Acute Liver Failure Research Articles

Lactate as an early prognostic indicator in yellow phosphorus rodenticide-induced acute hepatic failure: a retrospective observational study in a tertiary care hospital

Introduction Acute hepatic failure due to yellow phosphorus rodenticide ingestion is often lethal. This study aimed to analyze demographic characteristics and prognostic indicators, focusing on hyperlactataemia as a potential early indicator of mortality in patients poisoned with yellow phosphorus rodenticide. Materials and methods This was a retrospective study of 96 patients poisoned with a yellow phosphorus-containing rodenticide (Ratol paste, which contains 3% yellow phosphorus). We examined demographic details, clinical symptoms, and biochemical markers to identify prognostic indicators. Results Demographics were similar among survivors and non-survivors. Mortality (36.5%) correlated with a higher ingested dose and treatment delays, with a mean (±SD) of 5.26 ± 2.2 survival days among those who died. Symptoms, including gastrointestinal and neurological features, typically appeared 48 h after ingestion. Non-survivors developed increased aminotransferase activities (74.3%), prolonged prothrombin time (65.7%), and hyperbilirubinaemia (65.7%) during hospitalization, significantly more commonly compared to survivors (P < 0.0001). Hyperlactataemia (lactate concentration >2 mmol/L) was present in 97.1% of non-survivors, with increased serial lactate concentrations observed in 88.6%. The median (interquartile range) admission lactate concentration among non-survivors was 4.6 mmol/L (3.36–7.53 mmol/L), and their peak median (interquartile range) lactate concentration was 6.1 mmol/L (8.74–10.6 mmol/L). In non-survivors, an increased lactate concentration preceded increased aminotransferase activities and prolonged prothrombin time. Logistic regression and receiver operating characteristic curve analysis confirmed that a 24 h lactate concentration ≥2.67 mmol/L predicted death with 94.3% sensitivity and 91.8% specificity. Discussion The majority of patients who ingest yellow phosphorus remain asymptomatic initially and typically present to hospital following the onset of gastrointestinal symptoms, usually a day later. As progression to death occurs within a week of yellow phosphorus ingestion in most cases, determining prognosis as early as possible enables swift referral to a liver transplant centre. Based on our study, a 24 h lactate concentration ≥2.67 mmol/L appears to be an early prognostic indicator of death. In another study, a lactate concentration >5.8 mmol/L was found to be a poor prognostic indicator. Conclusions Hyperlactataemia on admission and increased serial lactate concentrations appear to be early poor prognostic signs in patients with yellow phosphorus-induced liver failure.

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure.

When massive necrosis occurs in acute liver failure (ALF), rapid expansion of HSCs called liver progenitor cells (LPCs) in a process called ductular reaction is required for survival. The underlying mechanisms governing this process are not entirely known to date. In ALF, high levels of retinoic acid (RA), a molecule known for its pleiotropic roles in embryonic development, are secreted by activated HSCs. We hypothesized that RA plays a key role in ductular reaction during ALF. RNAseq was performed to identify molecular signaling pathways affected by all-trans retinoid acid (atRA) treatment in HepaRG LPCs. Functional assays were performed in HepaRG cells treated with atRA or cocultured with LX-2 cells and in the liver tissue of patients suffering from ALF. Under ALF conditions, activated HSCs secreted RA, inducing RARα nuclear translocation in LPCs. RNAseq data and investigations in HepaRG cells revealed that atRA treatment activated the WNT-β-Catenin pathway, enhanced stemness genes (SOX9, AFP, and others), increased energy storage, and elevated the expression of ATP-binding cassette transporters in a RARα nuclear translocation-dependent manner. Further, atRA treatment-induced pathways were confirmed in a coculture system of HepaRG with LX-2 cells. Patients suffering from ALF who displayed RARα nuclear translocation in the LPCs had significantly better MELD scores than those without. During ALF, RA secreted by activated HSCs promotes LPC activation, a prerequisite for subsequent LPC-mediated liver regeneration.

Assessing Severity and Need for Delivery in Early Onset Preeclampsia Before 32 Weeks of Gestation: a Delphi Consensus Procedure.

Preeclampsia is a potentially life-threatening hypertensive pregnancy disorder that carries an acute risk of an unfavorable outcome of the pregnancy but also has consequences for the long-term health of the mother. Women who develop the early form of pre-eclampsia before the 32nd week of pregnancy have the highest risk and are also the most difficult to treat. The severity of pre-eclampsia is not characterized uniformly in Germany, so that the indication for delivery is rather individualized. The aim of this study was to reach a consensus on parameters that could serve as criteria for describing the severity of pre-eclampsia based on the urgency of delivery. To this end, a Delphi procedure was used to present a scenario in which a woman was admitted for preeclampsia before 32 gestational weeks and after completion of antenatal steroid therapy. Clinicians specialized in maternal-fetal medicine from German-speaking countries completed five rounds of a modified Delphi questionnaire. Presented parameters were selected by the section "Hypertensive Pregnancy Diseases and Fetal Growth Restriction" of the German Society of Gynecology and Obstetrics after reviewing the literature. These included objectifiable laboratory or clinical parameters as well as subjective symptoms of the patient. In addition, nine fetal parameters were taken into account. The clinicians were asked to rate presented parameters as an indication for delivery on a Likert scale from 0 to 4 (no indication to absolute indication without delay). For each item, the predefined cut-off for group consensus was ≥70% agreement. A total of 126 experts were approached. Sixty-nine experts (54.8%) took part in the first round; of those 50 completed the entire Delphi procedure. A consensus was reached on 14 parameters to be considered rapid preparation for delivery without delay (4 points on the Likert scale). These were among others hepatic hematoma or liver capsule rupture, acute liver failure with fulminant coagulation disorder or disseminated intravascular coagulation, eclampsia, pathologic findings in imaging (e.g. cMRI) or electrocardiogram arranged for new onset of headache or retrosternal pain, respectively. Twenty-six parameters were rated as factors that should be considered in the decision without being absolute (1 to 3 points), and 13 parameters should have no influence on the decision to deliver (0 points). No consensus on severe hypertension as an indication for delivery could be reached for blood pressure values below 220/140mmHg. A consensus was reached on whether to deliver in preeclampsia typic clinical findings and symptoms. The results can serve as guidance for current clinical practice and for the definition of clinical endpoints in intervention studies. Nevertheless, the isolated criteria are a theoretical construction since the combined deterioration or summation of several factors rather than a single factor most likely influences the decision to deliver and reflect the severity of preeclampsia. Moreover, the degree of hypertension as an indication for delivery remains controversial, unless the patient suffers additionally from complaints. Future research should be enforced to incorporate long-term risks for the mother into a decision aid.

Intestinal Dysbacteriosis Contributes to Persistent Cognitive Impairment after Resolution of Acute Liver Failure

Regulating the gut microbiota alleviates hepatic encephalopathy (HE). It remains unclear whether it is imperative to withhold treatment for microbial imbalance after liver functional recovery. The aim of this work was to elucidate the alterations in cognitive behavior, liver function, synaptic transmission, and brain metabolites in acute liver failure (ALF) mice before and after hepatic function recovery. In this study, thioacetamide was injected intraperitoneally to establish an ALF mouse model, which induced HE. By performing hierarchical clustering analysis, we showed that the liver functions normalized, but cognitive dysfunction and intestinal dysbacteriosis were found in the ALF mice 14 days after thioacetamide injection. In addition, fecal microbiota transplantation from the ALF mice with liver function recovery could induce liver injury and cognitive impairment. Moreover, alterations in synaptic transmission were found in the ALF mice with liver function improvement, and the correlations between the gut bacteria and synaptic transmission in the cortex were significant. Finally, we detected apparent alterations in the brain metabolic profiles of the ALF mice after liver function improvement by performing 1H nuclear magnetic resonance spectroscopy, suggesting a risk of HE. These results show that intestinal dysbacteriosis in ALF mice with liver function recovery is sufficient to induce liver injury and cognitive impairment. These results indicate that continuous care may be necessary for monitoring microbial imbalance even in patients with ALF-induced HE whose liver function has recovered significantly.

A Severe Reaction After Phototherapy in a Neonate With X-Linked Protoporphyria.

Protoporphyria is a subtype of porphyria characterized primarily by painful phototoxic skin reactions after light exposure at specific wavelengths. Historically, phototherapy is not contraindicated in patients with protoporphyria since there have not been any reports of phototoxic reactions. However, patients with protoporphyria are advised to avoid direct sunlight. In this case report, we describe a neonate not known to have X-linked protoporphyria who received phototherapy for 1 to 2 hours. Within hours after initiation of phototherapy, this neonate developed a life-threatening reaction consisting of rash over the distribution of phototherapy, acute liver failure with coagulopathy, diffuse hypotonia with diaphragmatic failure, and subsequent acute respiratory failure that required mechanical ventilation. As in this case, patients with protoporphyria-related acute liver failure can have signs and symptoms similar to that of an acute hepatic porphyria attack. Neither neonatal reactions to phototherapy nor liver failure temporally associated with phototherapy have been reported in patients with X-linked protoporphyria. Early recognition of this entity is crucial in light of potential life-threatening complications. Therefore, providers must react quickly when neonates have abnormal reactions to phototherapy and consider protoporphyria in the differential diagnosis.

Necrotic Liver Lesion Resolution: Another Mode of Liver Regeneration.

The liver has the great ability to regenerate after partial resection or injury, and the mechanisms underlying liver regeneration have been extensively investigated. Interestingly, acute liver injuries triggered by various etiologies are associated with the formation of necrotic lesions, and such necrotic lesions are also rapidly resolved. However, how necrotic liver lesions are repaired has not been carefully investigated until recently. In this review, we briefly summarize the spatiotemporal process of necrotic liver lesion resolution in several liver injury models including immune-mediated liver injury and drug-induced liver injury. The roles of liver nonparenchymal cells and infiltrating immune cells in controlling necrotic liver lesion resolution are discussed, which may help identify potential therapies for acute liver injury and failure.

Mechanism of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata herbal pair in promoting hepatocellular regeneration in chronic acute liver failure based on HGF/PI3K/Akt signaling axis

Based on the hepatocyte growth factor(HGF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling axis, this study investigated the therapeutic effect of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata(PRR-ALRP) her-bal pair on acute-on-chronic liver failure(ACLF) rats and its impact on hepatocellular regeneration. The rat model of ACLF was constructed by subcutaneous and tail vein injection of bovine serum albumin combined with intraperitoneal injection of lipopolysaccharides(LPS)+D-galactosamine(D-GalN). The rats were divided into normal control(NC) group, model(vehicle) group, PRR-ALRP(5.85 g·kg~(-1)) group, and hepatocyte growth factor granules(HGFG, 4.05 g·kg~(-1)) group. Hematoxylin-eosin(HE) staining was used to observe pathological changes in rat liver tissues. Serum alanine aminotransferase(ALT), aspartate transaminase(AST), and total bilirubin(TBIL) were detected using an automatic biochemical analyzer. The levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) inflammatory factors were detected by ELISA. Immunofluorescence staining was used to detect the positive expression of proliferating cell nuclear antigen(PCNA), antigen identified by monoclonal antibody(Ki67), and cell cycle protein B1(CyclinB1). Real-time fluorescence-based quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of HGF, growth factor receptor-bound protein 1(Gab1), PI3K, Akt, phosphorylated PI3K(p-PI3K), and phosphorylated Akt(p-Akt). The results showed that compared with the vehicle group, the PRR-ALRP group had reduced liver tissue pathological scores, improved liver function, and reduced inflammatory response, with enhanced PCNA, Ki67, and CyclinB1 fluorescence expression. Furthermore, compared with the model group, the PRR-ALRP group showed upregulated expression of HGF and Gab1 proteins, as well as activation of PI3K and Akt phosphorylation. These findings suggest that PRR-ALRP herbal pair exerts anti-liver failure effects by alleviating hepatocyte inflammatory damage and promoting hepatocellular regeneration, and its specific regulatory mechanism may be related to the activation of the HGF/PI3K/Akt signaling pathway.

Macrophage manufacturing and engineering with 5′-Cap1 and N1-methylpseudouridine-modified mRNA

Macrophage-based cell therapeutics are an emerging modality to treat cancer and repair tissue damage. A reproducible manufacturing and engineering process is central to fulfill their therapeutical potential. Here, we establish a robust macrophage manufacturing platform (Mo-Mac), and demonstrate that macrophage functionality can be enhanced by N1-methylpseudouridine (m1Ψ)-modified mRNA. Using single-cell transcriptomic analysis as an unbiased approach, we found that >90% cells in the final product were macrophages, and the rest primarily comprised T cells, B cells, natural killer cells, promyelocytes, promonocytes and hematopoietic stem cells. This analysis also guided the development of flow cytometry strategies to assess cell compositions in the manufactured product to meet requirements by the National Medical Products Administration. To modulate macrophage functionality, as an illustrative example, we examined whether the engulfment capability of macrophages could be enhanced by mRNA technology. We found that efferocytosis was increased in vitro when macrophages were electroporated with m1Ψ-modified mRNA encoding CD300LF (CD300LF-mRNA-macrophage). Consistently, in a mouse model of acute liver failure, CD300LF-mRNA-macrophage facilitated organ recovery from acetaminophen-induced hepatotoxicity. These results demonstrate a GMP-compliant macrophage manufacturing process, and indicate that macrophage can be engineered by versatile mRNA technology to achieve therapeutic goals.

Effect of ferroptosis inhibitors in a murine model of acetaminophen-induced liver injury.

Liver injury caused by acetaminophen (APAP) overdose is the leading cause of acute liver failure in western countries. The mode of APAP-induced cell death has been controversially discussed with ferroptosis emerging as a more recent hypothesis. Ferroptosis is characterized by ferrous iron-catalyzed lipid peroxidation (LPO) causing cell death, which can be prevented by the lipophilic antioxidants ferrostatin-1 and UAMC-3203. To assess the efficacy of these ferroptosis inhibitors, we used two murine models of APAP hepatotoxicity, APAP overdose alone or in combination with FeSO4 in fasted male C57BL/6J mice. APAP triggered severe liver injury in the absence of LPO measured as hepatic malondialdehyde (MDA) levels. In contrast, ferrous iron co-treatment aggravated APAP-induced liver injury and caused extensive LPO. Standard doses of ferrostatin-1 did not affect MDA levels or the injury in both models. In contrast, UAMC-3203 partially protected in both models and reduced LPO in the presence of ferrous iron. However, UAMC-3203 attenuated the translocation of phospho-JNK through downregulation of the mitochondrial anchor protein Sab resulting in reduced mitochondrial dysfunction and liver injury. Thus, APAP toxicity does not involve ferroptosis under normal conditions. The lack of effects of ferroptosis inhibitors in the pathophysiology indicates that ferroptosis signaling pathways are not relevant therapeutic targets.

On-site sensing for aflatoxicosis poisoning via ultraviolet excitable aptasensor based on fluorinated ethylene propylene strip: a promising forensic tool

The environmental contamination by extremophile Aspergillus species, i.e., Aflatoxin B1, is hardly controllable in Southeast Asia and Sub-Saharan Africa, which lack handling resources and controlled storage facilities. Acute aflatoxicosis poisoning from aflatoxin-prone dietary staples could cause acute hepatic necrosis, acute liver failure, and death. Here, as the cheaper, more straightforward, and facile on-site diagnostic kit is needed, we report an ultraviolet-excitable optical aptasensor based on a fluorinated ethylene propylene film strip. Molecular dynamics on the aptamer.AFB1 complex revealed that the AFB1 to the aptamer increases the overall structural stability, suggesting that the aptamer design is suitable for the intended application. Under various influencing factors, the proposed label-free strategy offers a fast 20-min on-site fabrication simplicity and 19-day shelf-life. The one-pot incubation provides an alternative to catalytic detection and exhibited 4 times reusability. The recovery of crude brown sugar, processed peanuts, and long-grain rice were 102.74 ± 0.41 (n = 3), 86.90 ± 3.38 (n = 3), and 98.50 ± 0.42 (n = 3), comparable to High-Performance Liquid Chromatography-Photodiode Array Detector results. This study is novel owing to the peculiar UV-active spectrum fingerprint and the convenient use of hydrophobic film strips that could promote breakthrough innovations and new frontiers for on-site/forensic detection of environmental pollutants.

Acute liver failure: A clinically severe syndrome characterized by intricate mechanisms.

Acute liver failure presents as a clinical syndrome characterized by swift deterioration and significant mortality rates. Its underlying mechanisms are intricate, involving intricate interplays between various cells. Given the current scarcity of treatment options, there's a pressing need to diligently uncover the disease's core mechanisms and administer targeted therapies accordingly.

Auxiliary Partial Orthotopic Liver Transplantation Is a Safe and Effective Option for Yellow Phosphorus Toxin-induced Acute Liver Failure.

Ingestion of yellow phosphorus-containing rodenticides (YPR) or firecrackers is an important cause of acute liver failure (ALF) in young adults and children, particularly in South and South-East Asia and South America. Emergency liver transplantation is indicated in cases refractory to intensive supportive therapy, including low-volume plasma exchange. There are no published reports on the feasibility of auxiliary partial orthotopic liver transplantation (APOLT) for YPR-induced ALF. Clinical details of patients undergoing APOLT for YPR-induced ALF in 1 unit are reported. Details of postoperative follow-up, native remnant regeneration, and immunosuppression withdrawal are also reported. Between January 2021 and December 2023, 3 patients (4 y, 1.5 y, and 26 y) underwent emergency living donor liver transplantation for YPR-induced ALF. All patients were refractory to supportive therapies, including therapeutic plasma exchange, and demonstrated progression of liver injury in the form of severe encephalopathy needing intubation, ventilation, and organ support. APOLT was considered because of their young age and minimal intraoperative inotropic requirement. All explants showed confluent parenchymal necrosis with microvesicular and macrovesicular steatosis. Patients were initially maintained on standard immunosuppression. Good remnant regeneration was noted on follow-up imaging in all cases, enabling gradual withdrawal of immunosuppression. Currently, 1 child has been off immunosuppression for 15 mo and 2 others are on reduced doses of immunosuppression. All patients demonstrated good liver function. APOLT procedure can be an appropriate transplant option in YPR-related ALF for children and young adults without severe hemodynamic instability.

Clinical characteristics and prognosis of liver injury induced by immune checkpoint inhibitors in patients with malignancies: A real-world retrospective study.

Programmed cell death receptor (ligand)-1 inhibitors (PD-(L)1), as the preferred immunotherapy, have been widely used in the Chinese mainland and drug-induced liver injury (DILI) has been reported. The study aimed to investigate the clinical features or risk factors for immunotherapy-related DILI. Patients who received PD-(L)1 inhibitors from January 2020 to July 2021 were retrospectively reviewed. The likelihood of DILI was adjudicated by the Roussel-Uclaf causality assessment. A total of 1175 patients were included in the study and 89 patients (7.6%) developed DILI, of which 12 (13.5%) progressed to acute liver failure (ALF) and three (3.4%) died. Among the DILI population, 56 (62.9%) had a cholestatic pattern and exhibited a prolonged treatment course and duration for resolution compared to the hepatocellular and mixed patterns. Hepatocellular carcinoma (HCC), hepatitis B virus (HBV) and abnormal baseline of alkaline phosphatase (ALP) had increased risks of DILI by 2.1-fold (95% confidence interval [CI], 1.231-3.621), 1.9-fold [95% CI, 1.123-3.325] and 2.1-fold [95% CI, 1.317-3.508], respectively. The model for end-stage liver disease (MELD) score had a c-statistic of 0.894 (95% CI, 0.778-1.000) with a sensitivity of 67% and a specificity of 95% for poor outcomes. COX analysis showed that the MELD ≥ 18 was predictive of immunotherapy-related ALF or death. PD-(L)1 inhibitor-related liver injury manifests primarily as a cholestatic pattern, on which corticosteroid treatment has minimal effect compared to hepatocellular and mixed patterns. MELD score ≥ 18 at the time of liver injury performed best in the prediction of ALF or death in immune checkpoint inhibitor (ICI)-related DILI.

Liver transplantation in acute and acute-on-chronic liver failure

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are diseases with arapidly progressive course and high mortality. Apart from treating the underlying triggers and intensive care measures, there are very limited therapeutic options for either condition. Liver transplantation is often the only life-saving treatment, but it cannot always be employed due to contraindications and severe disease progression. ACLF is characterized by underlying liver cirrhosis and typical triggers such as bacterial infections, bleeding, or alcohol binges. ALF occurs in previously healthy livers, usually as aresult of purely hepatotoxic events. Disease differences are also reflected in the course and regulations of liver transplantation. Newer prognostic parameters and prioritization programs for ACLF can help improve both waiting list mortality and outcomes after transplantation.

Hepatic microcirculatory disturbance in liver diseases: intervention with traditional Chinese medicine.

The liver, a complex parenchymal organ, possesses a distinctive microcirculatory system crucial for its physiological functions. An intricate interplay exists between hepatic microcirculatory disturbance and the manifestation of pathological features in diverse liver diseases. This review updates the main characteristics of hepatic microcirculatory disturbance, including hepatic sinusoidal capillarization, narrowing of sinusoidal space, portal hypertension, and pathological angiogenesis, as well as their formation mechanisms. It also summarized the detection methods for hepatic microcirculation. Simultaneously, we have also reviewed the characteristics of microcirculatory disturbance in diverse liver diseases such as acute liver failure, hepatic ischemia-reperfusion injury, viral hepatitis, non-alcoholic fatty liver disease, hepatic fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Finally, this review also summarizes the advancement in hepatic microcirculation attributed to traditional Chinese medicine (TCM) and its active metabolites, providing novel insights into the application of TCM in treating liver diseases.

Prophylactic Effects of Methanolic Leaf Extract of Momordica balsamina Against CCL4 Induced Liver Injury in Wistar Rats

Introduction: Liver injury can result from various causes, including alcohol consumption, viral infections (such as hepatitis), autoimmune diseases, metabolic disorders, and exposure to certain chemicals, drugs or toxins. It can manifest as inflammation, fatty liver disease, cirrhosis, or acute liver failure, depending on the cause and severity. Treatment often involves addressing the underlying cause, lifestyle changes (such as avoiding alcohol or certain medications), and sometimes medication to support liver function or manage specific conditions. Early detection and management are crucial for preventing further damage and promoting liver health. Studies have reported the effects of Momordica balsamina on liver injury. Aim: This study aim to evaluate the prophylactic effect of methanolic leaf extract of Momordica balsamina against CCL4-induced liver injury in Wistar Rats. Methodology: The fresh leaves of Momordica balsamina were purchased at Marina Market, Sokoto, the plant was air dry at room temperature for 2 weeks and the air-dried leaves were processed with methanol to obtain methanolic extract. An acute toxicity study of M. balsamina extract was conducted with six doses (10, 100, 1000, 1600, 2900 and 5000 mg/kg) to evaluate its safety. Phytochemical analysis of the extract was carried out to detect the presence or absence of carbohydrates, saponins, flavonoids, tannins, phenols, protein, alkaloids, cardiac glycosides and steroids. A total of 42 Wistar rats (170±20g) of either sex roughly of the same age (8-10 weeks) were used for the study. After two weeks of acclimatization, the rats were randomly divided into six groups of seven rats each; group 1 (normal control) treated with distilled water and vital feeds; groups 2 (Negative control) CCl4 treated with liver injury not on treatment; group 3 (Standard control) CCl4 liver injury treated with 50 mg/kg Silymarin; group 4 (500 mg/kg M. balsamina + 2mL CCl4); group 5 (1000 mg/kg M. balsamina + 2mL CCl4) and group 6 (1500 mg/kg M. balsamina + 2mL CCl4) for 4 weeks. On the last day, the rats were anaesthetized, and blood and liver organ were collected for biochemical and histomorphology study. Results: The prophylactic effects of methanolic leaf extract of Momordica balsamina against CCl4-induced liver injury were evaluated on liver function tests (LFTs) and Malondialdehyde (MDA). This study shows that Momordica balsamina extract significantly (P&lt; 0.05) decreased the level of serum AST, ALT, ALP, TB and DB positively by inhibiting their raise at dose-dependent manner compared to the negative control, equally, the extract increased the serum level of Albumin and total protein when compared to the negative control. On the other hand, the extract shows significant reduction of serum level of Malondialdehyde (MDA) near to normal at varying dose. The finding of the prophylactic effect of methanolic leaf extract of Momordica balsamina on histology shows significant improvement on liver cell with notable recovery and appearance of the histological architecture of the hepatocyte at the highest dose (1500 mg/kg+2mL CCl4) compared to negative control group. Conclusion: The presence of phytochemical compounds and antioxidant properties as well as a gene that is responsible for its prophylactic effect may be one of the mechanisms through which the plant extract was able to exert prophylactic effect on CCl4 induced liver injury in Wistar rats. This study suggests that M. balsamina extract may be considered as an affordable and non-invasive treatment option for liver injury in human.

Hubungan Antara Pemeriksaan Antibodi IgG Dengan Uji SGOT SGPT Pada Pasien Demam Berdarah Dengue Di RSU Sinar Kasih Purwokerto

Dengue Hemorrhagic Fever (DHF) is a disease caused by infection with the dengue virus which is transmitted through the bite of the Aedes aegypti mosquito. The main clinical manifestations of this disease can be an increase in body temperature ≥ 38°C for 2 - 7 days, bleeding which is usually preceded by the appearance of red spots (petechiae), headache, joint pain accompanied by leukopenia, lymphadenopathy, thrombocytopenia and hemorrhagic diathesis. Liver dysfunction is one of the consequences of dengue infection that often occurs in patients. The liver is the target organ of the dengue virus which often appears in the form of hepatomegaly and a mild-moderate increase in aminotransferase enzyme levels although jaundice and acute liver failure are rare. Dengue patients have an increase in SGOT and SGPT levels. This study aims to determine whether there is a relationship between dengue IgG levels and SGOT and SGPT in Dengue Hemorrhagic Fever patients at RSU Sinar Kasih Purwokerto. The type of research used is an analytical study with a cross-sectional approach. Sampling was carried out using a consecutive sampling technique. Results were obtained from 100 samples with normal SGOT SGPT examination results, namely 10 patients and high results, namely 90 patients. The results of SGOT and SGPT examinations in dengue IgG positive patients increased &gt;3 times which was included in category B and there was a significant relationship between SGOT and SGPT levels in Dengue IgG positive patients, with a p-value of 0.000, indicating a strong relationship between SGOT levels and SGPT with IgG examination results.

Chrysosaxillins A-E, cucurbitane triterpenoid derivatives from Chrysosplenium axillare Maxim. (Yajima) and their cytotoxic activities

Chrysosplenium axillare Maxim. is used in traditional Tibetan medicine for the treatment of various human diseases, such as fever, headache, cholecystitis, acute icterohepatitis and acute liver necrosis. In this study, five new cucurbitane triterpenoid derivatives, chrysosaxillins A-E (1–5), along with three known structurally related compounds (6–8) have been isolated from whole herb of C. axillare. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR, HRESIMS, UV, IR, ECD and single-crystal X-ray diffraction. All isolates were evaluated for cytotoxic activities against four tumor cell lines including PC-3, A549, MCF-7, and HepG2. The results discovered that compound 1 possessed the most potent cytotoxicity against A549 cells with IC50 value of 0.05 μM, while compounds 2 and 4 have mild cytotoxicities against cells tested with IC50 values ranging from 8.78 to 41.72 μM. Our study suggests that C. axillare might serve as a valuable source of cucurbitane triterpenoids potentially useful for the development of new anti-tumor agents and support its use as a crop benefits to local economic.

Hepatitis E virus: from innate sensing to adaptive immune responses.

Hepatitis E virus (HEV) infections are a major cause of acute viral hepatitis in humans worldwide. In immunocompetent individuals, the majority of HEV infections remain asymptomatic and lead to spontaneous clearance of the virus, and only a minority of individuals with infection (5-16%) experience symptoms of acute viral hepatitis. However, HEV infections can cause up to 30% mortality in pregnant women, become chronic in immunocompromised patients and cause extrahepatic manifestations. A growing body of evidence suggests that the host immune response to infection with different HEV genotypes is a critical determinant of distinct HEV infection outcomes. In this Review, we summarize key components of the innate and adaptive immune responses to HEV, including the underlying immunological mechanisms of HEV associated with acute and chronic liver failure and interactions between T cell and B cell responses. In addition, we discuss the current status of vaccines against HEV and raise outstanding questions regarding the immune responses induced by HEV and treatment of the disease, highlighting areas for future investigation.

Ammonia and urea metabolism in acute liver failure: A multicentre cohort study.

Ammonia is metabolized into urea in the liver. In acute liver failure (ALF), ammonia has been associated with survival. However, urea variation has been poorly studied. Observational cohort including ALF patients from Curry Cabral Hospital (Lisbon, Portugal) and Clinic Hospital (Barcelona, Spain) between 10/2010 and 01/2023. The United States ALF Study Group cohort was used for external validation. Primary exposures were serum ammonia and urea on ICU admission. Primary endpoint was 30-day transplant-free survival (TFS). Secondary endpoint was explanted liver weight. Among 191 ALF patients, median (IQR) age was 46 (32; 57) years and 85 (44.5%) were males. Overall, 86 (45.0%) patients were transplanted and 75 (39.3%) died. Among all ALF patients, following adjustment for age, sex, body weight, and aetiology, higher ammonia or lower urea was independently associated with higher INR on ICU admission (p < .009). Among all ALF patients, following adjustment for sex, aetiology, and lactate, higher ammonia was independently associated with lower TFS (adjusted odds ratio (95% confidence interval [CI]) = 0.991 (0.985; 0.997); p = .004). This model predicted TFS with good discrimination (area under receiver operating curve [95% CI] = 0.78 [0.75; 0.82]) and reasonable calibration (R2 of 0.43 and Brier score of 0.20) after external validation. Among transplanted patients, following adjustment for age, sex, actual body weight, and aetiology, higher ammonia (p = .024) or lower (p < .001) urea was independently associated with lower explanted liver weight. Among ALF patients, serum ammonia and urea were associated with ALF severity. A score incorporating serum ammonia predicted TFS reasonably well.