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Heavy Consumption of Alcohol is Not Associated With Worse Outcomes in Patients With Idiosyncratic Drug-induced Liver Injury Compared to Non-Drinkers.

ABSTRACT: BACKGROUND & AIMS:The relationship between alcohol consumption and idiosyncratic drug-induced liver injury (DILI) is not well understood. We investigated the relationship between heavy consumption of alcohol and characteristics and outcomes of patients with DILI enrolled in the Drug-induced Liver Injury Network (DILIN) prospective study. METHODS:We collected data from 1198 individuals with definite, highly likely, or probable DILI enrolled in the DILIN study from September 2004 through April 2016. At enrollment, all participants were asked about alcohol consumption; those with any alcohol consumption during previous 12 months were asked to complete the Skinner questionnaire to assess drinking history. Heavy consumption of alcohol was defined as more than 3 drinks, on average, per day by men or more than 2 drinks, on average, per day by women. RESULTS:Of the 601 persons who reported consuming at least 1 alcoholic drink in the preceding 12 months, 348 completed the Skinner questionnaire and 80 reported heavy consumption of alcohol. Heavy drinkers were younger (average age, 42 years) than non-drinkers (average age, 49 years) and a higher proportion were men (63% of heavy drinkers vs 35% of nondrinkers) (P < .01 for each comparison). Anabolic steroids were the most common cause of DILI among heavy drinkers (in 13% vs 2% in non-drinkers) (P < .001). Heavy drinkers had significantly higher peak serum levels of alanine aminotransferase (1323 U/L) than non-drinkers (754 U/L) (P = .02) and higher levels of bilirubin (16.1 mg/dL vs 12.7 mg/dL in non-drinkers) (P = .03) but there was no significant difference in liver-related death or liver transplantation between heavy drinkers (occurred in 10%) vs non-drinkers (occurred in 6%) (P = .18). CONCLUSION:In an analysis of data from the DILIN, we found anabolic steroids to be the most common cause of DILI in individuals who are heavy consumers of alcohol. Compared to non-drinkers, DILI was not associated with a greater proportion of liver-related deaths or liver transplantation in heavy drinkers.

SUBMITTER: Dakhoul L

PROVIDER: S-EPMC5911195 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Heavy Consumption of Alcohol is Not Associated With Worse Outcomes in Patients With Idiosyncratic Drug-induced Liver Injury Compared to Non-Drinkers.

Dakhoul Lara L Ghabril Marwan M Gu Jiezhun J Navarro Victor V Chalasani Naga N Serrano Jose J

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20180103 5

<h4>Background & aims</h4>The relationship between alcohol consumption and idiosyncratic drug-induced liver injury (DILI) is not well understood. We investigated the relationship between heavy consumption of alcohol and characteristics and outcomes of patients with DILI enrolled in the Drug-induced Liver Injury Network (DILIN) prospective study.<h4>Methods</h4>We collected data from 1198 individuals with definite, highly likely, or probable DILI enrolled in the DILIN study from September 2004 th ...[more]

PMID: 29306044

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Project description:Background: Alcohol-associated liver disease (ALD) is the most common disorder of prolonged drinking. Mechanisms underlying cirrhosis in such patients remain unclear. MicroRNAs play regulatory role in several diseases, are affected by alcohol and may be important players in alcohol use disorders, such as cirrhosis. Methods: We investigated serum samples from heavy chronic alcohol users (80 g/day (male) and 50 g/day (female) for ≥10 years) that were available from our previously reported GenomALC study. A subset of GenomALC drinkers with liver cirrhosis (cases, n = 24) and those without significant liver disease (drinking controls, n = 23) were included. Global microRNA profiling was performed using high-throughput real-time quantitative PCR to identify the microRNA signatures associated with cirrhosis. Ingenuity Pathway Analysis (IPA) software was utilized to identify target mRNAs of significantly altered microRNAs, and molecular pathways were analysed. Identified microRNAs were analysed for correlation with traditional liver disease biomarkers and risk gene variants previously reported from GenomALC genome-wide association study. Results: The expression of 21 microRNAs was significantly downregulated in cases compared to drinking controls (p < 0.05, ∆∆Ct > 1.5-fold). Seven microRNAs (miR-16, miR-19a, miR-27a, miR-29b, miR-101, miR-130a, and miR-191) had a highly significant correlation (p < 0.001) with INR, bilirubin and MELD score. Three microRNAs (miR-27a, miR-130a and miR-191) significantly predicted cases with AUC-ROC 0.8, 0.78 and 0.85, respectively (p < 0.020); however, INR performed best (0.97, p < 0.001). A different set of six microRNAs (miR-19a, miR-26a, miR-101, miR-151-3p, miR-221, and miR-301) showed positive correlation (ranging from 0.32 to 0.51, p < 0.05) with rs10433937:HSD17B13 gene variant, associated with the risk of cirrhosis. IPA analysis revealed mRNA targets of the significantly altered microRNAs associated with cell death/necrosis, fibrosis and increased steatosis, particularly triglyceride metabolism. Conclusions: MicroRNA signatures in drinkers distinguished those with liver cirrhosis from drinkers without liver disease. We identified mRNA targets in liver functions that were enriched for disease pathogenesis pathways.

Project description:AimTo investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology.MethodsCaucasian heavy drinkers (n = 521) with a mean alcohol consumption of 192.1 g/d (median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography (Fibroscan, Echosens SA, Paris, France). LS and serum markers were prospectively studied in these patients with all stages of alcoholic liver disease (steatosis, steatohepatitis, fibrosis) prior and after alcohol detoxification with a mean observation interval of 6.2 ± 3.2 d. A liver biopsy with histological analysis including the Kleiner score was obtained in 80 patients.ResultsThe PNPLA3 rs738409 genotype distribution for CC, CG and GG was 39.2%, 52.6% and 8.2%. GG genotype primarily correlated with histological steatohepatitis (r = 0.404, P < 0.005), ballooning (r = 0.319, P < 0.005) and less with steatosis (r = 0.264, P < 0.05). Mean LS was lowest in CC carriers (13.1 kPa) as compared to CG and GG carriers (17.6 and 17.2 kPa). Notably, LS primarily correlated with fibrosis stage (r = 0.828, P < 0.005), ballooning (r = 0.516, P < 0.005), steatohepatitis (r = 0.319, P < 0.005) but not with steatosis. After alcohol withdrawal, LS did not change in CC carriers, significantly decreased in CG-carriers from 17.6 to 12.7 kPa but to a lesser extent in GG carriers from 17.6 to 14.5 kPa. This was due to prolonged resolution of inflammation with significantly elevated aspartate transaminase levels after alcohol withdrawal in GG carriers. Non-invasive fibrosis assessment by LS in all patients showed a significantly higher F0 rate as compared to the biopsy cohort (47% vs 6%) with 3.8% more CC carriers while 3.7% less were seen in the F4 cirrhosis group. Thus, about 20% of patients with alcoholic liver cirrhosis would be attributable to PNPLA3 G variants. The OR to develop cirrhosis corrected for age, gender and body mass index was 1.295 (95%CI: 0.787-2.131) for CG + GG carriers.ConclusionIn heavy drinkers, PNPLA3 GG primarily correlates with ballooning/steatohepatitis but not steatosis resulting in a delayed inflammation-associated resolution of LS. Consequently, sustained ballooning-associated LS elevation seems to be a potential risk factor for fibrosis progression in PNPLA3 GG carriers.

Project description:Background and aimsCannabis is commonly used among people who drink alcohol, but evidence suggests a nuanced relationship between alcohol consumption and cannabis use. In particular, among individuals undergoing alcohol treatment the impact of cannabis on alcohol intake may depend upon cannabis use frequency. We aimed to test the effects of within-day cannabis use on total drinks consumed and likelihood of binge drinking on a given day among all participants and compare these relationships between males and females and between individuals who reported infrequent and frequent cannabis use.DesignThis observational study is a substudy of a larger randomized controlled trial (RCT). Individuals were included from the RCT if they reported any cannabis use and were divided into groups based on cannabis use patterns. Alcohol use was compared within and between groups.SettingIndividuals were recruited from 2016 to 2020 from community and university settings in Denver and Boulder, CO, USA.ParticipantsOf the 182 individuals enrolled in the RCT, 96 cannabis-using subjects were included in these analyses.MeasurementsSubjects completed a time-line follow-back (TLFB) at baseline, 4, 8 (end of treatment) and 20 weeks. Daily data on alcohol and cannabis use from the TLFB at all time-points were analyzed.FindingsAcross the sample (n = 96), individuals drank approximately 29% fewer drinks [95% confidence interval (CI) = 18-39%, P < 0.001] and were 2.06 times (95% CI =1.37-3.08, P < 0.001) less likely to have a binge-drinking episode on days that cannabis was used compared with days that cannabis was not used. These patterns were observed in males, females and the infrequent and frequent cannabis use groups. Findings were inconclusive regarding differences in the association between cannabis use and alcohol outcomes when comparing males and females and when comparing infrequent and frequent cannabis use groups.ConclusionsHeavy drinkers engaged in treatment to reduce their alcohol consumption who also use cannabis appear to increase their cannabis use on days when they reduce their alcohol consumption.

Dataset Information

Heavy Consumption of Alcohol is Not Associated With Worse Outcomes in Patients With Idiosyncratic Drug-induced Liver Injury Compared to Non-Drinkers.

Publications

Heavy Consumption of Alcohol is Not Associated With Worse Outcomes in Patients With Idiosyncratic Drug-induced Liver Injury Compared to Non-Drinkers.

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