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Aims Royal jelly, a creamy substance secreted by honeybees, has been reported to have beneficial effects against dyslipidemia and metabolic syndrome. However, the effects of royal jelly on atherogenesis remain unknown. Hence, we prospectively evaluated whether royal jelly augments vascular endothelial function, which can reflect early atherogenesis, in healthy volunteers. Methods This was a single-center, double-blind, 1:1 randomized placebo-controlled study conducted from October 2018 to December 2019. A total of 100 healthy volunteers were randomly assigned to receive either royal jelly 690 mg or placebo daily for 4 weeks. The primary endpoint was augmentation in vascular endothelial function as assessed using the change in the reactive hyperemia peripheral arterial tonometry index (RH-PAT) index, and the secondary endpoints were the changes in liver function and lipid profiles between baseline and 4 weeks after enrollment. Results The mean age of the participants was 35.0±9.3 years in the placebo group and 36.1±9.1 years in the royal jelly groups; 45% and 50% of the placebo and the royal jelly groups, respectively, were male. The percentage relative change in the RH-PAT index was significantly higher in the royal jelly group than in the placebo group (21.4%±53.1% vs. 0.05%±40.9%, P=0.037). The percentage relative changes in alanine aminotransferase and γ-glutamyl transpeptidase were significantly lower in the royal jelly group than in the placebo group (alanine aminotransferase: -6.06%±22.2% vs. 11.6%±46.5%, P=0.02; γ-glutamyl transpeptidase: -3.45%±17.8% vs. 4.62%±19.4%, P=0.045). Lipid profiles were not significantly different between the two groups. Conclusions Royal jelly might have antiatherogenic property by improving vascular endothelial function. It also augmented liver functions in healthy volunteers.

Objectives Renal failure and hepatic cirrhosis are mutually aggravating factors. However, no specific therapeutic strategies for hepatic encephalopathy (HE) and end-stage kidney disease have been established. The coexistence, with an extremely poor prognosis, makes randomized controlled trials unfeasible. We evaluated whether an infusion of branched-chain amino acids was associated with mortality in patients hospitalized for HE and end-stage kidney disease. Design and Methods Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified patients with HE and end-stage kidney disease who received hemodialysis within 2 days of admission from July 2011 to March 2017. We divided the patients into those who received branched-chain amino acid infusion within 2 days of admission and those who did not. We conducted analyses using overlap weights based on propensity scores to compare in-hospital mortality between the groups. Sub-group analysis was conducted by stratifying patients by Child-Pugh class. Results We identified 553 eligible patients, including 503 patients who received branched-chain amino acid infusion and 50 who did not. The patients who received branched-chain amino acid infusion had lower mortality than those who did not (10.2% vs. 20.1%, relative risk 0.51, 95% confidence interval 0.27-0.95). Sub-group analysis showed that branched-chain amino acid infusion was associated with decreased in-hospital mortality in patients with Child-Pugh class C (16.2% vs. 39.0%, relative risk 0.41, 95% confidence interval 0.23-0.76). Conclusions Branched-chain amino acid infusion may improve the prognosis of HE in patients with end-stage kidney disease, particularly those with lower liver function. Further research is necessary to provide a suitable treatment for HE in patients with end-stage kidney disease.

A 77-year-old woman presented with a 2-week history of malaise, prostration, anorexia, abdominal pain, vomiting and diarrhoea. She had been taking systemic corticosteroids for the past year. During hospitalisation, renal insufficiency, ionic changes and liver function abnormalities were detected and corrected. However, the patient developed total dysphagia. UGE revealed multiple shallow ulcers below the cricopharyngeal level and in the distal oesophagus, with normal-appearing intervening mucosa. Histological examination allowed the diagnosis of herpes simplex virus esophagitis. Treatment with intravenous acyclovir was instituted for 14 days. In the elderly, herpetic esophagitis may present with non-specific complains, such as prostration or anorexia. In the reported case, dysphagia was only detected as a late symptom, addressing the importance of maintaining a high degree of suspicion for the diagnosis of herpes simplex virus esophagitis.

Autoimmune hepatitis (AIH) is a chronic and progressive inflammatory process of the liver, with standard treatments including prednisone, azathioprine, and ultimately liver transplant. While there are many integrative and ayurvedic treatment options that have been shown to be helpful for other liver diseases, there are no studies that have been performed to evaluate these therapies particularly in AIH with cirrhosis. We detail the case of a 55-year-old female with cirrhosis in the setting of AIH placed on a liver transplant list after being treated with conventional therapies. She was started on various nutritional supplements and ayurvedic treatments which resulted in a significant decrease in her Model for End-Stage Liver Disease score, which was sustained at 7 months. This is the first case report to our knowledge detailing an integrative approach to cirrhosis in the setting of AIH showing such an improvement in liver function.

Objective Mapping the long-term prognosis of Budd-Chiari syndrome (BCS) is difficult, as the prognosis is associated with changes in the liver function. The present study evaluated the time course changes in the liver function in a treatment group with percutaneous old balloon angioplasty (POBA) and a non-treatment group using the albumin-bilirubin score (ALBI) and Child-Pugh score during long-term follow-up. Methods In this retrospective study, 13 consecutive patients diagnosed with BCS at our hospital between 2007 and 2020 were categorized into a treatment group (n=8), which received POBA, and a non-treatment group (n=5). Differences in the liver function in the ALBI and Child-Pugh scores between the initial visit and one- and three-year follow-up were calculated and statistically evaluated. We investigated the changes in the liver function during the long-term follow-up, including events such as re-stenosis and re-treatment. Results While the Child-Pugh scores in the treatment group did not differ significantly between the initial visit and 1- or 3-year follow-up, the ALBI scores in this group improved significantly between the initial visit and the 1- or 3-year follow-up visit (p=0.0078 and 0.0156, respectively). The liver function according to the ALBI score in the treatment group showed gradual improvement from the initial value but gradual worsening in the non-treatment group. The ALBI scores also revealed that the liver function varies according to re-stenosis and re-POBA in BCS patients. Conclusion Unlike the Child-Pugh score, the ALBI score was able to capture changes in the liver function of BCS patients during the long-term course of BCS.

BACKGROUND: Critically ill patients commonly suffer from infections that require antimicrobial therapy. In previous studies, liver dysfunction was shown to have an essential impact on the dose selection in these patients. This pilot study aims to assess the influence of liver dysfunction, measured by the novel LiMAx test, on clinical outcomes in critically ill patients treated with linezolid. METHODS: Twenty-nine critically ill patients were included and treated with linezolid. Indications for linezolid therapy were secondary or tertiary peritonitis (46.7%), bloodstream infection (6.7%) and 46.7% were other infections with gram-positive bacteria. Linezolid Cmin, maximal liver function capacity (LiMAx test) and plasma samples were collected while linezolid therapy was in a steady-state condition. Furthermore, potential factors for the clinical outcome were investigated using logistic regression analysis. Clinical cure was defined as the resolution or significant improvement of clinical symptoms without using additional antibiotic therapy or intervention. RESULTS: Cured patients presented lower median linezolid Cmin yet a significantly higher mean LiMAx-value compared to the clinical failure group (1.9 mg/L vs. 5.1 mg/L) (349 μg/kg/h vs. 131 μg/kg/h). In the logistic regression model, LiMAx < 178 μg/kg/h was the only independent predictor of clinical failure with a sensitivity of 77% and specificity of 93%. CONCLUSIONS: The LiMAx test predicts clinical failure more precisely than linezolid trough levels in critically ill surgical patients. Therefore liver failure may have a stronger impact on the outcome of critically ill surgical patients than low linezolid Cmin. While linezolid Cmin failed to predict patient’s outcome, LiMAx results were the only independent predictor of clinical failure.

BACKGROUND/OBJECTIVES: Cirrhosis of liver is associated with loss of liver function, portal hypertension, and pancreatic β-cell dysfunction leading to hepatogenous diabetes (HD). Often HD is an underestimated and understudied problem, particularly in the Indian subcontinent, where the prevalence of both Chronic liver disease (CLD) and diabetes is high. Hence this study was planned to highlight the prevalence of HD and its association with the severity of cirrhosis. METHODS: A total of 121 cirrhotic patients without a history of diabetes were included in this prospective cross-sectional study. Seventy five g oral glucose tolerance test (OGTT) was done in all patients. Fasting serum insulin levels were done to calculate insulin resistance (IR) using homeostatic model assessment-insulin resistance (HOMA-IR). Upper gastrointestinal endoscopy was done to detect varices. Patients were divided into HD group and non-HD group for comparison of results. RESULTS: HD was seen in 52 (42.98%) patients; among them, 63.4% did not show evidence of HD by fasting plasma glucose (FPG) levels. Impaired glucose tolerance (IGT) was seen in 58 (47.93%) patients. Compared with the non-HD group, the HD group had significantly higher model for end-stage liver disease (MELD) score (P = 0.038), HOMA-IR (P 15), CTP score (>10), higher bilirubin levels, large varices, bleeding varices, and HCC. FPG levels and glycated hemoglobin (HbA1c) cannot be relied upon, and OGTT aids in the unmasking of HD in these patients.

Introduction: Immunosuppressive therapy for uveitis may cause liver damage. Methods: To investigate incidence of liver damage during uveitis treatment, we compared serological Hepatitis B core antibody (HBcAb) status with risk of liver dysfunction in all participants (n = 992), in anterior uveitis (AU) (n = 489), and combined of intermediate, posterior, or panuveitis (IPPU) patients (n = 503). The primary endpoint was incidence of elevated serum alanine aminotransferase level above 2-fold upper limits of normal within 6 months. Results: The incidence rate of primary endpoint for HBcAb-negative and HBcAb-positive patients was 65 and 212 per 1,000 person years, respectively. The absolute rate difference was 147 (95% confidence interval [CI], 80–213) per 1,000 person years. HBcAb positivity was associated with a higher risk for primary endpoint in all participants (adjusted hazard ratio [aHR], 3.53; 95% CI, 1.79–6.99; p value = 2.8 × 10−4) and in IPPU (aHR, 3.80; 95% CI, 1.61–9.01; p value = 0.002). No significant association with primary endpoint was observed for HBcAb positivity in AU (aHR, 3.21; 95% CI, 0.94–10.95; p value = 0.063). AU was mainly treated with topical eye drops (74.0%), whereas IPPU cases received systemic therapy including prednisone (94.0%), cyclosporine (80.9%), or other additionally combined immunomodulatory agents (14.9%). Conclusion: Noninfectious uveitis cases with HBcAb positivity have an increased risk of liver damage. This association was predominantly driven by IPPU but was not significant in AU, suggesting that the association is mediated by systemic therapy.

Liver function test is the first step to diagnose various liver diseases by measuring certain proteins and liver enzymes from the blood sample. After getting the required data of the clinical parameters from the blood test it is possible to calculate Child-Pugh (CTP), AST to PLT ratio (APRI) and Model for end-stage liver disease (MELD) clinical scores that help the doctors about the severity of the disease progression. Volatile organic compounds (VOCs) found in-breath and monitoring their concentration may be a prevailing method for disease diagnosis. In this work, Isoprene, Limonene, and Dimethyl sulphide (DMS) are considered as a potential breath biomarker related to liver disease. A dataset is designed, that includes the biomarkers concentration analysed from the breath sample before and after study subjects performed an exercise. Four regression methods are performed to predict the clinical scores using breath biomarkers data as features set by the machine learning techniques. Regression methods on the dataset for prediction are evaluated by mean absolute error and root mean square error. A significant difference observed for isoprene concentration (p

The objective of the study — to assess the correlation between resistin and indexes of the functional state of the liver in patients with non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (DM) and with their combination. Materials and methods. 110 patients were examined, among them 20 patients with NAFLD, 20 patients with DM type 2 and 70 patients with comorbidity (NAFLD + DM type 2), they were divided into 2 subgroups — 20 patients with normal body weight and 50 obese patients. The control group consisted of 20 apparently healthy individuals. Comprehensive clinical, laboratory (with determination of indicators of protein, pigment, enzyme and carbohydrate metabolism, resistin level), instrumental (ultrasound of the liver and liver biopsy (8 patients)) examinations were carried out. Results. Significant increase in plasma resistin levels in patients with comorbidity was revealed. Significant correlations between resistin levels and indicators of the functional state of the liver in these patients were established. Conclusion. In patients with NAFLD, DM type 2 and their combination, especially with concomitant obesity, there is an imbalance of fatty tissue products, a sign of which is the increase of resistin level. The relationship between resistin and indicators of the functional state of the liver mainly in the subgroup with comorbid disorders and obesity give reason to believe that hormone and metabolic disorders that affect liver function activate and worsen in obesity.

Following curative liver resection (LR), resectable tumor recurrence in patients with preserved liver function leads to deciding between a repeat LR and a salvage liver transplantation (LT), if a donor's liver is available. This retrospective study compared survival outcomes and recurrence pattern following salvage living donor LT (LDLT) and repeat LR in patients with recurrent hepatocellular carcinoma (HCC). We reviewed the medical records of patients who underwent repeat LR (n = 163) or LDLT (n = 84) for recurrent HCC following curative resections, between January 2005 and December 2017 at a single institution. A 1:1 propensity score matching led to 42 patients per group. Disease-specific and recurrence-free survival were significantly better in the salvage LDLT group than in the repeat LR group (p = .042; HR = 2.40; 95% CI, 0.69-6.00 and p < .001; HR = 4.23; 95% CI, 2.05-8.71, respectively). Despite significant differences in recurrence patterns between the two groups (p = .019), the patient death rates, after recurrence, were similar for both groups (p = .760). This study indicates that salvage LDLT is superior to repeat LR for treating patients with transplantable, intrahepatic HCC recurrence, even in patients with Child-Pugh class A liver cirrhosis.

Background: The aim of this study is to evaluate the outcomes and prognostic factors in patients with hepatocellular carcinoma (HCC) and Child–Turcotte–Pugh (CTP) class B liver function after stereotactic ablative radiotherapy (SABR). Materials and Methods: This retrospective study evaluated patients with HCC and impaired liver function who underwent SABR between December 2007 and August 2016. All patients had CTP class B liver function before treatment. Local control (LC) rate, overall survival (OS) rate, prognostic factors, and radiation-related toxicity were evaluated. Results: This study included 34 patients. The majority had a CTP score of B7 (52.9%) and advanced HCC (91.2%). The median survival time was 4.8 months, and the 1-year OS rate was 21.4%. Only the tumor number (multiple vs. single) was identified as an independent predictor of survival. The 1-year LC rate was 95.8%. Eight patients (23.5%) developed the radiation-induced liver disease, and 15 (44.1%) had a CTP score decline of ≥2 within 3 months. Other toxicities were generally tolerable. Conclusion: SABR may be considered as an alternative option for patients with HCC and CTP class B liver function, particularly for those with a single lesion.

OBJECTIVE To study the association of hyperuricaemia with clinical and pathological characteristics of patients with IgA nephropathy, and to clarify adverse effects of hyperuricaemia on the onset and progression of IgA nephropathy. METHODS A total of 244 patients with IgA nephropathy enrolled in Jiangjin Center Hospital were divided into a group with normal serum uric acid level and a group with elevated level. Age, gender, course of disease, blood pressure, liver function, renal function, blood lipid levels, blood glucose level, 24-hour urine protein level and pathological grades were recorded. The correlations of serum uric acid level with clinical indices and pathological grades were analyzed. RESULTS The incidence rate of IgA nephropathy complicated with hyperuricaemia was 25.4%. The two groups had significantly different course of disease, body mass index (BMI), and levels of urea nitrogen, creatinine, triglyceride and urine protein (p

Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is an intractable drug hypersensitivity disease with high mortality. The current standard treatment requires high-dose and long-term systemic corticosteroids, which may lead to adverse effects and intolerability of patients. Objective To evaluate the efficacy and safety of cyclosporine in patients with corticosteroid-dependent DRESS or intolerance to systemic corticosteroids. Methods A retrospective review of 8 patients with corticosteroid-dependent DRESS who were treated with cyclosporine as an alternative treatment owing to suboptimal response to regular doses of systemic corticosteroids for at least 3 weeks, flare-ups when tapering corticosteroids, or experiencing intolerable adverse effects of corticosteroids. Results In all 8 patients (4 women and 4 men; age range, 15-75 years), either intractable skin eruptions, persistent eosinophilia, or elevated liver function was noted after at least 3 weeks of treatment with systemic corticosteroids. The patients had marked cutaneous improvement and normalization of liver function and eosinophil count after adding cyclosporine, and the systemic corticosteroid treatment was smoothly tapered down. The mean dosage of cyclosporine was 1.68 ± 0.73 mg/kg/d, and the mean duration of cyclosporine treatment was 76.13 ± 35.64 days. Their serum eosinophil counts, serum alanine aminotransferase levels, and serum thymus and activation-regulated chemokine levels were all elevated at baseline and then significantly decreased during the recovery stage after cyclosporine therapy (P Conclusion Cyclosporine is an effective and safe therapeutic alternative as a steroid-sparing agent for corticosteroid-dependent DRESS. Further prospective randomized controlled studies are required to confirm these preliminary results.

Introduction Obesity has been reported as a risk factor for COVID‐19 prognosis. However, the long‐term effects of obesity on patients discharged from the hospital are unclear, and the present study aims to address this issue. Methods A cohort study was conducted using data from patients diagnosed with COVID‐19 who were discharged from Wuhan Union Hospital between February 20, 2020, and March 20, 2020. The 118 patients with COVID‐19 were divided into the non‐obesity group and the obesity group according to their body mass index (BMI). All the patients were invited to fill out a series of scales to assess cardiopulmonary function. Data on population baseline characteristics, clinical manifestations, laboratory examinations, chest computed tomography (CT), and lung function were collected and analyzed. Results The clinical manifestations and pathological changes on CT images of obese patients were more serious after discharge than those of non‐obese patients. In addition, we found significant abnormalities in metabolic indicators such as blood lipids, uric acid, and liver function in obese patients. Most importantly, the antibody titer of COVID‐19 obese patients was inversely correlated with BMI. Conclusion In the long term, obesity affects clinical manifestations, immune function and endocrine metabolism in patients discharged after recovering from COVID‐19., In the long term, obesity affects clinical manifestations, immune function, and endocrine metabolism in patients discharged after recovering from COVID‐19.

Background Non-alcoholic fatty liver disease (NAFLD) is a frequently occurring clinical disease, which could be treated by traditional Chinese medicine. However, the effects and mechanisms of xiao-zhi-fang (XZF) alone or in combination with fructooligosaccharides (FOS) on NAFLD remains unclear. Methods This study established the NAFLD mouse model by feeding with a high-fat diet and by administering with XZF and/or FOS. Moreover, the fat content in the liver tissues was evaluated by oil red O and hematoxylin and eosin staining, and the liver function indices were examined using a biochemical analyzer. Changes in the intestinal flora were monitored using 16S rRNA gene sequencing. The results of the current study showed that the alanine aminotransferase, aspartate aminotransferase, total triglyceride, total cholesterol levels, and the amount of lipid accumulation were markedly elevated in NAFLD mice. Results XZF alone or in combination with FOS significantly reduced lipid accumulation in the liver and blood lipid levels in NAFLD mice. Moreover, XZF alone or in combination with FOS notably altered the intestinal flora structure in NAFLD mice. Consequently, 17 operational taxonomic units were decreased and nine were increased in the XZF and/or FOS groups. Conclusions FOS may accelerate the intestinal microecological balance in NAFLD mice after treatment with XZF by promoting intestinal flora growth, thereby enhancing the therapeutic effect of XZF on NAFLD.

Western-style high-fat/high-sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD-induced change of gut microbiota. Then, we studied the effects of the changed gut microbiota on BA composition and liver function. Male wild-type (WT) and human-like Cyp2a12/Cyp2c70 double knockout (DKO) mice derived from C57BL/6J were fed with normal chow or HFHSD for 4 weeks. Gut microbiomes were analyzed by fecal 16S ribosomal RNA gene sequencing, and BA composition was determined by liquid chromatography-tandem mass spectrometry. The DKO mice exhibited significantly reduced fecal BA concentration, lacked muricholic acids, and increased proportions of chenodeoxycholic and lithocholic acids. Despite the marked difference in the fecal BA composition, the profiles of gut microbiota in the two mouse models were quite similar. An HFHSD resulted in a significant increase in the BA pool and fecal BA excretion in WT mice but not in DKO mice. However, microbial composition in the two mouse models was drastically but similarly changed by the HFHSD. In addition, the HFHSD-induced change of gut microbiota inhibited BA deconjugation and 7α-dehydroxylation in both types of mice, which improved chronic liver injury observed in DKO mice. Conclusion: The HFHSD itself causes the change of gut microbiota due to HFHSD, and the altered composition or concentration of BAs by HFHSD is not the primary factor. On the contrary, the gut microbiota formed by HFHSD affects BA composition and ameliorates liver injury in the mouse model with human-like hydrophobic BA composition.

This is a summary of a research study (known as a clinical trial) called CROWN. The study tested two medicines called lorlatinib and crizotinib in participants with untreated non-small cell lung cancer that had spread to other parts of their body. All those who took part had changes in a gene called ALK, which is involved in cell growth. In total, 296 participants from 23 countries took part. Half the participants took lorlatinib and half took crizotinib. After participants started taking lorlatinib or crizotinib, they were checked regularly to see if their tumors had grown or spread to other parts of their body (known as tumor progression) and to monitor any side effects. After 1 year of treatment, the participants who took lorlatinib were twice as likely to be alive with no tumor growth as the participants who took crizotinib. More participants who took lorlatinib had cancer that shrank (76%) compared with the participants who took crizotinib (58%). This was also true of the participants whose cancer had spread to their brain. The most common side effects in participants who took lorlatinib were increases in the amount of cholesterol and triglycerides (a type of fat) in their blood, swelling, weight gain, nerve damage, unclear thoughts, and diarrhea. Among the participants who took crizotinib, the most common side effects were diarrhea, feeling like you want to throw up, sight problems, swelling, vomiting, changes in liver function, and feeling tired. Overall, the CROWN study showed that fewer participants with advanced ALK+ non-small cell lung cancer died or had tumor growth with lorlatinib compared with crizotinib treatment. ClinicalTrials.gov NCT number: NCT03052608 .

More than 80% of global hepatocellular carcinoma (HCC) patients are estimated to occur in sub-Saharan Africa (SSA) and Eastern Asia. The most common risk factor of HCC in SSA is chronic hepatitis B virus (HBV) infection, with the incidence highest in West Africa. HBV is highly endemic in SSA and is perpetuated by incomplete adherence to birth dose immunization, lack of longitudinal follow-up care, and impaired access to antiviral therapy. HBV may directly cause HCC through somatic genetic alterations or indirectly through altered liver function and liver cirrhosis. Other risk factors of HCC in SSA include aflatoxins and, to a lesser extent, African iron overload. HIV plus HBV co-infection increases the risk of developing HCC and is increasingly becoming more common because of improving the survival of patients with HIV infection. Compared with the rest of the world, patients with HCC in SSA have the lowest survival. This is partly due to the late presentation of HCC with advanced symptomatic disease as a result of underdeveloped surveillance practices. Moreover, access to care and resource limitations further limit outcomes for the patients who receive a diagnosis in SSA. There is a need for multipronged strategies to decrease the incidence of HCC and improve its outcomes in SSA.

Ketotic dairy cows exhibit a state of negative energy balance (NEB) characterized by elevated circulating levels of β-hydroxybutyrate (BHB) and fatty acids. Impaired hepatic insulin signaling in dairy cows occurs frequently during the transition into lactation, but its role on liver function during this period is not well known. In nonruminants, endoplasmic reticulum (ER) stress is a causal factor contributing to impaired insulin signaling in the liver. Thus, the aim of this study was to investigate the status of hepatic insulin and ER stress signaling and whether ER stress contributes to impaired insulin signaling in dairy cows with ketosis. Healthy (control cows, n = 10, BHB ≤0.6 mM) and ketotic (ketotic cows, n = 10, BHB ≥1.2 mM) cows at 3 to 10 d in milk were selected for liver biopsy and blood sampling before feeding. In vitro experiments were conducted with isolated hepatocytes from 5 healthy calves (1 d old, fasted female, 30-40 kg of body weight). Treatments included BHB (0, 0.9, 1.8, 3.6 mM), tauroursodeoxycholic acid (TUDCA, a canonical inhibitor of ER stress), and different incubation times (0.5, 1, 2, 3, 5, 7, 9, or 12 h). Ketotic cows had lower daily milk yield (median: 29.50 vs. 23.00 kg), higher plasma nonesterified fatty acid (NEFA) (median: 0.33 vs. 1.17 mM), BHB (median: 0.43 vs. 3.22 mM), aspartate aminotransferase (median: 70.58 vs. 155.70 U/L), alanine aminotransferase (median: 18.31 vs. 37.90 U/L), lower plasma glucose (median: 4.32 vs. 2.37 mg/dL), and revised quantitative insulin sensitivity check index (median: 0.39 vs. 0.37) compared with healthy cows. Increased abundance of phosphorylated insulin receptor substrate-1 (IRS1) and decreased abundance of phosphorylated protein kinase B (AKT) and glycogen synthase kinase-3β (GSK3β) in ketotic cows indicated a state of insulin resistance. In addition, abundance of phosphorylated protein kinase RNA-like ER kinase (PERK) and inositol requiring protein-1α (IRE1α), and cleavage of activating transcription factor-6 (ATF6) were greater in the liver of ketotic cows. In vitro, at the early stages of incubation, treatment with BHB upregulated abundance of phosphorylated of IRE1α, PERK, and the cleavage of ATF6, as well as several unfolded protein response genes [X-box-binding protein-1 (XBP1), 78 kDa glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP)]. Furthermore, in response to increasing doses of BHB, the phosphorylation level of PERK, IRE1α, and the cleavage of ATF6, and the abundance of XBP1, GRP78, and CHOP increased. In addition, BHB treatment increased phosphorylation of IRS1 and decreased phosphorylation of AKT and GSK3β, and upregulated abundance of gluconeogenic genes (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase). Importantly, these changes were reversed by inhibiting ER stress with TUDCA treatment. Overall, the present study indicated that reversing ER stress during ketosis might help alleviate hepatic insulin resistance. Targeting ER stress may represent a potential therapeutic target for controlling the negative aspects of ketosis on liver function.

Objective: To analyze the effect and value of vitamin C in the treatment of sepsis. Methods: Forty-four patients with sepsis treated in our hospital from June 2019 to June 2021 were investigated. The above subjects were divided into conventional group and research group, each with 22 cases, using the method of drawing lots. Routine treatment was applied in the conventional group, and the patients of the research group were treated with vitamin C on the basis of the routine method. The effective rate after treatment and the score of liver and kidney function in patients with sepsis were compared between the two groups. Results: The total effective rate (95.45%) of the research group with increased vitamin C in the treatment of sepsis was much higher than that of the conventional group (72.72%), and the scores of liver function and renal function in the research group were much higher than those in the conventional group at different times (P < 0.05). Conclusion: Vitamin C has a good effect in the treatment of sepsis. It not only greatly reduces the mortality of sepsis patients, but also effectively improves the liver function and renal function of sepsis patients. It is of high application value. It is recommended to be popularized for applications.

By inhibiting the growth of pathogenic bacteria and modulating the local intestinal immune system, probiotics may reduce bacterial translocation and systemic endotoxaemia, factors partially responsible for post-operative complications following liver resection for hepatocellular carcinoma in patients with cirrhosis. Patients with resectable hepatocellular carcinoma developed in the setting of chronic liver disease were prospectively divided into two equal-sized groups: one receiving probiotic treatment 14 days prior to surgery and the other receiving placebo. The primary endpoint was the level of circulating endotoxins after hepatectomy. Secondary endpoints were systemic inflammation (inflammatory cytokine levels), post-operative liver function and overall post-operative complication rate. From May 2013 to December 2018, 64 patients were randomized, and 54 patients were included in the analysis, 27 in each arm. No significant change in endotoxin levels was observed over time in either group (P = 0.299). No difference between the groups in terms of post-operative liver function and overall complication rates was observed. The only differences observed were significant increases in the levels of TNFalpha (P = 0.019) and interleukin 1-b (P = 0.028) in the probiotic group in the post-operative period. Contrary to the modest data reported in the literature, the administration of probiotics before minor liver resection for hepatocellular carcinoma developed in the setting of compensated chronic liver disease does not seem to have an impact on circulating endotoxin levels or post-operative complication rates. Trial registration: NCT02021253.

OBJECTIVE Hepatocellular carcinoma (HCC) is the sixth among the most common cancers and the fourth among cancer-related causes of death in the world. In the evaluation of liver function in HCC patients, parameters such as albumin-bilirubin, prothrombin time-international normalized ratio (PT-INR) to albumin ratio (PTAR) are used among new methods other than Child-Pugh and MELD scores. Biomarkers are widely used in clinical practice in cases such as diagnosing various diseases, evaluating treatment response and predicting prognosis. We aimed to evaluate the prognostic role of serum ferritin and INR/albumin ratio in patients with chronic liver disease who develop HCC. METHODS This retrospective study included 534 patients who were followed up with the diagnosis of HCC between 2009 and 2020. The patients with HCC etiology were evaluated in 3 groups (chronic hepatitis B group, chronic hepatitis C group, and other group). When comparing serum ferritin level and prothromin time-international normalized ratio to albumin ratio with Child Pugh score (CTP) in chronic liver patients with HCC, liver functional reserve and its role in predicting prognosis were investigated. RESULTS The serum ferritin level was 226 ± 334 in the CTP A group, 239 ± 302 in the CTP B group, and 678 ± 966 in the CTP C group, and the p value was 0.001. The PTAR CTP group was 0.35 ± 0.10, the CTP B group was 0.50 ± 0.26, the CTP C group was 1.18 ± 6.01, and the p value was 0.001. Multivariant analysis results showed that ferritin hazard ratio is 1.00, 95% CI 0.99-1.00, and p value was 0.09, and PTAR hazard ratio is 1.38, 95% CI 2.37-8.00, and p value was 0.49. The etiological distribution of HCC was determined as HBV (61.6%), HCV (19.9%), and other etiologies (18.5%). Significant values were determined for age, gender, glucose, GGT, T. cholesterol, and tumor diameter parameters according to etiological distribution. CONCLUSIONS Serum ferritin level and PTAR score increased in proportion to the severity of liver disease and were associated with poor prognosis. We think that high serum ferritin and PTAR score is a prognostic biomarker in predicting the synthesis function of the liver and mortality in critically ill patients with cirrhosis.

The formation of the liver cirrhosis (LC) is an unfavorable event of the natural history of chronic liver diseases being accompanied by complications that often cause a fatal outcome. The study of the effectiveness of drugs that affect various etiopathogenetic mechanisms of this condition is an urgent problem of modern hepatology.The aim of the review was to show the role of antiviral therapy (AVT) in the management of patients with LC associated with chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection.PubMed database, Google Scholar search engine, Cochrane Systematic Reviews, eLIBRARY.RU electronic scientific library, as well as the reference lists of articles were used to search for scientific articles. The relevant objectives of the review of the publications were identified for the period since 2000 up to 2021 by the search queries as following: «liver cirrhosis», «liver fibrosis», «chronic HBV infection», «chronic HCV infection», «portal hypertension», «treatment». The inclusion criteria were restricted to the management of patients with LC associated with chronic HBV and HCV infection.Current guidelines recommend indefinite treatment of patients with HBV-associated LC with nucleos(t)ide analogues regardless of serum HBV DNA levels, while the modern concept of using direct-acting antiviral drug combinations has become the standard treatment for HCV-associated cirrhosis. Studies have shown the ability of AVT to inhibit and reverse fibrotic processes in LC associated with chronic HBV and HCV infection. It has also been reported that HBV/HCV eradication prior to orthotopic liver transplantation improves long-term overall survival.This, in turn, can reduce the severity of portal hypertension and decrease the risk of associated complications, as well as normalize liver function. Thus, ensuring the availability of drugs for those in need of AVT will not only help prevent the development of LC, but also improve the quality of life and increase its expectancy of patients suffering from this disease.

Ornithine Transcarbamylase (OTC) is an enzyme of the urea cycle, which converts ammonia into urea in the liver cells. OTC plays a crucial role in the breakdown and removal of nitrogen in the body. OTC deficiency is a rare X-linked recessive disorder that classically presents in early life with signs of hyperammonemia and progressive central nervous system involvement resulting in seizures, coma, and death. Sentinel presentation in adulthood is quite rare. A 29-year-old man developed altered mental status after receiving an epidural steroid injection 3 days earlier for back pain. He presented to the emergency department severely agitated, and his workup revealed an elevated ammonia level of 125 µmol/L. He refused admission and was discharged against medical advice. The following day, his mentation deteriorated, he developed status epilepticus, and was transported to another emergency department. He was admitted with worsening hyperammonemia (levels rising to over 700 µmol/L). His clinical condition progressive deteriorated, and he developed encephalopathy and diffuse cerebral edema. Liver function testing indicated progressive liver damage, and amino acids were detected in his blood and urine. Clinical and laboratory findings suggested undiagnosed OTC enzyme deficiency. He died 2 days after admission. An autopsy showed an 1890 g liver with diffuse yellow discoloration and softening. Histology and electron microscopy revealed findings suggestive of urea cycle disorder, such as microvesicular steatosis, apoptosis, and scattered mitosis, clusters of clear hepatocytes at the PAS stain, and mitochondria abnormalities. Genetic analysis revealed a hemizygous pathogenic variant of the OTC gene (c.622G>A). OTC deficiency should be suspected in subjects with hyperammonemic encephalopathy. If a genetic mutation is identified in the deceased, surviving family members should be screened to prevent potential life-threatening complications.

There is no specific treatment for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). It is not clear when transjugular intrahepatic portosystemic shunt (TIPS) should be implemented in PA-HSOS patients. This study aimed to evaluate the timing of TIPS using total bilirubin (TBIL) as a measure, and to investigate efficacy of TIPS. We retrospectively analyzed the medical records of 10 PA-HSOS patients, among whom 4 patients had received TIPS (TIPS group), and the remaining patients were assigned to the internal medicine group. In the TIPS group, the TBIL level before TIPS was 84.4 ± 45.2 µmol/L (> 3 mg/dL), and TBIL levels were increased to different degrees after TIPS. With the extension of time, serum TBIL levels gradually decreased, and no liver failure occurred. With regards to the short-term outcomes, 3 patients recovered, 1 developed chronic illness and 0 died in the TIPS group. Moreover, 0 patients recovered, 5 developed chronic illness and 1 died in the internal medicine group. The rank sum test of group design revealed significant differences in clinical outcomes (P = 0.02). It was suggested that when the internal medicine effect of PA-HSOS patients is poor, TIPS should be considered, which is no trestricted to the limit of 3 mg/dL TBIL. It was also found TIPS effectively promote the recovery of liver function and reduce the occurrence of chronicity.

Sphingosine kinase 2 (SphK2) inhibitors are developed for tumor therapy as considering its anti-tumor effect. Many studies also explored SphK2 modulated glucose and lipid homeostasis, which extended its potential function for metabolic diseases therapy. In this study, we discovered a significant reduction of hepatic lipid accumulation as well as recovery of liver function in ob/ob mice with intraperitoneal injection of K145. Also, db/db mice received K145 showed improvement of both NALFD and hyperglycemia. We furtherly analyzed the genes associated with lipid metabolism and found a remarkable decreased expression of lipogenic genes including FAS, ACC1 and SREBP1c whereas elevated mitochondrial fatty acid β-oxidation (FAO) related genes expression including CPT1A, MCAD, LCAD, PPAR-α, UCP2. Consistent to in vivo study, in vitro study also confirmed the role of K145 in decreasing lipid accumulation in human HL7702 cells, while inhibiting FAS, ACC1 and SREBP1c mRNA expression. It indicated a possible mechanism of K145 induced improvement of hepatic lipid accumulation partly via inhibition of lipigenesis. Our study suggested a promising role of K145 in drug development for NAFLD and diabetes therapy.

The use of gamma glutamyl transpeptidase (GGT) levels as screening test for liver function is controversial. The GGT main utility is in cases in which alkaline phosphatase (ALP) is elevated. We aimed to investigate the request over time for alanine amino transferase (ALT), ALP and GGT, study the effect of a new demand management (DM) intervention for optimal GGT measurement in primary care. Our descriptive study was conducted from January 2010 to December 2020. The intervention was established in November 2019 and consisted of the laboratory information system would automatically remove GGT, if the test had been ordered simultaneously with ALP and there was no prior pathological result on record. We counted the absolute number of measured ALT, ALP and GGT, and calculated the ratios for each of the three markers related to creatinine, and GGT related to ALT in a monthly basis. The number of measured GGT increased slightly and progressively along the study until October 2019, when a decrease was observed. The ALT and ALP request from primary care also increased slightly along years. However, the GGT/ALT ratio never reached the 0.2 goal. Out of the 57,614 GGT requested in primary care patients, 38,167 (66.2%) were not measured. 7633.4€ were saved in reagent. The DM intervention to reduce the measurement of GGT when requested redundantly with ALP in primary care was successful, and the results have been maintained over time as observed by monitoring the GGT/CREA and GGT/ALT indicator results.

Background: Using nationally representative data, we examined the age-, sex-, and ethnic-specific variation in the ratio of serum aspartate aminotransferase and alanine aminotransferase (AST-to-ALT...

Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

Objectives This study evaluated the long-term efficacy of a standard antithrombotic strategy versus half-dose direct oral anticoagulation (DOAC) after Watchman implantation. Background No consensus currently exists on the selection of the most effective antithrombotic strategy to prevent device-related thrombosis (DRT) in patients undergoing endocardial left atrial appendage closure. Methods After successful left atrial appendage closure, consecutive patients were prescribed a standard antithrombotic strategy (SAT) or long-term half-dose DOAC (hdDOAC). The primary composite endpoint was DRT and thromboembolic (TE) and bleeding events. Results Overall, 555 patients (mean age 75 ± 8 years, 63% male; median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category] score 4 [interquartile range (IQR): 3-6]; median HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] score 3 [IQR: 2-4]) were included. Patients were categorized into 2 groups (SAT: n = 357 vs hdDOAC: n = 198). Baseline clinical characteristics were similar between groups. The median follow-up duration was 13 months (IQR: 12-15 months). DRT occurred in 12 (2.1%) patients, all in the SAT group (3.4% vs 0.0%; log-rank P = 0.009). The risk of nonprocedural major bleeding was significantly more favorable in the hdDOAC group (0.5% vs. 3.9%; log-rank P = 0.018). The rate of the primary composite endpoint of DRT and TE and major bleeding events was 9.5% in SAT patients and 1.0% in hdDOAC patients (HR: 9.8; 95% CI: 2.3-40.7; P = 0.002). Conclusions After successful Watchman implantation, long-term half-dose DOAC significantly reduced the risk of the composite endpoint of DRT and TE and major bleeding events compared with a standard, antiplatelet-based, antithrombotic therapy.

Background Current vaccines for the Coronavirus Disease of 2019 (COVID-19) have demonstrated efficacy with low risk of adverse events. However, recent reports of thrombosis with thrombocytopenia syndrome (TTS) associated with adenovirus vector vaccines have raised concern. Objective This narrative review summarizes the current background, evaluation, and management of TTS for emergency clinicians. Discussion TTS, also known as vaccine-induced immune thrombotic thrombocytopenia, is a reaction associated with exposure to the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and AD26.COV2·S (Johnson & Johnson) vaccine, which may result in thrombocytopenia and thrombotic events. There are several case series of patients diagnosed with TTS, but the overall incidence is rare. TTS is characterized by exposure to one of the aforementioned vaccines 4–30 days prior to presentation, followed by thrombosis, mild-to-severe thrombocytopenia, and a positive platelet factor-4 (PF4)-heparin enzyme-linked immunosorbent assay (ELISA). Thrombosis typically involves atypical locations, including cerebral venous thrombosis and splanchnic vein thrombosis. Evaluation should include complete blood count, peripheral smear, D-dimer, fibrinogen, coagulation panel, renal and liver function, and electrolytes, as well as PF4-heparin ELISA if available. Consultation with hematology is recommended if suspected or confirmed. Treatment may include intravenous immunoglobulin and anticoagulation, while avoiding heparin-based agents and platelet transfusion. Conclusions With increasing vaccine distribution, it is essential for emergency clinicians to be aware of the evaluation and management of this condition.

Pregnancy toxemia (PT) is the most frequent metabolic disease of sheep during late pregnancy, which can lead to enormous economic losses in sheep farm industry. However, the underlying mechanism of PT in sheep has not been fully elucidated. High levels of β-hydroxy butyric acid (BHBA) exist in PT sheep. The AMP-activated protein kinase (AMPK) pathway plays a major role in regulating liver function. The aim of this study was to explore the effects of gradient concentrations of BHBA on lipid metabolism of sheep hepatocytes and the underlying molecular mechanism in vitro. The results showed that 0.6, 1.2 mmol/L BHBA could activate AMPKα, promoted the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and its target genes, and inhibited the expressions of sterol regulatory element binding protein-1c (SREBP-1c) as well as its downstream genes. When the concentration of BHBA was beyond 1.2 mmol/L, the expressions of the above-mentioned proteins and genes were just the opposite. However, the expressions of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) did not change significantly. The levels of very low density lipoprotein (VLDL), triglyceride (TG) and cholesterol (T-CHOL) showed a gradually increasing trend with the increase of BHBA concentration. According to the results above, it demonstrates that high levels of BHBA can inhibit the expression of the AMPK pathway and cause lipid metabolism disorders in sheep hepatocytes, which may lead to the occurrence of PT.

Background The majority of dogs with coccidioidomycosis recover with administration of fluconazole or itraconazole, although some cases are refractory or the dogs do not tolerate administration of these medications. Objectives The objective was to describe the treatment outcomes and therapeutic monitoring of 8 dogs with refractory coccidioidomycosis treated with posaconazole. Animals Eight dogs with refractory coccidioidomycosis. Methods Retrospective case series. Medical records from Veterinary Specialty Center of Tucson were searched to identify dogs with refractory coccidioidomycosis that were treated with posaconazole. Clinical information and the results of monitoring trough serum posaconazole concentrations were retrieved. Results Eight dogs with refractory coccidioidomycosis were treated with 2.5 to 10 mg/kg per day of posaconazole. Six of 8 dogs recovered or developed clinical remission while administered posaconazole. Thirteen serum concentrations from 8 dogs tested were >1 μg/mL (range, 1.52 to >6 μg/mL) and the drug was well‐tolerated by 7 dogs. One dog required dosage reductions and treatment was ultimately discontinued because of hepatotoxicosis. Conclusions and Clinical Importance Posaconazole should be considered as a treatment option for dogs with refractory coccidioidomycosis. Monitoring of indicators of liver function or injury along with therapeutic drug monitoring is recommended to tailor dosage in the event of hepatic toxicosis.

Direct-acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection, and interferon-free DAA treatment has improved liver function of HCV patients. The risk of hepatocellular carcinoma (HCC) occurrence following HCV eradication has been previously reported, but HCC may have been missed following imaging diagnosis before DAA administration in previous studies. Therefore, the present study aimed to identify definite predictors of HCC occurrence ≥1 year after DAA treatment. Among 956 patients receiving DAAs for HCV infection, 567 patients who achieved sustained virologic response with no history of HCC treatment were enrolled in this study between September 2014 and July 2021. The incidence of HCC in HCV-infected patients ≥1 year following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinical characteristics and blood test results. In the present study, 25 patients developed HCC. The incidence of HCC was 1.4%, 3.2%, 4.9% and 6.8% at 2, 3, 4 and 5 years, respectively, from the end of treatment with DAAs. Multivariate logistic analysis revealed serum α-fetoprotein level at end of treatment (EOT-AFP) >3.8 ng/ml ≥1 year following treatment with DAAs (HR, 9.7; p

Background: People with malignancy are under increased threat in the current COVID-19 pandemic. It is crucial to study the severity of COVID-19 in different cancer type as the microenvironments are different. Besides, the effect on specific organs should be studied to understand the long-term consequences of both the diseases and its treatment. Methods: In our retrospective case series, we are presenting degree of severity in 5 cancer-COVID patients based on their clinical characteristics. All the patients were RT-PCR confirmed COVID-19 patients with malignancy. The demographic and clinical data of the patients were retrieved from the hospital database.Results: The cancers include; stomach (1), bladder (2), glioma (3), lungs (4) and hard palate cancer (5). Patient-4 and 5 were receiving chemotherapy when they got infected and had highly dysregulated liver function and higher CT severity score (19/25) compared to the nonrecipients. In patient-2 inflammatory and other haematological parameters we highly dysregulated suggesting a possible bottle neck of older age. Interestingly in the patient-3 the COVID-19 markers like lymphocyte, neutrophil and platelet levels were close to or within the normal limits unlike other patients. Conclusions: All the patents included in our report died during hospitalization. The patients receiving chemotherapy had possible impaired liver function and died early compared to the nonrecipients. The characteristic COVID-19 markers like lymphopenia, neutrophilia and thrombocytopenia did not occur in the glioma patient. The effect of cancer-COVID and its treatment on specific organs like the liver and kidney need to be studied during treatment and follow-up.

Background Namodenoson, an A3 adenosine receptor (A3AR) agonist, improved liver function/pathology in non-alcoholic steatohepatitis (NASH) preclinical models. Aim To evaluate the efficacy and safety of namodenoson for the treatment of non-alcoholic fatty liver disease (NAFLD) with or without NASH METHODS: This phase 2 study included 60 patients with NAFLD (ALT ≥60 IU/L) who were randomised (1:1:1) to oral namodenoson 12.5 mg b.d. (n = 21), 25 mg b.d. (n = 19), or placebo (n = 20) for 12 weeks (total follow-up: 16 weeks). The main efficacy endpoint involved serum ALT after 12 weeks of treatment. Results Serum ALT decreased over time with namodenoson in a dose-dependent manner. The difference between change from baseline (CFB) for ALT in the namodenoson 25 mg b.d. arm vs placebo trended towards significance at 12 weeks (P = 0.066). Serum AST levels also decreased with namodenoson in a dose-dependent manner; at 12 weeks, the CFB for 25 mg b.d. vs placebo was significant (P = 0.03). At Week 12, 31.6% in the namodenoson 25 mg b.d. arm and 20.0% in the placebo arm achieved ALT normalisation (P = 0.405). At week 16, the respective rates were 36.8% and 10.0% (P = 0.038). A3AR expression levels were stable over time across study arms. Both doses of namodenoson were well tolerated with no drug-emergent severe adverse events, drug-drug interactions, hepatotoxicity, or deaths. Three adverse events were considered possibly related to study treatment: myalgia (12.5 mg b.d. arm), muscular weakness (25 mg b.d. arm), and headache (25 mg b.d. arm). Conclusion A3AR is a valid target; namodenoson 25 mg b.d. was safe and demonstrated efficacy signals (ClinicalTrials.gov #NCT02927314).

Background After cold storage (CS) and subsequent transplantation, fatty liver is more inclined to develop liver dysfunction and serious postoperative complications in contrast to healthy liver. Hypothermic oxygenated perfusion (HOPE) is a safe and efficacious system, which can repair fatty liver and reduce ischemia-reperfusion injury. The aim of this research is to investigate the function of Brg1/Nrf2/HO-1 signaling pathway in the protective effect of HOPE on ischemia-reperfusion injury of fatty liver. Methods The mouse fatty liver model was successfully established and verified by hematoxylin-eosin (HE) staining and oil red O staining. The animals were divided into Control group, CS group and HOPE group. The levels of liver enzyme and lactate in the perfusate were used to measure liver function and cellular metabolism. HE staining and TUNEL staining were utilized to assess the tissue structure and apoptosis, respectively. The levels of superoxide dismutase, malondialdehyde and reactive oxygen species in liver tissue were measured to quantitatively analyze the degree of oxidative stress, and the expressions of protein Brg1, Nrf2 and HO-1 were detected by means of the western blot. Double-labeling immunofluorescence was to explore the colocalization of Brg1 and Nrf2. Results The injury of the liver in the CS group was more serious than that in the control group. However, HOPE could significantly reduce the injury, which was manifested by the improvement of liver function and cellular metabolism, and the lower degrees of apoptosis, necrosis and oxidative stress. Furthermore, the expressions of Brg1, Nrf2 and HO-1 in the HOPE group were significantly increased than those in the CS group. Conclusions One-hour HOPE treatment before reperfusion can obviously improve the injury of fatty liver in mice. The underlying mechanism may be that the interaction of Brg1 and Nrf2 can selectively activate the transcription of HO-1.

The article deals with the questions of L-ornithine L-aspartate (Hepa-Merz) effect on the protein-synthesizing function of the liver at its resection in the primary or metasta­tic lesions. L-ornithine L-aspartate — the salt of natural amino acids of ornithine and aspartate, which improve the survival of hepatocytes, increases their number and significantly increases secretion of transferrin in vitro. At the premises of the department of anesthesiology and intensive care of National Cancer Institute (Kyiv), a prospective study was conducted on the efficacy of L-ornithine L-aspartate when used in oncological patients in the perioperative period, it included 42 patients operated under general inhalation anesthesia in combination with extended epidural anesthesia, who were divi­ded into two groups. Patients of group 1 received L-ornithine L-aspartate in a dose of 10 ml (5 g) once daily 2 days before and 3–4 days after the surgery, patients in the control group didn’t take L-ornithine L-aspartate. It was demonstrated that the perioperative administration of L-ornithine L-aspartate in patients with liver resection can positively affect the synthetic function of the liver.

PURPOSE To compare the survival outcomes of patients treated with transarterial ethanol ablation (TEA) with those treated with liver resection (LR) for solitary HCC less than 5 cm in diameter, in patients stratified according to liver function using ALBI grade. MATERIALS AND METHODS This retrospective study approved by the Institutional Committee included all treatment-naive patients with solitary HCC (≤ 5 cm) and Child-Pugh score 5, and who had received TEA (33 patients) or LR (192 patients) between 2004 and 2012. Treatment outcomes were compared between patients treated with TEA and LR after a period of at least 7 years of follow-up. Comparison was repeated for those patients with ALBI grade 2 or 3. RESULTS Both overall survival (OS, months) and recurrence-free survival (RFS months) were significantly longer in the LR group (OS: LR 129.7[119.5, 140], TEA 69.1[55.9, 82.3], P

Hepatic encephalopathy (HE) is a common, incapacitating complication of cirrhosis that affects many patients with cirrhosis. Although several therapies have proven effective in the treatment and prevention of this condition, several patients continue to suffer from covert disease or episodes of relapse. The circadian rhythm has been demonstrated to be pivotal for many body functions, including those of the liver. Here, we explore the impact of circadian rhythm-dependent signaling on the liver and discuss the evidence of its impact on liver pathology and metabolism. We describe the various pathways through which circadian influences are mediated. Finally, we introduce a novel method for improving patient response to drugs aimed at treating HE by utilizing the circadian rhythm. A digital system that introduces a customization-based technique for improving the response to therapies is presented as a hypothetical approach for improving the effectiveness of current medications used for the treatment of recurrent and persistent hepatic encephalopathy.

Background: Combination therapy with anti-programmed death-ligand 1 monoclonal antibody atezolizumab plus anti-vascular endothelial growth factor agent bevacizumab (Atezo/Bev) was approved in 2020 as a first-line treatment for unresectable hepatocellular carcinoma (HCC). Atezo/Bev therapy is relatively well tolerated, however, factors that can predict its response have not yet been reported. Thus, we aimed to investigate whether the pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict the therapeutic response in patients with HCC treated with Atezo/Bev therapy. Methods: We analyzed the course of 40 patients with HCC who received Atezo/Bev therapy at our hospital and attempted to identify pretreatment factors that could predict response by comparing those who achieved disease control with those who did not. Results: The pretreatment NLR value in patients who achieved disease control was significantly lower than that in patients with disease progression (2.47 vs. 4.48, p = 0.013). Using the optimal NLR cut-off value for predicting response (3.21) determined by receiver operating characteristic curve analysis, patients with NLR ≤ 3.21 had significantly better progression-free survival than those with NLR &gt, 3.21 (p &lt, 0.0001), although there were no significant differences in liver function or tumor-related background factors between the two groups. Conclusions: The pretreatment NLR value may be a useful predictor of response to Atezo/Bev therapy for HCC.

Background The incidence of hepatocellular carcinoma (HCC) has been increasing among the elderly populations. Trans-arterial chemoembolization (TACE), a widely used first-line non-curative therapy for HCCs is an issue in geriatrics. We investigated the prognosis of elderly HCC patients treated with TACE and determined the factors that affect the overall survival. Methods We included 266 patients who were older than 65 years and had received TACE as initial treatment for HCC. We analyzed the skeletal muscle index (SMI) and visceral-to-subcutaneous fat ratio (VSR) around the third lumbar vertebrae using computed tomography scans. Muscle depletion with visceral adiposity (MDVA) was defined by falling below the median SMI and above the median VSR value sex-specifically. We evaluated the overall survival in association with MDVA and other clinical factors. Results The mean age was 69.9 ± 4.5 years, and 70.3% of the patients were men. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, 29, 136, and 101 patients were classified as BCLC 0, A, and B stages, respectively, and 79 (29.7%) had MDVA. During the median follow-up of 4.1 years, patients with MDVA had a shorter life expectancy than those without MDVA (P = 0.007) even though MDVA group had a higher objective response rate after the first TACE (82.3% vs. 75.9%, P = 0.035). Multivariate analysis revealed that MDVA (Hazard ratio [HR] 1.515) age (HR 1.057), liver function (HR 1.078), tumor size (HR 1.083), serum albumin level (HR 0.523), platelet count (HR 0.996), tumor stage (stage A, HR 1.711; stage B, HR 2.003), and treatment response after the first TACE treatment (HR 0.680) were associated with overall survival. Conclusions MDVA is a critical prognostic factor for predicting survival in the elderly patients with HCC who have undergone TACE.

Summary Background Both modified Child-Pugh (MCP) and Albumin-bilirubin (ALBI) grade were reported that simpler, more objective and evidence-based alternative to the Child-Pugh (CP) class for assessing liver function. Aims To investigate whether the MCP and ALBI grade could better evaluate the liver reserve of Hepatocellular Carcinoma (HCC) patients treated with TACE (transcatheter arterial chemoembolization) than CP grade. Methods Three hundred seventy-six consecutive HCC patients treated with TACE between December 2007 and October 2011 were enrolled. The baseline characteristics and clinical information were collected. Homogeneity and discriminatory ability were compared between the MCP grade and ALBI class or CP grade. Results Compared with the CP and ALBI, the MCP grade had a higher predictive accuracy for overall survival (OS) in terms of homogeneity and discriminatory ability. Most of the HCC patients had CP class A disease (84.0%) at presentation, and within this CP class, although the ALBI grade revealed two clear and nonoverlapping groups, the MCP grade revealed three clearly different prognostic groups. Both in the ALBI grade 1 or ALBI grade 2 group, the MCP grade still showed a significant progressive decrease in OS from the smallest to the largest grades, but the CP class was unsatisfactory in stratifying these patients. Conclusions The stratification ability and prognostic predictive power of the MCP grade for HCC patients treated with TACE may be better than that of the ALBI grade or CP class.

Methylated septin 9 (mSEPT9) has a role in hepatocarcinogenesis. We evaluated mSEPT9 performance in patients with hepatocellular carcinoma (HCC) and those at risk of HCC METHODS: Using Epi-proColon® V2.0 assay adapted for 1 mL plasma, we investigated mSEPT9 sensitivity, specificity, associations with influential covariates and relation to death.Of 141 participants included, 136 had liver disease, 38 with HCC (mean-age 71 years) and 103 without HCC (mean-age 56.8 years), with further five without liver disease. 41 patients died (23 HCC) by the end of the study follow-up period. In HCC, mSEPT9 sensitivity and specificity were 89.47% (CI:75.20%-97.06%) and 81.55% (CI:72.70%-88.51%), whilst alpha fetoprotein (AFP) sensitivity and specificity were 50% (CI:33.38%-66.62%) and 97.09% (CI:91.72%-99.40%), respectively. Age-adjusted logistic regression showed mSEPT9 was associated with age, body mass index, HCC, liver cirrhosis, AFP, platelets, neutrophil-to-lymphocyte-ratio, albumin-bilirubin grade and fibrosis-4 index (p 0.05). Odds for HCC patients to have positive mSEPT9 were 27.4 times more than those without HCC. Time-to-death was associated with mSEPT9 positivity (p 0.05). Kaplan-Meier curves showed higher HCC survival with mSEPT9 compared to AFP.The mSEPT9 offers potential diagnostic and prognostic biomarker for HCC. After adjusting for age, mSEPT9 remained associated with liver function, liver fibrosis and inflammatory surrogate markers.

Yue-Rong Zhang,1 Hui Wang,2 Ning Zhou,2 Yao-Di Zhang,1,2 Yan Lin,1,2 Li-Yang Wu,1,2 Shi-Fang Wei,2 Yan-Yun Ma,2,3 Chun-Xia Wang3 1Department of Gastroenterology, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Infectious Diseases, The First People’s Hospital of Lanzhou, Gansu, 730050, People’s Republic of China; 3Department of Laboratory, The First People’s Hospital of Lanzhou, Gansu, 730050, People’s Republic of ChinaCorrespondence: Yue-Rong ZhangDepartment of Gastroenterology, University-Town Hospital of Chongqing Medical University, No. 55 University Town Middle Road, Shapingba District, Chongqing, 401331, People’s Republic of ChinaTel/Fax +86 102365714142Email zhang_yue_rong@163.comObjective: To explore the feasibility of treating cirrhosis using a multidisciplinary team approach (MDT) and to pinpoint the key factors influencing its implementation.Methods: The data of 307 patients with decompensated cirrhosis were studied retrospectively. Patients who received more than two treatment measures were assigned to the MDT group (n=228), and patients who received symptomatic medical drug treatment only were assigned to the traditional treatment group (n=79). The follow-up period ranged from 4 to 10 years, and the average follow-up period was 5.7 years. The results of the biochemical tests for hepatitis B virus deoxyribonucleic acid, hepatitis C virus ribonucleic acid, and autoantibodies to liver disease were analyzed.Results: The differences in gender and Child–Pugh grade of liver function between the two groups were not statistically significant. The MDT group had obvious advantages over the traditional treatment group in occupational composition, etiology composition, 5-year survival rate and annual hospitalization times. The leading causes of death in the MDT group, in descending order, were liver cancer, infection, mesenteric thrombosis, and non-hepatic disease, and, in the medical treatment group, they were liver failure, gastrointestinal bleeding, infection, and liver cancer. There was a significant statistical difference between the two groups (p < 0.05). In the multidisciplinary treatment, etiological treatment was the most widely used treatment, accounting for 79.8%, followed by endoscopic treatment (33.3%), peritoneal drainage and ascites reinfusion (25%), splenectomy combined with devascularization (11.4%) and stem cell transplantation and liver transplantation (1.8%).Conclusion: An MDT can improve the efficacy and prognosis of patients with cirrhosis and improve patient compliance. After multi-disciplinary intervention, the mortality spectrum of long-term survival patients with cirrhosis changes, and the mortality rate of liver cancer and non-liver disease increases.Keywords: liver cirrhosis, decompensated period, multidisciplinary team mode, traditional treatment, retrospective study

Objective. To investigate the effect of electroacupuncture (EA) on cognitive dysfunction in rats with hepatic encephalopathy and its underlying mechanism. Methods. Fifty Wistar rats were randomly divided into a normal group (n = 10) and model group (n = 40). Rat models of hepatic encephalopathy were established by administration of carbon tetrachloride and thioacetamide for a total of 12 weeks. At the 9th week after modeling, rats with cognitive impairment in the model group were identified by conducting the Morris water maze test, which were then randomly divided into a control group (CCl4) and treatment groups including EA group (CCl4 + EA), lactulose group (CCl4 + Lac), and EA plus lactulose group (CCl4 + CM), with 9 rats in each group. At the end of the 9th week, rats in CCl4 + Lac and CCl4 + CM groups had lactulose gavage at a dose of 10 mL/kg body weight, while normal control and CCl4 groups had gavage with the same volume of normal saline once a day for 21 days until the end of the experiment. Rats in CCl4 + EA and CCl4 + CM groups underwent acupuncture at Baihui (GV[DU]20), Shenting (GV[DU]24), and Zusanli (ST36) acupoints, among which EA at Baihui and Shenting acupoints were given once daily for 30 min lasting for 21 consecutive days. The effect of the treatment was measured by the Morris water maze test for learning and memory ability and magnetic resonance spectroscopy (MRS) for neuronal metabolism in the hippocampus of rats with hepatic encephalopathy. Pathological change in the rat hippocampus was observed by HE staining, while serum ammonia and liver function markers were detected. Western blot and real-time fluorescent quantitative PCR were used to detect the expressions of specific genes and proteins in the brain tissue. Results. Compared with those in the control group, rats undergoing EA had significantly shortened escape latency and increased number of platform crossing. H&E staining confirmed that EA improved brain tissue necrosis and ameliorated nuclear pyknosis in rats with hepatic encephalopathy. Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB). In addition, EA inhibited the brain expressions of TNF-α, IL-1β, IL-6, iNOS, TLR4, MyD88, NF-κB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-α, IL-6, TLR4, MyD88, NF-κB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3. MRS showed increased Glx/Cr and decreased NAA/Cr, Cho/Cr and mI/Cr in the control group, and EA significantly reversed such changes in Glx/Cr and mI/Cr values. Conclusion. EA ameliorated the production of excessive proinflammatory cytokines in the hippocampus of rats with cognitive dysfunction secondary to hepatic encephalopathy, which also gave rise to subsequent changes such as reduced blood ammonia level, brain-protective activated astrocytes, and lower degree of brain tissue injury. The p38MAPK/STAT3 and TLR4/MyD88/NF-κB signaling pathways may be involved. EA can also improve the metabolism of NAA and Cho in the rat hippocampus and thereby improve learning and memory abilities.

Chemosaturation (CS; CHEMOSAT®, Delcath Systems Inc.) temporarily administers melphalan into the liver by percutaneous hepatic perfusion (PHP). CS-PHP can effectively control growth in liver tumors, but efficacy and tolerability of sequential treatments are unclear. We analyzed outcomes of sequential CS-PHP treatment. Patients with either unresectable intrahepatic metastases of ocular melanoma (OM, n = 9), cholangiocarcinoma (CCA, n = 3), or hepatocellular carcinoma (HCC, n = 1) were recruited retrospectively. Response was assessed by tomography imaging. Ten patients (mean age 60 years) with more than one CS-PHP treatment were included. CS-PHP was administered 2–6 times in the OM patients, 3 times in the CCA, and the HCC patient received 6 treatments. Overall response rate (ORR) to CS-PHP was 80%, and stable disease was achieved in one patient. Median hepatic progression-free survival (hPFS) was 336 days (range 0–354) for OM, 251 days for the CCA patient, and 256 days for the HCC patient. At the end of observation (153–701 days after first CS-PHP), 6/10 patients were still alive (5/9 with OM, 0 with CCA, and 1 with HCC). Death cases were not related to CS-PHP. Adverse events were mostly hematologic, grade I-IV, and self-resolving. The liver function was not deteriorated by CS-PHP. We conclude that repeated CS-PHP treatments were effective and well tolerated in the long term.

It is of interest to assess the inflammatory marker profile in SARS-CoV-2 patients and to correlate the levels of systemic inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), C-Reactive Protein CRP, Ferritin, Creatine kinase (CK), Lactate dehydrogenase (LDH) and liver function analytes total serum proteins, albumin, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with the severity of SARS-CoV-2 infections. A total of 1000 COVID-19 positive patient’s data were collected. Laboratory assessments consisted of NLR (neutrophil-lymphocyte ratio) by cell counter, C Reactive Protein (CRP) by immunoturbidimetry, Ferritin by electrochemiluminescence (ECLIA) and Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total Bilirubin, Direct Bilirubin, Total Protein and Albumin by spectrophotometry. The mean plasma CRP levels, NLR, ferritin, CK and LDH levels were higher in severe cases than in non-severe cases, and the difference was statistically significant (p