An Assessment of the Psychosocial Evaluation for Early Liver Transplantation in Patients with Acute Alcoholic Hepatitis in the context of Alcohol Use Disorder, A Case Control Study

Background Severe acute alcoholic hepatitis (AAH) has an excessive mortality rate. As a result, many centers, including our own, have allowed transplant listing patients for transplantation prior to achievement of 6-months sobriety. Concurrently, scoring systems have been proposed to identify patients with alcohol use disorder (AUD) predisposed to relapse after liver transplantation. These scoring systems target patients with a minimal period of sobriety. Methods We conducted a retrospective case control study of 11 patients who underwent early liver transplantation for AAH matched with 11 controls who were declined secondary to low insight into AUD. Blinded raters confirmed the severity of the DSM-5 diagnosis and scored the patients on a variety of structured psychometric scales used to predict alcohol relapse. These included the High Risk for Alcohol Relapse scale (HRAR), Stanford Integrated Psychosocial Assessment Tool (SIPAT), Alcohol Relapse Risk Assessment (ARRA), Hopkins Psychosocial Scale (HPSS), Michigan Alcoholism Prognosis Score (MAPS), Alcohol Use Disorders Identification Test -Consumption (AUDIT-C) and Sustained Alcohol Use Post-Liver Transplant (SALT) scales. All patients who underwent transplantation were followed for harmful and non-harmful drinking until the end of the study period. Results Mean psychometric scores of the transplanted cases were significantly different than the controls. Cases chosen for transplant had significantly favorable MAPS, HRAR, SIPAT, ARRA, and HPSS scores with cut-offs matching their prior research. The SALT and AUDIT-C scores were not predictive of our selection of patients for transplant. Despite expedited assessment and no significant period of sobriety, our case cohort had a 30% relapse to harmful drinking after an average of 6.6 years (5 to 8.5 years) of follow-up. Discussion Despite the expedited assessment and short to no period of sobriety, the patient cohort demonstrated a 30% relapse to harmful drinking, consistent with the reported 20-30% after liver transplantation for all forms of alcoholic liver disease. The average MAPS, HRAR, SIPAT, ARRA, and HPSS scores all corroborated our current stratification procedures, with lower risk mean scores found in the transplanted group. Conclusion The traditional psychosocial selection criteria for patients with alcoholic hepatitis at our institution is consistent with four of the five investigated scoring systems.

Neuroimmune and Mu-Opioid Receptor Alterations in the Mesocorticolimbic System in a Sex-Dependent Inflammatory Pain-Induced Alcohol Relapse-Like Rat Model

Evidence concerning the role of alcohol-induced neuroinflammation in alcohol intake and relapse has increased in the last few years. It is also proven that mu-opioid receptors (MORs) mediate the reinforcing properties of alcohol and, interestingly, previous research suggests that neuroinflammation and MORs could be related. Our objective is to study neuroinflammatory states and microglial activation, together with adaptations on MOR expression in the mesocorticolimbic system (MCLS) during the abstinence and relapse phases. To do so, we have used a sex-dependent rat model of complete Freund’s adjuvant (CFA)-induced alcohol deprivation effect (ADE). Firstly, our results confirm that only CFA-treated female rats, the only experimental group that showed relapse-like behavior, exhibited specific alterations in the expression of phosphorylated NFκB, iNOS, and COX2 in the PFC and VTA. More interestingly, the analysis of the IBA1 expression revealed a decrease of the microglial activation in PFC during abstinence and an increase of its expression in the relapse phase, together with an augmentation of this activation in the NAc in both phases that only occur in female CFA-treated rats. Additionally, the expression of IL1β also evidenced these dynamic changes through these two phases following similar expression patterns in both areas. Furthermore, the expression of the cytokine IL10 showed a different profile than that of IL1β, indicating anti-inflammatory processes occurring only during abstinence in the PFC of CFA-female rats but neither during the reintroduction phase in PFC nor in the NAc. These data indicate a downregulation of microglial activation and pro-inflammatory processes during abstinence in the PFC, whereas an upregulation can be observed in the NAc during abstinence that is maintained during the reintroduction phase only in CFA-female rats. Secondly, our data reveal a correlation between the alterations observed in IL1β, IBA1 levels, and MOR levels in the PFC and NAc of CFA-treated female rats. Although premature, our data suggest that neuroinflammatory processes, together with neural adaptations involving MOR, might play an important role in alcohol relapse in female rats, so further investigations are warranted.

Cognitive impairment following clinical or recreational use of gamma-hydroxybutyric acid (GHB). A systematic review

Background: GHB (gamma-hydroxybutyric acid; sodium oxybate) is a general anaesthetic that is clinically used for the treatment of narcolepsy, cataplexy, alcohol withdrawal and alcohol relapse prevention. In addition, GHB is recreationally used. Most clinical and recreational users regard GHB as an innocent drug devoid of adverse effects, despite its high dependence potential and possible neurotoxic effects. At high doses, GHB may lead to a comatose state. This paper systematically reviews possible cognitive impairments due to clinical and recreational GHB use. Methods: PubMed and PsychINFO were searched for literature data about the acute and residual cognitive deficits following GHB use. This review is conducted using the PRISMA protocol. Results: A total of 43 reports covering human and animal data on GHB-induced cognitive impairments were eligible and reviewed. This systematic review found no indication for cognitive impairments after clinical GHB use. However, it supports the view that moderate GHB use may result in acute short-term cognitive impairments, whereas regular high-dose GHB use and/or multiple GHB-induced comas are probably neurotoxic resulting in long-term residual cognitive impairments. Conclusion: These results emphasize the need for awareness among clinicians and recreational users to minimize negative health consequences of recreational GHB use, particularly when high doses are used, and GHB-induced comas occur.

Portuguese validation of the Alcohol Craving Questionnaire–Short Form–Revised

Alcohol craving has been described as a strong subjective desire to drink, being considered highly valuable in the clinical practice, as it is recognized as a strong predictor of alcohol relapse in alcohol-dependent individuals. However, to date, there is not a multifactorial questionnaire available for assessing short-term acute craving experience in Portugal. The aim of the present study was to validate a swift and efficient tool for the assessment of acute alcohol craving in a sample of Portuguese citizens. For that purpose, the Alcohol Craving Questionnaire–Short Form–Revised (ACQ-SF-R) was translated into European Portuguese and administered to a sample of 591 college participants with ages between 18 and 30 years. Results suggested that a three-factor model (i.e., Emotionality, Purposefulness, and Compulsivity) proved to be most suitable for the Portuguese sample. Overall, the ACQ-SF-R exhibited good psychometric properties, having a good internal consistency both for the general craving index (Cronbach’s α = 0.85) and each subscale (Cronbach’s α = 0.66–0.83), as well as an appropriate convergent validity with the Penn Alcohol Craving Scale (r = 0.65, p<0.001), suggesting a good construct validity. In addition, the ACQ-SF-R also showed a good concurrent validity with the Alcohol Use Disorders Identification Test (r = 0.57, p<0.001), indicating that risky alcohol use patterns are associated with increased craving scores in the ACQ-SF-R. Collectively, these findings suggest that the Portuguese version of the ACQ-SF-R can accurately measure alcohol craving at a multifactorial level, being a valid and reliable tool to use in Portuguese samples in research settings.