Forms Of Alcoholic Liver Disease Research Articles

Screening of liver protective effect of herbal hepatoprotective product in ethanol induced hepatotoxicity in Wister rats

Background: liver is highly susceptible to the toxic and adverse effects of various metabolites and xenobiotics such as alcohol etc. Alcohol abuse leads to hepatotoxicity that is presented in the form of Alcoholic Liver Disease. Aims and Objectives: The present study was conducted to evaluate hepatoprotective activity of polyherbal formulation. The test drug was studied in comparison with marketed formulations in ethanol induced hepatotoxicity in wistar albino rats. Methods: Total 7 groups of animals were studied comparatively to evaluate efficacy of various formulations. Results: It was found that all the formulations tested including all the dosages of Polyherbal Capsule significantly reduced levels of SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamate pyruvate transaminase), Alkaline phosphatase (ALP) and Total Bilirubin when compared to ethanol group. There was significant increase in total protein level in Ariliv Tablet, Silymarin and marketed formulation groups. Also, all the formulations tested effectively preserved the structural integrity of the hepatocellular membrane and liver cell architecture damaged by ethanol. When compared between formulation groups there was no statistical significant difference. Conclusion: It can be concluded that Polyherbal Capsule possesses hepatoprotective activity in ethanol induced hepatotoxicity in rats. Polyherbal Capsule can be effectively used in hepatitis caused due to alcohol.

Collagens of the third and fourth types in various forms of alcoholic liver disease

The aim of the study was to determine the clinical and diagnostic significance of collagens of the third type (Col3) and the fourth type (Col4) in various forms of alcoholic liver disease (ALD). Materials and methods. 98 patients with ALD were examined: 13 (13.3%) with liver steatosis (LS), 15 (15.3%) with steatohepatitis (SH), 56 (57.1%) with liver cirrhosis (LC), 14 (14.3%) with severe alcoholic hepatitis against the background of liver cirrhosis (SAH-LC). Among the examined there were 59 (60.2%) men and 39 (39.80%) women, the average age was 53.48±11.45 years. The content of fibrogenesis proteins in the blood serum - type III collagen (Col3) and type IV collagen (Col4) was determined by enzyme immunoassay (test systems “Kit For Collagen Type III (Col3)” and “Kit For Collagen Type IV (Col4)”, “Cloud-Clone Corp”, USA), a marker of hepatocyte apoptosis - fragments of cytokeratin-18 (FCK-18) (“Biotech” test system, Sweden), cytokines - IL-1β, IL-4, IL-6, IL- 8, TNF-α (“Vector-Best”, Russia). Results. The level of Col3 in healthy individuals was 6.12±0.73 ng/ml and Col4-9.45±0.32 ng/ml. In all forms of ALD, the content of both types of collagen exceeded that in healthy individuals: Col3 in LS was 6.52±0.94 ng/ml (p<0.05), in SH it was 12.50±3.18 ng/ml (p<0.05), in LC - 20.96±4.93 ng/ml (p<0.05), in SAH-LC - 26.90±3.87 ng/ml (p<0.05); Col4-10.14±0.66 ng/ml, 13.87±1.15 ng/ml, 79.56±33.10 ng/ml and 107.12±39.09 ng/ml, respectively. Col3 positively correlated with ALT (r=0.27, p=0.02) and alkaline phosphatase (r=0.28, p=0.04). Col4 correlated with bilirubin (r=0.74), AST (r=0.65), glutamyl transpeptidase (r=0.58), cytokeratin-18 (r=0.56), sedimentation rate of erythrocytes (r=0.61), C-reactive protein (r=0.59), IL -6 (r= 0.51) and leukocytes (r=0.45) (all p<0.001). Conclusion. Col4 demonstrated greater diagnostic and clinical significance in alcoholic liver disease compared to Col3. The level of Col4 increased by an average of 8 times with the progression of the disease from liver steatosis to cirrhosis, and Col3 - only by 3 times. There were more diverse and stronger associations between Col4 and markers of hepatocellular damage and inflammation than between Col3 and these indicators. The maximum rise in the levels of both types of collagen found in SAH-LC confirmed the important role of this form of liver disease in the development of fibrosis, and hence in the further decompensation of liver cirrhosis.

Incidental Findings of Silent Liver Diseases in Autopsy: A Study at Tertiary Care Hospital

Autopsy survey of 80 cases of liver specimens over a period of 2 years done in Vydehi Institute of Medical Science and Research Center, Department of Pathology, Bangalore. Quite rightly liver is, called “The custodian of the milieu interior” Autopsy study is useful to monitor the cause of death and to planning medical strategy. The term “alcoholic liver disease” encompasses a spectrum of pathologic conditions ranging from isolated steatosis to established cirrhosis. Within this spectrum, varying degrees of inflammation, hepatocellular ballooning degeneration, hepatocyte necrosis, cholestasis, and fibrosis may be encountered. This article reviews the characteristic histologic features of the many forms of alcoholic liver disease.

Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation of Glutathione Metabolism in Livers from Patients with Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there is no efficacious treatment aiding most patients. AH manifests differently in individuals, with some patients showing debilitating symptoms more so than others. Previous studies showed significant metabolic dysregulation associated with AH. Therefore, we sought to analyze how the activity of metabolic pathways differed in the liver of patients with varying degrees of AH severity. We utilized a genome-scale metabolic modeling approach that allowed for integration of a generic human cellular metabolic model with specific RNA-seq data corresponding to healthy and multiple liver disease states to predict the metabolic fluxes within each disease state. Additionally, we performed a systems-level analysis of the transcriptomic data and predicted metabolic flux data to identify the regulatory and functional differences in liver metabolism with increasing severity of AH. Our results provide unique insights into the sequential dysregulation of the solute transport mechanisms underlying the glutathione metabolic pathway with increasing AH disease severity. We propose targeting of the solute transporters in the glutathione pathway to mimic the flux activity of the healthy liver state as a potential therapeutic intervention for AH.

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 extremely poor prognosis with a high short term mortality rate. As a result, many centers, including our own, have allowed transplant patients to be listed for transplantation prior to achieving 6-months of sobriety. Several scoring systems, designed to target patients with a minimal period of sobriety, have been proposed to identify patients with alcohol use disorder (AUD), who would be predisposed to relapse after liver transplantation. We investigated whether these scoring systems corroborated the results of the non-structured selection criteria used by our center regarding decision to list for transplant.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 diagnosis of DSM-5 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:The transplant recipients had significantly favorable MAPS, HRAR, SIPAT, ARRA, and HPSS scores with cutoffs that matched their previous research. The SALT and AUDIT-C scores were not predictive of our selection of patients for transplantation. Despite an expedited evaluation and no significant period of sobriety, our case cohort had a 30% relapse to harmful drinking after an average of 6.6 years (5-8.5 years) of follow-up.Discussion:Despite the rapid assessment and the short to no period of sobriety, the patient cohort demonstrated a 30% relapse to harmful drinking, consistent with the 20% to 30% relapse to drinking rate reported after liver transplantation for all forms of alcoholic liver disease. Average scores from MAPS, HRAR, SIPAT, ARRA, and HPSS corroborated our current stratification procedures, with lower mean risk scores found in the transplanted group.Conclusion:Patients with AUD and severe AAH who obtain new insight into their disease and posses other favorable psychosocial factors have low rates of AUD relapse post-liver-transplantation. The psychosocial selection criteria for patients with alcoholic hepatitis in our institution are consistent with 4 of the 5 scoring systems investigated in their prediction of sobriety post-transplant.

Arrb2 causes hepatic lipid metabolism disorder via AMPK pathway based on metabolomics in alcoholic fatty liver

Abstract Background and aims: Alcoholic fatty liver (AFL) is an early form of alcoholic liver disease (ALD) that usually manifests as lipid synthesis abnormalities in hepatocytes. β-arrestin2 (Arrb2) is involved in multiple biological processes. The present study aimed to explore the role of Arrb2 in the regulation of lipid metabolism in AFL and the underlying mechanism and identify potential targets for the treatment of AFL. Methods: The expression of Arrb2 was detected in liver tissues obtained from AFL patients and Gao-binge AFL model mice. In addition, we specifically knocked down Arrb2 in AFL mouse liver in vivo and used Arrb2-siRNA or pEX3-Arrb2 to silence or overexpress Arrb2 in AML-12 cells in vitro to explore the functional role and underlying regulatory mechanism of Arrb2 in AFL. Finally, we investigated whether Arrb2 could cause changes in hepatic lipid metabolites, thereby leading to dysregulation of lipid metabolism based on liquid chromatography-mass spectrometry (LC-MS) analysis. Results: Arrb2 was up-regulated in the livers of AFL patients and AFL mice. The in vivo and in vitro results confirmed that Arrb2 could induce lipid accumulation and metabolism disorders. Mechanistically, Arrb2 induced hepatic metabolism disorder via AMP-activated protein kinase (AMPK) pathway. The results of LC-MS analysis revealed that hepatic lipid metabolites with the most significant differences were primary bile acids. Conclusions: Arrb2 induces hepatic lipid metabolism disorders via AMPK pathway in AFL. On one hand, Arrb2 increases fatty acid synthesis. On the other hand, Arrb2 could increase the cholesterol synthesis, thereby leading to the up-regulation of primary bile acid levels.

Hepatocellular damage and inflammation in various forms of alcoholic liver disease

The aim of the study was to evaluate hepatocellular damage and immune inflammation in various forms of alcoholic liver disease (ALD). 104 patients with ALD were examined: 15 (14.4%) with liver steatosis (LS), 19 (18.3%) with steatohepatitis and 70 (67.3%) with liver cirrhosis (LC); men 50 (48.1%), women 54 (51.9%); age 45.78.4 years. Traditional clinical, laboratory, instrumental studies were performed, the levels of fragments of cytokeratin-18 (FCK-18), cytokines IL-1, TNF-, IL-4, IL-6, IL-8 were determined by ELISA. The control group consisted of 39 healthy individuals: men 20 (51.2%), women 19 (48.7%), age 48.58.3 years. In LS, an increase in the level of FCK-18 was noted with normal aminotransferase activity, the content of TNF-, IL-6, IL-1, IL-8 increased and the level of IL-4 decreased compared to those in healthy individuals. In steatohepatitis, a triple increase in aminotransferases and FCK-18 was observed compared with LS, as well as an increase in the level of inflammatory mediators, to a greater extent IL-6, to a lesser extent IL-8, TNF-, a decrease in IL-4, IL-1 remained at the same level. In LC, there was a further increase in FCK-18, significantly more pronounced than an increase in AST, and the increase in cytokines continued to the same extent, the levels of IL-6 and IL-8, to a lesser extent IL-1 and TNF-, and the level of IL-4. With the progression of ALD from LS to steatohepatitis, hepatic cell damage was carried out by equally pronounced processes of hepatocyte necrosis and apoptosis, with the development of cirrhosis of the liver, parenchyma damage occurred mainly due to hepatocyte apoptosis. The immuno-inflammatory process progressively increased from the stage of LS to LC with IL-6 and IL-8 undergoing the greatest dynamics. FCK-18 can serve as a non-invasive marker of hepatic cell damage, and IL-6 and IL-8 markers of immune inflammation in ALD.

Novel Biomarker for the Diagnosis and Prognosis of Acute Alcoholic Hepatitis.

Alcohol use disorder (AUD) characterized by heavy and prolonged alcohol intake could cause various forms of alcoholic liver disease (ALD). The spectrum of alcoholic liver disease (ALD) consists of steatosis, steatohepatitis, cirrhosis and hepatocellular carcinoma depending on the duration and severity of alcohol intake [1,2]. Interestingly only one-third of heavy drinkers (typically a sub-group of AUD patients), who exhibit specific heavy drinking patterns [3,4] would develop any clinically relevant form of liver damage.

NLRP6 exerts a protective role via NF-kB with involvement of CCL20 in a mouse model of alcoholic hepatitis

Alcoholic hepatitis (AH) is an important form of alcoholic liver disease (ALD), and its incidence is continuously increasing leading to advanced disease burden. The NOD-like receptors (NLRs) are a specialized group of intracellular pattern recognition receptors, which participate in inflammatory diseases. However, the role of NLRs in the pathogenesis of AH still remain obscure. The animal model of alcoholic hepatitis in mice was established according to National Institute on Alcohol Abuse and Alcoholism (NIAAA) method. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of NLR family members in liver tissues of the ethanol-fed(EtOH-fed)group and pair-fed group. NLRP6 was overexpressed in mice by injecting Recombinant Adeno-Associated Virus into the tail vein. Mouse Cytokines and Chemokines RT2 Profiler PCR Array was used to analyze the related cytokines and chemokines involved in the development of alcoholic hepatitis. Among the NLR family members, the expression of NLRP6 decreased most significantly in the animal model of AH. Our results demonstrated that overexpression of NLRP6 in vivo obviously alleviated steatosis, inflammation and fibrosis in liver. Meanwhile, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice also decreased. Besides, Chemokine (C–C motif) ligand 20(CCL20) was one of the most significantly up-regulated chemokines in the mouse AH model and CCL20 was participated in NLRP6-mediated AH. NLRP6 could inhibit the activation of nuclear factor (NF)-κB signaling pathway in vitro and in vivo. Furthermore, the activation, proliferation, and migration of hepatic stellate cells was enhanced after downregulation of NLRP6. In summary, NLRP6 may play a protective role in the development of AH. NLRP6 could inhibit activation of NF-κB signaling pathway in AH.

Inflammation in Primary and Metastatic Liver Tumorigenesis-Under the Influence of Alcohol and High-Fat Diets.

The liver plays an outsized role in oncology. Liver tumors are one of the most frequently found tumors in cancer patients and these arise from either primary or metastatic disease. Hepatocellular carcinoma (HCC), the most prevalent form of primary liver cancer and the 6th most common cancer type overall, is expected to become the 3rd leading cause of cancer mortality in the US by the year 2030. The liver is also the most common site of distant metastasis from solid tumors. For instance, colorectal cancer (CRC) metastasizes to the liver in two-thirds of cases, and CRC liver metastasis is the leading cause of mortality in these patients. The interplay between inflammation and cancer is unmistakably evident in the liver. In nearly every case, HCC is diagnosed in chronic liver disease (CLD) and cirrhosis background. The consumption of a Western-style high-fat diet is a major risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), both of which are becoming more prevalent in parallel with the obesity epidemic. Excessive alcohol intake also contributes significantly to the CLD burden in the form of alcoholic liver disease (ALD). Inflammation is a key component in the development of all CLDs. Additionally, during the development of liver metastasis, pro-inflammatory signaling is crucial in eliminating invading cancer cells but ironically also helps foster a pro-metastatic environment that supports metastatic seeding and colonization. Here we review how Westernized high-fat diets and excessive alcohol intake can influence inflammation within the liver microenvironment, stimulating both primary and metastatic liver tumorigenesis.

Identification of key genes, MicroRNAs and potentially regulated pathways in alcoholic hepatitis by integrative analysis

Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease associated with high mortality. Current pharmacological treatment options are not fully effective, and novel target therapies are urgently needed. Until now, key genes, miRNAs and potential signaling pathways in AH remain unclear. Here, we integrated mRNA and miRNA expression profiles to reveal 1411 differentially expressed genes (DEG) and 69 differentially expressed miRNAs (DEM) in AH. And then 51 overlapping genes were identified by compared with miRNA target genes and DEGs, which named as consistent expression genes (CEGs). Pathway analysis showed that CEGs were mainly enriched in PI3K-Akt signaling pathway, MicroRNAs in cancer, FoxO signaling pathway, TNF signaling pathway and P53 signaling pathway. A total of 8 hub genes，FOS, FOXO1, SIRT1, ESR1, BCL2L11, CDK1, CCNB1 and CDKN1A, were screened using protein-protein interaction network analysis. In the regulatory network of miRNA and hub genes, a total of five miRNAs, miR-29c, miR-92b, miR-132, miR-221, miR-222, were identified as key miRNAs. Among them, miR-132 has been shown to target SIRT1, FOXO1, CDKN1A and BCL2L11, and miR-92b targets SIRT1 and BCL2L11. miR-221 and miR-222 both target FOS, ESR1, and BCL2L11. In addition, miR-29c is one of the major down-regulated miRNAs in AH, targeting FOS. Western blot analysis showed that SIRT1 and FoxO1 were expressed at low levels (P < 0.05) and CDK1 was highly expressed in the AH group (P < 0.05). The other five proteins were not significantly different between the two groups (P > 0.05). RT-PCR results showed that miR-132 was significantly higher in the AH group than in the normal group (P < 0.05), while miR-29c was lower than the normal group (P < 0.05), and the other three miRNAs were not significantly different between the two groups (P > 0.05). Therefore, SIRT1, FOXO1, CDK1, miR-132 and miR-29c are involved in the regulation of FoxO and P53 signaling pathways, cell cycle and other biological processes, which may play a key role in the pathogenesis of AH.

Glucocorticosteroids for people with alcoholic hepatitis.

Glucocorticosteroids for people with alcoholic hepatitis.

Burden of Alcoholic Liver Disease in a Tertiary Care Center: A Descriptive Cross-sectional Study

Alcoholic liver disease is a serious health problem related to an unhealthy lifestyle. The three most widely recognized forms of alcoholic liver disease are alcoholic fatty liver, acute alcoholic hepatitis, and alcoholic cirrhosis. The main aim of our study is to find out the prevalence of alcoholic liver disease in tertiary care center. A descriptive cross-sectional study was conducted among inpatient cases admitted in the medicine department of tertiary care center from 1st June 2018 to 31st May 2019. Ethical approval was taken for the study. Convenience sampling method was used. All the biochemical parameters were expressed as mean±standard deviation for each group and point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. Prevalence of alcoholic liver disease is 50 (50%) at a 95% Confidence Interval (40.2%-59.8%) and non-alcoholic fatty liver disease is also the same. The mean age of alcoholic liver disease was 59±12 years where as the mean age for non-alcoholic fatty liver disease was 46±18 years. Out of fifty patients of alcoholic liver disease, majority 48 (96%) of the cases were males which suggests that the prevalence of alcoholic liver disease is very common in males. Similarly, for non-alcoholic fatty liver disease, prevalence was 34 (68%) showing higher prevalence than that of females. Prevalence of alcoholic liver disease is low compared to previous studies done in the similar settings. Monitoring these biochemical parameters in alcoholic liver disease at early stage could guide in planning the protocol for the initial treatment.

Alcoholic Hepatitis: Lost in Translation.

Alcoholic hepatitis is the most severe and acute form of alcoholic liver disease. The mortality rate associated with alcoholic hepatitis is high, largely due to the lack of suitable pharmacological interventions. While there has been substantial research in the area, generating pharmacological interventions has been plagued by the lack of a robust mouse model both for testing and for understanding the underlying pathology. A number of major notable advances have been made in this area recently, with the goal of generating a mouse model of alcoholic hepatitis. The purpose of this article is to review recent advances in modeling alcoholic liver disease both in vitro and in vivo in the mouse, and place them in the context of the greater spectrum of alcoholic liver disease, with a focus on how we can translate current advances into a high-fidelity model of alcoholic hepatitis. In addition, we will review the basic mechanisms of alcoholic hepatitis as it is currently understood, focusing on recent advancements in diagnosis, prognosis and current pathophysiology, especially as it relates to the profound immune dysfunction present during alcoholic hepatitis.

Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long-term survival.

Complete abstinence after an episode of AH positively impacts long-term survival. The combination of 2 variables easily obtained at admission might be useful to predict long-term abstinence after an episode of AH. Strategies aimed at promoting alcohol abstinence in these patients are necessary. (Hepatology 2017;66:1842-1853).

Glucocorticosteroids for people with alcoholic hepatitis.

Glucocorticosteroids for people with alcoholic hepatitis.

Controversies in clinical trials for alcoholic hepatitis

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease, contributing to significant morbidity and mortality. Yet, the only available therapies that improve survival are corticosteroids and liver transplantation, with no new drugs successfully developed for decades. This article briefly describes the current state of affairs in AH therapy and examines the practical and ethical challenges of conducting controlled trials in patients with severe AH. While prednisolone is considered standard of care in severe AH, this recommendation remains controversial given the marginal benefits and questionable long-term safety of steroids. Placebo-controlled trials without steroids may be necessary and ethically justified in certain populations with AH who have not been adequately investigated. Ultimately, we suggest that the field will advance with the development of a plausible animal model of true AH, a consensus on a composite clinical endpoint that does not rely solely on mortality, as well as the adoption of the NIAAA Alcoholic Hepatitis Consortia recommendations regarding standard definitions and when to request a liver biopsy prior to study entry.

ПАТОМОРФОЛОГИЧЕСКАЯ ОЦЕНКА ОТРАВЛЕНИЙ ЭТАНОЛОМ НА ФОНЕ АЛКОГОЛЬНОЙ БОЛЕЗНИ ПЕЧЕНИ

Morphological pattern of alcohol poisoning and its evaluation remains controversial issue to date. In this paper we analyzed and evaluated pathologic features ethanol intoxication in patients with various forms of alcoholic liver disease (ALD).

Interobserver Variability in Scoring Liver Biopsies with a Diagnosis of Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is one of the most severe forms of alcoholic liver disease. Recently, a histologic scoring system for predicting prognosis in this patient cohort was proposed as Alcoholic Hepatitis Histologic Score (AHHS). We aimed to assess interobserver variability in recognizing histologic features of AH and the effect of this variability on the proposed AHHS categories. Hematoxylin-eosin- and trichrome-stained slides from 32 patients diagnosed with AH with liver biopsies within 1month of presentation (2000 to 2015) were reviewed by 5 pathologists including 3 liver pathologists and 2 gastrointestinal (GI) pathologists masked to the clinical findings or outcome. Histologic features of AH were assessed, the AHHS was calculated, and an AHHS category (mild, moderate, severe) was assigned. The Fleiss' kappa coefficient (κ) analysis was performed to determine the interobserver agreement. A slight-to-moderate level of interobserver agreement existed among 5 reviewers on histopathologic features of AH with κ value ranging from 0.20 (95% confidence interval (CI): 0.03 to 0.46, megamitochondria) to 0.52 [95% CI: 0.40 to 0.68, polymorphonuclear leukocyte (PMN) infiltration]. There was only a fair level of agreement in assigning AHHS category (κ=0.33, 95% CI: 0.20 to 0.51). While overall fibrosis and neutrophilic inflammation were comparably evaluated by 3 liver pathologists and 2 GI pathologists, bilirubinostasis and megamitochondria were more consistently diagnosed by liver pathologists. Overall, 18 of 32 (56%) were uniformly assigned to an AHHS category by all liver pathologists with a κ value of 0.40 (95% CI: 0.22 to 0.60). In general, features of AH can be recognized with a slight-to-moderate level of interobserver agreement and there was fair interobserver agreement on assigning an AHHS category. Significant interobserver variability among pathologists revealed by the current study can limit its usefulness in everyday clinical practice.

LPS-TLR4 Pathway Mediates Ductular Cell Expansion in Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there are no effective therapies. Patients with AH show impaired hepatocyte proliferation, expansion of inefficient ductular cells and high lipopolysaccharide (LPS) levels. It is unknown whether LPS mediates ductular cell expansion. We performed transcriptome studies and identified keratin 23 (KRT23) as a new ductular cell marker. KRT23 expression correlated with mortality and LPS serum levels. LPS-TLR4 pathway role in ductular cell expansion was assessed in human and mouse progenitor cells, liver slices and liver injured TLR4 KO mice. In AH patients, ductular cell expansion correlated with portal hypertension and collagen expression. Functional studies in ductular cells showed that KRT23 regulates collagen expression. These results support a role for LPS-TLR4 pathway in promoting ductular reaction in AH. Maneuvers aimed at decreasing LPS serum levels in AH patients could have beneficial effects by preventing ductular reaction development.