For those patients without the favourable genotype, the doctor can proceed with treatment, knowing it is better to treat early than waiting until the condition has become chronic.”

The findings will be published this week in the journal Hepatology.

Source
Novel Agents Will Also Yield Faster Treatment Initiation of Newly Diagnosed HCV Patients, According to a New Report from Decision Resources

BURLINGTON, Mass., Sept. 27 /PRNewswire/ -- Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that the launch of novel therapies for the treatment of Hepatitis C Virus (HCV), including Vertex/Johnson & Johnson/Mitsubishi Tanabe's telaprevir and Merck's boceprevir, will precipitate several changes in HCV treatment. According to Patient Flow in Hepatitis C Virus, surveyed physicians plan to initiate treatment in at least half of their "warehoused" HCV1 patients one year after novel therapies become available. Patient "warehousing" is a term that has been coined to characterize the phenomenon of HCV patients opting out of treatment with current standard of care in anticipation of new therapies; psychiatric events, adverse events and liver health are top reasons keeping patients away from current therapies.

The report also finds that time from initial diagnosis to treatment initiation will decrease once novel HCV therapies are available. On average, surveyed physicians stated they wait 17 months to initiate treatment in HCV1 treatment-naive patients; this time will decrease to 7 months once novel treatment options are available.

"The arrival of telaprevir and boceprevir will alter more than the drug-treatment rate and treatment initiation timing in HCV," said Alexandra Makarova, M.D., Ph.D. "Physicians indicate they would increase the capacity of their HCV practice to accommodate the additional patients expected once novel therapies are available."

About Patient Flow in Hepatitis C Virus

Patient Flow in Hepatitis C Virus is a 15-year, annualized patient forecast for each of the G7 countries that estimates the total size of the declining prevalent HCV population and segments it by viremic status, HCV genotype and line of therapy. It includes two components: an Excel workbook containing quantitative analysis, including patient forecast and modifiable assumptions and a PowerPoint slide deck of primary research survey results of 100 U.S. gastroenterologists and hepatologists.

About Decision Resources

Decision Resources (http://www.decisionresources.com/) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources, Inc. company.

About Decision Resources, Inc.

Decision Resources, Inc. is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions. Please visit Decision Resources, Inc. at http://www.decisionresourcesinc.com/.

All company, brand or product names contained in this document may be trademarks or registered trademarks of their respective holders.

For more information, contact:

Decision Resources
Lisa Osgood
781-993-2606
losgood@dresources.com

Decision Resources, Inc.
Chris Comfort
781-993-2597
ccomfort@dresources.com

SOURCE Decision Resources

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September 26, 2010

Hepatitis C in Minority Populations

American Gastroenterological Association
AGA Perspectives
August-September 2010

by Andrea E. Reid, MD. MPH

Since its discovery in 1989, hepatitis C virus (HCV) has emerged as one of the leading causes of chronic liver disease. Racial and ethnic disparities in HCV prevalence have been appreciated since its discovery. In the third National Health and Nutrition Examination survey (NHANES III), the prevalence of HCV in African Americans was 3.2 percent, compared to 2.1 percent in Mexican Americans and 1.5 percent in non-Hispanic whites.1 Almost 10 percent of African American males age 40 to 49 years had HCV. NHANES data from 1999 to 2002 showed smaller disparities in HCV prevalence. However, the HCV prevalence rate among African American men age 40 to 49 years and Mexican-American men age 50 to 59 years remained high at 13.4 percent and 10 percent, respectively.2 African-American women also had higher HCV prevalence than non-Hispanic white and Mexican-American women.

HCV prevalence in other Hispanic populations has not been investigated adequately, but evidence suggests that they may have higher HCV prevalence than non-Hispanic whites, and may progress to fibrosis and cirrhosis faster.3 Chronic liver disease, due predominately to HCV and/or alcohol, is the seventh leading cause of death among Hispanics, while it is the twelfth leading cause of death in other groups. The impact of this disparity on the health-care system is significant since Hispanics are the fastest-growing demographic in the U.S.

Native American/Alaskan Natives (NA/AN) are burdened disproportionately by chronic liver disease, however HCV prevalence in NA/AN is unknown. One study documented anti-HCV antibody in 28/243 (11.5 percent) of NA patients at a large urban clinic,4 while a study of pregnant NA women documented HCV infection in 3.1 percent. The actual prevalence of HCV in NA/AN probably lies between these numbers. HCV incidence is declining for all racial/ethnic groups, however, persistent racial and ethnic differences in chronic HCV, especially among people > 40 years, illuminate an important cohort effect that will persist as infected people age.

High HCV prevalence among African Americans and Hispanics translates into a substantial risk of HCV-associated cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). A recent study documented a two- to three-fold higher incidence of HCC among African Americans and Hispanics compared to non-Hispanic whites. Much of the burden of HCC in minority populations is attributable to HCV.5

In order to prevent HCV-associated complications, we need treatment against HCV that is well tolerated and effective in most patients. Unfortunately, standard treatment for HCV — peginterferon and ribavirin — is neither. Treatment is effective in only 50 percent of patients infected with genotype 1 HCV, and African Americans and Hispanics may respond less to antiviral treatment than non-Hispanic whites. Furthermore, there are virtually no treatment data for NA/AN, as they are poorly represented in clinical trials. The Virahep-C study, a large study of African Americans and whites with genotype 1 HCV treated with peg-interferon α-2a and ribavirin, demonstrated a significantly lower sustained virologic response (SVR) rate in African Americans compared to whites (28 percent versus 52 percent).6 Inferior treatment response in African Americans has also been demonstrated with peg-interferon α-2b, and in patients with HCV genotypes two and three.

A recent study of white Hispanics with HCV suggests that they may not respond as well to antiviral treatment as non-Hispanic whites. The LATINO study demonstrated lower SVR to peginterferon and ribavirin in white Hispanics with genotype one HCV compared to non-Hispanic whites (34 percent versus 49 percent).7 However, the inclusion/exclusion criteria for this study were very narrow, and the study did not measure insulin resistance, which is prevalent in Hispanics and is associated with lower response to HCV treatment. Therefore, the LATINO study results may not apply to most HCV-infected Hispanics. Studies have shown that Hispanics are more likely than other groups to refuse treatment or to discontinue treatment prematurely. This impacts SVR and may increase the risk of HCV progression in Hispanics.

The big question remains: why don’t African Americans, and possibly Hispanics, respond to HCV treatment as well as whites? There are many theories but few answers. Racial and ethnic differences in intrinsic interferon signaling, HCV-specific T cell responses, viral kinetic response or cytokine production may play a role. Differences in body mass index, insulin resistance, steatosis, fibrosis and medication adherence have been examined, and racial and ethnic differences in these factors are insufficient to explain the inferior treatment response among African Americans and some Hispanic groups.

I am most intrigued by the recent identification of a genetic polymorphism near the IL28B gene, which encodes interferon-λ-3 and is associated with a two- to three-fold difference in treatment response among whites, African Americans and Hispanics.8 Investigators estimate that half the difference in SVR between populations can be explained by variable frequency of the CC genotype of IL28B. This genotype is found in higher frequency among whites and East Asians (groups that respond best to anti-HCV therapy) than among African Americans and Hispanics. This is a groundbreaking discovery that has the potential to change practice once a commercial test for IL28B is available. Such a test may identify patients who will respond best to antiviral therapy, and may help to identify novel targets for anti-HCV treatments.

We are on the cusp of elucidating the role(s) of race and ethnicity in HCV infection. Progress will be enhanced by well-designed clinical trials that recruit adequate numbers of racial and ethnic minorities. In the meantime, we should tell our minority patients that treatment for HCV is available, tolerable and sometimes successful; encourage their participation in clinical trials; educate our patients about the risk of HCV progression; and aggressively screen appropriate patients for HCC.

References

1.Alter MJ, Kruszon-Moran D, Nainan OV, et al. The Prevalence of hepatitis C virus infection in the United States, 1988-1994. N Engl J Med 1999;341:556-62.

2.Armstrong GL, Wasley A, Simard EP, et al. The Prevalence of Hepatitis C Virus Infection in the United States, 1999 through 2002. Ann Intern Med 2006;144:705-14.

3.Verma S, Bonacini M, Govindarajan S, et al. More advanced hepatic fibrosis in Hispanics with chronic hepatitis C infection: role of patient demographics, hepatic necroinflammation, and steatosis. Am J Gastroenterol 2006;101:1817-23.

4.Neumeister AS, Pilcher LE, Erickson JM, et al. Hepatitis-C prevalence in an urban Native-American clinic: a prospective screening study. J Natl Med Assoc 2007 Apr;99: 389-92.

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Stigma and Hepatitis C

• Foreword

Millions of Americans live with the hepatitis C virus (HCV). Although potentially life threatening, the vast majority of those with HCV will die with it and not of HCV. HCV is manageable and treatable. HCV touches the homes, workplace and communities of all those within its reach, and HCV may test the physical, emotional and spiritual health of those with it.

An often overlooked and painful component of HCV is stigma. Although invisible, stigma is a harsh reality. For some, the stigma of HCV hurts more than HCV itself. This guide discusses the ways in which HCV is stigmatized and provides tools for confronting and living with HCV’s senseless labels. Stigmas hurt all of us. We may not all have HCV, but we all live with it. Living with compassion and without stigmas is just plain good sense.

Lucinda K. Porter, RN
Writer, Hepatitis C Support Project and HCV Advocate

1. Stigma

According to the Oxford Dictionary, the definition of stigma is “a mark of disgrace associated with a particular circumstance, quality or person.” The Greek and Latin roots of stigma mean “to mark, brand or tattoo.” The dictionary Encarta defines stigma as “a sign of social unacceptability: the shame or disgrace attached to something regarded as socially unacceptable.” Merriam-Webster’s descriptions of stigma include “a mark of shame or discredit; an identifying mark or characteristic; a specific diagnostic sign of a disease.”

Sadly, hepatitis C does carry a stigma, probably for several reasons. First, HCV is potentially infectious. Although not easily transmitted, people are nevertheless fearful and shun those who have the disease. Fear and ignorance have cost patients their jobs, friendships and marriages. Hugs and kisses cease. Sexual relationships stop or are never initiated. In the extreme, even marriages have been challenged.

Another stigma associated with HCV is connected in a more general way. Some people do not like to be around people who are “sick.” The disease itself does not seem to matter. It does not have to be an infectious disease, nor one with obvious symptoms. This is probably due to fear. Some people are afraid of illness and death. They may be uncomfortable around others who have a disease or illness. Consciously or unconsciously, this discomfort may cause them to avoid those with diseases. They may also be afraid that someone they care for will die, so they reject that person rather than risk the loss.

A third stigma connected to hepatitis C is from its association with injection drug use. Misinformed people sometimes assume that all hepatitis C patients have a history of injection drug use in spite of the many ways hepatitis C can be acquired. Our society lacks compassion and understanding about injection drug use. Those who never used injection drugs do not want to carry that label. Former injection drug users feel haunted by their past and want to avoid this label. Active injection drug users carry the burden of having two stigmatized diseases—addiction and hepatitis C.

Effects of Stigma

The potentially damaging effects of stigma are elegantly described in Stigma: Hepatitis C and Drug Abuse, by Astone-Twerell, Strauss, and Munoz-Plaza.1 The authors report some of these effects as: “reduced self-esteem, diminished mental health, less access to medical care, and fear of disclosing a positive status.” Fear of disclosure may lead to reduced social support and reluctance by medical providers to care for HCV-positive patients. In particular, injection drug users have trouble accessing medical care and other human services.

In the January 2006 issue of Hepatitis magazine, the staff conducted an informal web poll about stigma and viral hepatitis (Vol. 8, No. 1, p. 53). The article reported both good and bad news. First the good news: 42% of the participants felt they had not faced any stigma due to living with hepatitis B (HBV) or hepatitis C (HCV). Now the bad news: 20% felt they had experienced job discrimination due to HBV or HCV; 13% reported hepatitis-related social stigma; 13% had been alienated from family and friends because of viral hepatitis. The most remarkable report was that 8% of those in this informal survey felt that medical professionals had denied service to them because of HBV or HCV.

It is tragic to witness this unnecessary and avoidable ostracism. Those struggling to live with a chronic disease need more support, not less. To some, the isolation is worse than the virus. This is distressing, especially when patients are newly diagnosed and need the most support.

Living with the Labels of Others

How you acquired HCV is nobody’s business. You do not need to tell anyone you have hepatitis C. However, HCV is a community problem that needs a community response. It is time to look at solutions rather than problems. Dropping the stigma is a good place to start.

What can we do about this? First, start with yourself. Do you label yourself? Do you expect to be shunned? Do you fear that others will reject you in some way? Do you have your own fears about having HCV? If so, talk about this. The best place to discuss these feelings is at an HCV support group. Learn how others live with HCV.

Do you feel like you deserve HCV as a consequence of current or past behavior? If so, there is something you need to know—no one deserves HCV. It does not matter how you acquired HCV. This virus is not a punishment or natural consequence——it is an unfortunate but unintended outcome. Guilt and remorse will not improve your health and may have a negative effect. If you struggle with negative emotions, talk to your medical provider. You may need some counseling.

Important Note: If you have thoughts of suicide or of hurting yourself or others, seek immediate professional help.

Breaking Free from Our Own Labels

We live in a label-conscious society. Clothes, sports apparel, handbags, even our eyewear dons some sort of label. But what happens if you label yourself? What would you say if you were asked, “Who are you?” Take a moment and answer that question. Make a list of everything you are. You might answer, “I am a mother or a father; a spouse, a partner, or a friend; a Buddhist, a Methodist, a Jew; a carpenter; a dentist; a hepatitis C patient. If you labeled yourself as a hepatitis C patient, this section is for you.

Labels define us. They tell others who we are. They tell us about our values and beliefs. Some labels describe our relationships and identify the people in our lives. Some labels describe what we do, such as an occupation or hobby. Declaring our religious preferences gives insight into our spiritual beliefs. However, being a hepatitis C patient is quite different from being a parent or a nurse. Saying, “I am a hepatitis C patient” defines me. It says, “I am sick.” It ties me to a state of disease rather than to a state of health.

It is easy to identify with an illness. Hepatitis C (HCV) can be all encompassing at times. Sometimes it is in the foreground; other times in the background. Nevertheless, it is always there. However, living with HCV is not the same as being an HCV patient.

This may seem like hair splitting. Before dismissing this idea, try an experiment. If you imagine or describe yourself as an HCV patient, try substituting more powerful images and words. Imagine yourself as strong and calm. Say to yourself, “I am living with hepatitis C, but I am much more than this.” How does this feel as compared to “I am a hepatitis C patient”?

There is a healthy side of identifying with an illness. We can’t let go of something without first accepting it. An important part of moving through HCV is to acknowledge it, reflect on it and recognize its meaning. In Man’s Search for Meaning, Viktor Frankl notes, “seriously ill people are often not given the opportunity to suffer bravely, and thereby retain some dignity.” He goes on to say that when we tell people to cheer up and be optimistic, the ill are made to feel ashamed of their pain and unhappiness.

Frankl is imminently qualified to speak about the human search for meaning. His contributions to modern psychotherapy were forged by his experiences as a Holocaust survivor. Frankl spent three years in Nazi death camps, including Auschwitz. The Nazis slaughtered his family. Frankl endured more than most of us. He did not let pain, torture, or grief interfere with living a life filled with compassion and integrity.

The problem occurs when a line is crossed between finding the meaning in the illness versus letting the illness define you. What does having HCV mean to you? Does it mean a lifetime of fatigue? Loss of opportunity? Perhaps HCV is a wake-up call, motivating you to make lifestyle choices that bring renewed vigor. Maybe you appreciate life more because of HCV.

A Buddhist principle is that our energy follows our attention. If we focus on illness, that is where our energy will go. Illness can take over, robbing meaning and joy from our lives. The entire self is defined by illness.

If this rings true for you, consider an attitude adjustment. Try to live in the positive rather than the negative side of life. Optimism is not wishful thinking. If an earthquake is rocking the world, it is foolhardy to act as if you are on steady ground. The wise thing is to protect yourself and others, and to try to minimize the damage. Once the shaking stops, evaluate the damage and make a recovery plan. The optimist looks at what is left and plans around this. The pessimist looks only at what is gone and in doing so, lives in the loss and pain.

Tips for Developing a Healthy Attitude

• Be honest and realistic. Do not base your attitude on thinking things are worse than they are or better than they are.

• Make sure you know the truth. Get accurate information about HCV. Some people think that HCV is an automatic death sentence. This is not true. The majority will die with HCV, not of HCV. This does not excuse you from taking care of your health, but it may free you from living with a sword over your head.

• Stay in the present. Don’t make things worse by imagining a future with pain, disability or loss.

• Accept your situation, but don’t overly identify with it. HCV may be a part of your life, but that doesn’t mean it should control your life.

• Maintain your perspective. Focus your attention on something that brings peace, joy, laughter and meaning.

• Watch your words. If you hear yourself talking negatively, substitute positive phrases. Say, “I am finding a way to live with HCV” rather than “HCV is ruining my life.”

• Try to relax. Tell yourself that difficult moments will pass.

• Visualize health, not illness. Visualization is a powerful tool for self-transformation.

• Practice gratitude. Make it a habit to find things for which you are grateful.

• Learn what you can control and what you cannot. There are things you cannot control, such as the fact that you have HCV. However, there are things you can control, such as your attitude and what you say to yourself about having HCV.

• Learn from HCV. Ask yourself what HCV can teach you about living.

• Get support. Being with others who are dealing with the same issues can bring encouragement and hope. See if there is an HCV support group in your area.

• Help others. When it comes to stepping outside of ourselves, probably nothing works as well as reaching out to others who are also struggling.

In Minding the Body, Mending the Mind, Joan Borysenko writes, “Adversity is the crucible in which the spirit is forged.” A similar expression is “that which does not kill us, makes us stronger.” Hepatitis C is an invitation to cherish each day, to live fearlessly and fully. It is the opportunity to wear a new label.

Acting Responsibly

You are not legally required to disclose your hepatitis C status. However, there are certain moral responsibilities that come with having a potentially infectious virus. First, do not attempt to donate blood, tissue or organs without complete and honest disclosure about your health. There are certain conditions in which donation is appropriate, such as for research purposes. Hepatitis C-positive organs are used in certain circumstances. Educate yourself about ways you can reduce your risk of HCV transmission to others. Act from a place of responsibility rather than a place of fear.

One final thought for reflection – there is another definition of stigma. In botany, the stigma is the part of a plant where bees deposit pollen. The stigma bears the fragrant sweet solution that attracts bees. It is a place of fertilization. For those with HCV, it may be the place where shame blossoms into hope. It is time to bring hepatitis C out of the closet and into the sunshine.

Topics for Thought or Discussion

• Do you tell others that you have hepatitis C? Whom do you tell and whom do you not tell? What are the reasons for withholding this information?

• Have you ever felt that others are uncomfortable because you have hepatitis C? If so, why do you think that is?

• Do you believe that hepatitis C carries a stigma? Why do you think this is?

• Have you ever felt uncomfortable around others who have an illness? If so, what makes you uncomfortable?

• What are your feelings about having HCV? What label(s) do you give yourself? Do you see yourself as a victim of HCV? Do you feel like you are “dirty” or a risk to others? Do you feel like your health and future have been ruined?

• Do you feel like you deserve HCV as a consequence of current or past behavior?
 
• Has hepatitis C influenced your life in any positive ways?

• Is there anything you can do to address the stigma of hepatitis C?

• What do you want others to know about your life with HCV?

• What are some actions that you might take if you felt a medical provider behaved improperly because of your HCV status?

• What are your thoughts on this statement: “I deserve HCV because I used injection drugs 20 years ago.”

• Do you have any advice for those who are newly diagnosed with HCV?

Coping with Stigma

• Educate yourself and others. Inaccurate information can perpetuate stereotypes.

• Get support. We can achieve together what we may not be able to do alone.

• Laugh at yourself and with others who have HCV. Laughing with those who share our experiences can lighten the load of HCV.

• Speak the truth, but don’t criticize or blame others. Stigma comes from ignorance and fear. Educating others may be all that is needed in order to break through stigma.

• Join a patient advocacy group.

• Tell the media or other agencies if you are offended by how HCV is portrayed. There was a tasteless and misinformed comment about hepatitis C in the film Bewitched. A letter to the movie producers is a proactive response to this stereotyping.

• Challenge stereotypes. If you do not like how marketers portray people with hepatitis C, let them know.

• Take action. Send letters, emails, faxes and phone calls to legislators, policy-makers and agencies. These are powerful tools for political and social change.

• Think globally, act locally. See if your community has an HCV task force and become a member.

• Maintain your focus and resolve. Margaret Mead said, “Never doubt that a small group of thoughtful, committed citizens can change the world. Indeed, it is the only thing that ever has.”

Resources

• Hepatitis C Support Project
- http://www.hcvadvocate.org/

• Hepatitis C Advocacy Coalition
- http://www.hepcadvocacy.org/

• Hepatitis Education Project
- http://www.hepeducation.org/

• Hep C Connection
- http://www.hepc-connection.org/

• National Hepatitis C Advocacy Council
- http://www.hepcnetwork.org/

Notes

1 “Stigma: Hepatitis C and Drug Abuse”, by Janetta Astone-Twerell, Ph. D., Shiela M. Strauss, Ph.D., and Corrine Munoz-Plaza, M.PH. National Development and Research Institutes, Inc. (2006) This article can be found under “Medical Writers’ Circle” at http://www.hcvadvocate.org/.

Copyright, September 2010
Hepatitis C Support Project / HCV Advocate http://www.hcvadvocate.org/ – All Rights Reserved.

Reprint is granted and encouraged with credit to the Hepatitis C Support Project
 
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September 25, 2010

Prevalence of Vitamin D Deficiency in Chronic Liver Disease

Authors: Arteh, J.1; Narra, S.2; Nair, S.3

Source: Digestive Diseases and Sciences, Volume 55, Number 9, September 2010 , pp. 2624-2628(5)

Publisher: Springer

Abstract:
 
Vitamin D deficiency has been associated with cholestatic liver disease such as primary biliary cirrhosis. Some studies have suggested that cirrhosis can predispose patients to development of osteoporosis because of altered calcium and vitamin D homeostasis. The aim of this study was to determine the prevalence of vitamin D deficiency in patients with chronic liver disease.

One hundred and eighteen consecutive patients (43 with hepatitis C cirrhosis, 57 with hepatitis C but no cirrhosis, 18 with nonhepatitis C-related cirrhosis) attending the University of Tennessee Hepatology Clinic had their 25-hydroxyvitamin D level measured. Severity of vitamin D deficiency was graded as mild (20-32 ng/ml), moderate (7-19 ng/ml) or severe (<7 ng/ml), normal being >32 ng/ml.

Of patients, 109/118 (92.4%) had some degree of vitamin D deficiency. In the hepatitis C cirrhosis group, 16.3% (7/43) had mild, 48.8% (21/43) had moderate, and 30.2% (13/43) had severe vitamin D deficiency. In the hepatitis C noncirrhotic group, 22.8% (19/57) had mild, 52.6% (30/57) had moderate, and 14% (8/57) had severe vitamin D deficiency. In the nonhepatitis C-related cirrhosis group, 38.9% (7/18) had mild, 27.8% (5/18) had moderate, and 27.8% (5/18) had severe vitamin D deficiency. Severe vitamin D deficiency (<7 ng/ml) was more common among patients with cirrhosis compared with noncirrhotics (29.5% versus 14.1%, P value = 0.05). Female gender, African American race, and cirrhosis were independent predictors of severe vitamin D deficiency in chronic liver disease.

Vitamin D deficiency is universal (92%) among patients with chronic liver disease, and at least one-third of them suffer from severe vitamin D deficiency. African American females are at highest risk of vitamin D deficiency.

Keywords: Vitamin D deficiency; Chronic liver disease; Cirrhosis

Document Type: Research article

DOI: 10.1007/s10620-009-1069-9

Affiliations: 1: Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN, USA 2: Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA 3: Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA, Email: snair@utmem.edu

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