Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of Differences Between Alcohol-Related and Non-Alcohol-Related Cirrhosis Candidates

Abstract

Background:Monitoring sobriety is mandatory for liver transplant (LT) candidates with alcohol-related cirrhosis in Germany.Prior to listing, abstinence of 6 months is required. However, little is known about biomarker performance in alcohol-related cirrhosis. Routine testing of ethyl glucuronide in urine (uEtG) or hair (hEtG) is prone to manipulation or is unfeasible in anuria. Phosphatidylethanol (PEth) in dried-blood spots is a promising alternative. We compared PEth with routine parameters and self-reports in alcohol-related and non-alcohol-related cirrhosis at our transplant center. Material/Methods:All patients received self-report questionnaires (AUDIT & TLFB). Blood, urine and hair samples, as well as PEth dried-blood spots were drawn at baseline. In addition, survival analyses were conducted. Results:Out of 66 patients, 53 were listed for LT and 13 were candidates not listed so far. An alcohol-use disorder was found in 25 patients. Positive results for uEtG, hEtG, and PEth were found in 5/65, 9/65, and 34/66 cases, respectively. PEth positivity was found in 52% of patients with alcohol-related cirrhosis, while 53% of patients with other liver diseases were positive. While uEtG, hEtG, and TLFB correlated with higher PEth values, active waiting list status was significantly correlated with negative PEth values. During the mean follow-up of 41.15 months, 23 patients were transplanted (34.9%). None of the biomarkers significantly predicted survival. Conclusions:PEth can importantly assist abstinence monitoring in LT candidates due to its high validity and objectivity. The high percentage of patients with alcohol consumption in the non-alcoholic liver disease cohort underscores the importance of testing all transplant candidates.

Role of Biomarkers to Assess the Use of Alcohol

“…Self-reporting with TLFB remains useful and has been validated across studies but remains limited, as noted in abstinence monitoring studies with patients testing positive for PEth despite denying alcohol use. [15][16][17]53 It is reasonable to argue whether these are false-positive results, but the presence of multiple different positive biomarkers across studies raises the concern for inaccurate self-reports of abstinence from the patients. 15,17,43 When assessing recent sobriety, we recommend pursuing a combination of biomarkers in addition to validated self-reporting and the results should be taken into consideration along with the patient's clinical presentation.…”

“…The reference standard in nearly all studies discussed above remains self-reporting, which by design, these biomarkers are trying to replace. Self-reporting with TLFB remains useful and has been validated across studies but remains limited, as noted in abstinence monitoring studies with patients testing positive for PEth despite denying alcohol use 15–17,53 . It is reasonable to argue whether these are false-positive results, but the presence of multiple different positive biomarkers across studies raises the concern for inaccurate self-reports of abstinence from the patients 15,17,43 .…”

“…However, reliant subjective history is often challenging to obtain from patients with AUD because of the nature of the disorder and its associated secrecy, stigma with the disease, and recall bias, where patients may often under-report the severity of their alcohol use. Such minimizing is particularly brought to light during a liver transplant evaluation where a patient may under-report their alcohol use due to the fear of being deemed a poor candidate for transplantation or because recent alcohol use may delay their transplant evaluation and listing 15,28 . Therefore, although subjective measures remain the best tools to evaluate chronic alcohol use in clinical practice, objective measures are needed in AUD patients to assist providers to assess recent sobriety and more importantly in monitoring for relapses so early interventions can be implemented.…”

“…12 Among prospective transplant candidates, relapse in alcohol use was associated with negative consequences to their transplant candidacy, with potential for deferment in listing for liver transplantation, denials for transplantation, and increased mortality. [14][15][16][17][18] Relapse in alcohol use among liver transplant recipients increases the risk of medical noncompliance, recurrent cirrhosis, hepatic decompensations, graft loss, and mortality. 19 Early detection of relapse may prevent worsening complications among all 3 patient groups -patients with chronic liver disease, transplant candidates, and transplant recipients.…”

“…Abstinence from alcohol remains the cornerstone in the treatment of ALD, as continued alcohol use is directly linked to higher rates of ascites, variceal bleeding, hepatic encephalopathy, hepatocellular carcinoma, and mortality 12 . Among prospective transplant candidates, relapse in alcohol use was associated with negative consequences to their transplant candidacy, with potential for deferment in listing for liver transplantation, denials for transplantation, and increased mortality 14–18 . Relapse in alcohol use among liver transplant recipients increases the risk of medical noncompliance, recurrent cirrhosis, hepatic decompensations, graft loss, and mortality 19 .…”