Liver Dysfunction Research Articles

Physician and Patient Preferences for the Treatment of Metastatic Castration-Sensitive and Castration-Resistant Prostate Cancer: A Best-Worst Scaling Study in Japan.

Despite many prostate cancer (PC) treatment options in Japan, physicians' and patients' preferences in metastatic castration-sensitive PC (mCSPC) and castration-resistant PC (CRPC) are unclear. For this cross-sectional study, an online questionnaire survey based on the best-worst scaling (profile case) approach was designed. Physicians' and patients' questionnaires, comprising six attributes (efficacy, safety, target patients, dosage, administration, and medical expenditures), had 24 and 26 items for mCSPC and CRPC surveys, respectively. Four items were presented during each session; respondents selected the "most important" and "least important" among these. The objective was to elicit attributes important for treatment and their relative importance levels among physicians and patients and to explore similarities and differences in choices. Multinomial logit and hierarchical Bayesian models were applied, and preferences were presented as relative importance and utility values. Responses of 177 physicians (urologists: 173; oncologists: 4) and 292 patients (mCSPC: 94; CRPC: 198) were analyzed. Most patients with CRPC (63.1%) had no metastases. Efficacy was the most important attribute overall. Physicians considered patient survival the most important among efficacy items (11.1%), whereas patients with mCSPC prioritized prevention of metastases spread (9.7%) and prostate-specific antigen (PSA) elevation (9.3%). In CRPC, both physicians and patients prioritized prevention of metastasis development or its spread (physicians: 9.6%; patients: 8.3%) and PSA elevation (physicians: 9.3%; patients: 7.9%). After efficacy, physicians prioritized items related to target patients (cardiovascular disorders; mCSPC: 4.8%; CRPC: 3.4%), whereas patients prioritized safety (mCSPC: falls or fractures [5.6%]; CRPC: liver dysfunction [4.7%]). Patients with mCSPC were also concerned about rising medical expenditures (5.4%). Treatment efficacy was the most important attribute for both physicians and patients in Japan in mCSPC and CRPC settings, although their preferences differed in priority based on outcomes. These findings may be useful to improve shared decision-making for PC treatment in Japan.

Early Sepsis Metabolic Changes in Kidney and Liver Precede Clinical Evidence of Organ Dysfunction.

Organ-specific metabolic pathways, including those related to mitochondrial metabolism, could provide insight to mechanisms underlying sepsis-induced organ dysfunction. However, it remains unclear if metabolic changes result from or precede clinical organ dysfunction. To determine if blood levels of the mitochondrial metabolites acetylcarnitine and L-carnitine correlate with organ-specific signals of sepsis-induced dysfunction, we performed a series of translational analyses of two cohorts of human sepsis and experiments using a murine model of polymicrobial sepsis. We evaluated the association between mitochondrial metabolites and clinical indices of organ function. In the blood of patients with sepsis or septic shock, we found metabolic signals of dysfunctional mitochondrial b-oxidation that were correlated with clinical measures of renal and liver dysfunction. The relevance of these findings was corroborated in an experimental model that showed distinct patterns of change in organ metabolism that correlated with the blood acetylcarnitine to L-carnitine ratio. In addition, sepsis-induced changes in organ metabolism were distinct in the liver and kidney highlighting the unique energy economies of each organ. Importantly, metabolic changes preceded changes in clinical indices of organ function and histological evidence of cellular apoptosis. Based on these findings, sepsis-induced disruption in blood levels of specific metabolites could serve as more physiologically relevant indicators of early organ dysfunction than those we presently use. These early metabolite signals provide mechanistic insights to altered metabolism that may hold the key to timely identification of impending organ dysfunction. This could lead to strategies directed at the interruption of sepsis-induced organ failure.

C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. Complement component 3 (C3), a central effector molecule in three separate complement pathways, has been linked to inflammatory diseases. Hence, we aimed to investigate the clinical significance of C3 in adult HLH. In this study, our retrospective cohort involved patients meeting ≥5 of 8 HLH-2004 criteria were classified as the HLH group (n=627), while those meeting <5 criteria were the partial HLH group (n=588). C3 was significantly lower in the HLH group compared to the partial HLH group (P<0.0001) and low C3 was an independent factor predicting progression from partial HLH to HLH (OR=3.94, P<0.001). Low C3 was associated with more severe cytopenia, coagulation abnormalities, and liver dysfunction. Additionally, patients with low C3 had poorer overall survival (P=0.00099) and low C3 was an independent risk factor for early death in HLH (HR=1.64, P=0.019). The majority of HLH patients had normal C3 before HLH onset, followed by a decline after HLH development (P<0.0001). Moreover, survivors showed increasing C3 (P=0.0003), while non-survivors exhibited decreasing C3 (P=0.90). In conclusion, our study identified C3 as a valuable predictive and prognostic biomarker in adult HLH. Monitoring the dynamic changes in C3 levels may reflect therapeutic response and timely guide clinical interventions.

Dengue with Sickle Cell Anaemia Associated with Acute Liver Failure: A Case Report

Aim: Dengue fever is a major health risk in endemic regions, and its complications can be severe in individuals with underlying haematological conditions like sickle cell anaemia (SCD). SCD increases the risk of Vaso-occlusive crises, haemolysis, and multi-organ dysfunction, which can be exacerbated by dengue’s endothelial damage. This case highlights the rare and complex interaction between SCD and dengue fever, particularly the severe hepatic complications due to co-existing illness, emphasizing the need for specialized treatment strategies. Case Presentation: A female patient from Chikkaballapur, Karnataka, India, with sickle cell anaemia (SCD), presented with dengue shock syndrome and severe hepatic complications. She experienced fever, shock, and liver dysfunction, worsened by both dengue and SCD. Diagnostic challenges arose due to overlapping symptoms. Management included careful hydration, pain control, and transfusion therapy, with close monitoring. Conclusions: This case demonstrates the complexities of managing patients with both SCD and dengue fever. The interaction between dengue-induced endothelial damage and SCD can lead to severe complications, including organ failure and death. Timely intervention, close monitoring, and a multidisciplinary approach are essential for improving outcomes. This case underscores the need for specific treatment guidelines for managing dengue in SCD patients to reduce morbidity and mortality.

Metabolomic Insights into Smoking-Induced Metabolic Dysfunctions: A Comprehensive Analysis of Lipid and Amino Acid Metabolomes

Background: Cigarette smoking is a leading cause of preventable mortality, largely due to the absence of effective, non-invasive biomarkers for early disease detection. Profiling serum metabolomics to identify metabolic changes holds the potential to accelerate the detection process and identify individuals at risk of developing smoking-related diseases. Objectives: This study investigated the biochemical and metabolomic changes induced by nicotine exposure, with a focus on disruptions in amino acid, lipid, and carbohydrate metabolism. Methods: Liquid chromatography–tandem mass spectrometry (LC-MS/MS) was employed to observe significant disruptions in lipid and amino acid metabolism, along with alterations in key metabolic pathways. A total of 400 smokers and 100 non-smokers were included to evaluate the biomarkers related to insulin resistance, blood lipid profile, inflammation, and kidney and liver function. Results: The results demonstrated significantly elevated (p &lt; 0.05) levels of glycemic markers in smokers, including fasting blood glucose; glycated hemoglobin (HbA1c); and inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). Smokers also exhibited dyslipidemia, with increased total cholesterol (154.888 ± 35.565) and LDL levels (117.545 ± 24.138). Impaired liver and kidney function was evident, with significantly higher levels (p &lt; 0.05) of AST, ALP, ALT, blood urea nitrogen, and creatinine in smokers. A total of 930 metabolites were identified, of which 343 exhibited significant alterations (p &lt; 0.05) in smokers compared to non-smokers. Among these, 116 metabolites were upregulated, and 127 were downregulated. Metabolomic pathway analysis revealed eight significant pathways. The study also identified three lipid metabolites specific to smokers and seven unique to non-smokers. Through LC-MS/MS, fragments of phenylalanine, tryptophan, valine, histidine, carnitine, and sphinganine were detected. Several lipidomic changes associated with insulin resistance and cardiovascular complications were observed. Cadmium (Cd) levels were higher in smokers than non-smokers (1.264 ppb vs. 0.624 ppb) and showed a strong negative correlation (R2 = 0.8061, p-value = 0.015) with serum zinc (Zn), likely due to Cd displacing Zn in proteins and causing nephrotoxicity through accumulation. Conclusions: This study highlights the distinct metabolic disruptions caused by smoking that could serve as potential biomarkers for the early detection of metabolic diseases. It emphasizes the importance of metabolomics in identifying systemic indicators of smoking-related health issues, providing new opportunities for preventive and therapeutic interventions.

Clinical and biochemical characteristics for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome: a pilot observational study

BackgroundPolyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is rare life-threatening condition associated with a clonal plasma cell neoplasm.ObjectiveThe aim of this study is to investigate the clinical and biochemical features in patients with POEMS syndrome before and post-therapy.MethodsCharacteristics of demographic information, underlying diseases, clinical manifestations, laboratory indicators, and imaging examination were retrospectively collected when diagnosed and post-therapy in the patients POEMS syndrome between 2018 and 2024.ResultsNineteen newly-diagnosed, treatment-naïve patients with POEMS syndrome were enrolled. The diagnosis of POEMS syndrome was re-analyzed and matched the diagnostic criteria updated in 2023. All patients presented the symptoms of polyneuropathy and positive for M-protein. Most patients suffered with hyperpigmentation (n = 18), organomegaly (n = 18), elevated vascular endothelial growth factor (VEGF) (n = 17), extravascular volume overload (n = 15), sclerotic bone lesions (n = 11), and hypothyroidism (n = 10). Serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total protein, and albumin levels were down-regulated, while uric acid level was up-regulated in patients with POEMS syndrome. Reduced triiodothyronine, thyroxine, free triiodothyronine levels were negatively correlated with urea nitrogen, creatinine, and uric acid levels in patients with POEMS syndrome. VEGF level, which was negatively correlated with Ca2+ level (r = −0.56), was reduced in most patients with POEMS syndrome receiving bortezomib/ixazomib and lenalidomide/thalidomide therapy. Aspartate aminotransferase, total protein, and estimated glomerular filtration rate levels were increased, while creatinine and uric acid levels were reduced post-therapy in patients with POEMS syndrome.ConclusionPatients with POEMS syndrome had impaired liver and renal function, and effective therapy might partly repair the liver and renal dysfunction.

Analysis of the efficacy of multidisciplinary integration based on 3D reconstruction technology for the treatment of gout stone

ObjectiveThis study investigates the efficacy of multidisciplinary fusion therapy based on 3D reconstruction technology for the treatment of gouty stone by comparing the efficacy of multidisciplinary fusion therapy with pharmacologic therapy.MethodsThis study is a cohort study.Patients who underwent gout stone surgery at the Affiliated Hospital of Qingdao University from November 2020 to November 2022 were included in this study, totaling 85 to form the MDT surgery group, and matched among gout stone patients in the outpatient clinic during the same period to form the medication group. Patients in the 2 groups were followed up for 6 months to compare baseline and follow-up data.ResultsBoth groups experienced a decrease in uric acid levels and an increase in SF-36 scores during follow-up. After adjusting for confounders, multifactorial logistic regression showed that the uric acid attainment rate of patients in the MDT surgery group was 4.011 times higher than that of the drug group (OR: 4.011, 95% CI: 1.595, 10.086, P = 0.003); the proportion of patients with an increase in SF-36 in the MDT surgery group was 4.976 times higher than that of the drug group (OR: 4.976, 95% CI: 2.243, 11.040, P < 0.001); the proportion of patients treated with high-dose medication in the MDT surgery group was 1.8% of that of patients in the drug group (OR: 0.018, 95% CI: 0.002, 0.148, P < 0.001); and the proportion of patients in the MDT surgery group who developed frequent gout was 2.8% of that in the drug group (OR: 0.028 95% CI: 0.003, 0.2398, P = 0.001). the proportion of patients in the MDT surgery group who developed abnormal liver function was 0.317 times higher than that in the drug group (OR: 0.317, 95% CI: 0.121, 0.831, P = 0.019).ConclusionThe multidisciplinary integration of 3D reconstructive techniques for gout stone treatment resulted in an increase in uric acid compliance, a decrease in the frequency of gout and the appearance of liver impairment; and a greater benefit in terms of improvement in the quality of life of the patients after treatment.

Pattern analysis of activated partial thromboplastin time clot waveform for detection of hemostatic changes in sepsis patients

Objectives: Coagulation is a dynamic process. Quantitative data on fibrin polymerization can be obtained by thoroughly analyzing the optical profile of the process of coagulation. This study aims to identify the changes in the activated partial thromboplastin time (APTT) clot waveform analysis (CWA) in sepsis. Materials and Methods: Blood samples of sepsis patients from the intensive care unit received for evaluation of APTT were taken for study. The samples were run in Automated Coagulation Analyzer Sysmex - coagulation system (CS) 2400, and APTT CWA was done. Statistical analysis: Statistical analysis was performed using IBM Statistical Package for the Social Sciences Statistics for Windows, version 20.0 NY. The clot waveform of APTT was analyzed in patients with sepsis. Sensitivity, specificity, positive, and negative predictive values of biphasic form in detecting disseminated intravascular coagulation (DIC) in sepsis patients were calculated. Results: A total of 133 blood samples were analyzed. Prolonged APTT was seen in 23% (n = 44). Among the patients with prolonged APTT, 79.5% (n = 35) cases had an altered CWA. In patients with altered CWA, 34% (n = 45) had sepsis with an abnormal wave pattern, and 11% (n = 15) had a biphasic waveform (BPW). DIC was diagnosed in 41% of cases (n = 55). The APTT CWA of sepsis patients with DIC revealed abnormal wave patterns in 31% (n = 17) and biphasic waveforms (BPW) in 18% (n = 10). The sensitivity, specificity, positive, and negative predictive values of the biphasic waveform in detecting DIC in sepsis patients were 18%, 93.5%, 66.6%, and 61.8%, respectively. Conclusions: The study demonstrated significant changes in the APTT CWA in sepsis. The presence of abnormal wave patterns in sepsis suggests liver dysfunction progressing to liver failure. A BPW in sepsis has a high specificity for DIC, which warrants immediate clinical intervention.

Rutaecarpine alleviates hepatic ischemia‒reperfusion injury in liver transplantation by inhibiting inflammatory response and oxidative stress

BackgroundDonation after circulatory death (DCD) livers are limited by mandatory warm ischemia and are more susceptible to ischemia‒reperfusion injury (IRI). Inflammation and oxidative stress play key roles in the development of hepatic IRI, and Rutaecarpine (Rut) has anti-inflammatory and anti-oxidative stress effects. The aim of this study was to investigate whether Rut can alleviate hepatic IRI in liver transplantation (LT) and to explore the underlying mechanisms.MethodsRat DCD LT and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established to clarify the effect of Rut on hepatic IRI. The key molecules involved in the hepatoprotective effects of Rut were identified through joint analysis of data from LT patients and drug targets. The target was further validated by in silico, in vivo and in vitro experiments.ResultsRut significantly alleviated liver dysfunction, pathological injury, and apoptosis and improved the survival rate of the rats subjected to LT. In addition, Rut significantly inhibited inflammatory response and oxidative stress. Rut also had similar effects on OGD/R-induced hepatocyte injury. Mechanistically, bioinformatics analysis and in vivo and in vitro experiments revealed that PDE4B may be a key target by which Rut exerts its protective effect, and molecular docking and cellular thermal shift assay confirmed this result. The function of PDE4B was studied via gene intervention technology, and the results showed that PDE4B can aggravate hepatic IRI. Furthermore, PDE4B overexpression abrogated the protective effect of Rut on the liver in LT.ConclusionRut alleviates hepatic IRI by targeting PDE4B to inhibit inflammation and oxidative stress. These findings highlight the potential of Rut as a drug candidate for the treatment of patients undergoing LT.

Tacrolimus and mycophenolate mofetil in corticosteroid-resistant hepatitis secondary to tislelizumab: a case report

Tislelizumab is a monoclonal antibody with high binding affinity for programmed death-1 (PD-1) receptors. In patients with extensive-stage small-cell lung cancer (ES-SCLC), the first-line use of tislelizumab combined with chemotherapy has shown significant efficacy. However, with the widespread use of PD-1 inhibitors, there are increasing reports of immune-related adverse events (irAEs) in clinical practice, with immune-related hepatitis (IRH) being particularly common. This article reports a case of an ES-SCLC patient (cT3N3M0 cStage IIIB) who developed corticosteroid-resistant hepatitis and recovered through dual immunosuppressant therapy. The patient was a 67-year-old male, diagnosed with ES-SCLC, who received a combination therapy of etoposide, cisplatin, and tislelizumab. Three weeks after the fourth treatment cycle, the patient experienced symptoms, such as decreased appetite, itching, yellow urine, and jaundice, and was diagnosed with IRH, manifested as “Grade 3 total bilirubin increase,” “Grade 3 alanine transaminase increase,” and “Grade 3 aspartate transaminase increase.” Despite intravenous injection of methylprednisolone (MP) 100 mg/day (2 mg/kg) and oral administration of mycophenolate mofetil (MMF) 1 g twice daily, liver function continued to be impaired. In this context, tacrolimus (TAC) (5 mg, twice daily) was added to the therapy, and the IRH level was reduced from Grade 3 to normal. Subsequently, TAC and MMF were gradually reduced and eventually discontinued. Unfortunately, after discontinuing immunosuppressants, IRH recurred. Although the patient still responded to TAC combined with MMF, liver function recovery took a longer time. Due to persistent liver dysfunction, the patient failed to receive second-line chemotherapy and ultimately passed away due to disease progression. Through this case, we hope to emphasize the importance of reasonably extending the use of immunosuppressants to avoid the recurrence of IRH and reduce the premature discontinuation of immunosuppressants. Besides, when tumor progression and IRH recurrence occur simultaneously, providing effective immunosuppressive therapy and reasonably arranging systemic anti-tumor therapy may bring clinical benefits to patients.

Nonalcoholic fatty liver disease and chronic kidney disease: random connections or two manifestations of metabolic syndrome?

Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are two global public health problems that affect almost 30% and up to ~10-15%, respectively, of the general adult population in many parts of the world. It is quite obvious that NAFLD is a “multisystem disease” associated not only with impaired liver function and the development of hepatocellular carcinoma, but also with an increasing risk of developing cardiovascular diseases (the main cause of death in such patients), chronic kidney disease (CKD). However, the mechanisms underlying this association remain largely unknown. The aim of this review is to report on the epidemiology and pathophysiology of the relationship between NAFLD and CKD and to describe the different methods of kidney function assessment in patients with NAFLD as well as to discuss the potential for promising pharmacotherapy with simultaneous benefit for the outcomes of both diseases.

Comparison of Changes in Liver Function Tests in Pregnant Women with Mild and Severe COVID-19

Objective: Some pregnancies are affected by liver dysfunction, and differentiating them from possible liver dysfunction caused by COVID-19 in pregnancy will lead to a better therapeutic approach and management. Aims: The current study was conducted with the aim of investigating changes in liver function tests (LFTs) in pregnant women with mild and severe COVID-19. Methods: In this retrospective observational study, 130 pregnant women with COVID-19 were examined in two referral hospitals in Iran in 2021-2022. COVID-19 was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and WHO guidelines. Pregnant women were assigned into two categories of mild and severe COVID-19 based on clinical symptoms and radiologic chest evaluation. Demographic and clinical data of women were recorded. The level of liver enzymes AST, ALT, ALP, total and direct bilirubin was measured in all patients. Fever, oxygen saturation level, preterm delivery, and maternal mortality were reported as final clinical outcomes and compared in two groups. Results: Forty-nine pregnant women with severe COVID-19 and 81 pregnant women with mild COVID-19 were matched in terms of demographic data. The proportion of women with abnormal AST and ALT in the severe COVID-19 group was significantly higher than in the mild group (p&lt;0.05). However, the proportion of women with abnormal ALP levels in the mild COVID-19 group was significantly higher than in the severe group. Moreover, there was no significant difference between the two groups in terms of the proportion of women with abnormal levels of total and direct bilirubin. Most pregnant women with severe COVID-19 (50%) had a hepatocellular abnormality, while most women with mild COVID-19 (42%) had abnormalities in cholestasis (p=0.003). Conclusion: According to the present findings, liver dysfunction and increased liver enzymes in pregnant women with COVID-19 were related to the severity of the disease, and most women with severe COVID-19 had hepatocellular abnormality, respectively. Therefore, pregnant women with COVID-19 should be closely monitored for LFTs assessment.

Deficiency of Calpain-1 attenuates atherosclerotic plaque and calcification and improves vasomotor dysfunction in Apolipoprotein E knockout mice through inhibiting inflammation.

Atherosclerosis (AS) and atherosclerotic calcification (AC) are closely related to the cardiovascular diseases, largely due to its induction of vasomotor dysfunction. We previously reported that Calpain-1 inhibitor attenuated AS and AC. The present study was designed to investigate the effects and potential mechanisms of Calpain-1 knockout (Calpain-1 KO) in Apolipoprotein E KO (ApoE KO) mice on AS, AC, aortic vasomotor function as well as the liver dysfunction. We hybridized ApoE KO mice with Calpain-1 KO mice to obtain ApoE/Calpain-1 double KO (A×C DKO) mice. The formation of AS and AC was evaluated and liver function was determined. Aortic vasomotor function was assessed. Contents of TNF-α, IL-6, IL-18, IL-1β and NO and the activity of AST, ALT, ALP and eNOS in serum were quantified. The mRNA expression of CD68, SR-A, CD36, PPAR-γ, LXR-α, ABCA1, BMP-2, OPN, ALP and Runx2 in aorta and/or liver were measured. The results showed that in comparison to C57 mice, ApoE KO mice demonstrated the significant increases in the areas of AS and AC, the increases in the mRNA expression of CD68 in the aorta, the increases in the AST, ALT and ALP activity in serum. ApoE KO mice also showed the dysfunction of the aortic contraction induced by phenylephrine and of the relaxation induced by acetylcholine. However, compared with ApoE KO mice, A×C DKO mice exhibited the significant attenuation of AS and AC and the downregulation of mRNA expression of CD68 in aorta. A×C DKO mice revealed the reduction of AST, ALT and ALP activity in serum, the improvements in aortic contraction and relaxation as well as the increases in eNOS activity and NO content in serum. A×C DKO mice also showed the decreases in the contents of TNF-α, IL-6, IL-18 and IL-1β in serum. The mRNA expression of CD68 in aorta, SR-A and CD36 in both aorta and liver of A×C DKO mice was downregulated, while that of PPAR-γ, LXR-α, and ABCA1 was upregulated in comparison of ApoE KO mice. In addition, the mRNA expression of BMP-2, OPN, ALP and Runx2 in aorta of A×C DKO mice was downregulated in comparison of ApoE KO mice. The results suggested that deficiency of Calpain-1 attenuated the formation of AS and AC and improved vasomotor and liver dysfunction in ApoE KO mice through anti-inflammation, and modulation of the mRNA expression of genes related to AS and AC.

Investigating the prevalence and associated factors of elevated liver enzymes and dyslipidemia during pregnancy

Liver dysfunctions during pregnancy can either be pregnancy-specific or preexisting in acute or chronic form. Data on the prevalence of abnormal liver functions and dyslipidemia during pregnancy in Bangladesh are scarce since these tests are not typically done in routine prenatal screening. This study aims to investigate the prevalence of elevated liver enzymes and dyslipidemia and associated risk factors in a cohort of pregnant women in Bangladesh. This cross-sectional study included 194 pregnant women participants from different trimesters. A standardized questionnaire was used to collect baseline, demographic, and lifestyle data. Blood samples were collected from each participant to measure biochemical parameters such as liver enzymes (ALT and GGT), lipid profile (TC, TG, HDL-C, and LDL-C), glucose, and creatinine levels in the serum. Logistic regression analysis was applied to identify factors associated with liver dysfunction and lipid profile abnormalities. The average age of the participants was 25 ± 5 years. Overall, the prevalence of preeclampsia was 12.4%. Among participants, 27% had increased ALT levels, most in their third trimester, while 11.8% had elevated GGT levels, mostly in early pregnancy. 83.8% of the study subjects had general dyslipidemia, with the highest prevalence in the second trimester and 5.2% had mixed dyslipidemia. Several factors were significantly associated with ALT elevation, such as preeclampsia, elevated blood pressure, low HDL-C levels, high parity number, having a higher number of children, hypertensive disorders during pregnancy and inadequate knowledge about pregnancy diet. On the other hand, advanced maternal age, high gravidity, and mixed dyslipidemia were associated with elevated GGT levels. Conversely, age, hypertensive disorders during pregnancy, preeclampsia, and diabetes were associated with dyslipidemia. In conclusion, elevated levels of liver enzymes and an abnormal lipid profile are common among pregnant women in Bangladesh. Various factors are linked to abnormal liver enzymes and dyslipidemia in these participants. Monitoring liver function and lipid levels, along with proper prenatal care, can help reduce the risk of maternal and neonatal mortality.

Polysaccharides from hawthorn fruit alleviate high-fat diet-induced NAFLD in mice by improving gut microbiota dysbiosis and hepatic metabolic disorder.

Hawthorn fruit, renowned as both a functional food and herbal medicine with lipid-lowering effects, is abundant in polysaccharides. However, there is limited research on the effects and mechanisms of hawthorn fruit polysaccharides (HP) in addressing non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the effects of HP on NAFLD both in vivo and in vitro, and to elucidate the underlying mechanisms by which HP exerts its anti-NAFLD activity. NAFLD mice induced by a high-fat diet were employed as the in vivo model, while oleate/palmitate-induced HepG2 cells served as the in vitro model. H&E and Oil Red O staining were employed to examine fat accumulation in hepatocytes. Serum aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were measured using corresponding ELISA kits. Hepatic metabolomics analysis based on UHPLC-QTOF/MS was utilized to examine the role of HP in improving hepatic metabolic disorders. 16S rRNA sequencing was conducted to explore the effect of HP in alleviating gut microbiota dysbiosis. GC-MS was applied to detect short-chain fatty acids (SCFAs) to clarify the impact of HP in NAFLD mice. HP significantly inhibited weight gain and hepatic fat accumulation in NAFLD mice. The reduction in serum ALT and AST levels indicated that HP mitigated liver function damage, while the decreased MDA levels and increased SOD activity suggested that HP alleviated hepatic oxidative stress. Furthermore, HP diminished the release of inflammatory cytokines such as IL-1β and IL-6 in the liver. HP significantly regulated metabolic pathways related to amino acids, lipids, and vitamins. Key metabolites such as l-tyrosine, urocanic acid, undecanedioic acid, oleamide, vitamin A, and vitamin B7 were restored to near-normal levels under the regulatory effects of HP. Gut microbiota dysbiosis in NAFLD mice was also ameliorated by HP, with genera such as unclassified_f__Lachnospiraceae and Dubosiella being notably affected. Correlation analysis indicated a significant correlation between the regulatory effects of HP on liver metabolism and gut microbiota. Additionally, HP showed no effect in vitro but increased acetic acid level in the gut of NAFLD mice. These findings demonstrate that HP exhibits its anti-NAFLD effects, including alleviating lipid accumulation, liver dysfunction, oxidative stress, and inflammation. Mechanistically, HP primarily improves gut microbiota dysbiosis, thereby elevating intestinal SCFA levels and restoring hepatic metabolic disorders in NAFLD mice.

The Wood Element and Chinese Herbal Medicine

The Liver is the Zang-fu organ that corresponds to the Wood element and springtime according to the Five Element theory of traditional Chinese medicine (TCM). It is often referred to as "the viscus of Wind and Wood". As in nature, after a quiet dormant winter, we enter into spring with a burst of energy and new growth. The Liver regulates the free flow of Qi, regulates and stores the Blood, regulates the emotions, governs the tendons/ligaments (sinews), nourishes and supports the eyes, and helps regulate the hormones to promote normal reproductive health. If these functions are disrupted, then Stagnation of Qi and fundamental substances can occur which leads to problems with digestion, blood circulation, reproduction, vision, weakness/inflexibility of the joints and emotional disorders. There are many patterns of disharmony identified in Chinese medicine that cause Liver dysfunction and disease. This paper is intended to discuss the five most common patterns and their pathophysiology to promote clarity and understanding of how these patterns develop and to help the practitioner of traditional Chinese veterinary medicine (TCVM) to advance their knowledge and use of Chinese herbal medicine to treat disharmonies of the Wood element. The patterns of Liver disharmony that will be reviewed are, Liver Qi Stagnation, Liver Fire and Liver Yang Rising, Liver-Spleen disharmony and Liver Blood Deficiency.

Real-world experience with atezolizumab plus bevacizumab (A+/-B) in Hispanic patients with advanced hepatocellular carcinoma (HCC) at a Hispanic-majority cancer center.

549 Background: Combination of atezolizumab (A), a programmed death-ligand 1 (PD-L1) inhibitor, and bevacizumab (B), a vascular endothelial growth factor (VEGF) inhibitor, has demonstrated efficacy for first-line treatment for HCC. However, real-world data on the outcomes of this combination therapy in diverse patient populations, particularly in Hispanic U.S. patients, remains limited. This study aims to evaluate the clinical outcomes of patients intended to treat with A+/-B at a Hispanic-majority U.S. cancer center. Methods: This retrospective study of patients diagnosed with advanced unresectable HCC who received treatment with A+B at a Hispanic-serving NCI-designated cancer center. Patients were included if they received at least one dose of A, either as monotherapy or in combination with B, between January 2019 and April 2022. Demographic and clinical data, including age, gender, ethnicity, liver disease etiology, Child-Pugh (CP) classification, comorbidities, and treatment details, were collected. The primary endpoints were the overall response rate (ORR) and complete response (CR) rate. Statistical analyses were conducted to evaluate the association between baseline characteristics and clinical outcomes. The median overall survival (mOS) evaluated by Kaplan-Meier Method. Results: 38 patients received at least A (84% A+B, 6 patients had B held due to bleeding risk after consent). Median age 65 years (45-90). 32 (84%) patients were male. 22 (58%) patients were Hispanic. 45% had HCV-related liver disease. 32% had CP B with no statistically significant association between CP Class and ethnicity. 53% had concurrent diabetes. 26% patients had obesity. The median time on treatment was 7.5 mo (1- 24 mo) with no statistical difference between Hispanics and non-Hispanics (9 vs 6 mo, p 0.70). CR 37% with ORR of 42%. Using Fisher’s exact test, no association was noted between obesity, ethnicity, treatment option or CP class to occurrence of complete or partial response. mOS was 19 mo. There was no statistical difference in mOS between CP A and CP B (19 vs 10 mo, p value 0.6) and no difference between Hispanics (14 mo) vs non-Hispanics (19 mo) (p 0.5), using log rank test. Conclusions: This real-world analysis of a Hispanic-majority U.S. cohort of patients with advanced HCC shows 42% ORR and 37% CR. The findings suggest that this regimen is effective across a diverse patient population, including those with comorbid conditions, such as liver dysfunction (CP B 32%), HCV (45%), diabetes (53%, and obesity (26%). Limitations are the small study population and retrospective nature of the study. Evaluation of toxicity data is ongoing. Further prospective studies are needed to identify biomarkers of outcomes in Hispanic patients with HCC, which is ongoing at our cancer center (NCT03894917).

Start small, think big: MicroRNAs in diabetes mellitus and relevant cardiorenal-liver metabolic health spectrum.

Diabetes mellitus (DM), co-existing with metabolic disorder of cardio-renal-liver, is one of the most difficult problems in medicine that attracts global concern with high mortality. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that negatively regulates gene expression and exerts active against a large proportion of the transcriptome, due to their high evolutionary conservation. Emerging evidence prove that miRNAs are involved in the pathogenesis of DM and associated metabolic disorders, manifested by their variable alteration in the blood, urine, tissues, or organs, principally contributing to modulate the interconnections between DM and cardio-renal-liver metabolism. Mechanistically, miRNAs regulate various biological processes, such as metabolism of insulin, lipid, glucose, inflammatory response, fibrosis, oxidative stress, apoptosis, and angiogenesis, etc. This review emphasizes the function of miRNAs and highlights the physiopathological regulation of miRNA in DM and related complications, especially the dysfunction of cardiovascular system, kidneys, and liver, with the aim of providing promising biomarkers for assisting early diagnosis of DM with cardio-renal-liver- specific metabolic disorders, as well as for the development of miRNA-targeting agents.

Risk factors for postoperative liver dysfunction in robot-assisted gastrectomy for gastric cancer

Risk factors for postoperative liver dysfunction in robot-assisted gastrectomy for gastric cancer

KIRROS: A phase II trial in progress of first-line atezolizumab (atezo) with or without bevacizumab (bev) in patients with unresectable hepatocellular carcinoma (HCC) and Child-Pugh B (CPB) cirrhosis.

TPS647 Background: HCC treatment is more complex for the sizable proportion of patients with CPB cirrhosis. These patients have poor survival due to both the cancer and underlying liver dysfunction. As such, they are typically excluded from pivotal clinical trials for first-line systemic therapy for unresectable HCC. The IMbrave150 trial established atezo + bev as a global standard of care for unresectable HCC, demonstrating a statistically significant improvement in overall survival (OS), progression-free survival (PFS) and confirmed objective response rate (ORR) of atezo + bev vs sorafenib (Finn N Engl J Med 2020; Cheng J Hepatol 2022). Real-world studies have consistently suggested benefit of atezo + bev in patients with HCC and CPB cirrhosis (e.g., Tanaka Hepatol Res 2022, D’Alessio Hepatol [Baltimore, Md] 2022). However, prospective clinical trial data are needed to comprehensively characterize safety and efficacy in this population. Single-agent immunotherapy is often used in patients with HCC and CPB cirrhosis given potential safety concerns of combination therapy. Safety data from real-world studies are limited by ascertainment and measurement biases. Therefore, a prospective study is warranted to address the unmet need for safety and efficacy data for first-line atezo ± bev in patients with CPB cirrhosis. Methods: KIRROS (NCT06096779) is a prospective, open-label, multicohort, multicenter phase II study in patients aged ≥18 years who have measurable and confirmed unresectable HCC, and CPB-7 or -8 cirrhosis who have not received prior systemic therapy. Eligible patients will be recruited into 2 cohorts for which endpoints will be non-comparatively assessed: Cohort A (n=60) patients will be treated with atezo 1200 mg intravenous (IV) + bev 15 mg/kg every 3 weeks (Q3W), and Cohort B (n=60) patients, those who do not meet Cohort A inclusion criteria (e.g., main portal vein tumor thrombus and proteinuria), will receive atezo 1200 mg IV Q3W only. Patients will receive treatment until unacceptable toxicity or loss of clinical benefit. The primary objective is to evaluate the safety of the treatment regimens as determined by incidence, nature and severity of adverse events and laboratory abnormalities graded per the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Secondary objectives are to estimate efficacy with ORR, duration of response, and PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC modified RECIST, as well as OS. Quality-of-life secondary endpoints include patient-reported tolerability of the treatment regimens assessed by PRO-CTCAE and EORTC IL46, and health-related quality of life per EORTC QLQ-C30 and QLQ-HCC18 scores. As of September 2024, the KIRROS study is recruiting patients at 40 sites in the US and Puerto Rico. Clinical trial information: NCT06096779 .