Yale’s Section of Digestive Diseases has long been a leader in research, clinical care, and training. Due to their exceptional expertise, many of its 60 full-time faculty have been tapped to create guidelines for the treatment of digestive ailments ranging from gastrointestinal bleeding to fatty liver disease.
Below are some highlights of their work:
Advanced Hepatocellular Carcinoma (HCC), Hepatocellular Carcinoma, and Non-Invasive Liver Disease Assessment
Tamar Taddei, MD, has been interested in liver cancer since her fellowship days. From that interest, she became a clinical program builder in liver cancer and a clinical investigator studying outcomes in liver cirrhosis and liver cancer. These studies have elucidated gaps in our understanding of how best to identify and treat liver cancer, and she is currently working on clinical trials aimed at improving diagnosis and treatment of patients with liver disease.
She was asked to join the American Society for Clinical Oncology’s writing group for the advanced HCC guidelines by Michal Rose, MD. “The fact that they actually sought the advice of other disciplines shows that they understand the need for diverse inputs,” said Taddei. These guidelines, Taddei remembers, were put together and published fairly quickly after several calls and extensive literature review. The American Association for the Study of Liver Disease (AASLD) non-invasive liver disease assessment guidelines, on the other hand, is a more intense endeavor, with over 800 papers reviewed during the process of writing a guideline document and three accompanying systematic reviews. Taddei appreciates the intellectual stimulation from discussions with her co-writers, “We really sit down and hash it out, which is nice. You learn a lot from others and gain new insight from different perspectives.” As these guidelines wrap-up, Taddei will serve as a co-chair of the AASLD guidelines for HCC.
Autoimmune Hepatitis and Primary Sclerosing Cholangitis
David N. Assis, MD, realized his passion for autoimmune liver diseases after performing research and interacting with liver disease patients at the clinic of his mentor, James Boyer, MD. “It was a great experience to realize that I could focus on these conditions by treating patients in clinic, doing laboratory and clinical research on these same conditions to create new innovations, and now, additionally focus on education and guidelines to bring the field forward,” explained Assis.
As a member of the writing group for the autoimmune hepatitis (AIH) guidelines, and current co-chair of the primary sclerosing cholangitis (PSC) guidelines, Assis recalls the fulfillment of getting to know his co-writers and knowing the guidelines’ impact on patients and providers across the country. Furthermore, both AIH and PSC are rare diseases, often lacking the high-impact, randomized controlled trials with large numbers of patients that is typical of other fields and thus, currently rely more upon smaller studies and expert interpretation to craft the guidelines. “It was eye-opening for me to realize in more detail the limitations of the data in existence. Frankly, it also highly motivated me and the rest of the writing groups to push forward and expand our research so we can improve the data quality and care recommendations for future guidelines.”
Looking forward, Assis emphasizes the American Association for the Study of Liver Disease’s (AASLD) plan to involve patients, caregivers, providers, treatment centers, and patient foundations in efforts to improve the field and show their voice in the guidelines. “These efforts are not being done in a vacuum, and we want the guidelines to benefit all aspects of patient care.”
Cirrhosis, COVID, Hepatitis B & C, Liver Elastography, and Liver Function Test
Joseph Lim, MD, has been involved in a number of guidelines from organizations such as the American Gastroenterological Association (AGA), the American College of Gastroenterology (ACG), and the national VA System addressing topics including hepatitis B, hepatitis C, cirrhosis, abnormal liver tests, and liver elastography. However, the COVID-19 guidelines he worked to develop were different. At the beginning of the pandemic, simple questions needed answers: “What are the requirements for gastroenterologists to perform upper endoscopy and colonoscopy in a manner that keeps endoscopists, staff, and patients safe, recognizing that GI endoscopy could be considered an aerosol-generating procedure? Do we need a surgical mask or a N95 mask? Is pre-procedure COVID testing needed? Is a negative-pressure room necessary?” So unlike other guidelines, which easily take two years to develop, Lim and six other faculty members put together the first draft of the guideline in nine days, and the final manuscript was accepted and published online in Gastroenterology eight days later.
“It was a very unique and meaningful experience. To do something in that short time frame was because of a shared sense of purpose by a small group of gastroenterologists who were committed to doing their best to provide time-sensitive, evidence-based guidance to our GI community.”
To ensure the standardization of guidelines so that the guidance is objective, reproducible, and of direct clinical relevance to physicians, the AGA uses GRADE methodology in guideline development (Grading, Recommendations, Assessment, Development and Evaluation), developing evidence profiles to address questions based on a principle called PICO (Patient population, Intervention, Comparator, and Outcome of Interest). “Ultimately, we have a responsibility to develop practical recommendations that can be directly applicable to real-world medical decisions.”
Cirrhosis, Portal Hypertension, and Variceal Hemorrhage
For Guadalupe Garcia-Tsao, MD, her interest in the liver started with a little booklet back in medical school called The Jaundiced Patient, a book that detailed the pathways leading to a patient developing jaundice. She was always interested in working up patients with jaundice and sought mentorship in Hepatology in Mexico, her native country and then at Yale New Haven Hospital and the VA-CT Healthcare system. Garcia-Tsao recalls an annual liver meeting she was invited to as a medical student, “From there, I just absolutely loved the liver. To me, that was the most interesting part of medicine.”
Garcia-Tsao remembers fondly her work on a cirrhosis guideline for the Department of Veterans Affairs (VA), that encompassed management of all complications of cirrhosis “It was a ‘tour de force’ and I am very proud of it.” From this, the VA Cirrhosis Quicknotes emerged. Her expertise was sought after to co-author multiple guidelines for the American Association Study of Liver Disease and the American College of Gastroenterology, including one in development for portal hypertension and variceal hemorrhage. She emphasizes the importance of patient care in developing guidelines, “Expertise in patient care can offer a little more than what you can glean from looking at leading papers.”
At the end of the day, Garcia-Tsao looks forward to spreading the word of new advancements in liver disease treatment and improving the care for cirrhosis patients. “My hope is that we can finish these guidelines soon, so that people can start treating patients with the state-of-the-art type of therapy and make them live longer and better.”
Deborah Proctor, MD, is an expert in complex cases of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. The American Gastroenterology Association (AGA), of which she has been involved for 30 years, reached out to her via her colleague, Thiruvengadam Muniraj, MD, FRCP, who was on its Clinical Guidelines Committee. They were seeking an update to treating patients with Crohn’s disease that have moderate to severe diseases, a treatment that requires very complex and multifaceted medications, and asked Proctor to be on the clinical guidelines writing committee.
“And I said, ‘Yes, of course.’”
The process took about two and a half years, and two committees, all experts on inflammatory disease. Proctor’s group was focused on the literature review and the guideline suggestions, aided by specialists who helped them sift through the 200-300 references eventually used in the guidelines. Once compiled, the other group would rewrite the technical language used by the first to make it readable and digestible. From there, the guidelines are uploaded for membership discussion, which are addressed, and then published. Proctor remembers the process fondly, “It was fun from several aspects. One, that from my deeper dive into the literature than normal, I learn. And the second thing is I got to work with a lot of people and got to know them better. And that to me, was a lot of fun.”
Endoscopic Resection and Pancreatic Cancer Screening
Harry Aslanian, MD, grew interested in advanced endoscopy because of the wide spectrum of gastrointestinal malignancies that can be diagnosed and treated. As endoscopic technologies evolved from mucosal resection to treating more complex lesions and resect deeper depths into the intestinal wall, he notes the importance of finding its place among surgical approaches, “Endoscopists look to evaluate how these fit in with other approaches and what data is available to guide balancing risks and benefits when approaching different clinical problems.”
His interest in pancreatic cancer arose from wanting to improve outcomes and early detection of one of the most common causes of cancer death in the United States. “Early detection can provide an opportunity to pursue curative resection while lesions are localize to the pancreas. The potential for screening to have an impact has increased as high risk groups are identified and imaging and other techniques advance to improve early detection.”
The recent endoscopic full-scope resection guidelines were prepared by the American Society of Gastrointestinal Endoscopy (ASGE) technology committee and the pancreatic cancer screening guideline was commissioned by the American Gastroenterology Association (AGA), Aslanian’s experience in building guidelines for both was the same. “Participation in guideline preparation can be very rewarding, working with colleagues and analyzing data and opinions to provide a concise document that can impact patient care.”
Loren Laine, MD, worked to become a gastrointestinal (GI) bleeding specialist since the beginning of his professional career. Knowing that GI bleeding was the major emergency seen by gastroenterologists and the most common reason for hospitalization among GI diagnoses, Laine says, “I felt that this was an important area of clinical care and research in GI.” Now, a content expert and methodologic expert in GI bleeding, Laine was invited to participate in the recent International Guidelines as a member of the steering committee overseeing development of those guidelines and as the lead author of the 2021 U.S. American College of Gastroenterology (ACG) guidelines.
His interest in guidelines has been long-standing. From 2012 to 2013, he was president of the American Gastroenterological Association (AGA). A year earlier, the Institute of Medicine (now, the National Academy of Medicine) published “Clinical Practice Guidelines We Can Trust,” which pointed out the flaws in documents published as guidelines in the past, and outlined how guidelines should be developed so that they would be trustworthy and reliable. That, along with the incorporation of the GRADE methodology in guideline development during that last 10 years, has bolstered the development of trustworthy clinical guidelines. As president, “one of my initiatives was to ensure our organization was more rigorous in its guideline development process.”
Wilson’s Disease and Liver Transplant during COVID-19
Michael Schilsky, MD, FAASLD, was involved in the writing of the first American Association for the Study of Liver Diseases (AASLD) Guidelines for the Diagnosis and Treatment of Wilson disease at its inception in 2003. In this effort, he partnered with his colleague Eve Roberts, MD, PhD, an expert in pediatric liver disease. Eighteen years later, Schilsky and Roberts again take the lead as co-first authors and chairs for the updated and soon to be released AASLD guidance on Wilson disease, this time incorporating a multidisciplinary writing group.
“We took the opportunity to have our guidance reflect the multidisciplinary care model for these patients, and included colleagues from neurology, psychiatry, dieticians, as well as pathology, which had never been done before in any of the society guidelines.” said Schilsky.
The inception for the AASLD-sponsored COVID guidelines was born from a need to disseminate the evolving practices for liver transplantations during a rapidly evolving pandemic. “[We realized] that there were a number of common practice adaptations by members from around the country to deal with the crisis, and many knowledge gaps that needed filling very quickly.” One project that he’s proud of was to help organize discussion on healthcare disparities uncovered by the pandemic, socioeconomic, ethnic, and other categories among different groups in North America and the UK. This became the subject of an AASLD sponsored webinar and a follow up manuscript on which he was senior author, “COVID-19 and the uncovering of healthcare disparities in the US, UK and Canada: Call to action,” that soon will be published in Hepatology Communications.
Since forming one of the nation’s first sections of hepatology and then gastroenterology over 50 years ago, Yale’s Section of Digestive Diseases has had an enduring impact on research and clinical care in gastrointestinal and liver disorders. To learn more about their work, visit Digestive Diseases.