Impaired Liver Function Research Articles

The role of ferroptosis-related non-coding RNA in liver fibrosis

Liver fibrosis represents a reversible pathophysiological process, caused by chronic inflammation stemming from hepatocyte damage. It delineates the initial stage in the progression of chronic liver disease. This pathological progression is characterized by the excessive accumulation of the extracellular matrix (ECM), which leads to significant structural disruption and ultimately impairs liver function. To date, no specific antifibrotic drugs have been developed, and advanced liver fibrosis remains largely incurable. Liver transplantation remains the sole efficacious intervention for advanced liver fibrosis; nevertheless, it is constrained by exorbitant costs and the risk of postoperative immune rejection, underscoring the imperative for novel therapeutic strategies. Ferroptosis, an emergent form of regulated cell death, has been identified as a pivotal regulatory mechanism in the development of liver fibrosis and is intricately linked with the progression of liver diseases. Recent investigations have elucidated that a diverse array of non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, are involved in the ferroptosis pathway, thereby modulating the progression of various diseases, including liver fibrosis. In recent years, the roles of ferroptosis and ferroptosis-related ncRNAs in liver fibrosis have attracted escalating scholarly attention. This paper elucidates the pathophysiology of liver fibrosis, explores the mechanisms underlying ferroptosis, and delineates the involvement of ncRNA-mediated ferroptosis pathways in the pathology of liver fibrosis. It aims to propose novel strategies for the prevention and therapeutic intervention of liver fibrosis.

Prenatal exposure to PM2.5 disturbs the glucose metabolism of offspring fed with high-fat diet in a gender-dependent manner

Studies have shown that maternal exposure to PM2.5 could potentially disrupt glucose and lipid metabolism in offspring supplied with high-fat diet, yet whether this effect is gender-dependent or not and the underlying biological mechanisms are not well understood. In our current research, female ICR mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) before and during pregnancy. The offspring mice were fed with control diet (CD) or high-fat diet (HFD) for 9 weeks, and their metabolic conditions were analyzed. Our findings reveal that maternal exposure to PM2.5 induced glucose intolerance and insulin resistance in female offspring fed with HFD but not in males. Specifically, hepatic insulin resistance as indicated by significantly decreased AKT phosphorylation (p-AKT) level, changed liver structure as indicated by increased ballooning and steatosis based on H&E staining images, and impaired liver function as indicated by up-regulated ALT activity were observed in HFD-fed female offspring from CAP-exposed mothers in comparison to those from FA-exposed ones. Further analysis indicated that these impacts of prenatal PM2.5 exposure on glucose metabolism in offspring may result from disturbed gluconeogenesis and induced inflammatory response in liver. Our research underscores that prenatal PM2.5 exposure induces glucose metabolism abnormalities in offspring fed with HFD in a gender-dependent manner, and the liver potentially serves as a key player in mediating these effects of maternal PM2.5 exposure.

Histological Improvement of Hepatic Fibrosis of Decompensated Liver Cirrhosis after Prednisolone and Azathioprine Treatment in a Patient with Autoimmune Hepatitis.

The treatment of the underlying cause of liver disease may potentially reverse hepatic fibrosis. However, it remains uncertain whether improvement in fibrosis can be observed in decompensated liver cirrhosis (LC). Here, we present a case of autoimmune hepatitis (AIH)-related LC in which histological improvement of fibrosis was achieved despite the presence of decompensated LC. A Japanese female in her 20s was initially identified as having liver function impairments during her employment medical checkup. Following a laparoscopic liver biopsy, she was diagnosed with AIH-related decompensated LC (F4 and A3) with a Child-Pugh score of 10. The patient initially received treatment with prednisolone at a daily dose of 40 mg, followed by 20 mg/day of prednisolone plus 25 mg/day of azathioprine (subsequent increase of azathioprine to 100 mg/day). With this treatment, the abnormal serum marker levels returned to normal, thereby enabling the patient to avoid liver transplantation eight months after the initiation of treatment. Moreover, marked improvement was observed in non-invasive tests for hepatic fibrosis, including the FIB-4 index and FibroIndex, as well as liver stiffness evaluated by FibroScan®. Eleven months after diagnosis, the patient developed a cholestatic liver injury and was diagnosed with drug-induced cholestatic liver disease (azathioprine overcapacity as the causative agent). By percutaneous liver biopsy at this point, hepatic fibrosis (F2-3) was markedly improved compared with that at the diagnosis. Along with the improvement of hepatic fibrosis, notable improvements were also observed in patient-reported outcomes such as the SF-36® score and chronic liver disease questionnaire. In this report, we first described a case of AIH that showed a histological improvement of hepatic fibrosis even in decompensated LC by treatment with prednisolone and azathioprine.

The Association Between Brominated Flame Retardants Exposure and Liver-Related Biomarkers in US Adults

Background: Emerging studies demonstrate that exposure to brominated flame retardants (BFRs) can have harmful effects on human health. Our study focused on the relationship between exposure to various BFRs and markers of liver function. Methods: To further explore the association between BFR exposure and liver function impairment, we used data from the National Health and Nutrition Examination Surveys (NHANES) for three cycles from 2009 to 2014, leaving 4206 participants (≥20 years of age) after screening. Nine BFRs and eight liver function tests (LFTs) were measured in the participants’ serum to represent BFRs and liver function impairment in vivo. To investigate whether there is a relationship between BFRs and health outcome, statistical research methods such as the weighted linear regression model, restricted cubic spline (RCS), weighted quantile sum (WQS), quantile-based g computing (QGC), and the Bayesian Kernel Machine Regression (BKMR) were used to evaluate the correlation between serum BFRs and LFTs. Results: The studies reveals that exposure to BFRs is associated with liver function biomarkers. In a weighted linear regression model, we found that PBB153, PBDE99, PBDE154, PBDE209, PBDE85 exposure was positively correlated with AST, ALT, GGT, ALP, TP, and SL risk. In RCS model, the nonlinear relationships between PBB153 and AST, ALT, and GGT and PBDE209 and ALT and TP are the most significant. The exposure to combined BFRs was positively correlated with AST, ALT, and GGT in WQS and QGC models. BKMR analysis showed that BFR exposure was positively correlated with AST, ALT, ALP, and GGT. Conclusions: Exposure to BFRs is associated with liver function impairment, suggesting that BFR exposure is potentially toxic to the human liver, but more in-depth studies are needed to explore this correlation.

Use of Non-Invasive Biomarkers and Clinical Scores to Predict the Complications of Liver Cirrhosis: A Bicentric Experience.

Background and objectives: Liver cirrhosis is a chronic, progressive condition characterized by fibrosis and architectural distortion of the liver, leading to impaired liver function and severe complications. Accurately predicting these complications is crucial to the improvement of patient outcomes. Therefore, this study aimed to evaluate the accuracy of various non-invasive biomarkers and clinical scores in assessing the risk of complications among cirrhotic patients. Materials and methods: We conducted an observational retrospective study involving 236 cirrhotic patients from two tertiary care hospitals in Italy and Romania, in a timespan ranging from January 2021 to March 2024. Data on clinical characteristics, liver function tests, hematological indices, various non-invasive biomarkers, and clinical scores were collected and analyzed. Receiver operating characteristic analysis was performed to assess the accuracy of these biomarkers and clinical scores in predicting complications, including the presence of varices and hepato-renal syndrome. Results: The Child-Pugh score showed the highest accuracy for cirrhosis-related complications, with an area under curve (AUC) = 0.667. The red cell distribution width coefficient of variation followed closely with an AUC = 0.646. While the Child-Pugh score had a high specificity (85.42%), its sensitivity was low (37.97%). In patients with varices, non-invasive scores such as platelet distribution width (PDW) and the RDW-to-platelet ratio (RPR) showed modest predictive ability, with an AUC = 0.594. For hepato-renal syndrome, the Model for End-Stage Liver Disease (MELD) score showed the highest diagnostic accuracy with an AUC = 0.758. Conclusions: The most reliable biomarkers for detecting complications, varices, and hepato-renal syndrome, are, respectively, the Child-Pugh Score, PDW along with RPR, and the MELD score. However, while these scores remain valuable, the moderate diagnostic accuracy of other indices suggests the need for a more integrated approach to risk stratification. Future research should focus on validating these tools across different populations and incorporating emerging biomarkers to enhance predictive accuracy and inform more effective clinical decision-making.

A rat model of cirrhosis with well-differentiated hepatocellular carcinoma induced by thioacetamide

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA. These rats received bi-weekly injections of either 200 mg/kg TAA or saline (as a control) over a period of 34 weeks. The development of cirrhosis and hepatocarcinogenesis was monitored through histopathological examinations, biochemical markers, and immunohistochemical analyses. Our results demonstrated that chronic TAA administration induced cirrhosis aggressive cholangiocarcinoma in addition to well-differentiated HCC, providing a model for early-stage, stage and a mixed liver cancer phenotype. This model is characterized by increased fibrosis, altered liver architecture, and increased hepatocyte proliferation. Biochemical analyses revealed significant alterations in liver function markers, including elevated alpha-fetoprotein (AFP) levels, without affecting kidney function or causing significant weight loss or mortality in rats. This TAA-induced cirrhosis and mixed HCC rat model successfully replicates the clinical progression of human HCC, particularly in terms of liver function impairment and early-stage liver cancer characteristics. It serves as a valuable tool for future research on the mechanisms of antitumor drugs in tumor initiation and development.

Therapeutic Effectiveness of Prunus dulcis for Nephroprotective and Hepatoprotective in Albino Mice

Background: Nephrotoxicity caused by GM is a complicated occurrence that results in a variety of structural and functional changes, including lesions in the glomerular region and proximal tubule damage, which leads to sudden kidney failure. The production of reactive oxygen species (ROS) has also been linked to GM. Acute hepatic impairments caused by medication might lead to rapid deterioration of liver function. Objective: The purpose of this study was to evaluate the suspension of nuts of Prunus dulcis at a lower dose (800 mg/kg, b.w.) and a higher dose (1600 mg/kg, b.w.) for nephroprotective and hepatoprotective activities. Materials and Methods: Drug-induced nephrotoxicity and drug-induced hepatotoxicity models were used to evaluate the nephroprotective and hepatoprotective activity using albino mice. A histopathological study was also performed. Results: Suspension of nuts Prunus dulcis exhibited significant nephroprotective and hepatoprotective activity. Suspension of nuts from Prunus dulcis at a higher dose (1600 mg/kg b.w.) showed higher nephroprotective and hepatoprotective activity compared to the lower dose (800 mg/kg). The nephroprotective activity was evident by decreased serum creatinine, uric acid, serum urea, and BUN, which were confirmed by histological study. The hepatoprotective effect was confirmed by significantly decreased serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, and total bilirubin levels in treated groups, which were further confirmed by histopathological study. Conclusion: The result suggests that Prunus dulcis possesses nephroprotective and hepatoprotective activities.

Key Factors Influencing Liver Function Injury in Elderly Patients with Newly Diagnosed Pulmonary Tuberculosis Complicated by Diabetes after Antituberculosis Treatment.

This study addressed the factors influencing liver injury in elderly patients newly diagnosed with pulmonary tuberculosis and diabetes after antituberculosis treatment. From January 2021 to June 2023, 218 elderly patients with early treatment of pulmonary tuberculosis (N = 218) combined with diabetes (N = 218) were collected as research subjects. All patients were treated with the same antituberculosis treatment regimen and were divided into a nonhepatotoxicity group (N = 92) and a hepatotoxicity group (N = 126) according to whether drug-induced liver injury occurred within 3 months after taking tuberculosis drugs. The levels of alanine aminotransferase and aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, albumin, lipoprotein(a), prothrombin time, and hemoglobin A1c (HbA1c) were detected by biochemical analyzer. The extent of pulmonary tuberculosis lesions was examined by computed tomography imaging. Influencing factors of antituberculosis drug-induced liver injury were analyzed by logistic multivariate analysis. The hepatotoxicity group exhibited a higher average age than the nonhepatotoxicity group (P <0.05). Additionally, there was a greater prevalence of patients with a history of alcohol consumption in the hepatotoxicity group than in the nonhepatotoxicity group (P <0.05). And the hepatotoxicity group showed a greater extent of tuberculosis lesions (P <0.05). Logistic multivariate analysis identified advanced age, body mass index of <18.5, lesion range of ≥2 lung lobes, history of alcohol consumption, and HbA1c of ≥8% as relevant factors associated with liver function impairment in older adults patients undergoing early treatment of pulmonary tuberculosis combined with diabetes after antituberculosis therapy. These findings underscore the importance of monitoring and addressing these factors during antituberculosis therapy in the elderly population to mitigate the risk of liver function impairment.

New Scenarios in Liver Transplantation for Hepatocellular Carcinoma.

Despite liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC), particularly in patients with impaired liver function, the shortage of donors has forced the application of very restrictive criteria for selecting ideal candidates for whom LT can offer the best outcome. With the evolving LT landscape due to the advent of direct-acting antivirals (DAAs) and the steady increase in donors, major efforts have been made to expand the transplant eligibility criteria for HCC. In addition, the emergence of immune checkpoint inhibitors (ICIs) for the treatment of HCC, with demonstrated efficacy in earlier stages, has revolutionized the therapeutic approach for these patients, and their integration in the setting of LT is challenging. Management of immunological compromise from ICIs, including the wash-out period before LT and post-LT immunosuppression adjustments, is crucial to balance the risk of graft rejection against HCC recurrence. Additionally, the effects of increased immunosuppression on non-hepatic complications must be understood to prevent them from becoming obstacles to long-term OS. In this review, we will evaluate the emerging evidence and its implications for the future of LT in HCC. Addressing these novel challenges and opportunities, while integrating the current clinical evidence with predictive algorithms, would ensure a fair balance between individual patient needs and the overall population benefit in the LT system.

Can Fasting Practices Improve Vitamin D Levels?

Vitamin D deficiency is emerging as a very serious public health problem. Numerous epidemiological studies link vitamin D deficiency to the pathophysiological process of several acute and chronic diseases. Sun exposure, vitamin D supplementation, and fortification of foods with vitamin D are the present strategies adopted to tackle this epidemic. While this can be effective, recent evidence suggests the need to consider the multifaceted causation of vitamin D deficiency such as impaired liver function, kidney function, hyperparathyroidism, and endocrine dysfunction. Therapeutic fasting, a popular nutritional approach has shown to have a positive association with vitamin D levels. This perspective attempts to provide an overview of literature discussing fasting and vitamin D, the possible mechanisms behind this association, and discusses the future possibilities of using fasting as a public/clinical tool in mitigating vitamin D deficiency.

Atezolizumab/bevacizumab and lenvatinib for hepatocellular carcinoma: A comparative analysis in a European real-world cohort.

Immunotherapy-based combinations are currently the standard of care in the systemic treatment of patients with HCC. Recent studies have reported unexpectedly long survival with lenvatinib (LEN), supporting its use in first-line treatment for HCC. This study aims to compare the real-world effectiveness of LEN to atezolizumab/bevacizumab (AZ/BV). A retrospective analysis was conducted to evaluate the effectiveness and safety of frontline AZ/BV or LEN therapy in patients with advanced HCC across 18 university hospitals in Europe. The study included 412 patients (AZ/BV: n=207; LEN: n=205). Baseline characteristics were comparable between the 2 treatment groups. However, patients treated with AZ/BV had a significantly longer median progression-free survival compared to those receiving LEN. The risk of hepatic decompensation was significantly higher in patients with impaired baseline liver function (albumin-bilirubin [ALBI] grade 2) treated with AZ/BV compared to those with preserved liver function. Patients with alcohol-associated liver disease had poorer baseline liver function compared to other etiologies and exhibited a worse outcome under AZ/BV. In this real-world cohort, survival rates were similar between patients treated with LEN and those treated with AZ/BV, confirming that both are viable first-line options for HCC. The increased risk of hepatic decompensation in patients treated with AZ/BV who have impaired baseline liver function underscores the need for careful monitoring. Future trials should aim to distinguish more clearly between metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease.

The Inter-Laennec Approach for Liver Tumors in Contact with Hepatic Veins in Laparoscopic Liver Resection.

Patients with liver tumors that are in contact with the major hepatic veins may require hepatic vein resection to achieve an adequate surgical margin; however, the potential for venous congestion and impaired remnant liver function must be considered. We introduce the anatomy of the hepatic vein related to Laennec's capsule as well as the surgical techniques to overcome these limitations in the laparoscopic approach.1,2 PATIENTS AND METHODS: A patient with hepatocellular carcinoma underwent resection of the paracaval portion of the caudate lobe. A 4.5-cm tumor was located on the hepatic hilum, compressing the middle and right hepatic veins (MHV and RHV). The Laennec's capsule around the hepatic veins consists of cardiac and hepatic layers. In the inter-Laennec approach, the hepatic veins and inferior vena cava were continuously exposed from the root side, during entry into the space between the hepatic and cardiac Laennec's capsules.3,4 Hence, the cardiac Laennec's capsule was preserved on the venous side, and the strength of the hepatic vein walls was maintained without exposing the tumor. Parenchymal transection was performed while preserving the MHV and RHV. The operative time was 331 min, with minimal estimated blood loss. The patient was discharged on postoperative day 6 without complications. A pathological examination revealed the presence of focal capsular invasion; however, the surgical margin was maintained by leaving the hepatic Laennec's capsule on the tumor side. Understanding the structure of the Laennec's capsule can contribute to the establishment of safe and feasible liver resection techniques.

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

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

Liver function tests in patients receiving high-intensity care after hospital admission for acute heart failure: the STRONG-HF trial

Abstract Background/Introduction Episodes of acute heart failure (AHF) unfavorably affect extra-cardiac organs such as the liver due to altered hemodynamics and neurohormonal activation. In AHF, elevated levels of levels of alanine aminotransferase (ALT) and total bilirubin (tBil) may reflect congestion and impaired liver function, while lower levels of ALT (which is also produced in muscle cells) correlate with malnutrition and sarcopenia. Thus, the clinical importance of these markers in AHF and the post-discharge period is unclear. Purpose To assess circulating concentrations of ALT and tBil in patients with AHF before discharge and during high-intensity care (HIC) vs usual care follow-up in association with clinical outcomes. Methods ALT and tBil concentrations were measured 1-2 days before discharge in patients hospitalized for AHF (baseline), and again after 90 days of either HIC or usual care according to the STRONG-HF protocol. Baseline values and changes in ALT and tBil were analyzed in association with the primary outcome of all-cause death or HF readmission by day 180. Results At baseline, the median (Q1-Q3) concentrations of ALT and tBil were 21 (15-32) U/L and 14 (10-21) umol/L, respectively. Lower levels of both ALT and tBil were associated with female sex, Black race, lower BMI, higher LVEF, lower hemoglobin, lower creatinine and less frequent atrial fibrillation/flutter, while there were no significant associations with age. Patients with lower ALT, but not tBil, were more likely to have edema, elevated JVP and orthopnea, and used higher loop diuretic doses and less beta-blockers, pre-randomization (Figure, panel A). ALT was inversely associated with risk for the primary outcome (HR 0.81 [95%CI 0.65,1.00) per log increment, p=0.05), while there was no association with risk for tBil (HR 1.04 [95%Ci 0.84-1.28], p=0.73) (Figure, panel B). After 90 days, ALT and tBil concentrations were lower than at baseline, with a greater reduction in tBil in the HIC group vs usual care group (mean -1.7 [95%CI -3.0,-0.4] umol/L, p=0.01), while there was no significant between-group differences in ALT changes (mean -0.6 [95%CI -4.7,3.4] U/L, p=0.75) (Figure, panel C). The treatment effect of HIC over usual care on the primary outcome was consistent across the range of baseline ALT (P-interaction=0.30) and tBil (P-interaction=0.80) (Figure, panel D). Conclusion Contrary to our hypothesis of higher liver function tests with hepatic congestion in AHF, lower ALT was associated with more congestion and worse outcomes among patients hospitalized for AHF in STRONG-HF. There was no prognostic value from tBil levels. This suggests that ALT may be a marker of sarcopenia in these patients. Importantly, the beneficial effect of HIC on clinical outcomes is consistent irrespective of ALT and tBil levels at discharge.Figure

Impact of CFTR modulatory therapies on liver function and fibrosis indices in cystic fibrosis patients: a retrospective analysis from two Romanian medical centers

Background. Patients with cystic fibrosis (CF) frequently require modulatory therapies such as Lumacaftor/Ivacaftor (LI) and Elexacaftor/Tezacaftor/Ivacaftor (ETI) to manage their condition. Given the potential hepatic complications associated with CF, it is critical to understand the impact of these therapies on liver function and fibrosis indices. This study aimed to evaluate the changes in liver function markers and fibrosis indices in CF patients undergoing LI and ETI therapies, with a specific focus on the influence of underlying hepatic disease. Methods. In this retrospective analysis, liver function markers and fibrosis indices were assessed in CF patients receiving ETI (n=24), LI (n=4), or a combination of both (LI/ETI, n=8). Key liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, platelet count, and fibrosis indices (APRI and FIB-4), were measured at baseline and at various time points up to 12 months. Results. In patients receiving LI therapy, ALT and AST levels demonstrated a slight but non-significant decrease over six months, accompanied by significant fluctuations in total bilirubin levels. Among those receiving ETI therapy, ALT and AST levels initially increased but stabilized over time, while total bilirubin levels significantly increased from baseline to 12 months. No significant differences were observed in liver function markers between patients with and without hepatic disease under ETI therapy. Trends in fibrosis indices (APRI and FIB-4) were modest and largely non-significant across both therapies. Conclusions. ETI therapy appears to be safe for CF patients, including those with pre-existing hepatic disease, with no significant deterioration in liver function over a 12-month period. However, the observed fluctuations in bilirubin levels underscore the necessity for ongoing monitoring. Further research is warranted to investigate the long-term hepatic effects of LI and ETI therapies.

Changes in interoception before and after treatment in patients with alcohol use disorder.

To investigate the factors associated with interoception in patients with alcohol use disorder and determine whether treatment causes changes in their interoception. The Body Perception Questionnaire-Body Awareness ultra-short version Japanese version (BPQ-BAVSF-J) was used to measure interoception in 50 alcohol-dependent participants (27 in the inpatient group and 23 in the outpatient group). The BPQ-BAVSF-J was administered and data on aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), mean corpuscular volume, platelet count, and Fib-4 index were extracted at admission and immediately before discharge for the inpatient group and at the first outpatient visit and approximately 3 months after the visit for the outpatient group. The mean age of the 50 participants was 51.0 ± 12.3 years. Significant associations were found between the BPQ-BAVSF-J and Fib-4 index and AST. The BPQ-BAVSF-J score significantly decreased at discharge in the inpatient group. AST, ALT, γ-GTP, and Fib-4 index of liver function were also significantly lower at discharge. In contrast, in the outpatient group, there were no significant changes in the BPQ-BAVSF-J score, AST level, ALT level, γ-GTP level, and Fib-4 index between at the first outpatient visit and approximately 3 months after the visit. Interoception in patients with alcohol use disorder increased with worsening liver function and decreased with improvement in liver function owing to treatment. This suggests that the BPQ-BAVSF-J score, an easily accessible scale, may be used to detect early deterioration of liver function through regular administration.

Association of initial serum sodium change and clinical outcome in patients with diabetes receiving sodium-glucose cotransporter-2 inhibitor therapy: A multicentre database analysis in Taiwan.

The study aimed to assess the impact of varying degrees of initial serum sodium change among patients with type 2 diabetes (T2D) starting sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy and their subsequent clinical outcome. We used medical data from a multicentre health care provider in Taiwan and recruited 4400 patients with T2D with baseline normal serum sodium (135-145 mmol/L) and follow-up serum sodium measures available after 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2021. After a median of 2.9 (2.4, 3.4) months of SGLT2i treatment, overall, there was a minimal change in serum sodium levels (from 139.6 ± 2.4 to 139.5 ± 3.7 mmol/L). Most patients (87.8%) maintained normal sodium levels, while 8.6% (n = 378) experienced hyponatraemia (<135 mmol/L) and 3.6% (n = 158) hypernatraemia (>145 mmol/L). Factors independently associated with hyponatraemia included cancer history, chronic lung disease, insulin use, higher glycated haemoglobin, impaired liver function, lower baseline sodium and greater initial decline in kidney function. Conversely, factors linked to hypernatraemia included older age, absence of cancer history, loop diuretic and non-steroidal anti-inflammatory drug use, higher baseline sodium and a lesser initial decline in kidney function. Over a median of 26.0 months of follow-up, hyponatraemia shortly after starting SGLT2i therapy was associated with significantly increased risks of major adverse cardiovascular events [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.83-3.48], heart failure for hospitalization (HR: 1.66; 95% CI: 1.16-2.37), major adverse renal events (HR: 2.27; 95% CI: 1.73-2.96) and all-cause death (HR: 2.98; 95% CI: 2.17-4.11) after adjusting for clinically relevant factors. Non-linear analysis indicated that a more pronounced initial decline in serum sodium levels correlated steeply with higher risks of these adverse events. While most patients with T2D maintain stable serum sodium homeostasis on SGLT2i therapy, a subset may experience dysnatraemic events with potential worse clinical consequences. Physicians should be vigilant about monitoring sodium levels and considering the associated risks when initiating SGLT2i therapy in patients with risk.

A Practical Study on the Relationship between Serum Iron Elevation and Liver Enzymes Plus Other Factors in Patients with Beta-Thalassemia

Thalassemia is a genetic condition characterized by faulty hemoglobin synthesis and low hemoglobin concentration. Overload of iron is an unavoidable condition experienced by severe thalassemia patients as a result of excessive blood transfusions. We looked at impaired liver function in thalassemia individuals with Iraq as a result of these issues. Our findings demonstrated serum activity in hepatocytes, as well as a large rise in GOT and AIP in patients with elevated iron levels and a substantial rise in TSB. All of these elements may work together or independently to create chronic liver disease by causing damage in cells via oxidative mechanisms.

Chronic active Epstein–Barr Virus infection in a teenage girl with suspect autoimmune Hepatitis

BackgroundThe pathogenesis of chronic active Epstein–Barr virus (EBV) disease (CAEBV) is complex, involving infection, inflammation, and in some cases malignancy. EBV reactivates in some patients, who develop a chronic disease with infectious mononucleosis-like symptoms. On occasion, it might be confused with autoimmune hepatitis (AIH), based on the similar symptoms and elevated liver enzymes. We aimed to describe a similar case to remind reader of this disease.Case Presentation: A 14-year-old girl was diagnosed with AIH based on biopsy and biomarker findings 1 year prior to admission and initially presented with elevated liver enzymes, portal hypertension, and parenchymal liver disease. Despite steroid administration, her condition fluctuated, and she was admitted to the hospital several times. She underwent a renal biopsy because of massive ascites, hypoalbuminemia, and increased renal echogenicity. An evaluation for impaired liver function showed positivity for EBV IgM, IgG, and early antigen (EBEA) antibodies. A PCR-based assay showed 5265 copies/mL of EBV DNA in peripheral blood. Epstein–Barr encoding region (EBER) in situ hybridization revealed abundant positive cells. Immunohistochemistry for CD56 also showed abundant positive cells, and CAEBV was diagnosed on this basis. Chemotherapy, hematopoietic stem cell transplantation (HSCT), and liver transplantation were proposed but her family refused.ConclusionsCAEBV should be considered when diagnosing AIH or in cases of treatment-refractory AIH.

Innovative approaches to metabolic dysfunction-associated steatohepatitis diagnosis and stratification

The global rise in Metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic dysfunction-associated steatohepatitis (MASH) highlights the urgent necessity for noninvasive biomarkers to detect these conditions early. To address this, we endeavored to construct a diagnostic model for MASLD/MASH using a combination of bioinformatics, molecular/biochemical data, and machine learning techniques. Initially, bioinformatics analysis was employed to identify RNA molecules associated with MASLD/MASH pathogenesis and enriched in ferroptosis and exophagy. This analysis unveiled specific networks related to ferroptosis (GPX4, LPCAT3, ACSL4, miR-4266, and LINC00442) and exophagy (TSG101, HGS, SNF8, miR-4498, miR-5189–5p, and CTBP1-AS2). Subsequently, serum samples from 400 participants (151 healthy, 150 MASH, and 99 MASLD) underwent biochemical and molecular analysis, revealing significant dyslipidemia, impaired liver function, and disrupted glycemic indicators in MASLD/MASH patients compared to healthy controls. Molecular analysis indicated increased expression of LPCAT3, ACSL4, TSG101, HGS, and SNF8, alongside decreased GPX4 levels in MASH and MASLD patients compared to controls. The expression of epigenetic regulators from both networks (miR-4498, miR-5189–5p, miR-4266, LINC00442, and CTBP1-AS2) significantly differed among the studied groups. Finally, supervised machine learning models, including Neural Networks and Random Forest, were applied to molecular signatures and clinical/biochemical data. The Random Forest model exhibited superior performance, and molecular features effectively distinguished between the three studied groups. Clinical features, particularly BMI, consistently served as discriminatory factors, while biochemical features exhibited varying discriminant behavior across MASH, MASLD, and control groups. Our study underscores the significant potential of integrating diverse data types to enable early detection of MASLD/MASH, offering a promising approach for non-invasive diagnostic strategies.