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Letter: are opioid prescriptions associated with hepatic encephalopathy in patients with compensated cirrhosis?

EDITORS, We read with great interest the article by Dr Moon et al.1 In this retrospective cohort study, the authors showed that opioid prescriptions, regardless of short-term (1-89 days) or chronic (90180 days) use, were associated with the risk of incident hepatic encephalopathy (HE) among patients with compensated cirrhosis. Therefore, the authors suggested that opioid use should be minimised in patients with cirrhosis and, when required, limited to short duration. Although innovative, several points warrant further clarification. Firstly, as we believe, most physicians are very cautious in clinical practice when prescribing opioid analgesics to their patients, especially those with cirrhosis or other chronic liver diseases. Opioid use would be considered as a last resort when those cirrhotic patients have unbearable pain from a variety of causes, possibly due to the avoidance of nonsteroidal anti-inflammatory drugs and acetaminophen.2 However, in the Moon et al study, the causes of pain were not provided, and this is important to let us understand the differences in baseline characteristics among three groups: no opioids (n = 4645), short-term opioids (n = 1505) and chronic opioids (n = 301). As shown in Table 1 of this study, there were significant differences in many variables among these three groups, including male sex, Charlson Comorbidity Index >2, diabetes mellitus, cirrhosis aetiology, tricyclic antidepressant use, prior opioids use (all P < 0.001). Were those patients using short-term or chronic opioid analgesics doing so because of benign diseases, nonliver malignancies, or intraoperative or post-operative analgesia? Secondly, in this study, liver function of enrolled patients, reflecting severity of liver disease, such as serum bilirubin, albumin and transaminase values, or composite Child-Pugh score, etc was not provided. Despite well-compensated cirrhosis for participants, was the liver function of those chronic opioids users worse than those of nonor short-term opioids users? Thus, due to the absence of some potentially important confounding variables associated with opioids use and the outcome event of HE, the results of this study may be subject to selection bias and should be interpreted cautiously. Lastly, the authors stated ‘in light of this potential harm (increased risk of HE) of opioid prescriptions, these medications should be avoided when possible even in patients with well-compensated cirrhosis’. However, when it comes to necessary pain relief for patients with compensated or even decompensated cirrhosis, what are the alternatives to opioids? Undoubtedly, nonsteroidal anti-inflammatory drugs and acetaminophen are not good options. But do Moon et al have any better alternatives?