Alcoholic Liver Disease Among Patients with Wernicke Encephalopathy: A Multicenter Observational Study

Novo-Veleiro, Ignacio; Herrera-Flores, Javier; Rosón-Hernández, Beatriz; Medina-García, José-A.; Muga, Roberto; Fernández-Solà, J; Martín-González, M. Candelaria; Seco-Hernández, Elena; Suárez-Cuervo, Carlos; Mateos-Díaz, Ana-M.; Monte-Secades, Rafael; Machado-Prieto, Begoña; Puerta-Louro, Rubén; Prada-González, Cristina; Fernández-Rial, Álvaro; Sabio-Repiso, Patricia; Vázquez-Vigo, Rocío; Antolí-Royo, Ana-C.; Gomila-Grange, Aina; Felipe-Pérez, Nieves-C.; Sanvisens-Bergé, Arantza; Antúnez-Jorge, Emilia; Fernández-Rodríguez, C.; Alvela-Suárez, Lucía; Fidalgo-Navarro, Alba; Castro, Joaquín; Polvorosa-Gómez, María-A.; Valle-Sánchez, Mario Del; Castro, José López; Chamorro, Antonio-Javier; Marcos, Miguel

doi:10.1016/j.drugalcdep.2021.109186

Cited by 12 publications

(9 citation statements)

References 32 publications

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“…For instance, a retrospective cohort study of 1,244 patients indicated that anemia was an independent risk factor for hepatic decompensation in compensated patients [33]. Several studies have also revealed that anemia is associated with a higher mortality rate in patients with alcoholic liver disease, pyogenic liver abscess, acute-on-chronic liver failure, and hepatic encephalopathy [15,[42][43][44]. In our cohort, WD patients with anemia had a higher risk of developing an advanced Child-Pugh classification, indicating that anemia may promote WD progression.…”

Section: Discussionmentioning

confidence: 99%

Anemia Is Associated with Disease Severity, Hepatic Complications, and Progression of Wilson Disease: A Retrospective Cohort Study

Wang

Zhan

Huang

et al. 2023

Dig Dis

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Introduction: Anemia is a common manifestation of chronic liver diseases. It is a predictor of severe disease, a high risk of complications, and poor outcomes in various liver diseases. However, it remains unclear whether anemia serves as a similar indicator in patients with Wilson disease (WD). Therefore, this study aimed to investigate the relationship between anemia and severity, hepatic complications, and the progression of WD. Methods: Medical data were collected retrospectively from January 1, 2016, to December 31, 2020. Univariate and multivariate analyses were carried out to investigate the relationship between anemia and liver-associated disease severity, hepatic complications, and the progression of WD. Results: A total of 288 WD patients (48 with and 240 without anemia) were enrolled in the study. Multivariate linear regression revealed that WD patients with anemia had significantly higher levels of bilirubin, alanine transaminase, prothrombin time, international normalized ratio, type Ⅳ collagen, and hyaluronic acid and significantly lower levels of albumin, total cholesterol, and high-density lipoprotein-cholesterol (all P < 0.05). Multivariate logistic regression showed that anemia was a risk factor for gastric varices and ascites (all P < 0.05). Fully adjusted Cox regression revealed that anemia was an independent risk factor for advanced Child–Pugh classification (P = 0.034). Conclusions: Anemia was common in WD patients and was associated with greater disease severity, a higher risk of hepatic complications, and a faster progression.

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Section: Discussionmentioning

confidence: 99%

Anemia Is Associated with Disease Severity, Hepatic Complications, and Progression of Wilson Disease: A Retrospective Cohort Study

Wang

Zhan

Huang

et al. 2023

Dig Dis

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“…However, in spite of alcohol consumption is the main cause of WE, the prevalence and characteristics of the relationship between ALD and WE remain unclear due to the lack of available data (Chamorro Fernández et al, 2011). ALD is a possible comorbidity in WE patients, which present specific clinical, analytical and radiological characteristics and a poorer prognosis compared to alcoholic WE patients without ALD (Novo-Veleiro et al, 2022). Hepatic encephalopathy (HE) induced by chronic alcohol consumption is the extreme example of brain and liver interaction.…”

Section: Discussionmentioning

confidence: 99%

“…Other factors, such as oxidative stress, neurosteroids, systemic inflammation, increased bile acids, impaired lactate metabolism, and altered blood-brain barrier permeability likely contribute to the process of HE (Liere et al, 2017;Hadjihambi et al, 2018). In patients with underlying liver cirrhosis, distinguishing between HE and WE sometimes becomes a tough problem (Novo-Veleiro et al, 2022). HE is characterized by a wide spectrum of nonspecific neurological, psychiatric and motor disturbances, so most of them may coincide with those in WE, since no mental alteration is unique for both disorders.…”

Section: Discussionmentioning

confidence: 99%

“Upregulation of TLR4/MyD88 pathway in alcohol-induced Wernicke’s encephalopathy: findings in preclinical models and in a postmortem human case”

Moya

Escudero

Gómez-Blázquez

et al. 2022

Preprint

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Wernicke encephalopathy (WE) is a neurologic disease caused by vitamin B1 or thiamine deficiency (TD), being the alcohol use disorder (AUD) its main risk factor. WE patients present limiting motor, cognitive and emotional alterations related to a selective cerebral vulnerability. Neuroinflammation has been proposed as one of the phenomena contributing to brain damage. Our previous studies provide evidence for the involvement of the innate immune receptor Toll-like (TLR) 4 in the inflammatory response induced in the frontal cortex and cerebellum in TD animal models (animals fed with TD diet and receiving pyrithiamine). However, the effects of the combination of chronic alcohol consumption and TD on TLR4 and their specific contribution to the pathogenesis of WE are currently unknown. Additionally, no studies on TLR4 have been conducted on WE patients since brains from these patients are difficult to achieve. Here, we used rat models of chronic alcohol (CA; 9 months of forced consumption of 20% (w/v) alcohol), TD hit (TDD; TD diet + daily 0.25 mg/kg i.p. pyrithiamine during 12 days), or a combined treatment (CA+TDD) to check the activation of the proinflammatory TLR4/MyD88 pathway and related markers in the frontal cortex and the cerebellum. In addition, we characterized for the first time the TLR4 and its co-receptor MyD88 signature, along with other markers of this proinflammatory signaling such as phospo-NFkappaB; p65 and IkappaB, in the post-mortem human frontal cortex and cerebellum (gray and white matter) of an alcohol-induced WE patient, comparing it with negative (no disease) and positive (aged brain with Alzheimer disease) control subjects for neuroinflammation. We found an increase in the cortical TLR4 and its adaptor molecule MyD88, together with an upregulation of the proinflammatory signaling molecules p-NFkappaB and IkappaB in the CA+TDD animal model. In the patient diagnosed with alcohol-induced WE we observed cortical and cerebellar upregulation of the TLR4/MyD88 pathway. Thus, our findings provide evidence, both in the animal model and the human postmortem brain, of the upregulation of the TLR4/MyD88 proinflammatory pathway in WE related to alcohol consumption.

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“…However, despite alcohol consumption being the main cause of WE, the prevalence and characteristics of the relationship between ALD and WE remain unclear because of the lack of available data ( Chamorro Fernández et al, 2011 ). ALD is a possible comorbidity in WE patients, which presents specific clinical, analytical, and radiological characteristics and a poorer prognosis compared with alcoholic WE patients without ALD ( Novo-Veleiro et al, 2022 ). Hepatic encephalopathy (HE) induced by CA consumption is an extreme example of brain and liver interaction.…”

Section: Discussionmentioning

confidence: 99%

“…Other factors, such as oxidative stress, neurosteroids, systemic inflammation, increased bile acids, impaired lactate metabolism, and altered blood–brain barrier permeability likely contribute to the process of HE ( Liere et al, 2017 ; Hadjihambi et al, 2018 ). In patients with underlying liver cirrhosis, distinguishing between HE and WE sometimes becomes a tough problem ( Novo-Veleiro et al, 2022 ). HE is characterized by a wide spectrum of nonspecific neurological, psychiatric, and motor disturbances; hence, most of them may coincide with those in WE, since no mental alteration is unique for both disorders.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of TLR4/MyD88 pathway in alcohol-induced Wernicke’s encephalopathy: Findings in preclinical models and in a postmortem human case

et al. 2022

View full text Add to dashboard Cite

Wernicke’s encephalopathy (WE) is a neurologic disease caused by vitamin B1 or thiamine deficiency (TD), being the alcohol use disorder its main risk factor. WE patients present limiting motor, cognitive, and emotional alterations related to a selective cerebral vulnerability. Neuroinflammation has been proposed to be one of the phenomena that contribute to brain damage. Our previous studies provide evidence for the involvement of the innate immune receptor Toll-like (TLR)4 in the inflammatory response induced in the frontal cortex and cerebellum in TD animal models (animals fed with TD diet [TDD] and receiving pyrithiamine). Nevertheless, the effects of the combination of chronic alcohol consumption and TD on TLR4 and their specific contribution to the pathogenesis of WE are currently unknown. In addition, no studies on TLR4 have been conducted on WE patients since brains from these patients are difficult to achieve. Here, we used rat models of chronic alcohol (CA; 9 months of forced consumption of 20% (w/v) alcohol), TD hit (TDD + daily 0.25 mg/kg i.p. pyrithiamine during 12 days), or combined treatment (CA + TDD) to check the activation of the proinflammatory TLR4/MyD88 pathway and related markers in the frontal cortex and the cerebellum. In addition, we characterized for the first time the TLR4 and its coreceptor MyD88 signature, along with other markers of this proinflammatory signaling such as phospo-NFκB p65 and IκBα, in the postmortem human frontal cortex and cerebellum (gray and white matter) of an alcohol-induced WE patient, comparing it with negative (no disease) and positive (aged brain with Alzheimer’s disease) control subjects for neuroinflammation. We found an increase in the cortical TLR4 and its adaptor molecule MyD88, together with an upregulation of the proinflammatory signaling molecules p-NF-ĸB and IĸBα in the CA + TDD animal model. In the patient diagnosed with alcohol-induced WE, we observed cortical and cerebellar upregulation of the TLR4/MyD88 pathway. Hence, our findings provide evidence, both in the animal model and the human postmortem brain, of the upregulation of the TLR4/MyD88 proinflammatory pathway in alcohol consumption–related WE.

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Alcoholic Liver Disease Among Patients with Wernicke Encephalopathy: A Multicenter Observational Study

Cited by 12 publications

References 32 publications

Anemia Is Associated with Disease Severity, Hepatic Complications, and Progression of Wilson Disease: A Retrospective Cohort Study

Anemia Is Associated with Disease Severity, Hepatic Complications, and Progression of Wilson Disease: A Retrospective Cohort Study

“Upregulation of TLR4/MyD88 pathway in alcohol-induced Wernicke’s encephalopathy: findings in preclinical models and in a postmortem human case”

Upregulation of TLR4/MyD88 pathway in alcohol-induced Wernicke’s encephalopathy: Findings in preclinical models and in a postmortem human case

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