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Archives for Gastroenterology

Two-Week International Diet Swap Shows Potential Effects of Diet on Colon Cancer Risk

PITTSBURGH, April 28, 2015 – African-Americans and Africans who swapped their typical diets for just two weeks similarly exchanged their respective risks of colon cancer as reflected by alterations of their gut bacteria, according to an international study led by researchers at the University of Pittsburgh School of Medicine published online today in Nature Communications.

Principal investigator Stephen O’Keefe, M.D., professor of medicine, Division of Gastroenterology, Hepatology and Nutrition, Pitt School of Medicine, observed while practicing in South Africa that his rural patients rarely had colon cancer or intestinal polyps, which can be a cancer precursor. In the Western world, colon cancer is the second-leading cause of cancer death and African-Americans carry the greatest disease burden in the United States.

“The African-American diet, which contains more animal protein and fat, and less soluble fiber than the African diet, is thought to increase colon cancer risk,” Dr. O’Keefe explained. “Other studies with Japanese migrants to Hawaii have shown that it takes only one generation of Westernization to change their low incidence of colon cancer to the high rates observed in native Hawaiians. In this project, we examined the impact of a brief diet change on the colon in a controlled setting where we didn’t have to worry about the influence of smoking and other environmental factors on cancer risk.”

After assessment of their in-home diets, 20 African-American and 20 rural South African volunteers ages 50 to 65 were housed at a University of Pittsburgh site and at an African lodging facility respectively. There they ate meals prepared by the researchers using ingredients and cooking techniques typical of the other group. The team examined fecal and colon content samples, obtained during colonoscopy, of each volunteer at baseline and after the two-week study period.

Although the diet change was brief, each group took on the other’s rates of turnover of cells of the intestinal lining, levels of fiber fermentation, and markers of bacterial metabolic activity and inflammation associated with cancer risk. In particular, African-Americans experienced an increase in butyrate production, which is thought to play a key role in anti-cancer pathways. The researchers also noted they removed intestinal polyps from nine of the African-American volunteers, but none were present in the Africans.

“We can’t definitively tell from these measurements that the change in their diet would have led to more cancer in the African group or less in the American group, but there is good evidence from other studies that the changes we observed are signs of cancer risk,” said co-author Jeremy Nicholson, Ph.D., of Imperial College London.

According to Dr. O’Keefe, increasing the amount of fiber in the diet – from approximately 10 grams to more than 50 for African-Americans in the diet swap – likely led to biomarker changes reflecting reduced cancer risk, but eating less animal fat and proteins also could be helpful.

“These findings are really very good news,” he said. “In just two weeks, a change in diet from a Westernized composition to a traditional African high-fiber, low-fat diet reduced these biomarkers of cancer risk, indicating that it is likely never too late to modify the risk of colon cancer.”

The team included other researchers from the University of Pittsburgh and Imperial College London, as well as Wageningen University in the Netherlands; University of Helsinki, Finland; University of Illinois; and the University of KwaZulu-Natal in South Africa.

Funding for the study was provided National Institutes of Health grants CA135379, RR024153 and TR000005; the National Institute for Health Research Imperial Biomedical Research Centre, UK; the Academy of Medical Sciences; the Spinoza Award of the Netherlands Organization for Scientific Research, the European Research Council and the Academy of Finland.

Pitt Collaborates with Janssen to Study and Tailor New Treatments for Inflammatory Bowel Disease

PITTSBURGH, April 8, 2015 – Researchers at the University of Pittsburgh will collaborate with Janssen Research & Development, LLC (Janssen) on a project to study the effectiveness of potential new therapies for inflammatory bowel disease (IBD).

A research team led by Ian McGowan, M.D., Ph.D., professor of medicine, Pitt School of Medicine, will use tissue samples from patients with Crohn’s disease and ulcerative colitis, two types of IBD, as well as from healthy volunteers, to evaluate experimental medicines developed by Janssen.

“This is a wonderful opportunity to advance future therapeutic approaches that may one day benefit patients living with IBD,” Dr. McGowan said. “We hope that this process will guide us to more effective treatments for these complex immune-mediated diseases.”

More than 6,000 IBD patients are seen each year by physicians in the Division of Gastroenterology, Hepatology, and Nutrition at Pitt and UPMC, which is led by David Whitcomb, M.D., Ph.D., Giant Eagle Foundation Professor of Cancer Genetics and professor of medicine, Pitt School of Medicine.

“The integration of an outstanding clinical IBD program with cutting-edge basic science research teams to introduce the best new therapies to patients who desperately need them can only happen in a few places in the world,” Dr. Whitcomb said. “Everyone here is committed to the success of this program at every level, by every measure.”

The project was coordinated by the university’s Pharmaceutical Collaborations Committee, which is chaired by D. Lansing Taylor, Ph.D., director of Pitt’s Drug Discovery Institute.

Smoking, Alcohol, Gene Variant Interact to Increase Risk of Chronic Pancreatitis, Says Pitt Team

PITTSBURGH, January 14, 2015 – Genetic mutations may link smoking and alcohol consumption to destruction of the pancreas observed in chronic pancreatitis, according to a 12-year study led by researchers at the University of Pittsburgh School of Medicine. The findings, published today in Nature Publishing Group’s online, open-access journal Clinical and Translational Gastroenterology, provides insight into why some people develop this painful and debilitating inflammatory condition while most heavy smokers or drinkers do not appear to suffer any problems with it.

The process appears to begin with acute pancreatitis, which is the sudden onset of inflammation causing nausea, vomiting and severe pain in the upper abdomen that may radiate to the back, and is typically triggered by excessive drinking or gallbladder problems, explained senior investigator David Whitcomb, M.D., Ph.D., chief of gastroenterology, hepatology and nutrition, Pitt School of Medicine. Up to a third of those patients will have recurrent episodes of acute pancreatitis, and up to a third of that group develops chronic disease, in which the organ becomes scarred from inflammation.

“Smoking and drinking are known to be strong risk factors for chronic pancreatitis, but not everyone who smokes or drinks damages their pancreas,” Dr. Whitcomb said. “Our new study identifies gene variants that when combined with these lifestyle factors make people susceptible to chronic pancreatitis and may be useful  to prevent patients from developing it.”

In the North American Pancreatitis Study II consortium, researchers evaluated gene profiles and alcohol and smoking habits of more than 1,000 people with either chronic pancreatitis or recurrent acute pancreatitis and an equivalent number of healthy volunteers. The researchers took a closer look at a gene called CTRC, which can protect pancreatic cells from injury caused by premature activation of trypsin, a digestive enzyme inside the pancreas instead of the intestine, a problem that has already been associated with pancreatitis.

They found that a certain variant of the CTRC gene, which is thought to be carried by about 10 percent of Caucasians, was a strong risk factor for alcohol- or smoking-associated chronic pancreatitis. It’s possible that the variant fails to protect the pancreas from trypsin, leaving the carrier vulnerable to ongoing pancreatic inflammation and scarring.

“This finding presents us with a window of opportunity to intervene in the diseases process,” Dr. Whitcomb said. “When people come to the hospital with acute pancreatitis, we could screen for this gene variant and  do everything possible to help those who have it quit smoking and drinking alcohol, as well as test new treatments, because they have the greatest risk of progressing to end-stage chronic pancreatitis.”

Whitcomb’s team has been implementing more personalized approaches to pancreatic diseases in the Pancreas Center of Excellence within the Digestive Disorders Center at UPMC and hopes to learn whether use of genetic information can, in fact, reduce the chances of chronic disease in high-risk patients.

The study team includes Jessica LaRusch, Ph.D., Antonio Lozano-Leon, Ph.D., Kimberly Stello, Amanda Moore, Venkata Muddana, M.D., Michael O’Connell, Ph.D., Brenda Diergaarde, Ph.D., and Dhiraj Yadav, M.D., all of the University of Pittsburgh.

The project was funded by National Institutes of Health grants DK061451, DK077906 and DK063922, and the Conselleria de Industria e Innovación, Xunta de Galicia, Spain.

Gastroenterology Experts Present at AIBD 2014

PITTSBURGH, Dec. 8, 2014 – Faculty from the Division of Gastroenterology, Hepatology, and Nutrition were among the experts who presented at the recent 2014 Advances in Inflammatory Bowel Diseases, Crohn’s & Colitis Foundation’s Clinical & Research Conference in Orlando, Fla. Faculty research was presented in both oral and poster presentations, and covered a wide range of topics, including:

  • A Model Integrating Genetic and Environmental Factors Can Differentiate Crohn’s Disease from Ulcerative Colitis
    UPMC Co-Author: Richard Duerr, MD
  • The Patient-Centered IBD Medical Home: Will This Be the Future of IBD Healthcare Delivery?
    Presented by Miguel Regueiro, MD
  • E. Management of Psycho-Social Issues in IBD Patients: Case Studies
    Co-presented by Eva Szigethy, MD, PhD
  • Clinical Predictors of Moderate Depression and Suicidality in Adults with IBD
    UPMC co-Authors: Victor Chedid, MD, Jana Al Hashash, MD, Gregory Thorkelson, MD, Claudia Rivers-Ramos, MD, David Binion, MD, Miguel Regueiro,MD, Eva Szigethy, MD, PhD
  • What is the Optimal Medical Management of Post-Operative Crohn’s Disease?
    Presented by Miguel Regueiro, MD
  • Stop the Scanners! External Validation of Algorithms Predicting Complications in Patients with Crohn’s Disease Presenting to the Emergency Department
    UPMC Co-Author Jason Swoger, MD
  • Preventing and Treating Narcotic Dependence in Our IBD Patients
    Presented by Eva Szigethy, MD, PhD
  • IBD CONNECT: A Novel Inflammatory Bowel Disease Volunteer Program for Hospitalized Crohn’s Disease and Ulcerative Colitis Patients
    UPMC Co-Authors: Miguel Regueiro, MD, Eva Szigethy, MD, PhD

For more information on the conference, please visit AdvancesInIBD.com.

Physicians and Researchers Present at AASLD 2014

PITTSBURGH, Dec. 1, 2014 – Faculty from the Division of Gastroenterology, Hepatology, and Nutrition and the Thomas E. Starzl Transplantation Institute were well-represented at The Liver Meeting® held by the American Association for the Study of Liver Diseases in Boston. Experts from the division gave oral and poster presentations on topics such as:

  • BPAR (Biopsy Proven Acute Rejection) During Protocolized Immunosuppression Withdrawal (ISW) is Readily Reversed in Pediatric Liver Transplant (Tx) Recipients
    UPMC Contributors: Veena Venkat, MD, George Mazariegos, MD, Anthony Demetris, MD
  • Incremental Dose Model Identified GSK3β and β-catenin as Potential Targets for Regenerative Therapies for Acetaminophen-Induced Acute Liver Failure
    UPMC Contributor: Satdarshan (Paul) Singh Monga, MD
  • Cost-Effectiveness of Novel Hepatitis C Drug Regimens Among Treatment-Experiences U.S. Veterans
    UPMC Contributors: Cindy Bryce, PhD, Michael Fine, MD, MSc, Chester Good, MD, MPH, Larissa Myaskovsky, PhD, Vinod Rustgi, MD, MBA, Allan Tsung, MD, Kenneth Smith, MD, MS
  • Infection Challenges in the Cirrhotic Patient
    UPMC Contributor: Kapil Chopra, MD
  • The Economic Impact of Sofosbuvir-and Simeprevir-Based HCV Treatment in the Unites States
    UPMC Contributors: Mark Roberts, MD, and Michael Dunn, MD
  • Predictors of Mortality in Patients With Low MELD on the Liver Transplant Wait List
    UPMC Contributors: Swaytha Ganesh, MD, Chandraprakash Umapathy, MD, Abhinav Humar, MD, Christopher Hughes, MD, Mark Sturdevant, MD, Elizabeth Kallenborn, MSN, RN, Vinod Rustgi, MD, MBA, Shahid Malik, MD, Amit Tevar, MD
  • HCV Infection in Opiod-Using (OU) Pregnant Women
    UPMC Contributors: Elizabeth Krans, MD, MSc, Vinod Rustgi, MD, MBA
  • All Oral Treatment for Genotypr 4 Chronic Hepatitis C Infection With Sofosbuvir and Ledipasvir: Interim Results from the NIAID SYNERGY Trial
    UPMC Contributor: Vinod Rustgi, MD, MBA
  • Prevalence of Precore and Dual Basal Core Promoter HBV Variants in a Racially Diverse Cohort of Patients With Chronic HBV Infection in North America
    UPMC Contributors: Obaid Shaikh, MD, Abdus Wahed, PhD
  • ABT-450/r/Ombitasvir + Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Patients Receiving Stable Opioid Substitution Treatment: Pooled Analysis of Efficacy and Safety in Phase 2 and Phase 3 Trials
    UPMC Contributor: Vinod Rustgi, MD, MBA
  • Safety of ABT-450/r/Ombitasvir + Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Patients ≥65 Years of Age: Results From Phase 2 and 3 Trials
    UPMC Contributor: Vinod Rustgi, MD, MBA

For more information on The Liver Meeting, please visit the conference page.

Higher Risk of GI, Major Bleeding in Atrial Fibrillation Patients Taking Blood Thinner Dabigatran

PITTSBURGH, Nov. 3, 2014 – Patients with atrial fibrillation who take the blood thinner dabigatran are at greater risk for major bleeding and gastrointestinal bleeding than those who take warfarin, according to a new study by researchers at the University of Pittsburgh Graduate School of Public Health.

The findings, based on Medicare claims data and published today in JAMA Internal Medicine, indicate greater caution is needed when prescribing dabigatran to certain high-risk patients.

Atrial fibrillation, an arrhythmia in which the heart’s upper chambers irregularly contract, can send tiny clots from the heart to the blood vessels in the brain, explained the study’s senior author Yuting Zhang, Ph.D., associate professor and director of the Pharmaceutical Economics Research Group in Pitt Public Health’s Department of Health Policy and Management. For that reason, these patients often are prescribed a blood thinner to limit clot formation with the aim of preventing strokes.

“Dabigatran was introduced in 2010 and, at the time of approval, it was the only available alternative to warfarin,” Dr. Zhang said. “Warfarin dosing can be tricky and regular monitoring with blood tests is required, so doctors and patients were glad to have a drug that was easier to manage. But some recent studies suggest that dabigatran is associated with a higher risk of bleeding.”

To investigate that possibility, the study’s first author, Inmaculada Hernandez, Pharm.D., Pitt Public Health, and the team looked back at pharmacy and medical claims data, which employ a unique identifier code rather than patient names, from 2010 and 2011 of a random national sample of Medicare beneficiaries. They tracked 1,302 dabigatran users and 8,102 warfarin users to see whether they experienced bleeding episodes, classifying the events as major, such as intracranial bleeding or gastrointestinal bleeding requiring a hospital or emergency room stay, or minor, such as gastrointestinal bleeding that was treated on an outpatient basis, or nose bleeds.

They also looked more closely at bleeding episodes in four high-risk subgroups: those who were 75 and older; African-Americans; those with chronic kidney disease; and those with seven or more co-existing medical problems.

Medicare data showed that the incidence of major bleeding was 9 percent and of any bleeding was 32.7 percent in the dabigatran group and 5.9 percent and 26.6 percent, respectively, in the warfarin group. In other words, dabigatran users were 58 percent more likely to have a major bleed and 30 percent more likely to have any kind of bleed than those taking warfarin. African-Americans and patients with chronic kidney disease using dabigatran were about twice as likely to have a major bleed as those taking warfarin. In addition, dabigatran users were more likely than warfarin users to experience gastrointestinal or vaginal bleeding, or blood in the urine, joints or sputum. However, the dabigatran group had a lower risk for bleeding in the brain.

“These findings indicate that physicians should be cautious when prescribing dabigatran, particularly to African-Americans and patients with kidney impairments,” Dr. Hernandez said. “Also, the incidence of gastrointestinal bleeding was high in all the subgroups, so we recommend doctors explain to patients how to detect it so that it can be treated promptly.”

“We plan to examine 2012 data to monitor the risk of stroke for patients on dabigatran, which is the primary indication for taking the blood thinner,” Dr. Zhang said. “It’s possible that for some patients a greater reduction in the risk of stroke will outweigh the higher risk of bleeding with dabigatran compared to warfarin.”

Other co-authors are Seo Hyon Baik, Ph.D., of Pitt Public Health; and Antonio Piñera, M.D., of La Paz University Hospital, Madrid, Spain.

The project was funded by the Commonwealth Foundation for Public Policy Alternatives and the Agency for Healthcare Research and Quality.

Physicians and Researchers Present at 2014 American College of Gastroenterology Annual Meeting

PITTSBURGH, Oct. 31, 2014 – The University of Pittsburgh Division of Gastroenterology, Hepatology, and Nutrition was well-represented in Philadelphia at the recent American College of Gastroenterology (ACG) Annual Meeting. Faculty research was featured in both oral and poster presentations throughout the conference, including:

  • Pancreatic Cancer: The Genes You Need to Know
    Presented by Randall Brand, MD
  • Perceived Effectiveness of Endoscopic and Surgical Treatments Among North American Women With Complications of Chronic Pancreatitis (2014 ACG Presidential Poster Award winner)
    UPMC co-authors: Jyothsna Talluri, MD; Dhiraj Yadav, MD; David Whitcomb, MD, PhD
  • Antibiotic-Associated Microbiome Changes in Health Volunteers and Corrective Impact of the Probiotic Saccharomyces Boulardii (2014 ACG Presidential Poster Award winner)
    UPMC co-author: Toufic Kabbani, MD
  • Stratification of Crohn’s Disease Patients Using the Lemann Index to Quantify Gut Damage: A 5-Year Prospective Study (2014 ACG Presidential Poster Award winner and 2014 ACG Governor’s Award for Excellence in Clinical Research)
    UPMC co-authors: Claudia Rivers-Ramos, MD; Miguel Regueiro, MD; Jason Swoger, MD; Marc Schwartz, MD; Leonard Baidoo, MD; Jana Al Hashash, MD; Arthur Barrie III, MD; Michael Dunn, MD; David Binion, MD
  • Association of Mean Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Prospective Study
    UPMC co-presenters: Toufic Kabbani, MD; Claudia Rivers-Ramos, MD; Jason Swoger, MD; Miguel Regueiro, MD; Arthur Barrie III, MD; Marc Schwartz, MD; Jana Al Hashash, MD; Leonard Baidoo, MD; Michael Dunn, MD; David Binion, MD

For more information on ACG’s Annual Meeting, please visit the conference page.

UPMC Investigation into GI Scope-Related Infections Changes National Guidelines

PITTSBURGH, Oct. 9, 2014 – National guidelines for the cleaning of certain gastrointestinal (GI) scopes are likely to be updated due to findings from UPMC’s infection prevention team.

The research and updated disinfection technique will be shared Saturday in Philadelphia at ID Week 2014, an annual meeting of health professionals in infectious disease fields.

“Patient safety is our top priority,” said senior author Carlene Muto, M.D., M.S., director of infection prevention at UPMC Presbyterian Hospital. “We are confident that the change from disinfection to sterilization of GI scopes is necessary in preventing serious infections and we are glad to share our findings with hospitals nationwide.”

After tracking and monitoring  an uptick in antibiotic-resistant infections in 2012 in patients who had undergone an Endoscopic Retrograde Cholangiopancreatography (ERCP) procedure with flexible endoscopy scopes, UPMC began investigating the devices, which are equipped with an “elevator channel” used to deflect accessories passed through the biopsy channel and assist clinicians in examining a patient’s gastrointestinal tract. The elevator channel is most commonly found on ERCP and endoscopic ultrasound scopes.

UPMC took the scopes out of service, notified the manufacturer and began an investigation into the disinfecting process that takes place between each use. When it was ultimately determined that the normal process failed to eliminate all bacteria, UPMC switched to gas sterilization using ethylene oxide to ensure proper disinfection of the scopes.

“Throughout UPMC, no additional health care-associated infections have been linked to scopes since switching to sterilization,” said Dr. Muto.

The move from high-level disinfection of endoscopes to sterilization of them was foreshadowed earlier this year at the Association for Professionals in Infection Control and Epidemiology annual conference in Anaheim, Calif., by Bill Rutala, Ph.D., M.P.H., author of the Centers for Disease Control and Prevention Guideline for Disinfection and Sterilization in Healthcare Facilities. He said he believed the transition would take place in the next five years.

Approximately 11 million gastrointestinal endoscopies are performed annually in the U.S. and contaminated scopes have been linked to more hospital-acquired infections than any other type of medical device.

Pitt Drug Discovery Researchers Receive $5.8 Million Federal Grant to Build 3D Liver Model

PITTSBURGH, Sept. 23, 2014 – With a new $5.8 million, three-year award from the National Institutes of Health (NIH), researchers at the University of Pittsburgh School of Medicine will further develop a state-of-the-art, microfluidic 3D model system that mimics structure and function of the liver to better predict organ physiology, assess drug toxicity and build disease models.

The funding supports the next phase of the NIH’s Tissue Chip for Drug Screening program, which aims to improve ways of predicting drug safety and effectiveness. Researchers from 11 institutions will collaborate over three years to refine existing 3-D human tissue chips and combine them into an integrated system that can mimic the complex functions of the human body.

“We are very enthusiastic about the potential of these microphysiology systems to serve as powerful platforms for studying human diseases and identifying human toxic liabilities,” said the Pitt project’s principal investigator D. Lansing Taylor, Ph.D., Allegheny Foundation Professor of Computational and Systems Biology, Pitt School of Medicine, and director, University of Pittsburgh Drug Discovery Institute.

“The development of tissue chips is a remarkable marriage of biology and engineering, and has the potential to transform preclinical testing of candidate treatments, providing valuable tools for biomedical research,” said NIH Director Francis S. Collins, M.D., Ph.D.

The Pitt research team, along with additional collaborators, is creating models of the functional unit of the liver, called the acinus, using human liver cells and eventually liver cells derived from precursor cells known as induced pluripotent stem cells, as well as three additional cell types. The liver platform includes microfluidic devices, human cells, engineered matrix materials, fluorescence-based biosensors for real-time physiological read-outs, and biochemical and mass spectrometry measurements to determine acute and chronic toxicity effects. They also will build a “microphysiology database” to manage, analyze and model the data collected from the liver constructs.

With such a platform, biomedical scientists will be able to test treatment efficacy in conditions such as non-alcoholic fatty liver disease, liver cancer and breast cancer that has spread to the liver, as well as liver damage including immune-mediated toxicology and fibrosis.  Also, a team of institutions and investigators has been assembled to integrate the liver, kidney and gut models to recapitulate the organ system that is central to drug absorption and metabolism.

The integrated platform will involve the creation of a universal medium, the development of the proper “scaling” of the interacting organ constructs, physiologically relevant flow, incorporation of a micro-formulator to add factors from missing organs and micro-analyzers for monitoring parameters such as pH and oxygen.

Fifteen NIH Institutes and Centers are involved in the coordination of the tissue chip program. Current funding is being provided by the National Center for Advancing Translational Sciences, the National Institute for Biomedical Imaging and Bioengineering, the National Cancer Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, NIH Common Fund and NIH Office of Research on Women’s Health.

Collaborators include Martin Yarmush, M.D., Ph.D., of Massachusetts General Hospital; John Wikswo, Ph.D., of Vanderbilt University; Jonathan Himmelfarb, M.D., of the University of Washington; Mark Donowitz, M.D., of Johns Hopkins University; and Mary Estes, Ph.D., of Baylor University.

Screening and Drug Therapy Predicted to Make Hepatitis C a Rare Disease

PITTSBURGH, Aug. 4, 2014 – Newly implemented screening guidelines and improved, highly effective drug therapies could make hepatitis C a rare disease in the United States by 2036, according to the results of a predictive model developed at the University of Pittsburgh Graduate School of Public Health.

The results of the analysis, funded by the National Institutes of Health (NIH) and performed with the University of Texas MD Anderson Cancer Center, are published in the Aug. 5 issue of the Annals of Internal Medicine.

A “rare” disease is one that affects at most one in every 1,500 people. Approximately one in every 100 people in the U.S. currently has chronic hepatitis C, a viral infection that compromises liver function.

“Making hepatitis C a rare disease would be a tremendous, life-saving accomplishment,” said lead author Mina Kabiri, M.S., a doctoral student in Pitt Public Health’s Department of Health Policy and Management. “However, to do this, we will need improved access to care and increased treatment capacity, primarily in the form of primary care physicians who can manage the care of infected people identified through increased screening.”

In the U.S., hepatitis C is the leading cause of chronic liver disease and the leading reason for liver transplantation. At 15,100 deaths annually, hepatitis C surpassed the annual number of deaths from HIV in 2007. The economic burden associated with chronic infection is estimated at $6.5 billion a year.

“This is, indeed, a very interesting time for hepatitis C patients and providers,” said senior author Jagpreet Chhatwal, Ph.D., now of the University of Texas MD Anderson Cancer Center, who performed most of the research while at Pitt Public Health. “Several changes have happened in the last two years, including screening policy updates and availability of highly effective therapies.”

In 2012, the Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommended that anyone born between 1945 and 1965 — encompassing about 81 percent of chronically infected people — receive a one-time screening for hepatitis C. Hepatitis C often is asymptomatic, meaning that infected people do not know they have it until it is detected through a blood screening.

In early 2014, hepatitis C drug regimens that could be taken orally were introduced to the market, allowing primary care physicians and infectious disease specialists to take on the role of treating hepatitis C patients. The drugs have been shown to be highly effective in making the virus almost undetectable in the blood of patients previously found positive for hepatitis C.

The research team created a highly detailed computer model of the natural history and progression of hepatitis C, both with and without treatment. The model predicts the number of hepatitis C infections in the U.S. at any given time from 2001 to 2050, under multiple potential scenarios describing future treatment, while taking into consideration infection status awareness, stage of disease, treatment history and continued drug development, based on data from the National Health and Nutrition Examination Survey (NHANES) and published clinical studies.

To validate the prediction, the researchers ran the model for the years 2003 to 2010 and predicted 2.7 million cases of hepatitis C, which equaled the actual number of cases reported by NHANES.

The research team then considered what would happen if the guidelines were increased to include a one-time universal screening for hepatitis C among all U.S. citizens, not just baby boomers.

“In that scenario, nearly 1 million cases of hepatitis C would be identified in the next 10 years,” said Ms. Kabiri. “And that translates into making hepatitis C a rare disease by 2026, a decade earlier than we’d predicted with the current screening guidelines.”

The researchers note that such a measure would bring increased costs. The oral therapy regimen costs as much as $1,000 per day.

The model estimated that universal screening coupled with the new drug therapies would reduce liver-related deaths by 161,500 and liver transplants by 13,900 from 2014 to 2050.

“Though impactful, the new screening guidelines do not identity the large number of hepatitis C patients who would progress to advanced disease stages without treatment and could die,” said Dr. Chhatwal. “More aggressive screening recommendations are essential in further reducing the burden, preventing liver-related deaths and eventually eradicating hepatitis C.”

Future research will be needed to determine how the reduction in deaths and transplants offsets the increased costs of screening and drug therapy.

Additional researchers on this study are Alison B. Jazwinski, M.D.; Mark S. Roberts, M.D.; and Andrew J. Schaefer, Ph.D., all of Pitt.

This study was supported by the National Center for Advancing Translational Sciences of the NIH under award number KL2TR000146.

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