Journal of Clinical Medicine

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12 pages, 1236 KiB

Open AccessArticle

Day-4 Lille Score Is a Good Prognostic Factor and Early Predictor in Assessing Therapy Response in Patients with Liver Cirrhosis and Severe Alcoholic Hepatitis

by Camelia Gianina Foncea, Ioan Sporea, Raluca Lupușoru, Tudor Voicu Moga, Felix Bende, Roxana Șirli and Alina Popescu

J. Clin. Med. 2021, 10(11), 2338; https://doi.org/10.3390/jcm10112338 - 27 May 2021

Cited by 15 | Viewed by 6904

Abstract

Lille score at Day 7 (LM7) helps to predict the outcome of patients with severe alcoholic hepatitis (sAH) undergoing corticotherapy. Several scores such as Maddrey’s discriminant function (MDF), MELD, ABIC, and GAHS are used for a 28-day mortality prognosis. Our study aimed to [...] Read more.

Lille score at Day 7 (LM7) helps to predict the outcome of patients with severe alcoholic hepatitis (sAH) undergoing corticotherapy. Several scores such as Maddrey’s discriminant function (MDF), MELD, ABIC, and GAHS are used for a 28-day mortality prognosis. Our study aimed to evaluate if the assessment of the Lille score at 4 days (LM4) is as useful as the Lille score at Day 7 (LM7) to predict response to corticosteroids and 28-day mortality and evaluate the utility of severity scores at admission for predicting the prognosis of patients with liver cirrhosis (LC) and severe alcoholic hepatitis (sAH). A retrospective study was performed, and all consecutive patients with AH and MDF > 32 without contraindications to corticosteroids were included. Prognostic scores were evaluated at admission, and 28-day mortality was assessed. Response to corticotherapy was assessed by LM4 and LM7. Results: A total of 55/103 patients with sAH (51.5%) had MDF > 32 and received corticosteroids. There was no difference between the proportion of patients with a responder LM4 versus LM7 (27% vs. 36%, p = 0.31). The mean value for LM4 was 0.64 ± 0.3 versus 0.60 ± 0.3 for LM7 (p = 0.48). Precisely 90.3% of patients were correctly identified as responders or not by LM4 compared with LM7. The best model for predicting 28-day mortality was composed of MELD and LM4/LM7, with an accuracy of 0.90 for both combinations. Conclusion: LM4 could be used instead of LM7 for predicting response to corticosteroid therapy in patients with sAH and LC, as well as 28-day mortality. Using LM4, we could avoid prolonged use of this therapy and its complications. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

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12 pages, 1377 KiB

Open AccessArticle

The Impact of Binge Drinking on Mortality and Liver Disease in the Swiss HIV Cohort Study

by Bernard Surial, Nicolas Bertholet, Jean-Bernard Daeppen, Katharine E. A. Darling, Alexandra Calmy, Huldrych F. Günthard, Marcel Stöckle, Enos Bernasconi, Patrick Schmid, Andri Rauch, Hansjakob Furrer, Gilles Wandeler and The Swiss HIV Cohort Study

J. Clin. Med. 2021, 10(2), 295; https://doi.org/10.3390/jcm10020295 - 14 Jan 2021

Cited by 12 | Viewed by 2648

Abstract

Whereas excessive alcohol consumption increases liver disease incidence and mortality, evidence on the risk associated with specific drinking patterns is emerging. We assessed the impact of binge drinking on mortality and liver disease in the Swiss HIV Cohort Study. All participants with follow-up [...] Read more.

Whereas excessive alcohol consumption increases liver disease incidence and mortality, evidence on the risk associated with specific drinking patterns is emerging. We assessed the impact of binge drinking on mortality and liver disease in the Swiss HIV Cohort Study. All participants with follow-up between 2013 and 2020 were categorized into one of four drinking pattern groups: “abstinence”, “non-hazardous drinking”, “hazardous but not binge drinking” (Alcohol Use Disorder Identification Test Consumption [AUDIT-C] score ≥ 3 in women and ≥4 in men), and “binge drinking” (≥6 drinks/occasion more than monthly). We estimated adjusted incidence rate ratios (aIRR) for all-cause mortality, liver-related mortality and liver-related events using multivariable quasi-Poisson regression. Among 11,849 individuals (median follow-up 6.8 years), 470 died (incidence rate 7.1/1000 person-years, 95% confidence interval [CI] 6.5–7.8), 37 experienced a liver-related death (0.6/1000, 0.4–0.8), and 239 liver-related events occurred (3.7/1000, 3.2–4.2). Compared to individuals with non-hazardous drinking, those reporting binge drinking were more likely to die (all-cause mortality: aIRR 1.9, 95% CI 1.3–2.7; liver-related mortality: 3.6, 0.9–13.9) and to experience a liver-related event (3.8, 2.4–5.8). We observed no difference in outcomes between participants reporting non-hazardous and hazardous without binge drinking. These findings highlight the importance of assessing drinking patterns in clinical routine. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

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7 pages, 210 KiB

Open AccessArticle

Wernicke’s Encephalopathy in Alcohol Use Disorder Patients after Liver Transplantation: A Case Series and Review of Literature

by Gabriele A. Vassallo, Antonio Mirijello, Tommaso Dionisi, Claudia Tarli, Giuseppe Augello, Antonio Gasbarrini, Giovanni Addolorato and on behalf of the Gemelli OLT Group

J. Clin. Med. 2020, 9(12), 3809; https://doi.org/10.3390/jcm9123809 - 25 Nov 2020

Cited by 4 | Viewed by 2212

Abstract

Wernicke’s encephalopathy (WE) is an acute neurological disorder resulting from thiamine deficiency, commonly found in alcohol use disorder (AUD) patients. Liver transplantation (LT) could represent a risk factor for the onset of WE in AUD patients, due to the onset of chronic depletion [...] Read more.

Wernicke’s encephalopathy (WE) is an acute neurological disorder resulting from thiamine deficiency, commonly found in alcohol use disorder (AUD) patients. Liver transplantation (LT) could represent a risk factor for the onset of WE in AUD patients, due to the onset of chronic depletion of thiamine in this population and the high metabolic demand of surgery and the postoperative period. However, few data are available about the risk of the onset of WE in AUD patients after LT. Here we report three cases of AUD patients who developed WE with confusion and delirium after LT. Prompt parenteral administration of thiamine led to a rapid improvement of the clinical condition and a complete remission of neurological symptoms after 3–4 days. In addition, a search of the available English literature was conducted in order to perform a review of the possible association between the onset of WE and LT in AUD patients. A prophylactic treatment regimen based on the administration of thiamine could be suggested in AUD patients before and after LT. Further studies are needed to determine the optimal regimen of thiamine in the prevention of WE in this setting. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

11 pages, 604 KiB

Open AccessArticle

Incidence and Risk Factors of Alcohol Relapse after Liver Transplantation: Analysis of Pre-Transplant Abstinence and Psychosocial Features

by Tien-Wei Yu, Yu-Ming Chen, Chih-Chi Wang, Chih-Che Lin, Kuang-Tzu Huang, Yueh-Wei Liu, Li-Wen Hsu, Wei-Feng Li, Yi-Chai Chan, Chao-Long Chen and Chien-Chih Chen

J. Clin. Med. 2020, 9(11), 3716; https://doi.org/10.3390/jcm9113716 - 19 Nov 2020

Cited by 3 | Viewed by 2468

Abstract

Alcohol-associated liver disease (ALD) is a common indication for liver transplantation (LT). Alcohol relapse after LT is associated with graft loss and worse prognosis. Over the past 20 years, the number and prevalence of living donor liver transplantations (LDLTs) have increased in Taiwan. [...] Read more.

Alcohol-associated liver disease (ALD) is a common indication for liver transplantation (LT). Alcohol relapse after LT is associated with graft loss and worse prognosis. Over the past 20 years, the number and prevalence of living donor liver transplantations (LDLTs) have increased in Taiwan. The aims of this retrospective study are to analyze the incidence and risk factors of alcohol relapse after LT at a single center in Taiwan. A total of 98 patients with ALD who underwent LT from January 2012 to December 2018 were retrospectively evaluated by chart review. Pre-transplant characteristics as well as psychosocial and alcoholic history were used to test the possible associations among the risk factors studied and post-LT alcohol relapse. The incidence of post-LT alcohol relapse was 16.3%. The median duration of alcohol relapse after liver transplantation was 28.1 months (range: 1–89.4 months). The cumulative incidence was 12% and 19% at 1 year and 3 years after LT, respectively. The most powerful risk factors were a pre-LT abstinence period less than 6 months and younger age of starting alcohol. For predicting alcohol relapse, the accuracy rate of abstinence less than 6 months was up to 83.7%. In summary, pre-abstinence period plays a role in predicting post-LT alcohol relapse. Post-LT interventions should be considered specifically for the patients with short abstinence period. Long-term follow-up, patient-centered counseling, and enhancement of healthy lifestyle are suggested to prevent alcohol relapse. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

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9 pages, 266 KiB

Open AccessArticle

Phosphatidylethanol for Monitoring Alcohol Use in Liver Transplant Candidates: An Observational Study

by Pablo Barrio, Antoni Gual, Anna Lligoña, Lidia Teixidor, Wolfgang Weinmann, Michel Yegles and Friedrich M. Wurst

J. Clin. Med. 2020, 9(9), 3060; https://doi.org/10.3390/jcm9093060 - 22 Sep 2020

Cited by 10 | Viewed by 3324

Abstract

Liver transplantation remains an essential procedure for many patients suffering from alcoholic liver disease. Alcohol use monitoring remains paramount all through the stages of this complex process. Direct alcohol biomarkers, with improved specificity and sensibility, should replace traditional indirect markers. Phosphatidylethanol (PEth) has [...] Read more.

Liver transplantation remains an essential procedure for many patients suffering from alcoholic liver disease. Alcohol use monitoring remains paramount all through the stages of this complex process. Direct alcohol biomarkers, with improved specificity and sensibility, should replace traditional indirect markers. Phosphatidylethanol (PEth) has been recently tested in alcoholic liver disease patients, but more evidence is needed, especially in comparison with other direct biomarkers. We conducted an observational study among patients awaiting liver transplantation. We analyzed Peth in blood, ethylglucuronide (EtG) in hair and urine and ethylsulphate (EtS) in urine, using mass spectrometry methods. In addition, transaminases, and self-reports were analyzed. A total of 50 patients were included (84% men, mean age 59 years (SD = 6)). 18 patients (36%) screened positive for any marker. Self-reports were positive in 3 patients. EtS was the biomarker with more positive screens. It also was the most frequently exclusive biomarker, screening positive in 7 patients who were negative for all other biomarkers. PEth was positive in 5 patients, being the only positive biomarker in 2 patients. It showed a false negative in a patient admitting alcohol use the previous week and screening positive for EtG and EtS. Hair EtG was positive in 3 patients who had negative Peth, EtG. EtG did not provide any exclusive positive result.A combination of biomarkers seems to be the best option to fully ascertain abstinence in this population. Our study suggest EtS might also play a significant role. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

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10 pages, 614 KiB

Open AccessArticle

Active Smoking Before Liver Transplantation in Patients with Alcohol Use Disorder: Risk Factors and Outcomes

by Ana Isabel López-Lazcano, Antoni Gual, Jordi Colmenero, Elsa Caballería, Anna Lligoña, Miquel Navasa, Gonzalo Crespo, Eva López and Hugo López-Pelayo

J. Clin. Med. 2020, 9(9), 2710; https://doi.org/10.3390/jcm9092710 - 21 Aug 2020

Cited by 5 | Viewed by 2601

Abstract

Tobacco use is more prevalent among alcohol liver disease (ALD) transplant patients and exerts harmful effects to the patient and to the graft. The aims of this study were to examine the impact of smoking status (nonsmoker, ex-smoker, active smoker) on patient survival [...] Read more.

Tobacco use is more prevalent among alcohol liver disease (ALD) transplant patients and exerts harmful effects to the patient and to the graft. The aims of this study were to examine the impact of smoking status (nonsmoker, ex-smoker, active smoker) on patient survival and clinical outcomes, and to assess risk factors for active smoking before and after liver transplant (LT). An observational retrospective cohort study with 314 ALD patients undergoing LT from January 2004 to April 2016. Recipients were followed until April 2017 or death. Kaplan–Meier and Cox proportional hazards regression analyses were used to assess risk of mortality according to smoking status before LT. Smokers had a 79% higher risk of dying than those who had never smoked or quit smoking before LT. Ex-smokers had a greater survival probability (96.2%, 93.8%, 86.9%, and 83.1% at 1, 3, 5, and 10 years after LT) than active smokers until LT (96.0%, 85.6%, 80.0%, and 70.4%). Active smokers before LT with poor toxicity awareness had more than a twofold higher risk of mortality (Cox HR = 2.20, 95% CI: 1.05–4.58, p = 0.04) than ex-smokers. Younger age (OR = 94), higher Model for End-Stage Liver Disease (MELD) (OR = 1.06), and comorbid substance use disorder (OR = 2.35) were predictors of smoking until LT. Six months or less of alcohol abstinence (OR = 3.23), and comorbid substance use disorder (OR = 4.87) were predictors of active smoking after LT. Quitting smoking before transplantation improved survival. Evidence based smoking cessation interventions should be offered before and after LT. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

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Review

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16 pages, 1178 KiB

Open AccessReview

PCSK9 and the Gut-Liver-Brain Axis: A Novel Therapeutic Target for Immune Regulation in Alcohol Use Disorder

by Ji Soo Lee, Emma M. O’Connell, Pal Pacher and Falk W. Lohoff

J. Clin. Med. 2021, 10(8), 1758; https://doi.org/10.3390/jcm10081758 - 18 Apr 2021

Cited by 18 | Viewed by 4297

Abstract

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by an impaired ability to control or stop alcohol intake and is associated with organ damage including alcohol-associated liver disease (ALD) and progressive neurodegeneration. The etiology of AUD is complex, but organ injury [...] Read more.

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by an impaired ability to control or stop alcohol intake and is associated with organ damage including alcohol-associated liver disease (ALD) and progressive neurodegeneration. The etiology of AUD is complex, but organ injury due to chronic alcohol use can be partially attributed to systemic and local inflammation along the gut-liver-brain axis. Excessive alcohol use can result in translocation of bacterial products into circulation, increased expression of pro-inflammatory cytokines, and activation of immune cells, including macrophages and/or microglia in the liver and brain. One potential mediator of this alcohol-induced inflammation is proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is primarily known for its regulation of plasma low-density lipoprotein cholesterol but has more recently been shown to influence inflammatory responses in the liver and brain. In rodent and post-mortem brain studies, chronic alcohol use altered methylation of the PCSK9 gene and increased expression of PCSK9 in the liver and cerebral spinal fluid. Additionally, PCSK9 inhibition in a rat model of ALD attenuated liver inflammation and steatosis. PCSK9 may play an important role in alcohol-induced pathologies along the gut-liver-brain axis and may be a novel therapeutic target for AUD-related liver and brain inflammation. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

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20 pages, 370 KiB

Open AccessReview

The History of Alcoholic Liver Disease: From an Unrecognized Disease to One of the Most Frequent Diseases in Hepatology

by Helmut K. Seitz and Manuela G. Neuman

J. Clin. Med. 2021, 10(4), 858; https://doi.org/10.3390/jcm10040858 - 19 Feb 2021

Cited by 24 | Viewed by 3249

Abstract

This review describes the history of alcoholic liver disease from the beginning of the 1950s until now. It details how the hepatotoxicity of alcohol was discovered by epidemiology and basic research primarily by using new feeding techniques in rodents and primates. The article [...] Read more.

This review describes the history of alcoholic liver disease from the beginning of the 1950s until now. It details how the hepatotoxicity of alcohol was discovered by epidemiology and basic research primarily by using new feeding techniques in rodents and primates. The article also recognizes the pioneering work of scientists who contributed to the understanding of the pathophysiology of alcoholic liver disease. In addition, clinical aspects, such as the development of diagnostics and treatment options for alcoholic liver disease, are discussed. Up-to-date knowledge of the mechanism of the disease in 2020 is presented. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

18 pages, 2580 KiB

Open AccessReview

Gut Microbiota at the Intersection of Alcohol, Brain, and the Liver

by Haripriya Gupta, Ki Tae Suk and Dong Joon Kim

J. Clin. Med. 2021, 10(3), 541; https://doi.org/10.3390/jcm10030541 - 2 Feb 2021

Cited by 23 | Viewed by 25357

Abstract

Over the last decade, increased research into the cognizance of the gut–liver–brain axis in medicine has yielded powerful evidence suggesting a strong association between alcoholic liver diseases (ALD) and the brain, including hepatic encephalopathy or other similar brain disorders. In the gut–brain axis, [...] Read more.

Over the last decade, increased research into the cognizance of the gut–liver–brain axis in medicine has yielded powerful evidence suggesting a strong association between alcoholic liver diseases (ALD) and the brain, including hepatic encephalopathy or other similar brain disorders. In the gut–brain axis, chronic, alcohol-drinking-induced, low-grade systemic inflammation is suggested to be the main pathophysiology of cognitive dysfunctions in patients with ALD. However, the role of gut microbiota and its metabolites have remained unclear. Eubiosis of the gut microbiome is crucial as dysbiosis between autochthonous bacteria and pathobionts leads to intestinal insult, liver injury, and neuroinflammation. Restoring dysbiosis using modulating factors such as alcohol abstinence, promoting commensal bacterial abundance, maintaining short-chain fatty acids in the gut, or vagus nerve stimulation could be beneficial in alleviating disease progression. In this review, we summarize the pathogenic mechanisms linked with the gut–liver–brain axis in the development and progression of brain disorders associated with ALD in both experimental models and humans. Further, we discuss the therapeutic potential and future research directions as they relate to the gut–liver–brain axis. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

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24 pages, 800 KiB

Open AccessReview

Magnesium, Calcium, Potassium, Sodium, Phosphorus, Selenium, Zinc, and Chromium Levels in Alcohol Use Disorder: A Review

by Jacek Baj, Wojciech Flieger, Grzegorz Teresiński, Grzegorz Buszewicz, Ryszard Sitarz, Alicja Forma, Kaja Karakuła and Ryszard Maciejewski

J. Clin. Med. 2020, 9(6), 1901; https://doi.org/10.3390/jcm9061901 - 18 Jun 2020

Cited by 53 | Viewed by 23828

Abstract

Macronutrients and trace elements are important components of living tissues that have different metabolic properties and functions. Trace elements participate in the regulation of immunity through humoral and cellular mechanisms, nerve conduction, muscle spasms, membrane potential regulation as well as mitochondrial activity and [...] Read more.

Macronutrients and trace elements are important components of living tissues that have different metabolic properties and functions. Trace elements participate in the regulation of immunity through humoral and cellular mechanisms, nerve conduction, muscle spasms, membrane potential regulation as well as mitochondrial activity and enzymatic reactions. Excessive alcohol consumption disrupts the concentrations of crucial trace elements, also increasing the risk of enhanced oxidative stress and alcohol-related liver diseases. In this review, we present the status of selected macroelements and trace elements in the serum and plasma of people chronically consuming alcohol. Such knowledge helps to understand the mechanisms of chronic alcohol-use disorder and to progress and prevent withdrawal effects, also improving treatment strategies. Full article

(This article belongs to the Special Issue Alcohol, Brain, and the Liver: A Troubled Relationship)

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