Risk factors for acute myocardial infarction in patients with alcohol-related cirrhosis - a Danish nested case-control study.

BACKGROUND & AIMS: Alcohol-related cirrhosis (ALD cirrhosis) has a weaker effect on acute myocardial infarction (MI) than on other arterial or venous thromboses, and the reasons for this pattern are unclear. This study aimed to identify risk factors of MI amongst patients with ALD cirrhosis. METHODS: This nationwide register-based nested case-control study was conducted within a cohort of all Danish patients diagnosed with ALD cirrhosis from 2000-2019. Patients with first-time MI after diagnosis of ALD cirrhosis were identified as cases, and matching cohort members (10:1) with no history of MI, using risk-set sampling. We selected candidate risk factors a priori and used conditional logistic regression to study the association between them and the adjusted odds ratio of MI. RESULTS AND CONCLUSIONS: We included 373 cases and 3,730 controls. We identified the following risk factors for MI: hospitalization for infection (adjusted odds ratio 2.26 [95% CI 1.38-3.71]), recent surgery (adjusted odds ratio 1.82 [95% CI 1.18-2.81]), history of atherosclerosis (adjusted odds ratio 1.89 [95% CI 1.39-2.57]), cardiac ischemia (adjusted odds ratio 6.23 [95% CI 4.30-9.04]), heart failure (adjusted odds ratio 2.83 [95% CI 1.90-4.22]) or chronic obstructive pulmonary disease (COPD) (adjusted odds ratio 2.26 [95% CI 1.62-3.17]). Use of anticoagulants had a protective effect (adjusted odds ratio 0.47 [95% CI 0.25-0.91]). Our findings contribute to the understanding of risk factors for MI in patients with ALD cirrhosis. They may have clinical implications e.g. for the decision to offer thromboprophylaxis.

Imaging of Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (ALD) continues to be a global health concern, responsible for a significant number of deaths worldwide. Although most individuals who consume alcohol do not develop ALD, heavy drinkers and binge drinkers are at increased risk. Unfortunately, ALD is often undetected until it reaches advanced stages, frequently associated with portal hypertension and hepatocellular carcinoma (HCC). ALD is now the leading indication for liver transplant. The incidence of alcohol-associated hepatitis (AH) surged during the COVID-19 pandemic. Early diagnosis of ALD is therefore important in patient management and determination of prognosis, as abstinence can halt disease progression. The spectrum of ALD includes steatosis, steatohepatitis, and cirrhosis, with steatosis the most common manifestation. Diagnostic techniques including ultrasound, CT, and MRI provide useful information for identifying ALD and excluding other causes of liver dysfunction. Heterogeneous steatosis and transient perfusion changes on CT and MRI in the clinical setting of alcohol-use disorder are diagnostic of severe AH. Elastography techniques are useful for assessing fibrosis and monitoring treatment response. These various imaging modalities are also useful in HCC surveillance and diagnosis. This review discusses the imaging modalities currently used in the evaluation of ALD, highlighting their strengths, limitations, and clinical applications.

Serum Vascular Adhesion Protein-1 and Endothelial Dysfunction in Hepatic Cirrhosis: Searching for New Prognostic Markers.

Endothelial dysfunction plays a key role in the development of liver cirrhosis. Among the biomarkers of endothelial dysfunction, the soluble form of Vascular Adhesion Protein-1 (sVAP-1) is an unconventional and less known adhesion molecule endowed also with amine oxidase activity. The aim of this study was to explore and correlate the behavior of sVAP-1 with that of the soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) and with the severity of liver cirrhosis. A cross-sectional study was carried out by enrolling 28 controls, 59 cirrhotic patients without hepatocellular carcinoma, and 56 patients with hepatocellular carcinoma (HCC), mainly caused by alcohol abuse. The levels of adhesion molecules and of the pro-inflammatory cytokines (IL-6 and TNF-αα) were determined by immunoassay and the enzymatic activity of sVAP-1 by a fluorometric assay. In non-diabetic patients without HCC, a specific behavior of sVAP-1 was highlighted. Differently from sVCAM-1, sICAM-1, and cytokines, the sVAP-1 level was significantly increased only in the early stage of disease, and then, it decreased in the last stage (866 ± 390 ng/mL vs. 545 ± 316 ng/mL, in Child-Pugh class A vs. C, respectively, p < 0.05). Bivariate analysis correlates sVAP-1 to sVCAM-1, in the absence of HCC (Spearman's rho = 0.403, p < 0.01). Multiple linear regression analysis revealed that sVCAM-1 appears to be a predictor of sVAP-1 (ß coefficient = 0.374, p = 0.021). In conclusion, in non-diabetic and non-HCC cirrhotic patients, sVAP-1 may be a potential prognostic biomarker that, together with sVCAM-1 and pro-inflammatory cytokines, may provide information on the progression of sinusoidal liver endothelium damage.

Risk of Fractures and Subsequent Mortality in Alcohol-Related Cirrhosis: A Nationwide Population-Based Cohort Study.

BACKGROUND AND AIMS: Alcohol-related cirrhosis is linked to increased risk of fractures, but this has seldom been quantified nationally or compared against control subjects without cirrhosis. Here, we determined the rate and risk of fractures and postfracture mortality in patients with alcohol-related cirrhosis compared with individuals from the general population. METHODS: In this nationwide population-based cohort study, data were retrieved from the Swedish National Patient Registry on 25,090 patients with alcohol-related cirrhosis from 1969-2016. Patients were matched for sex, age, and municipality with 239,458 control subjects from the Swedish Total Population Registry. Cox regression models were fitted to investigate the rates of fractures and postfracture mortality. The cumulative incidence of fractures was calculated while accounting for competing risks (death or liver transplantation). RESULTS: A total of 48,635 fractures occurred during 3,468,860 person-years of follow-up. Patients with alcohol-related cirrhosis had a higher fracture rate per 1000 person-years (38.7) than control subjects (13.3; adjusted hazard ratio, 3.8; 95% confidence interval, 3.6-3.9). The cumulative incidence of fractures was elevated for patients the first 19 years of follow-up, with a 5-year risk of 9.6% compared with 4.5% for control subjects. Patients with alcohol-related cirrhosis had a higher postfracture mortality rate compared with control subjects who also experienced a fracture, at both 30 days (adjusted hazard ratio, 1.6; 95% confidence interval, 1.4-1.8) and 1 year (adjusted hazard ratio, 1.8; 95% confidence interval, 1.7-2.0). CONCLUSIONS: Alcohol-related cirrhosis is associated with an almost 4-fold increased fracture rate, a higher risk of fractures the first 2 decades after initial diagnosis, and higher postfracture mortality. Preventive interventions to reduce modifiable fracture risk factors in this population are justified.

Efficacy of bile acid profiles in diagnosing and staging of alcoholic liver disease.

AIM: The diagnosis of alcoholic liver disease (ALD) is still a great challenge. Therefore, the purpose of this study is to identify and characterize new metabolomic biomarkers for the diagnosis and staging of ALD. METHODS: A total of 127 patients with early liver injury, 40 patients with alcoholic cirrhosis (ALC) and 40 healthy controls were included in this study. Patients with early liver injury included 45 patients with alcoholic liver disease (ALD), 40 patients with non-alcoholic fatty liver disease (NAFLD) and 40 patients with viral liver disease (VLD). The differential metabolites in serum samples were analyzed using ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry, and partial metabolites in the differential metabolic pathway were identified by liquid chromatography- tandem mass spectrometry. RESULTS: A total of 40 differential metabolites and five differential metabolic pathways in the four groups of patients with early liver disease and healthy controls were found, and the metabolic pathway of primary bile acid (BA) biosynthesis was the pathway that included the most differential metabolites. Therefore, 22 BA profiles were detected. The results revealed that the changes of BA profiles were most pronounced in patients with ALD compared with patients with NAFLD and VLD, in whom 12 differential BAs were diagnostic markers of ALD (AUC = 0.883). The 19 differential BAs in ALC and ALD were diagnostic markers of the stage of alcoholic hepatic fibrosis (AUC = 0.868). CONCLUSION: BA profiles are potential indicators in the diagnosis of ALD and evaluation of different stages.

ABO blood group does not influence Child-Pugh A cirrhosis outcome: An observational study from CIRRAL and ANRS CO12 CIRVIR cohorts.

BACKGROUND AND AIMS: Non-O blood group promotes deep vein thrombosis and liver fibrosis in both general population and hepatitis C. We aimed to evaluate the influence of Non-O group on the outcome of Child-Pugh A cirrhotic patients. METHODS: We used two prospective cohorts of Child-Pugh A cirrhosis due to either alcohol or viral hepatitis. Primary end point was the cumulated incidence of 'Decompensation' at 3 years, defined as the occurrence of ascites , hydrothorax, encephalopathy, gastrointestinal bleeding related to portal hypertension, or bilirubin >45 µmol/L. Secondary end points were the cumulated incidences of (1) 'Disease Progression' including a « decompensation¼ or « the occurrence of one or more parameters ¼ among: prothrombin time (PT) <45%, albumin <28 g/L, Child-Pugh worsening (B or C vs A or B, C vs B), hepatorenal syndrome, and hepato-pulmonary syndrome, (2) other events such as non-malignant portal vein thrombosis (nmPVT), and (3) overall survival. RESULTS: Patients (n = 1789; 59.9% Non-O group; 40.1% group O) were followed during a median of 65.4 months. At 3 years cumulated incidence of Decompensation was 8.3% in Non-O group and 7.2% in group O (P = .27). Cumulated incidence of Disease Progression was 20.7% in Non-O group and 18.9% in group O (P = .26). Cumulated incidence of nmPVT was 2.7% in Non-O group and 2.8% in group O (P = .05). At 3 years overall survival was 92.4% in Non-O group and 93.4% in group O (P = 1). CONCLUSION: Non-O group does not influence disease outcome in Child-Pugh A cirrhotic patients. Clinicals trial number NCT03342170.

Killer Cell Immunoglobulin-like Receptors (KIR) and Human Leucocyte Antigen C (HLA-C) Increase the Risk of Long-Term Chronic Liver Graft Rejection.

Chronic liver rejection (CR) represents a complex clinical situation because many patients do not respond to increased immunosuppression. Killer cell immunoglobulin-like receptors/Class I Human Leukocyte Antigens (KIR/HLA-I) interactions allow for predicting Natural Killer (NK) cell alloreactivity and influence the acute rejection of liver allograft. However, its meaning in CR liver graft remains controversial. KIR and HLA genotypes were studied in 513 liver transplants using sequence-specific oligonucleotides (PCR-SSO) methods. KIRs, human leucocyte antigen C (HLA-C) genotypes, KIR gene mismatches, and the KIR/HLA-ligand were analyzed and compared in overall transplants with CR (n = 35) and no-chronic rejection (NCR = 478). Activating KIR (aKIR) genes in recipients (rKIR2DS2+ and rKIR2DS3+) increased CR compared with NCR groups (p = 0.013 and p = 0.038). The inhibitory KIR (iKIR) genes in recipients rKIR2DL2+ significantly increased the CR rate compared with their absence (9.1% vs. 3.7%, p = 0.020). KIR2DL3 significantly increases CR (13.1% vs. 5.2%; p = 0.008). There was no influence on NCR. CR was observed in HLA-I mismatches (MM). The absence of donor (d) HLA-C2 ligand (dC2-) ligand increases CR concerning their presence (13.1% vs. 5.6%; p = 0.018). A significant increase of CR was observed in rKIR2DL3+/dC1- (p = 0.015), rKIR2DS4/dC1- (p = 0.014) and rKIR2DL3+/rKIR2DS4+/dC1- (p = 0.006). Long-term patient survival was significantly lower in rKIR2DS1+rKIR2DS4+/dC1- at 5-10 years post-transplant. This study shows the influence of rKIR/dHLA-C combinations and aKIR gene-gene mismatches in increasing CR and KIR2DS1+/C1-ligands and the influence of KIR2DS4+/C1-ligands in long-term graft survival.

Liver transplant recipients have an increased risk of developing colorectal adenomas: Results from a retrospective study.

BACKGROUND: Liver transplant recipients have an increased incidence of malignancies, but it is unclear whether they have a higher risk of colorectal cancer. AIM: To investigate whether liver transplant recipients have an increased risk of developing colorectal adenomas (a surrogate marker of colorectal cancer risk). PATIENTS AND METHODS: One hundred thirty-nine liver transplant recipients (excluding primary sclerosing cholangitis) who underwent a colonoscopy and polypectomy before and after transplantation, and 367 nontransplanted patients who underwent a colonoscopy for colorectal cancer screening and a second colonoscopy later were retrospectively studied. The risks of incident colorectal adenomas and high-risk adenomas (advanced or multiple adenomas or carcinomas) were compared between both cohorts. RESULTS: Incident colorectal adenomas were found in 40.3% of the transplanted patients and 30.0% of the nontransplanted patients (15.1% and 5.5%, respectively, had high-risk adenomas). After adjusting for age, sex, presence of adenomas in the baseline endoscopy, and interval between colonoscopies, transplant recipients showed a higher risk of developing colorectal adenomas (OR: 1.61; 95% CI: 1.05-2.47; p = .03) and high-risk adenomas (OR: 2.87; 95% CI: 1.46-5.65; p = .002). CONCLUSIONS: Our results suggest that liver transplant recipients have an increased risk of developing colorectal adenomas and lesions with high risk of colorectal cancer.

Enterococcus hirae bacteremia associated with acute pyelonephritis in a patient with alcoholic cirrhosis: a case report and literature review.

BACKGROUND: Infections caused by Enterococcus hirae are common in animals, with instances of transmission to humans being rare. Further, few cases have been reported in humans because of the difficulty in identifying the bacteria. Herein, we report a case of pyelonephritis caused by E. hirae bacteremia and conduct a literature review on E. hirae bacteremia. CASE PRESENTATION: A 57-year-old male patient with alcoholic cirrhosis and neurogenic bladder presented with fever and chills that had persisted for 3 days. Physical examination revealed tenderness of the right costovertebral angle. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) of the patient's blood and urine samples revealed the presence of E. hirae, and pyelonephritis was diagnosed. The patient was treated successfully with intravenous ampicillin followed by oral linezolid for a total of three weeks. CONCLUSION: The literature review we conducted revealed that E. hirae bacteremia is frequently reported in urinary tract infections, biliary tract infections, and infective endocarditis and is more likely to occur in patients with diabetes, liver cirrhosis, and chronic kidney disease. However, mortality is not common because of the high antimicrobial susceptibility of E. hirae. With the advancements in MALDI-TOF MS, the number of reports of E. hirae infections has also increased, and clinicians need to consider E. hirae as a possible causative pathogen of urinary tract infections in patients with known risk factors.

Managing medicines in alcohol-associated liver disease: a practical review.

People with alcohol-associated liver disease often take medicines to manage complications of liver disease and comorbidities. However, patients may be at increased risk of drug-related harm Assessing the severity of liver disease is fundamental to management, as disease staging (steatosis, early fibrosis, cirrhosis) affects medication safety and guides treatment While clinically significant pharmacokinetic and pharmacodynamic changes predominantly occur in cirrhosis, people with early alcohol-associated liver disease may still experience adverse events with potentially inappropriate medicines such as proton pump inhibitors, opioids and benzodiazepines Regular medication review is essential to ensure ongoing appropriateness and safety Alcoholic hepatitis and cirrhosis require specialist gastroenterology or hepatology management. However, general practitioners will remain the cornerstone of day-to-day medication management.

[Clinical diagnosis of alcoholic hepatitis in Tongliao City, Inner Mongolia].

Objective: To explore the current status of alcoholic hepatitis diagnosis by clinicians' in China. Methods: Clinical data of inpatients confirmed with alcohol-associated liver disease diagnosed at Tongliao Infectious Disease Hospital of Inner Mongolia from June 1, 2018 to May 31, 2019 were retrospectively analyzed. The consistency of clinical diagnosis of alcoholic hepatitis was judged according to the diagnostic criteria recommended by the National Institute of Alcohol Abuse and Alcoholism (USA), and then the alcoholic hepatitis severity assessment model recommended by international guidelines, including Maddrey discriminant function, Model for end-stage liver disease, and Glasgow alcoholic hepatitis score and ABIC scores (age, total bilirubin, international normalized ratio and creatinine) were applied to evaluate this group of cases. Results: Among 79 cases with alcohol-associated liver disease, 75 were males and 4 were females, age ranged between 27~75 (51.1±8.8) years. Alcohol consumption varied from 60 g/d to 600g/d, with an average consumption of 148.8 ± 76.6 g/d. The alcohol consumption duration ranged from 4 to 50 [average (23.9 ± 9.6)] years. According to the initial discharge diagnosis, there were 47 and 32 cases in alcoholic hepatitis and alcoholic liver cirrhosis group, respectively. The mean erythrocyte volume, serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were increased in alcoholic liver cirrhosis than alcoholic hepatitis group, while albumin and total cholesterol were lowered in alcoholic liver cirrhosis than alcoholic hepatitis group, and coagulation indexes were significantly extended. Alpha-fetoprotein of both groups were in the normal range; however, it was significantly higher in the alcoholic hepatitis group than the alcoholic cirrhosis group. The 10 cases in the alcoholic cirrhosis group met the definition and diagnosis of alcoholic hepatitis defined by the National Institute of Alcohol Abuse and Alcoholism (USA), but there was no case in the alcoholic hepatitis group. Among the 10 diagnosed cases of alcoholic hepatitis, 5, 6, 1 and 3 cases met the diagnostic criteria of Maddrey discriminant function, Model for end-stage liver disease, Glasgow alcoholic hepatitis score, and ABIC score for severe alcoholic hepatitis, respectively. The Maddrey discriminant function, ABIC score, and Glasgow alcoholic hepatitis score within the Model for end-stage liver disease scores> 20 points had 5, 1, and 3 cases, respectively. Conclusion: Alcoholic hepatitis is over-diagnosed by clinicians. Alcoholic hepatitis patients have the base of liver cirrhosis who meet the diagnostic criteria of National Institute of Alcohol Abuse and Alcoholism (USA). Patients with Model for end-stage liver disease score > 20 points have good consistency with Maddrey discriminant function score ≥ 32 points, and both can be used to evaluate the alcoholic hepatitis patient clinical severity.

Karnofsky Performance Status Following Liver Transplantation in Patients With Multiple Organ Failures and Probable Acute-on-Chronic Liver Failure.

BACKGROUND & AIMS: Little is known about outcomes of patients who underwent liver transplantation for acute on chronic liver failure (ACLF) and multiple organ failures. We compared Karnofsky Performance Status (KPS) before and after liver transplantation among patients with different numbers of organ failures and probable ACLF. METHODS: We performed a retrospective cohort study of adults who underwent liver transplantation within 30 days of listing with the United Network for Organ Sharing (UNOS) network from January 1, 2006, through September 30, 2016. We determined the prevalence of organ failures using a modified version of the Chronic Liver Failure-Sequential Organ Failure Assessment scale and collected KPS scores at the time of transplantation and at intervals of 3 to 12 months after liver transplantation. Multivariate analyses were performed to adjust for confounders including UNOS region. RESULTS: At the time of liver transplantation, 2838 patients had no organ failure, 2944 had 1 to 2 organ failures, and 1342 patients had 3 or more organ failures. KPS scores following liver transplantation improved significantly in all groups; scores ranged from 81 in patients with no organ failure to 72 in patients with 5 to 6 organ failures. Excellent performance status (KPS score, ≥80) by 1 year after transplantation was achieved by 60% of patients with 5 to 6 organ failures, 64% to 66% of patients with 3 to 4 organ failures, and 70% to 71% of patients with 1 to 2 organ failures, compared with 72.5% of patients without organ failure. Patients with 1 to 4 organ failure were more likely to achieve KPS scores of 80 or more than patients without organ failure, after we adjusted for other covariates and UNOS region. In addition, black patients were less likely, and patients with alcoholic cirrhosis were more likely, to have KPS scores of 80 or more after liver transplantation. CONCLUSIONS: In a retrospective cohort study of patients with probable ACLF who underwent liver transplantation within 30 days of listing with the UNOS network, 60% to 66% of patients with 3 or more organ failures achieved excellent performance 3 to 12 months later.

Time-dependent incidence and risk for myocardial infarction in patients with alcoholic cirrhosis.

BACKGROUND: It remains unsettled whether alcoholic cirrhosis is a risk factor for myocardial infarction (MI). METHODS: We used data from nationwide healthcare registries to study all Danes diagnosed with alcoholic cirrhosis in 1996-2014, and five controls were matched to each of them on gender and age. We excluded everyone with ischaemic heart disease and used Cox regression to estimate the incidence rate ratio of MI adjusted for potential cardiovascular confounders. Further, we described the MI-risk with non-MI death as a competing risk. RESULTS: We included 22 867 patients (67% men) with a median age of 57 years. During the first year of follow-up, their incidence rate ratio of MI was increased to 1.24 (95% CI: 0.94-1.62), driven by the effect among women (2.13, 95% CI: 1.17-3.87) and those with most severe cirrhosis (1.32, 95% CI: 0.91-1.90). After the first year, the overall incidence rate ratio fell to (0.89, 95% CI: 0.76-1.05). Patients were more likely to die from non-MI causes (33.7% vs 1.0%), which protected them against MI. The overall 1-year MI-risk was similar in patients and controls: 0.38% (95% CI: 0.30-0.47%) vs 0.34% (95% CI: 0.31-0.38%). After five years of follow-up, male patients had lower MI-risk than their controls, whereas women with cirrhosis had an increased MI-risk throughout follow-up. CONCLUSIONS: The incidence rate of MI was increased the first year following a diagnosis of alcoholic cirrhosis, in particular in women and those with most severe liver disease. Due to the competing risk of non-MI mortality, the MI-risk was not increased.

Continued muscle loss increases mortality in cirrhosis: Impact of aetiology of liver disease.

BACKGROUND AND AIMS: Sarcopenia or skeletal muscle loss adversely affects outcomes in cirrhosis. The impact of aetiology of liver disease on the severity or the rate of muscle loss is not known. METHODS: Consecutive, well-characterized adult patients with cirrhosis due to viral hepatitis (VH), alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) and non-diseased controls with at least two temporally distinct abdominal CT (computed tomography) scans were evaluated. Psoas, paraspinal and abdominal wall muscle areas at the L3 vertebra level were quantified on the CT scans. Standardized rate of change in muscle area was expressed as change in area/100 days. Univariate and multivariable analyses were performed to identify contributors to rate of muscle loss and survival. RESULTS: Among 83 cirrhotics (NAFLD n = 26, ALD n = 39, VH n = 18), there were 20 (24.1%) deaths over 62.7 ± 41.3 months. The mean percentage change in psoas area was -0.03 ± 0.05/100d in controls and -3.52 ± 0.45/100d in cirrhosis (P < .001). The mean percentage change in psoas area was -1.72 ± 0.27/100d in NAFLD, -5.28 ± 0.86/100d in ALD and -2.29 ± 0.28/100d in VH. Among cirrhotics, patients with ALD had the lowest initial muscle area and most rapid rate of reduction in muscle area. Aetiology of liver disease, model for end-stage liver disease (MELD) and the rate of loss of muscle area were independent risk factors for survival. CONCLUSIONS: Aetiology of liver disease is an independent risk factor for sarcopenia with the greatest rate of muscle loss noted in ALD. Survival in cirrhosis was dependent on initial muscle mass, rate of muscle loss and MELD score.

Extracellular vesicle-associated soluble CD163 and CD206 in patients with acute and chronic inflammatory liver disease.

Background: Extracellular vesicles (EVs) are implicated in intercellular communication in liver diseases. An EV-associated fraction of the macrophage biomarker soluble CD163, denoted EV-CD163, was recently identified. EV-CD163 may be released during later phases of the inflammatory response as opposed to the acute shedding of CD163 ectodomain (Ecto-CD163). Total sCD163 is a well-described biomarker in liver inflammation, and we investigated the distribution of CD163 fractions along with EV-associated soluble CD206 (EV-CD206) in patients with acute and chronic alcoholic liver inflammation.Methods: Patients with acute alcoholic hepatitis (AH) (n = 48) and alcoholic cirrhosis (AC) (n = 26) were enrolled. Patients with AH were followed for 30 days after diagnosis. Healthy blood donors (n = 30) served as a reference group. Fractions of sCD163 and sCD206 were separated using ExoQuick™ and measured by ELISA.Results: We demonstrated a possible EV-associated fraction of CD206 in plasma, correlating with levels of EV-CD163 (rs = 0.46, p < .001). The distribution of biomarker fractions was skewed toward EVs in chronic cirrhosis for both biomarkers (median: 35.8% EV-CD163, 58.8% EV-CD206) as compared to AH patients (median: 26.2% EV-CD163 p < .0001, 48.8% EV-CD206, p < .01). In AH patients, total sCD163 and Ecto-CD163 at inclusion were related to survival, whereas EV-CD163 was not.Conclusion: Extracellular vesicles of macrophage origin associated with membrane receptors CD163 and CD206 are present in liver disease. We observed a shift in the distribution towards an increased EV fraction in chronic liver cirrhosis. These data support that Ecto and EV fractions may be markers of different inflammatory processes, possibly resulting from a switch in macrophage phenotype.

Gender Disparities in Alcohol Use Disorder Treatment Among Privately Insured Patients with Alcohol-Associated Cirrhosis.

BACKGROUND: The burden of alcohol-associated cirrhosis (AC) is high, and though alcohol cessation improves mortality, many patients fail to engage in alcohol use disorder (AUD) treatment and continue drinking. Our aim was to determine rates, predictors, and outcomes of AUD treatment utilization in AC patients with private insurance. METHODS: We collected data from persons with AC (diagnosed by ICD-9/ICD-10 codes), aged 18 to 64 years, enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009 to 2016). We determined rates and predictors of substance abuse treatment visits as well as rates of alcohol relapse prevention medication prescriptions, weighted to the national employer-sponsored insured population. Effects of AUD treatment utilization on decompensation rates were calculated using proportional hazards regression with propensity score adjustment. RESULTS: A total of 66,053 AC patients were identified, 32% were female, and mean age at diagnosis was 54.5 years. About 72% had insurance coverage for substance abuse treatment. Overall, AUD treatment utilization rates were low, with only 10% receiving a face-to-face mental health or substance abuse visit and only 0.8% receiving a Food and Drug Administration (FDA)-approved relapse prevention medication within 1 year of index diagnosis. Women were less likely to receive a face-to-face visit (hazard ratio [HR] 0.84, p < 0.001) or an FDA-approved relapse prevention medication (0.89, p = 0.05) than men. AC patients who had a clinic visit for AUD treatment or used FDA-approved relapse medication showed decreased risk of decompensation at 1 year (HR 0.85, p < 0.001 for either). CONCLUSIONS: AUD treatment utilization is associated with lower decompensation rates among privately insured patients with AC. Women were less likely to utilize AUD treatment visits. Efforts to reduce gender-specific barriers to treatment are urgently needed to improve outcomes.

Hepatocellular Carcinoma and Associated Clinical Features in Latino and Caucasian Patients from a Single Center.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and has seen a rapid increase in incidence in the United States. Racial and ethnic differences in HCC incidence have been observed, with Latinos showing the greatest increase over the past four decades, highlighting a concerning health disparity. The goal of the present study was to compare the clinical features at the time of diagnosis of HCC in Latino and Caucasian patients. MATERIAL AND METHODS: We retrospectively screened a total of 556 charts of Latino and Caucasian patients with HCC. RESULTS: The mean age of HCC diagnosis was not significantly different between Latinos and Caucasians, but Latinos presented with higher body mass index (BMI). Rates of hypertension, diabetes, and hyperlipidemia were similar in the two groups. The most common etiology of liver disease was alcohol drinking in Latinos, and chronic hepatitis C in Caucasian patients. Non-Alcoholic Steatohepatitis (NASH) was the associated diagnosis in 8.6% of Latinos and 4.7% of Caucasians. Interestingly, alpha-fetoprotein (AFP) levels at time of diagnosis were higher in Latino patients compared to Caucasians, but this difference was evident only in male patients. Multifocal HCC was slightly more frequent in Latinos, but the two groups had similar cancerous vascular invasion. Latino patients also presented with higher rates of both ascites and hepatic encephalopathy. CONCLUSION: Latino and Caucasian patients with HCC present with a different profile of etiologies, but cancer features appear to be more severe in Latinos.

Fatal Pneumocystis jirovecii pneumonia in a non-immunocompromised patient with alcohol-related liver cirrhosis.

This report presents the fatal case of a 63-year-old man with a new presentation of liver cirrhosis, presumed concurrent acute alcoholic hepatitis and development of Pneumocystis jirovecii pneumonia. The patient had none of the traditional immunosuppressing risk factors associated with Pneumocystis jirovecii pneumonia such as corticosteroid use, haematological malignancy or HIV infection. In the literature, there are two case reports and a case series of two patients which describe the development of Pneumocystis jirovecii pneumonia in acute alcoholic hepatitis. However, all of these previously described cases include identifiable risk factors - namely corticosteroid use and HIV infection. This case suggests that special consideration should be given to Pneumocystis jirovecii pneumonia as a cause of opportunistic infection in acute alcoholic hepatitis.

[Diagnosis of anemia associated with alcoholic cirrhosis]. / Diagnostic différentiel de l'anémie dans la cirrhose éthylique.

We report here the case of a 62-year-old patient with Child-Pugh stage C ethylic cirrhosis associated with severe macrocytic anaemia, refractory to iterative transfusions and withdrawal. After a haemorrhagic, deficiency-related, or sideroblastic etiology was ruled out, haemolytic anaemia was suspected. A blood smear allowed diagnosis of haemolytic anaemia with acanthocytes. This offers the opportunity to discuss anaemia in patients with alcoholic cirrhosis, a frequent complication spanning a broad severity range and having the potential to be life-threatening. Its origin can be multifactorial : acute haemorrhage, dilution, haemolysis (here due to acanthocytosis), marrow insufficiency caused by direct alcohol toxicity, malnutrition, iron deficiency, vitamin B9 or B12 deficiency, chronic inflammation, splenic sequestration induced by portal hypertension...

Nous rapportons le cas d'une patiente de 62 ans atteinte d'une cirrhose éthylique de stade Child-Pugh C associée à une anémie macrocytaire sévère, réfractaire aux transfusions itératives et au sevrage. Après avoir exclu les étiologies hémorragiques, carentielles et sidéroblastiques, une anémie hémolytique (AH) est suspectée. La réalisation d'un frottis sanguin a permis le diagnostic d'une anémie hémolytique à acanthocytes. L'opportunité nous est donnée de discuter de l'anémie chez le patient cirrhotique alcoolique, complication fréquente recouvrant un large spectre de gravité et pouvant menacer la survie. Elle peut être multifactorielle : hémorragie aiguë, dilution, hémolyse (dans le cas particulier, liée à une acanthocytose), insuffisance médullaire par toxicité directe de l'alcool, malnutrition, carence martiale, déficit en vitamine B9 ou B12, inflammation chronique, séquestration splénique induite par l'hypertension portale….

Is cryptogenic cirrhosis different from NASH cirrhosis?

BACKGROUND & AIMS: We hypothesized that patients currently diagnosed with cryptogenic cirrhosis (CC) have truly 'cryptogenic' liver disease, which is unlikely to have evolved from NASH. The aim of this study is to characterize patients with CC, and compare their characteristics to patients with cirrhosis of other etiologies. METHODS: To investigate this, we compared the clinical characteristics of adults with CC (n = 7,999) to those with cirrhosis caused by non-alcoholic steatohepatitis (NASH) (n = 11,302), alcohol (n = 21,714) and autoimmune hepatitis (n = 3,447), using the UNOS database from 2002-16. We performed an age, gender and year of listing matched comparison of CC and NASH (n = 7,201 in each group), and also stratified patients by the presence of obesity or diabetes mellitus (DM). RESULTS: From 2002 to 2016, patients listed with a diagnosis of NASH increased from about 1% to 16% while CC decreased from 8% to 4%. A logistic regression model using the entire United Network for Organ Sharing data (n = 138,021) suggested that the strongest predictors of NASH were type 2 DM, obesity, age ≥60 years, female gender and white race. Type 2 DM was more common in patients with NASH (53%) than those with CC (29%), alcoholic cirrhosis (16%) and autoimmune hepatitis (16%), and obesity was more common in NASH (65.3%) compared to the other three groups (33-42%). There were more white individuals (82.3%) in the NASH group and a lower prevalence of black, Hispanic and Asian individuals, compared to the other three groups. Hepatocellular carcinoma was more commonly seen in NASH (19% vs. 9-13% in the other groups) and this is not influenced by obesity and type 2 DM. The differences between CC and NASH remained unchanged even when two groups were matched for age, gender and year of listing, or when stratified by the presence or absence of obesity or type 2DM. CONCLUSIONS: Based on risk perspectives, CC should not be equated with the term 'NASH cirrhosis'. LAY SUMMARY: We hypothesized that cryptogenic cirrhosis is a distinct condition from cirrhosis caused by non-alcoholic steatohepatitis (NASH). By comparing cryptogenic cirrhosis with cirrhosis of other causes, we found clear clinical differences. Therefore, cryptogenic cirrhosis should not be considered the same as NASH cirrhosis. Further investigations are required to identify unknown causes of cirrhosis.