Although research into the benefits of palliative and supportive care for patients with advanced chronic liver disease involves real challenges, such studies are both feasible and sorely needed, according to authors of an article in the Journal of Hepatology.
“The reason you haven’t heard about the great benefits of these interventions in advanced liver disease …. is not because they don’t work.”
“The reason you haven’t heard about the great benefits of these interventions in advanced liver disease, while they are well established in patients with cancer, is not because they don’t work; it’s that there are real challenges to doing palliative care studies in populations with advanced liver disease,” said Myrick C. Shinall, M.D., an associate professor of surgery and medicine at Vanderbilt University Medical Center.
“‘Absence of evidence is not evidence of absence,’” he added, quoting Carl Sagan.
Too Little, Too Late
Just a minority of patients with advanced liver disease are eligible for curative treatment, yet the use of palliative and supportive care has also been suboptimal, the authors stated. One important reason, among many, for this issue is the lack of evidence-based palliative and supportive interventions to draw from.
A structured review by Shinall’s group of existing literature on palliative care for patients with advanced chronic liver disease identified barriers to such research and suggested approaches to overcome those barriers. Many of the studies included in the structured review were written by the authors of the article.
Large Target Population
“People with advanced chronic liver disease are a population that is really ripe for palliative care and supportive-care interventions,” Shinall said. “They are very sick with a lot of symptoms, and they come to the hospital a lot. They can be complicated to manage.”
“These patients have so many unmet supportive care needs. They are an important group of patients, and this is an important problem.”
Such patients are also numerous. Chronic liver disease is the ninth leading cause of death in United States, according to the National Center for Health Statistics. More than 50,000 deaths were attributed to it in 2021. Furthermore, chronic liver disease mortality rose 65 percent between 1999 and 2016, largely due to an increase in alcohol-related liver disease.
“These patients have so many unmet supportive care needs. They are an important group of patients, and this is an important problem,” Shinall said.
Study Barriers Begin Early
Early-stage barriers include how to define a uniform cohort of patients likely to benefit from a trial palliative-care intervention. The nature of these patients poses specific difficulties. Patients with advanced chronic liver disease are a highly heterogenous group. Those in the last weeks or days of life are unlikely to benefit from participating in a trial, the authors noted.
“Studies should ideally target those with a life expectancy of at least 3-6 months,” the authors wrote, although such patients often rapidly deteriorate. As patients grow sicker, withdrawal from any study becomes more likely.
Capacity Concerns
Among people with advanced chronic liver disease, hepatic encephalopathy patients are some of the sickest and most vulnerable. Hepatic encephalopathy is a nervous system disorder that can cause confusion, anger and irritability, poor concentration, and personality changes.
“Despite poor health-related quality of life … it is often this cohort that is excluded from research due to informed-consent issues. [Yet] it is imperative that such patients are not excluded,” the team wrote. To further this goal of inclusion, the researchers suggested enrollment of patient-caregiver dyads.
Lack of funding for palliative and supportive care poses a serious challenge for many patients, not just those with liver disease.
“In the U.S., federal funding for palliative-care research comprises less than 0.1 percent of the grant portfolio of the National Institute of Diabetes and Digestive and Kidney Diseases,” the authors wrote.
Smoothing a Path Forward
Increased involvement of patient and public groups in all stages of trial development and execution has the potential to help to improve this situation. Major funders view such patient and public involvement as an important consideration when evaluating trials, the group noted.
“For us, one goal was to help other researchers who want to do these studies and to spare them reinventing the wheel in overcoming certain barriers,” Shinall said. “We also want to raise the issue of the need for more evidence in the broader community of people caring for patients with advanced liver disease.”
Greater awareness will lead to more funding and more palliative-care studies, the researcher believes.
