Expert: ‘Valuable, real-world data’ combats rising prevalence of NAFLD

LONDON — Longitudinal serum alanine aminotransferase trajectories remained stable over time among a subset of patients with nonalcoholic fatty liver disease, according to research presented at the International Liver Congress.

In a Healio exclusive interview, Arun J. Sanyal, MBBS, MD, director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, interim chair of the division of gastroenterology, hepatology and nutrition, and Z. Reno Vlahcevic professor of medicine, physiology and molecular pathology at Virginia Commonwealth University School of Medicine, highlights key takeaways from the study and discusses how these real-world results could inform patient care going forward.

Healio: Why did your team explore this topic?

Sanyal: Serum ALT has been a commonly used tool to assess trajectory of liver disease for many decades. The pattern of ALT movement over time in NAFLD — especially as a function of baseline levels at the time of diagnosis — was not known. This gap in knowledge is significant because once therapies are started, it becomes challenging to figure out whether a change in liver enzyme level reflects the course of the disease or the drug effect.

As a first step to resolving this unmet need, we analyzed patterns of liver enzymes over time in a large cohort of patients with NAFLD in a real-world setting. Global prevalence of NAFLD is estimated at 25%, and diagnoses have increased over the past two decades. It is a growing public health concern, with few treatment options.

Healio: How was this study designed?

Sanyal: This real-world study analyzed over 3,600 adult patients with NAFLD in the U.S. with three or more ALT measures. ALT categories were defined as normal ( 30 U/L), slightly high (1-2 times normal), high (2-3 times normal) and very high (> 3 times normal). Patients were followed over a median of 38.2 months with 3.9 months between ALT measures. The median age of patients was 59 years, with a history of hypertension (74%), type 2 diabetes (54%), cardiovascular disease (22%) and statin use (46%). Patients in higher ALT categories at baseline were younger with a higher proportion of Hispanic or Latino participants in comparison to lower ALT categories.

Sponsored by Target RWE, TARGET-NASH is a longitudinal, observational cohort of adult and pediatric participants with NAFLD and/or NASH receiving usual care from academic and community centers in the U.S. and Europe, enrolling over 7,000 participants to date. Real-world data is collected from consented participants, who may also provide patient-reported outcome measures and biospecimens.

Healio: What were the key takeaways?

Sanyal: This study found that longitudinal ALT trajectories remained relatively stable over time for many participants with NAFLD.

Patients in higher ALT categories at baseline were younger with a greater percentage of Hispanic or Latino participants vs. lower ALT categories. At baseline, 33%, 38%, 15% and 14% of patients had normal ALT, slightly high, high and very high ALT levels, respectively. In the unadjusted model, 39% with normal ALT at baseline remained in that category during follow-up.

In the routine clinical settings, having normal liver enzymes is often construed as evidence of lack of liver disease. This study shows that 71% of this cohort either had either normal or near-normal liver enzymes. This reinforces the concept that the presence of fatty liver disease cannot be ruled in or out by the liver enzyme levels and requires consideration of background risk factors and demonstration of fat in the liver.

Healio: How will these results inform patient care going forward?

Sanyal: Understanding the course of ALT fluctuations is important for helping to differentiate natural variation from potential hepatotoxic or beneficial effects of treatments and to create models to assess disease trajectory to clinic outcomes.

Healio: What additional research, if any, is needed?

Sanyal: Researchers have not been able to keep pace with the rapidly growing disease burden of NAFLD that is an increasing concern from a public health standpoint. It is important to continue to generate valuable, real-world data to battle the rising global prevalence of NAFLD. Further research and analyses are needed to explore ALT trends associated with probability of clinical outcomes.

Healio: Is there anything else you would like our readers to know?

Sanyal: We were proud that this research was selected by EASL to be a part of the poster tours at the International Liver Congress. I believe that this speaks to both the academic rigor of the research as well as the need for real-world evidence to help guide clinicians who care for the majority of patients who fall outside of a controlled clinical trial setting.