FDA Investigates Multistate Outbreak of Hepatitis A Illnesses Potentially Associated with a Frozen Fruit Blend

FDA Investigates Multistate Outbreak of Hepatitis A Illnesses Potentially Associated with a Frozen Fruit Blend

Posted June 29, 2013
Available En Español¹
Source - FDA

Related - CDC-Multistate outbreak of Hepatitis A infections linked to pomegranate seeds from Turkey

 

 

Updates June 29, 2013  The U.S. Food and Drug Administration (FDA) will detain shipments of pomegranate seeds2 from Goknur Gida Maddeleri Ithalat Ihracat Tic (Goknur Foodstuffs Import Export Trading) of Turkey when they are offered for import into the United States.   This action results from the investigation by the FDA, the Centers for Disease Control and Prevention, and state and local health authorities into a multi-state outbreak of Hepatitis A illnesses associated with Townsend Farms Organic Antioxidant Blend, a frozen food blend containing pomegranate seed mix. By combining information gained from the FDA’s traceback and traceforward investigations and the CDC’s epidemiological investigation, the FDA and CDC have determined that the most likely vehicle for the Hepatitis A virus appears to be a common shipment of pomegranate seeds from Goknur used by Townsend Farms to make the Townsend Farms and Harris Teeter Organic Antioxidant Blends that were recalled in June.   These seeds were also used by Scenic Fruit Company to make their recently recalled Woodstock Frozen Organic Pomegranate Kernels. “This outbreak highlights the food safety challenge posed by today’s global food system,” said Michael R. Taylor, Deputy Commissioner for Foods and Veterinary Medicine. “The presence in a single product of multiple ingredients from multiple countries compounds the difficulty of finding the cause of an illness outbreak.  The Hepatitis A outbreak shows how we have improved our ability to investigate and respond to outbreaks, but also why we are working to build a food safety system that more effectively prevents them.” The FDA reviewed records and determined that the pomegranate seeds from this shipment were the only ingredient common to all of the recalled Townsend Farms and Harris Teeter Organic Antioxidant Blend.  FDA will be working with the firms that have distributed pomegranate seeds from this shipment from Turkey to help ensure that all recipients of these seeds are notified. The CDC reports that as of June 27, 2013, 127 people have been confirmed to have become ill with Hepatitis A after eating Townsend Farms Organic Antioxidant Blend.  The illnesses have been reported from 8 states: Arizona, California, Colorado, Hawaii, Nevada, New Mexico, Utah, and Wisconsin.  The people who were reported ill in Wisconsin were exposed to the product in California. The CDC reports that the outbreak strain of hepatitis A virus, belonging to genotype 1B, was found in clinical specimens of 56 people in seven states: AZ (6), CA (15), CO (22), HI (4), NM (4), NV (4) and WI (1; the person was exposed in California). This subtype is rarely seen in the Americas but circulates in North Africa and the Middle East.

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The U.S. Food and Drug Administration and the Centers for Disease Control and Prevention (CDC) and state and local officials are investigating a multi-state outbreak of Hepatitis A illnesses potentially associated with a frozen food blend. We are moving quickly to learn as much as possible and prevent additional people from becoming ill. We recognize that people will be concerned about this outbreak, and we will continue to provide updates and advice.  What is the Problem and What is Being Done About It?  The FDA, the CDC, and state and local officials are investigating a multi-state outbreak of Hepatitis A illnesses potentially associated with Townsend Farms Organic Antioxidant Blend, a frozen blend containing pomegranate seed mix.   As of June 27, 2013, 127 people infected with Hepatitis A have been reported from 8 states: Arizona, California, Colorado, Hawaii, Nevada, New Mexico, Utah, and Wisconsin. The cases from Wisconsin were exposed to the product in California. The CDC reports that the outbreak strain of Hepatitis A virus (HAV), belonging to genotype 1B, was found in clinical specimens of 56 people in 7 states.  This strain is rarely seen in the Americas but circulates in North Africa and the Middle East. On June 4, 2013, Townsend Farms, Inc. of Fairview, Oregon, recalled certain lots of its frozen Organic Antioxidant Blend3, because it has the potential to be contaminated with Hepatitis A virus.  No other Townsend Farms products, frozen or fresh, are covered by this voluntary recall or linked to the illness outbreak at this time.   The product was sold at Costco warehouse stores under the product name Townsend Farms Organic Antioxidant Blend4, 3 lb. bag and UPC 0 78414 404448. The recalled codes are located on the back of the package with the words “BEST BY”; followed by the code T012415 sequentially through T053115, followed by a letter. All of these letter designations are included in this recall for the lot codes listed above.   The product was also sold at Harris Teeter stores from April 19 until May 7, 2013, under the product name Harris Teeter Organic Antioxidant Berry Blend5, 10 oz. bag and UPC 0 72036 70463 4, with Lot Codes of T041613E or T041613C and a “BEST BY” code of 101614.   On June 28, 2013, Townsend Farms, Inc. expanded its recall6 to include Townsend Farms Organic Antioxidant Blend, 3 lb. bag with UPC number 0 78414 40444 8. The recall codes are located on the back of the package with the words “BEST BY” followed by the code T122114 sequentially through T053115, followed by a letter. All letter designations are included in the recall. On June 14, 2013, the Jackson County Oregon Health Department warned customers of Evo’s Coffee Lounge, in Ashland, Oregon, that they may have been exposed to Hepatitis A in the coffee shop's "Radically Free" smoothie served between May 17 and June 12, 2013.  The coffee shop used Townsend Farms Organic Antioxidant Blend to produce this menu item. The Jackson County Health Department also alerted those who may have been exposed in the last 14 days of the availability of Hepatitis A vaccine in the local area. On June 19, 2013, the Mendocino County Public Health Department warned customers of A Frame Espresso in Fort Bragg Calif. that they may have been exposed to Hepatitis A in the coffee shop's "Mixed Berry" smoothie served between March 4 and June 8, 2013.  The smoothies may have contained Townsend Farms Organic Antioxidant Blend. On June 26, 2013, Scenic Fruit Company of Gresham, Oregon recalled specific lots of Woodstock Frozen Organic Pomegranate Kernels7 because they have the potential to be contaminated with the Hepatitis A virus. Woodstock Organic Pomegranate Kernels are sold in eight-ounce (227 gram) resealable plastic pouches (see image8) with UPC Code 0 42563 01628 9. Specific coding information to identify the product can be found on the back portion of these pouches below the zip-lock seal. The following lots are subject to this recall:   C 0129 (A,B, or C) 035 with a best by date of 02/04/2015   C 0388 (A,B, or C) 087 with a best by date of 03/28/2015   C 0490 (A,B, or C) 109 with a best by date of 04/19/2015   The recalled Scenic Fruit products  were shipped from February 2013 through May 2013 to United Natural Foods, Inc. (UNFI) distribution centers in California, Colorado, Connecticut, Florida, Georgia, Indiana, Iowa, New Hampshire, Pennsylvania, Rhode Island, Texas, and Washington State. UNFI distribution centers may have further distributed products to retail stores in other states. The FDA has finalized a protocol to test berries for the Hepatitis A virus (HAV), and is testing samples related to the outbreak for the presence of HAV. The FDA has also inspected the processing facilities of Townsend Farms of Fairview, Oregon. By combining information gained from the FDA’s traceback and traceforward investigations and the CDC’s epidemiological investigation, the FDA and CDC have determined that the most likely vehicle for the Hepatitis A virus appears to be a common shipment of pomegranate seeds from Goknur used by Townsend Farms to make the Townsend Farms and Harris Teeter Organic Antioxidant Blends that were recalled in June.   These seeds were also used by Scenic Fruit Company to make their recently recalled Woodstock Frozen Organic Pomegranate Kernels. The FDA reviewed records and determined that the pomegranate seeds from this shipment were the only ingredient common to all of the recalled Townsend Farms and Harris Teeter Organic Antioxidant Blend.  FDA will be working with the firms who have distributed pomegranate seeds from this shipment from Turkey to help ensure that all recipients of these seeds are notified. The FDA is working closely with the CDC and state and local agencies and will provide updates as soon as they become available.

What is Hepatitis A?
Hepatitis A is a contagious liver disease that results from infection with the Hepatitis A virus. It can range in severity from a mild illness lasting a few weeks to a severe illness lasting several months. Hepatitis A is usually spread when a person ingests fecal matter — even in microscopic amounts — from contact with objects, food, or drinks contaminated by the feces, or stool, of an infected person.

What are the Symptoms of Hepatitis A?
Illness occurs within 15 to 50 days of exposure and includes fatigue, abdominal pain, jaundice, abnormal liver tests, dark urine and pale stool.

Who is at Risk?
Hepatitis A is a human disease and usually occurs when an infected food handler prepares food without appropriate hand hygiene.  However, food contaminated with HAV, as is suspected in this outbreak, can cause outbreaks of disease among persons who eat or handle food.

In rare cases, particularly in patients with pre-existing severe illness or immune compromise, HAV infection can progress to liver failure and death.  Persons with underlying liver conditions should be vaccinated.

What is being Recalled?
On June 4, 2013, Townsend Farms, Inc. of Fairview, Oregon, recalled certain lots of its frozen Organic Antioxidant Blend⁹ on June 4, 2013, because it has the potential to be contaminated with Hepatitis A virus.  No other Townsend Farms products, frozen or fresh, are covered by this voluntary recall or linked to the illness outbreak at this time. The product was sold at Costco warehouse stores under the product name Townsend Farms Organic Antioxidant Blend¹⁰, 3 lb. bag and UPC 0 78414 404448. The recalled codes are located on the back of the package with the words “BEST BY”; followed by the code T012415 sequentially through T053115, followed by a letter. All of these letter designations are included in this recall for the lot codes listed above.The product was also sold at Harris Teeter stores from April 19 until May 7, 2013, under the product name Harris Teeter Organic Antioxidant Berry Blend¹¹, 10 oz. bag and UPC 0 72036 70463 4, with Lot Codes of T041613E or T041613C and a “BEST BY” code of 101614.

On June 28, 2013, Townsend Farms, Inc. expanded its recall¹² to include Townsend Farms Organic Antioxidant Blend, 3 lb. bag with UPC number 0 78414 40444 8. The recall codes are located on the back of the package with the words “BEST BY” followed by the code T122114 sequentially through T053115, followed by a letter. All letter designations are included in the recall.

On June 26, 2013, Scenic Fruit Company of Gresham, Oregon recalled specific lots of Woodstock Frozen Organic Pomegranate Kernels¹³ because they have the potential to be contaminated with the Hepatitis A virus.

Woodstock Organic Pomegranate Kernels are sold in eight-ounce (227 gram) resealable plastic pouches (see image¹⁴) with UPC Code 0 42563 01628 9. Specific coding information to identify the product can be found on the back portion of these pouches below the zip-lock seal. The following lots are subject to this recall:

  C 0129 (A,B, or C) 035 with a best by date of 02/04/2015
  C 0388 (A,B, or C) 087 with a best by date of 03/28/2015
  C 0490 (A,B, or C) 109 with a best by date of 04/19/2015
 

The recalled Scenic Fruit products were shipped from February 2013 through May 2013 to United Natural Foods, Inc. (UNFI) distribution centers in California, Colorado, Connecticut, Florida, Georgia, Indiana, Iowa, New Hampshire, Pennsylvania, Rhode Island, Texas, and Washington State. UNFI distribution centers may have further distributed products to retail stores in other states.

On June 26, 2013, Scenic Fruit Company of Gresham, Oregon recalled specific lots of Woodstock Frozen Organic Pomegranate Kernels¹⁵ because they have the potential to be contaminated with the Hepatitis A virus.

Woodstock Organic Pomegranate Kernels are sold in eight-ounce (227 gram) resealable plastic pouches (see image¹⁶) with UPC Code 0 42563 01628 9. Specific coding information to identify the product can be found on the back portion of these pouches below the zip-lock seal. The following lots are subject to this recall:

  C 0129 (A,B, or C) 035 with a best by date of 02/04/2015
  C 0388 (A,B, or C) 087 with a best by date of 03/28/2015
  C 0490 (A,B, or C) 109 with a best by date of 04/19/2015
 

The recalled Scenic Fruit products  were shipped from February 2013 through May 2013 to United Natural Foods, Inc. (UNFI) distribution centers in California, Colorado, Connecticut, Florida, Georgia, Indiana, Iowa, New Hampshire, Pennsylvania, Rhode Island, Texas, and Washington State. UNFI distribution centers may have further distributed products to retail stores in other states.

What Do Consumers and Retailers Need To Do?

Consumers should not eat the recalled products and should discard any remaining product from their freezers. Even if some of the product has been eaten without anyone in your home becoming ill, the rest of the product should be discarded.

Retailers and other food service operators should not sell or serve the recalled products.

See the CDC's recommendations concerning vaccination for Hepatitis A in regard to this outbreak here¹⁷.

Who Should be Contacted?
For more information on the Townsend Farms recall, consumers may contact a Townsend Farms Customer Service Representative by phone or e-mail at 1-800-875-5291; townsendfarms5148@stericycle.com.  Customer service representatives will be available Monday through Friday, 7 a.m. to 4 p.m. PDT to respond to inquiries.

For more information on the Scenic Fruit Company recall, consumers may contact the Scenic Fruit Company at 877-927-3434 or email to info@scenicfruit.com from Monday through Friday, 8 a.m. to 8 p.m. PDT

For information on Hepatitis A and the vaccine, consumers may call the CDC information line at 1-800-CDC INFO between 8 a.m. and 8 p.m. Eastern time.

The FDA encourages consumers with questions about food safety to call 1-888-SAFEFOOD Monday through Friday between 10 a.m. and 4 p.m. Eastern time, or to consult the fda.gov website: www.fda.gov¹⁸.

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The information in this release reflects the FDA’s best efforts to communicate what it has learned from the manufacturer and the state and local public health agencies involved in the investigation. The agency will update this page as more information becomes available. For more information:

• CDC:   Multistate outbreak of Hepatitis A potentially associated with "Townsend Farms Organic Antioxidant Blend" frozen berry and pomegranate mix ¹⁹
• FoodSafety.gov on Hepatitis A²⁰

 

Hope for HCV Patients Who Failed Therapy With Telaprevir or Boceprevir

Clinical Care Options
Hope for HCV Patients Who Failed Therapy With Telaprevir or Boceprevir

Mark S. Sulkowski, MD - 6/28/2013

*Free registration required to view article and links

Sky-High Expectations, Tempered by Reality
In 2011, the FDA approved the first 2 DAAs: boceprevir and telaprevir. They represented a new era of agents that directly attacked the hepatitis C virus itself, instead of working indirectly by stimulating the patient’s native antiviral immune system. With the new DAAs in combination with peginterferon/ribavirin came higher rates of SVR and the perception that hepatitis C therapy had turned a corner into a very promising future. However, not every patient benefited from that promise, and for an unfortunate group of patients who failed to achieve SVR with triple therapy, the future has been clouded with uncertainty, including questions over the clinical significance, if any, of the selection and enrichment of a population of telaprevir- and boceprevir-resistant HCV variants to protease inhibitors that they invariably developed.

A Robust Pipeline
Now, we’re beginning to recognize that these patients are not without HCV treatment options. New classes of drugs with multiple agents in development are extending and expanding the optimism first engendered by the first-generation DAAs. In clinical trials, drugs from classes as diverse as NS3/NS4A protease inhibitors, nucleos(t)ide analogues, NS5A inhibitors, and NS5B polymerase inhibitors are demonstrating greater efficacy with fewer adverse events and shorter treatment courses with and without peginterferon/ribavirin.

Initial clinical trials have reported very promising efficacy in HCV treatment-naive patients as well as those who have failed previous therapy with peginterferon/ribavirin, including “null” responders. Amidst this flood of new data, those patients who did not achieve SVR when treated with telaprevir or boceprevir finally have data that are very encouraging. At the 2013 European Association for the Study of the Liver conference, my colleagues and I presented data demonstrating that an all-oral, once-daily combination of sofosbuvir and daclatasvir, without even ribavirin, administered for 24 weeks produced 12-week SVR rates of 95% to 100% in genotype 1 HCV–infected virologic nonresponders to previous telaprevir- or boceprevir-based therapy. Indeed, the overall SVR rate was 100%. These rates remained constant even in the presence of baseline NS3 variants conferring resistance to these first-generation protease inhibitors. Although not yet presented in a scientific forum, similar treatment success was recently announced in the LONESTAR study in which triple therapy failures were treated with sofosbuvir and ledipasvir with and without ribavirin.

Reassurance for DAA “Pioneers”
Such was the excitement generated by the first DAAs that many patients and clinicians were quick to take advantage of them. Fortunately, many patients treated with telaprevir or boceprevir triple therapy achieved SVR. However, for an unfortunate minority of these DAA “pioneers,” treatment failed either due to toxicity or virologic failure. For these patients, we now have very promising data that should reassure them that they have not reached the end of their treatment options. I believe the important message here is that a cure is not only possible for patients who failed previous HCV protease inhibitors, but it may be even be “easy” in the future using combinations of oral DAAs that attack the virus at the viral polymerase (nucleos(t)ide analogues) and the NS5A glycoprotein. While we wait for the approval and greater availability of such therapies, I’ve been educating my patients about these future approaches and focusing my attention on modifiable factors to improve hepatic health, namely avoiding alcohol, achieving or maintaining a normal body mass index and, perhaps, consuming more coffee. Yes, more coffee; I’ll save further discussion of coffee and the liver for another time!

Your Thoughts?
How do you manage your DAA treatment failure patients? Are you counseling your patients to begin treatment with the new drugs as soon as they become available, or are you urging patience to wait for the optimal regimens to be identified??

Topics: HCV - Treatment 

 

Related from CCO-

HCV Approved & Phase III - Source: 2013 Annual Meeting of the European Association for the Study of the Liver*  

 

CDC-Multistate outbreak of Hepatitis A infections linked to pomegranate seeds from Turkey

CDC-Multistate outbreak of Hepatitis A infections linked to pomegranate seeds from Turkey

Posted June 28, 2013 2:00 PM ET

CDC is collaborating with public health officials in several states and the US Food and Drug Administration (FDA) to investigate a multistate outbreak of Hepatitis A illnesses. Results from the ongoing investigation are highlighted below.

Highlights

Epidemiologic Investigation:

Read the Advice to Consumers »
As of June 27, 2013, 127 people have been confirmed to have become ill from Hepatitis A after eating ‘Townsend Farms Organic Anti-oxidant Blend’ in 8 states: Arizona (17), California (64), Colorado (25), Hawaii (7), New Mexico (5), Nevada (5), Utah (2), and Wisconsin (2).
[Note: The cases reported from Wisconsin resulted from exposure to the product in California.]

71 (58%) ill people are women

Ages range from 2 – 84 years;
74 (61%) of those ill were between 40 – 64 years of age.
6 children under age 18 were also ill. None were previously vaccinated.
Illness onset dates range from 3/31/2013 – 6/15/2013
55 (45%) ill people (all over 18 years of age) have been hospitalized, and no deaths have been reported

All those who reported eating this product purchased it from Costco markets; however, the product was also sold at Harris Teeter stores. No cases have been identified that bought the product at Harris Teeter at this time.

Laboratory Investigation:

The outbreak strain of hepatitis A virus, belonging to genotype 1B, was found in clinical specimens of 56 people in seven states: AZ (6), CA (15), CO (22), HI (4), NM (4), NV (4) and WI (1; the person was exposed in California). This subtype is rarely seen in the Americas but circulates in North Africa and the Middle East.

This genotype was identified in a 2013 outbreak in Europe linked to frozen berries and another 2012 outbreak in British Columbia related to a frozen berry blend with pomegranate seeds from Egypt. However, there is no evidence at this time that these outbreaks are related to the ongoing U. S. outbreak.

Regulatory Investigation:

On June 3, 2013, Townsend Farms, Inc. of Fairview, Oregon voluntarily recalled certain lots of its frozen Organic Antioxidant Blend because it has the potential to be contaminated with hepatitis A virus.

FDA is inspecting the processing facilities of Townsend Farms of Fairview, Oregon.
By combining information gained from the FDA’s traceback and trace forward investigations and the CDC’s epidemiological investigation, FDA and CDC have determined that the most likely vehicle for the Hepatitis A virus is appears to be a common shipment of pomegranate seeds from Turkey used by Scenic Fruit Company to make the recalled Woodstock Frozen Organic Pomegranate Kernels and by Townsend Farms to make the recalled Townsend Farms and Harris Teeter Organic Anti-Oxidant Blend.

The FDA reviewed records and determined that the pomegranate seeds from this shipment were the only ingredient common to all of the recalled Townsend Farms and Harris Teeter Organic Anti-Oxidant Blend.

On June 26, 2013, Scenic Fruit Company of Gresham, Oregon recalled specific lots of Woodstock Frozen Organic Pomegranate Kernels.
Combining information gained from the FDA’s traceback and trace forward investigations and the CDC’s epidemiological investigation, it has been determined that the vehicle for the Hepatitis A virus is a common shipment of pomegranate seeds from Turkey used by Scenic Fruit Company in making the recalled Woodstock Frozen Organic Pomegranate Kernels and by Townsend Farms in making Townsend Farms Organic Anti-Oxidant Blend

FDA will be working to identify and contact other food processors who may have also received pomegranate seeds from this shipment from Turkey, so that products using these seeds may be recalled.

FDA has finalized a protocol to test berries for the Hepatitis A virus, and is testing samples related to the outbreak for the presence of the virus.

According to the label, the “Townsend Farms Organic Anti-Oxidant Blend” frozen berry and pomegranate mix associated with illness contained products originating from the U.S., Argentina, Chile, and Turkey.

At a Glance:

• Cases exposed to ‘Townsend Farms Organic Anti-oxidant Blend’: 127
• States: 8*
• Deaths: 0
• Hospitalizations: 55
• Recall: Yes

*The cases reported from Wisconsin resulted from exposure to the product in California

Vaccine and IG Information:
Hepatitis A Vaccine Schedule
Postexposure Prophylaxis - Use of vaccine and IG
Source for IG

More Information:
Advice to Consumers & Retailers
Hepatitis A Information
Key Resources
 

Mediterranean diet improved hepatic steatosis, insulin sensitivity in patients with NAFLD

Mediterranean diet improved hepatic steatosis, insulin sensitivity in patients with NAFLD

Ryan MC. J Hepatol. 2013;59:138-143.

June 28, 2013

Patients with nonalcoholic fatty liver disease reduced their liver steatosis and improved their insulin sensitivity by adhering to a 6-week Mediterranean diet without experiencing weight loss in a recent study.

Using a cross-over dietary intervention study, researchers compared the results of 12 participants (six men, six women), all with biopsy-proven nonalcoholic fatty liver disease (NAFLD). All were randomly assigned to both a Mediterranean diet and a low-fat, high-carbohydrate diet (LF/HCD) with a 6-week washout period between diets. The MD was high in monounsaturated fats from olive oil and omega 3 polyunsaturated fatty acids. The LF/HCD was low in saturated and unsaturated fats and included more carbohydrates than the MD...

Full Story »

Updates: Idenix FDA's No New 'Nuc' Attitude and Interferon Free Drugs Near Approval

 

Website Updates:

In The News June 27

Investment Commentary
Idenix Maintains HCV Hopes Despite FDA's No New 'Nuc' Attitude
On June 20, the company announced that the FDA asked for additional preclinical safety  information on IDX20963. Initiating clinical trials for this one will need to  wait until the FDA is finished playing the wait-respond-wait game.

Idenix's recently shelved IDX20963 is a uridine nucleotide prodrug. Although Idenix insists that it is significantly different than BMS-094, I don't think the FDA is about to allow any "nucs" to enter clinical trials without excessive preclinical safety data. Luckily, Idenix is still in the HCV race with its NS5A  inhibitor samatasvir.

Fruit Company recalls pomegranate kernels in 12 states due to Hepatitis A risk
In a press release this morning, The FDA announced the voluntary recall of Woodstock Frozen Organic Pomegranate Kernels, produced by the Scenic Fruit Company of Gresham, Oregon

All-oral HCV therapies near approval
Source: Nature Reviews Drug Discovery
Published online May 31 2013

Delivering a cure for hepatitis C infection
MedNous  June 2013
Business strategy
This article was prepared by the editors on the basis of a literature review and interviews and email correspondence with Medivir AB; Janssen Research & Development LLC; Gilead Sciences Inc; AbbVie Inc; Inovio Pharmaceuticals Inc; and the European Medicines Agency

Interferon Free Therapies In Development To Treat Hepatitis C

In Case You Missed It - Review Article: Hepatitis C Virus Infection: Looking for Interferon Free Regimens
Recent developments of new drugs' combinations are changing the treatment paradigm in hepatitis C virus infection. Due to the side effect profile of pegylated interferons, interferon-sparing regimens have become the main target in chronic hepatitis C treatment research.

FDA takes action to protect consumers from dangerous medicines sold by illegal online pharmacies
The U.S. Food and Drug Administration, in partnership with international regulatory and law enforcement agencies, took action this week against more than 9,600 websites that illegally sell potentially dangerous, unapproved prescription medicines to consumers. These actions include the issuance of regulatory warnings, and seizure of offending websites and $41,104,386 worth of illegal medicines worldwide.

Related@CNN
FDA shuts down 1,677 online pharmacies
The FDA said it has shut down 1,677 sites for selling counterfeit or substandard medication, or for selling drugs without appropriate safeguards. Other sites received regulatory warnings. Officials said they also arrested 58 people and seized more than $41 million worth of illegal medicines.

Many experts agree the problem is daunting. The National Association of Boards of Pharmacy recently performed an analysis of more than 10,000 websites, and found that 97% did not fully comply with state and federal regulations. It said 88% did not require a valid prescription, and almost half sold medicines lacking FDA approval

HCV triple therapy post-liver transplant yields moderate response, significant adverse events

Presentation, Outcomes, and Response to Therapy Among Patients with Acute Exacerbation of Chronic Hepatitis C - spikes in ALTs in chronic infection

HHS releases new Public Health Service guideline to reduce disease transmission through organ transplantation

Hepatitis C Treatment – A Five Part Series: Part One – The Evolution of Hepatitis C Treatment 
Lucinda K. Porter, RN, author of Free from Hepatitis C and the upcoming Hepatitis C Treatment One Step at a Time (Sept release by Demos Health) blogs at www.LucindaPorterRN.com

The debate is over – hepatitis C is curable. When I was infected in 1988, this virus didn’t even have a name, let alone a treatment for it. Not only is there treatment for hepatitis C, there is more than one, and many more in development.

Read article here...

In part 2, I will discuss the most common side effects of current hepatitis C treatment. In part 3 I will suggest tips to manage common side effects, and in part 4 I will give some specific, tried and true suggestions for managing the most common side effects that occur during triple therapy.  Part 5 is devoted to what is ahead for hepatitis C treatment. 

 

Emerging Therapeutic Targets for Hepatitis C Virus Infection

The era of DAA therapy in the treatment of hepatitis C is evolving rapidly. The leap forward from the initial proof of concept that HCV infection can be cured without IFN to showing that cure can be attained in an extraordinarily high proportion of patients has occurred more quickly than most observers had anticipated

NICE issues guideline on the diagnosis and management of chronic hepatitis B
NICE has published its clinical guideline on the diagnosis and management of chronic hepatitis B. It aims to ensure the growing number of people with this potentially life-threatening disease are referred to a specialist and receive the right treatments.

Book raises alarms about alternative medicine - USA Today
The 12-year-old girl arrived at the hospital wracked with abdominal pain.
Doctors diagnosed her with acute pancreatitis, in which pancreatic enzymes begin digesting not just food, but the pancreas itself.
The most likely cause of the girl's condition: toxic side effects from more than 80 dietary supplements, which the girl's mother carried in a shopping bag, says Sarah Erush, clinical pharmacy manager at Children's Hospital of Philadelphia, where the girl was treated last summer

Of Interest
How do you sleep?

Modern sleep patterns cause ill health, so it is time to work out how much rest we really need.

Additional updates on the website:

2013 - HCV Triple-therapy Side Effects
HCV triple therapy post-liver transplant yields moderate response, significant adverse events
Webcast - Managing Rashes Associated with Anti-HCV Triple Therapy
Hep C Treatment: Ten Factors Make a Difference with Side Effects
Video- Hepatologist Urges caution among clinicians in the administration of telaprevir
HCV treatment improves survival among anemic patients

Stem Cells
A Science First: Japanese researchers grow human liver using stem cells
Death of 3 politicians following stem cell treatment probed
New Liver Cell for Cellular Therapy to Aid in Liver Regeneration

2013/HCV Multimedia Videos Podcasts
Contemporary Clinical Medicine: Great Teachers: Hepatitis C: From Hippocrates to Cure

Liver Health
Nature - Gut microbes spur liver cancer in obese mice

Intestinal bacteria of obese mice brew up carcinogens to trigger liver cancer.

Healio: HCV triple therapy post-liver transplant yields moderate response, significant adverse events

HCV triple therapy post-liver transplant yields moderate response, significant adverse events
June 27, 2013

Liver transplant recipients with hepatitis C experienced moderate early response rates but frequent side effects from triple therapy with antivirals in a recent study.

Researchers evaluated 60 liver transplant recipients with recurrent HCV genotype 1 and significant fibrosis who underwent treatment with pegylated interferon alfa-2a and ribavirin (PEG/RBV) and either telaprevir (TVR) (n=35) or boceprevir (BOC) (n=25), with a minimum follow-up of 12 weeks (mean follow-up, 35 weeks).
Full Story » 

USPSTF recommends HCV testing for high-risk adults, baby boomers June 26, 2013
The United States Preventive Services Task Force recently recommended screening for adults at high risk for hepatitis C virus infection and one-time screening for all Americans born between 1945 and 1965 because the birth cohort is at greater risk for infection compared with other age groups.
Full Story

 Meta-analysis linked NAFLD, vitamin D deficiency
June 26, 2013
Researchers performed a systematic review of 17 case-control and cross-sectional studies, assessing the association between nonalcoholic fatty liver disease (NAFLD) and serum levels of 25-hydroxy vitamin D (25[OH]D). Included studies were selected from PubMed and EMBASE databases and published before April 22, 2013, evaluated vitamin D levels among cases and controls, and were based in North America (six studies), Asia (four studies) and Europe or Israel (seven studies).
Full Story...

Drug-Induced Liver Injury Is On the Rise

Drug-Induced Liver Injury Is On the Rise

Bethesda, MD (June 26, 2013) — More people are being affected by drug-induced liver injury (DILI) than ever before, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association. This type of liver injury results from the use of certain prescription and over-the-counter medications, as well as dietary supplements, and is among the more challenging forms of liver disease due to its difficulty to predict, diagnose and manage.

Investigators conducted a population-based study in Iceland uncovering 19.1 cases of drug-induced liver injury per 100,000 inhabitants, per year. These results are significantly higher than the last population-based study of this kind, conducted in France from 1997-2000, which reported 13.9 cases per 100,000 inhabitants, per year.

The most commonly implicated drugs were amoxicillin-clavulante (penicillin used to fight bacteria), azathioprine (an immunosuppressive drug used in organ transplantation and autoimmune diseases) and infliximab (also used to treat autoimmune disease).

“Drug-induced liver injury is not a single, uncommon disease of the general population, but rather a series of rare diseases that occur only in persons who take specific medications,” said Einar S. Björnsson, lead study author from the department of internal medicine, section of gastroenterology and hepatology, National University Hospital, Reykjavik, Iceland, and faculty of medicine at the University of Iceland. “Our study identified which medications put patients most at risk for developing liver diseases. With this information, physicians can better monitor and manage patients who are prescribed potentially liver-injuring drugs.”

The study also showed that drug-induced liver injury was caused by a single prescription medication in 75 percent of cases, by dietary supplements in 16 percent and by multiple agents in 9 percent. Further, the incidence was similar in women and men, but increased with age; not surprising since the need for medication also increases with age.

Jaundice and other symptoms highly suggestive of liver injury, such as itching, nausea, abdominal discomfort and lethargy, were present in the majority of patients. Most patients had a favorable outcome after receiving care.

For more, watch Dr. Björnsson discuss his research in a Gastroenterology video abstract.
About the AGA Institute



 The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. www.gastro.org

http://www.gastro.org/news/articles/2013/06/26/drug-induced-liver-injury-is-on-the-rise

Telaprevir Activity in Treatment-Naïve Genotype 4 Hepatitis C-Infected Patients: A Randomized Trial

Telaprevir Activity in Treatment-Naïve Genotype 4 Hepatitis C-Infected Patients: A Randomized Trial

Yves Benhamou1, Joseph Moussalli1, Vlad Ratziu1,2, Pascal Lebray1, Katrien De Backer3, Sandra De Meyer3, Anne Ghys3, Donghan Luo4, Gaston Picchio4 and Maria Beumont3

+ Author Affiliations
1Service d'Hépato-Gasteroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
2Université Pierre et Marie Curie, Paris VI, Paris, France
3Janssen Infectious Diseases BVBA, Beerse, Belgium
4Janssen Research and Development, Titusville, NJ, USA
Correspondence: Dr Yves Benhamou, Hôpital Pitié-Salpêtrière, 47–83 Boulevard de l'Hôpital, Paris, France (ybenhamou@teaser.fr)

Abstract
Background. 
The partially-blinded, randomized, phase IIa C210 study evaluated the antiviral activity of telaprevir-based regimens in treatment-naïve, genotype 4 chronic hepatitis C virus (HCV)-infected patients.

Methods. 
Patients (n=24) received 15 days of telaprevir 750 mg every 8 hours (T; n=8), telaprevir in combination with peginterferon alfa-2a and ribavirin (Peg-IFN/RBV; TPR; n=8), or Peg-IFN/RBV plus placebo (PR; n = 8), followed by Peg-IFN/RBV for 46 or 48 weeks. The primary objective was to assess the effect of telaprevir on HCV RNA levels.

Results. 
HCV RNA levels decreased slightly with T and PR; TPR produced substantial, rapid declines. At Day 15, median HCV RNA reductions from baseline were -0.77, -4.32, and -1.58 log10 IU/mL for T, TPR and PR, respectively, and 0 (T), 1 (TPR), and 0 (PR) patients had undetectable HCV RNA. Five/eight patients who received telaprevir monotherapy had viral breakthrough within 15 days of treatment. Adverse event incidence was similar across treatments and comparable with previous clinical trials. One patient (T group) had a serious adverse event (considered unrelated to telaprevir) that led to treatment discontinuation.

Conclusions. 
Telaprevir with Peg-IFN/RBV had greater activity against HCV genotype 4 than Peg-IFN/RBV or telaprevir monotherapy. Telaprevir was generally safe and well tolerated. Further investigation of telaprevir combination therapy in genotype 4 patients is warranted.

http://jid.oxfordjournals.org/content/early/2013/06/24/infdis.jit274.abstract

Research shows strong link between liver disease, cardiovascular disease risk

Saint Luke’s collaborative research shows strong link between liver disease, cardiovascular disease risk

Fatty liver disease growing concern among clinicians

June 20, 2013

KANSAS CITY, Mo. (June 20, 2013) — Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the general population, and in most cases causes no signs, symptoms, or complications. Now liver specialists and cardiologists at Saint Luke’s are adding to a growing body of research indicating a direct link between NAFLD and a high risk for cardiovascular disease. The research is compelling enough that cardiologists at Saint Luke’s are considering changing their practices to include liver and spleen images in CT scans as a screening indicator of coronary artery disease risk. 

 

Saint Luke’s Liver Disease Management Center gastroenterologists Rajiv Chhabra, M.D., and John Helzberg, M.D., presented new research at the Digestive Disease Week conference of the American Gastroenterological Association Annual Meeting in May. Their study showed that as independent conditions, NAFLD and coronary artery disease are strongly predictive of each other. Cardiologists James O’Keefe, M.D., and Randall Thompson, M.D., also contributed to the research. 

 

The study assessed upper abdominal CT images from 377 non-symptomatic patients undergoing non-contrast CT scans to determine coronary calcium scores. Using expanded imaging “windows” to include the liver and spleen, researchers found that patients with fatty liver disease were more likely to also have coronary artery disease. The link between the two was stronger than other more traditional risk factors for coronary artery disease, such as smoking, hypertension, male gender, diabetes, high cholesterol, or metabolic syndrome. 

 

Non-alcoholic fatty liver disease is the accumulation of fat in the liver in people who drink little to no alcohol. The fat can cause inflammation and scarring in the liver. Its most serious form can progress to cirrhosis, liver failure, or liver cancer. It is the most common liver disorder among Western countries and one of the fastest growing concerns among clinicians due to escalating obesity and diabetes.  

 

“If current trends continue, the prevalence of NAFLD is expected to increase to 40 percent of the population by 2020,” said Dr. Helzberg.

 

While more research is needed to explore the relationship between the two conditions, the growing number of patients with NAFLD suggests a potential role for increased screening among the medical community. “These findings suggest that patients with coronary artery disease should be screened for liver disease, and likewise NAFLD patients should be evaluated for coronary artery disease,” said Dr. Chhabra. Treatments now primarily include lifestyle changes like diet, exercise, and increased monitoring. 

 

A research partnership between physicians at Saint Luke’s Liver Disease Management Center and Saint Luke’s Mid America Heart Institute continues to explore the issue. Funding was provided through a research grant from the Saint Luke’s Foundation.

 

“This study is another example of what can arise from cross-disciplinary collaboration that is increasingly common at Saint Luke’s. By pooling our knowledge and insights, we are able to identify promising areas for research that may have a powerful impact on our ability to practice medicine and to improve the lives of our patients,” said David J. Cohen, M.D., M.Sc., director of Cardiovascular Research at Saint Luke’s Hospital.  

 

About Saint Luke’s Liver Disease Management Center

At Saint Luke’s Liver Disease Management Center, patients throughout the Midwest and across the United States have access to liver disease treatment options provided by a multidisciplinary physician group. From preventive care to liver transplantation, Saint Luke’s provides a full range of services for patients with disorders of the liver, bile ducts, and pancreas.

 

About Saint Luke’s Mid America Heart Institute

Saint Luke’s Mid America Heart Institute, a member of Saint Luke’s Health System and a teaching affiliate of the University of Missouri-Kansas City, is one of the preeminent cardiovascular programs in the country. Its legacy of innovation began more than 25 years ago when it opened as the nation’s first heart hospital. Since then, the Heart Institute has earned a world-wide reputation for excellence in the treatment of heart disease, including interventional cardiology, cardiovascular surgery, imaging, heart failure, transplant, heart disease prevention, women’s heart disease, electrophysiology, outcomes research, and health economics.  With more than 50 full-time board certified cardiovascular specialists on staff, the Heart Institute offers one of the largest heart failure/heart transplant programs in the country, has the largest experience with transcatheter aortic valve replacement in the Midwest, and is a global teaching site for the newest approaches to opening challenging blocked arteries using minimally invasive techniques.

https://www.saintlukeshealthsystem.org/about/news/saint-luke-s-collaborative-research-shows-strong-link-between-liver-disease

Harm reduction more effective than war on drugs in B.C.

Harm reduction more effective than war on drugs in B.C.

15-year study finds fewer people using, injecting illicit drugs

The Canadian Press 
Posted: Jun 24, 2013 7:59 PM ET

Harm reduction — not a war on drugs — has reduced illicit drug use and improved public safety in what was once Ground Zero for an HIV and overdose epidemic that cost many lives, says a 15-year study of drug use in Vancouver's impoverished Downtown Eastside. 

The report by the B.C. Centre for Excellence in HIV/AIDS found that from 1996 to 2011, fewer people were using drugs and, of those who were, fewer were injecting drugs, said Dr. Thomas Kerr, co-author of the report and co-director of the centre's Urban Health Research Initiative. 

"A public health emergency was declared here because we saw the highest rates of HIV infection ever seen outside of sub-Saharan Africa — in this community. At the same time, the community was being levelled by an overdose epidemic," Kerr said after presenting his findings to members of the group affected at a community centre in the heart of the neighbourhood. 

Vancouver took a public health approach to the crisis, opening the country's first supervised injection site in 2003, and Kerr said the statistics show that approach was successful. 

There were fewer people sharing needles in 2011, and there were fewer new infections of HIV and Hepatitis C related to sharing needles, the study found....

Continue to full article..........

A Genetic Biomarker for Long-Term Prognosis of HCV-Related Cirrhosis

A Genetic Biomarker for Long-Term Prognosis of HCV-Related Cirrhosis

Profiling a 186-gene signature from needle-biopsy specimens could improve targeting of intensive surveillance to the highest-risk patients.

Hepatitis C virus (HCV)–related cirrhosis is a leading cause of liver-related morbidity and mortality. Identifying prognostic biomarkers of long-term outcomes might allow clinicians to risk-stratify their patients with cirrhosis and target high-risk patients for closer, more-intensive monitoring. In the current study, investigators assessed whether a 186-gene signature from liver tissue can predict death, progression of cirrhosis, or hepatocellular carcinoma (HCC) in HCV-infected patients with cirrhosis.

Researchers performed whole-genome gene expression profiling on archived liver biopsy tissue of 216 HCV-infected patients with Child-Pugh Class A cirrhosis (identified only by histology). The patients had been enrolled in a long-term, cohort study between 1985 and 1998 (N Engl J Med 1991; 325:675). During median follow-up of 10 years, 66 patients died (31%; 28 from HCC, 20 from liver failure, and 15 from non-liver–related causes), 71 (34%) developed hepatic decompensation, 66 (31%) progressed to Child-Pugh class B or C, 65 (30%) developed HCC (annual incidence, 2.9%), and 12 patients underwent liver transplantation.

Using the gene expression signature, patients were categorized by prognosis: poor (25%); intermediate (47%), or good (28%). In multivariate analysis, having a poor-prognosis signature was significantly associated with increased risk for death (P=0.004), liver disease progression (P<0.001), and HCC development (P=0.009). In the poor-, intermediate-, and good-prognosis groups, 10-year survival rates were 63%, 74%, and 85%, respectively, and annual HCC incidence rates were 5.8%, 2.2%, and 1.5%.

Comment: This study has significant clinical implications. First, such prognostic data will allow clinicians to advise patients with hepatitis C virus and early cirrhosis on their long-term prognoses. Second, these data will enable clinicians and public health programs to more appropriately target intensive surveillance practices to high-risk patients. Finally, genome-wide profiling can seemingly be performed on needle-biopsy specimens, thus allowing these important data to be gathered during routine clinical care. Once this 186-gene signature is further validated, it will become an important clinical tool.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology June 21, 2013
Citation(s):

Hoshida Y et al. Prognostic gene expression signature for patients with hepatitis C–related early-stage cirrhosis. Gastroenterology 2013 May; 144:1024. (http://viajwat.ch/1c3YQqs)
Medline abstract (Free)

Medicare/private insurers-Can get tested for HCV without copayment

Baby Boomers Should Get Tested for HCV
A small change in rating from the US Preventive Services Task Force has incredible consequences -- allowing baby boomers to get tested for HCV without copayment....

The American Association for the Study of Liver Diseases (AASLD) applauds the US Preventive Services Task Force (USPSTF) decision of June 24, 2013 giving a "B" rating for testing baby boomers for hepatitis C virus. This seemingly small change -- from a "C" to a "B" -- in the USPSTF rating signals an incredible change in the lives of patients who have HCV and are unaware of it. A "B" rating allows for payment by Medicare and private insurers for testing with no copayment by patients.

More than 75 percent of the estimated 3 million US citizens with HCV are baby boomers. This new USPSTF "B" rating for HCV testing of baby boomers matches its rating for HCV testing among injection drug users and others at high risk. 

Earlier this year, the Centers for Disease Control and Prevention (CDC) recommended an age-based screening strategy that required a one-time test for everyone born between 1945 and 1965. The USPSTF had initially recommended a "C" rating for this birth cohort in a draft proposal, conflicting with the CDC recommendation and creating confusion in the primary care community. The change from a "C" to a "B" rating gives primary care clinicians the absolute clarity of the hepatology community -- early detection of HCV allows for the drastically greater possibility of treatment success for patients.

HCV is usually an asymptomatic disease, and three out of four of those afflicted are unaware of their infection until their liver disease is far advanced. To allow the disease to progress to the point where a patient is showing symptoms greatly increases the danger of the disease, decreases our abilities to treat these patients, and often results in the development of liver cancer, frequently requiring liver transplantation -- at best. Liver cancer is one of the few cancers increasing in frequency and has one of the highest mortality rates. The ability of a patient to be tested and treated for HCV at the earliest possible date allows him or her to avoid the disease’s progression to liver cancer.

Liver transplantation is an expensive procedure and testing for HCV with subsequent treatment is expected to decrease the number of patients who would otherwise require transplantation and provides a significant financial savings to the nation’s healthcare system. It is worthy of note that these recommendations come at a time when the treatments for hepatitis C are becoming both more effective and easier to tolerate.  The other savings is even greater -- decreasing the number of patients requiring and waiting for a liver transplantation equals saving lives. The number of livers available does not match the number of patients who currently require a transplantation, which means that patients die while on the waiting list. In 2012, there were 6,256 liver transplantations performed. As of June 7, 2013, there are 16,484 patients waiting for a suitable organ.

The CDC recommended one-time age-based screening allowing for early detection of HCV reduces the chance of progression to liver cancer, and decreases the number of patients requiring a liver transplantation. The new "B" rating by the USPSTF means that a large number of patients can be tested and successfully treated with new direct-acting antiviral drugs that have allowed the medical community to cure HCV. Ten years ago, we were not able to cure patients of HCV, but research in liver disease has led to these new drugs. Treatment is still difficult and expensive, but it is constantly improving, and we anticipate the FDA to approve numerous new drugs over the next three to five years. New drugs currently in the pipeline will allow us to increase the cure rate and decrease treatment side effects.

AASLD is a subspecialty society representing clinicians and researchers in liver disease. The work of our members has laid the foundation for the development of drugs used to treat patients with HCV. Our members are on the frontline of treating and curing these patients. This decision by the USPSTF helps us help patients.

###

AASLD is the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease. AASLD was founded in 1950 by a small group of leading liver specialists and has grown to an international society responsible for all aspects of hepatology.

Top Medicare Prescribers Rake In Speaking Fees From Drugmakers

Top Medicare Prescribers Rake In Speaking Fees From Drugmakers

by Charles Ornstein, Tracy Weber and Jennifer LaFleur
ProPublica, June 25, 2013, 12:02 a.m.

This story was co-published with NPR

When the blood pressure drug Bystolic hit the market in 2008, it faced a crowded field of cheap generics. 

So its maker, Forest Laboratories, launched a promotional assault on the group in the best position to determine Bystolic's success: those in control of prescription pads. It flooded the offices of health professionals with drug reps, and it hired doctors to persuade their peers to choose Bystolic — even though the drug hadn't proved more effective than competitors. 

The strategy worked. In the 2012 fiscal year, sales of Bystolic reached $348 million, almost double its total from two years earlier, the company reported. 

Now, data obtained and analyzed by ProPublica suggest another factor in Bystolic's rapid success: Many of the drug's top prescribers have financial ties to Forest. 

At least 17 of the top 20 Bystolic prescribers in Medicare's prescription drug program [2] in 2010 have been paid by Forest to deliver promotional talks. In 2012, they together received $283,450 for speeches and more than $20,000 in meals............ 

 

Full article available here.........

Screen All Baby Boomers for Hepatitis C, Expert Panel Says

Links:
Updated recommendations from the US Preventive Services Task Force include hepatitis C screening among all persons born between 1945 and 1965.
Full Text : Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation
Source - Annals Of Internal Medicine

Also See - Medicare/private insurers-Can get tested for HCV without copayment

In The News

Screen All Baby Boomers for Hepatitis C, Expert Panel Says

This generation has highest rate of infection, likely contracted decades ago

June 24, 2013 


By Steven Reinberg
HealthDay Reporter

MONDAY, June 24 (HealthDay News) -- All adults born between 1945 and 1965 -- the baby boom generation -- should be screened for the hepatitis C virus along with injection-drug users and anyone transfused before 1992, according to new recommendations from the U.S. Preventive Services Task Force.

The guidelines, released Monday, mirror recommendations from the U.S. Centers for Disease Control and Prevention and provide a long-awaited policy from the task force, an independent panel of experts.

"For everyone born between 1945 and 1965 we recommend a one-time screening," said task force member Dr. Kirsten Bibbins-Domingo, an associate professor in residence at the University of California, San Francisco, School of Medicine.

People in this age group account for three-quarters of all hepatitis C cases in the United States, Bibbins-Domingo said. Many contracted the disease decades ago but don't know it.

Hepatitis C -- a leading cause of liver damage and liver disease in the United States -- is considered a silent killer because it progresses without any indications of illness. More than 30 percent of U.S. patients needing liver transplants have end-stage liver disease related to hepatitis C.

"The challenge is that many people have hepatitis C and don't have signs and symptoms of the disease," Bibbins-Domingo said. "Those people should be identified and consider treatment."

An estimated 3.9 million people are infected with hepatitis C in the United States, the task force said. Unlike other types of hepatitis, there is no vaccine for hepatitis C.

In its 2004 statement, the task force advised against routine screening of adults without symptoms and high risk of infection. It also said it had too little evidence to recommend for or against routine screening for adults with high risk of infection.

It became apparent, however, that two-thirds of infected people weren't getting screened, while treatment was becoming more successful.

"Many people appear to benefit from treatment," Bibbins-Domingo said. "That is what led the task force to conclude that it is beneficial for people to find out they have hepatitis C in order to seek treatment."

Dr. Marc Siegel, an associate professor of medicine at NYU Langone Medical Center in New York City, said he welcomes the new guidelines, which were published June 25 in the Annals of Internal Medicine.

"I am absolutely thrilled that the U.S. Preventive Services Task Force, which has had a head-in-the-sand approach toward screening, has come out for a one-time screening for hepatitis C," Siegel said.

Siegel encourages everyone at risk to get tested.

Screening for hepatitis C involves a simple, inexpensive blood test. Those who test positive usually receive a course of antiviral medication over several months. Most people have no detectable virus following treatment, Bibbins-Domingo said.

"Treatment is effective in preventing the complications of hepatitis C," Bibbins-Domingo said. "Treatments have gotten better, and I suspect treatments will continue to get better."

Many people who test positive for the virus have no signs of active infection. Whether they should be treated should be discussed with their doctor, she said.

Although baby boomers should have a one-time screening, those who continue to be at risk for the infection should be screened more often, Bibbins-Domingo said.

Past or current injection-drug use is the greatest risk for hepatitis C infection. Also at high risk are people with a history of blood transfusions before widespread adoption of screening and infection-control measures in 1992; people who have undergone long-term dialysis treatment; and those with exposure to hepatitis C in health care settings. People with HIV/AIDS, a history of intranasal drug use or tattoos from unregulated or unsafe parlors also are at greater risk than the general population.

This expanded screening may identify millions of Americans who were unaware of their infection, the task force said.

More information

For more information on hepatitis C, visit the U.S. Centers for Disease Control and Prevention.

Vitamin D Levels and Liver Fibrosis Severity in Hepatitis C

Association of Vitamin D Serum Levels and Its Common Genetic Determinants, With Severity of Liver Fibrosis in Genotype 1 Chronic Hepatitis C Patients

S. Petta, S. Grimaudo, V. D. Marco, C. Scazzone, F. S. Macaluso, C. Cammà, D. Cabibi, R. Pipitone, A. Craxì

J Viral Hepat. 2013;20(7):486-493.

Abstract and Introduction
Abstract
Lower 25-hydroxyvitamin D [25(OH)D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D-binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023–1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974–0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002–1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919–0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106–16.120; P = 0.03), moderate–severe steatosis (OR, 2.588; 95% CI, 1.355–4.943; P = 0.004) and moderate–severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307–4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.

Introduction
The key issue in patients with chronic hepatitis C (CHC) is the progression of liver fibrosis as a consequence of various mechanisms of tissue damage caused by viral infection,^[1] with the ultimate development of cirrhosis and its complications.

Other than well known risk factors for fibrosis severity, like liver necroinflammation, older age, consumption of alcohol, duration of infection and viral coinfections,^[2] metabolic alterations, namely steatosis,^[3] insulin resistance (IR)^[4] and menopause (in females)^[5] can affect the degree of liver fibrosis.

In this complex and interesting interplay between liver and metabolic factors, growing evidence also suggest a role of vitamin D status on liver disease severity in patients with chronic hepatitis C. In particular, we firstly reported that fully compensated genotype 1 (G1) CHC patients are characterized by a higher prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency compared to a control population, also showing in this clinical setting an independent inverse relationship between 25(OH)D serum levels and liver fibrosis severity.^[6] These clinical data not only were further confirmed by other groups,^[7,8] but also their strength was supported by experimental studies showing that vitamin D, acting via its nuclear vitamin D receptor, exerts its protective effect by inhibiting stellate cell proliferation and their profibrogenic activation.^[9]
                       
Vitamin D has therefore a relevant role in patients with CHC, and its metabolism is regulated by several environmental factors, in particular sunlight and diet. In addition, a recent genome-wide association study (GWAS), in a large screening population of about 30 000 European descent individuals divided in a training and a validation set demonstrated that serum concentrations of 25(OH)-vitamin D are influenced by variants near genes involved in cholesterol synthesis (7-dehydrocholesterol reductase -DHCR7), vitamin D hydroxylation (CYP2R1) and vitamin D transport (vitamin D-binding protein–GC).^[10]
                       
With this in mind, in a cohort of biopsy-proven G1 CHC patients, we aimed to assess the association between vitamin serum levels and its genetic determinants, with the severity of liver fibrosis.

Materials and Methods
Patients

Two hundred and sixty consecutive patients with G1 CHC, recruited at the Gastrointestinal and Liver Unit at the University Hospital in Palermo and fulfilling all inclusion and exclusion criteria detailed below, were assessed. Patients were included if they had a histological diagnosis of CHC (any degree of fibrosis, including cirrhosis) on a liver biopsy performed within 6 months prior to enrolment. G1 CHC patients were characterized by the presence of anti-HCV and HCV RNA, with persistently abnormal alanine aminotransferase (ALT) levels, and by alcohol consumption of <20 g/day in the last year or more, evaluated by a specific questionnaire. Exclusion criteria were (i) advanced cirrhosis (Child-Pugh B and C); (ii) hepatocellular carcinoma; (iii) other causes of liver disease of mixed aetiologies (excessive alcohol consumption, hepatitis B, autoimmune liver disease, Wilson's disease, hemochromatosis, α1-antitrypsin deficiency); (iv) HIV infection; (v) previous treatment with antiviral therapy, immunosuppressive drug and/or regular use of steatosis-inducing drugs (corticosteroids, valproic acid, tamoxifen, amiodarone); (vi) therapy with medications known to affect vitamin D3 metabolism, including vitamin/mineral supplements; and (vii) active IV drug addiction.

The study was performed in accordance with the principles of the Declaration of Helsinki and its appendices, and with local and national laws. Approval was obtained from the hospital's Institutional Review Board and Ethics Committee, and written informed consent was obtained from all patients.

Clinical and Laboratory Assessment
Clinical and anthropometric data were collected at the time of liver biopsy. BMI was calculated on the basis of weight in kilograms and height (in metres), and patients were classified as normal weight (BMI, 18.5–24.9 kg/m²), overweight (BMI, 25–29.9) or obese (BMI ≥ 30). The diagnosis of arterial hypertension was based on the following criteria: systolic blood pressure ≥135 mm Hg and/or diastolic blood pressure ≥85 mm Hg (measured three times within 30 min, in the sitting position and using a brachial sphygmomanometer) or use of blood pressure–lowering agents. The diagnosis of type 2 diabetes was based on the revised criteria of the American Diabetes Association, using a value of fasting blood glucose ≥126 mg/dL on at least two occasions.^[11] In patients with a previous diagnosis of type 2 diabetes, current therapy with insulin or oral hypoglycaemic agents was documented.

A 12-hour overnight fasting blood sample was drawn at the time of biopsy to determine serum levels of ALT, total cholesterol, HDL and LDL cholesterol, triglycerides, plasma glucose concentration, insulin and platelet count. Insulin resistance (IR) was determined with the homoeostasis model assessment (HOMA), using the following equation:^[12] insulin resistance (HOMA-IR) = fasting insulin (μU/mL) × fasting glucose (mm)/22.5. HOMA-IR has been validated in comparison with the euglycemic/hyperinsulinemic clamp technique in both diabetic and nondiabetic patients.^[13]
The analysis of serum 25(OH) D was performed using a Chromosystem reagent kit and a chromatographic system equipped with a Waters 1525 Binary high-pressure liquid chromatography pump connected to a photo diode array detector, and detection was carried out at 265 nm. 25(OH)D serum levels <10 μg/L, from 10 to 30 μg/L, and >30 μg/L, were considered the threshold values for identifying deficiency, insufficiency and normality of vitamin D levels, respectively.
All patients were tested at the time of biopsy for HCV RNA (RT-PCR homemade; limit of detection: 12 IU/mL). Genotyping was performed by INNO-LiPA, HCV II, Bayer.

Genetic Analyses. DNA was purified using the QIAmp blood Mini Kit (Qiagen, Mainz, Germany), and DNA samples were quantified using spectrophotometric determination.

Genotyping for IL28B (rs12979860), PNPLA3 (rs738409), CYP2R1 (rs 10741657), NADSYN1(rs 12785878) and GC (rs 2282679) was carried out using the TaqMan SNP genotyping allelic discrimination method (Applied Biosystems, Foster City, CA, USA). Commercial genotyping assays were available for the SNPs: rs738409 (cat. C_7241_10), rs 10741657 (cat. C_2958430_10); rs 12785878 (cat. C_32063037_10); rs 2282679 (cat. C_26407519_10). Instead, a custom assay has been created by AB for rs12979860.

The genotyping call was performed with SDS software v.1.3.0 (ABI Prism 7500, Foster City, CA, USA). Genotyping was conducted in a blinded fashion relative to patient characteristics.

Histology
Slides were coded and read by one pathologist (D.C.), who was unaware of the patient's identity and history. A minimum length of 15 mm of biopsy specimen or the presence of at least 10 complete portal tracts was required.^[14] Biopsies were classified according to the Scheuer numerical scoring system.^[15] The percentage of hepatocytes containing macrovescicular fat was determined for each 10× field. An average percentage of steatosis was then determined for the entire specimen. Steatosis was assessed as the percentage of hepatocytes containing fat droplets (minimum 5%) and evaluated as a continuous variable. Steatosis was classified as absent-mild at <20% or moderate–severe at ≥20%.

Statistics. Continuous variables were summarized as mean ± standard deviation and categorical variables as frequency and percentage. The Student's t-test and analysis of variance were used when appropriate. Multiple linear regression analysis was performed to identify independent predictors of 25(OH)D serum levels as a continuous dependent variable. As candidate risk factors for low serum levels of 25(OH)D, we selected age, sex, body mass index, baseline ALT, platelet count, total cholesterol, high-density lipoprotein cholesterol, triglycerides, blood glucose, insulin, HOMA score, diabetes, arterial hypertension, DHCR7,CYP2R1 and CG SNPs, HCV RNA levels, steatosis and activity score.

Multiple logistic regression models were used to assess the relationship of fibrosis to the demographic, metabolic, genetic and histological characteristics of patients. In the model, the dependent variable was severe fibrosis coded as 1 = F3–F4 in the fibrosis score versus 0 = F1–F2. As candidate risk factors, we selected the same independent variables included in the 25(OH)D model and added 25(OH)D serum levels as an additional independent variable.

In all analyses, DHCR7 SNP was evaluated as TT/TG vs GG, CYP2R1 as AA/AG vs GG, and CG as TT/TG vs GG, according to published data on genotypes associated with lower vitamin D levels.^[10]
Variables associated with the dependent variable at univariate analyses (probability threshold, P < 0.10) were included in the multivariate regression models. Regression analyses were performed by SAS.^[16]

Results
Patient Features and Histology
The baseline features of the 260 patients are shown in Table 1. Most of our patients were in the overweight to obesity range. One patient in four had fibrosis of at least three by Scheuer score, with a high prevalence of moderate/severe necroinflammation (grading 2–3). One patient in three had histological evidence of steatosis of moderate/severe grade.
Mean serum values of 25(OH)D were 24.5 ± 8.4 μg/L. Accordingly, vitamin D deficiency, insufficiency and normality were observed in 0.4%, 75% and 24.6% of G1 CHC patients, respectively.

DHCR7 rs12785878 TT genotype was present in 114 (43.8%) patients, compared to 133 (51.2%) and 13 (5%) with TG and GG variants, respectively. The CYP2R1 rs10741657 AA genotype was observed in 29 patients (11.1%) compared with 109 (41.9%) and 122 (46.9%) with AG and GG variants, respectively. Finally, GC rs7041 TT genotype was present in 149 patients (57.3%) compared with 94 (36.2%) and 17 (6.5%) with TG and GG variants, respectively.

Serum 25(OH)D Levels
Older age (P = 0.002), female sex (P = 0.03), DHCR7 GG (P = 0.003), GC GG (P = 0.05) and the severity of fibrosis (P = 0.001) were associated with lower 25(OH)D levels in G1 CHC, although only DHCR7 GG (P = 0.003) (P = 0.008) and the severity of fibrosis (P = 0.03) were independent factors in multiple linear regression analysis (Table 2). Figure 1 shows the distribution of serum 25(OH)D levels in relation to DHCR7 genotype.

Figure 1.

25(OH)D serum levels according to DHCR7 genotype, in 260 patients with genotype 1 chronic hepatitis C.

Accordingly, all patients with DHCR7 GG genotype had vitamin D insufficiency/deficiency, compared to 74% with DHCR7 TT/TG genotype (P = 0.03).

Variables Related to Severe Fibrosis
The univariate and multivariate comparison of variables between patients with and without severe fibrosis (F3–F4) are reported in Table 3. Older age, male sex, high baseline values of ALT, low cholesterol, high triglycerides, high blood glucose, high HOMA, diabetes, low 25(OH)D, vitamin D insufficiency/deficiency, DHCR7 GG genotype, moderate–severe steatosis and moderate–severe necroinflammatory activity were associated with severe fibrosis (P < 0.10). Multivariate logistic regression analysis showed that the following features were independently linked to severe fibrosis (Scheuer score ≥3): older age (OR, 1.056; 95% CI, 1.023–1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974–0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002–1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919–0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106–16.120; P = 0.03), moderate–severe steatosis (OR, 2.588; 95% CI, 1.355–4.943; P = 0.004) and moderate–severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307–4.763; P = 0.001). The overall area under the curve (AUC) of this model was good (AUC, 0.870). Figure 2 showed the prevalence of severe fibrosis, according to DHCR7 genotype

Figure 2.

Prevalence of severe liver fibrosis according to DHCR7 genotype, in 260 patients with genotype 1 chronic hepatitis C.

Discussion
In this study, we have shown that, in a cohort of patients with biopsy-proven G1 CHC, DHCR7 GG genotype, other than being associated with lower vitamin D serum levels, was also independently linked to the severity of liver fibrosis, together with well known risk factors for fibrosis, including lower vitamin D serum levels.

Different lines of evidence showed a relevant role of vitamin D status in patients with CHC patients, and with neoplastic and cardiometabolic disorders,^[6,17] prompting genetic, clinical and experimental research on vitamin D metabolism and actions.

In our study we showed that, in G1 CHC patients, lower levels of serum 25(OH)D were independently linked to the DHCR7 GG genotype. Our data are in agreement with the GWAS study of Wong and colleagues on a cohort of about 30 000 subjects that identified the DHCR7 gene as able to affect vitamin D serum levels, with the lowest values in GG patients.^[10] In addition, the presence of lower vitamin D serum levels in patients with the DHCR7 GG genotype was also recently reported in a large cohort of Caucasian patients with chronic liver diseases due to different aetiologies.^[18] In our study, we did not identify a link between CYP2R1 and GC SNPs, also linked to vitamin D deficiency in the above quoted GWAS study,^[10] and vitamin D serum levels. This issue could be related to the demographic, clinical and biochemical characteristics of our studied population, like the very high prevalence of vitamin D deficiency, as well as to the relative low number of included patients.

This study offers the first evidence that the DHCR7 GG genotype, together with lower 25(OH)D serum levels, and with other known risk factors for fibrosis severity, such as older age, low cholesterol and high triglycerides levels, moderate–severe steatosis and high necroinflammatory activity, is independently associated with the presence of severe liver fibrosis in G1 CHC patients. Grünhage and colleagues,^[18] in a cohort of more than seven hundred patients with mostly clinically diagnosed chronic liver disease due to different aetiologies (60% HCV related), showed that, among subgroups of patients with liver stiffness measurement (LSM) lower than 7 kPa and lower than 9.5 kPa, the DHCR7 GG genotype was associated with higher LSM values. These data therefore suggested, with limits related to LSM use as surrogate marker of fibrosis, and to subgroups analyses, a potential association between severity of liver disease and the DHCR7 GG genotype. In this line, our study added further and relevant evidence about this issue, demonstrating the association between the DHCR7 GG genotype and severity of histological liver fibrosis, in a cohort of compensated, homogeneous and fully characterized biopsy-proven G1 CHC patients.

Another relevant finding of our study is that both the DHCR7 genotype and vitamin D levels were independently linked to the presence of severe liver fibrosis. This issue suggests that the association between the DHCR7 GG genotype and liver fibrosis is far complex. In fact, on the one hand, it is plausible that DHCR leads to fibrosis via lowering vitamin D serum levels.^[10] Experimental evidence in fact suggests that vitamin D, via interaction with VDR, is able to inhibit stellate cell proliferation and their profibrogenic activation.^[9] On the other hand, our results suggest that DHCR7 genotype could prompt fibrogenesis also via other direct/indirect mechanisms. However, literature data do not provide us with further help on this issue, and therefore, additional experimental work is needed.

The main limitation of this study lies in the low number of patients carrying the at-risk DHCR7 GG genotype. This issue could affect the interpretation of our results. However, the similar low prevalence of DHCR7 GG genotype reported in other studies,^[10,18] then our biologically plausible results^[9,10] and the presence in the literature of similar results^[10,18] makes us confident about the accuracy of our data, which obviously needs further validation in large cohort studies. Another limitation of our study is its cross-sectional nature and its inability to dissect the temporal relation between DHCR7 genotype, 25(OH)D and fibrosis. A further methodological drawback is the potentially limited external validity of the results for different populations and settings. Another limitation of this study is the lack of data on the potential confounders that may influence the levels of vitamin D, such as exposure to sunshine, dietary intake and the prevalence of osteoporosis. However, all of the subjects involved in this study lived in Sicily, where sunshine is abundant.

In conclusion, this study showed that in a homogeneous cohort of compensated biopsy-proven G1 CHC patients, DHCR7 GG genotype, other than leading to lower vitamin D serum levels, is also associated with the severity of liver fibrosis, suggesting a complex interplay between liver damage, vitamin D and genetic determinants of vitamin D deficiency.

Abstract and Introduction

Materials and Methods

Results 

Discussion

Abbreviations                
AUC, area under the curve; CHC, chronic hepatitis C; DHCR7, dehydrocholesterol reductase; G1, genotype 1; GC, vitamin Dbinding protein; GWAS, genome-wide association study; HCV, hepatitis C virus; HOMA, homoeostasis model assessment; IR, insulin resistance; LSM, liver stiffness measurement.

Contributors          
S. Petta designed the study, contributed to data acquisition, was responsible for writing the manuscript and participated in statistical analysis. C. Camma', V. Di Marco and A. Craxì (Director of the GI and Liver Unit) were responsible for the project and writing of the manuscript. D. Cabibi, S. Grimaudo, F.S. Macaluso, R. Pipitone and C. Scazzone participated in patient management and data collection. All authors have seen and approved the final version of the manuscript.
J Viral Hepat. 2013;20(7):486-493. © 2013  Blackwell Publishing

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