Thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy/renal dysfunction, and organomegaly (TAFRO) syndrome are infrequent conditions with diverse clinical and pathological characteristics related to multi-organ damage. There are few reports of TAFRO syndrome accompanied by liver damage with hyperbilirubinemia. We describe the case of a 61-year-old male who presented with sudden onset abdominal pain accompanied by liver damage with hyperbilirubinemia. His symptoms worsened, leading to fever, hepatic insufficiency, serous cavity effusions, thrombocytopenia, and acute renal failure. Fever and anasarca relapsed after steroid discontinuation. The patient was ultimately diagnosed with TAFRO syndrome by biopsies taken from the axillary lymph nodes. He was then administered steroids, which resolved his symptoms almost completely. Our case was notable for its atypical signs and total remission of TAFRO syndrome.

Intravascular hemolysis is a central feature of congenital and acquired hemolytic anemias, complement disorders, infectious diseases, and toxemias. Massive and/or chronic hemolysis is followed by the induction of inflammation, very often with severe damage of organs, which enhances the morbidity and mortality of hemolytic diseases. Galectin-3 (Gal-3) is a β-galactoside-binding lectin that modulates the functions of many immune cells, thus affecting inflammatory processes. Gal-3 is also one of the main regulators of fibrosis. The role of Gal-3 in the development of different kidney and liver diseases and the potential of therapeutic Gal-3 inhibition have been demonstrated. Therefore, the objective of this review is to discuss the possible effects of Gal-3 on the process of kidney and liver damage induced by intravascular hemolysis, as well as to shed light on the potential therapeutic targeting of Gal-3 in intravascular hemolysis.

UNASSIGNED: Hepatitis B virus (HBV) remains a public health concern. Blood donors screened for HBV surface antigen (HBsAg) along with aspartate transaminase (AST)/alanine aminotransferase (ALT) could play a key in providing safe blood products. We investigated the features related to HBV infection among rejected blood donors in Luanda, Angola.
UNASSIGNED: This was a cross-sectional study conducted with 164 rejected donors. Donors were screened for HBsAg from March to May 2022. Overall, 63.4% tested positive for HBV.
UNASSIGNED: The mean age of the HBV-positive (29.2 ± 8.02) was lower than the HBV-negative (33.9 ± 10.0) (p < 0.001). Donors between 20 and 40 years (odds ratio [OR]: 2.34, p = 0.045), females (OR: 1.40, p = 0.516), residents in urbanized areas (OR: 1.23, p = 0.530), low educational (OR: 1.54, p = 0.458), unemployed (OR: 1.65, p = 0.271), and unmarried (OR:1.41, p = 0.616) might be likely to contract HBV. AST/ALT ratio was higher in HBV-infected (2.07 ± 1.42) than in HBV-uninfected (1.90 ± 1.14). About 20% of HBV-positive were classified as having acute liver disease, while 80% with chronic liver disease, based on AST/ALT ratio. Age ranged from 20 to 40 years (OR: 1.97, p = 0.305), females (OR: 1.61, p = 0.557), donors from non-urbanized (OR: 1.69, p = 0.557), a low educational (OR: 1.64, p = 0.571), and unemployed donors (OR: 1.81, p = 0.289) were likely to develop chronic liver disease.
UNASSIGNED: Our findings indicated the failure of viral hepatitis control measures. Authorities should consider including HBV nucleic acid testing to ensure early identification of HBV in Angola.

UNASSIGNED: The homeostasis of the cellular transcriptome depends on transcription and splicing mechanisms. Moreover, the fidelity of gene expression, essential to preserve cellular identity and function is secured by different quality control mechanisms including nonsense-mediated RNA decay (NMD). In this context, alternative splicing is coupled to NMD, and several alterations in these mechanisms leading to the accumulation of aberrant gene isoforms are known to be involved in human disease including cancer.
UNASSIGNED: RNA sequencing, western blotting, qPCR and co-immunoprecipitation were performed in multiple silenced culture cell lines (replicates n ≥4), primary hepatocytes and samples of animal models (Jo2, APAP, Mdr2 -/- mice, n ≥3).
UNASSIGNED: Here we show that in animal models of liver injury and in human HCC (TCGA, non-tumoral = 50 vs. HCC = 374), the process of NMD is inhibited. Moreover, we demonstrate that the splicing factor SLU7 interacts with and preserves the levels of the NMD effector UPF1, and that SLU7 is required for correct NMD. Our previous findings demonstrated that SLU7 expression is reduced in the diseased liver, contributing to hepatocellular dedifferentiation and genome instability during disease progression. Here we build on this by providing evidence that caspases activated during liver damage are responsible for the cleavage and degradation of SLU7.
UNASSIGNED: Here we identify the downregulation of UPF1 and the inhibition of NMD as a new molecular pathway contributing to the malignant reshaping of the liver transcriptome. Moreover, and importantly, we uncover caspase activation as the mechanism responsible for the downregulation of SLU7 expression during liver disease progression, which is a new link between apoptosis and hepatocarcinogenesis.
UNASSIGNED: The mechanisms involved in reshaping the hepatocellular transcriptome and thereby driving the progressive loss of cell identity and function in liver disease are not completely understood. In this context, we provide evidence on the impairment of a key mRNA surveillance mechanism known as nonsense-mediated mRNA decay (NMD). Mechanistically, we uncover a novel role for the splicing factor SLU7 in the regulation of NMD, including its ability to interact and preserve the levels of the key NMD factor UPF1. Moreover, we demonstrate that the activation of caspases during liver damage mediates SLU7 and UPF1 protein degradation and NMD inhibition. Our findings identify potential new markers of liver disease progression, and SLU7 as a novel therapeutic target to prevent the functional decay of the chronically injured organ.

Modulators of cystic fibrosis transmembrane conductance regulator (CFTR) improved cystic fibrosis (CF) patients\' outcome. The elexacaftor/tezacaftor/ivacaftor (ETI) combination was safe and effective improving lung function in patients with different CFTR genotypes, including at least one F508del mutation. However, cases with liver damage were reported. We describe 105 CF patients heterozygous for F508del in trans with another CFTR mutation, treated for 1 year with ETI. We analyzed liver biochemical parameters and cholesterol metabolism, including lathosterol and phytosterols, surrogate markers of cholesterol de-novo synthesis and absorption, respectively. The treatment significantly improved sweat chloride, body mass index and forced expiratory volume in 1 s, whereas it caused a significant increase of total and conjugated bilirubin, ALT and GGT, even if no patients developed CF liver disease. Such alterations were less relevant than those previously observed in ETI-treated F508del homozygous patients. Furthermore, ETI treatment significantly increased serum cholesterol by enhancing its absorption (correlation between serum cholesterol and phytosterols). Whereas, we observed a normalization of de-novo biosynthesis (lathosterol reduction) that was not observed in homozygous patients. These data suggest that the second mutation in trans with the F508del contributes to reduce the liver cholesterol accumulation and thus, the triggering of liver inflammation. However, no differences in the alteration of biochemical indexes were observed between CF patients with and without liver steatosis, and between patients with different mutations in trans with the F508del. Such data suggest to further investigate the effects of ETI therapy on liver function indexes and new predictive biomarkers.

Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant inherited disorder prevalent among adolescents. Typically, it manifests with hyperglycemia before the age of 25. MODY5 is attributed to a mutation in the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. A complete absence of HNF-1β is observed in 50% of those with MODY5. The 17q12 microdeletion syndrome closely linked with MODY5. Its incidence in the general population is around 1 in 14,500 and is linked with facial deformities, diabetes, polycystic kidneys, pancreatic hypertrophy, liver anomalies, and neuropsychological impairments. The most primary clinical signs are predominantly associated with the HNF-1β gene deletion. We chronicle the case of a male of 19 years of age diagnosed with diabetes, who, alongside persistent liver damage and polycystic kidneys, was referred from a community hospital to the Xuzhou Central Hospital. His clinical presentation included diabetes, liver dysfunction, polycystic kidneys, lipid irregularities, insulin resistance, and fatty atrophy. Subsequent genetic screening unveiled a 17q12 chromosomal deletion and an absence of the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. Hence, for adolescent patients lacking a familial diabetes history but exhibiting symptoms like polycystic kidneys, liver damage, lipid irregularities, and fatty atrophy, a thorough assessment for the 17q12 microdeletion syndrome becomes imperative.

UNASSIGNED: Acute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia-reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated.
UNASSIGNED: New Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated.
UNASSIGNED: After IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted.
UNASSIGNED: This study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.

BACKGROUND: Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes.
METHODS: In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC).
RESULTS: Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21-35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8-14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214-0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217-0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170-40.833, p = 0.032).
CONCLUSIONS: Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted.
Carnitine is an amino acid derivative that plays an important role in the promotion and regulation of fatty acid metabolism, and carnitine deficiency is assumed in patients with anorexia nervosa associated with chronic starvation, but there are few reports on this issue. This study represents the inaugural documentation of hypocarnitinemia in severely malnourished patients with eating disorders, including anorexia nervosa. Hypocarnitinemia, particularly in cases of severe undernutrition (BMI < 13 kg/m2) was observed during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment was considered a potential indicator of hypocarnitinemia. Although no apparent association with adverse events other than anemia during refeeding was identified, clinical manifestations of hypocarnitinemia may occur when a sudden increase in energy demand is added to a change in the physical condition of the patient group. Further investigation is required to determine the clinical significance of hypocarnitinemia.

Cardiac arrest is a leading cause of mortality globally, and mechanical CPR devices like the LUCAS system are designed to improve outcomes by enhancing consistency and reducing rescuer fatigue. However, this case report of a 76-year-old female who suffered cardiac arrest post-flight reveals significant complications associated with mechanical CPR. Despite achieving initial resuscitation, she developed extensive liver damage and additional complications, which ultimately led to her death. This case underscores the importance of precise training and strict adherence to guidelines when using mechanical CPR devices. It highlights that while these devices offer potential benefits, they also pose risks, especially for vulnerable patients, necessitating careful consideration and ongoing evaluation to optimize safety and effectiveness.

This review examines information from systematic reviews and meta-analyses, research studies, and case reports to present current knowledge about liver damage in pregnant patients having Covid-19 during pregnancy. Problems with diagnosis and differential diagnosis are examined in the context of the need to rule out other causes of liver dysfunction, including pregnancy-related liver disease. In this paper we give an overview of COVID-19 liver problems during pregnancy. Mechanisms of liver involvement in COVID-19 infection are being examined. An overview of the assessment of abnormal liver biological syndromes in pregnant patients is provided. Differential diagnostic algorithms for primary liver damage established in a pregnant woman in the context of the Covid-19 pandemic are presented. Challenges in diagnosis and etiology assessment methods and customized management options are described. The management of pregnant women with hepatic dysfunction onset on the Covid-19 background and subsequently aggravated is discussed. The importance of anticoagulant therapy as an essential measure of symptomatic management of Covid-19 in pregnant women is emphasized, as both pregnancy and COVID-19 are thrombogenic. Hypercoagulability appears to adversely affect the pregnant women liver with Covid-19 and post Covid-19 and anticoagulant therapy has benefits in the management of liver damage associated with Covid-19. The COVID-19 liver problems in a 33-year-old woman who was not vaccinated for Covid-19, without a history of chronic liver disease, was tested positive for Covid-19 at 33 weeks of gestation is discussed. The report of the diagnostics, differential diagnosis, and management questions in the context of liver dysfunction manifested by a significant increase in alanine aminotransferase cytolysis syndrome. The positive effect of anticoagulant therapy in resolving cytolytic syndrome is emphasized. The good maternal and perinatal result is also mentioned.