Severe alcohol-related hepatitis (sAH) is a potentially life-threatening complication of alcohol-related liver disease. SIRS criteria have been related to disease severity and may be a prognostic factor. Recently, qSOFA has been shown to be more prognostically accurate than SIRS in other inflammatory conditions. To determine whether qSOFA is a better prognostic score than SIRS criteria in sAH. We included 62 consecutive patients admitted for sAH, defined by modified Maddrey DF ≥ 32. MELD-Na, SIRS criteria and qSOFA score were calculated. Survival at 180 days was assessed. Twenty-four patients (38.7%) died after 180 days. Three or more SIRS criteria and two or more qSOFA criteria were associated with 180-day mortality (LR = 12.09, p = 0.001; LR = 4.81, p = 0.028, respectively). Patients with MELD-Na >30 points died during follow-up more frequently (LR = 5.997; p = 0.014). SIRS respiratory criterion (B = 5.113; p = 0.023) and qSOFA respiratory criterion (B = 5.985; p = 0.05), bilirubin (>10 mg/dL; LR = 5.43, p = 0.006), creatinine (>1 mg/dL; B = 5.885, p = 0.015) and hyponatraemia (LR= 5.75, p = 0.018) were associated with mortality. Cox Regression model revealed that only SIRS and MELD-Na were independent prognostic factors. SIRS criteria seem to be more useful for patients with sAH, as well as MELD-Na. In contrast, qSOFA has no independent prognostic value in patients with sAH.

Patients with liver disease in the intensive care unit (ICU) face a unique susceptibility to infection due to the complex immune dysfunction resulting from hepatic failure. Bacterial infections are commonly present in these patients upon arrival to the hospital, often being the primary reason for ICU admission. In contrast, invasive fungal infections (IFIs) afflict a smaller percentage of patients and are usually discovered in the course of the ICU stay. IFI diagnosis in the ICU, particularly in patients with liver disease, is often delayed or overlooked, contributing to the extremely high ICU mortality associated with IFI in these patients despite the availability of effective (and largely safe) antifungal therapy. Thus, to improve outcomes, it is crucial for intensive care clinicians to be vigilant for IFIs in patients with liver disease. This review aims to contribute to the intensive care literature in this regard. We begin with an overview of normal antifungal immunity followed by a summary of how it may become compromised in the setting of hepatic dysfunction. Next, a general discussion of IFIs in liver disease is presented and then the three most relevant fungal pathogens, namely Candida, Aspergillus, and Cryptococcus, are individually examined. This review concludes by highlighting key knowledge and practice gaps that require attention by the scientific and clinical communities in the coming years.

Corticosteroids are recommended by multiple society guidelines for the treatment of severe alcohol-associated hepatitis (AH). However, their use remains controversial due to inconsistent studies regarding their survival benefit.

This was a retrospective cohort study of first-time hospitalizations for severe AH (Maddrey discriminant function ≥ 32) admitted to the Veterans Health Administration between January 3, 2005, and December 5, 2020, (i) evaluating the effect of corticosteroid therapy on all-cause survival, (ii) characterizing the clinical and psychosocial factors associated with corticosteroid use, and (iii) determining the effect of duration of corticosteroid therapy on all-cause survival among treatment-responsive patients (Lille score < 0.45).

During the study period, 2,618 patients were admitted with severe AH, of whom 1,083 (41.37%) received corticosteroids. Although corticosteroids were significantly associated with improved all-cause survival in the unadjusted model ( P = 0.022), no survival benefit was observed in the adjusted model after accounting for baseline and admission characteristics (adjusted hazard ratio [aHR] = 1.01, P = 0.818). Psychiatry consultation was the only factor evaluated that was protective against mortality (aHR = 0.67, P < 0.001). Among the 428 patients (49.7%) responsive to corticosteroids, duration of therapy was not associated with overall survival on unadjusted ( P = 0.696) or adjusted models (aHR = 1.12, P = 0.710 for a ≥28-day course compared with a ≤7-day reference).

Despite being recommended by clinical guidelines for severe AH, corticosteroids have low utilization with no survival benefit after accounting for differences in patient characteristics and practice patterns. Among patients with treatment response per the Lille score, no difference was observed in overall survival between shorter and longer durations of corticosteroid therapy.

Alcohol use disorder (AUD) is present in the majority of patients with alcohol-associated liver disease (ALD), which leads to about 50% of cirrhosis-related hospitalizations and over 25% of deaths worldwide. Patients with ALD often present at an advanced stage, like cirrhosis with its complications and alcohol-associated hepatitis (AH), which has high short-term mortality. Current treatments are limited, with the limited benefit of glucocorticoids only in the short-term among patients with AH, highlighting an urgent need for novel therapies.

This review applies the PIRO (Predisposition, Injury, Response, Organ dysfunction) concept to ALD, understanding an ongoing process of liver damage, and opportunities to address and halt the progression. We also highlight the significance of treating AUD to improve long-term outcomes in ALD.

Personalized therapies targeting specific genetic profiles and multiple pathogenic pathways are crucial in managing ALD. Emerging therapies like gut-liver-brain axis modulators like fecal microbiota transplant and probiotics, interleukin-22, granulocyte-colony stimulating factor (G-CSF) and stem cells, epigenetic regulators of inflammation and regeneration are encouraging with the potential of efficacy in patients with ALD. Liver transplantation (LT) is a definitive therapy for advanced cirrhosis with increasing impetus on early LT select patients with active alcohol use.

Background/Objectives: Bacterial infections (BI) are a major cause of mortality in patients with alcohol-associated hepatitis (AH); however, only a few studies have investigated BI in AH in the last decade. Therefore, we aimed to assess the features and outcomes of BI in patients with AH. Methods: This observational descriptive study included patients with AH admitted to a tertiary academic hospital between 2016 and 2021. Clinical and complete microbiological data were recorded and complications, including acute-on-chronic liver failure (ACLF), and mortality over 90-days were compared between infected and noninfected patients. Results: Overall, 115 patients with AH were recruited and 75 had severe AH; among them, 66 started corticosteroid treatment. We identified 69 cases of BI in 44 patients; the incidence of BI upon hospital discharge was 32.2%, which reached 38.2% at 90 days. The predominant infection site was the chest (35%). Among the identified bacteria (52.1%), half were gram positive and half gram negative. A low rate of multidrug-resistant bacteria (14%) was also noted. Infected patients during hospitalization (n = 37) exhibited higher rates of hepatic decompensation and ACLF (p = 0.001) and lower survival (81.8% vs. 95.8%, p = 0.015) than did noninfected patients (n = 78). In-hospital infected patients (n = 22) exhibited worse survival (72.7%) than did those infected upon admission (93.3%) or noninfected patients (94.9%) (p = 0.009). Corticosteroid-treated patients displayed a nonsignificant increase in the total number of BI; however, without greater mortality. Conclusions: BI were common in our cohort of patients with AH. Patients with in-hospital infections commonly experienced serious complications, including high ACLF and death rates. Infections diagnosed upon admission were treated without affecting survival.

This research aims to evaluate the efficacy and safety of prophylactic antibiotics in patients with alcohol-related liver disease (ALD).

We systematically searched databases including PubMed, Embase, Cochrane, and Web of Science up to October 2023. Our scope encompassed the influence of prophylactic antibiotics on all-cause mortality, infection, variceal bleeding, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), adverse events (AE), fungal infection, clostridioides difficile infection (CDI), and multidrug-resistant (MDR) bacterial infection. Additionally, total bilirubin, creatinine, platelet counts, and plasma endotoxin levels were also analyzed.

After comprehensive selection, 10 studies with 974 participants were included for further analysis. The study demonstrated that prophylactic antibiotic therapy was associated with reductions in infection rates, HE incidence, variceal bleeding, and all-cause mortality. The treatment did not increase the incidence of AE, fungal infection, and CDI, but it did raise the MDR bacteria infection rate. The analysis revealed no significant protective effect of antibiotic prophylaxis on total bilirubin and creatinine levels. Furthermore, the administration of antibiotics led to marginal increases in platelet counts, a minor reduction in endotoxin concentrations, and a subtle enhancement in HRS; however, these changes did not reach statistical significance.

Prophylactic antibiotic therapy was an effective and safe treatment for advanced ALD. To mitigate the risk of MDR bacterial infections, a strategy of selective intestinal decontamination could be advisable. Future investigations should prioritize varied ALD patient populations with extended follow-up periods and assorted antibiotic regimens to solidify the efficacy and safety of ALD treatments.

Severe alcoholic hepatitis is the most lethal complication in alcohol dependent patients. The concurrence of infections in these patients is very frequent. Both produce a systemic inflammatory response syndrome (SIRS), secondary to intense release of inflammatory cytokines, which can complicate the diagnosis. In our study, Interleukin (IL)-6 and IL-10 levels are higher in patients with SIRS (p<0.001 and p = 0.033, respectively). IL-4, IL-6, Interferon-gamma (IFNγ), Tumor necrosis factor alpha (TNFα) and IL-17 levels correlate with liver function, as estimated by MELD-Na (p = 0.018, p = 0.008, p = 0.009, p = 0.016 and p = 0.006, respectively). Malondialdehyde (MDA), a product of lipid peroxidation and marker of cell damage, also correlates with liver function (p = 0.002), but not with SIRS or infections. Only elevated IL-6 correlates independently with the presence of infections (RR=1.023 IC 95% 1.000-1.047), so it may be useful for the correct diagnosis in these patients. Values greater than 30 pg/mL have a sensitivity: 86.7% and specificity: 94.7% for the diagnosis of infections.

Alcohol is the leading cause of preventable liver morbidity and mortality worldwide, as it is also the most frequent cause of advanced liver disease. Alcohol-associated liver disease (ALD) covers different phenotypes ranging from steatosis to the development of inflammation (steatohepatitis), fibrosis and ultimately, in a proportion of patients, the development of liver cirrhosis and its associated complications. ALD has a complex pathogenesis that includes the interplay of both genetic and environmental factors, yet the precise mechanisms are largely unknown. Alcohol-associated hepatitis (AH) is a severe clinical presentation of ALD, which is characterized by abrupt jaundice and clinical decompensations of liver disease. AH occurs in a percentage of patients with underlying ALD and active alcohol consumption. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD and halt the progression of the disease, therefore alcohol abstinence is the most effective measure to improve prognosis in this patient population. In this regard, alcohol cessation remains the first-line treatment in all stages of alcohol disease. In patients with advanced ALD nonresponding to medical therapy, liver transplantation is the only approach that improves prognosis, and it should be considered in patients with decompensated cirrhosis. In the last years, AH has emerged as a new indication of early liver transplantation in non-responders to medical therapy, with promising results in highly selected patients. In this review, we provide an update on the epidemiology, risk factors, natural history, diagnosis, pathogenesis, and current treatments for ALD, taking into account the importance of assessing and managing alcohol consumption as the etiological factor and the main driver of prognosis in patients with ALD.

Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful alcohol use as the primary risk factor, increasing alcohol use over the past decade has resulted in rapid growth of the ALD-related healthcare burden. The spectrum of ALD ranges from early asymptomatic liver injury to advanced disease with decompensation and portal hypertension. Compared with those with other etiologies of liver disease, patients with ALD progress faster and more often present at an advanced stage. A unique phenotype of advanced disease is alcohol-associated hepatitis (AH) presenting with rapid onset or worsening of jaundice, and acute on chronic liver failure in severe forms conveying a 1-month mortality risk of 20%-50%. The model for end stage disease score is the most accurate score to stratify AH severity (>20 defined as severe disease). Corticosteroids are currently the only available therapeutic with proven efficacy for patients with severe AH, providing survival benefit at 1 month in 50%-60% of patients. Abstinence of alcohol use, a crucial determinant of long-term outcomes, is challenging to achieve in ALD patients with concurrent alcohol use disorder (AUD). As patients with ALD are rarely treated for AUD, strategies are needed to overcome barriers to AUD treatment in patients with ALD and to promote a multidisciplinary integrated care model with hepatology, addiction medicine providers, and social workers to comprehensively manage the dual pathologies of liver disease and of AUD. Liver transplantation, a definitive treatment option in patients with advanced cirrhosis, should be considered in selected patients with AH, who are unresponsive to medical therapy and have a low risk of relapse to posttransplant alcohol use. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the American College of Gastroenterology Practice Parameters Committee.

Hepatitis B and C are important and relatively common health issues. It is known that many patients who underwent total knee and hip arthroplasty were also diagnosed with hepatitis. These patients are at higher risk of periprosthetic joint infection (PJI). This study aimed to investigate the differences in PJI cases in hepatitis B and C patients.

This is a retrospective case-controlled single-center study. A total of 270 patients with hepatitis and non-hepatitis (control group) who underwent one-stage septic exchange to the hip and knee joints were included in the study. All patients' previous surgical histories, infective organisms, C-reactive protein (CRP) values before septic exchange, and demographic data were evaluated. All microbiological and laboratory evaluations were performed separately for knee and hip arthroplasty.

The mean CRP levels of Hep B- and C-positive patients, who underwent one-stage septic exchange in the knee joint, were 23.6 mg/L. In the control group, this value was 43.1 mg/L and a statistically significant difference was found between the groups (p = 0.004). Gram-negative organisms were identified in a larger proportion of patients with hepatitis who developed PJI in both hip and knee joints and underwent one-stage septic exchange (p = 0.041/p = 0.044).

PJIs caused by Gram-negative bacteria are encountered more frequently in patients with hepatitis than in the control group. In addition, the CRP rise is less in patients with hepatitis compared to PJI cases in the control group. Patient-specific evaluation is required in cases of PJI in patient groups with co-existing hepatitis.

Alcohol-related liver disease (ALD) is the most common cause of liver-related ill health and liver-related deaths in the UK, and deaths from ALD have doubled in the last decade. The management of ALD requires treatment of both liver disease and alcohol use; this necessitates effective and constructive multidisciplinary working. To support this, we have developed quality standard recommendations for the management of ALD, based on evidence and consensus expert opinion, with the aim of improving patient care.

A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology ALD Special Interest Group developed the quality standards, with input from the British Liver Trust and patient representatives.

The standards cover three broad themes: the recognition and diagnosis of people with ALD in primary care and the liver outpatient clinic; the management of acutely decompensated ALD including acute alcohol-related hepatitis and the posthospital care of people with advanced liver disease due to ALD. Draft quality standards were initially developed by smaller working groups and then an anonymous modified Delphi voting process was conducted by the entire group to assess the level of agreement with each statement. Statements were included when agreement was 85% or greater. Twenty-four quality standards were produced from this process which support best practice. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice and an audit tool provided.

It is hoped that services will review their practice against these recommendations and key performance indicators and institute service development where needed to improve the care of patients with ALD.

Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse.

This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021.

Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse.

eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

Alcohol related liver disease (ARLD) is one of the major chronic liver diseases worldwide. This review aimed to describe the global prevalence, incidence, and outcomes of ARLD.

Medline, Embase, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to May 31, 2022. The language was restricted to English or Chinese. According to the criteria, articles describing the basic characteristics of the population were selected. Two reviewers extracted the data independently.

A total of 372 studies were identified: 353 were used for prevalence analysis, 7 were used for incidence analysis, and 114 were used to for outcome analysis. The prevalence of ARLD worldwide was 4.8%. The prevalence in males was 2.9%, which was higher than female (0.5%). Among the ethnic groups, the percentage was highest in Caucasians (68.9%). Alcoholic liver cirrhosis comprised the highest proportion in the disease spectrum of ARLD at 32.9%. The prevalence of ascites in ARLD population was highest (25.1%). The ARLD population who drinking for > 20 years accounted for 54.8%, and the average daily alcohol intake was 146.6 g/d. About 59.5% of ARLD patients were current or former smokers, and 18.7% were complicated with hepatitis virus infection. The incidence was 0.208/1000 person-years. The overall mortality was 23.9%, and the liver-related mortality was 21.6%.

The global prevalence of ARLD was 4.8% and was affected by sex, region, drinking years, and other factors. Therefore, removing the factors causing a high disease prevalence is an urgent requisite.

PROSPERO Nr: CRD42021286192.

Severe alcoholic hepatitis (sAH) is defined by a modified discriminant function ≥32 or model for end-stage liver disease (MELD) >20. Patients with sAH are in an immunocompromised state attributed to cirrhosis-related immunoparesis and corticosteroid use. Individuals with sAH often develop severe infections that adversely impact short-term prognosis. Currently, the corticosteroid prednisolone is the only treatment with proven efficacy in sAH; however, the combination of corticosteroid treatment and altered host defense in sAH has been thought to increase the risk of acquiring of bacterial, opportunistic fungal, and viral infections. Newer studies have shown that corticosteroids do not increase occurrence of infections in those with sAH; unfortunately, the lack of response to corticosteroids may instead predispose to infection development. Prompt and appropriate antibiotic treatment is therefore essential to improving patient outcomes. This review highlights common infections and risk factors in patients with sAH. Additionally, current diagnostic, therapeutic, and prophylactic strategies in these patients are discussed.

Severe alcohol-related hepatitis (AH) is associated with an increased risk of infection, but the impact of pneumonia has not been specifically analyzed in a specific cohort.

All patients admitted for severe AH between 2002 and 2020 were prospectively included. Systematic screening for infection was performed at admission and renewed in the case of clinical suspicion.

We included 614 patients (60.4% men, mean age 49.9 years, median model for end-stage liver disease [MELD] 25.2, bilirubin 18.1 mg/dL), 202 (32.9%) with infections at admission (73 lung infections). Encephalopathy ( P = 0.006), MELD score ( P = 0.0002), and tobacco exposure (past vs never smokers: P = 0.002 or active vs past smokers: P = 0.005) were associated with lung infection at admission on multivariate analysis. Factors independently associated with death before steroid initiation were encephalopathy ( P = 0.003), MELD score ( P = 0.05), and especially lung infection ( P < 0.0001). Thus, patients with a lung infection had a lower probability of receiving steroids than those with other infections and noninfected patients: 54.8 vs 88.4 vs 98.1% ( P < 0.0001). One hundred forty-six of the 558 patients who received corticosteroids developed infection, including 57 (39.04%) pneumonias. The risk of respiratory and nonrespiratory infection was higher in nonresponders to steroids (Lille score ≥0.45) than in responders: 13% vs 7.6%, P = 0.03 and 27.9% vs 10.6%, P < 0.001, respectively. The variables independently associated with 3-month mortality after steroid initiation were lung infection ( P = 0.004), nonresponse to steroids ( P < 0.0001), MELD score ( P = 0.0003), ascites ( P = 0.003), and encephalopathy ( P = 0.018), whereas nonrespiratory infections were not ( P = 0.91).

Lung infection is frequent during severe AH and influences mortality at admission and after steroid initiation. These results emphasize the need for specific management of lung infection during the course of AH.

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil-lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9-86.5) vs. 16% (12.6-23.1) vs. 7.05% (1.4-9.5), p < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229-1828) vs. 853 (20-968) vs. 99.5 (54.7-140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area under curve (AUC) of 0.95. At a cut-off value of 0.261 ng/ml, the sensitivity and specificity of serum procalcitonin was 83% and 72%, respectively, with AUC of 0.86. Serum CRP, total leukocyte count, NLR had AUCs of 0.78, 0.63 and 0.64, respectively. Quantitative measurement of nCD64 can better distinguish systemic bacterial infection and inflammation in SAH as compared to traditional biomarkers.

Mucosal-associated invariant T (MAIT) cells have been described in liver and non-liver diseases, and they have been ascribed antimicrobial, immune regulatory, protective, and pathogenic roles. The goals of this review are to describe their biological properties, indicate their involvement in chronic liver disease, and encourage investigations that clarify their actions and therapeutic implications. English abstracts were identified in PubMed by multiple search terms, and bibliographies were developed. MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines. Diverse pro-inflammatory, anti-inflammatory, and immune regulatory cytokines are released; infected cells are eliminated; and memory cells emerge. Circulating MAIT cells are hyper-activated, immune exhausted, dysfunctional, and depleted in chronic liver disease. This phenotype lacks disease-specificity, and it does not predict the biological effects. MAIT cells have presumed protective actions in chronic viral hepatitis, alcoholic hepatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, and decompensated cirrhosis. They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis. Local factors in the hepatic microenvironment (cytokines, bile acids, gut-derived bacterial antigens, and metabolic by-products) may modulate their response in individual diseases. Investigational manipulations of function are warranted to establish an association with disease severity and outcome. In conclusion, MAIT cells constitute a disease-nonspecific, immune response to chronic liver inflammation and infection. Their pathological role has been deduced from their deficiencies during active liver disease, and future investigations must clarify this role, link it to outcome, and explore therapeutic interventions.

Excessive alcohol consumption is responsible for approximately 50% of all deaths due to cirrhosis. Although the duration and amount of alcohol consumption are the primary factors responsible for the liver injury caused by consuming alcohol, the pathogenesis of the 3 stages of alcohol-associated liver disease (ALD)-fatty liver, alcoholic hepatitis (AH), and cirrhosis- is likely multifactorial. Preexisting obesity, dysbiosis of the gut microbiome, activation of proinflammatory cytokines, and genetic factors can all contribute to the risk of developing ALD. The cornerstone of therapy for all stages of ALD is abstinence from drinking alcoholic beverages. Severe AH, defined by a Maddrey discriminant function greater than 32, warrants additional therapy. The results of multiple studies evaluating the use of glucocorticoids in the treatment of severe AH led to guidelines from international societies that recommend glucocorticoid therapy in patients with severe AH without active infection. Liver transplantation provides an effective treatment option for patients who fail glucocorticoid therapy. Recent advances in understanding the pathogenesis of AH have led to the investigation of potential therapies directed at preventing the development of steatosis, inhibiting the innate immune response, modifying the gut microbiome, and stimulating liver regeneration.

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.

Deoxynivalenol (DON) is one of the most common mycotoxins which contaminate cereals and their by-products worldwide. Previous studies have stated toxic effects of DON on liver. Heme oxygenase-1 (HO-1) plays a potential role in protecting liver and maintaining gut microbiota homeostasis. Therefore, a study on the potential and basic interaction between DON, HO-1 and intestinal flora would be helpful for better understanding DON-induced hepatotoxicity. In the present study, male C57BL6/J mice were exposed to 25 μg/kg bw/day DON for 30 days. Compared with control group, liver lymphocytes accumulation and elevated ALT activity were observed in DON group, however, AST activity was not notably changed. Several genera, including Parabacteroides and Enterobacter, were significantly increased after DON administration while Lactobacillus, Odoribacter and Lachnospiracea incertae sedis were mostly reduced. The top distinct microbial pathways predicted by PICRUSt included signal transduction, metabolism and genetic information processing. Importantly, liver-specific knockdown of HO-1 caused more severe pathological alterations in liver after DON administration and overexpression of HO-1 protected against DON-induced liver inflammation. The gut microbiota and related microbial pathways were changed in different ways after gene-editing. In conclusion, low dose of DON triggered low-grade inflammation in liver and changes in gut microbiota. HO-1 could attenuate DON-induced inflammation in liver, where gut microbiota may play an important role. HO-1 also could be a potential protective factor between homeostasis of gut microbiota and DON-induced hepatotoxicity in animal models.

Alcoholic hepatitis is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by prolonged heavy alcohol use. Treatment is mostly supportive. The short-term prognosis of acute alcoholic hepatitis depends on liver recovery, and ranges widely from rapid improvement to grim multiorgan failure despite treatment. Refinement of scoring systems have enhanced prognostication to guide clinical decision making in alcoholic hepatitis. Recent advances in the treatment of alcoholic hepatitis have solidified corticosteroids as the cornerstone of treatment to enhance short-term survival, but not intermediate or long-term survival.

Severe alcoholic hepatitis (SAH) is a costly and worldwide public health issue with high morbidity and mortality. Specific effective treatments for SAH have yet to be established. The aim of the present article is to review the current knowledge of the pathogenesis, assessment and treatment options in patients with SAH. To date, alcohol abstinence and enteral nutrition are the recommended first-line treatments. Although corticosteroids remain the preferred therapy for certain patients with a modified Maddrey discriminant function level greater than 54, they only improve short-term survival rates. New research focuses on liver inflammation, liver regeneration, the gut-liver axis, human induced pluripotent stem cells and extracorporeal albumin dialysis. Liver transplantation is considered the last medical option for patients with SAH who are nonresponsive to other medical treatments.