Phosphatidylethanol Aids Detection of Alcohol Relapse Post-Liver Transplant

Akshay Shetty, MD

Credit: University of California at Los Angeles

A direct alcohol biomarker, phosphatidylethanol (PEth), could positively impact the surveillance of alcohol use after liver transplantation in patients with alcohol-related liver disease (ALD), according to a recent single-center retrospective study.¹

These findings suggested PEth use could provide rapid and early detection of alcohol use among those transplanted for ALD— a population of 46 patients with ≥1 alcohol relapse episode revealed approximately 76% detected by PEth alone.

“We hope that the utilization of alcohol biomarkers, such as PEth, can lead to early detection of relapse so patients can be referred to more intensive treatment programs and return to abstinence with the long-term goal of improved graft and patient outcomes,” wrote the investigative team, led by Akshay Shetty, MD, department of medicine at the University of California at Los Angeles.

The previous decade has experienced a steady rise in ALD, with a subsequent increase in ALD-related hospitalizations—in the United States, ALD has become the leading indication for liver transplantation.² Alcohol abstinence is the cornerstone of ALD management, making monitoring alcohol use critical for optimizing pre- and post-liver transplant outcomes

Multiple alcohol biomarkers are used to detect alcohol use in liver transplantation—in a previous analysis, Shetty and colleagues reviewed PEth’s diagnostic accuracy as a sensitivity and specific biomarker of recent alcohol use.³ For this analysis, the investigative team described the effect of PEth on alcohol detection in an orthotopic liver transplant (OLT) population.¹

This single-center retrospective analysis evaluated 263 patients transplanted for ALD from January 2016 to December 2022 at the investigator’s institution. With follow-up limited to 3 years post-OLT, Group 1 comprised transplants between 2016 and 2018 before the introduction of PEth, and Group 2 comprised transplants between 2019 and 2022 after its introduction. Alcohol relapse status post-OLT was also evaluated, without a follow-up time limitation.

Among the study cohort, the primary indication for liver transplantation was ALD, with concurrent diagnoses of HCV (15.2%), HCC (12.2%), MASH (8.7%), HBV (0.8%), autoimmune hepatitis (0.4%), and hemochromatosis (0.4%). Overall, 46 (17.5%) patients experienced ≥1 episode of alcohol relapse post-OLT.

Most alcohol relapses were detected by PEth alone (74%), followed by self-reporting (17%). The remaining alcohol relapses were detected by both PEth and self-reporting (9%).

Compared with non-relapse cohorts, those with alcohol relapse experienced more episodes of elevated liver enzymes (4.35 vs. 2.46 episodes; P <.001). Hospitalizations were additionally elevated in relapsed patients than in non-relapsed patients, but this difference was not statistically significant (2.85 vs. 2.50, respectively; P = .307).

Overall, the number of individuals with ≥1 episode of alcohol relapse was significantly higher in Group 2 compared with Group 1 (17% vs. 7%, respectively; P = .012), with both cohorts adjusted for a 3-year follow-up. Rates of mortality did not differ between patients who did or did not relapse (P = .819).

In their summary, Shetty and colleagues noted these data could help initiate surveillance protocols for alcohol use after liver transplantation. A multimodal approach, consisting of standardized self-reported surveys and the collection of alcohol biomarkers, including PEth, could occur monthly in the first year after transplant, followed by every 3-month surveillance.

“Combining alcohol biomarkers with self-reported questionnaires is likely to add to early acknowledgments of the relapse by the patient and aid in the physician-patient relationship,” they wrote. “Early referrals to, or inclusion of, behavioral medicine providers in the posttransplant management of ALD OLT recipients may expedite return to abstinence for these patients.”

References

1. _{De La Torre SA, Ibrahim B, Meneses K, Saab S, Shetty A. Impact of phosphatidylethanol in the surveillance for alcohol use in post-liver transplant population: A retrospective study. Alcohol Clin Exp Res (Hoboken). 2024 Oct 31. doi: 10.1111/acer.15474. Epub ahead of print. PMID: 39482857.}
2. _{Kwong AJ, Ebel NH, Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, Foutz J, Gauntt K, Cafarella M, Snyder JJ, Israni AK, Kasiske BL. OPTN/SRTR 2020 Annual Data Report: Liver. Am J Transplant. 2022 Mar;22 Suppl 2:204-309. doi: 10.1111/ajt.16978. PMID: 35266621.}
3. _{Shetty A, De La Torre S, Ibrahim B, Hong A, Meza J, Saab S. Role of Biomarkers to Assess the Use of Alcohol. J Clin Gastroenterol. 2023 Jul 1;57(6):537-545. doi: 10.1097/MCG.0000000000001852. PMID: 37039472.}