Lifetime drinking history in patients with alcoholic liver disease and patients with alcohol use disorder without liver disease

Objective: To determine the differences in lifetime alcohol intake (LAI) and drinking patterns between patients with alcoholic liver disease (ALD) and alcohol use disorder (AUD) without notable liver injury and between males and females with ALD.

Methods: Alcohol drinking patterns were assessed using the Lifetime Drinking History (LDH) a validated questionnaire, during an outpatient visit. Patients with AUD, currently in addiction treatment, were matched for gender and age (±5 years) with the ALD group.

Results: A total of 39 patients with ALD (26 males and 13 females; median age 58) and equal number of AUD patients were included (median age 56 years). The onset age for alcohol drinking and duration of alcohol consumption was similar in ALD and AUD. The number of drinking days was higher in women with ALD than in women with AUD: 4075 [(3224–6504) versus 2092 (1296–3661), p?=?.0253]. The LAI and drinks per drinking day (DDD) were not significantly different between patients with ALD and AUD. Females with ALD had lower LAI than males with ALD: 32,934 (3224–6504) versus 50,923 (30,360–82,195), p?=?.0385, fewer DDD (p?=?.0112), and lower proportion of binge drinking as compared to males with ALD (p?=?.0274).

Conclusions: The total LAI was similar in patients with ALD and AUD. The number of drinking days over the lifetime was associated with the development of ALD in females. Females with ALD had significantly lower alcohol consumption than men with ALD despite similar duration in years of alcohol intake which supports the concept of female propensity of ALD.     

Lifetime alcohol intake and pattern of alcohol consumption in patients with alcohol-induced pancreatitis in comparison with patients with alcohol use disorder

Objective: To examine lifetime drinking patterns in men and women with alcohol-induced pancreatitis (AIP) in comparison with patients with alcoholic use disorder (AUD) without pancreatic disease.

Methods: Alcohol consumption patterns were assessed using a validated questionnaire, the Lifetime Drinking History (LDH), during an outpatient visit. Patients diagnosed with AIP were matched for gender and age (+/? 5 years) with patients with AUD in addiction treatment.

Results: A total of 45 patients with AIP (35 males, 10 females) and 45 AUD patients were included. Alcohol consumption patterns were not significantly different between males and females with AIP and those with history of acute AIP and chronic pancreatitis (CP). Alcohol consumption patterns of AIP and AUD patients were similar in terms of onset age and duration of alcohol consumption, lifetime alcohol intake and drinks per drinking day. A higher proportion of binge drinking was found among patients with AUD than those with AIP (median 1.00 vs. 0.94, p?=?.01). Males with AUD had lower onset age (15 vs. 16 years, p?=?.03), higher total amount of spirits (35520 vs. 10450 drinks, p?=?.04) and higher proportion of binge drinking (1.00 vs. 0.97, p?=?.01) than males with AIP, whereas females with AIP and AUD had similar drinking patterns.

Conclusions: Alcohol drinking patterns and lifetime drinking history was similar in patients with AIP and patients with AUD. Males with AIP had lower total amount of spirits and lower proportion of binge drinking than those with AUD, suggesting the idiosyncratic etiology of AIP.     

Longitudinal gut microbiome changes in alcohol use disorder are influenced by abstinence and drinking quantity

ABSTRACT

Many patients with alcohol use disorder (AUD) consume alcohol chronically and in large amounts that alter intestinal microbiota, damage the gastrointestinal tract, and thereby injure other organs via malabsorption and intestinal inflammation. We hypothesized that alcohol consumption and subsequent abstinence would change the gut microbiome in adults admitted to a treatment program. Stool and oral specimens, diet data, gastrointestinal assessment scores, anxiety, depression measures and drinking amounts were collected longitudinally for up to 4 weeks in 22 newly abstinent inpatients with AUD who were dichotomized as less heavy drinkers (LHD, <10 drinks/d) and very heavy drinkers (VHD, 10 or more drinks/d). Next-generation 16 S rRNA gene sequencing was performed to measure the gut and oral microbiome at up to ten time points/subject and LHD and VHD were compared for change in principal components, Shannon diversity index and specific genera. The first three principal components explained 46.7% of the variance in gut microbiome diversity across time and all study subjects, indicating the change in gut microbiome following abstinence. The first time point was an outlier in three-dimensional principal component space versus all other time points. The gut microbiota in LHD and VHD were significantly dissimilar in change from day 1 to day 5 (p = .03) and from day 1 to week 3 (p = .02). The VHD drinking group displayed greater change from baseline. The Shannon diversity index of the gut microbiome changed significantly during abstinence in five participants. In both groups, the Shannon diversity was lower in the oral microbiome than gut. Ten total genera were shared between oral and stool in the AUD participants. These data were compared with healthy controls from the Human Microbiome Project to investigate the concept of a core microbiome. Rapid changes in gut microbiome following abstinence from alcohol suggest resilience of the gut microbiome in AUD and reflects the benefits of refraining from the highest levels of alcohol and potential benefits of abstinence.     

Tryptophan-kynurenine metabolism during acute alcohol withdrawal in patients with alcohol use disorder: The role of immune activation

Background

Recent research has suggested that excessive alcohol consumption in patients with alcohol use disorder (AUD) is associated with chronic immune activation, which affects the metabolism of the neurotransmitter precursor amino acid tryptophan (TRP) and contributes to the complex pathophysiology of AUD. Our study investigated possible immune-associated alterations of TRP to kynurenine (KYN) metabolism in patients with AUD during acute alcohol withdrawal.

Methods

We measured serum concentrations of TRP, KYN, quinolinic (QUIN), kynurenic acid (KYNA), and the immune activation marker neopterin (NEO) at the first, fifth and 10th day of alcohol withdrawal in patients with AUD, who attended a standardized in-patient treatment program and underwent a detailed clinical assessment.

Results

Data from these individuals were compared to data from a reference control group (RCG). The primary outcome measures were the differences in serum concentrations of metabolites between AUD patients and RCG and correlations between NEO and metabolites of the tryptophan-kynurenine pathway. r = 0.695, p < 0.001) in the AUD group. Mixed models analysis showed that NEO concentrations were positively associated with QUIN but not with KYNA concentrations. Several behavioral symptoms correlated positively with QUIN concentrations and negatively with the KYNA/QUIN ratio.

Conclusions

Our findings demonstrate that the changes in TRP catabolism in acute alcohol withdrawal resulting in increased KYN production could reflect the involvement of immune-associated activation of the enzyme indoleamine 2,3-dioxygenase, as NEO concentrations correlated with the KYN/TRP ratio. In addition, our data show that this low-grade immune activation may cause an imbalance in the production of neurotoxic and neuroprotective kynurenine metabolites in AUD.     

Medications for treating alcohol use disorder: A narrative review

Chronic heavy alcohol use impacts all major neurotransmitter systems and is associated with multiple medical, psychiatric, and social problems. Available evidence-based medications to treat alcohol use disorder (AUD) are underutilized in clinical practice. These medications promote abstinence or reduce alcohol consumption, though there are questions regarding their optimal dosage, length of treatment, and utility in combination with one another. Pharmacogenetic approaches, which use a patient's genetic make-up to inform medication selection, have garnered great interest but have yet to yield results robust enough to incorporate them in routine clinical care. This narrative review summarizes the evidence both for medications approved by the Food and Drug Administration (disulfiram, oral naltrexone, acamprosate, and extended-release naltrexone) and those commonly used off-label (e.g., gabapentin, baclofen, and topiramate) for AUD treatment. We discuss these drugs' mechanisms of action, clinical use, pharmacogenetic findings, and treatment recommendations. We conclude that the most consistent evidence supporting the pharmacotherapy of AUD is for the opioid antagonists, naltrexone and nalmefene (which is not approved in the United States), and topiramate. These medications demonstrate consistent small or moderate effects in reducing the frequency of drinking and/or heavy drinking. Lastly, we make suggestions for research needed to refine and expand the current literature on effective pharmacotherapy for AUD.     

The association between alcohol use trajectories from adolescence to adulthood and cannabis use disorder in adulthood: a 22-year longitudinal study

Background: Due to the increasing prevalence of cannabis use disorder (CUD), the impact of cannabis use on public health may be significant. Objective: The present study seeks the possible precursors (e.g., alcohol use) of CUD in order to minimize the potential negative consequences of CUD such as impaired coordination and performance. Method: The Harlem Longitudinal Development Study included 674 participants (53% African Americans, 47% Puerto Ricans), with 60% females (n=405) from a six wave survey. We used a growth mixture model to obtain the trajectories of alcohol use from the mean ages of 14 to 36. To examine the associations between alcohol use trajectories and CUD, we used logistic regression analyses with the indicator of CUD as the dependent variable and the indicator of membership in each trajectory group as the independent variables. Results: A three alcohol use trajectory group model was selected. Male gender, higher frequency of cannabis use in adolescence, and a lower educational level were associated with an increased likelihood of having CUD. Membership in the increasing alcohol use group (OR=27.44, p < .01; AOR=15.54, p < .01) and the moderate alcohol use group (OR=10.40, p < .05; AOR=8.63, p < .05) were associated with an increased likelihood of having CUD compared with the membership in the no or low alcohol use group. Conclusions: The findings of our study support the hypothesis that addressing alcohol use at an early age could impact later CUD.