Clinical review and literature analysis of hepatic epithelioid angiomyolipoma in alcoholic cirrhosis: A case report.

BACKGROUND: Hepatic epithelioid angiomyolipoma (HEA) has a low incidence and both clinical manifestations and imaging lack specificity. Thus, it is easy to misdiagnose HEA as other tumors of the liver, especially in the presence of liver diseases such as hepatitis cirrhosis. This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis, and analyzed the literature, in order to improve the understanding of this disease. CASE SUMMARY: A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver. Based on the patient's history, laboratory examinations, and imaging examinations, a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed. Postoperative pathology showed HEA. During outpatient follow-up, the patient showed no sign of recurrence. CONCLUSION: HEA is difficult to make a definite diagnosis before surgery. HEA has the potential for malignant degeneration. If conditions permit, surgical treatment is recommended.

Critical misconceptions and knowledge gaps regarding alcohol cessation and risk of relapse in alcohol-related liver disease patients: A qualitative mental models study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

REAC Reparative Treatment: A Promising Therapeutic Option for Alcoholic Cirrhosis of the Liver.

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.

Hepatic venous pressure gradient: Inaccurately estimates portal venous pressure gradient in alcoholic cirrhosis and portal hypertension.

BACKGROUND: Portal hypertension (PHT) in patients with alcoholic cirrhosis causes a range of clinical symptoms, including gastroesophageal varices and ascites. The hepatic venous pressure gradient (HVPG), which is easier to measure, has replaced the portal venous pressure gradient (PPG) as the gold standard for diagnosing PHT in clinical practice. Therefore, attention should be paid to the correlation between HVPG and PPG. AIM: To explore the correlation between HVPG and PPG in patients with alcoholic cirrhosis and PHT. METHODS: Between January 2017 and June 2020, 134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures. Correlations were assessed using Pearson's correlation coefficient to estimate the correlation coefficient (r) and determination coefficient (R2). Bland-Altman plots were constructed to further analyze the agreement between the measurements. Disagreements were analyzed using paired t tests, and P values < 0.05 were considered statistically significant. RESULTS: In this study, the correlation coefficient (r) and determination coefficient (R2) between HVPG and PPG were 0.201 and 0.040, respectively (P = 0.020). In the 108 patients with no collateral branch, the average wedged hepatic venous pressure was lower than the average portal venous pressure (30.65 ± 8.17 vs. 33.25 ± 6.60 mmHg, P = 0.002). Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography (19.4%), while the average PPG was significantly higher than the average HVPG (25.94 ± 7.42 mmHg vs 9.86 ± 7.44 mmHg; P < 0.001). The differences between HVPG and PPG < 5 mmHg in the collateral vs no collateral branch groups were three cases (11.54%) and 44 cases (40.74%), respectively. CONCLUSION: In most patients, HVPG cannot accurately represent PPG. The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.

Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients: A propensity-matched analysis from the United States.

BACKGROUND: Alcohol-associated cirrhosis (AC) contributes to significant liver-related mortality in the United States. It is known to cause immune dysfunction and coagulation abnormalities. Patients with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019 (COVID-19). The specific association between AC and COVID-19 mortality remains inconclusive, given the lack of robust clinical evidence from prior studies. AIM: To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United States. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database 2020. Patients were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC. A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser comorbidities. Primary outcomes included median length of stay, median inpatient charges, and in-hospital mortality. Secondary outcomes included a prevalence of systemic complications. RESULTS: A total of 1325 COVID-19 patients with AC were matched to 1135 patients without AC. There was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC (P > 0.05). There was an increased prevalence of septic shock (5.7% vs 4.1%), ventricular fibrillation/ventricular flutter (0.4% vs 0%), atrial fibrillation (13.2% vs 8.8%), atrial flutter (8.7% vs 4.4%), first-degree atrioventricular nodal block (0.8% vs 0%), upper extremity venous thromboembolism (1.5% vs 0%), and variceal bleeding (3.8% vs 0%) in the AC cohort compared to the non-AC cohort (P < 0.05). There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC, with an odds ratio of 0.97 (95% confidence interval: 0.78-1.22, P = 0.85). Predictors of mortality included advanced age, cardiac arrhythmias, coagulopathy, protein-calorie malnutrition, fluid and electrolyte disorders, septic shock, and upper extremity venous thromboembolism. CONCLUSION: AC does not increase mortality in patients hospitalized with COVID-19. There is an increased association between inpatient complications among COVID-19 patients with AC compared to non-AC.

The causality between gut microbiome and liver cirrhosis: a bi-directional two-sample Mendelian randomization analysis.

Background and aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis. Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations. Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05). Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis.

Ileocecal Mesentery Arteriovenous Malformation as a Rare Cause of Ectopic Variceal Bleeding in a 58-Year-Old Male With Cirrhosis.

Ectopic varices can be defined as dilated portosystemic venous collaterals that are located at a site other than the esophagus or stomach. These varices can be seen in patients with underlying portal hypertension, but bleeding from them is quite rare. The bleeding usually occurs in patients with a history of intra-abdominal surgery and adhesions. These varices are commonly found in the duodenum or rectum, but they can be present anywhere along the gastrointestinal tract. Currently, there are no well-established guidelines regarding the diagnosis and management of these variceal bleeds, and further investigations with randomized controlled or large-scale trials are required. Here, we report an unusual case of ectopic variceal bleeding from an ileal arteriovenous malformation (AVM), which presented as syncope associated with an acute abdomen in a patient with no prior history of intra-abdominal surgery.

Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles?

Decompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation directly into the peritoneal cavity. Alcohol consumption is one of the main risks of developing alcoholic cirrhosis (AC), but not all AC patients develop ascites. Avoiding the development of ascites is crucial, given that it deteriorates prognosis and increases the patient mortality patient. The innate immune system plays a crucial role in cirrhosis through natural killer cells, which are abundant in the liver. The aim of this study was to analyze the KIR/HLA-C genetic profile in AC patients with and without ascites to understand this pathology and find predictive clinical susceptibility biomarkers that can help to establish risks and prevent the development of ascites in AC patients. A total of 281 AC patients with and without ascites were analyzed and compared with 319 healthy controls. Genomic DNA was extracted from peripheral blood in all groups. A PCR-SSO assay was performed for KIR/HLA genotyping analysis. A total of 16 activating and inhibitor KIR genes and their corresponding known ligands, epitopes of HLA-C, and their genotypes were analyzed. According to our analysis, C1 epitopes were statistically significantly decreased in AC patients with and without ascites. When comparing AC patients with ascites and healthy controls, a significant decrease in C1 epitope frequency was also observed. A statistically significant decrease was also found when comparing the C1C2 genotype in AC patients without ascites with controls. In conclusion, the absence of KIR2DL2 and KIR3DL1 genes may be a predisposing factor for the development of ascites in AC patients. The KIR2DS2/KIR2DL2 may could be involved in grade I ascites development, and the presence of the C1+ epitope and the homozygous C2C2 genotype may be protective genetic factors against ascites development in AC patients.

Nosocomial vs healthcare associated vs community acquired spontaneous bacterial peritonitis: Network meta-analysis.

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a common complication in decompensated liver cirrhosis with ascitic fluid polymorphonuclear cell count > 250/mm3. Community acquired SBP (CA-SBP) occurs within the first 48 hours after hospital admission. Nosocomial SBP (N-SBP) occurs 48-72 hours after hospitalization. Healthcare associated SBP (HA-SBP) occurs in patients hospitalized in the preceding 90 days to months. We aim to evaluate mortality and resistance patterns to third generation cephalosporin among the three types. METHODS: Multiple databases were systematically searched from inception through August 1st, 2022. Both pairwise (direct) and network (direct + indirect) meta-analysis was performed using a random effects model and DerSimonian Laird approach. Relative Risk (RR) with 95% confidence intervals (CI) were calculated. Network meta-analysis was conducted using frequentist approach. RESULTS: A total of 14 studies with a total of 2302 SBP episodes were evaluated. On direct meta-analysis, mortality rate was higher in N-SBP compared to HA-SBP (RR 1.84, CI 1.43- 2.37) and CA-SBP (RR 1.69, CI 1.4-1.98), but not significantly different between HA-SBP and CA-SBP (RR=1.40, CI=0.71-2.76). Resistance to third generation cephalosporins was significantly higher in N-SBP compared to HA-SBP (RR=2.02, CI 1.26-3.22) and CA-SBP (RR=3.96, CI=2.50-3.60) as well as in HA-SBP compared to CA-SBP (RR=2.25, CI=1.33-3.81). CONCLUSIONS: Our network meta-analysis shows increased mortality and antibiotic resistance with nosocomial SBP. We recommend clearly identifying such patients to manage accordingly as well as developing guidelines geared towards nosocomial infections to be able to optimally steer resistance patterns and reduce mortality.

Hemoglobin and Endotoxin Levels Predict Sarcopenia Occurrence in Patients with Alcoholic Cirrhosis.

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.

The Pattern of Alcohol Use in Alcohol-Related Cirrhosis in Indian Patients: AUDIT Indian Liver Study.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Presence of KIR2DL2/S2, KIR2DL5, and KIR3DL1 Molecules in Liver Transplant Recipients with Alcoholic Cirrhosis Could Be Implicated in Death by Graft Failure.

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.

Transfusion-Related Acute Lung Injury in an Alcoholic Hepatic Cirrhosis Patient: A Case Report.

Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related mortality in the United States. It is a rare, potentially fatal complication of blood product transfusion, often seen in one in 5000 transfusion cases. On average, studies show a reported estimated fatality rate of 5-24% with a mortality rate of 12%. In the US, TRALI has been responsible for 30% of transfusion-related deaths. In this report, we discuss a case of a 51-year female with a past medical history of alcohol dependence and depression who presented complaining of dizziness and lightheadedness for 1 week. Subsequent diagnostic assessment and therapeutic interventions included various imaging studies, serial hematological evaluations, and eventual administration of blood transfusions, intravenous corticosteroids, supplemental oxygenation, and diuresis for clinical management. The occurrence of TRALI is often underreported due to a lack of timely recognition resulting in delayed treatment. Overall, we were able to not only diagnose TRALI in this patient but also effectively comprehend the significance of guiding appropriate management strategies due tohuman leukocyte antigen (HLA) TRALI-mediating antibodies to potentially reduce the overall incidence of such transfusion reactions.

Nutritional Support for Alcoholic Liver Disease.

Malnutrition is a common finding in alcohol use disorders and is associated with the prognosis of patients with alcoholic liver disease (ALD). These patients also frequently show deficiencies in vitamins and trace elements, increasing the likelihood of anemia and altered cognitive status. The etiology of malnutrition in ALD patients is multifactorial and complex and includes inadequate dietary intake, abnormal absorption and digestion, increased skeletal and visceral protein catabolism, and abnormal interactions between ethanol and lipid metabolism. Most nutritional measures derive from general chronic liver disease recommendations. Recently, many patients with ALD have been diagnosed with metabolic syndrome, which requires individualized treatment via nutritional therapy to avoid overnutrition. As ALD progresses to cirrhosis, it is frequently complicated by protein-energy malnutrition and sarcopenia. Nutritional therapy is also important in the management of ascites and hepatic encephalopathy as liver failure progresses. The purpose of the review is to summarize important nutritional therapies for the treatment of ALD.

The Impact of Metabolic Syndrome on the Prognosis of High-Risk Alcoholic Hepatitis Patients: Redefining Alcoholic Hepatitis.

Background: Alcoholic hepatitis (AH) is characterized by acute symptomatic hepatitis associated with heavy alcohol use. This study was designed to assess the impact of metabolic syndrome on high-risk patients with AH with discriminant function (DF) score ≥ 32 and its effect on mortality. Methods: We searched the hospital database for ICD-9 diagnosis codes of acute AH, alcoholic liver cirrhosis, and alcoholic liver damage. The entire cohort was categorized into two groups: AH and AH with metabolic syndrome. The effect of metabolic syndrome on mortality was evaluated. Also, an exploratory analysis was used to create a novel risk measure score to assess mortality. Results: A large proportion (75.5%) of the patients identified in the database who had been treated as AH had other etiologies and did not meet the American College of Gastroenterology (ACG)-defined diagnosis of acute AH, thus had been misdiagnosed as AH. Such patients were excluded from analysis. The mean body mass index (BMI), hemoglobin (Hb), hematocrit (HCT), and alcoholic liver disease/non-alcoholic fatty liver disease index (ANI) were significantly different between two groups (P < 0.05). The results of a univariate Cox regression model showed that age, BMI, white blood cells (WBCs), creatinine (Cr), international normalized ratio (INR), prothrombin time (PT), albumin levels, albumin < 3.5, total bilirubin, Na, Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), MELD ≥ 21, MELD ≥ 18, DF score, and DF ≥ 32 had a significant effect on mortality. Patients with a MELD greater than 21 had a hazard ratio (HR) (95% confidence interval (CI) of 5.81 (2.74 - 12.30) (P < 0.001). The adjusted Cox regression model results showed that age, Hb, Cr, INR, Na, MELD score, DF score, and metabolic syndrome were independently associated with high patient mortality. However, the increase in BMI and mean corpuscular volume (MCV) and sodium significantly reduced the risk of death. We found that a model including age, MELD ≥ 21, and albumin < 3.5 was the best model in identifying patient mortality. Our study showed that patients admitted with a diagnosis of alcoholic liver disease with metabolic syndrome had an increased mortality risk compared to patients without metabolic syndrome, in high-risk patients with DF ≥ 32 and MELD ≥ 21. A bivariate correlation analysis revealed that patients with AH with metabolic syndrome were more likely to have infection (43%) compared to AH (26%) with correlation coefficient of 0.176 (P = 0.03, CI: 0.018 - 1.0). Conclusion: In clinical practice, the diagnosis of AH is inaccurately applied. Metabolic syndrome significantly increases the mortality risk in high-risk AH. It signifies that the presence of features of metabolic syndrome modifies the behavior of AH in acute settings, warranting different therapeutic strategies. We propose that in defining AH, patients overlapping with metabolic syndrome may need to be excluded as their outcome is different with regard to risk of renal dysfunctions, infections and death.

Epidemiology and Disease Burden of Alcohol Associated Liver Disease.

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.

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.

Recaída en el consumo de alcohol después del trasplante de hígado por hepatopatía alcohólica / Alcohol relapse after liver transplantation for alcoholic liver disease

Introducción. La enfermedad hepática inducida por uso de alcohol se ha considerado una enferme-dad autoinfligida que limitaba el acceso al trasplante. Actualmente es una de las principales indicacio-nes de trasplante hepático en Colombia y el mundo, con excelente sobrevida. Metodología. Estudio descriptivo observacional donde se realizó una caracterización de los pacientes con trasplante hepá-tico por hepatopatía alcohólica en una institución de cuarto nivel, que incluyó un estudio cualitativo de la recaída en el consumo de alcohol postrasplante. Resultados. De 87 pacientes de una cohorte inicial de 96 pacientes trasplantados entre 2003 y 2021, se describieron características sociodemo-gráficas, comorbilidades previas y adquiridas posterior al trasplante, supervivencia del paciente y del injerto, y factores de riesgo asociados al consumo de alcohol. Adicionalmente, a 65 pacientes se les pudo realizar una entrevista estructurada para evaluar la recaída en el consumo de alcohol, 41,53 % volvieron a consumir alcohol; 23,07 % en patrón de riesgo de recaída y 18,46 % en patrón de slip (desliz). El antecedente de hepatitis alcohólica tuvo un RR de 3,273 (1,464­7,314) y p=0,007 para recaída en el consumo de alcohol, y la comorbilidad psiquiátrica un RR de 2,395 (1,002­5,722) y p=0,047. Finalmente, haber presentado al menos una recaída postrasplante tuvo un RR de 5,556 (1,499­20,588) con p=0,005 para rechazo del injerto. Conclusiones. La recaída en el consumo de alcohol fue frecuente, la hepatitis alcohólica previa y la comorbilidad psiquiátrica son factores de riesgo asociados. La recaída se asoció a rechazo del injerto sin afectar la sobrevida del paciente.

Introduction. Alcohol-induced liver disease has been considered a self-inflicted disease that limited access to transplantation. It is currently one of the main indications for liver transplantation in Colom-bia and the world, with excellent survival. Methodology. Observational descriptive study where a characterization of liver transplant patients due to alcoholic liver disease was carried out in a fourth level institution, which included a qualitative study of relapse in post-transplant alcohol consumption. Results. Of 87 patients from an initial cohort of 96 transplant patients between 2003 and 2021, sociodemographic characteristics, previous and acquired post-transplant comorbidities, patient and graft survival, and risk factors associated with alcohol consumption were described. Additionally, 65 patients were able to undergo a structured interview to assess relapse in alcohol consumption, 41.53% returned to alcohol consumption; 23.07% in risk relapse pattern, and 18.46% in slip pattern. The history of alcoholic hepatitis had a RR of 3.273 (1.464-7.314) and a p=0.007 for relapse in alcohol consumption, and psychiatric comorbidity a RR of 2.395 (1.002-5.722) and a p=0.047. Finally, having presented at least one post-transplant relapse had a RR of 5.556 (1.499-20.588) with ap=0.005 for graft rejection. Conclusions. Relapse in alcohol consumption was fre-quent, previous alcoholic hepatitis and psychiatric comorbidity were associated risk factors. Relapse was associated with graft rejection without affecting patient survival.