Q&A with Dr. Rohit Loomba: The Liver, a Fascinating Organ

Dr. Rohit Loomba
Professor of Medicine
Director, NAFLD Research Center
Director of Hepatology
Vice Chief, Division of Gastroenterology
UC San Diego

Dr. Loomba is an internationally recognized thought leader in Nonalcoholic Fatty Liver Disease (NAFLD). NAFLD is estimated to affect 80 to 100 million people in the United States. It has few symptoms, but has been linked to obesity, type 2 diabetes, and family history. Dr. Loomba describes the liver as a “fascinating organ,” drawn to it as an area of specialty while being mentored by outstanding hepatologists at medical school, during his residency, and as an NIH fellow. But foremost, he is a teacher, listing that as his title on Profiles.

Dr. Loomba is the featured speaker at the ACTRI Seminar on July 19 at 2 p.m. at the ACTRI Building Auditorium, where he will present, “Innovations in Non-invasive Imaging Assessment of Treatment Response in NASH.” The talk will focus on some of the work Dr. Loomba and his colleagues have been doing in advanced imaging to non-invasively assess fibrosis. He will discuss how that assessment relates to treatment response, briefly summarize the history of NAFLD, and how work performed here has transformed treatment trial design.

Dr. Loomba is a prolific user of the ACTRI research clinic, where he conducts dozens of NAFLD clinical trials. He has written more than 200 papers published in peer-reviewed journals, including, “Novel link between gut-microbiome derived metabolite and shared gene-effects with hepatic steatosis and fibrosis in NAFLD,” published earlier this spring in Hepatology. He is the recipient of numerous research grants and prestigious awards, and strives to balance teaching, research and serving patients – and maintain a healthy family life.

Dr. Loomba sat down this spring in his ACTRI Building office to discuss his work with ACTRI communications director Patricia Wieser.



Q: As a gastroenterologist, how did you choose hepatology as a subspecialty? And what drew you to NAFLD and NASH?

A: I had great mentors who were hepatologists at the Armed Forces Medical College in India. Then I came to the United States for my residency and worked with Dr. Brent Tetri and Bruce Bacon, two renowned hepatologists at St. Louis University. After that I went to the NIH in Maryland and did three years of fellowship in liver disease and clinical investigation, and worked under the mentorship of the legendary hepatologist, Jay Hoofnagle, and Jake Liang, Chief, Liver Diseases Branch (LDB). I always found that liver was just a fascinating organ — it is at the intersection of metabolism, endocrine and liver disease. Early on there weren’t a lot of therapies for liver disease and when I was at the NIH they were trying to work on hepatitis C. I was fortunate enough to work alongside Harvey Alter who won the Lasker Award for his contributions to define hepatitis B and hepatitis C as the cause of transfusion associated hepatitis. LDB was focused on viral hepatitis, but I was fortunate enough to be given a project to study the role of metformin for the treatment of NASH. I took over that project and it gave a purpose to the rest of my investigative career. After finishing my liver fellowship at NIH, I came to UC San Diego. San Diego has a large Hispanic population and fatty liver disease is prevalent among this population, and that’s how I became interested in developing a NASH and NAFLD program. As a fellow here I started working on developing a large NAFLD cohort and NAFLD research program. I was inspired by a quartet of key mentors here at UC San Diego, including Elizabeth Barrett-Connor, Daniel O’Connor, John Carethers and David Brenner. At that time, it began as a NAFLD clinic, but over the years we have grown into one of the largest NAFLD programs in the world.

This area of research is also large within the ACTRI. I am told that about one in six patients seen in the ACTRI clinic is in our NAFLD research program and our goal is to double the number of these research visits in the next two years. We have several prospective studies that are underway and each study is designed to answer a clinical question. NASH is the second leading indication for liver transplantation. There is no approved therapy. Our central mission is to replace liver biopsy with a non-invasive assessment for disease severity for NASH, and then to develop therapies for treatment of NASH and NASH liver fibrosis. 

Q: When was diet and obesity first linked to liver health?

A: We are finding that diabetics may have a higher predisposition to fatty liver disease. To that end we have started a diabetes screening program which is free of cost. We screen any patient 50 and older with type 2 diabetes for liver disease – for advanced fibrosis and cirrhosis. We use an advanced MRI liver stiffness ultrasound and scan. This work is being done in collaboration with faculty in internal medicine and family medicine so we are extremely grateful to our referring providers for their support of our research mission.

Q: Tell me about your upcoming (July 19) seminar at ACTRI , Innovations in Non-invasive Imaging Assessment of Treatment Response in NASH.

A: We lead the world in advanced imaging in liver fibrosis. The first trial to use an MRI as the primary endpoint was designed by me and we did it here. Now there are 25 other trials using an MRI for treatment response assessment. We collaborate closely with the liver imaging group, which is headed by Dr. Claude B. Sirlin, and with Dr. Michael Middleton now focusing on central reading for multicenter studies. We are also working on genome-based biomarkers, microbiome biomarkers, plasma-based biomarkers, and urine-based biomarkers to determine the NASH or liver fibrosis.

Q: What has been the biggest surprise – “aha moment” – you have found in your research?

A: Our moment is still to be arrived when we will replace the need for a liver biopsy for institution of treatment in NASH.

Q: What is the top recommendation you give to patients to stay healthy, specifically to keep their livers healthy?

A:

  • Watch sugar and sugar-contained beverages
  • Limit portion size
  • Adopt and minimize alcohol use to one drink in 24 hours
  • Exercise 30-45 minutes 3-5 times a week

Q: Tell me about your experience mentoring students, especially through the TL1 program. What is the most important aspect of mentoring? And what did you learn?

A: I have gained so much from my mentors and my goal is to “pay it forward.” I’ve probably worked with more than 40 students and trainees (among them TL1). Many students are looking for clinical research opportunities and that’s why they come to our lab. Our projects are exciting and diverse, ranging from biomarker-based studies, imaging assessment, epidemiology of NAFLD, familial risk, twin genetics to microbiome. We’re screening patients and family members of patients with NASH cirrhosis. If someone is diagnosed with cirrhosis, we bring in their family members and do an MRI and MRE [magnetic resonance elastography] to look for liver fat fibrosis and see what prevalence of advanced fibrosis.

Several of our students have had really amazing publications. Some of them have been first authors publishing in Hepatology and Gastroenterology, which are major journals in the fields with high-impact factors. Students enjoy working here because our projects are clinical and have a direct implication on clinical practice, and we are defining the use of these methods in the field. We have several patients who have improved their liver fibrosis or reversed their NASH, and our students see that. They see the impact of our research right now.

One student spent a year here after she had finished her MD and was transitioning to residency. She was the first author on a JCI paper during that transition. I also had a high school student who worked with me and now he is going to UC Berkeley for his undergraduate degree. It is gratifying to see students take part in research and then go on and excel in whatever field that they have chosen. As a middle school student, my son worked with Dr. Claude Sirlin for a month in the Liver Imaging Group and learned how to quantify liver fat. Engaging students at a younger age can transform them for the future.

Q: From what you mentioned earlier, it sounds like there were special mentors who have had a dramatic influence on your own life.

A: I’ve had several mentors and they’ve had major impact on my life. I will start with acknowledging my parents and my elder brother and sister who were my first mentors. I met my wife right after medical school and she was instrumental in inspiring me to continue my passion for liver research, which led me to join NIH for a fellowship rather than take a lucrative private practice job. Drs. Jay Hoofnagle and T. Jake Liang at NIH. Both of them really transformed how I think. I learned research integrity and courage to state the truth with clarity from Jay, and Jake taught me how to be efficient and how to be a team leader. My research program is largely inspired by what I learned from them. Then my quartet of mentors at UC San Diego helped sharpen by skills in epidemiology, twin genetics and establishing synergistic collaborations across silos.

Q: How do teaching/mentoring, clinic, and research work together? What are the impacts of each on the other?

A: There is a great misunderstanding that researchers can’t be good teachers or great clinicians. You can be all three. My research inspires me to take better care of my patients and that inspires me to teach students what I have learned through my research and clinic.

When you meet with a mentor you understand how they approach a problem. I teach and mentor in how to think differently. There is diversity in teaching styles and mentoring at universities. Some teachers do great classroom teaching and some do great one-on-one mentoring. My passion is one-on-one mentoring because that’s how I learned and how my future was made.

It is important to understand the steps in treating a patient, and that you can modify that treatment in the future. We haven’t solved all the diseases and all the problems associated with them. Some of facts I read in Harrison’s Principles of Internal Medicine 30 years ago aren’t true anymore because someone challenged the existing paradigm and then generated evidence to establish the current paradigm. My goal is to support the new genre of trainees to challenge the current way of the practice of medicine and then develop evidence to impact clinical practice within our lifetime.

Q: How do you organize your time – and also manage to write papers, give lectures …and have a life?

A: If you enjoy doing what you’re doing, the enjoyment manages your time. If you dread something, then you need to work to organize your time. I prioritize around things that can only be done by me. I’m a dad and nobody can be a dad to my kids except me so that comes first. It’s my top priority. The same idea for our patients. If something is clinically important and can only be done by a doctor, then we perform that task. We prioritize lectures based upon audience and venue, which means we have to say no to a lot of lectures. Paper prioritization is based upon the clinical impact of the paper. We are writing 35 papers a year and not able to write about 15 more. If something is important we write that first because it will affect patient care.

Clinical trials are also for our patients. We have two missions: The first is to develop non-invasive biomarkers and the second is to develop a treatment for NASH. Anything that’s aligned to those two we do. And we don’t take on clinical trials in other liver diseases. The reason we are big in NASH is because of our focus – because we don’t do other things that would dilute us.

Q: What do you like to do in your “free” time?

A: I watch movies with my family and I like to run with my wife. I also enjoy traveling with my family.

Q: Favorite movies?

A: Bollywood movies. Guru (2007 biographical drama), Yeh Jawaani Hai Deewani (2013 romantic drama) and Sholay (1975 action-adventure) are three favorites.

Q: What makes UC San Diego so important to your research and success?

A: I wouldn’t have been able to achieve what I have achieved anywhere else in the world. UC San Diego allows you to create something and all the leaders support you in one way or another. They see the value of providing the best quality research that can be aligned with clinical care to our patients.

We have a uniquely collaborative environment. I work very closely with so many other researchers on campus and various institutes on the Mesa, including JCVI and the Salk Institute. This is probably one of the most collaborative universities in the world and I have been fortunate to receive the fruits of that creative and collaborative environment.

Q: If you had not gone into Medicine, what would you have done?

A: I have always been interested in medicine, even as a child. I grew up in India and my mom had a skin condition. She wanted at least one of us to be a doctor [Loomba is one of three children] and it ended up being me.

These are exciting times in clinical research. As a hepatologist in clinical research, if I were to redo my training it would be exactly same. In all of medicine, hepatology is the most exciting area to practice now and will continue to be in the future. If you want to be a top-notch hepatologist, this is the place to be in the world. We attract the best and the brightest. We could design any study to answer a clinically relevant question with a goal to improve clinical practice and that’s the beauty of UC San Diego.

Q: How has ACTRI, especially the clinic and staff, been helpful to you in your clinical trials and research?

A: We see approximately 20 patients a week in research – and that would not be possible without the help of the ACTRI clinic staff, the ACTRI director (Gary S. Firestein, MD), and the IRB director (Anthony Magit, MD). When I request something, they ask how they can help. We are trying to improve the research environment and clinical care, and see how we can align them. Vice Chancellor David Brenner and my Division Chief Dr. Bill Sanborn and Department Chair Dr. Wolfgang Dillmann have also been extremely supportive and we work closely together.

The ACTRI facility has been a big boon to our research, but our program has exponentially grown so we need more space now. Among all aspects of medicine, NASH is probably one of the top areas for drug development currently. We lead all the UCs – we’re the topmost NAFLD center on the west coast if not in the world. It is largely due to our strategic focus on clinical investigation in NAFLD and a collaborative network of multi-disciplinary teams of investigators.

Q: If you could collaborate with anyone, dead or alive, who would you pick?

A: Mahatma Gandhi and Albert Einstein.


About UC San Diego Altman Clinical and Translational Research Institute:

UC San Diego Altman Clinical and Translational Research Institute (ACTRI) is part of a national Clinical and Translational Science Award consortium, led by the National Institutes of Health National Center for Advancing Translational Science. Established in 2010, ACTRI provides infrastructure and support for basic, translational and clinical research throughout the San Diego region to bring discoveries from the laboratory to the bedside, and facilitates training and education of the next generation of researchers. ACTRI carries out its activities in collaboration with institutional and corporate partners and currently has more than 1,425 members.

actri.ucsd.edu