Alcoholic Etiology Research Articles

Impact of MASLD on Portal Vein Thrombosis Following Hepatectomy for Liver Cancer.

Background: Due to the increasing global prevalence of non-alcoholic fatty liver disease (NAFLD), which is closely linked to metabolic disorders, there has been a rise in the number of patients with NAFLD undergoing hepatectomy. The metabolic disorders, as well as NAFLD, increase venous thrombotic risk. NAFLD was recently updated to a new concept of hepatic steatosis: metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the impact of MASLD on post-hepatectomy portal vein thrombosis (PH-PVT). Methods: A total of 106 patients who underwent hepatectomy for liver cancer were included. Steatotic liver disease (SLD) was diagnosed using a CT L/S ratio of <1.1. SLD was classified as follows: MASLD, SLD associated with metabolic factors without alcohol consumption; MetALD, SLD with metabolic factors and moderate alcohol consumption; Other SLD, alcohol or other specific etiology of SLD; and No SLD, no hepatic steatosis. Results: PH-PVT was detected in 12/106 patients (11.3%); MASLD, 7/20 (35%); MetALD, 1/5 (20%); Other SLD, 1/13 (8%); and No SLD, 3/68 (4.4%). Multivariate analysis showed that the MASLD group (including MASLD and MetALD) (odds ratio [OR], 9.27) and left lateral sectionectomy (OR, 6.22) were significant independent risk factors for PH-PVT. Additionally, the incidence of PH-PVT was significantly higher in patients with MASLD than in those without SLD, along with metabolic factors, excluding alcohol consumption. Conclusions: MASLD and MetALD were identified as independent and significant risk factors for PH-PVT. Consideration was given to the idea that hepatic steatosis and metabolic dysfunction play synergistic roles in PH-PVT development.

Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis

IntroductionAlcohol consumption and hepatitis B virus (HBV) infection are common risk factors for hepatocellular carcinoma (HCC). However, few studies have focused on elucidating the mechanisms of HCC with combined alcohol and HBV etiology. ObjectivesWe aimed to investigate the molecular features of alcohol and HBV on HCC and to seek out potential therapeutic strategies. MethodsTwo independent cohorts of HCC patients (n = 539 and n = 140) were included to investigate HCC with synergetic alcohol and HBV (AB-HCC) background. Patient-derived cell lines, organoids, and xenografts were used to validate the metabolic fragile. High-throughput drug screening (1181 FDA-approved anticancer drugs) was leveraged to explore the potential therapeutic agents. ResultsHere, we delineated AB-HCC as a distinctive metabolic subtype, hallmarked by oncogenic cholesterol, through the integration of clinical cohorts, proteomics, phosphoproteomics, and spatial transcriptome. Mechanistically, our findings revealed that cholesterol directly binds to CSNK2A1 (Casein Kinase 2 Alpha 1), augmenting its kinase activity and leading to phosphorylation of IGF2R (Insulin-Like Growth Factor 2 Receptor) at Ser2484. This cascade rewires lipid-driven mitochondrial oxidative phosphorylation, spawns reactive oxygen species measured by malondialdehyde assay, and perpetuates a positive feedback loop for cholesterol biosynthesis, ultimately culminating in tumorigenesis. Initial transcriptional activation of CSNK2A1 is driven by upregulation of RAD21 in AB-HCC. Our cholesterol profiling exposes AB-HCC’s compensatory mechanism of AB-HCC, which capitalizes on both uptake and biosynthesis of cholesterol to confer survival edge. Moreover, high-throughput drug screening coupled with in vivo validation has uncovered the susceptibilities of AB-HCC, which can be effectively addressed by a combination of dietary cholesterol restriction and oral administration of Fostamatinib. The CSNK2A1-mediated cholesterol biosynthesis pathway has been implicated in various cancers characterized by cholesterol metabolism. ConclusionThese findings not only pinpoint the oncogenic metabolite cholesterol as a hidden culprit in AB-HCC subtype, but also enlighten a novel combination strategy to rejuvenate tumor metabolism.

Dexamethasone improves clinical and biological tolerance of transcatheter arterial chemoembolization for hepatocellular carcinoma

BackgroundTransarterial chemoembolization (TACE) is widely used for hepatocellular carcinoma treatment but side effects hamper tolerance. Dexamethasone reduces TACE side effects in patients with viral hepatitis, but data regarding alcohol and metabolic liver diseases are lacking. We aimed to evaluate the efficacy of dexamethasone in preventing TACE-associated adverse events in European populations with predominantly alcoholic and metabolic cirrhosis. MethodsAll cirrhotic patients undergoing TACE in our center between 2017 and 2021 were included. Dexamethasone was added to our protocol from 2019. Using a quasi-experimental study design, patients before and after introduction of dexamethasone in our procedure were compared. Factors associated with TACE adverse events were assessed by univariate and multivariate analysis. A sensitivity analysis was performed using propensity scores for covariate adjustment. Results234 patients undergoing 398 TACE procedure were included. Cirrhosis was predominantly of alcohol or metabolic etiology (86.7 %). Dexamethasone was administered in 99 procedures (24.9 %). Incidence of fever and encephalopathy at day 2 after TACE was lower in the Dexamethasone group (p < 0.001; p = 0.02 respectively). In multivariate analysis, dexamethasone was associated with lower occurrence of fever (OR=0.03; p < 0.001), lower analgesics use (OR=0.11; p = 0.002), milder liver and kidney function impairment (OR=0.98; p = 0.001 and OR=0.94; p < 0.001 for bilirubin and creatinine variation respectively). Propensity score-adjusted analyses yielded similar results. ConclusionDexamethasone improves TACE tolerance in a population of predominantly metabolic and alcohol cirrhosis.

Nutritional risk assessment using the Nutritional Prognostic Index predicts mortality in Advanced Chronic Liver Disease patients

ObjectivesEarly clinical prognosis and mortality reduction remains a challenge in chronic liver disease (CLD). The full potential of the Nutritional Prognostic Index (NPI) for nutritional assessment and management in CLD patients remains unexplored. The aim of this study was to establish an NPI cutoff point for the identification of nutritional risk in advanced CLD (ACLD) patients, as well as to assess the NPI's ability to predict ACLD-associated mortality. MethodsThis ethically approved prospective cohort study investigated malnutrition risk using both the NPI and the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) in patients hospitalized for ACLD. NPI reference values were determined using a receiver operating characteristic curve. Associations between nutritional risk identified by the RFH-NPT and the NPI were assessed using Fisher's exact test, and agreement between tools was assessed using the Kappa index. The association between NPI-defined nutritional risk and 12-mo mortality was examined using Pearson Chi-square test. ResultsThe sample population consisted of 120 adults, comprising 84 (70%) male and 57 (50.9%) of alcoholic etiology and presenting as Child-Pugh A, B, or C at admission. The identified cutoff point for NPI was <41, identifying nutritional risk in 82.5% of patients. The NPI presented a statistically significant association with the RFH-NPT, with a substantial agreement coefficient of 0.34. An association between NPI <41 cutoff and mortality were observed, with 82.1% of the sample below cutoff experiencing mortality within 12 mo. ConclusionsThe NPI is a valuable nutritional marker for the identification of nutritional risk in ACLD and is a simple and effective assessment tool that can aid in early CLD prognosis assessment. Validation, however, remains necessary in other CLD populations of different etiologies.

VALUE OF AMINOTRANSFERASES IN LIVER CIRRHOSIS

Aim: To ditermine values of ASAT and ALAT and their ratio in different stages of liver cirrhosis. Material and methods: A retrospective study was conducted, including patients with newly diagnosed liver cirrhosis from 01.01. 2017 to 31.12. 2021. Of all, 258 (71%) were men and 103 (29%) were women. The mean age of the study population was 57±11.4 years, with alcohol as the leading etiology in 262 (72.6%) of all cases. AT were measured at an upper reference limit of 40UI/ml. All were staged by Child-Pough and MELD Na score. IBM SPSS 26 and Excel statistics for data processing were used at a significant level of p&lt; 0.05. Results: Of all 361 individuals, normal AT were measured at 89 (24.7%), at 96 (25.76%) only with normal ASAT and at 233 (66.77%) only with normal ALAT. The mean value of ASAT increases significantly depending on the Child stage (p=.004) and is close to the significance of MELD Na (p=.036). Mean ALAT values were minimal to moderately elevated, with no significant association with them (p=.647, p=.020). 90% of individuals had an ASAT/ALAT ratio above 1, which showed substantial dependence on Child and MELD Na (p=.000, p=.000). A ratio above 2 was found at 194 (53.7%) mainly in Child C, which was associated with alcohol etiology. Conclusion: The absolute values of ASAT and ALAT have no relationship with the severity of liver cirrhosis, unlike their ratio, which significantly increases.

Diagnostic models for differentiating fatty liver disease of alcohol and non-alcoholic genesis

Introduction. Fatty liver disease is the largest contributor to the burden of chronic liver disease worldwide. Current approaches do not allow sufficient differentiation between alcoholic and non-alcoholic etiology of the process.Aim. Create diagnostic panels including electrical and viscoelastic parameters of erythrocytes to differentiate fatty liver disease of alcoholic and non-alcoholic genesis.Materials and methods. The study included 38 men (47.5 ± 2.9 years) with NAFLD; 31 men with alcoholic fatty liver disease (AFLD) (45.1 ± 3.1 years) according to ultrasound of the abdominal organs, the degree of fibrosis did not exceed F1 (FibroScan® 502). Electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis using an electro-optical cell detection system. To determine the parameters of erythrocytes – biomarkers for distinguishing between AFLD and NAFLD, a system of machine learning methods – Random Forest was used.Results. Electrical, viscoelastic parameters of erythrocytes, which are biomarkers for distinguishing between AFLD and NAFLD, were established: cell membrane capacity (p = 1.21E-11), the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz (p = 2.38E-08), cell polarizability at a frequency of 106 Hz (p = 9.38E-08), the speed of erythrocyte movement to the electrodes (p = 4.32E-06), the magnitude of the dipole moment (p = 1.66E-05), relative polarizability (p = 2.35E-05), the index of erythrocyte destruction at a frequency of 5 x 105 Hz (p = 0.016), the position of the crossover frequency (p = 2.13E- 06). The diagnostic model, including five parameters – the position of the crossover frequency, cell polarizability at a frequency of 106 Hz, cell electrical conductivity, membrane capacity, the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz, provided the highest diagnostic accuracy with an AUC of 0.975, a sensitivity of 96.3%, and a specificity of 91.8% in differentiating between AFLD and NAFLD.Conclusion. Thus, systematic exposure to alcohol modifies the structure of erythrocyte membranes, leading to a decrease in the surface charge, the barrier function of membranes, reducing the resistance of cells, their ability to deform, which determines the key role of the identified electrical, viscoelastic parameters of erythrocytes in differentiating between AFLD and NAFLD.

An intensified trans-sectoral nutritional intervention in malnourished patients with chronic pancreatitis improves diseases prognosis and identifies potential biomarkers of nutritional status.

Malnutrition is a common complication in chronic pancreatitis and associated with reduced quality of life and life expectancy. Nutritional support is considered mandatory in malnourished patients with chronic pancreatitis but there is only scarce evidence on optimal treatment modalities and the efficacy of nutrition therapy. Here, we investigated the feasibility and efficacy of an intensified nutritional intervention in malnourished patients with chronic pancreatitis and aimed to identify suitable indicators for monitoring nutritional status. We performed a single-arm feasibility study, in which malnourished patients with chronic pancreatitis received an intensified trans-sectoral nutritional intervention for 6 months. Multimodal treatment comprised face-to-face dietary counseling, oral nutritional supplementation, and a complementary telephone-based nutrition and exercise coaching. Patients underwent follow-up examinations after 28, 90, and 180 days, when we assessed changes in anthropometric and body composition measures, muscle function, Chronic Pancreatitis Prognosis Score (COPPS), as well as blood parameters and intestinal microbiota composition. Eleven out of 73 patients initially screened for study participation were enrolled in the trial of which 9 subjects (age (mean ± SD): 56.2 (±14.8) years; male: 67%; alcoholic etiology: 44%) underwent the complete intervention. Patients gained a median of 5.3 kg (8.6%) body weight, including 1.6 kg skeletal muscle mass, and significantly increased gait speed (p < 0.001). Ameliorated nutritional status and muscle function were associated with increased blood levels of IGF-1 and cholinesterase as well as altered gut microbiota composition on the phyla and genera level. Moreover, significant improvements in COPPS indicated reduced disease severity after 90 and 180 days. Malnourished patients with chronic pancreatitis benefit from intensified nutritional therapy. Besides ameliorated nutritional status, a multimodal intervention can improve muscle function as well disease prognosis. Future studies are needed to prove superiority to standard-of-care and to validate potential biomarkers for prospective monitoring of nutritional status. https://clinicaltrials.gov/study/NCT04476056, NCT04476056.

A Nonrandomized Pilot Study to Investigate the Acceptability and Feasibility of LivR Well: A Multifaceted 28-Day Home-Based Liver Optimization Program for Acute-on-Chronic Liver Failure

Background and AimsAcute-on-chronic liver failure (ACLF) has a 22-74% 28-day mortality rate and 30-40% 30-day re-admission rate. We investigated the acceptability and feasibility of a multimodal community intervention for ACLF. MethodsA single-arm, non-randomized pilot study of consecutive participants with ACLF was conducted in a tertiary health service. Participants received weekly medical and nursing reviews, dietetics, physiotherapy, pharmacy, social work, addiction medicine, and/or neuropsychiatry. A digital platform included remote weight monitoring, and online surveys. The primary outcome was acceptability/feasibility. Secondary outcomes included safety, mortality, re-admission, liver disease severity, and costs. ResultsFifty-nine patients were enrolled with median age 51 years (IQR: 45-59); majority alcohol etiology (74%),and median Model for End-Stage Liver Disease Sodium (MELD-Na) score 16 (IQR: 12-21). LivR Well was acceptable with low attrition (8/59), adherence to the program including home visits (mean 8.4±4.2) and consultations (mean 2.4±1.5) per patient. This was supported by positive feedback and themes identified through a qualitative sub-analysis. Feasibility was demonstrated by recruitment rate of 4.94 patients/month and 86% completion. Mortality was lower than expected at 3%, 30-day readmission rate was 15%, and median MELD-Na score reduced to 15 (p = 0.01). Median 6-month costs reduced from $30,454 (IQR: 21953-$65657) to $17, 657 ($4249-42876) (p=0.009). The total 6-month healthcare cost was $1,868,859 (95% CI 1,081,821-2,655,897) compared to $2,518,227 (95% CI 1,959,610-3,076,844). ConclusionLivR Well was acceptable, feasible and safe with low short-term mortality and readmission rates. Healthcare costs were reduced by 26% driven by a 40% reduction in 30-day re-admission. Further evaluation includes a randomized, controlled trial of LivR Well compared to standard care.

Vliv polymorfizmů PNPLA3 rs738409 a TM6SF2 rs58542926 dárce a příjemce na dlouhodobé přežívání pacientů po transplantaci jater

Summary Introduction: The variants rs738409 c.444C&gt;G (p.I148M) in patatin-like phospholipase domain-containing 3 (PNPLA3) and rs58542926 c.499G&gt;A (p.E167K) in TM6SF2 (transmembrane 6 superfamily member 2) are significant genetic risk factors of development and progression of non-alcoholic fatty liver disease (NAFLD). In both variants, increased liver-specific mortality was described, while the impact on all-cause mortality was not proved. The aim of the study was to evaluate the impact of PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively on long-term patient survival after LT. Methods: We evaluated long-term patient survival in a cohort of 268 adult LT recipients, in whom PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively were available and steatosis was evaluated in liver graft biopsy 6–30 months after LT. The median fol low-up was 17 years. The Kaplan-Meier model was used for the survival estimates and the Cox proportional hazard model was used to assess the predictive value of the chosen variables. Results: Increased recipient age (P &lt; 0.001), male sex (P = 0.014), alcoholic (P = 0.021) or HCV (P = 0.042) etiology of liver cirrhosis, and presence of hepatocellular carcinoma (P = 0.009) negatively influenced long-term patient survival after LT. PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the recipient and donor respectively had no effect on patient survival. Conclusion: Although PNPLA3 c.444G and TM6SF2 c.499A variants of the donor increase the risk of steatosis of the liver graft after LT, we did not prove a negative impact of these genotypes of the donor and recipient on long-term patient survival after LT. Keywords PNPLA3, TM6SF2, steatosis, MASLD, NAFLD, liver transplantation, patient survival

Dexamethasone and N-acetylcysteine before transarterial chemoembolization in hepatocellular carcinoma: A Western perspective.

Post-embolization syndrome (PES) is the most common complication in patients with hepatocellular carcinoma treated with transarterial chemoembolization. Many strategies have been evaluated to reduce the incidence of PES, but no standard prevention guidelines currently exist. In a single-center, placebo-controlled trial, Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES (from 80% to 6%), of post-procedural liver decompensation (from 14% to 0%), and a shorter hospital stay (4 days vs 6 days), alongside an acceptable safety profile. The results of this study raise several controversial points regarding their applicability in the Western world. In the West, there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis, so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone prophylaxis. Furthermore, in the West, there is a preferred use of drug-eluting beads loaded with doxorubicin, which are associated with a lower incidence of PES. A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.

Comparison of gastrointestinal bleeding in patients with and without liver cirrhosis

Objectives Upper gastrointestinal bleeding (GIB) in patients has been well-characterized in liver cirrhosis but studies on lower GIB are limited. The clinical characteristics, management and outcomes in patients with and without liver cirrhosis was compared to determine the overall features of GIB in patients with liver cirrhosis compared with non-cirrhotics. Methods A retrospective study on cirrhotics hospitalized for GIB 2010–2021, matched with control group of non-cirrhotics (1:4) for upper vs. lower GIB. Patients with overt bleeding leading to hospitalization were included. Results Overall, 396 patients had cirrhosis, 267 (67%) men, median age 62, alcoholic etiology 177/396 (45%), median MELD 12 (range 6–32). Overall 102 cirrhotics had GIB, matched with 391 non-cirrhotics. Overall 87 (85%) cirrhotic patients had upper and 15% lower GIB. Compared to non-cirrhotics, the cause of GIB was more commonly acute variceal bleeding (AVB) (42% vs. 1%), hemorrhoids 40% vs. 6% (p = 0.002), less commonly gastric ulcer 13% vs. 31% (p < 0.001), duodenal ulcer 9% vs. 29% (p < 0.001), 5% of cirrhotics used NSAIDs vs. 26% of controls (p < 0.001). Rebleeding occurred in 14% of cirrhotics vs. 3% in controls (p < 0.001). Only one cirrhotic patient (1%) died from GIB vs. 0.8% of controls within 45 days. Overall mortality 45 days after hospitalization was 10% in cirrhotics vs. 5% in controls (p < 0.001) Conclusions Bleeding from gastric and duodenal ulcers were less common in cirrhotics than in controls. Bleeding from hemorrhoids was more common in cirrhotics. Mortality due to GIB was low in both groups but overall mortality was significantly higher in cirrhotics.

Prevalence of exocrine pancreatic insufficiency at 12 months after acute pancreatitis: a prospective, multicentre, longitudinal cohort study

Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort. In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200μg/g; severe FE-1 level ≤100μg/g; mild FE-1 101-200μg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398. EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7±14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n=39) developed severe EPI at 12 months (prevalence 12.8%). EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening. This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc.

Alcoholic Etiology, Severity of Liver Disease, and Post-Transplant Adherence Are Correlated with Worse Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) in Liver Transplant Candidates.

Introduction: Psychosocial pre-transplant evaluation in patients undergoing liver transplantation (LT) could help identify those patients at higher risk of pharmacological non-adherence, organ rejection, and mortality. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a validated tool for assessing LT candidates' psychosocial well-being. Data on the ability of the SIPAT evaluation to predict post-transplant outcomes are sparse. Material and Methods: clinical and psychosocial data from a sample of 134 candidates for LT were analyzed. Moreover, the association between pre-transplant psychosocial evaluation and post-transplant clinical outcomes, including organ rejection, mortality, and immunosuppressant drug adherence, was calculated. Results: At the pre-transplant evaluation, patients who showed high SIPAT scores (77, 57%) also had more liver disease assessed by model for end-stage liver disease (MELD; F = 5.04; p < 0.05), alcoholic etiology (F = 35.80; p < 0.001), encephalopathy (F = 5.02; p < 0.05), and portal hypertension (F = 7.45; p < 0.01). Of the 51 transplant patients, those who had a high pre-transplant SIPAT score showed lower post-transplant immunosuppressive adherence, linked to more frequent immunological events. Conclusions: Patients with an alcoholic etiology of liver disease and more severe liver dysfunction are likelier to not adhere to medical prescriptions following transplantation. Current data suggests that this specific group of patients could benefit from early psychological pre-habilitation before undergoing liver transplantation.

Characteristics and Outcomes Among US Commercially Insured Transgender Adults With Cirrhosis: A National Cohort Study.

The National Institute on Minority Health and Health Disparities has noted that transgender individuals experience unique health disparities. We sought to describe the landscape of transgender patients with cirrhosis. We identified all transgender and cisgender adults in Optum's deidentified Clinformatics Data Mart Database between 2007 and 2022 using validated billing codes and calculating age-standardized prevalence of cirrhosis among cisgender vs transgender adults. Among those with incident cirrhosis diagnoses, we calculated age-standardized incidence densities of liver-related outcomes (decompensation, transplantation, hepatocellular carcinoma) and all-cause mortality. We examined 5-year survival using inverse probability treatment weighting to balance transgender and cisgender populations on demographic and clinical characteristics. Among 64,615,316 adults, 42,471 (0.07%) were transgender. Among 329,251 adults with cirrhosis, 293 (0.09%) were transgender. Trans- (vs cis-) genders had higher prevalence of cirrhosis (1,285 [95% confidence interval (CI) 1,136-1,449] per 100,000 vs 561 [559-563] per 100,000). Among adults with cirrhosis, trans- (vs cis-) genders had higher proportions of anxiety (70.7% [56.9-86.9] vs 43.2% [42.7-43.8]), depression (66.4% [53.3-81.7] vs 38.4% [37.9-38.9]), HIV/AIDS (8.5% [3.9-16.1] vs 1.6% [1.5-1.7]), and alcohol (57.5% [46.0-71.1] vs 51.0% [50.5-51.6]) and viral (30.5% [22.8-39.8] vs 24.2% [23.9-24.5]) etiologies, although etiologies had overlapping CIs. Trans- (vs cis-) genders had similar incidence densities of death (12.0 [95% CI 8.8-15.3] vs 14.0 [13.9-14.2] per 100 person-years), decompensation (15.7 [10.9-20.5] vs 14.1 [14.0-14.3]), and liver transplantation (0.3 [0.0-0.8] vs 0.3 [0.3-0.4]). In inverse probability treatment weighting survival analysis, transgender and cisgender individuals had similar 5-year survival probabilities (63.4% [56.6-71.1] vs 59.1% [58.7-59.4]). Trans- (vs cis-) gender adults have double the prevalence of cirrhosis, and the majority have a diagnosis of anxiety and/or depression. These results are informative for researchers, policymakers, and clinicians to advance equitable care for transgender individuals.

Predicting the dynamics of organ failure in patients with acute pancreatitis depending on the mean platelet volume

BackgroundThe aim of this study is to determine the correlation between the blood serum mean platelet volume (MPV) and the dynamics of the OF course during the early phase in patients with moderately severe and severe acute pancreatitis (AP). MethodsThe predetermined criterion was the presence of the OF according to the revised Atlanta criteria 2012 for moderately severe and severe AP. A prospective sample of patients was stratified by severity, and two groups were defined based on MPV. Demographic indicators, comorbidities and clinical outcomes were compared between these groups. Multifactorial analysis determined whether an elevated MPV is independently associated with early OF and other unfavorable outcomes. ResultsOut of 108 patients, 20 had moderately severe AP and 88 had severe AP. The blood serum MPV, measured within 72 h of the onset of AP symptoms was lower 11.8 fL in 32 patients and equal to or greater 11.8 fL in 76 patients. Patients with elevated MPV were older (63 vs. 48 years), had obesity (59.2 % vs. 25 %), diabetes mellitus (DM) (51.3 % vs. 12.5 %), ischemic heart disease (70.8 % vs. 28.1 %) and more frequently experienced persistent OF (93.4 % vs. 53.1 %) compared to those with MPV lower 11.8 fL. The incidence of early OF increased proportionally with the severity of MPV (81.6 % vs. 34.4 % in the group with MPV lower 11.8 fL, Ptrend < 0.0001). In multifactorial analysis, adjusted for body mass index and DM, MPV equal to or greater 11.8 fL was independently associated with early OF. ConclusionsElevated blood serum MPV of patients with AP are independently and proportionally correlated with early organ failure in patients with alcoholic and idiopathic etiology of AP. Key messageThe study provides an evaluation of MPV as a prognostic marker for organ failure within the initial 7 days following the onset of acute pancreatitis symptoms. Additionally, alterations in MPV were identified in patients with acute pancreatitis who had diabetes or ischemic heart disease within the first 24 h of hospitalization.

Impact of Cirrhosis Etiology on the Risk for Venous Thromboembolism.

Cirrhosis is associated with an increased risk for both bleeding and venous thromboembolic (VTE) complications. The data regarding the impact of etiology of cirrhosis on VTE risk is poorly understood. In this retrospective observational analysis of the US Nationwide readmissions database 2019, we identified hospitalized patients who had cirrhosis from alcohol, viral, or nonalcoholic steatohepatitis (NASH) etiologies. We identified patients who had acute VTE, chronic/history of VTE, and portal venous thrombosis (PVT). Overall VTE risk was defined as the composite of acute and chronic VTE or PVT. The impact of etiology of cirrhosis on the crude and risk adjusted rates of VTE and PVT was studied. Of 432,383 patients with cirrhosis, 41.4% patients had NASH-cirrhosis, 39.7% had alcohol-related cirrhosis, and 18.9% had viral cirrhosis. The overall VTE rate was highest in patients with NASH cirrhosis (10.8%) followed by viral cirrhosis (9.7%) and alcohol-related cirrhosis (7.5%; P < 0.001). Similar results were observed for acute and chronic VTE. After risk adjustment, patients with NASH (OR 1.48 95% CI 1.42-1.54) and viral cirrhosis (OR 1.22 95% CI 1.17-1.29) had significantly higher overall VTE risk compared with alcohol-related cirrhosis. When separately evaluated, the adjusted risk for acute and chronic VTE was similar between patients with alcohol-related and viral cirrhosis but higher with NASH cirrhosis. PVT rate was highest with viral cirrhosis (4.3%) followed by NASH (2.8%) and alcohol-related cirrhosis (2.4%; P < 0.001). The adjusted risk of PVT was higher with viral (OR 1.61 95% CI 1.50-1.72) and NASH cirrhosis (OR 1.41 95% CI 1.31-1.52). NASH cirrhosis was associated with a higher VTE risk compared with alcohol-related and viral etiologies. As NASH cirrhosis increases in prevalence as the major etiology of cirrhosis, it is important to understand the increased VTE risk associated with this condition to improve management strategies and patient outcomes.

SEVERE ACUTE PANCREATITIS REVEALING EXTENSIVE AORTIC DISSECTION: A CASE REPORT AND LITERATURE REVIEW

Severe acute pancreatitis is a frequent reason for hospitalization in the intensive care unit. Biliary and alcoholic etiologies are the most frequent. Vascular etiology, particularly ischemic etiology, is rare. Its often-serious consequences raise the question of how to proceed: should surgical treatment be provided, or should medical care be delayed? This study reports the case of an 87-year-old patient, known to be hypertensive, admitted to the emergency department of the Oued Eddahab military hospital with excruciating epigastric abdominal pain. Investigations revealed severe acute pancreatitis of ischemic origin following thoracoabdominal aortic dissection extending to the superior mesenteric artery. A review of the literature revealed only 15 similar cases of acute pancreatitis of ischemic origin associated with aortic dissection. This underlines the rarity of this situation, and the absence of standardized recommendations for the management of this exceptional situation, which presents the clinician with the dilemma of whether to opt for surgical or medical management. This case demonstrated the exceptional role of medical imaging in the context of severe acute pancreatitis, in terms of diagnosis, prognosis and etiology. It also highlighted the importance of an individualized approach based on multidisciplinary consultation, given the absence of recommendations and the paucity of literature.

Matrix metalloproteinases and morphological features in chronic liver diseases

Aim of investigation. To study the relationship of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) with a morphological features of chronic liver diseases (CLD). Materials and methods. 76 patients with CLD of viral or alcoholic etiology aged from 18 to 64 years were examined. Chronic hepatitis was diagnosed in 59 patients, liver cirrhosis (class A according Child-Pugh score) was detected in 17 cases. The control group consisted of 72 practically healthy people. The blood levels of MMP-1, MMP-9, TIMP-1 were determined by enzyme immunoassay, and the ratio of TIMP-1/MMP-1, TIMP-1/MMP-9 was calculated. Results. There was an increase in the concentration of TIMP-1 and MMP-1 in the blood, the ratio of TIMP-1/MMP-9, a decrease in the ratio of TIMP-1/MMP-1 in CLD. In moderate and severe histological activity of CLD the levels of TIMP-1 and MMP-9 were higher, and the ratio of TIMP-1/MMP-9 was lower than in patients with histological activity index values less than 9 points. In patients with liver cirrhosis (fibrosis F4), the maximum values of TIMP-1, TIMP-1/MMP-1 and TIMP-1/MMP-9 were determined, which differed from the corresponding values for fibrosis F0-1 and F2. The blood levels of MMP-9 more than 410 ng/ml predicted severe inflammation in CLD with an accuracy of 82.9 %. The blood levels of TIMP-1 above 624 ng/ml, TIMP-1/MMP-1 more than 37.1, TIMP-1/MMP-9 more than 7.33 had high accuracy (82.9, 80.3, 80.3 %, respectively) in the prediction of liver cirrhosis (fibrosis F4). Conclusion. The imbalance in the matrix metalloproteinase system is associated with the morphological features of CLD and is characterized by hyperexpression of MMP-9 in cases of severe inflammation and increased activity of TIMP-1 in severe stages of liver fibrosis.

Epidemiology, therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont, Italy.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate. HCC patients have increasingly complex and constantly changing characteristics, thus up-to-date and comprehensive data are fundamental. To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019. In this retrospective study, we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at "Santa Croce e Carle" Hospital in Cuneo (Italy) between 1 January 2010 and 31 December 2019. To highlight possible changes in HCC patterns over the 10-year period, we split the population into two 5-year groups, according to the diagnosis period (2010-2014 and 2015-2019). Of the 328 HCC patients who were included (M/F 255/73; mean age 68.9 ± 11.3 years), 154 in the first period, and 174 in the second. Hepatitis C virus infection was the most common HCC risk factor (41%, 135 patients). The alcoholic etiology rate was 18%, the hepatitis B virus infection etiology was 5%, and the non-viral/non-alcoholic etiology rate was 22%. The Child-Pugh score distribution of the patients was: class A 75%, class B 21% and class C 4%. The average Mayo end-stage liver disease score was 10.6 ± 3.7. A total of 55 patients (17%) were affected by portal vein thrombosis and 158 (48%) by portal hypertension. The average nodule size of the HCC was 4.6 ± 3.1 cm. A total of 204 patients (63%) had more than one nodule < 3, and 92% (305 patients) had a non-metastatic stage of the disease. The Barcelona Clinic Liver Cancer (BCLC) staging distribution of all patients was: 4% very early, 32% early, 23% intermediate, 34% advanced, and 7% terminal. Average survival rate was 1.6 ± 0.3 years. Only 20% of the patients underwent treatment. Age, presence of ascites, BCLC stage and therapy were predictors of a better prognosis (P < 0.01). A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology (P < 0.05) and alpha-fetoprotein (AFP) levels (P < 0.01). In this study analyzing patients with a new diagnosis of HCC between 2010-2019, hepatitis C virus infection was the most common etiology. Most patients presented with an advanced stage disease and a poor prognosis. When comparing the two 5-year groups, we observed a statistically significant difference only in global etiology (P < 0.05) and AFP levels (P < 0.01).

Prediction and evaluation of a nomogram model for recurrent acute pancreatitis.

The purpose of this study was to investigate the influencing factors for recurrent acute pancreatitis and construct the nomogram model to predict the risk of recurrent acute pancreatitis. Patients diagnosed with acute pancreatitis in the Affiliated Hospital of Southwest Medical University were enrolled. We collected these patients' basic information, laboratory data, imaging information. Using Logistic regression and least absolute shrinkage and selection operator regression to select risk factor for Cross-Validation Criterion. To create nomogram and validated by receiver operator characteristic curve, calibration curves and decision curve analysis. A total of 533 patients with acute pancreatitis were included, including 99 recurrent acute pancreatitis patients. The average age of recurrent acute pancreatitis patients was 49.69 years old, and 67.7% of them were male. At the same time, in all recurrent acute pancreatitis patients, hypertriglyceridemic pancreatitis is the most important reason (54.5%). Regression analysis and least absolute shrinkage and selection operator regression showed that smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis were identified and entered into the nomogram. The area under the receiver operator characteristic curve of the training set was 0.747. The calibration curve showed the consistency between the nomogram model and the actual probability. In conclusion, some high-risk factors like smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis may predict recurrent pancreatitis and their incorporation into a nomogram has high accuracy in predicting recurrence.