Patent Application Titled "Compositions and Methods for Repair Or Regeneration of Soft Tissue" Published Online

http://news1.equities.com/2013/05/29/1456151.html

 

Purdue Research FoundationNewsRx.com

By a News Reporter-Staff News Editor at Health & Medicine Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a patent application by the inventors Nauman, Eric Allen (West Lafeyette, IN); Dickerson, Darryl (West Lafayette, IN); Dunn, Jocelyn Teresia (Lafayette, IN), filed on November 16, 2012, was made available online on May 23, 2013 (see also Purdue Research Foundation).

The assignee for this patent application, patent application serial number 679248, is Purdue Research Foundation.

Reporters obtained the following quote from the background information supplied by the inventors: "Repair of soft tissue damage resulting from injury or disease presents an important medical challenge. The ability to regenerate organs in whole or part would advance treatment of diseases such as liver disease, kidney disease, and diabetes. Repair or replacement of soft tissue would also be useful in repairing or replacing heart valves, blood vessel valves, and in repairing ligaments and tendons. Reconstructive and cosmetic surgery would also be advanced by the ability to generate soft connective tissues and adipose tissue.

"Tissue engineering has long sought to develop replacement tissues for patients suffering from organ failure, often utilizing embryonic or adult stem cells as agents of tissue repair or regeneration. Unfortunately, there have been numerous demonstrations that simply injecting stem cells, even those that have been differentiated in vitro, is insufficient. Successful tissue regeneration requires the ability to promote integration with the host and to direct the tissue growth and cell differentiation, processes that depend largely on the transport characteristics of the graft as demonstrated by Hui et al. (Journal of Biomechanics 1996; 29(1):123-132).

"Three dimensional scaffolds such as collagen-based hydrogels or poly-lactic-co-glycolic acid (PLGA)-based polymer foams, have demonstrated considerable potential, but the long-term outcomes of therapies employing these scaffolds are far from satisfactory. Collagen hydrogels are contracted by resident cells as much as 90%, making it extremely difficult to promote integration with the host tissue and to generate the necessary tissue mass for organ regeneration. In addition, as hydrogels contract, they exhibit a 100-1000 fold decrease in permeability which limits their ability to transport nutrients and waste products through the implant. The primary limitation of PLGA foams is that they degrade through an autocatalytic process into acidic by-products that are technically biocompatible, but substantially lower the pH within the tissue and often lead to cyst formation. Additional challenges posed by various formulations of PLGA include low mechanical strength relative to most tissues and a surprisingly low permeability compared to structures with similar porosities.

"There remains a need in the art for compositions and methods for regenerating damaged or diseased soft tissue."

In addition to obtaining background information on this patent application, NewsRx editors also obtained the inventors' summary information for this patent application: "In certain embodiments, the present invention provides a biocompatible scaffold made from demineralized cancellous bone that has been treated to inhibit osteoinductivity. The demineralized cancellous bone includes a region in which the collagen of the demineralized bone is stiffened. The region of demineralized bone may be stiffened by crosslinking or by physicochemically, including, but not limited to, by heating or stretching, i.e., strain hardening. The biocompatible scaffold is substantially free of mineralized bone.

"In certain embodiments the bone is cancellous or corticocancellous bone. In certain embodiments the biocompatible scaffold is machined to match, approximate, or be compatible with the shape of a soft tissue or a soft tissue defect.

"In certain embodiments, there is variation in the degree or type of crosslinking of the collagen within the crosslinked region. In certain embodiments, crosslinking is relatively low in the portion of the crosslinked region proximal to the interface between the uncrosslinked and crosslinked regions, and increases continuously or discontinuously in portions of the crosslinked region distal to the interface between the crosslinked and uncrosslinked regions.

"In certain embodiments, in the region of the biocompatible scaffold containing crosslinked demineralized bone has increased mechanical strength and/or increased resistance to degradation, e.g., enzymatic degradation, relative to the region containing uncrosslinked demineralized bone. In certain embodiments the at least one region comprising crosslinked demineralized bone does not exhibit cell attachment that is substantially different relative to the cell attachment to the at least one region comprising contiguous uncrosslinked demineralized bone. In certain embodiments the at least one region comprising crosslinked demineralized bone exhibits altered cell attachment, e.g. increased or decreased, relative to the cell attachment to the at least one region comprising contiguous uncrosslinked demineralized bone.

"In certain embodiments of the above described biocompatible scaffold, at least some portion of the scaffold, including at least some of the pores, contain a hydrogel. In certain further embodiments the hydrogel contains biomolecules. In certain other embodiments of the above described biocompatible scaffold, least some portion of the scaffold, including at least some of the pores, contain a polymer. In certain further embodiments the polymer comprises biomolecules. In certain other embodiments of the above described biocompatible scaffold, the scaffold comprises surface chemistry that includes covalently attached biomolecules and/or adsorbed biomolecules. In certain other embodiments of the above described biocompatible scaffold, the scaffold comprises a surface that has acquired texture, roughness, or three-dimensional unevenness by chemical etching and/or physical etching and/or laser etching. In certain other embodiments of the above described biocompatible scaffold, some or all regions are encapsulated by a biocompatible layer. In certain further embodiments the biocompatible layer is semipermeable and/or bioresorbable.

"Turning to another embodiment, there is provided a method for repairing or regenerating soft tissue comprising implanting in the soft tissue in need of repair or regeneration, any of the herein described biocompatible scaffolds. In certain embodiments, the soft tissue comprises organ tissue, e.g., liver tissue.

"It is an advantage that a bioscaffold according to the present invention can be designed to have features and performance characteristics suitable for the particular application(s) in which the bioscaffold will be used, including, for example, permeability needed for fluid transport, strength, flexibility, cell attachment, shape retention, porosity, connectivity, and the like.

"These and other aspects and embodiments of the herein described invention will be evident upon reference to the following detailed description and attached drawings. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference in their entirety, as if each was incorporated individually. Aspects and embodiments of the invention can be modified, if necessary, to employ concepts of the various patents, applications and publications to provide yet further embodiments.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

"FIG. 1 shows MicroCT images of vertebral (top), pelvic (middle) and femoral (bottom) porcine cancellous bone.

"FIG. 2 shows compressive stress-strain curves for demineralized cancellous bone.

"FIG. 3 is a plot of compressive tissue modulus as a function of volume fraction for various demineralized cancellous bone.

"FIG. 4 is a plot of porosity as a function of permeability.

"FIG. 5 shows compressive stress-strain curves for crosslinked and uncrosslinked samples.

"FIG. 6 is an image of a scaffold with Hoechst stained, rat fibroblast cells attached."

For more information, see this patent application: Nauman, Eric Allen; Dickerson, Darryl; Dunn, Jocelyn Teresia. Compositions and Methods for Repair Or Regeneration of Soft Tissue. U.S. Patent Application Serial Number 679248, filed November 16, 2012, and posted May 23, 2013. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=1344&p=27&f=G&l=50&d=PG01&S1=20130516.PD.&OS=PD/20130516&RS=PD/20130516

Keywords for this news article include: Tissue Engineering, Biomedical Engineering, Biomedicine, Patents, Legal Issues, Bone Research, Bioengineering, Purdue Research Foundation, Extracellular Matrix Proteins.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2013, NewsRx LLC

Source

INCIVO® (telaprevir) Receives European Commission Approval for Twice Daily Dosing for Treatment of Genotype-1 Chronic Hepatitis C Virus (HCV)

PR Newswire

BEERSE, Belgium, May 31, 2013 /PRNewswire/ --

-INCIVO® triple therapy now offers a twice daily HCV treatment regimen which should improve patient adherence^[1] -

Janssen Infectious Diseases-Diagnostics BVBA (Janssen) announced today that the European Commission (EC) has approved a new twice daily (BID) dosing of INCIVO® (telaprevir), a direct acting antiviral (DAA) protease inhibitor, in combination with pegylated-interferon and ribavirin (PR) for naive and previous treatment experienced patients. The newly approved dosing regimen for INCIVO® is now 1,125 mg twice daily in combination with PR, which aligns a morning and evening dose to the already twice daily dosing schedule for ribavirin versus 750 mg every 8 hours in combination with PR.

The EC approval is based on results from OPTIMIZE, a randomized, open-label, multicenter Phase III study in treatment naive patients with genotype-1 chronic HCV infection, which demonstrated that twice daily dosing of INCIVO® 1,125mg in combination with PR was non-inferior to the previously approved dosing every 8 hours in the proportion of patients who achieved sustained virologic response (74% versus 73%).^[2] Twice daily dosing also showed similar cure rates with twice daily or every 8 hours INCIVO dosing in patients with cirrhosis.^[3]

"The approval of INCIVO® twice daily is good news for patients with genotype-1 chronic HCV infection. Making treatments more simple and easier to manage, without compromising efficacy, will help to increase adherence and give patients an even greater chance of achieving a cure," said Dr Maria Buti, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain.

The availability of new DAAs like telaprevir has transformed treatment options for HCV.^[4] Telaprevir has already played a significant role in improving treatment outcomes with more than 80,000 patients treated with telaprevir combination therapy worldwide since it was first approved in 2011.^[5] It also offers the shortest total treatment duration of any available HCV therapy, for a high proportion of treatment-naïve or relapse patients.^[6],[7]

"Before the availability of direct acting antivirals like telaprevir, the best clinicians could hope for was to cure only 40-50% of our genotype-1 HCV patients. DAAs now offer us the chance to cure approaching 80% of these patients, for many in a shorter amount of time. Successful treatment is effectively a cure and causes a massive reduction in the complications of HCV, such as liver cancer and cirrhosis. As with many diseases early therapy is most effective and has the greatest impact on complications. The twice daily dosing of telaprevir makes the treatment easier to administer and will make it easier for patients to take advantage of the opportunity for a cure. We now need to ensure that patients with HCV are identified and offered therapy, before their disease progresses," said Graham Foster, Consultant Hepatologist, Barts Health London.

"We are pleased by the European Commission approval of twice daily dosing for telaprevir, which marks an improvement on an already important treatment option for HCV. This medicine is the cornerstone of our efforts to improve the lives of more people living with HCV and supporting healthcare professionals around the world," said Gaston Picchio, Hepatitis Disease Area Leader at Janssen.

Telaprevir was first approved by the U.S. Food and Drug Administration (FDA) in May 2011, marketed by Vertex Pharmaceuticals under the brand name INCIVEK^[TM], and by the European Commission in September 2011, marketed by Janssen Pharmaceutical Companies under the brand name INCIVO®.

About OPTIMIZE

740 naïve patients chronically infected with genotype-1 HCV were treated with either a twice daily dosing of INCIVO 1,125 mg or dosing every 8 hours of INCIVO 750 mg, each in combination with PR. At Week 12, telaprevir treatment ended and patients continued on PR alone for an additional 12 or 36 weeks depending on their viral response at Week 4. Patients were evaluated 12 weeks after treatment ended (SVR12) to monitor sustained virological response (SVR) rates.^[2]

The SVR12 rate for the twice daily group was 74% (274/369) compared to 73% (270/371) in the every 8 hour group with 95% confidence interval of the difference: -4.9%, 12.0%. The lower limit of the 95% CI (-4.9%) was greater than the pre-determined non-inferiority margin of -11% and therefore the non-inferiority of twice daily group over every 8 hour group was demonstrated.^[7]

About INCIVO® (telaprevir)

INCIVO® (telaprevir), in combination with peginterferon alfa and ribavirin (PR), is indicated for the treatment of genotype-1 chronic HCV in adult patients with compensated liver disease (including cirrhosis) who are treatment naïve, and who have previously been treated with interferon alfa (pegylated or non pegylated) alone or in combination with ribavirin, including relapsers, partial responders and null responders.^[7] INCIVO® is a small molecule, selective inhibitor of the HCV serine protease, and a member of the new class of medicine for the treatment of genotype-1 chronic HCV, direct acting antivirals (DAAs). Unlike previous treatments, DAAs act directly on viral enzymes and prevent the virus from replicating. INCIVO® was approved by the European Commission on the 19^thSeptember 2011.

INCIVO, 1,125 mg (three 375 mg film-coated tablets) should be taken orally twice daily (BID) with food. Alternatively, 750 mg (two 375 mg tablets) can be taken orally every 8 hours (q8h) with food. The total daily dose is 6 tablets (2,250 mg).^[7]

Telaprevir was developed by Janssen Infectious Diseases-Diagnostics BVBA, one of the Janssen Pharmaceutical Companies, in collaboration with Vertex Pharmaceuticals Incorporated (Vertex) and Mitsubishi Tanabe Pharma Corporation (Mitsubishi Tanabe Pharma). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK^[TM]. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries where it is being marketed as TELAVIC®.

Important Safety Information

Please see full Summary of Product Characteristics or visit http://www.emea.europa.eu for more details.

The overall safety profile of telaprevir is based on the Phase II/III clinical development programme containing 3,441 patients who received a telaprevir based regimen. In clinical trials, the incidence of adverse events of at least moderate intensity was higher in the telaprevir group than in the placebo group (both groups receiving peginterferon alfa and ribavirin). The most frequently reported adverse reactions (incidence ≥ 5.0%) of at least grade 2 in severity were anemia, rash, pruritus, nausea, and diarrhoea during the telaprevir treatment phase, and the most frequently reported adverse reactions (incidence ≥ 1.0%) of at least Grade 3 were anemia, rash, thrombocytopenia, lymphopenia, pruritus, and nausea.^[7] INCIVO® prescribing information includes special warnings and pre-cautions for use with regards to rash including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens - Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), where INCIVO, peginterferon alfa and ribavirin should be immediately and permanently discontinued and a specialist in dermatology consulted.^[7] In cases of mild and moderate rash discontinuation of INCIVO® is not always required and patients are advised to consult with a healthcare professional. In cases of severe rash immediate discontinuation of INCIVO® is required and consultation with a specialist in dermatology is recommended.^[7]

Rash events were reported in 55% of patients with a telaprevir based regimen compared to 33% of patients treated with peginterferon alfa and ribavirin only and more than 90% of rashes were of mild or moderate severity. Severe rashes were reported with telaprevir combination treatment in 4.8% of patients. Rash led to discontinuation of telaprevir alone in 5.8% of patientsand 2.6% of patients discontinued telaprevir combination treatment for rash events compared to none of those receiving peginterferon alfa and ribavirin.^[7]

Hemoglobin values of < 10 g/dl were observed in 34% of patients who received telaprevir combination treatment and in 14% of patients who received peginterferon alfa and ribavirin. In placebo-controlled Phase 2 and 3 trials, 1.9% of patients discontinued telaprevir alone due to anemia, and 0.9% of patients discontinued INCIVO combination treatment due to anemia compared to 0.5% receiving peginterferon alfa and ribavirin.^[7]

About HCV

Hepatitis C (HCV) is a contagious liver disease which is spread through blood-to-blood contact and is usually symptomless at the outset.^[8] With an estimated 150 million people infected worldwide,^[9] and three to four million people newly infected each year, HCV puts a significant burden on patients and society.^[10] Estimations indicate that HCV kills more than 350,000 people worldwide per year, accounting for approximately 1% of deaths worldwide.^[9] It is the world's primary cause of cirrhosis and liver cancer^[11] with an estimated 20-30% of patients developing liver cirrhosis^[12] and a further 7% developing liver cancer.^[13] The estimated annual cost of HCV (medical and work loss) is more than $1 billion in the U.S. alone.^[14]

About Janssen

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in infectious diseases and vaccines, oncology, immunology, neuroscience, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Please visit http://www.janssenrnd.com for more information.

###

References:

1. Sievert W et al. Adherence with Telaprevir BID vs. Q8h Dosing in Treatment Naive HCV-infected Patients: Results from the Phase III OPTIMIZE Study. J Hepatol 2013; 58(Suppl 1): S373.
2. Buti M, Agarwal K, Horsmans Y, et al. OPTIMIZE Trial: Non-inferiority of twice-daily telaprevir versus administration of every 8 hours in treatment-naïve, genotype 1 HCV infected patients. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract. (Final ID: LB-8).
3. Horsmans Y, Brown Jr. RS, Buti M, et al. Safety and efficacy of twice daily versus every 8 hour telaprevir with peginterferon/ribavirin (PR) in patients with cirrhosis. 2013. European Association for the Study of the Liver (EASL) Abstract 862.
4. Casey L C, Lee W M. Hepatitis C Virus Therapy Update 2013. Curr Opin Gastroenterol. 2013;29(3):243-249.
5. Janssen data on file.
6. Sherman K, et al. Duration of Initial Telaprevir Treatment for HCV Infection: A phase 3 study of treatment duration. N Engl J Med. 2011;365:1014-24.
7. INCIVO® Summary of Product Characteristics updated 2013.
8. Centers for Disease Control and Prevention. Hepatitis C FAQs. Available at: http://www.cdc.gov/hepatitis/C/cFAQ.htm#transmission (last accessed May 2013).
9. World Health Organization. Hepatitis C Fact Sheet. Available at: http://www.who.int/mediacentre/factsheets/fs164/en/index.html (last accessed May 2013).
10. WHO. State of the art of vaccine research and development. Viral Cancers. Available at: http://www.who.int/vaccine_research/documents/Viral_Cancers.pdf (last accessed May 2013).
11. Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med. 2011 Jun 23;364(25):2429-38.
12. Hep C Trust: Overview of Stages. Available at: http://www.hepctrust.org.uk/Hepatitis_C_Info/Stages+of+Hepatitis+C/Overview+of+the+stages (last accessed May 2013).
13. Blachier M, Leleu H, Peck-Radosavljevic M, et al. The Burden of liver disease in Europe: A review of available epidemiological data. European Association for the Study of the Liver 2013.
14. El Khoury A, Klimack W, Wallace C, et al. Economic burden of hepatitis C-associated diseases in the United States. J Viral Hep. 2012 March;19:153-160

Source

Widen care network to help target hepatitis C

Boston Globe

Letters

May 29, 2013

Your May 27 editorial “Rhode Island: Targeting a baby-boomer scourge” highlights the prevalence of the hepatitis C virus in baby boomers. The majority of new cases are between 48 and 68 years old, and most are unaware that they carry the virus. At the Boston Public Health Commission, we encourage all those born between 1945 and 1965 to get tested by their doctor, and we work to connect those without a primary care provider to care.

However, as many as 40 percent of people have not seen their primary care provider in a given year but have visited a dentist. That’s why we look for innovative ways to reach people with information about hepatitis C and testing.

Dentists and other oral health providers have a unique opportunity to provide information and link people to testing and care. With a variety of different health care professionals raising the topic of the hepatitis C virus with their patients, we hope to increase the number of those tested and linked to treatment.

Helene Bednarsh – Director - HIV dental program - Boston Public Health - Commission

Source

Can radiation therapy help resolve the liver cancer 'paradox'?

Bryant Furlow

May 29, 2013

Incidence and mortality of hepatocellular carcinoma (HCC) are increasing rapidly, and HCC is now the third leading cause of cancer death.¹ While localized, HCC is potentially curable with surgery, liver transplantation, or radiofrequency ablation.² Tragically, HCC represents a unique paradox in clinical practice, notes Theodore S. Hong, MD, of Harvard Medical School and Massachusetts General Hospital, in Boston, Massachusetts. Although HCC is localized within the liver at diagnosis, few patients (less than 30%) are candidates for potentially curable treatment strategies.^1,2 The reason for this is largely because in most cases localized HCC is diagnosed only after tumors have become multifocal, large (greater than 10 cm), and invade the vasculature, which is often associated with tumor thrombus.² Frequently, comorbidities (and risk factors for HCC) such as hepatitis B or C infection, alcohol abuse, and liver cirrhosis also compromise liver function and limit treatment options² (Table 1). Liver cirrhosis eventually develops into HCC in 5% of patients with the condition; however, up to 80% of patients with HCC have underlying liver cirrhosis. Cirrhosis-associated HCC is usually multifocal.⁵

Transarterial chemoembolization (TACE) can improve survival times for patients with HCC who are not candidates for surgery and whose tumors have not led to major vascular thrombosis.¹ Among those patients with HCC who are not candidates for TACE, sorafenib (Nexavar) may improve 1-year survival by 15%.¹ However, neither TACE nor sorafenib is curative; tumor progression is nearly universal despite these interventions.¹

Table 1. Risk Factors for hepatocellular carcinoma

α-fetoprotein (aFp) >50 ng/ml	Age >40 years
Alcohol use	Asian ethnicity (for patients with underlying liver disease)
Diabetes mellitus	Hepatitis B
Hepatitis C	Liver cirrhosis
Male sex	Tobacco use

RADIOTHERAPY OPTIONS

Until recently, the risk of radiation-induced liver disease (RILD) precluded external-beam radiotherapy as a treatment option for most patients with HCC.² Historically, two-dimensional (2D) radiography treatment planning involved large treatment volumes and precluded the determination of volumetric dose-toxicity relationships in the liver.² Delivery of potentially curative doses of ionizing radiation to tumor tissues required irradiation of relatively large volumes of nontarget liver tissue, increasing the likelihood of RILD.

But with 3D computed tomography (CT)-based treatment planning and improvements in the conformally targeted delivery of radiation doses to tumor tissue contours, radiotherapy has emerged as a more promising solution to the HCC treatment conundrum, and is becoming a more commonly used modality for HCC.^2,6 In conjunction with 3D planning tools, clinical trials and evidence-based planning to reduce the risk of RILD were also developed.² Stereotactic body radiotherapy (SBRT) allows HCC radiotherapy delivery in fewer than six dose fractions.^1,2

A new report of results from phase 1 and phase 2 nonrandomized clinical trials provide additional support for cautious optimism that SBRT is a viable option for patients who are not candidates for surgery or other curative-intent treatments.¹ Among those patients who are not candidates for surgery, TACE, or radiofrequency ablation, SBRT can yield improved survival rates with low risk of serious toxicity, according to Alexis Bujold, MD, of the Princess Margaret Hospital, University of Toronto, Canada, and colleagues.¹ Their trials enrolled 101 patients with localized HCC, more than 50% of whom had tumor vascular thrombus and a Cancer Liver Italian Program (CLIP) score of 2-4, and the median diameter of their largest tumors was 7.2 cm.¹

CLIP is one of several staging systems that, unlike traditional TNM staging, account for liver function status as well as tumor morphology and extent; the inclusion of functional criteria is believed to improve prognostic utility.^7,8 CLIP combines Child-Turcotte-Pugh (CTP) functional cirrhosis assessment scores (Table 2) with assessment of portal vein tumor invasion, number of tumors (imaged nodules), degree of liver involvement, and α-fetoprotein levels, assigning each of these factors a value of 0, 1, or 2 as follows.⁸

• CTP score Stage A, 0 points; stage B, 1 point; stage C, 2 points.
• Tumor morphology One nodule, 0 points; multinodular, 1 point; massive tumors or extension greater than 50%, 2 points.
• α-fetoprotein level Less than 400 ng/mL, 0 points; 400 mg/mL or more, 1 point.
• Portal vein tumor thrombosis No, 0 points; yes, 1 point.

The values are added together to yield an overall CLIP score. Lower CLIP scores are associated with better patient prognosis.⁸

Table 2. Calculating the CTP score for cirrhosis severity

Pointsa
	1	2	3
Albumin	>3.5 g/dl	2.8-3.5 g/dl	<2.8 g/dl
Ascites	none	Mild/moderate (diuretic-responsive)	Severe (diuretic-refractory)
Bilirubin	<2 mg/dl	2-3 mg/dl	>3 mg/dl
PT (sec prolonged) or INR	<4	4-6	>6
	<1.7	1.7-2.3	2.3
aChild-Turcotte-pugh (CTP) score is obtained by adding the scores of each parameter. CTP class: A, 5-6 points; B, 7-9 points; C, 10-15 points. Key: CTP, Child-Turcotte-Pugh; INR, international normalized ratio; PT, prothrombin time; sec, second.

In spite of the high-risk status of the study populations, Bujold's team reported achieving a 1-year local tumor control rate of 87% with SBRT.¹ Grade 3+ adverse events occurred in 30% of the trial participants (grade 3, 26.5%; grade 4, 2.9%), with seven deaths possibly related to treatment.¹ A total of 11 patients experienced serum AST/ALT abnormalities (all grade 3), nine patients experienced grade 3 platelet abnormalities, and five patients experienced grade 3 or 4 bilirubin abnormali-ties.¹ Other grade 3+ toxicities were rare, affecting two or fewer patients.¹ Median overall survival was 17 months (10.4 to 21.3 months).¹ Although promising, the authors noted that the results should be confirmed in a randomized clinical trial.

CONCLUSION

The findings contribute to a growing body of evidence that durable local control of liver tumors can be achieved with radiation.² Liver transplantation and partial hepatectomy clearly remain the gold standards for curative-intent treatment of HCC, Hong wrote; how-ever, in light of the new study, SBRT appears to be an additional alternative treatment for patients who are not candidates for curative-intent interventions, and results in outcomes com-parable to treatment with sorafenib in patients who are not candidates for sur-gery.² SBRT might therefore become a common treatment for these patients. Phase 2 local control outcomes with SBRT in patients previously treated with incomplete transarterial chemoembolization are also promising.¹⁰ Importantly, tumor vascular thrombus appears to be treatable (recanalized) with radiotherapy, presumably restoring vascular function to some degree.^1,2

The results of this trial add to the evidence base only for SBRT, and not other radiotherapy modalities such as intensity-modulated radiotherapy (IMRT). Radiotherapy planning and performance, modalities and equipment, and fractionation vary from facility to facility, cautions Hong, and these factors might affect patient outcomes.² Hong emphasized that although the study by Bujold and colleagues clearly shows that radiation is an effective local modality for treating high-risk HCC, that radiation therapy will ultimately improve survival is not a foregone conclusion.² “Even if radiation can

ablate a tumor and tumor thrombus, the competing risks of distant disease progression and underlying liver disease remain significant,” reported Hong.²ONA

---

Bryant Furlow is a medical journalist based in Albuquerque, New Mexico.

---

REFERENCES

1. Bujold A, Massey CA , Kim JJ , et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013;31(13):1631-1639. doi:10.1200/JCO .2012.44.1659.

2. Hong TS. Radiotherapy for hepatocellular carcinoma with tumor vascular thrombus: ready for prime time? J Clin Oncol. 2013;31(13):1619-1620. doi:10.1200/JCO .2012.48.2703.

3. H a NB, Ha NB, Ahmed A, et al. Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case-control study. Cancer Causes Control. 2012;23(3):455-462. doi:10.1007/s10552-012-09895-z.

4. What are the risk factors for liver cancer? American Cancer Society Web site. http://www.cancer.org/cancer/livercancer/detailedguide/liver-cancer-risk-factors. Accessed May 14, 2013.

5. Adult primary liver cancer treatment (PDQ). National Cancer Institute Web site. http://www.cancer.gov/cancertopics/pdq/treatment/adult-primary-liver/HealthProfessional/page1. Accessed May 14, 2013.

6. Klein J, Dawson LA . Hepatocellular carcinoma radiation therapy: review of evidence and future opportunity. Int J Radiat Oncol Biol Phys. 2012;pii:SO360-3016(12)03510-9. doi:10.1016/j.ijrobp.2012.08.043.

7. How is liver cancer staged? American Cancer Society Web site. http://www.cancer.org/cancer/livercancer/detailedguide/liver-cancer-staging. Accessed May 14, 2013.

8. Daniele B, Annunziata M, Barletta E, et al. Cancer of the Liver Italian Program (CLIP) score for staging hepatocellular carcinoma. Hepatol Res. 2007;37(suppl2):S206-S209. doi:10.1111/j.1872.034X.2007.00186.x.

9. Child-Turcotte-Pugh (CTP) calculator. United States Departments of Veterans Affairs Web site. http://www.hepatitis.va.gov/provider/tools/child-pugh-calculator.asp. Accessed May 14, 2013.

10. Kang JK, Kim MS, Cho CK, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012;118(21):5424-5431. doi:10.1002/cncr.27533.

Source

MicroRNA HCV Therapy Has Big Promise

By Michael Smith, North American Correspondent, MedPage Today

Published: March 27, 2013

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

Action Points

• A nonpharmaceutical approach to hepatitis C (HCV) treatment demonstrated promising efficacy and safety results in an early stage trial.
• Point out that the antisense oligonucleotide miravirsen, which binds miR-122, had no dose-limiting adverse events and did not appear to give rise to resistance.

A nonpharmaceutical approach to hepatitis C (HCV) treatment demonstrated promising efficacy and safety results in an early stage trial, researchers reported.

Blocking the liver-expressed microRNA-122 (miR-122) led to dose-dependent and persistent declines in HCV, according to Harry Janssen, MD, PhD, of the University Health Network in Toronto, and colleagues.

The antisense oligonucleotide miravirsen, which binds miR-122, had no dose-limiting adverse events and did not appear to give rise to resistance, Janssen and colleagues reported online in the New England Journal of Medicine.

The researchers noted that miR-122 binds to two sites in the HCV genome – an attachment that is essential for the "stability and propagation" of the virus. Miravirsen, in turn, binds to miR-122, making it unavailable to HCV.

Their findings – from a randomized, double blind, placebo-controlled, Phase IIa study – suggest that miravirsen might play a role in treating chronic HCV infection, the researchers concluded.

But exactly what that role is will depend on further study, experts outside the industry-supported study commented.

The results so far are "very exciting," according to Stacey Rizza, MD of the Mayo Clinic in Rochester, Minn.

"One of the challenges in hepatitis C is always resistance," she told MedPage Today. "These microRNA (inhibitors) are targeting very conserved parts of the hepatitis virus so the chance of resistance is much lower."

But, she cautioned, "It's still very early, we don't know if it's actually going to lead to the outcomes we need it to lead to -- i.e. cure – and we're not sure yet long-term whether this is going to be safe."

Indeed, the long-term safety of the substance may be important, since one of the functions of miR-122 is to act as a tumor suppressor, commented Judy Lieberman, MD, PhD, of Harvard Medical School, and Peter Sarnow, PhD, of Stanford University in Palo Alto, Calif.

But, they concluded in an accompanying editorial in the journal, "pending satisfactory answers to the questions regarding safety," miravirsen or other microRNAs might be useful in a cocktail of anti-HCV agents that would have various targets.

Miravirsen, Janssen and colleagues reported, suppressed HCV in animal studies and showed no adverse events in healthy volunteers. To advance the clinical trials, they enrolled 36 treatment-naïve patients with genotype 1 HCV and randomly assigned them to placebo or one of three doses of miravirsen -- 3, 5, or 7 milligrams per kilogram of body weight.

Patients got five subcutaneous injections over a 29-day period and were followed for 18 weeks.

Miravirsen, they reported, led to dose-dependent reduction in HCV RNA, Specifically, the average maximum drop in HCV RNA (in log₁₀ IU per milliliter) was:

• 1.2 for patients receiving 3 milligrams per kilogram, a change that was significant (P=0.01).
• 2.9 for those getting 5 milligrams per kilogram ( P=0.003).
• 3.0 for patients given 7 milligrams per kilogram, (P=0.002).
• 0.4 in the placebo group.

During the 14 weeks of follow-up after the end of treatment, HCV was not detected at some points in one patient in the 5-milligram group and in four patients in the 7-milligram group.

Several of those patients had viral rebound, suggesting that 4 weeks of miravirsen is not enough to lead to sustained virological responses, Janssen and colleagues reported.

Only two of the 112 adverse events reported miravirsen patients were above grade 2, the researchers reported, but none was dose limiting.

As well, the researchers reported that they found no mutations in the miR-122 binding sites of the HCV genome that would lead to resistance.

Rizza told MedPage Today that therapy for HCV is advancing rapidly, to the point where investigational all-oral regimens are possible that avoid the standard but difficult-to-take pegylated interferon and ribavirin.

But even those novel regimens may not be useful in all patients, so a therapy like miravirsen is likely to find a role, she said.

The study was supported by Santaris Pharma. Janssen reported financial links with the company as well as with Roche, Merck, Abbott, Anadys, Medtronic, Gilead, and Tibotec. Several authors are employees of Santaris.

Lieberman reported financial links with Alnylam. Sarnow did not report any potential conflicts.

Primary source: New England Journal of Medicine
Source reference:
Janssen HLA, et al "Treatment of HCV infection by targeting microRNA" N Engl J Med 2013; DOI: 10.1056/NEJMoa1209026.

Additional source: New England Journal of Medicine
Source reference:
udy Lieberman,Peter Sarnow "Micromanaging hepatitis C virus" N Engl J Med 2013; DOI: 10.1056/NEJMe1301348.

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Trimethylamine breath concentrations identified patients with acute alcoholic hepatitis

Provided by Healio

May 30, 2013

ORLANDO, Fla. — Acute alcoholic hepatitis can be identified via a noninvasive test measuring concentrations of trimethylamine in exhaled breath, according to data presented at Digestive Disease Week.

In a prospective, single-center study, researchers evaluated volatile breath compounds in 22 patients with acute alcoholic hepatitis (AH), 25 with acute nonalcoholic hepatitis, 30 with chronic alcoholic liver disease and 42 with chronic nonalcoholic liver disease, along with 10 healthy alcoholic and 32 healthy nonalcoholic controls. Samples were analyzed via selected-ion flow-tube mass spectrometry.

“AH is a common disease that happens in young individuals, typically after binge drinking,” researcher Ibrahim A. Hanouneh, MD, chief fellow in the gastroenterology and hepatology department of the Digestive Disease Institute at Cleveland Clinic, told Healio.com. “It’s a life-threatening disease; mortality can reach 40% to 60% in severe cases. The gold standard for the diagnosis of AH right now is liver biopsy, which can be challenging in these individuals. … We tried to come up with a noninvasive test that hopefully can replace liver biopsy.”

Of 14 evaluated compounds, seven were more prominent among patients with liver disease than controls, including acetaldehyde (P=.004), acetone (P<.001), ammonia (P<.001), ethanol (P<.001), pentane (P=.02), trimethylamine (TMA; P<.001) and 2-propanol (P<.001). TMA in particular was significantly elevated among patients with AH compared with controls and participants with other liver diseases (P<.001).

ROC analysis indicated a specificity of 94% and sensitivity of 98% for AH diagnosis with a TMA cutoff value of 31 ppb (AUC=0.99; 95% CI, 0.977-1). Researchers also observed a correlation between TMA concentration and MELD score among patients with AH (0.53; 95% CI, 0.04-1).

“If this is validated in larger trials, we can hopefully rely on breath test analysis to diagnose AH without performing invasive tests such as liver biopsy,” Hanouneh said. “When [physicians] face difficulty in making the diagnosis of AH; particularly when the patient cannot provide accurate history of alcohol intake … the breath test would be the way to go.”

Hanouneh said additional patients have been recruited for the study, and results remain unchanged. He hopes to observe a correlation between liver disease severity and the three compounds during future analysis.

Disclosure: The researchers report numerous financial disclosures.

For more information:

Hanouneh IA. Su1282: A Novel Noninvasive Breath Test in Patients with Acute Alcoholic Hepatitis. Presented at: Digestive Disease Week 2013; May 18-21, Orlando, Fla.

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New agent inhibits HCV replication in mouse models -- No resistance seen

Public release date: 30-May-2013

Contact: James Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology

Treatments against hepatitis C virus have only been partially successful. A major problem is that antivirals generate drug resistance. Now Seong-Wook Lee of Dankook University, Yongin, Republic of Korea and his collaborators have developed agents that bind to the business end of a critical protein, disabling it so successfully that no resistance has arisen. The research is published in the June 2013 issue of the Journal of Virology.

The target protein for the new agents is the NS5B replicase protein, which is the central catalytic enzyme in HCV replication. The researchers developed "RNA aptamers" which bind tightly to the part of that protein that performs the catalysis, disabling the replicase. Aptamers are short nucleic acids or peptides that provide the same level of recognition and binding ability that is common to antibodies.

The aptamers inhibited HCV replication without generating escape mutants, says Lee. Moreover, the aptamers inhibited diverse genotypes of HCV, neither causing toxicity nor inducing innate immunity, he says. Lee notes that in the study, therapeutic quantities of ligand-conjugated aptamer penetrated the liver tissue in the mice, raising the likelihood that therapeutically effective quantities could ultimately be achieved in HCV patients.

Roughly 170 million people worldwide are infected with HCV, says Lee, and it is the major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. There is as yet "no efficient and specific single regimen against HCV," says Lee. Current treatments are associated with many side effects, partly because rapid generation of drug-resistant virus has forced clinicians to use combinations of several drugs, resulting in greater numbers of side effects in patients than if a single agent could be used. And even with the drug combinations only some patients can generate a sustained antiviral response.

###

A copy of the article can be found online at http://bit.ly/asmtip0513c.

(C.H. Lee, Y.J. Lee, S.-W. Lee et al. Inhibition of hepatitis C virus (HCV) replication by specific RNA aptamers against HCV NS5B RNA replicase. J. Virol. June 2013 87:7064-7074; published ahead of print 17 April 2013 ,doi:10.1128/JVI.00405-13)

The Journal of Virology is a publication of the American Society for Microbiology (ASM). The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

Source

Future Hepatitis C Blockbusters May Spawn Compulsory Generics

By Bloomberg on 7:53 pm May 30, 2013.
Category Health
Tags: hepatitis C, HIV/AIDS, pharmaceutical industry companies firms drug makers

Hepatitis C drugs like Gilead Sciences Inc.’s sofosbuvir, which analysts forecast will become the company’s top-seller, may spawn compulsory generics in countries that can’t afford them, according to a report backed by billionaire Richard Branson.

While health officials are negotiating with drugmakers including Gilead over the price of new medicines for the deadly liver virus, developing nations should issue so-called compulsory licenses for the therapies if price reductions aren’t sufficient, according to the report by the Global Commission on Drug Policy, of which Branson and former Federal Reserve Chairman Paul Volcker are members.

Under a World Trade Organization agreement known as trade- related aspects of intellectual property rights, or TRIPS, member countries can give licenses to generic-drug makers to make low-cost copies of treatments protected by patents that are needed to address a public health emergency.

“If the prices were to be unaffordable once more in history, it would be one more scandal around inequity of access to health care,” Michel Kazatchkine, the United Nations Secretary General’s Special Envoy on HIV/AIDS in Eastern Europe and Central Asia, said at a briefing in Geneva Thursday.

“There’s no reason why a country like Ukraine wouldn’t go for this and declare a public emergency.” Liver Damage About 170 million people are infected with hepatitis C, which is transmitted commonly among drug users who share contaminated needles, and can cause liver damage and cancer.

Of 16 million people estimated to inject drugs globally, about 10 million have hepatitis C, according to Thursday’s report, which didn’t specifically name sofosbuvir.

Spokeswomen for Gilead didn’t immediately respond to a call and e-mail requesting comment sent outside regular business hours.

Gilead applied for U.S. regulatory approval of sofosbuvir last month, and the drug may cost as much as $100,000 per patient, according to Mark Schoenebaum, an analyst at ISI Group in New York. The Foster City, California-based company gained the drug with its $11.1 billion acquisition of Pharmasset Inc. last year.

The pill may earn Gilead almost $4 billion in 2015 and $6.3 billion the following year, according to the average analyst estimates compiled by Bloomberg.

Johnson & Johnson, AbbVie Inc., Merck & Co., Bristol-Myers Squibb Co. and Vertex Pharmaceuticals Inc. are among other companies developing new hepatitis C treatments.

Bloomberg

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Idenix Pharmaceuticals Announces Initiation of Phase II All-Oral Combination Study of Samatasvir (IDX719) and Simeprevir (TMC435) for the Treatment of Hepatitis C Virus (HCV) Infection

May 30, 2013

 

Phase II HELIX-1 Trial is First HCV Clinical Study to Commence Through Collaboration Agreement With Janssen Pharmaceuticals, Inc.

CAMBRIDGE, Mass., May 30, 2013 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today announced the initiation of the phase II HELIX-1 clinical trial evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of samatasvir (IDX719), Idenix's once-daily pan-genotypic NS5A inhibitor, and simeprevir (TMC435), a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB.

The HELIX-1 trial is a 12-week, randomized, double-blind, parallel group study evaluating the safety and tolerability of samatasvir and simeprevir in addition to antiviral activity endpoints, with a target enrollment of 90 treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients. Patients will be randomized equally across three treatment arms, receiving either 50, 100, or 150 mg samatasvir once-daily for 12 weeks in combination with simeprevir plus ribavirin. The HELIX-1 trial is the first study in HCV-infected patients to commence under a non-exclusive collaboration agreement signed with Janssen in January 2013. A second trial (HELIX-2) of samatasvir, simeprevir and TMC647055, a once-daily non-nucleoside polymerase inhibitor boosted with low-dose ritonavir being developed by Janssen, is expected to initiate in the second half of 2013.

"We are pleased with the progress of our samatasvir program and its advancement into phase II following successful completion of a drug-drug interaction study with simeprevir earlier this year," said Ron Renaud, Idenix's President and Chief Executive Officer. "Our goal is to initiate multiple two- and three-DAA trials of samatasvir through the Janssen collaboration. Additionally, we look forward to advancing our own internal combination of samatasvir with our lead uridine nucleotide analog by the end of this year."

ABOUT THE IDENIX/JANSSEN COLLABORATION

In January 2013, Idenix entered into a non-exclusive collaboration with Janssen Pharmaceuticals, Inc. for the clinical development of all-oral direct-acting antiviral (DAA) HCV combination therapies. The collaboration will evaluate combinations including samatasvir, simeprevir, and TMC647055. In addition to the HELIX-1 phase II trial, the companies also plan to initiate HELIX-2 which will evaluate a three-DAA combination of samatasvir, simeprevir and TMC647055/r, with and without ribavirin. The clinical trials will be conducted by Idenix. Both Idenix and Janssen retain all rights to their respective compounds under the agreement.

ABOUT SAMATASVIR (IDX719)

Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers for up to 14 days duration and up to 100 mg in HCV-infected patients up to 3 days duration. There have been no treatment-emergent serious adverse events reported in the program. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log₁₀ IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.

ABOUT SIMEPREVIR (TMC435)

Simeprevir is a once-daily potent investigational hepatitis C protease inhibitor in late phase III clinical development being jointly developed by Janssen R&D Ireland and Medivir AB to treat chronic hepatitis C virus infections. Simeprevir is being investigated in combination with PegIFN/RBV in phase III trials and is also being evaluated with direct-acting antiviral (DAA) agents in three other phase II interferon-free combinations both with and without ribavirin (RBV). For further details please visit http://www.medivir.com.

ABOUT HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 170 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with hepatitis C virus (HCV) infection. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding the Company's future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the Company's potential pipeline candidates, including any expressed or implied statements regarding the efficacy and safety of IDX719 or any other drug candidate; the successful development of novel combinations of direct-acting antivirals for the treatment of HCV; the likelihood and success of any future clinical trials involving IDX719 or our other drug candidates; and expectations with respect to funding of operations and future cash balances. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; changes in the Company's business plan or objectives; the ability of the Company to attract and retain qualified personnel; competition in general; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's quarterly report on Form 10-Q for the quarter ended March 31, 2013 as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

Source: Idenix Pharmaceuticals

News Provided by Acquire Media

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Short disease duration, worsening IBD linked after liver transplantation

Provided by Healio

May 29, 2013

ORLANDO, Fla. — Liver transplant recipients with IBD are more likely to experience worsening disease post-transplant with shorter disease duration, according to data presented at Digestive Disease Week.

Researchers performed a retrospective chart analysis of 924 patients who underwent liver transplantation (LT) between 1998 and 2012. The cohort included 45 patients with post-transplant IBD, including 38 with previous IBD and seven who developed de novo IBD after the procedure. IBD severity was determined according to symptoms, complications, hospitalizations because of flares and use of steroids or immunosuppressive medications.

Among patients with prior IBD, 39% experienced a worsening of their condition after the procedure, 11% improved and the remaining 50% had inactive IBD. Twenty-two participants, including all seven who developed post-transplant IBD, had active disease after LT.

A shorter duration of IBD before transplantation was significantly associated with a risk for worsening disease post-transplant (P=3.261E-07), particularly among those with prior IBD for 8 years or fewer. No association was observed between the risk for increased IBD severity and gender (P=.7763) ethnicity (P=.5813), smoking (P=.6614) or cytomegalovirus infection (P=.2825). The researchers said primary sclerosing cholangitis existed in the majority of patients with active post-LT IBD, but could not determine its status as a risk factor for worsening IBD because it was the major indication for LT in the study population.

“We found that 8 years or less of IBD duration at time of liver transplant might be a potential risk factor,” researcher Maiyen Tran Hawkins, DO, a fellow at Georgetown University Hospital in Washington, told Healio.com. “In knowing that potential risk factor, more aggressive medical management might be needed for those patients who have a shorter duration of IBD prior to the liver transplant, to potentially prevent or reduce their risk of worsening disease.”

Disclosure: Researchers Kirti Shetty, MD,and Aline Charabaty, MD, reported numerous financial disclosures.

For more information:

Hawkins MT. Mo1280: Inflammatory Bowel Disease Activity Following Liver Transplantation: Potential Risk Factors for De Novo Disease and for Increase in Disease Severity. Presented at: Digestive Disease Week 2013; May 18-21, Orlando, Fla.

Source

Congress Offers Free Hepatitis Tests

Rep. Hank Johnson (D-Ga.), who once battled and overcame hepatitis C, is now a champion for early hepatitis testing. Members of the House offered free screenings for hepatitis B and hepatitis C on May 23 in honor of National Hepatitis Awareness Month. (Hank Johnson)

Legislators publicize condition during National Hepatitis Awareness Month

By Ron Dory, Epoch Times | May 28, 2013

Last Updated: May 28, 2013 8:31 pm

WASHINGTON—Members of the House offered free screenings for hepatitis B and hepatitis C on May 23 in honor of National Hepatitis Awareness Month. Many people who are infected do not know they have the illness.

“For years, I, too, was unaware. But I was tested, sought treatment, and I am very fortunate to have beaten this disease. I am living proof that testing saves lives,” said Rep. Hank Johnson (D-Ga.), who has recovered from hepatitis C. Rep. Johnson is a champion of hepatitis C awareness campaigns and an advocate of testing.

The illness often has no symptoms, but if it is diagnosed early, medications can save lives, according to the Centers for Disease Control (CDC). Untreated hepatitis can cause liver damage, cirrhosis, and cancer. Of the more than 5.3 million people in the U.S. with hepatitis B and/or hepatitis C, 65 to 75 percent are not aware they are infected, according to Johnson’s constituent newsletter.

All baby boomers, born between 1945 and 1965, should be tested, according to the CDC. All Americans of Asian heritage should also be tested, according to the CDC.

The National Viral Hepatitis Roundtable, the Hepatitis B Initiative of Washington, D.C., and the Congressional Viral Hepatitis Caucus presented the testing event, one of many other events raising awareness of the disease this month.

Congressmen Johnson, Bill Cassidy, Charlie Dent and Mike Honda, along with Ron Valdiserri, Deputy Assistant Secretary for Health & Human Services and John Ward, Director of the Division of Hepatitis at the Centers for Disease Control and Prevention attended.

House staffers, including security guards, took the tests.

Volunteers and supporters of the Hepatitis B Initiative of Washington, D.C., (HBI-DC) gathered for its third annual gala fundraiser on May 19 at China Garden restaurant in Rossyln. Community partners, corporate and individual donors, and doctors and nurses who provide free screening and vaccinations recognized HBI-DC’s accomplishments.

Half of all Americans with hepatitis B are Asian-American and Pacific Islanders, according to the CDC. Approximately one in 12 AAPIs have chronic hepatitis B.

Hepatitis is defined as an inflammation of the liver, but the word also refers to strains of viruses that affect the liver, including liver cancer, according to the CDC. Being blood borne, hepatitis B can be transmitted from an infected mother to her child at birth.

When Dr. Mark Li, physician and president of the Association of Chinese American Physicians Mid-Atlantic Chapter first began to advocate for hepatitis B screening, the disease was little known in the Asian community, according to Li, and hepatitis B and C advocates did not work together. He has worked to change that, and made progress.

“I was invited by the American Liver Foundation to do an event in Congress in 2009,” said Li.

In addition to advocating, Li has conducted research on hepatitis B. His Maryland hepatitis B project connected Asian-American doctors, and the results were published in a journal for the National Medical Association in 2007. HBI-DC presented Li with an award to recognize his pro bono work screening, educating, and vaccinating people for hepatitis B .

In D.C., funding is limited for hepatitis B testing programs, according Yujiang Jia, chief epidemiologist with the Washington D.C., Department of Health HIV/AIDS Administration. However, the city offers vaccinations for hepatitis free of charge through the Department of Health Immunization Program.

Pharmaceutical drug maker AbbVie announced early this month that its hepatitis C virus infection treatment has been designated as a breakthrough therapy by the Food and Drug administration.

The breakthrough therapy designation is intended to expedite the development and review of drugs for life-threatening conditions. The all-oral 12-week treatment is in phase three testing in which the drug is administered to people who are closely monitored. It’s the last step before a drug becomes available to the public.

Source

Liver cancer on the rise, but half of cases preventable: Cancer Society

Unlike breast cancer, prostate cancer, colorectal cancer and lung cancer, cases of liver cancer are rising.

By: Helen BranswellThe Canadian Press, Published on Wed May 29 2013

Ground is being gained on many fronts in the war against cancer, but one of the deadliest — liver cancer — is still on the rise, the Canadian Cancer Society said Wednesday.

About half of liver cancer cases in Canada are probably preventable, the research and advocacy organization said as it released its annual estimates of the toll cancers will exact in Canada in 2013.

Overall, the society estimates 187,600 people will learn they have a new cancer this year (excluding non-melanoma skin cancers) and 75,500 Canadians will die from some form of the disease.

The big four remain breast cancer, prostate cancer, colorectal cancer and lung cancer, but rates of these diseases are either stable or declining, says Prithwish De, a cancer epidemiologist with the cancer society.

But the same is not true for liver cancer, which currently claims the lives of four out of five people diagnosed with it. Since 1970, the incidence of liver cancer has tripled in Canadian men and doubled in women.

Primary liver cancer — as opposed to cancer that spreads from another site to the liver — is still rare. The society estimates 2,000 people will be diagnosed with it in 2013 and 1,000 people will succumb to the disease. Worldwide, liver cancer is the third leading cause of cancer deaths, after lung and stomach cancer.

The cancer is so deadly because most cases are not found until the disease has progressed beyond the point of cure. When liver cancer is found early it generally responds well to treatment, says Dr. Sean Cleary, a liver surgical oncologist at Toronto’s University Health Network.

“One of the problems with this disease is that it does not develop symptoms or patients aren’t aware that they have the problem until the disease is very advanced, at a very large and untreatable stage,” he said.

Science has made little progress improving the survival chances of people with liver cancer. Over the past 20 years, the survival rate has risen by only between two and three per cent, De says.

But the toll the disease takes could be dramatically lowered if people at high risk of developing the liver cancer took some proactive steps, experts say.

Excess alcohol consumption, obesity and diabetes are known to be risk factors for developing liver cancer. Cutting back on alcohol and taking steps to maintain a healthy weight should lower one’s liver cancer risk, they suggest.

Another way to combat the disease is by addressing two related conditions that can be precursors to liver cancer — hepatitis B and C, which are viral infections of the liver. There is currently a vaccine against hepatitis B, but none for hepatitis C.

People who are at high risk of having one or the other infection should consider talking with their doctors about being tested for hepatitis. Treatment can often clear the infections, the experts say.

“Many individuals who are infected with either acute or chronic hepatitis infections may not be aware that they’re infected. And we’re trying to let Canadians know that there is a way to get tested and find out if you are infected by either hepatitis B or C,” says De.

Last year the U.S. Centers for Disease Control urged all baby boomers to have a one-time test for hepatitis C because of the liver cancer risk. The Canadian Liver Foundation later echoed that advice.

But the Public Health Agency of Canada is studying whether it makes sense to issue a similar recommendation in Canada, where the rate of hepatitis C is lower than in the U.S. While it deliberates, the cancer society is content to wait for evidence-based advice.

“Because we’re lacking that evidence in Canada it’s kind of premature to say whether (across-the-board) screening would be beneficial to that age group,” De says.

“And so, from the Canadian Cancer Society’s perspective, we’d like to wait until there’s a good solid base of evidence before we say anything about screening in specific age cohorts.”

Instead, they recommend a discussion about screening for people who had a blood transfusion before 1990, who use or used intravenous drugs or who moved to Canada from parts of the world where hepatitis B and C are common — Asia and sub-Saharan Africa for hepatitis B, Japan and southern Europe for hepatitis C, Cleary says.

Others at risk are people who’ve had high-risk sexual contacts and received tattoos in non-reputable tattoo parlours, he said.

“Individuals who have those risk factors are definitely candidates for speaking to their doctors about finding out whether testing for hepatitis B or C and whether any other types of counselling would be beneficial for them for reducing their risk of liver cancer,” De says.

Source

Rapid Progress and Effective Cures Usher New Era for Hepatitis C

Released:5/29/2013 4:55 PM EDT
Source Newsroom:Saint Louis University Medical Center

Adrian Di Bisceglie, M.D., chair of internal medicine and co-director of the Liver Center at Saint Louis University, urges baby boomers to learn about the risk factors for hepatitis C and talk with their physicians about screening for the virus.

Newswise — In 1989, researchers first identified the hepatitis C virus, a health threat that had been worrying doctors as they noticed patients with unexplained liver damage occurring after receiving blood transfusions. The discovery of the potentially debilitating and deadly virus sparked several decades of productive research. Researchers made unusually rapid progress, in medical research terms, and developed therapies that had success in eliminating the virus, at least in some patients. Then, in 2011, two new drugs were brought to market that changed the landscape in a dramatic way, offering a cure for many more who suffer from a chronic form of the illness.

Currently, we estimate that 4 million people in the U.S. are infected with the virus, and at least 10,000 people in this country will die from its complications each year. Symptoms of hepatitis C can be quite variable and often only develop at the most advanced stages of liver disease, years after the virus was contracted. For this reason, it is believed that roughly 60 percent of those who have the virus are unaware of it. Patients who have a chronic infection can develop inflammation of the liver, leading to fibrosis and cirrhosis, as well as other complications that may result in liver cancer and death.

While hepatitis C is sometimes compared to HIV, and, indeed both are blood-borne, the viruses behave differently. For example, hepatitis C is not frequently spread through sexual contact. It is more likely to be transmitted from a needle stick, blood transfusion or organ transplant received before 1992, recreational drug use, or from mother to infant.

(In fact, reducing hepatitis C transmission by blood donation has been a success story of its own. In the mid-1960’s, approximately one in 10 transfusions was associated with hepatitis, initially referred to as non-A, non-B hepatitis, but now known as hepatitis C. Now, thanks to an all-volunteer blood donor system, as well as questionnaires that weed out donations from those with high risk behavior, and the routine testing of donated blood for various biomarkers of hepatitis, the risk is virtually nonexistent at one in five million.)

Today, we see hepatitis C patients from all walks of life. We see captains of industry who may have contracted the virus in their youth and healthcare workers who received accidental needle sticks on the job or even young people who acquired it from their mothers at birth. Because they may only begin to show symptoms decades later, it’s often impossible to pinpoint the exact way the virus was contracted.

However, there is an inexpensive and accurate blood test for hepatitis C. Liver disease specialists advocate that those at risk ask their doctor to be tested. In particular, the CDC now recommends that all baby boomers -- those born between 1945 and 1965 -- be screened. Doctors also urge those with risk factors such as a blood transfusion prior to 1992, a history of injection drug use and abnormal liver enzymes counts be tested.

With parallel clinical trials successfully concluding in recent years, two effective new drugs, Merck’s boceprevir and Vertex’s telaprevir, were FDA approved in 2011 to treat the virus. Added to the existing treatment regimen of peginterferon and ribavirin, these new medicines can cure nearly 80 percent of those with the disease.

Though the new treatments still require the use of peginterferon, which frequently causes taxing side effects, we’ve turned a corner. The new drugs lower the average treatment time from 1 year to 6 months. More antiviral drugs against hepatitis C are in the pipeline, and their use may eventually eliminate the need for interferon altogether.

But, right now, we can tell patients with hepatitis C that treatment time is expected to be much less than a year, is far more likely to cure them, and is likely to add years to their lives. The opportunity to halt progressive liver damage is a chance to save those with the virus from debilitating fatigue, cancer and death.

Physicians now can recommend testing to patients with the knowledge that we have effective medicines to treat the virus if we find it. These new medicines are revolutionizing the care of those with hepatitis C. It’s critical that those at risk be screened so the illness can be treated.

Adrian Di Bisceglie, M.D. is chair of the department of internal medicine and co-director of the Liver Center at Saint Louis University. He also served as Liver Diseases Section Chief at the National Institutes of Health where he supervised research in viral hepatitis and was among the first to use interferon when the illness simply was known as non-A, non-B hepatitis. Throughout the search for a cure for hepatitis C, Di Bisceglie led numerous research studies and recently co-authored a New England Journal of Medicine paper on the successful telaprevir clinical trial.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.

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War on drugs 'driving hepatitis C pandemic'

Hepatitis C virus can lead to fatal liver disease

29 May 2013 Last updated at 19:44 ET

The global war on drugs is fuelling a hepatitis C pandemic causing millions of needless infections, the Global Commission on Drug Policy has warned.

Repressive drug law enforcement is driving high rates of infection among injecting drug users, it said.

Resources need to be redirected into treatment and prevention.

The Commission estimated that of 16 million people worldwide who inject drugs, 10 million are living with hepatitis C.

This puts them at risk of fatal and debilitating liver disease.

The Global Commission called on governments to decriminalise drug use and provide schemes, such as those which give access to sterile needles, to halt the spread of the disease.

"The war on drugs is a war on common sense.”

End Quote Ruth Dreifuss Global Commission on Drug Policy

The group, which includes seven former presidents, ex-UN chief Kofi Annan and other world leaders, has previously linked the "failed" war on drugs with the spread of HIV.

In its latest report it says in some countries with the harshest drug policies more than 90% of people who inject drugs are living with hepatitis C.

Eastern Europe and Central Asia have seen the fastest spread of infection and the highest number of infections has been reported in China, the Russian Federation and the USA.

Strongly enforced policies criminalising drug use force users away from public health services and locking up vast numbers of injecting users perpetuates the spread of the infection, the Commission warned in the latest report.

Hidden epidemic

Hepatitis C is highly infectious and around a quarter of those with chronic infection will develop fatal liver disease.

But the disease can go undetected for several years with no or few symptoms and many people are completely unaware they are infected.

Governments "must immediately redirect resources away from the 'war on drugs' and into public health approaches that maximise hepatitis C prevention and care", the report recommended.

Hepatitis C

• Hepatitis C is most commonly spread through blood-to-blood contact
• It is three times more prevalent than HIV among injecting drug users
• Initially it can cause no or very mild symptoms such as fever, nausea and fatigue
• In 80% of those infected the infection becomes chronic and the virus remains in the body long-term
• A quarter of those with chronic infection will develop potentially fatal liver disease
• Many people do not know they are infected until they get advanced liver disease

"Hepatitis C has to be one of the most grossly miscalculated diseases by governments on the planet," said commissioner Michel Kazatchkine, who is also the UN secretary-general's special envoy on HIV/AIDS in Eastern Europe and Central Asia.

"It is a disgrace that barely a handful of countries can actually show significant declines in new infections of hepatitis C among people who inject drugs."

The report highlighted Scotland's national Hepatitis C Action Plan as an example of best practice.

Launched in 2006, the strategy has led to a four-to-six-fold increase in the provision of sterile injecting equipment and an increase in the number of people, mainly in drug services and prisons, being tested for the infection.

The provisions put in place, which also include an eight-fold increase in the number of prisoners receiving treatment for hepatitis C, have led to falling rates of infection.

The Commission also highlights the potential for dramatic savings to countries' health and welfare budgets in the long term from preventing cases of liver disease.

"The war on drugs is a war on common sense," said commissioner Ruth Dreifuss, who is also the former president of Switzerland.

"Repressive drug policies are ineffective, violate basic human rights, generate violence and expose individuals and communities to unnecessary risks.

"The hepatitis C epidemic, totally preventable and curable, is yet another proof that the drug policy status quo has failed us all miserably."

The World Hepatitis Alliance said: "It is incomprehensible that hepatitis C, along with hepatitis B, is so consistently ignored.

"If you compare rates of hepatitis C in drug users in countries with good harm reduction and more enlightened drug policies with those in countries without, it is clear that regarding drug use exclusively as a criminal justice issue is a health disaster. Hepatitis C, its prevention, care and treatment must be addressed and must be addressed as the health issue it is."

A UK government spokesperson said: "This government is committed to breaking the vicious cycle of addiction and drug usage remains at its lowest level since records began.

"The best protection from drugs is not to take them in the first place, but we must ensure good healthcare is available for those who want to treat their addiction - and we are seeing a rise in the numbers of users exiting treatment programmes free of drugs."

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