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Gut Microbes Dec 2023The liver is rich in innate immune cells, such as natural killer (NK) cells, natural killer T cells, and Kupffer cells associated with the gut microbiome. These immune...
The liver is rich in innate immune cells, such as natural killer (NK) cells, natural killer T cells, and Kupffer cells associated with the gut microbiome. These immune cells are dysfunctional owing to alcohol consumption. However, there is insufficient data on the association between immune cells and gut microbiome in alcoholic liver disease (ALD). Therefore, the purpose of this study was to evaluate the effects of probiotic strains on NK cells in ALD patients. In total, 125 human blood samples [control ( = 22), alcoholic hepatitis ( = 43), and alcoholic cirrhosis ( = 60]) were collected for flow cytometric analysis. C57BL/6J mice were divided into four groups (normal, EtOH-fed, and 2 EtOH+strain groups [ and ]). Lymphocytes isolated from mouse livers were analyzed using flow cytometry. The frequency of NK cells increased in patients with alcoholic hepatitis and decreased in patients with alcoholic cirrhosis. The expression of NKp46, an NK cell-activating receptor, was decreased in patients with alcoholic hepatitis and increased in patients with alcoholic cirrhosis compared to that in the control group. The number of cytotoxic CD56dimCD16 NK cells was significantly reduced in patients with alcoholic cirrhosis. We tested the effect of oral administration and in EtOH-fed mice. and improved liver inflammation and intestinal barrier damage caused by EtOH supply and increased NK cell activity. Therefore, these observations suggest that the gut microbiome may ameliorate ALD by regulating immune cells.
Topics: Humans; Animals; Mice; Mice, Inbred C57BL; Liver Cirrhosis, Alcoholic; Hepatitis, Alcoholic; Gastrointestinal Microbiome; Liver Diseases, Alcoholic; Killer Cells, Natural; Ethanol
PubMed: 37988132
DOI: 10.1080/19490976.2023.2281014 -
Clinical Gastroenterology and... Apr 2024Alcoholic foamy degeneration (AFD) is a condition with similar clinical presentation to alcohol-associated hepatitis (AH), but with a specific histologic pattern....
BACKGROUND & AIMS
Alcoholic foamy degeneration (AFD) is a condition with similar clinical presentation to alcohol-associated hepatitis (AH), but with a specific histologic pattern. Information regarding the prevalence and prognosis of AFD is scarce and there are no tools for a noninvasive diagnosis.
METHODS
A cohort of patients admitted to the Hospital Clinic of Barcelona for clinical suspicion of AH who underwent liver biopsy was included. Patients were classified as AFD, AH, or other findings, according to histology. Clinical features, histology, and genetic expression of liver biopsy specimens were analyzed. The accuracy of National Institute on Alcohol Abuse and Alcoholism criteria and laboratory parameters for differential diagnosis were investigated.
RESULTS
Of 230 patients with a suspicion of AH, 18 (8%) met histologic criteria for AFD, 184 (80%) had definite AH, and 28 (12%) had other findings. In patients with AFD, massive steatosis was more frequent and the fibrosis stage was lower. AFD was characterized by down-regulation of liver fibrosis and inflammation genes and up-regulation of lipid metabolism and mitochondrial function genes. Patients with AFD had markedly better long-term survival (100% vs 57% in AFD vs AH; P = .002) despite not receiving corticosteroid treatment, even in a model for end-stage liver disease-matched sensitivity analysis. Serum triglyceride levels had an area under the receiver operating characteristic of 0.886 (95% CI, 0.807-0.964) for the diagnosis of AFD, whereas the National Institute on Alcohol Abuse and Alcoholism criteria performed poorly. A 1-step algorithm using triglyceride levels of 225 mg/dL (sensitivity, 0.77; specificity, 0.90; and Youden index, 0.67) is proposed for differential diagnosis.
CONCLUSIONS
AFD in the setting of suspicion of AH is not uncommon. A differential diagnosis is important because prognosis and treatment differ largely. Triglyceride levels successfully identify most patients with AFD and may be helpful in decision making.
Topics: Humans; End Stage Liver Disease; Severity of Illness Index; Hepatitis, Alcoholic; Prognosis; Triglycerides
PubMed: 38065374
DOI: 10.1016/j.cgh.2023.11.031 -
Hepatology (Baltimore, Md.) May 2018
Topics: Hepatitis, Alcoholic; Humans; Pyroptosis
PubMed: 29222919
DOI: 10.1002/hep.29725 -
World Journal of Gastroenterology Oct 2017To study differences of presentation, management, and prognosis of alcoholic hepatitis in Latinos compared to Caucasians. (Comparative Study)
Comparative Study
AIM
To study differences of presentation, management, and prognosis of alcoholic hepatitis in Latinos compared to Caucasians.
METHODS
We retrospectively screened 876 charts of Caucasian and Latino patients who were evaluated at University of California Davis Medical Center between 1/1/2002-12/31/2014 with the diagnosis of alcoholic liver disease. We identified and collected data on 137 Caucasians and 64 Latinos who met criteria for alcoholic hepatitis, including chronic history of heavy alcohol use, at least one episode of jaundice with bilirubin ≥ 3.0 or coagulopathy, new onset of liver decompensation or acute liver decompensation in known cirrhosis within 12 wk of last drink.
RESULTS
The mean age at presentation of alcoholic hepatitis was not significantly different between Latinos and Caucasians. There was significant lower rate of overall substance abuse in Caucasians compared to Latinos and Latinos had a higher rate of methamphetamine abuse (12.5% 0.7%) compared to Caucasians. Latinos had a higher mean number of hospitalizations (5.3 ± 5.6 2.7 ± 2.7, = 0.001) and mean Emergency Department visits (9.5 ± 10.8 4.5 ± 4.1, = 0.017) for alcohol related issues and complications compared to Caucasians. There was significantly higher rate of complications of portal hypertension including gastrointestinal bleeding (79.7% 45.3%, < 0.001), spontaneous bacterial peritonitis (26.6% 9.5%, = 0.003), and encephalopathy (81.2% 55.5%, = 0.001) in Latinos compared to Caucasians.
CONCLUSION
Latinos have significant higher rates of utilization of acute care services for manifestations alcoholic hepatitis and complications suggesting poor access to outpatient care.
Topics: Adult; Alcoholism; Amphetamine-Related Disorders; California; Female; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Hepatitis, Alcoholic; Hispanic or Latino; Hospitalization; Humans; Hypertension, Portal; Male; Methamphetamine; Middle Aged; Patient Acceptance of Health Care; Peritonitis; Prognosis; Recurrence; Retrospective Studies; Survival Rate; White People
PubMed: 29142474
DOI: 10.3748/wjg.v23.i40.7274 -
The Turkish Journal of Gastroenterology... Sep 2016Sepsis is frequently observed in patients with alcoholic hepatitis (AH) and is an important mortality predictor. Several studies have also identified systemic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Sepsis is frequently observed in patients with alcoholic hepatitis (AH) and is an important mortality predictor. Several studies have also identified systemic inflammatory response syndrome (SIRS) as a significant prognostic factor. The aim of this study was to systematically review and quantify the effect of SIRS and sepsis on mortality in patients with AH.
MATERIALS AND METHODS
MEDLINE and EMBASE were searched from its inception till January 2016. Participants in the included studies were adults with AH and those with developed SIRS or sepsis during hospitalization. We estimated the risk ratio (RR) with a 95% confidence interval (CI) of mortality by comparing participants with SIRS vs. non-SIRS and sepsis vs. non-sepsis.
RESULTS
Data were extracted from six studies involving 1,264 patients (of whom 507 had SIRS) and four studies involving 57,529 patients (of whom 1,449 had sepsis). SIRS and sepsis were both significantly associated with mortality with RRs of 2.7 (95% CI 1.74-4.14, I2=50%) and 2.8 (95% CI 1.58-4.93, I2=94%), respectively.
CONCLUSION
Not only is sepsis associated with mortality but also SIRS. SIRS may be the initial trigger of cascade events leading to mortality in patients with AH. Identification of the key element of SIRS may thus provide a potential therapeutic target.
Topics: Female; Hepatitis, Alcoholic; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Observational Studies as Topic; Odds Ratio; Risk Factors; Sepsis; Systemic Inflammatory Response Syndrome
PubMed: 27782895
DOI: 10.5152/tjg.2016.16188 -
Romanian Journal of Internal Medicine =... Jun 2024Harmful alcohol consumption is one of the leading risk factors for global disease burden and injury condition, causing death and disability early in life, with over 3...
INTRODUCTION
Harmful alcohol consumption is one of the leading risk factors for global disease burden and injury condition, causing death and disability early in life, with over 3 million deaths worldwide every year. Alcoholic hepatitis (AH) is a clinical syndrome characterized by hepatic failure with recent onset of jaundice, consequence of a heavy chronic alcohol drinking. The disease severity ranges from mild to severe cases, with high short-term mortality. Individual variety regarding disease outcome and therapeutic response complicates the prognosis stratification. Thus, novel parameters and continuously sought for a better disease outcome assessment.
AIMS AND OBJECTIVES
To highlight new parameters that accurately assess 30-day mortality (short-term) in patients with AH and to develop a new severity score that uses readily available parameters accessible to any clinician.
MATERIALS AND METHODS
This is a prospective study on patients diagnosed with AH between 2022-2023. We identified 70 patients with AH who met the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria for diagnosis after exclusion of patients with severe comorbidities that could influence disease outcome. Clinical and paraclinical parameters were assessed at least on admission and day 7. Mortality at 30-day was considered the endpoint. The database was composed using Microsoft Excel (Microsoft Corporation) and the data was analyzed using SPSS Statistics version 26 (IBM Corporation).
RESULTS
A total of 70 patients were included in the study with a mortality at 30-days of 22.9% (n=16). The independent variables associated with increased short-term mortality identified using the univariate analysis were: fever, infection, esophageal varices, prothrombin time PT, INR, total bilirubin, CRP, LDH and CHI (creatinine height index). Using multivariate regression we determined a novel prognostic score, with criterion for retaining variable being p<0.05. Total bilirubin day 7, CRP, PT, fever and CHI resulted after the analysis and were included into a new mortality score. Our Prognostic Model Score obtained an area under the ROC of 0.950 (95% CI: 0.890-0.980, p<0.001), with a cut-off value of 13.75 (Sn=87.5%, Sp=91%). Regarding the consecrated prognostic scores, MDF and Lille score obtained good AUROCs=0.839 and 0.881, respectively (p<0.000), with cut-off values comparable with literature (MDF=34.35 vs 32) and (Lille=0.475 vs 0.450). The discriminatory power for ABIC (p=0.58), GAHS (p=0.16), MELD-Na (p=0.61) was not significant.
CONCLUSION
We obtained a new prognostic score for the assessment of 30-day mortality in AH that includes markers of inflammation (CRP, fever) and markers of sarcopenia (CHI) along parameters of hepatic disfunction (total bilirubin and PT). Amongst consecrated prognostic models, MDF and Lille scores were representative for our study, while ABIC, GAHS and MELD-Na did not attain statistical significance. Our score is unique by the addition of CRP and this could prove to be a useful tool in AH severity stratification.
Topics: Humans; Hepatitis, Alcoholic; Prognosis; Severity of Illness Index; Male; Female; Prospective Studies; Middle Aged; Adult; ROC Curve; Aged; Bilirubin
PubMed: 38180800
DOI: 10.2478/rjim-2024-0001 -
Gene Expression Nov 2017Alcoholic liver disease encompasses the progressive stages of liver dysfunction that culminates in alcoholic cirrhosis (AC) and in severe cases alcoholic hepatitis (AH)....
Alcoholic liver disease encompasses the progressive stages of liver dysfunction that culminates in alcoholic cirrhosis (AC) and in severe cases alcoholic hepatitis (AH). Currently, prognostic scores have limited specificity and sensitivity. Plasma keratin-18 (K18) levels are elevated during liver disease and may be biomarkers of outcome. The objective of this study was to determine if total K18 (M65) or caspase-cleaved K18 (M30) levels were different between AC and AH patients. M65 and M30 levels were measured in the plasma of consented healthy controls and patients with AC and AH. Cell death was assessed by TUNEL staining and caspase activity. M65 and M30 values were significantly higher in AC patients compared to healthy controls and further increased in AH patients. The M65 values and the M30/M65 ratios of nonsurviving AH patients were significantly elevated above their surviving counterparts and healthy controls. Statistical analysis indicated that M30/M65 ratios outperformed current indices for accurately distinguishing the prognosis of AH patients. These scores occurred with minimal increase in plasma cell death markers such as ALT and AST. Serum caspase activity, TUNEL staining, and M30 immunohistochemistry in biopsies indicated that serum and tissue values may not correlate well with overall cell death. In conclusion, both M65 and M30 differentiate AH from AC patients, and M65 values and the M30/M65 ratio are capable of predicting early stage mortality; however, they may not accurately reflect pure hepatocyte cell death in these populations, as they do not strongly correlate with traditional cell death markers.
Topics: Adrenal Cortex Hormones; Adult; Animals; Biomarkers; Cell Death; Female; Hepatitis, Alcoholic; Humans; Keratin-18; Male; Mice, Inbred C57BL; Middle Aged; Pentoxifylline; Platelet Aggregation Inhibitors; Prognosis; ROC Curve; Survival Rate; Treatment Outcome
PubMed: 28770701
DOI: 10.3727/105221617X15016197658871 -
Alcohol (Fayetteville, N.Y.) Sep 2018Rising mortality in the United States due to alcoholic liver disease (ALD) and the dearth of effective treatments for ALD have led to increased research in this area,...
Rising mortality in the United States due to alcoholic liver disease (ALD) and the dearth of effective treatments for ALD have led to increased research in this area, particularly in alcoholic hepatitis. To understand the burden of illness and potential economic value of effective treatments, we conducted a health care claims analysis of over 15,000 commercially insured adults who were hospitalized with alcoholic hepatitis (AH) between 2006 and 2013 and followed for up to 5 years. Their average age was 54 years and 68% were male. Over 5 years, about two-thirds of these adults died (44% in the first year), and fewer than 500 received liver transplants. There were nearly 40,000 re-hospitalizations, with over 50% of the survivors re-hospitalized within a year and nearly 75% through the second year. The total costs were nearly $145,000 per patient, with costs decreasing over time from over $50,000 in the first year (including the index hospitalization) to about $10,000 per year in the later years. Total costs for the cohort over 5 years were $2.2 billion. Patients who received a liver transplant averaged about $300,000 in transplant-related costs and over $1,000,000 in total health care costs over 5 years. Average costs in years following the index hospitalization were similar to diabetes. AH has a high mortality and is a high-cost condition.
Topics: Female; Health Care Costs; Hepatitis, Alcoholic; Hospitalization; Humans; Insurance Claim Review; Liver Transplantation; Male; Middle Aged
PubMed: 30048829
DOI: 10.1016/j.alcohol.2018.02.003 -
Journal of Hepatology Apr 2015Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe and is the leading cause of death among adults with excessive alcohol... (Review)
Review
Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe and is the leading cause of death among adults with excessive alcohol consumption. There is a dose-response relationship between the amount of alcohol consumed and the risk of ALD. The relative risk of cirrhosis increases in subjects who consume more than 25 g/day. The burden of alcohol-attributable liver cirrhosis and liver cancer is high and is entirely preventable. Health agencies should develop population-based policies to reduce the prevalence of harmful and/or hazardous alcohol consumption and foster research in this field to provide new diagnostic and therapeutic tools. Disease progression of patients with ALD is heavily influenced by both genetic and environmental factors. Non-invasive methods for the diagnosis of fibrosis have opened new perspectives in the early detection of advanced ALD in asymptomatic patients. Alcoholic hepatitis, the most severe form of ALD, carries a high short-term mortality (around 30-50% at 3 months). Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis but duration of therapy should be adapted to early response. Liver transplantation is the best option for patients with severe liver dysfunction. However, alcohol relapse after transplantation remains a critical issue and drinking habits of transplanted patients need to be routinely screened.
Topics: Cost of Illness; Hepatitis, Alcoholic; Humans; Liver Diseases, Alcoholic; Liver Transplantation
PubMed: 25920088
DOI: 10.1016/j.jhep.2015.03.006 -
World Journal of Gastroenterology Mar 2014Severe alcoholic hepatitis (AH) is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of... (Review)
Review
Severe alcoholic hepatitis (AH) is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of alcohol. The diagnosis of AH is based on the appropriate alcohol intake history and is supported with clinical and histological features, and several scoring systems. Glucocorticoids are the mainstay for treating severe AH with pentoxifylline used as an alternative to steroids in addition to total alcohol abstinence. Liver transplantation is a possible therapeutic option for severe AH. Among the anti-craving medications able to improve abstinence rate, baclofen seems to be effective and safe in the alcoholic patients affected by severe liver damage.
Topics: Acute Disease; Alcohol Abstinence; Alcohol Deterrents; Anti-Inflammatory Agents; Antioxidants; Dietary Supplements; Glucocorticoids; Hepatitis, Alcoholic; Humans; Liver Transplantation; Phosphodiesterase Inhibitors; Risk Factors; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 24605014
DOI: 10.3748/wjg.v20.i9.2159