Adults with cirrhosis who reported pain, including widespread pain, were significantly more likely to also experience mood and cognitive disturbances, fatigue, poor sleep, and impaired physical and social function, based on data from more than 200 individuals.1

Nociplastic pain is, in particular, often associated with a range of comorbid non-pain symptoms including fatigue, sleep problems, memory or concentration problems, and mood disturbances that can have a negative effect on quality of life. Better recognition of pain classifications can inform treatment decisions, as nociceptive pain and nociplastic pain tend to respond to different treatment strategies.1

Study Overview


In the study, published in Hepatology Communications, Holman et al conducted a survey of adults with cirrhosis being treated at the University of Michigan. The study population included 238 patients aged 18 years and older who responded to the survey via email. The mean age of the participants was 58.8 years; 40.8% were men.

Widespread pain was assessed using the American College of Rheumatology Fibromyalgia Survey Criteria, which include the number of painful body regions, as well as problems with thinking, fatigue, and sleep. Pain intensity was assessed with the PROMIS Pain Intensity 3a.Non-pain symptoms were assessed using the Patient-Reported Outcome Measurement Information System 29-Item Profile, version 2 (PROMIS29+2).


Overall, pain and widespread pain were associated with higher levels of mood and cognitive disturbance, fatigue, sleep difficulty, and physical and social functioning.

PROMIS29+2 scores for pain interference, depression/sadness, anxiety/fear, fatigue, and sleep disturbance increased (indicative of worse symptoms) as the number of positive pain regions increased. Similarly, increases in the number of pain regions were associated with decreased scores (indicative of worse symptoms) for cognitive function, physical function, and the ability to participate in social roles and activities.

Pain Intensity PROMIS3a scores also increased as the number of pain regions increased.

The findings were limited by several factors, including the small sample size and mainly homogeneous white, educated population, which may limit generalizability, the researchers noted.

However, the results suggest that nociplastic pain is an important pain phenotype in people with cirrhosis, and that more attention may be needed for nonpharmacologic therapies and ways to improve non-pain symptoms and function, concluded the team.1

As noted, pain is extremely common in cirrhosis, and several recent studies have suggested a prevalence as high as 80%, said Jessica B. Rubin, MD, MPH, assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of California, San Francisco, in an interview.

Pain is often underrecognized in this population, and significantly impacts quality of life, but clinicians may be hesitant to prescribe medication due to concerns about side effects, said Dr. Rubin, who was not involved in Holman’s study.

The study is particularly timely for two reasons, she noted. First, in the wake of the opioid epidemic, pain management has become a public health research priority, especially for high-risk patients such as those with cirrhosis, she said. Second, the current study reflects the importance of reviewing patient-reported outcomes in patients with cirrhosis, with the goal of not only providing them with a longer and healthier life but also an enhanced quality of life.

They found similar use of analgesics between people with cirrhosis and non-cirrhosis control inpatients. However, inpatients with cirrhosis were significantly less likely than those without cirrhosis to receive acetaminophen (26% vs. 42%, P<0.01) or NSAIDs (3% vs. 7%, P<0.01), but significantly more likely to receive opioids (59% vs. 54%, P<0.01), although prescribing patterns varied between hospitals, wrote Dr. Rubin’s team.

Dr. Rubin said she was not surprised by the findings of Holman’s review. “It has been clearly demonstrated in other populations that pain, and particularly widespread pain, is associated with other bothersome symptoms and physical functioning, so it makes sense that the same is true in cirrhosis patients,” she said. “Given the high rates of pain in cirrhosis patients, which does not seem to be limited to those with specific cirrhosis complications (such as ascites), it is not surprising that nociplastic pain is a significant contributor; moreover, many of the risk factors for nociplastic pain are also risk factors for substance use disorders, which we know are very common in our population as well,” she said.

“I think the take-home message is that we need to be more thoughtful about managing pain in cirrhosis patients,” said Dr. Rubin. “Although these patients are often complex, with multiple cirrhosis-related complications and associated symptoms to think about and manage, pain is clearly an important driver of mood, mental health, and physical functioning in this population. It is something we should make time to ask about and treat effectively.”

In Dr. Rubin’s opinion, there are two significant challenges to managing pain in cirrhosis. First, more research along the lines of Holman’s study is needed to better characterize pain in cirrhosis in order to develop targeted pain management plans, she said. “The second challenge is that providers are often hesitant to prescribe analgesics due to concerns regarding hepatotoxicity and risk of adverse effects associated with multiple classes of pain medications such as acetaminophen, NSAIDs, and opioids.”

Unfortunately, real-world data on the actual risks of analgesic use in people with cirrhosis is limited, explained Dr. Rubin. “As a result, I think we likely tend to be overly cautious and undertreat pain in this population…. Generating these data is an essential first step in generating evidence-based guidance for providers to help them safely and effectively manage pain in cirrhosis patients.”


  1. Holman A, Parikh ND, Zhao Z, et al. Association between widespread pain and associated symptoms in patients with cirrhosis. Hepatol Commun. 2023;7(5):e0120. Published 2023 Apr 14. doi:10.1097/HC9.0000000000000120
  2. Rubin JB, Lai JC, Shui AM, Hohmann SF, Auerbach A. Cirrhosis Inpatients Receive More Opioids and Fewer Nonopioid Analgesics Than Patients Without Cirrhosis. J Clin Gastroenterol. 2023;57(1):48-56. Published 2023 Jan 1.