Q&A: Nearly a third of obese adults with NAFLD achieve weight loss
During a follow-up of 39 months, 32% of overweight or obese patients with nonalcoholic fatty liver disease achieved 5% or greater weight loss, according to results published in Clinical Gastroenterology and Hepatology.
Twenty-five percent of these patients maintained 5% or greater weight loss.
Healio Gastroenterology spoke with Anna S. Lok, MD, professor of internal medicine, director of clinical hepatology, University of Michigan, about results from the ongoing TARGET-NASH study assessing weight loss and weight regain in NAFLD patients.
Healio: What the purpose and design of the study?
Lok: The Target RWE study is a real-world study across multiple sites in the US. It's very broad so we can include anyone with a diagnosis of fatty liver or non-alcoholic fatty liver who we manage in the participating sites. It does not dictate how we manage them, how we treat them, how often we follow them and what tests we do. In fact, there isn't a real protocol. Once a patient has a diagnosis and provides consent, the consent allows us to extract relevant documents from the medical records and send to a centralized site, where there is a team of data abstractors. They follow a protocol, and they pull pre-defined data from those documents we sent. That includes clinic notes, radiology reports and pathology reports, and they enter those data into a big database. From that, all sorts of data analyses are performed depending on the purpose of each paper. With the patient's consent, they give us permission to go back 3 years prior to the consent and to prospectively collect data for another 5 years. So, potentially we could have a total of eight years data. Obviously, the study hasn't gone on long enough. We have a mean of about 2 to 3 years prospective data on most of the participants so far.
Healio: What were the results that came from this study on weight loss and weight regain?
Lok: Weight loss and weight regain is something that interests many of us in clinical practice. For patients with fatty liver, the most important thing that would benefit them is if they manage to lose weight, but it’s always hard. We were interested in knowing how often people lose weight. Many people do manage to lose weight at some point, it's just that they would gain it back. We also wanted to look at how many people regain weight among the people who lost weight during the study. We don't have a long duration of follow-up, so we start from the time we have the first record of weight.
We excluded people who underwent bariatric surgery during the study, obviously, that weight loss is related to this specific procedure. We also excluded patients with decompensated cirrhosis because ascites can influence the weight. Further exclusions involved patients who had a cancer diagnosis during the study period because that might account for the weight loss. Our question was what proportion of patients with fatty liver would lose weight.
We used a 5% or greater change in weight as a definition of weight loss, because people can have fluctuations in weight over time. If they lose 1% is that actually important? Median follow-up was 39 months, roughly 3 years. During that time, one-third of the patients had weight reduction of at least 5%.
We picked 5% because we know that 5% would result in some observable clinical benefit, such as improvement in liver enzymes and reduction in fat in the liver. But if you really want to see greater improvement, which include reversal of fibrosis, you need a 10% weight loss to achieve those more important outcomes. So, 5% is about the minimum to see a clinical benefit.
The bad news is, as we followed these people who lost weight, we over 2 and a half years –one-fifth of them had regained weight back to baseline and some of them even more than the baseline. Roughly 60% regained the weight back within the first year of the weight loss. This type of ‘yo-yo’ is what we see very often in clinical practice in real life.
Healio: What are the key takeaways from the study for other physicians looking at the weight loss and regain in patients with liver disease?
Lok: Patients were not offered any specific intervention in this study. We looked at the medical records to see if there was any record of the physicians telling the patients to lose weight, giving them guidance, and referring them to see dietician or helping them enroll into any lifestyle intervention program. Having said that, we also found that there are times when certain things we discuss with the patient is not always documented so just because you can't find the documentation in a medical record does not necessarily mean that it wasn't done. Also, we don't have details of what counseling was provided, because I could just say, “Well, you really need to lose weight, because you have fatty liver,” or I could have spent 20 minutes going over with the patient about diet and making very specific recommendations. Those details are not captured very well in medical records. So, we don't really know why some patients lost weight and other patients didn't and whether physician advice and counseling made a difference. What we learned is as physicians we need to do a better job at providing more structured guidance to our patients.
Healio: What is the next step in research?
Lok: The study is ongoing so it could go on for at least another 2 to 3 years, and probably longer because this is a disease that is increasingly more common, and the field is evolving. Most of our patients continue to be followed in this study. There's a very small proportion of patients who have withdrawn. And obviously, one of the things is to look at a longer period of time. Instead of looking at 2 to 3 years, we look at 5 or 6 years, what would be the results. As we become more cognizant that we need to do a better job in providing patients with more structured guidance, instead of just a quick recommendation, and we develop a better way of tracking things, we'll see whether there's any change in the outcomes.
The other thing that we will be interested in is looking specifically among the patients who have lost weight and are able to maintain the weight loss if there is any evidence that the liver disease really improved. This would be a real-world study where we can show that. If these patients lose weight and maintain weight loss over a 2-year, 3-year or 4-year period, if we gradually see an improvement in the liver disease, that will be an important piece of information.