Search Results (205)

Background/Objectives: Cirrhosis is an irreversible state of chronic liver disease. Systemic inflammatory response syndrome (SIRS) is a severe complication and significantly contributes to lethal outcomes in cirrhotic patients. We studied a group of cirrhotic patients with SIRS admitted to our centre, assessing the relationship with in-hospital outcomes. Methods: The study population included 102 patients with alcoholic cirrhosis and SIRS. Laboratory biomarkers, the model for end-stage liver disease, the model for end-stage liver disease—natrium, the Acute Physiology and Chronic Health Evaluation II score, CLIF-C organ failure, the systemic immune-inflammation index score (S II), and the Cirrhosis Acute Gastrointestinal Bleeding (CAGIB) score were tested in relation to the mortality risk using receiver operating characteristic (ROC) curves. Results: Our results demonstrated that values of sodium, chlorides, and albumin significantly correlated with 7-day survival. The area under the curve’s (AUCs) values for sodium, chlorides, and albumin were 0.542, 0.627, and 0.610, respectively, for 7-day mortality prediction. The CAGIB score significantly correlated with 7-day mortality, with the cut-off value of −7.86 (AUC: 0.674, 95% CI (0.555–0.794)). For the assessment of 28-day mortality, the AUC values for sodium, chlorides, and albumin were 0.630, 0.654, and 0.661, respectively. Additionally, the cut-off value of the CAGIB score was found to be −7.84 (AUC: 0.625, 95% CI (0.509–0.740)) in 28-day mortality prediction. Conclusions: Sodium, chlorides, albumin, and the CAGIB score are reliable predictors of 7-day and 28-day in-hospital mortality in patients with advanced alcoholic liver disease and SIRS. Full article

During pregnancy, a series of physiological changes occur in women, particularly affecting the cardiovascular system with significant hemodynamic alterations. Subsequently, this leads to renal adaptations manifesting through variations in glomerular filtration rate. This close interconnection between the heart and kidneys implies that issues arising in one organ will disrupt this fundamental balance, inevitably involving all associated organs. The purpose of this review is to gather all possible nephrological conditions that may arise during pregnancy, as well as pre-existing conditions that may become apparent or worsen during this period. This review describes the natural history, treatment, and impact of these conditions on pregnancy itself. Among the most common conditions are preeclampsia and HELLP syndrome, severe complications characterized by hypertension, proteinuria, and multiorgan damage that require immediate clinical attention. Additionally, women with chronic kidney disease are at higher risk of developing maternal–fetal complications, such as preterm birth and intrauterine growth restriction. Common causes of acute renal failure are also analyzed, including thrombotic microangiopathy, acute fatty liver of pregnancy, acute onset or flare of systemic lupus erythematosus, and catastrophic antiphospholipid antibody syndrome. Given the importance of proper renal function during pregnancy, it is essential to have a thorough understanding of nephrological diseases that may affect this phase of women’s lives. This knowledge is crucial for managing these conditions effectively to avoid risks to the survival of both the mother and the newborn. Full article

Background: In recent years, indications for liver transplantation have expanded, while the age of transplant recipients has significantly increased due to improvements in perioperative management. As clinical manifestations of posttransplant complications vary and are often nonspecific, the identification of appropriate biomarkers is important for the assessment of graft quality and early recognition of potential complications following liver transplantation. Liver-type FABP (L-FABP) is a small cytoplasmic protein found abundantly in hepatocytes and is involved in the intracellular transport of long-chain fatty acids. Elevated serum levels have been detected in acute and chronic liver failure, kidney failure, and some malignancies. Materials and Methods: We conducted a prospective, single-center study from July 2023 to January 2025, including 29 adult patients who underwent deceased-donor transplantation. Three patients were excluded due to inadequate sample withdrawals. Serum L-FABP was measured preoperatively and on postoperative days 1, 3, 5, 7, and 14. Clinical, surgical, and biochemical data were collected and analyzed using non-parametric statistical tests. Results: L-FABP levels were significantly higher on POD 7 in recipients of grafts from donors ≥ 65 years (p = 0.035), with no corresponding changes in standard liver function markers. While no significant differences in L-FABP levels were found between patients with and without infectious biliary or vascular complications (all p > 0.05), we proved a strong negative correlation between intraoperative blood transfusion volume and L-FABP levels on POD 5 (ρ = −0.677, p < 0.001) and POD 7 (ρ = −0.455, p = 0.025). Conclusions: Our findings suggest that L-FABP holds promise as a biomarker for the early detection of subclinical hepatic graft cellular injury, which is not detected by means of conventional biomarkers for liver function. Full article

Background/Objectives: Acute-on-chronic liver failure (ACLF) is a life-threatening complication of cirrhosis, characterized by organ failures and high short-term mortality. Alcohol-related cirrhosis is one of the most frequent underlying etiologies of ACLF in Europe. Infections, particularly those leading to sepsis are recognized triggers; however, their relative contribution, clinical features, and prognostic impact in critically ill patients with alcohol-related cirrhosis remain incompletely defined. This study aimed to systematically identify and characterize precipitating events of ACLF in this population and to compare outcomes between sepsis- and non-sepsis-related cases. Methods: We conducted a retrospective cohort study including 188 ICU patients with alcohol-related cirrhosis who were treated for ACLF at a tertiary university medical center. ACLF was defined and graded according to the European Association for the Study of the Liver—Chronic Liver Failure Consortium (EASL-CLIF) criteria, and sepsis was diagnosed according to Sepsis-3 definitions. Clinical data, precipitating events, microbiological evidence, organ support requirements, and in-hospital outcomes were systematically analyzed. Results: Sepsis was the most frequent precipitating event, identified in 118 patients (62.8%), while 70 patients (37.2%) developed ACLF due to non-septic triggers such as gastrointestinal bleeding. Patients with sepsis-associated ACLF presented with more advanced disease (ACLF grade 2–3 in 80.5% vs. 57.1%, p = 0.004), higher Chronic Liver Failure Consortium—Acute-on-Chronic Liver Failure Score (CLIF-C ACLF) scores (median 55 vs. 50, p = 0.04), longer ICU stays (median 11 vs. 4.5 days, p < 0.001), and markedly higher in-hospital mortality (60.2% vs. 20.0%, p < 0.001) compared to patients without sepsis. Pneumonia (48.3%), urinary infections (17.8%) and spontaneous bacterial peritonitis (16.1%) were the leading infectious foci triggering sepsis. Microbiological evidence was obtained in 82.2% of sepsis cases, with frequent polymicrobial infections and opportunistic pathogens including Enterococcus faecium and Candida albicans. Conclusions: In critically ill patients with alcohol-related cirrhosis, infections leading to sepsis are the predominant precipitating event of ACLF and the strongest determinant of short-term prognosis. Compared with non-sepsis triggers, sepsis-associated ACLF is characterized by more severe disease, greater need for organ support, longer ICU stays, and substantially higher mortality. These findings highlight the urgent need for early recognition, rapid diagnostic strategies, and optimized infection management to improve outcomes in this high-risk population. Full article

Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome characterized by an acute decompensation of chronic liver disease in association with extrahepatic organ failure(s) and a high short-term mortality. Despite its increasing clinical relevance, there is no internationally standardized definition of ACLF to date. This review provides a comprehensive overview of current ACLF definitions, underlying pathogenic mechanisms, frequent precipitating events, and current treatment strategies. While liver transplantation remains the only curative treatment option, its role in the setting of ACLF is controversially debated, and patient selection remains complex due to high perioperative risk. Thus, the review article describes the current role of liver transplantation in patients with ACLF and describes novel prognostic scoring systems (e.g., TAM core, SALT-M model) that may be helpful in selecting suitable transplant candidates. Further emerging treatment options for ACLF include extracorporeal liver support systems, therapeutic plasma exchange, and immune-modulating approaches targeting toll-like receptor signaling that offer promising adjunctive strategies, though clinical evidence remains limited. Given the high burden and complexity of ACLF, harmonized definitions and evidence-based therapeutic frameworks are urgently needed to improve patient care and optimize transplant prioritization. Full article

Hepatitis B virus (HBV) infection remains a significant global health burden, primarily due to its chronic complications, including acute exacerbation, cirrhosis, hepatocellular carcinoma (HCC), and related sequelae. Acute exacerbation of chronic hepatitis B (CHB-AE) is common and often represents the earliest clinical manifestation. The Hepatitis B virus X protein (HBx) (17-kDa) is not only essential for viral replication but also plays a role in the development of HCC. To investigate the role of HBx mutation in CHB-AE progression, we enrolled 33 hospitalized CHB-AE patients and 31 patients with HBV-related liver failure (controls) from mainland China between January 2017 and June 2018. Single mutation 36 of HBx was significantly more prevalent in CHB-AE patients (p < 0.05), whereas Joint Mutation 1 was more frequent in HBV-related liver failure patients (p < 0.05). HBx mutations, including Single mutation 36 and Joint Mutations 2 and 3, were significantly associated with high HBV DNA levels (p < 0.05), while Joint mutation 1 predominated in the low HBV DNA group (p < 0.01). Age-stratified analysis showed that Single mutation 36 and Joint Mutation 2 were more common in younger patients (<35 years old) (p < 0.05), whereas Joint mutation 1 was more frequent in older age (≥35 years old) (p < 0.05). Moreover, antiviral therapy markedly reduced the prevalence of Joint mutation 1 from 82.98% in treatment-naïve patients to 29.41% in treatment-experienced patients (p < 0.0001). These findings suggest that specific HBx mutations are associated with viral replication levels, disease progression, and patient demographics. Such mutations may serve as molecular markers for disease severity and potential therapeutic targets in both CHB-AE and HBV-related liver failure. Full article

Hepatitis A virus (HAV) infection sometimes results in the occurrence of acute liver failure and acute-on-chronic liver failure (ACLF), which is often fatal, especially in patients with diabetes mellitus or elderly individuals. ACLF is observed in patients with cirrhosis who occasionally have zinc deficiency. However, effective drugs for hepatitis A are currently unavailable. Glucose-regulated protein 78 (GRP78) is an antiviral agent that has been reported to prevent HAV replication. The effects of zinc acetate on HAV HA11-1299 genotype IIIA replication and changes in GRP78 levels in human hepatocytes with or without HAV infection were examined. Zinc acetate inhibited HAV HA11-1299 genotype IIIA replication in both Huh7 and GL37 cells. Zinc acetate also inhibited HAV replication in both low- and high-glucose media. Zinc acetate increased the expression of GRP78, in response to HAV replication. The combination of zinc acetate with ribavirin led to greater suppression of both HAV HA11-1299 genotype IIIA and HAV HM175/18f genotype IB replication in Huh7 cells than that of ribavirin alone. In conclusion, zinc acetate inhibits HAV replication in accompany with the elevation of GRP78 expression without causing cellular toxicity. Zinc compounds may be useful for the treatment of ACLF caused by HAV infection. Full article

Background/Objectives: The prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is significantly affected by inflammatory state and immune dysregulation. The systemic inflammatory response index (SIRI), which reflects neutrophil, monocyte, and lymphocyte dynamics, has emerged as a potential marker of immune-inflammatory status. However, its role in predicting HBV-ACLF outcomes remains unclear. This research aims to elucidate the prognostic value of SIRI and its dynamic changes combined with disease severity scores in predicting the outcomes of HBV-ACLF. Methods: The study included HBV-ACLF patients enrolled in a multicenter clinical study between July 2019 and April 2024. Based on 90-day outcomes, the participants were categorized into survival and death groups. Clinical data and SIRI values were collected on days 0 (baseline), 3, 7, and 14. Independent prognostic factors were identified using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. The predictive value of dynamic SIRI changes combined with disease severity scores was evaluated using receiver operating characteristic (ROC) curves. Results: A total of 153 patients with HBV-ACLF were analyzed, including 104 in the survival group and 49 in the death group. SIRI values were significantly lower in the survival group than in the death group across all time points. Multivariate Cox regression analysis identified that an increased ΔSIRI at day 3 (ΔSIRI3), a higher MELD score, and a lower albumin level were independently associated with increased 90-day mortality. The combination of SIRI on day three (SIRI3) and MELD-Na score on day three (MELD-Na3) demonstrated the highest predictive performance, with an AUC of 0.817 (95% CI: 0.750–0.883). Conclusions: The combination of the SIRI and MELD-Na score on day three provides a strong predictive value for the short-term prognosis of HBV-ACLF, highlighting its potential utility in early prognostic evaluation. Full article

Background: Hepatocellular carcinoma (HCC) is a major global health burden and a leading cause of cancer-related deaths. While aspirin has shown potential chemopreventive effects in chronic liver disease, its impact on clinical outcomes among patients hospitalized with HCC remains under-investigated. Methods: Using the National Inpatient Sample (NIS) from 2016 to 2022, we conducted a retrospective cohort study to evaluate the association between aspirin use and clinical outcomes in adult HCC hospitalizations. Patients were stratified based on documented aspirin use, and propensity score matching with inverse probability of treatment weighting (IPTW) was applied to minimize confounding. The primary outcome was in-hospital mortality; secondary outcomes included morbidity-related complications, hospital length of stay, and total charges. Results: Among 337,730 hospitalizations with HCC, 8.37% involved aspirin use. Aspirin users demonstrated significantly lower in-hospital mortality (5.2% vs. 10.09%), with an adjusted odds ratio (OR) of 0.58 (95% CI: 0.50–0.68; p < 0.001). Aspirin use was also associated with shorter hospital stays (5.42 vs. 6.39 days), lower total charges ($80,310 vs. $95,098), and reduced incidence of complications, including acute liver failure, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, sepsis, ICU admission, and acute kidney injury. Importantly, no statistically significant increase in gastrointestinal or variceal bleeding was observed among aspirin users. Conclusions: These findings suggest that aspirin use may reduce mortality, morbidity, and healthcare burden in patients hospitalized with HCC. Full article

Background Sex disparity has been highlighted in personalized medicine for various human diseases including acute/chronic liver diseases. In the transplant community, greater graft failure risk in female-to-male liver transplantation (LT) has been repeatedly reported, and a recent study in living donor LT reported that the inferiority of female-to-male LT is shown only when donor age is ≤40 y. We aimed to analyze the United Network for Organ Sharing (UNOS) database to test if the poorer outcome of female-to-male LT changes by donor age of 40 y in deceased donor LT, as shown in living donor LT. Methods In this retrospective cohort study, 11,752 adult patients in the UNOS registry who underwent deceased donor LT between 2000–2023 were analyzed. Multivariable analysis was performed to adjust the effects from transplant years, graft ischemia time, disease severity, and others. The primary outcome was graft failure. Results Within the subgroup of recipients with ≤40 y donors, graft failure risk was significantly greater in female-to-male LT than others (vs. female-to-female, HR = 1.43 [1.16–1.76], p < 0.001; vs. male-to-female, HR = 1.46 [1.18–1.81], p < 0.001; vs. male-to-male, HR = 1.26 [1.16–1.49], p = 0.009). In contrast, within the subgroup of recipients with >40 y donors, the risk was comparable between female-to-male LT and other donor-recipient sex groups (vs. female-to-female, p = 0.907; vs. male-to-female, p = 0.781; vs. male-to-male, p = 0.937). We tested various cutoff donor ages and determined that 40 y is the best cutoff value to define the risk subgroup in female-to-male LT. Conclusions In the current study, we found that the sex disparity shown in living donor LT is also observed in deceased donor LT. That is, post-transplant graft failure risk was greater in female-to-male LT than other donor–recipient sex groups only when donor age was ≤40 y. In contrast, graft failure risk was comparable irrespective of donor-recipient sex combinations when donor age was >40 y. Full article

Background: Human metapneumovirus (hMPV) is a respiratory pathogen that causes illness ranging from mild upper respiratory tract infections to severe pneumonia, particularly in individuals with comorbidities. Fatal cases of hMPV-induced hemorrhagic pneumonia are rare and likely under-reported. Diagnosis is often delayed due to overlapping symptoms with other respiratory viruses and the rapid progression of the disease. Case presentation: We report the case of a 55-year-old man with a complex medical history, including liver cirrhosis and diabetes mellitus, who developed acute viral pneumonia. Initial symptoms appeared three days before a sudden clinical deterioration marked by shortness of breath, hemoptysis, and respiratory failure. A nasopharyngeal swab taken on the third day of illness tested positive for hMPV by qRT-PCR. The patient died the following day. Postmortem molecular testing confirmed hMPV in lung tissue and alveolar contents. Autopsy revealed bilateral hemorrhagic pneumonia with regional lymphadenopathy. Histopathological examination showed alveolar hemorrhage, multinucleated cells, neutrophilic infiltration, activated autophagy in macrophages, and numerous cytoplasmic eosinophilic viral inclusions. Conclusions: This is the first documented case of fatal hMPV pneumonia in Armenia. It highlights the potential severity of hMPV in adults with chronic health conditions and emphasizes the need for timely molecular diagnostics. Postmortem identification of characteristic viral inclusions may serve as a cost-effective histopathological marker of hMPV-associated lung pathology. Full article

Liver failure, both acute and chronic, represents a complex, life-threatening condition frequently requiring intensive care unit (ICU) admission. Nutritional management is a crucial component of supportive therapy, aiming to mitigate catabolism, preserve lean body mass, and support immune and organ function. In acute liver failure (ALF), early nutritional intervention within 24–48 h and individualized energy–protein prescriptions are essential, even in the presence of hepatic encephalopathy. Chronic liver failure (CLF) and acute-on-chronic liver failure (ACLF) are often associated with severe malnutrition, sarcopenia, and systemic inflammation, necessitating tailored nutritional strategies. Subjective Global Assessment (SGA) and Royal Free Hospital Global Assessment (RFH-GA) tools are instrumental in identifying nutritional risk. Enteral nutrition (EN) is preferred across all stages, with parenteral nutrition (PN) reserved for contraindications. Special considerations include micronutrient repletion, prevention of refeeding syndrome, and perioperative nutritional support in transplant candidates and recipients. This clinical overview summarizes current evidence and guidelines on ICU nutrition in liver failure, emphasizing a multidisciplinary approach to improve outcomes. Full article

Background: Chronic intestinal failure (CIF), most commonly caused by short bowel syndrome (SBS), necessitates complex care. This review explores the gut microbiota’s role in intestinal adaptation in SBS, examining its potential as both a biomarker and therapeutic target. SBS results from extensive small bowel resection, leading to malabsorption and dependence on parenteral nutrition (PN). Post-resection, the gut microbiota undergoes significant alterations. While the small bowel microbiome typically comprises Streptococcus, Veillonella, and others, SBS patients often exhibit increased Gram-negative Proteobacteria. Dysbiosis is linked to adverse outcomes like liver disease and impaired growth, but beneficial effects such as energy salvage also occur. Intestinal adaptation, a process of increasing absorptive surface area in the remaining bowel, involves acute, remodeling, and maintenance phases. Preservation of ileum and stimulation with the oral diet are crucial. Biomarkers are needed to predict success, with gut microbiota composition emerging as a promising non-invasive option. The precise mechanisms driving adaptation remain incompletely understood. Conclusions: GLP-1 and GLP-2 analogues show promise in enhancing adaptation and reducing PN dependence. Surgical rehabilitation aims to maximize intestinal absorptive capacity, while transplantation remains a last resort due to high complication risks. Further research is needed to fully elucidate the microbiota’s role and harness its potential in managing SBS. Full article

Acute-on-chronic liver failure (ACLF) is a complex and severe condition marked by multiple organ failure and high short-term mortality. Coagulopathy, a key component of ACLF, is characterized by rebalanced hemostasis with both hypo- and hypercoagulable features, increasing the risk of bleeding and thrombosis. Conventional coagulation tests, including prothrombin time (PT) and platelet count, fail to fully capture the complexity of coagulation dysfunction in ACLF. Advanced diagnostic tools, like viscoelastic tests (VETs), offer a more comprehensive assessment, yet they remain limited in evaluating endothelial dysfunction and fail to account for reduced levels of anticoagulant factors. Emerging therapeutic strategies targeting coagulopathies in ACLF hold promise, but their clinical efficacy remains unclear. A more nuanced approach to diagnosing and managing coagulopathy in ACLF is needed, incorporating advanced hemostatic profiling to better inform prognosis and guide treatment decisions. Full article

ACLF is a severe stage of liver cirrhosis, characterized by multiple organ failure, systemic inflammation, and high short-term mortality. The intestinal microbiota (IM) influences its pathophysiology; however, there are currently no studies in Latin American populations. Therefore, we analyzed IM and its relationships with sepsis, organ failure, and mortality. In parallel, we quantified serum lipopolysaccharides as a marker of bacterial translocation. Fecal samples from 33 patients and 20 healthy controls (HCs) were obtained. The IMs were characterized by 16S-rRNA amplicon sequencing, the metagenomic functional predictive profiles were analyzed by PICRUSt2, and LPS quantification was performed by ELISA. Patients with ACLF showed significant alterations in alpha and beta diversity compared to the HCs. A strong dominance index accurately predicted 28-day and 90-day mortalities. The IMs showed a polarization toward Proteobacteria associated with increased LPS. The LPS correlated with clinical severity, organ dysfunction, and higher pathogenic taxa. The Klebsiella/Faecalibacterium ratio showed good performance in identifying sepsis (AUROC = 0.83). Furthermore, Morganella, Proteus, and Klebsiella were enriched in patients with multiorgan failure. Lactobacillus, Escherichia/Shigella, Veillonella, and Ruminococcus gnavus exhibited potential in predicting 28- and 90-day mortalities. The IM alterations in ACLF may be useful as clinical biomarkers of poor prognosis, primarily for mortality and sepsis. These findings are representative of western Mexico. Full article