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Commentaries

Opioid Use and Liver Transplantation

Braun, Hillary J. MD1; Ascher, Nancy L. MD, PhD1

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doi: 10.1097/TP.0000000000003156
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The US opioid epidemic began in the late 1990s, when healthcare providers began prescribing opioids at increasing rates after false reassurance from pharmaceutical companies that these medications would not be habit-forming. In 2016, the annual US death toll from opioid overdoses peaked at 42 000, and in 2017, the US Department of Health and Human Services declared a public health emergency and implemented a “5-Point Opioid Strategy” to combat opioid overdoses.1 The transplant community has been acutely aware of the public health impact of opioid overdoses, as the number of overdose deceased donors skyrocketed from 1.1% in 2000 to 13.4% in 2017.2 However, the impact of the opioid epidemic on transplant candidates and recipients has not been as widely discussed.

Opioid use in liver transplant (LT) candidates is controversial. As many as 77% of patients awaiting LT report moderate pain,3 and symptom relief is difficult to achieve given the metabolic derangements that accompany cirrhosis. Interestingly, >70% of LT programs do not have written policies on opioid use before LT, but in a recent survey of center practices, as many as 64% of transplant programs regard chronic opioid use or opioid substitution therapy as a relative, if not absolute, contraindication to LT.4 This concern is not unfounded; pre-LT opioid use has been associated with a 20%–50% higher risk of death and graft loss when compared with LT recipients without a history of opioid use before transplant.5

Opioid use after transplant in LT recipients is another area of concern. It has been widely established that 6% of opioid naïve patients develop chronic opioid use following surgery,6 so even those patients without opioid exposure before LT remain at risk for habit-forming dependence after transplant.

In the present study, Cron et al7 address both of these issues by providing a timely and important description of opioid use in LT recipients both before and after transplantation. To do this, the authors looked at changes in the duration of opioid use and prevalence of opioid prescription fills in the year before, and the year following, LT, among 1340 commercially insured LT recipients. While United Network for Organ Sharing data affords a more comprehensive sample of LT recipients, these data lack information on medications aside from immunosuppression, so we commend the authors on their use of this claims dataset to answer this important question regarding ongoing opioid use. Ultimately, Cron et al found that 45% of patients filled 1 or more opioid prescriptions within a year before LT, and 61% of patients filled 1 or more opioid prescriptions in the year following LT. Among LT recipients who were opioid naïve at the time of LT (55% of the cohort), 9%–12% of these patients filled 1 or more opioid prescriptions between 2 and 12 months after discharge, and 4% became chronic opioid users.

The study reviewed here has several notable limitations that the authors acknowledge. First, the cohort only includes patients with commercial insurance, and recent work from Locke and colleagues has shown that the majority of LT recipients are insured through either Medicare or Medicaid.8 It is not clear in which direction this may skew the results; however, it is important to keep this in mind when applying these results to other LT recipient populations. Second, there is no data available about individual programs’ approach to opioid use before LT. We go to great lengths to avoid any opioid administration to inpatients awaiting LT; we find the encephalopathy we see in patients with compromised liver function taking narcotics is difficult to manage. Additionally many of these patients have addiction histories. It was quite surprising for us to see that nearly half of all patients awaiting LT fill prescriptions for opioids within the year before LT. Finally, this analysis did not account for inpatient opioid use. While this was unavoidable given the articulated limitations inherent in this outpatient claims dataset, it has been established in surgical populations that the amount of opioids required in the hospital correlate with the amount of opioids prescribed at discharge, and subsequently with the amount of opioids consumed by patients.9 This is an area that absolutely warrants further investigation; as inpatient providers we have the ability, if not the responsibility, to make a significant impact as prescribers and stewards of opioid use.

Fundamentally, the critical issues for the transplant community regarding LT candidate and recipient opioid use are (1) the impact of opioid use on graft and patient survival in a setting where a limited resource must be responsibly allocated and (2) prevention of new opioid dependence following LT. While Cron et al do not investigate the impact of opioid use on survival, they do shed important light on the strikingly high use of opioids before and after LT. The authors should be commended on their creative and thoughtful approach, which lays a foundation for future work in this area.

REFERENCES

1. U.S. Department of Health and Human Services. Help and Resources: National Opioids Crisis. U.S. Department of Health and Human Services website. 2019. Available at hhs.gov/opioids. Accessed 2019. Accessed December 11, 2019.
2. Durand CM, Bowring MG, Thomas AG, et al. The drug overdose epidemic and deceased-donor transplantation in the United States: a national registry study. Ann Intern Med. 2018;168:702–711.
3. Madan A, Barth KS, Balliet WE, et al. Chronic pain among liver transplant candidates. Prog Transplant. 2012;22:379–384.
4. Fleming JN, Lai JC, Te HS, et al. Opioid and opioid substitution therapy in liver transplant candidates: a survey of center policies and practices. Clin Transplant. 2017;31:e13119
5. Randall HB, Alhamad T, Schnitzler MA, et al. Survival implications of opioid use before and after liver transplantation. Liver Transpl. 2017;23:305–314.
6. Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152:e170504
7. Cron DC TM, Lee JS, Waljee AK, et al. Prevalence and patterns of opioid use before and after liver transplantation. Transplantation. 2021;105:100–107.
8. DuBay DA, MacLennan PA, Reed RD, et al. Insurance type and solid organ transplantation outcomes: a historical perspective on how medicaid expansion might impact transplantation outcomes. J Am Coll Surg. 2016;223:611–620.e4.
9. Flanagan CD, Wysong EF, Ramey JS, et al. Understanding the opioid epidemic: factors predictive of inpatient and postdischarge prescription opioid use after orthopaedic trauma. J Orthop Trauma. 2018;32:e408–e414.
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