Search

Liver cirrhosis is a severe chronic disease that results from various etiological factors and leads to substantial morbidity and mortality. Alcoholic cirrhosis (AC) and non-AC (NAC) arise from prolonged and excessive consumption of alcohol and metabolic syndromes, respectively. Precise molecular mechanisms of AC and NAC are yet to be comprehensively understood for diagnostics and therapeutic advances to materialize. This study reports novel findings to this end by utilizing high-throughput RNA sequencing and microarray data from the Gene Expression Omnibus (GEO). We performed a meta-analysis of transcriptomics data to identify the differentially expressed genes specific to AC and NAC. Functional enrichment and protein–protein interaction network analyses uncovered novel hub genes and transcription factors (TFs) critical to AC and NAC. We found that AC is primarily driven by metabolic dysregulation and oxidative stress, with key TFs such as RELA, NFKB1, and STAT3. NAC was characterized by fibrosis and tissue remodeling associated with metabolic dysfunction, with TFs including USF1, MYCN, and HIF1A. Key hub genes such as ESR1, JUN, FOS, and PKM in AC, and CD8A, MAPK3, CCND1, and CXCR4 in NAC were identified, along with their associated TFs, pointing to potential therapeutic targets. Our results underscore the unique and shared molecular mechanisms that underlie AC and NAC and inform the efforts toward precision medicine and improved patient outcomes in liver cirrhosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (β 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. [ABSTRACT FROM AUTHOR]

Gastrointestinal bleeding (GIB) is a common cause of urgent hospitalization in patients with cirrhosis. However, limited studies have examined the prevalence and risk of these complications based on etiology. This study aims to compare the occurrence and risk of cirrhosis complications on inpatient mortality between alcoholic cirrhosis (ALC) and other etiology-induced cirrhosis (NALC). This retrospective analysis included 7,159,694 patients. ALC was diagnosed based on ICD-10, while NALC included primary and secondary biliary cirrhosis, nonalcoholic steatohepatitis (NASH), and unspecified cirrhosis of the liver. GIB included bleeding from esophageal and gastric varices. Bivariate analyses using appropriate statistical tests were performed to compare the two groups. ALC patients had a significantly higher incidence of GIB compared with NALC patients (10.8% vs. 6.4%, p < 0.01), with an associated 60% higher risk of GIB than NALC patients (p < 0.01). ALC was associated with a higher prevalence of ascites (45.6% vs. 27.9%, p < 0.01) and hepatic encephalopathy (HE) (45.5% vs. 27.2%, p < 0.01) compared with NALC patients. The risk of ascites and HE was 2.2 times and 2.3 times higher, respectively, in ALC patients compared with NALC patients (p < 0.01). Furthermore, ALC patients had higher hospital mortality rates compared with NALC patients, with a 47% higher risk of hospital mortality after adjustment (p < 0.01). ALC patients also had prolonged hospital stays, higher charges, more emergency room (ER) visits, and more frequent esophagogastroduodenoscopy (EGD) requirements compared with those of NALC patients (p < 0.01). ALC patients have a significantly higher risk of developing GIB, ascites, and HE compared with NALC patients, leading to increased mortality and greater medical burden on hospitals. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is a significant global health concern associated with excessive alcohol consumption. ALD encompasses various liver conditions with complex pathogenesis and progression influenced by environmental, genetic, and epigenetic factors. Alcoholic cirrhosis of the liver (ALC) is particularly prevalent among socially disadvantaged individuals, and current pharmacotherapy options provide limited treatment. This study aims to explore the potential benefits of radio electric asymmetric conveyer (REAC) technology and its tissue optimization reparative treatment (TO-RPR) in managing ALC. The liver possesses remarkable regenerative capabilities closely tied to its bioelectrical properties. REAC TO-RPR is a novel biotechnological therapeutic approach that aims to enhance and expedite reparative processes in injured tissues by restoring disrupted cellular endogenous bioelectric fields. This study seeks to optimize understanding of REAC TO-RPR's impact on liver function and clinical outcomes in ALC patients. By investigating the mechanisms underlying liver's reparative abilities and evaluating the efficacy of REAC TO-RPR, this research aims to address the urgent need for improved interventions in managing ALC. The findings hold potential for developing innovative treatment approaches, improving patient outcomes, and reducing the societal and individual burden associated with ALC. [ABSTRACT FROM AUTHOR]

[1] ALD describes a spectrum of disease from hepatic steatosis through to cirrhosis, including alcoholic hepatitis (AH), an acute form of ALD that can occur at any stage of disease but usually on a background of cirrhosis. [30] However, in a meta-analysis of patients with biopsy-proven disease, although a difference in mortality rate was seen between patients with cirrhosis who were abstinent or not (median annual mortality was 4.7% [IQR: 4-7%] vs. 8.0% [IQR: 6.2-11.2%] in abstinent patients and in non-abstinent patients, respectively), this was not statistically significant (Mann-Whitney test, I p i = 0.229). Keywords: alcohol; lifestyles; behavior; risk reduction; alcoholic cirrhosis EN alcohol lifestyles behavior risk reduction alcoholic cirrhosis 305 310 6 11/03/23 20230801 NES 230801 Lay Summary Alcohol-related liver disease (ALD) is a major cause of ill health and premature deaths. [Extracted from the article]

Alcohol is a major risk factor of liver cirrhosis (LC). This study aimed to elucidate a surrogate marker of sarcopenia in patients with LC of different etiology. Out of 775 patients with LC, 451 were assessed for handgrip strength and skeletal muscle mass (by computed tomography). They were then divided into two groups: alcoholic cirrhosis (AC; n = 149) and nonalcoholic cirrhosis (NAC; n = 302). Endotoxin activity (EA) levels were measured with an EA assay. Group AC showed significantly higher platelet counts (p = 0.027) and lower blood urea nitrogen levels and fibrosis-4 index than group NAC (p = 0.0020 and p = 0.038, respectively). The risk factors of sarcopenia were age ≥ 65 years, female sex, CP-C LC, Hb levels < 12 g/dL, and EA level > 0.4 in all patients with LC; hemoglobin (Hb) levels < 12 g/dL and EA level > 0.4 in group AC; and age ≥ 65 years, CP-C LC, and Hb levels < 12 g/dL in group NAC. The prediction accuracy of Hb for sarcopenia in group AC, group NAC, and all patients was 83.6%, 75.9%, and 78.1% (sensitivity: 92.0%, 69.0%, and 80.2%; specificity: 66.4%, 71.0%, and 64.0%), respectively. Although not significant, the predictive performance was better when using the combination of Hb and EA measurements than when using Hb alone in group AC but was comparable in all patients. Hb levels can predict sarcopenia in patients with LC, but in those with AC, the combination of Hb and EA improves the prediction performance. [ABSTRACT FROM AUTHOR]

Alcohol is one of the most common causes of liver cirrhosis. Yet, the pattern of alcohol consumption in cirrhosis is rarely studied. This study aims to study the drinking patterns along with the educational, socioeconomic, and mental health in a cohort of patients with and without liver cirrhosis. This prospective observational study was conducted at a tertiary-care hospital and included patients with harmful drinking. Demographic, alcohol intake history, assessment of socioeconomic and psychological status by modified Kuppuswamy scale and Beckwith Inventory, respectively, were recorded and analyzed. Cirrhosis was present in 38.31% of patients with heavy drinking (64%). Cirrhosis was more among illiterates (51.76%) with early onset (22.4. ± 7.30 yrs P = 0.0001) and longer duration of alcohol (12.5 ± 6.5 vs. 6.8 ± 3.4 P = 0.001). Higher education qualification was associated with lower cirrhosis (P < 0.0001). With the same employment and education qualifications, net income in cirrhosis was lower [USD 298 (175–435) vs. USD 386 (119–739) P = 0.0001]. Whiskey (86.8%) was the commonest drink consumed. Similar median alcoholic drinks per week were consumed by both groups [34 (22–41) vs. 30 (24–40), P = 0.625], while indigenous alcohol was more consumed in cirrhosis [105 (98.5–109.75) vs. 89.5.0 (69.25–110.0) P = 0.0001]. Loss of jobs (12.36%) and partner violence were more in cirrhotic (9.89% vs. 5.80%) with similar borderline depression. Alcohol use disorder-related cirrhosis is present in a quarter of patients with harmful early onset and longer duration of drinking and is inversely related to the education status and affects the socioeconomic, physical, and family health of patients. [ABSTRACT FROM AUTHOR]

Background: The second-most frequent diagnosis among patients receiving liver transplants (LTs) is alcoholic liver disease. The multifactorial pathophysiology of alcoholic liver disease depends on the innate immune system and the inflammatory cascade. According to recent studies on these receptors, killer-cell immunoglobulin-like receptors (KIRs) may be involved in sepsis, liver rejection, and virus relapse. We aimed to investigate the impact of preclinical issues like ascites and encephalopathy and KIR genetic traits on death from sepsis, multiorgan failure (MF), and graft failure (GF) in AC patients undergoing LTs. Methods: We retrospectively reviewed 164 consecutive and deceased Caucasian AC patients who underwent LTs. Pre-transplant complications, cause of death, and patient survival were analyzed. Genomic DNA was taken from peripheral blood, and PCR-SSO was used for genotyping KIR. Results: Compared to GF patients, there was a statistically significant increase in the frequency of KIR2DL2+ (75.8% vs. 51.2%; p = 0.047). Another increase in frequency was also observed in KIR2DS2+ in sepsis compared to the GF group (51.2% vs. 43.7%; p = 0.018). In patients who passed away from MF, a decrease in KIR2DL5+ was observed in AC patients with and without encephalopathy (p = 0.018). The frequency of KIR3DL1+ in the AC patients significantly increased the mortality from sepsis (p = 0.045), which was confirmed by multivariate logistic regression. The frequency of KIR3DL1+ in the AC patients significantly increased the mortality from sepsis (p = 0.012) and was confirmed by multivariate logistic regression. KIR2DS1+ and KIR2DS4+ showed increased mortality due to GF compared to patients without these genes (p = 0.011 and 0.012, respectively). However, this fact was confirmed only for KIR2DS1+ by multivariate logistic Cox regression. Conclusions: The presence of the KIR2DL2/S2+, KIR2DL5+, and KIR3DL1+ genes increases the frequency of death from multiple organ failure or graft failure. Our findings highlight the AC patient's vulnerability to a LT during hospitalization. Following the transplant and outside of it, we adopt essential preventive measures to create a routine healthcare screening to enhance and modify treatments to increase survival. [ABSTRACT FROM AUTHOR]

Cases of alcohol-associated liver disease (ALD) are increasing at a steady rate in the United States with more patients presenting with alcohol-associated hepatitis and alcohol-associated cirrhosis. While alcohol use has increased across many demographic groups, women are suffering from a greater increase in alcohol use disorder (AUD), and are at a greater risk of ALD due to pathophysiological differences which include absorption of alcohol, first pass metabolism, and hormonal differences. Differences across race have also been found with Native Americans and Hispanics suffering from some of the largest increases in ALD rates. Younger adults are heavily impacted by rising rates of both AUD and ALD. Comorbidities such as obesity and NASH have been shown to augment the deleterious effects of AUD and ALD, resulting in more advanced liver disease. Finally, COVID-19 and policies related to the pandemic have resulted in increased AUD across many cohorts, which have resulted in marked increases in ALD. In conclusion, ALD rates are rising, with young people and women particularly impacted. [ABSTRACT FROM AUTHOR]

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. 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. 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). BA profiles are potential indicators in the diagnosis of ALD and evaluation of different stages. [ABSTRACT FROM AUTHOR]

Consumption of alcohol in excess leads to substantial medical, economic, and societal burdens. Approximately 5.3% of all global deaths may be attributed to alcohol consumption. Moreover, the burden of alcohol associated liver disease (ALD) accounts for 5.1% of all disease and injury worldwide. Alcohol use disorder (AUD) affects men more than women globally with significant years of life loss to disability in low, middle and well-developed countries. Precise data on global estimates of alcohol related steatosis, alcohol related hepatitis, and alcohol related cirrhosis have been challenging to obtain. In the United States (US), alcohol related steatosis has been estimated at 4.3% based on NHANES data which has remained stable over 14 years. However, alcohol-related fibrotic liver disease has increased over the same period. In those with AUD, the prevalence of alcohol related hepatitis has been estimated at 10–35%. Globally, the prevalence of alcohol-associated cirrhosis has been estimated at 23.6 million individuals for compensated cirrhosis and 2.46 million for those with decompensated cirrhosis. The contribution of ALD to global mortality and disease burden of liver related deaths is substantial. In 2016 liver disease related to AUD contributed to 50% of the estimated liver disease deaths for age groups 15 years and above. Data from the US report high cost burdens associated with those admitted with alcohol-related liver complications. Finally, the recent COVID-19 pandemic has been associated with marked increase in alcohol consumption worldwide and will likely increase the burden of ALD. [ABSTRACT FROM AUTHOR]

Objective: Cirrhotic cardiomyopathy (CCM) is associated with increased morbidity and mortality in patients with liver cirrhosis. Yet, it remains an under-diagnosed entity. Further, its relation to the severity of cirrhosis is contradictory. We conducted this study on an Indian population to determine the cardiac dysfunctions in cirrhosis of the liver and correlations with etiologies and cirrhosis severity. Methods: This study enrolled patients with diagnosed liver cirrhosis without any cardiac disease or conditions affecting cardiac function. All participants were evaluated clinically, electrocardiographically, and echocardiographically. Cirrhosis severity was assessed by scores from the Model for End-stage Liver Disease (MELD) and Child–Turcotte–Pugh (CTP) tests. Cirrhotic cardiomyopathy was defined as diastolic dysfunction and/or systolic dysfunction with QT prolongation. Results: Ninety-six patients were evaluated, and CTP-A stage of cirrhosis was found in 23 (24%), CTP-B in 42 (43.8%), and CTP-C in 31 (32.3%) cases. Systolic dysfunction was most frequent (P=0.014), and left ventricular ejection fraction was significantly reduced (P=0.001) in CTP-C stage of cirrhosis. Cirrhotic cardiomyopathy was found in 39.6% (n=38) of patients; CCM patients had significantly higher CTP scores (9.6±2.6 versus 8.3±2.3, P=0.012) as well as MELD scores (19.72±4.9 versus 17.41±4.1, P=0.015) in comparison to patients without CCM. Conclusion: Cirrhotic cardiomyopathy has a positive relationship with the severity of cirrhosis. Systolic function declines with the severity of cirrhosis, and overt systolic dysfunction can be present, particularly in the advanced stage of cirrhosis of the liver. [ABSTRACT FROM AUTHOR]

BACKGROUND: Higher prevalence of alcohol-related gastrointestinal (GI) and liver diseases (ARGLDs) were anecdotally reported during the COVID-19 pandemic, but little published evidence exists. METHODS: A healthcare system audit of inpatient GI consults was performed during the pandemic's lockdown phase (3/23/2020-5/10/2020, n=558) and reopening phase (6/1/2020-7/19/2020, n=711) with comparison to those timeframes in 2019. RESULTS: Consult volume decreased by 27.7% during the lockdown, but the proportion of ARGLDs increased by 59.6% (p=0.03). This trend continued during reopening, with potentially more severe disease as more patients required endoscopic intervention. Patients with alcoholic hepatitis during reopening were younger compared to the lockdown. CONCLUSIONS: Our study demonstrates increased prevalence and severity of ARGLDs amongst younger individuals during the COVID-19 pandemic. This increase started during the lockdown but worsened despite relaxation of restrictions. Systems to increase screening for and treatment of alcohol use disorder as society recovers from the pandemic remain imperative. [ABSTRACT FROM AUTHOR]

Since excessive alcohol consumption is a shared risk factor for esophageal cancer and liver fibrosis, it is possible that patients with esophageal cancer may develop unknown liver fibrosis or cirrhosis. We applied preoperative transient elastography (TE) to patients without recorded cirrhosis undergoing esophagectomy to clarify the validity in predicting postesophagectomy hepatic failure. The cohort consisted of 107 patients who received TE before esophagectomy between June 2018 and December 2021. Patients were categorized into two groups based on the fibrosis score yielded by preoperative TE (mild group: 0~2, n = 92; severe group: 3~4, n = 15). There was no significant difference in demographic data nor surgical variables between the two groups. None of the cohort encountered hepatic failure, yet the severe fibrosis group had a significantly higher rate of pleural effusion (40.0% versus 15.2%, p = 0.03). The areas under the curve (AUCs) of TE in predicting postoperative complications and 180-day mortality were 0.60 (95% CI: 0.46–0.74) and 0.67 (95% CI: 0.51–0.83), respectively. In conclusion, stratification of patients with esophageal cancer who had liver fibrosis by preoperative TE demonstrates significant validity in predicting postoperative pleural effusions. Recruitment of noncirrhotic patients with higher TE scores is warranted to examine its power in other parameters. [ABSTRACT FROM AUTHOR]

Introduction: The clinical and pathological association between pancreatitis and alcohol abuse is well recognised, however the concurrence of prevalence of alcoholic related pancreatitis and liver disease is less well studied. Aim: To evaluate frequency of histomorphological changes in pancreas and liver among patients with history of alcohol abuse and observe the prevalence of coexistence between chronic pancreatitis and liver cirrhosis. Materials and Methods: This was observational cross-sectional study conducted in Department of Pathology at Lokmanya Tilak Municipal Medical College, Mumbai, Maharashtra, India, from July 2013 to July 2018. The study included 1917 autopsies and 107 cases with a documented history of chronic alcohol abuse. Haematoxylin and Eosin (H&E) staining was done on all sections and special stain like Masson's trichrome was performed as per indication. Gross and microscopy were studied under variable defined parameters. Data was entered in Microsoft Excel sheets. Results: Histomorphologically, 12 cases (11.21%) were diagnosed as pancreatitis; 10 cases (9.34%) were of acute pancreatitis and two cases (1.86%) were of chronic pancreatitis. Total 21 cases were diagnosed as liver cirrhosis. The most dominant pattern of fibrosis seen in pancreatitis was perilobular and interlobular periductal fibrosis. The frequency of pancreatitis (14.28%) and pancreatic fibrosis (38.09%) was found to be more in cirrhotics. Chronic pancreatitis was commonly seen in cirrhotics than in non cirrhotics. Similarly, liver cirrhosis was more commonly observed in cases of chronic pancreatitis. Conclusion: The frequency of histomorphological changes seen in pancreas and liver was observed considerably among patients giving history of alcohol abuse. The prevalence of co-existence of chronic pancreatitis and liver cirrhosis was 50%. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Alcoholic cirrhosis is an advanced form of alcohol-related liver disease. In the United States, between 2010 and 2016, alcohol-related liver disease was the primary cause of nearly 1 in 3 liver transplants, surpassing hepatitis C.Methods: We utilized the US Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research database to compare trends in mortality from alcoholic cirrhosis in the United States in 1999 and 2019. We defined mortality from alcoholic cirrhosis as International Classification of Diseases code K70.3 (alcoholic cirrhosis of liver). We calculated mortality rates and mortality rate ratios (MRRs) per 100,000 from alcoholic cirrhosis in 10-year age groups from 25 to 85+ as measures of effect and 95% confidence intervals to test for significance.Results: In 1999, there were 6007 deaths from alcoholic cirrhosis among 180,408,769 aged 25-85+ years, yielding a mortality rate of 3.3 per 100,000. In 2019, there were 23,780 deaths from alcoholic cirrhosis among 224,981,167 aged 25-85+ years, yielding a mortality rate of 10.6 per 100,000. The overall MRR of 3.2 was statistically significant. (P < .001), and was apparent in each 10-year age group.Conclusions: These alarming trends in mortality from alcoholic cirrhosis in the United States contribute to the formulation of many hypotheses. These require testing in analytic studies designed a priori to do so. Meanwhile, clinical and public health efforts are necessary to curb the epidemics of heavy alcohol consumption and overweight and obesity in the United States that may be contributing to these alarming trends. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, characterized by age-related muscle loss, is common in patients with liver cirrhosis (LC). LC's metabolic burdens include protein and energy metabolism disorders, potentially leading to secondary sarcopenia. This study explores the prognostic role of serum myostatin levels in predicting hepatocellular carcinoma (HCC) development in individuals with alcoholic liver cirrhosis (ALC). Aim of the Work: The aim of this study is to investigate the prognostic performance of serum myostatin levels on HCC development in patients with alcoholic liver cirrhosis (ALC). Patients and Methods: We conducted a retrospective observational study using stored serum samples from a single center. We analyzed serum myostatin levels and assessed their correlation with HCC development in ALC patients. Results: Serum myostatin levels were significantly higher in patients with HCC compared to those without (p<0.001). Our analysis revealed a significant correlation between baseline myostatin levels and various clinical parameters, including gender (p<0.0001), serum albumin (p<0.0001), prothrombin time (PT) (p = 0.0188), serum ammonia (p<0.002), and Child Pugh score (p<0.0001). Multivariate Cox analyses identified age, gender, body mass index (BMI), platelet counts, and serum myostatin levels as independent risk factors for HCC development (p<0.001). Conclusion: Elevated serum myostatin levels are associated with an increased risk of HCC development in ALC patients. Myostatin may play a role in hepatic fibrogenesis and carcinogenesis, making it a potential prognostic marker for HCC in this population. A serum myostatin level cutoff of 3.9 ng/ml exhibited high sensitivity (92.3%) and specificity (82.35%) for detecting HCC. These findings suggest that serum myostatin levels could serve as a valuable tool for identifying high-risk ALC patients who may benefit from closer monitoring for HCC development. [ABSTRACT FROM AUTHOR]

Glucocorticoids are used as a first-line treatment for severe alcoholic hepatitis, and albumin reduces both the number of hospitalizations and mortality in patients with decompensated cirrhosis. However, for acute-on-chronic liver failure (ACLF), there is no definitive evidence that glucocorticoid therapy is beneficial. In this case report, we describe a male patient who developed into ACLF based on alcoholic cirrhosis, whose symptoms and clinical indicators continued to deteriorate after initial symptomatic treatment. The patient's condition gradually improved after low-dose glucocorticoid therapy, and long-term albumin supplementation resulted in a satisfactory outcome. [ABSTRACT FROM AUTHOR]

Objective By reviewing the clinical data of liver transplantation in the treatment of alcoholic liver disease in a single center and analyzing the clinical characteristics, the long-term prognosis and main risk factors for early postoperative death were investigated. Methods The clinical data of 98 cases of orthotopic liver transplantation performed due to alcoholic liver disease were collected to explore the effect on survival following liver transplants. The patients had been treated in the Organ Transplantation Center of the Tianjin First Central Hospital from November 2011 to November 2020. Results The follow-up duration was 1–108 months. Nine cases died; among these cases, three died during the perioperative period. Univariate analysis revealed that daily ethanol intake, Model for End-Stage Liver Disease (MELD) scores, and preoperative liver failure were associated with perioperative death, and multivariate analysis revealed that daily ethanol intake was an independent risk factor for perioperative death (P = 0.048 < 0.05); the daily intake of ethanol in the death group was significantly higher than that in the survival group (293 ± 11.5 g vs. 178.3 ± 66.8 g, P = 0.004 < 0.05). Six patients died during long-term follow-up. The one-, five-, and nine-year cumulative survival rates were 96.8%, 92.0%, and 92.0%, respectively. Preoperative liver cancer was the main risk factor for long-term survival (ORR = 2884.3, P = 0.041 < 0.05). The primary cause of death was recurrence of malignant liver tumors, followed by new lung malignancies, intracerebral hemorrhage, and hepatic allograft dysfunction. Conclusion Alcoholic liver disease is a good indication for liver transplantation. Heavy daily drinking before an operation increases the risk of perioperative death. Recurrence of malignant liver tumors is the main risk factor affecting long-term survival. [ABSTRACT FROM AUTHOR]

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 « decompensation» or « the occurrence of one or more parameters » 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite the mortality benefits of alcohol cessation and alcohol treatment, few patients with alcohol-related liver disease (ALD) get such treatment. To understand reasons for low treatment rates, we performed a qualitative mental models study to explore how ALD patients understand factors influencing alcohol cessation, relapse and their liver health. Using a mental models framework, we interviewed experts in alcohol use disorder (AUD) and ALD to determine factors influencing alcohol cessation, risk of relapse and liver health. An expert influence diagram was constructed and used to develop a patient interview guide. We recruited participants with ALD enrolled in hepatology or transplant clinics at a single tertiary-care center. We conducted interviews either face-to-face or by phone, per participant preference. We transcribed all interviews verbatim and analyzed them using combined deductive coding schema based on both the interview guide and emergent coding. 25 (10 women, 15 men) participants with a mean age of 57 years completed interviews. 68 % had decompensated cirrhosis. Major omissions included gender (as a factor in alcohol use or liver disease) and the influence of benzodiazepines/opioids on relapse. Misconceptions were common, in particular the idea that the absence of urges to drink meant participants were safe from relapse. Conceptual differences from the expert model emerged as well. Participants tended to view the self as primary and the only thing that could influence relapse in many cases, resulting in a linear mental model with few nodes influencing alcohol cessation. Participants' risky drinking signals (i.e., elevated liver enzymes) differed from known definitions of hazardous or high-risk drinking, which largely emphasize dose of alcohol consumed irrespective of consequences. Finally, participants sometimes viewed stopping on one's own as the primary means of stopping alcohol use, not recognizing the many other nodes in the influence diagram impacting ability to stop alcohol. Patients with ALD had critical misconceptions, omissions, and conceptual reorganizations in their mental models of the ability to stop alcohol use. Attention to these differences may allow clinicians and researchers to craft more impactful interventions to improve rates of alcohol abstinence and AUD treatment engagement. • Patients with ALD frequently do not access alcohol treatment and struggle to stop drinking. • Misconceptions about alcohol use and treatment are common • ALD patients often emphasize the ability to stop alcohol use on their own. • Perceptions of relapse risk can form barriers to AUD treatment. [ABSTRACT FROM AUTHOR]

Plesiomonas shigelloides is a gram-negative bacillus that commonly causes self-limited diarrhea in humans. We present the case of P shigelloides bacteremia in a 49-year-old man with alcoholic cirrhosis who developed septic shock a day after eating Dojo nabe (loach hotpot), a Japanese traditional dish. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The Child-Pugh and model for end-stage liver disease (MELD) scores are widely used to predict the outcomes of liver transplant (LT). Both have similar prognostic values in most cases, although their benefits might differ in some specific conditions. The aim of our study was to analyze the influence of pre-transplant ascites and encephalopathy in post-transplant liver rejection development and survival in alcohol cirrhosis (AC) patients undergoing LT to determine the usefulness of the Child-Pugh score for the assessment of prognosis in such patients.Material and Methods: Two hundred and eighty-one AC patients, classified according to viral infections and pre-transplant complications, were analyzed. Acute (AR) and chronic (CR) liver rejections and Child-Pugh, MELD and albumin-bilirubin (ALBI) scores were studied in all cases.Results: Similar AC rejection percentages were observed in ascites or encephalopathy groups (18.5% and 16.5%, p = 0.735), although a higher but not statistically significant AC rate was observed in patients with grade III ascites (p = 0.777) and with grade II encephalopathy (p = 0.089). Chronic rejection was only developed by 9.1% of AC patients, regardless of the presence of ascites (6.2%) or encephalopathy (5.5%). The presence of ascites and encephalopathy complications did not seem to influence post-transplant survival. Neither the Child-Pugh nor the ALBI score can be considered the best for predicting patient survival in the short or long term.Conclusions: Ascites and encephalopathy do not seem to influence AC or CR in patient survival, regardless of the presence of viral infections, so in our study neither the Child-Pugh nor ALBI score seems to be the best score to predict the outcomes of these patients. [ABSTRACT FROM AUTHOR]

Introduction: The excessive and prolonged consumption of alcohol is associated with a high morbidity due to hepatic disorders and affections of other organs. Objective: To specify the hepatic lesions and their relationship with other diseases associated with alcohol and the nutritional state in patients with alcoholic hepatic disease. Methods: An observational, descriptive and cross-sectional study of 270 patients with alcoholic hepatic disease was carried out. They were assisted in the Internal Medicine Service and in the specialized visit of Hepatology from Saturnino Lora Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba who were clinically examined to detect symptoms and signs of hepatic disease and those associated with alcohol in different systems, during the decade 2010-2019. Results: There was a prevalence of men (234), of which 117 were in the group of 25 - 44 years of age. The preponderant clinical form was the hepatic cirrhosis in 109 patients, an important proportion of them were drinkers with more than 20 years of exhibition to the habit. The disease due to gastroesophagic reflux along with the forms of gastropathy and polyneuropathy in 89 and 96 affected patients, respectively, were the comorbidities more associated with the hepatic lesion. Different degrees of malnutrition were observed in 167 affected patients (61.8 %), of which those with hepatic cirrhosis prevailed, of these 51 (49.0 %) presented moderate malnutrition and 31 (49.2 %) a serious one. Conclusions: The presence of comorbidities in patients with alcoholic hepatic disease is high, which is associated to the nutritional deterioration and a prolong exposure to the harmful habit. [ABSTRACT FROM AUTHOR]

Spur cell anemia is acquired hemolytic anemia seen in patients with advanced liver disease, particularly in the setting of alcoholism, and warrants urgent liver transplant evaluation. We describe the case of a 58-year-old female with alcoholic cirrhosis who presented with worsening liver disease, profound anemia poorly responsive to blood transfusions, and multiple spur cells on the peripheral smear. She underwent a liver transplant, which led to the resolution of hematologic abnormalities and the need for transfusions. Our case highlights the significance of spur cell anemia as a harbinger of poor prognosis in patients with advanced liver disease and its reversibility with liver transplantation. [ABSTRACT FROM AUTHOR]

Introduction Cirrhosis is an irreversible disease, with high mortality and varied etiology. The most associated causes are alcohol abuse, hepatitis B and C viruses and autoimmune liver disease. Objective To describe the clinical and demographic characteristics of patients with liver cirrhosis at the Gustavo Nelson Collado Ríos Hospital. January- December 2019. Methodology An observational, descriptive and retrospective study was carried out, in which 42 clinical records of patients with liver cirrhosis who attended their appointments with the Gastroenterology service in 2019 were reviewed. Results The age group with the highest number of cases was 60-69 years with a predominance of the female gender. The most frequent associated factors were diabetes mellitus 2 (62%), overweight (38%), obesity (33%), alcohol habit (19%), autoimmune liver disease (12%), and hepatitis B virus (7%). We calculated a fatality of 20% for this cohort, a median survival of 2 years for patients alive at the time of the study, and a median survival of 18 months for patients who died in 2019. Conclusion In the central provinces of Panama, we observed a downward trend in cases of cirrhosis due to alcoholic and viral etiology, with an increase in metabolic diseases predominantly in the female gender that cause long-term liver damage. Cirrhosis is still a disease of high lethality; however, with a survival that exceeds 2 years if the patient is well treated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between Th17 and related cytokines with liver stiffness measurement (LSM), liver function and adiponectin (APN) levels in alcoholic cirrhosis patients. Methods: 72 cases of alcoholic cirrhosis patients admitted to our hospital from January 2018 to January 2020 were treated as alcoholic cirrhosis group, 100 healthy volunteers who underwent physical examination in our hospital during the same period were treated as healthy control group. Differences of Th17, interleukin-17 (IL-17), LSM, liver function indicators, APN levels between two groups were compared. Pearson test was used to evaluate the correlation between Th17 and IL-17 with disease related indicators in alcoholic cirrhosis patients. Results: Distribution ratio of Th17, IL-17 levels, LSM in alcoholic cirrhosis group were higher than those in healthy control group (P<0.05). The levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and serum total bilirubin (STB) in peripheral blood in alcoholic cirrhosis group were higher than those in healthy control group, albumin (ALB) was lower than that in healthy control group, the level of APN in serum was lower than that in healthy control group (P<0.05). The correlation analysis showed that the Th17 distribution ratio and IL-17 level in alcoholic cirrhosis patients were positively correlated with the levels of LSM, ALT, AST and STB, and negatively correlated with the levels of ALB and APN (P<0.05). Conclusion: The expression levels of Th17 and IL-17 increase abnormally in alcoholic cirrhosis patients, it may be a good indicator that reflects the degree of abnormal changes in disease. [ABSTRACT FROM AUTHOR]

Performing cardiothoracic surgery on patients with advanced liver failure and liver cirrhosis is high-risk for patients. Coronary artery bypass grafting is the most effective treatment for patients with liver failure that is complicated with severe coronary heart disease, and who cannot be treated using coronary stent intervention. In the current study, one case of coronary artery bypass grafting combined with liver transplantation was assessed, with the patient exhibiting advanced alcoholic liver cirrhosis. A coronary artery bypass graft was performed to relieve angina pectoris. Following surgery, wound exudation, secondary infection, liver failure, pleuroperitoneal fluid leakage, hypoproteinemia and other adverse treatment results occurred, and the chest wound did not heal. Allograft liver transplantation was subsequently performed and, following surgery, the chest wound healed gradually after debridement, and the patient recovered. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The pivotal role of the extracellular matrix (ECM) as both a cause and consequence of liver fibrosis is striking. However, mechanotransducer molecules and profibrogenic factors induced by liver stiffness are still unclear. The current study aimed to investigate liver stiffness and its correlation with the expression of the transcriptional coactivator with PDZ‐binding motif (TAZ) and serum osteopontin (OPN) in human cirrhosis. In this case−control study, liver tissue stiffness was determined using atomic force microscopy in cirrhotic livers (n = 38) of different etiologies and in controls (n = 10). Immunohistochemical and qRT‐PCR analyses were performed to analyze TAZ expression. Besides, western blotting and ELISA were performed to assess liver Indian hedgehog and serum OPN levels, respectively. Liver stiffness, TAZ expression, and hepatic gene expression and serum protein levels of OPN were significantly increased in patients with cirrhosis compared with the control groups (all P < 0.001), specifically in autoimmune‐ and alcohol‐related cirrhosis. In cirrhotic patients, liver stiffness was significantly associated with the expression of nuclear TAZ and OPN. The correlation between matrix stiffness as a mechanical property, TAZ as a potential mechanotransducer, and OPN as a matricellular factor suggests possible effects of mechanical features of the ECM on the expression of the aforementioned profibrogenic markers, which is predominant in autoimmune‐ and alcohol‐related cirrhosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Access to alcohol use treatment is critical for those with alcohol‐associated liver disease as alcohol cessation improves outcomes. In this study of a large population of privately insured US adults with alcohol‐associated cirrhosis, access to alcohol use treatment was low, and access to all forms of alcohol use treatment was lower in women compared to men. Those who received treatment were less likely to experience symptoms of cirrhosis. Future studies should determine how to improve rates of alcohol use treatment for those with alcohol‐associated cirrhosis. [ABSTRACT FROM AUTHOR]

Background: The relation between excessive alcohol consumption and coronary arteriosclerosis has remained controversial. The etiology of cirrhosis has been considered a substantial risk factor for development of arteriosclerotic lesions. The coronary artery calcium-score derived from coronary CT angiography is a robust marker of coronary arteriosclerosis.Aims: To study the burden of coronary arteriosclerosis in cirrhotic patients of various etiologies and association to cardiac dysfunction and survival.Methods: Fifty-seven patients with cirrhosis without cardiovascular disease underwent coronary CT angiography, tissue Doppler echocardiography, electrocardiogram and registration of clinical and biochemical characteristics.Results: In patients with cirrhosis the median coronary artery calcium-score was increased in comparison with age and race-adjusted healthy reference values (men: 328 vs. 9 HU and women: 136 vs. 0 HU; p < 0.001). Moreover, the coronary artery calcium-score in alcohol-related cirrhosis was significantly higher than in nonalcohol-related cirrhosis (362 vs. 46 HU, p < 0.001). Coronary artery calcium-score correlated with age (p = 0.002) but not with established cardiovascular risk factors including smoking, type 2 diabetes, hypertension, gender, or hypercholesterolemia. Coronary artery calcium-score was associated with diastolic dysfunction, lateral e´ (p = 0.025), but not with other markers of cardiac dysfunction. During a median follow-up of 25 months 12 patients (21%) died but coronary artery calcium-score was not associated with survival.Conclusions: Coronary arteriosclerosis was particular extensive in patients with alcoholic cirrhosis. However, the current results suggest that coronary arteriosclerosis only have limited influence on cardiac function and survival. Surprisingly, no other established risk factors apart from age seemed to interfere with coronary arteriosclerosis in cirrhotic patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary Alcohol-related liver disease (ALD) remains the most important cause of death due to alcohol. Infections, particularly bacterial infections, are one of the most frequent and severe complications of advanced ALDs, such as alcoholic cirrhosis and severe alcoholic hepatitis (sAH). The specific mechanisms responsible for this altered host defence are yet to be deciphered. The aim of the present study is to review the current knowledge of infectious complications in ALD and its pathophysiological mechanisms, distinguishing the role of alcohol consumption and the contribution of different forms of ALD. To date, corticosteroids are the only treatment with proven efficacy in sAH, but their impact on the occurrence of infections remains controversial. The combination of an altered host defence and corticosteroid treatment in sAH has been suggested as a cause of opportunistic fungal and viral infections. A high level of suspicion with systematic screening and prompt, adequate treatment are warranted to improve outcomes in these patients. Prophylactic or preemptive strategies in this high-risk population might be a preferable option, because of the high short-term mortality rate despite adequate therapies. However, these strategies should be assessed in well-designed trials before clinical implementation. [ABSTRACT FROM AUTHOR]

Aim: This paper will demonstrate that alcohol abstinence has a beneficial effect on liver function and survival in all types of alcoholic liver disease. Results: Daily alcohol consumption of more than 25 gram in men and half of that in women is a risk factor for alcoholic liver disease (ALD). ALD consists of fatty liver, steatohepatitis, fibrosis, cirrhosis and hepatocellular cancer. Alcohol abstinence is the major therapeutic option, since under alcohol abstinence alcoholic fatty liver normalizes. In alcohol hepatitis, a clinical syndrome with high mortality abstinence is absolutely mandatory to avoid early death. Even moderate hepatic fibrosis (perivenular and perisinusoidal) may regress during alcohol abstinence. In compensated and even decompensated cirrhosis of the liver mortality is significantly reduced when alcohol intake is stopped as compared to continuous drinking. Conclusion: Compared to other etiologies of hepatic cirrhosis as for example cirrhosis caused by hepatitis B or C virus, alcoholic cirrhosis has a significant better prognosis under alcohol abstinence. Thus alcohol abstinence is a good therapie and the success of each new therapy has to be compared to abstinence. [ABSTRACT FROM AUTHOR]

Background & Aims We aimed to determine associations between alcoholic cirrhosis and incidence of comorbidity, and to describe the clinical course of alcoholic cirrhosis in terms of comorbidity development. The comorbid diseases we studied were acute myocardial infarction, heart failure, peripheral arterial disease, chronic obstructive pulmonary disease, chronic kidney disease, epilepsy, diabetes and cancer. Methods This was a registry-based nationwide historical cohort study. We included 10 650 Danish citizens diagnosed with alcoholic cirrhosis at age 45-69 years in 1994-2014 and 43 150 age- and gender-matched persons. None of them had the comorbid diseases we studied at inclusion. We compared rates and cumulative risks of comorbidity development between patients and controls. Results Patients with alcoholic cirrhosis had a higher rate of comorbidity (hazard ratio for any comorbidity = 3.74, 95% CI 3.56-3.94), including all the non-cancer comorbidities (hazard ratio for any non-cancer comorbidity = 4.33, 95% CI 4.06-4.62) except acute myocardial infarction. They also had a higher rate of developing cancer (hazard ratio = 2.94, 95% CI 2.70-3.19). Still, relatively few patients actually lived to experience development of non-cancer (10-year risk: 21.4% vs. 13.2% for controls) or cancer comorbidity (10-year risk: 10.9% vs. 10.0%) because they died before they developed any comorbid disease. Hepatocellular carcinoma and oropharyngeal cancer were the only two comorbidities that were much more likely to develop in patients than in controls. Conclusions Alcoholic cirrhosis promotes development of several comorbid diseases, but only few patients with alcoholic cirrhosis live long enough to actually develop them. [ABSTRACT FROM AUTHOR]

Background Alcoholic cirrhosis ( AC) is a common cause of death among individuals abusing alcohol. In the last resort, liver transplantation ( LT) is considered the only solution to save the patient's life, generating socioeconomic and public health problems. Clinical and sociodemographic characteristics, rejection frequency, and short- and long-term graft survival are not well known in end-term AC patients undergoing LT. The aim was to determine the sociodemographic and clinical characteristics, their incidence in LT, main pre- and posttransplant complications, and short- and long-term post-transplant graft survival in AC patients in southeastern Spain. Methods The medical records of 1,026 patients who underwent LT over the last 23 years were retrospectively reviewed, and demographic data and posttransplant survivals were analyzed and compared. Biochemical characteristics, major pre- and posttransplant complications and short- and long-term survivals were analyzed in a total of 398 male patients with AC undergoing LT. Results AC and viral cirrhosis are the main indications for LT in our study. Mostly represented in our study are AC men without associated viral infections with a mean age of 53.06 years. Main pretransplant complications in AC patients are ascites (78.3%) and encephalopathy (43.5%), while acute graft rejection is the most common liver posttransplant complication (26.6%), nevertheless with low graft loss frequency (1.1%). AC and autoimmune cirrhosis show the best posttransplant survival in both the short and long term. Patients with AC included on the waiting list for LT were Child- Pugh class B (52.1%) and Model for End-Stage Liver Disease score of 10 to 19 (71.2%). The highest percentage of AC patient survival was observed at 1 year posttransplant (81.2%) and progressively decreased over time up to 10 years posttransplant (69.6%). Pretransplant complications such as ascites and encephalopathy did not have an influence on the percentage of posttransplant survivals, although better survival rates were observed in nonviral AC patients. Conclusions AC without viral infections is the main indication for LT in southeastern Spain although its frequency has decreased in last decade. AC is a good indication for LT for its high survival rate and few posttransplant complications. Despite having a high percentage of pretransplant complications (ascites and encephalopathy) but does not appear to influence survivals being observed posttransplant survival rates above those expected. Conversely, viral infections in the patient with AC decrease patient survivals. The main future goals are design new strategies to detect, treat, and reduce AC frequency in our population and know alcoholic recidivism rate posttransplant in our population. [ABSTRACT FROM AUTHOR]

Background & Aims Iron constitutes a potentially toxic element and consequently, hepatic iron overload may accelerate liver disease progression and development of hepatocellular carcinoma ( HCC). Hepcidin is the central negative regulator of iron metabolism that is produced primarily by the liver. Methods To study the prognostic significance of serum hepcidin, we assessed the influence of baseline serum hepcidin levels on the outcome of a French cohort encompassing 237 patients with alcoholic cirrhosis prospectively followed up in the setting of HCC screening. Results Hepcidin values correlated weakly with serum ferritin levels ( r = 0.33) and hepatic iron scores ( r = 0.3). After a median follow-up of 68 months, patients with baseline lower hepcidin level had a higher risk of HCC occurrence [hazard ratio, HR = 1.76 (1.01-3.06), P = 0.031] and overall death [ HR = 1.63 (1.07-2.44), P = 0.019]. According to Cox multivariate analyses, lower hepcidin levels were independently associated with death [ HR = 2.84 (1.29-6.25), P = 0.009] along with higher Child-Pugh score while HCC occurrence was mainly associated with clinical confounders interfering with iron metabolism (older age and higher BMI, adjusted P-value for hepcidin = 0.119). Conclusions In conclusion, low-serum hepcidin levels in patients with alcoholic cirrhosis bear a long-term prognostic significance warranting further explorations. [ABSTRACT FROM AUTHOR]

Alcohol consumption is increasing every day more and more and college students deserve special attention regarding the consumption consumption of alcohol, because this young population encompasses a large portion of the consumer universe of licit and illicit drugs. This study is based on a field with a quantitative approach and descriptive research conducted through a questionnaire applied to students of biomedicine course at a college of the Steel Valley region, the total of 110 students, 91 agreed to participate and They answered the questionnaire. The research covered the period from August to October 2015. The study aims to evaluate the consumption of alcohol among students and describe the relationship between alcohol consumption and the possibility of development of liver cirrhosis among them. If contacted that the questioned students, 76.92% consume alcohol and that There is an increase in consumption during the course. The intake occurs at an earlier age, pupils, 25.27% drank for the first time between 13 and 15 years old, influenced mostly by friends. Many of the students drink alcohol and sometimes ever happened alcohol overcome the physical limits of the individual. Those who drink every day are more likely the future development of liver cirrhosis, since the disease's main risk factor the the amount of alcohol consumed and the frequency of this consumption. [ABSTRACT FROM AUTHOR]

Aim To estimate sex differences in health-care utilization among harmful/hazardous drinkers in the period before alcoholic cirrhosis diagnosis, and estimate sex differences in the extent to which alcohol use and brief alcohol interventions were documented for these individuals compared with a control cohort. Design Retrospective study using linked general practice and hospital admissions data in England. Setting Three hundred and fifty-seven general practitioner (GP) practices in England. Participants A total of 2479 individuals with alcoholic cirrhosis (mean age at diagnosis = 56years), of whom 67% were men; and 24 790 controls without the disease. Measurements Rates of primary care visits and hospital admissions prior to the diagnosis of alcoholic cirrhosis for men and women, and the proportion of men and women with alcohol consumption and/or alcohol brief intervention documented in their medical record. Findings Compared with the general population, patients with alcoholic cirrhosis used primary and secondary health-care services more frequently in the years leading up to their diagnosis. In the years prior to diagnosis, men used primary and secondary health-care services more than did women ( P for sex interaction P < 0.0001). Men were more likely than women to have their alcohol use recorded [odds ratio (OR) men = 1.96, 95% confidence interval (CI) = 1.7-2.3; women = 1.63, 95% CI = 1.4-1.8, P for sex interaction P < 0.0017]. By contrast, alcohol interventions were recorded more commonly among women (OR men = 4.3, 95% CI = 3.7-4.9; women = 5.8, 95% CI = 4.7-6.9, P for sex interaction = 0.07), although less common with increasing age ( P for age interaction = 0.009). Conclusions In the United Kingdom, prior to alcoholic cirrhosis diagnosis, excess health-care utilization is higher in men than women and men are more likely than women to have their alcohol use recorded. However, women appear to be more likely than men to receive alcohol brief interventions. [ABSTRACT FROM AUTHOR]

The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and Prothrombin 20210A, were studied as risk factors in 865 Caucasian patients with liver cirrhosis, consecutively enrolled from June 2008 to January 2014. A total of 582 HCV, 80 HBV, 94 alcohol, (82 with more than one etiologic factor) and 191 cryptogenic patients with liver cirrhosis had been consecutively enrolled; 243 patients showed portal vein thrombosis (PVT). At least one of the above THRGFs was present in 339/865 patients (39.2%). PAI-1 4G-4G and MTHFR 677TT were the most frequent THRGFs, statistically significant in patients with alcohol, cryptogenic liver cirrhosis, and PVT: respectively 24 and 28, 50 and 73, and 65 and 83 (all chi-square tests > 3.84, and p values < 0.05). Two logistic regression analysis, using PAI-1 4G-4G and MTHFR 677TT, as dependent variable, confirmed the independent significant relationship of these THRGFs with alcohol, cryptogenic liver cirrhosis and PVT. PAI 1 and MTHFR 677 genotypes, deviated from those expected in populations in Hardy–Weinberg equilibrium (all p values < 0.05), in the subgroups of patients with alcohol, cryptogenic liver cirrhosis and presence of PVT. Our study shows the pivotal role of PAI-1 4G-4G and MTHFR 677TT in patients with alcohol, cryptogenic liver cirrhosis, and PVT, in a Caucasian population. In conclusion, thrombo and fibro-genetic mechanisms of PAI-1 4G-4G and MTHFR 677TT, could have a role in the development of liver cirrhosis, mainly in patients without HCV and HBV, and PVT. [ABSTRACT FROM AUTHOR]

Background & objectives: Earlier studies have documented high prevalence of undernutrition, morbidity and mortality among Chenchus, a tribal population in Telangana and Andhra Pradesh, India. The present study was carried out to assess diet and nutritional status of Chenchus and cause of death. Methods: A total of 42 Chenchu villages (gudems) were covered using systematic random sampling procedure. In each gudem, all the households with at least one child under the age of five years were covered for various investigations. Weighment diet survey was carried out on a sub-sample of households. In addition, information on cause of death in the selected 42 gudems was collected for past one year using verbal autopsy method. Results: A total of 1396 subjects of all age groups were covered for various investigations. The intakes of food and nutrients were lower than the recommended levels. The prevalences of underweight, stunting and wasting among under five children were 42 per cent (CI: 37.9-46.1), 53 and 13 per cent, respectively, while 41 per cent (CI: 37.8-47.2) men and 42 per cent (34.4-47.8) women had chronic energy deficiency (BMI<18.5 kg/m²). Sixty eight deaths were reported during the past one year in 42 Chenchu gudems. The major causes of death were premature delivery, low birth weight, alcoholic cirrhosis of liver, accidents, snakebite and pulmonary tuberculosis. Interpretation & conclusions: The prevalence of undernutrition in Chenchu population was comparable with other tribal and rural counterparts in Andhra Pradesh, however, the crude death rate (11.7/1000) was higher among the Chenchus. Steps may be taken to promote consumption of balanced diet and utilization of optimal healthcare facilities to control morbidity and mortality. [ABSTRACT FROM AUTHOR]

Aims To characterize serum amyloid A ( SAA)-positive hepatocellular neoplasms/nodules arising in alcoholic cirrhosis, which are detected as hypervascular hepatocellular nodules resembling hepatocellular carcinoma on imaging. Methods and results Fifty-three hepatocellular nodules were examined with immunostaining for SAA, glutamine synthetase and glypican-3 in 23 patients (four women and 19 men) with alcoholic cirrhosis. Sixteen nodules were examined with magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid enhancement ( EOB- MRI). Somatic mutations in IL6 ST, GNAS and STAT3 were examined in 19 nodules. Thirty-six nodules in 18 patients were diagnosed as SAA-positive hepatocellular neoplasms/nodules, and the remaining 17 nodules in eight patients were SAA-negative focal nodular hyperplasia ( FNH)-like nodules. SAA-positive hepatocellular neoplasms/nodules showed significantly more extensive sinusoidal dilatation, inflammatory reaction, abnormally thick arteries and cellular atypia than FNH-like nodules ( P < 0.05). Eight SAA-positive hepatocellular neoplasms/nodules (67%) showed slight hypointensity in the hepatobiliary phase on EOB- MRI, whereas all four FNH-like nodules showed iso-intensity ( P < 0.05). STAT3 mutations were detected in two of 17 SAA-positive hepatocellular neoplasms/nodules. Conclusions This study showed that approximately two-thirds of hypervascular hepatocellular nodules arising in alcoholic cirrhosis were SAA-positive hepatocellular neoplasms/nodules, which show different findings on the EOB- MRI. STAT3 mutations were detected in 11.8% of SAA-positive hepatocellular neoplasms/nodules, supporting a neoplastic nature. [ABSTRACT FROM AUTHOR]