Short-term Outcomes of Pancreatoduodenectomy in Patients with Liver Cirrhosis: A Systematic Review and Meta-analysis.

Objectives: The objective of this study was to compare short-term outcomes of pancreatoduodenectomy between patients with and without liver cirrhosis (LC). Background: It is not uncommon to encounter a patient with LC and with an indication for pancreatoduodenectomy; however, the knowledge on the outcomes after pancreatoduodenectomy in patients with LC is poorly developed. Methods: A systematic review and meta-analysis was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards. Short-term outcomes of pancreatoduodenectomy between patients with and without LC were compared using random effects modeling and the certainty of the evidence was assessed using the GRADE system. Results: Analysis of 18,184 patients from 11 studies suggested LC increased the risk of postoperative mortality (odds ratio [OR]: 3.94, P < 0.00001), major complications (OR: 2.25, P = 0.0002), and pancreatic fistula (OR: 1.73, P = 0.03); it resulted in more blood loss (mean difference [MD]: 204.74 ml, P = 0.0003) and longer hospital stay (MD: 2.05 days, P < 0.00001). LC did not affect delayed gastric emptying (OR: 1.33, P = 0.21), postoperative bleeding (OR: 1.28, P = 0.42), and operative time (MD: 3.47 minutes, P = 0.51). Among the patients with LC, Child-Pugh B or C class increased blood loss (MD: 293.33 ml, P < 0.00001), and portal hypertension increased postoperative mortality (OR: 2.41, P = 0.01); the other outcomes were not affected. Conclusions: Robust evidence with high certainty suggests LC of any severity with or without portal hypertension results in at least a fourfold increase in mortality and a twofold increase in morbidity after pancreatoduodenectomy. Whether such risks increase with the severity of the liver disease or decrease with optimization of underlying liver disease should be the focus of future research.

Atypical Presentation of Hepatocellular Carcinoma in a Chronic Alcoholic: Diagnostic Challenges and Therapeutic Approach.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, often arising in the context of chronic liver disease and cirrhosis. This case report describes the clinical presentation, diagnostic evaluation, and therapeutic intervention of a 72-year-old male with a long-standing history of alcohol use who presented with right hypochondrial pain. A 72-year-old male with a 20-year history of alcohol consumption presented with a one-month history of dull, aching pain in the right hypochondrium. Diagnostic imaging, including abdominal ultrasound and contrast-enhanced computed tomography (CECT), revealed significant hepatomegaly with nodular and irregular liver margins, free fluid in the abdomen and pelvis, and multiple hypodense nodules in both liver lobes. One nodule in the right lobe exhibited characteristic imaging features of hepatocellular carcinoma, including peripheral enhancement on the arterial phase and washout on the delayed phase. Histopathological analysis of a biopsy from the suspicious nodule confirmed the diagnosis of hepatocellular carcinoma. The patient was diagnosed with hepatocellular carcinoma based on clinical, radiological, and histopathological findings. He was subsequently scheduled for radiofrequency tumor ablation. This case underscores the importance of comprehensive diagnostic imaging and histopathological evaluation in patients with liver cirrhosis and suspected HCC, particularly in those with a history of chronic alcohol use.

Progression from Non-alcoholic Steatohepatitis to Advanced Liver Diseases and Mortality Among Medicare Patients.

INTRODUCTION: Non-alcoholic steatohepatitis (NASH) may progress to more advanced liver disease. This study aimed to characterize NASH progression and mortality in the Medicare population. METHODS: Patients with NASH in 100% Medicare fee-for-service claims accrued from 2015-2021 who were ≥ 66 years old at index diagnosis, continuously enrolled for ≥ 12 months prior to and ≥ 6 months following index (unless death), and had no evidence of other causes of liver disease were included. Diagnosis codes defined severity states: non-cirrhotic NASH, compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver transplant (LT). Survival analyses of disease progression and mortality were conducted for each state and by year of progression (Y1-5). Cox proportional hazards models assessed risk factors of worsening disease. RESULTS: Mean age and follow-up were 72.2 and 2.8 years in 14,806 unique patients (n = 12,990 NASH; 1899 CC; 997 DCC; 209 HCC; 140 LT). Progression rates were highest for patients with CC (11-37% for Y1-5), followed by DCC (3-18%), NASH (3-12%), and HCC (2-4%). Mortality rates were highest for patients with HCC (41-85% for Y1-5), followed by DCC (41-76%), LT (7-33%), CC (6-26%), and NASH (2-12%). Patients with any disease progression had a 5-year mortality rate more than double that of patients without progression (41% vs. 16%). Delayed progression from NASH was associated with lower mortality risk; the 5-year mortality rate was 26% lower for patients with progression in Y2 vs. Y1 (32% vs. 43%) and further decreased for progression in Y3-Y5. Risk factors included age, nursing home use, congestive heart failure, coagulopathy, fluid/electrolyte disorders, and unexplained weight loss. CONCLUSION: Medicare patients ≥ 66 years with NASH experience high risk of disease progression associated with increased mortality rates. Slower disease progression is associated with lower mortality rates, suggesting that therapies that can delay or prevent NASH progression may reduce morbidity and mortality.

Non-alcoholic steatohepatitis (NASH), or metabolic dysfunction-associated steatohepatitis, is a severe form of non-alcoholic fatty liver disease, or metabolic dysfunction-associated steatotic liver disease. NASH may progress to more advanced liver disease states that may lead to liver cancer, liver transplant, and/or death. The purpose of this study was to estimate Medicare patients' likelihood of progressing to a more advanced stage and death, and analyze how rates of death varied based on how quickly the disease progressed. We used 100% of Medicare fee-for-service claims accrued from 2015 to 2021 to understand who was diagnosed with NASH and how their disease progressed. We found that, within 5 years, 12% of patients with non-cirrhotic NASH progressed to a more advanced disease state. Those with more advanced disease were more likely to progress to the next advanced disease state and had higher risk of death compared to those with non-cirrhotic NASH. Patients with any disease progression had a higher 5-year death rate than those who did not progress, and patients with NASH progressing within 1 year had a higher 5-year death rate than those who progressed later. Older patients and patients with other health conditions showed an increased likelihood of progression or death. With therapies for NASH now available, this research can help patients and prescribers better understand the impact of NASH progression and help make informed treatment decisions.

Dietary total antioxidant capacity in relation to disease severity and risk of mortality in cirrhosis; results from a cohort study.

Liver Cirrhosis, defined as the final stage of chronic liver disease, may become more prevalent in the lower level of body defense against oxidation and inflammation. Therefore, we assessed the association of dietary total antioxidant capacity (DTAC) with the severity and mortality of cirrhosis in a cohort study. 120 newly diagnosed cirrhosis patients from Tehran, Iran, participated in this study. The patients' habitual diet was assessed using a 168-item validated food frequency questionnaire. Both ferric-reducing antioxidant potential (FRAP) and oxygen radical scavenging capacity (ORAC) methods were computed to achieve DTAC scores. The association between DTAC with disease severity and mortality was estimated by multivariate linear regression and cox proportional hazards regression models. Dietary total antioxidant capacity-ORAC had a significant inverse association with disease severity in both crude and adjusted models (P for trend: <0.001 and 0.016 respectively). The risk of mortality in the first and second tertiles of ORAC was 5.56 (95 % CI: 2.25-13.75; P = 0.002) and 3.20 (95 % CI: 1.25-8.19; P = 0.015) higher than those in the third category, respectively. In conclusion, a higher antioxidant capacity of diet is associated with less disease severity and mortality risk in cirrhosis.

Chemerin Levels in COVID-19 Are More Affected by Underlying Diseases than by the Virus Infection Itself.

BACKGROUND/OBJECTIVES: Chemerin is an adipokine involved in inflammatory and metabolic diseases, and its circulating levels have been associated with inflammatory parameters in various patient cohorts. Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which causes COVID-19, triggers inflammatory pathways. However, the association between serum chemerin levels and COVID-19 disease severity and outcomes has not been definitively established. METHODS: In this study, serum chemerin levels were analyzed in 64 patients with moderate COVID-19 and 60 patients with severe disease. RESULTS: The results showed that serum chemerin levels were comparable between these two groups and slightly higher than in healthy controls. Notably, COVID-19 patients with hypertension exhibited elevated serum chemerin levels, while those with liver cirrhosis had lower levels. When patients with these comorbidities were excluded from the analyses, serum chemerin levels in COVID-19 patients were similar to those in healthy controls. Positive correlations were observed between serum chemerin levels and markers such as alkaline phosphatase, C-reactive protein, eosinophils, and lymphocytes in the entire cohort, as well as in the subgroup excluding patients with hypertension and cirrhosis. Additionally, urinary chemerin levels were comparable between COVID-19 patients and controls, and neither hypertension nor dialysis significantly affected urinary chemerin levels. Both survivors and non-survivors had similar serum and urinary chemerin levels. CONCLUSIONS: In conclusion, this study suggests that comorbidities such as arterial hypertension and liver cirrhosis do have a more significant impact on serum chemerin levels than SARS-CoV-2 infection itself.

microRNAs and Other Serological Markers of Liver Fibrosis in Patients with Alcohol-Related Liver Cirrhosis.

Background: It is essential to identify novel non-invasive markers of liver fibrosis for clinical and scientific purposes. Thus, the goal of our survey was to assess the serological expression of selected microRNAs (miRNAs) in patients with alcohol-related liver cirrhosis (ALC) and to correlate them with other existing markers. Methods: Two hundred and thirty-nine persons were enrolled in the study: one hundred and thirty-nine with ALC and one hundred healthy controls. Serological expression of miR-126-3p, miR-197-3p and miR-1-3p was evaluated in all participants. Direct markers of liver fibrosis (PICP, PIIINP, PDGF-AB, TGF-α and laminin) together with indirect indices (AAR, APRI, FIB-4 and GPR) were also assessed. The additional evaluation concerned hematological parameters: MPV, PDW, PCT, RDW, MPR, RPR NLR, PLR and RLR. Results: The expression of miR-197-3p was lower in ALC compared to controls (p < 0.0001). miR-126-3p correlated negatively with AST (p < 0.05) and positively with miR-197-3p (p < 0.001). miR-197-3p correlated with direct markers of liver fibrosis-positively with PDGF-AB (p < 0.005) and negatively with TGF-α (p < 0.01). Significant negative relationships were noticed between miR-1-3p and the number of neutrophils (p < 0.05), TGF-α (p < 0.05) and laminin (p < 0.05). Conclusions: The achieved results and observed correlations prove the potential involvement of the examined miRNAs in the process of liver fibrosis, giving a novel insight into the diagnostics of liver cirrhosis.

Impact of Treatment with Direct Antivirals on Coagulation Parameters in Patients with Hepatitis C Virus-Related Liver Cirrhosis and Sustained Virological Response.

Background and Objectives: Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy.

The Impact of the G6PD Gene Mutations in Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals: A Multicenter Observational Study.

Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015-2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity-a common occurrence in countries such as Italy-proved to be highly effective and safe.

Liver Cirrhosis: The Immunocompromised State.

Systemic inflammation and immunodeficiency are important components of cirrhosis-associated immune dysfunction (CAID), the severity of which is dynamic, progressive, and associated with the greater deterioration of liver function. Two inflammation phenotypes have been described: low-grade and high-grade systemic inflammation. Both of these phenotypes are related to liver cirrhosis function; thus, high-grade inflammation is correlated with the severity of hepatic insufficiency, bacterial translocation, and organic insufficiency, with which the risk of infections increases and the prognosis worsens. Bacterial translocation (BT) plays a relevant role in persistent systemic inflammation in patients with cirrhosis, and the prophylactic employment of antibiotics is useful for reducing events of infection and mortality.

Selective Androgen Receptor Modulators Leading to Liver Injury: A Case Report.

Selective androgen receptor modulators (SARMs) have gained popularity for their alleged ability to selectively target androgen receptors, potentially offering muscle-building benefits with fewer side effects than traditional steroids. However, the safety profile of SARMs, including RAD-140, is not fully understood. This case report presents a 29-year-old male who developed liver injury after taking RAD-140. The patient experienced jaundice and elevated liver enzymes after three months of RAD-140 use. A liver ultrasound revealed hepatic steatosis and a hyperechoic lesion. Symptoms resolved after discontinuing RAD-140. Similar cases of liver injury associated with RAD-140 have been reported, highlighting the potential hepatotoxicity of this SARM. Discontinuation of RAD-140 appears to reverse liver injury, but the long-term effects and risks of SARM use remain unclear. This case highlights the need for caution and monitoring when considering SARMs for performance enhancement.

Role of Continuous Drainage of Tense Ascites in Peritoneal Dialysis: Mehandru/Masud Technique.

Insertion of a peritoneal dialysis (PD) catheter in end-stage renal disease (ESRD) patients with cirrhosis and tense ascites remains a challenge for nephrologists. Ascitic fluid leak at the surgical site, a common postoperative occurrence, leads to the disqualification of many patients who could be otherwise great candidates for PD. The ascitic fluid leak has been described to occur during or immediately after surgery even after the entire volume of ascitic fluid has been drained. In this study, we report a case study of three patients with ESRD, liver cirrhosis, and tense ascites on hemodialysis. The patients required super large volume paracentesis (SLVP), draining 9,000 - 15,000 cc of ascitic fluid twice weekly in an interventional radiology setup. Besides ascitic fluid drainage, the patients needed in-center hemodialysis (ICHD) 3 days a week, leading to their engagement in procedures 5 days a week. In addition, intradialytic symptomatic hypotension, hypoalbuminemia, and other adverse effects of hemodialysis lead to their poor lifestyle. To improve their lifestyle, all patients desired to switch to PD from ICHD. Upon the PD catheter insertion and drainage of the entire ascitic fluid, leaks developed at the insertion site within a few hours. To overcome these leaks, PD catheters of all three patients were attached via a transfer set to a bag for continuous drainage of ascitic fluid for about 2 weeks. No leak or complication was noted, leading to complete healing of insertion site. We recommend, for the patients with tense ascites requiring SLVP, approximately 2 weeks of healing period continuously be performed till initiation of PD training,.

Change of skeletal muscle mass in cirrhotic patients with hypersplenism after partial splenic artery embolization.

PURPOSE: Partial splenic artery embolization (PSAE) is an effective procedure for cirrhotic patients with hypersplenism. The aim of our study is to evaluate the effect of PSAE on skeletal muscle, and to identify the predictor for an improvement in skeletal muscle index (SMI) in cirrhotic patients with hypersplenism after PSAE. MATERIALS AND METHODS: 466 cirrhotic patients with hypersplenism underwent PASE between Dec 2013 and Mar 2022. Medical records and CT images of enrolled patients were analyzed. RESULTS: 105 cirrhotic patients with hypersplenism were enrolled. Sarcopenia was observed in 60.00 % (63/105) of these patients, 68.25 % (43/63) of male patients, and 31.75 % (20/63) of female patients. In cirrhotic patients, no significant change in the mean SMI at the third lumbar vertebra (L3) level after PSAE. In patients with sarcopenia, the L3 SMI increased from 36.77 cm2/m2 (baseline) to 43.38 cm2/m2 (P < 0.01), the L3 subcutaneous fat area (SFA) increased from 79.16 cm2 (baseline) to 103.52 cm2 (P < 0.01) at 12-month follow-up after PSAE. In patients without sarcopenia, the L3 SMI decreased from 58.38 cm2/m2 (baseline) to 49.44 cm2/m2 (P < 0.05), the L3 SFA increased from 89.63 cm2 (baseline) to 94.77 cm2 (P > 0.05) at 12-month follow-up after PSAE. Univariate and multivariate analysis demonstrated splenic infarction rate (OR: 0.01, P = 0.0032) and SMI (OR: 0.84, P < 0.001) were independent predictors for an improvement in skeletal muscle in patients with sarcopenia. CONCLUSIONS: In cirrhotic patients with sarcopenia, an improvement in skeletal muscle and fat mass was observed after PSAE; splenic infarction rate and the L3 SMI before PSAE predicted an improvement in skeletal muscle index in patients with sarcopenia after PSAE.

Biomarker Discovery in Liver Disease Using Untargeted Metabolomics in Plasma and Saliva.

Chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC), continue to be a global health burden with a rise in incidence and mortality, necessitating a need for the discovery of novel biomarkers for HCC detection. This study aimed to identify novel non-invasive biomarkers for these different liver disease states. We performed untargeted metabolomics in plasma (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 34) and saliva samples (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 22) to test for significant metabolite associations with each disease state. Additionally, we identified enriched biochemical pathways and analyzed correlations of metabolites between, and within, the two biofluids. We identified two salivary metabolites and 28 plasma metabolites significantly associated with at least one liver disease state. No metabolites were significantly correlated between biofluids, but we did identify numerous metabolites correlated within saliva and plasma, respectively. Pathway analysis revealed significant pathways enriched within plasma metabolites for several disease states. Our work provides a detailed analysis of the altered metabolome at various stages of liver disease while providing some context to altered pathways and relationships between metabolites.

Visceral Fat Associated with Worsening of Recurrent Esophageal Varices in Alcoholic/Nonalcoholic Steatohepatitis-Related Liver Cirrhosis.

BACKGROUND: Alcoholic steatohepatitis and nonalcoholic steatohepatitis-related liver cirrhosis (ASH/NASH-LC) are major causes of esophageal varices (EVs). However, the association between high visceral fat and exacerbation of EVs remains unclear. The aim of this study was to clarify the association of visceral fat and recurrence rate of EVs in ASH/NASH-LC and to identify independent predictors associated with recurrence. METHODS: We retrospectively evaluated data from 94 patients who underwent endoscopic injection sclerotherapy for EVs with ASH/NASH-LC. Using the receiver operating characteristic curve for the cut-off value of visceral fat index (VFI; 46.4 cm2/m2), we classified patients as having a high VFI (n = 53) or low VFI (n = 41). Propensity score matching was used to align for background factors, and the recurrence rate of EVs was compared between the two groups. Predictors associated with esophageal variceal recurrence were identified by multivariate analysis. The recurrence rate in patients with viral LC was also investigated. RESULTS: In the overall analysis, the recurrence rate was significantly higher in the high VFI group than in the low VFI group (P = 0.023). The recurrence rate was also higher in the high VFI group than in the low VFI group after propensity score matching, in which 19 patients were matched in each group (P = 0.048). VFI and Child-Pugh score were independently associated with recurrence. Recurrence rates were comparable between the two groups in viral LC patients. CONCLUSIONS: Worsening of variceal recurrence was observed in high visceral fat patients in ASH/NASH-LC but not in viral LC. Furthermore, high visceral fat was an independent predictor associated with variceal recurrence.

Effect of sarcopenia on liver cirrhosis with complicating oesophageal and gastric varices after endoscopic therapy.

Several investigators have reported that sarcopenia is common in patients with liver cirrhosis. However, few studies have probed the association between sarcopenia and liver cirrhosis complicated with oesophageal and gastric variceal bleeding (LC-EGVB). We aimed to investigate the impact of sarcopenia on rebleeding after endoscopic therapy in patients with LC-EGVB. Computed tomography (CT) radiographs from the third lumbar vertebra were selected to analyse body composition, including skeletal muscle tissue, visceral and subcutaneous adipose tissue using SliceOmatic software. Sarcopenia was defined using validated cutoff values for patients with liver cirrhosis: 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. A total of 187 patients with LC-EGVB and 309 controls were included in this study. The rate of sarcopenia in controls (17.4 %) was significantly lower than that in patients with LC-EGVB (41.2 %). Patients with LC-EGVB exhibiting sarcopenia showed a high prevalence of portal vein thrombosis and rebleeding rate at 1 year. The rate of sarcopenia in the rebleeding group was significantly higher than that in the non-rebleeding group. Univariate and multivariate analyses showed that sarcopenia was an independent risk factor for rebleeding within 1 year in patients with LC-EGVB. Patients with LC-EGVB displayed a high prevalence of sarcopenia. Sarcopenia was observed to be an independent risk factor for rebleeding within 1 year.

A landscape of liver cirrhosis and transplantation in Mexico: Changing leading causes and transplant as response.

Liver cirrhosis causes include alcoholism, viral infections (hepatitis B virus (HBV) and hepatitis C virus (HCV)), alcohol-associated liver disease (ALD), and metabolic dysfunction associated with steatotic liver disease (MASLD), among others. Cirrhosis frequency has increased in recent years, with a prevalence of 1395 cases per 100,000 and a mortality rate of 18 per 100,000, which corresponded to 1,472,000 deaths during 2017. In Mexico, liver disease is a public health problem since it was associated to 41,890 deaths in 2022, including liver cirrhosis (>25,000) and ALD (14,927). This represents 114 individuals daily due to these causes, and correspond to the 4th to 5th place of all causes. The global prevalence of MASLD is estimated to 25 % of the world's population, while in pediatric population could be higher. In Mexican population is more prevalent since estimations are up to 41.3 % in 2023. Alcohol consumption, a global health issue due to its high prevalence and associated morbidities, is associated to ALD in 32.9 %, with a mortality rate of 23.9 %, primarily due to liver-related causes. In Mexico, ALD is present in 23 % of all cirrhosis cases. already surpassed by hepatitis B cases in 2009. HCV and HBV frequencies changed due programs implementing screening detection, vaccines and direct-acting antivirals during the last years. A switch of causes has occurred, increasing MASLD and diminishing viral causes. Efficient performed liver transplantation has grown as response to increasing cirrhosis cases, including recent authorized centers. These efforts are necessary, whereas preventive strategies should be implemented according to leading causes.

The Impact of Liver Failure on the Immune System.

Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune response. This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation, which might result from acute-on-chronic liver failure (ACLF) and cirrhosis. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

The Use of Proton Pump Inhibitors in Patients with Liver Cirrhosis: Real Life Experience.

(1) Background: Proton pump inhibitors (PPIs) are commonly prescribed for gastric disorders. In patients with liver cirrhosis, PPI use is associated with an increased risk of spontaneous bacterial peritonitis and increased mortality rates; therefore, they should be used with caution. This study aims to evaluate the appropriateness of PPI prescriptions in hospitalized cirrhotic patients against current clinical guidelines to identify patterns of misuse and guide better prescribing practices. (2) Methods: A retrospective study was conducted on liver cirrhosis inpatients in an internal medicine department from January 2022 to May 2023. The primary measure was the proportion of PPI prescriptions aligned with clinical guidelines. Medical files were entirely reviewed by researchers to assess the appropriateness of PPI prescriptions using the current guidelines. Outcomes included the identification of common reasons for PPI prescription and the rate of inappropriate PPI use among the study population. (3) Results: The study included 189 cirrhotic patients, with PPIs prescribed to 95 (50.2%) patients during hospitalization and 75 (39.7%) patients at discharge. Among those, 47.4% of the inpatients and 34.7% at discharge had no valid indication for PPI administration. The most common reason for PPI prescription during hospital stays was gastritis, followed by antiplatelet use in high-risk patients, ulcers, and upper gastrointestinal bleeding. The most common inappropriate indication was portal hypertensive gastropathy (PHG), followed by treatment with corticosteroids and anticoagulants alone. We did not find an association between PPI administration during hospital stays and infections. Only in 4% of cases patients should have received PPIs and did not. (4) Conclusions: There is a concerning overprescription of PPIs in cirrhotic patients, often deviating from established guidelines. It subjects patients to unnecessary risks. There is an urgent need for increased awareness and adherence to clinical guidelines regarding PPI prescriptions in cirrhotic patients.

Spleen shear wave elastography measurements do not correlate with histological grading of liver fibrosis in Fontan physiology: a preliminary investigation.

BACKGROUND: Elevated spleen stiffness may be seen in patients with portal hypertension due to cirrhosis. In patients with Fontan physiology, elevated liver stiffness has been shown to correlate poorly with liver fibrosis. It is unknown whether spleen stiffness may instead serve as a surrogate marker of liver fibrosis in these patients. OBJECTIVE: To compare spleen stiffness determined by shear wave elastography (SWE) with histological findings of an ultrasound-guided liver biopsy in patients who had undergone Fontan palliation as a potential surrogate for Fontan-associated liver disease. MATERIALS AND METHODS: This was an IRB-approved single-center, retrospective study. Patients with Fontan palliation who had undergone both a spleen SWE study and a percutaneous liver biopsy between 2016 and 2020 were included. Biopsy, performed during cardiac catheterization, within 3 months of the SWE was required for inclusion. Using Kruskal-Wallis tests, spleen stiffness was compared with three liver biopsy scoring methods: Ishak, METAVIR, and congestive hepatic fibrosis score (CHFS). When available, Pearson's correlation was also used to compare collagen deposition determined using Sirius Red stain (%SR) with SWE values. A P-value < 0.05 was considered statistically significant. RESULTS: Twenty-two patients (15 males) were included in the study, with a median age of 17 years (IQR is 14.8-20.5 years; age range: 7 years to 30.2 years). The median spleen stiffness was 2.94 m/s (IQR: 2.57-3.61 m/s; range: 1.48-4.27 m/s). The median Fontan pressure was 11 mm Hg (IQR: 10-13.3 mm Hg; range: 7-19 mm Hg) obtained within a median of 10 days (IQR: 1-41 days) of SWE. Splenic stiffness did not correlate with the extent of fibrosis determined by histology (all P > 0.05). There was also no statistically significant correlation between the %SR staining and SWE-determined spleen stiffness (Pearson's correlation of 0.165, P = 0.59, n = 13). CONCLUSIONS: In this preliminary study, SWE spleen stiffness values did not correlate with biopsy-determined scoring of liver fibrosis in patients with Fontan physiology.

Associations between single nucleotide polymorphisms of cytokines and hepatitis B virus-related liver cirrhosis: A case-control study.

BACKGROUND AND AIMS: Various inflammatory and immune cytokines play key roles in the progression of hepatitis B virus (HBV)-related liver cirrhosis (LC). This study explored the relationship between single nucleotide polymorphisms (SNPs) in cytokines with the combined effect of polymorphisms and gender-polymorphisms interaction and LC risk. METHODS: In this study, a case-control design was used, samples were selected from 45 patients with hepatitis B-related cirrhosis and 45 age-gender-matched chronic HBV-infected patients without cirrhosis attending the tumor hospital of Wuwei Academy of Medical Sciences. Fifteen SNPs were examined using a real-time polymerase chain reaction allelic discrimination system. Logistic regression was utilized to assess cytokine-associated SNPs and the association between SNPs and LC progression in HBV-infected patients. RESULTS: The multivariate-adjusted logistic model revealed that the GG/AG dominant model (OR, 16.38; 95% CI, 1.13-236.70) and G allele (OR, 5.93; 95% CI, 0.98-36.01) of rs1800896 were associated with an increased risk of cirrhosis in CHB patients. Instead, rs2227306 CT presented a reduced cirrhosis risk (OR, 0.22; 95% CI, 0.04-1.38). Rs2055979 AA/AC was negatively associated with the risk of cirrhosis, potentially reversed in males (p = 0.021). Rs1799964 CC/CT was positively related to the risk of cirrhosis but reduced the risk of cirrhosis in males (OR, 0.13; 95% CI, 0.022-0.808; p = 0.028). Both rs1799964 TT and rs1799724 CT/TT genotype showed a synergistic effect in reducing the risk of cirrhosis with rs1800896 AA (OR, 0.08; 95% CI, 0.01-1.43 and OR, 0.12; 95% CI, 0.01-2.21). CONCLUSION: Polymorphisms rs1800896 and rs2227306 are potentially associated with the risk of cirrhosis. For the first time, the study highlights that the rs2055979 AA/AC and rs1799964 CC/CT polymorphism interact with gender and its potential reversal of cirrhosis risk in males. Furthermore, rs1800896 AA showed a synergistic effect with rs1799964 TT and rs1799724 CT/TT to prevent the progression of HBV infection to cirrhosis.