Patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis can suffer a variety of related symptoms, most notably significant fatigue, but also pruritus and abdominal discomfort, researchers have found.
The real-world analysis also found that these individuals can experience either spontaneous improvement or worsening of both fibrosis and patient-reported outcomes.
“The Global NASH Council collaborates on different aspects of NASH-related research throughout the world,” said Zobair Younossi, MD, MPH, the president of Inova Medicine and chairman of medicine at Inova Fairfax Medical Campus, in Falls Church, Va. “As part of that collaboration, we created the Global NAFLD/NASH Registry, which collects and manages clinical data and patient-reported outcomes. Now we have enough patients to examine changes in these outcomes over time, to see if patients are improving or worsening, as well as the variables that may predict those changes.”
Younossi and his colleagues analyzed the global registry, which compiled clinical end points and patient-reported outcomes at baseline and a one-year follow-up visit. Clinical end points included patient demographics, Fibrosis (FIB)-4 score, and liver stiffness by transient elastography. Patient-reported outcomes were the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), the Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis (CLDQ-NASH), and the Work Productivity and Activity Index (WPAI).
The presence of advanced fibrosis or cirrhosis was assessed by liver biopsy, transient elastography (=11.4 kPa) or FIB-4 score (=2.67). The researchers defined significant fatigue improvement or worsening as a change in the CLDQ-NASH score of 0.5 points from baseline. Finally, significant improvement or worsening of fibrosis was defined as a 25% change in liver stiffness or a 10% change in the FIB-4 score.
Not a Symptomless Disease
In a presentation at the 2020 digital Liver Meeting (abstract 701), Younossi reported that 5,148 NAFLD patients were enrolled in the registry from 18 countries in North America, the Middle East and North Africa, Europe and Australasia. Of these, 451 had baseline and follow-up patient-reported data, and 29% had advanced fibrosis or cirrhosis.
“When you look at patients’ baseline scores, one thing is pretty clear,” Younossi told Gastroenterology & Endoscopy News. “While most of us thought NASH is an asymptomatic disease, that is not true.”
In fact, Younossi’s team found, approximately 40% of NASH patients—even those in the early stages of disease—reported significant fatigue. “Furthermore, 20% to 25% of NASH patients have pruritus, which is not something we’ve thought about in NASH. Finally, we found that between 18% and 20% have some form of abdominal discomfort that they complain about,” he said.
At the one-year follow-up mark, 26% of patients reported an improvement in fatigue, while 10% experienced worsening. Patients whose fatigue improved were younger (49.8 vs. 54.1 years; P=0.019), more commonly men (59.3% vs. 31.9%; P=0.0038), and were less likely to have hypertension (42.4% vs. 57.4%; P=0.039). By comparison, patients whose fatigue worsened had a higher baseline fatigue score (5.1 vs. 4.5; P=0.0102).
A total of 329 patients had baseline and follow-up FIB-4 or liver stiffness data. Of these, 25% demonstrated an improvement in fibrosis (mean FIB-4 change, –0.29; mean liver stiffness change, –6.6 kPa), while another 29% worsened (FIB-4, +0.27; liver stiffness, +3.8 kPa). The only predictor of fibrosis improvement on multivariate analysis was the presence of advanced fibrosis at baseline (odds ratio, 2.36; P=0.0066). Worsening of fibrosis, on the other hand, was independently associated with a baseline body mass index of 30 kg/m2 or higher (odds ratio, 3.56; P=0.0005).
These findings could help pave the way toward improving patients’ quality of life and clinical outcomes. “We can use a lot of drugs, but it’s also important to focus on their lifestyle,” Younossi said. “That doesn’t only include weight and diabetes management, but also other comorbidities that we may not think are specifically related to fatty liver disease, because they can also impact quality of life.”
Sammy Saab, MD, MPH, a professor of medicine and surgery at the David Geffen School of Medicine at the University of California, Los Angeles, called the study “fascinating” because it showed that fatty liver disease is a dynamic process. “Some people may progress or they can have spontaneous improvement,” Saab said. “The same can be true for patient-related outcomes.”
Saab noted that patients who experienced the greatest improvements were those who started with better quality-of-life scores. “It argues that if we are going to intervene with the goal of improving people’s quality of life, we need to do so earlier rather than later,” he said.
Nevertheless, Saab said he was surprised by some of the study findings, particularly the relationship between type 2 diabetes mellitus and fibrosis, “because you would think that people who have worsening fibrosis would have a higher rate of diabetes.”
—Michael Vlessides
Younossi reported financial relationships with AbbVie, Bristol Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Merck, Novartis, Novo Nordisk, Shionogi, Siemens, Terns and Viking. Saab reported no relevant financial disclosures.
This article is from the May 2021 print issue.