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Background The aim of the present study was to evaluate the effects of curcumin supplementation on inflammatory indices, and hepatic features in patients with non-alcoholic fatty liver disease (NAFLD). Methods Fifty patients with NAFLD were randomized to receive lifestyle modification advice plus either 1500 mg curcumin or the same amount of placebo for 12 weeks. Results Curcumin supplementation was associated with significant decrease in hepatic fibrosis ( p  < 0.001), and nuclear factor-kappa B activity ( p  < 0.05) as compared with the baseline. Hepatic steatosis and serum level of liver enzymes, and tumor necrosis-α (TNF-α) significantly reduced in both groups ( p  < 0.05). None of the changes were significantly different between two groups. Conclusion Our results indicated that curcumin supplementation plus lifestyle modification is not superior to lifestyle modification alone in amelioration of inflammation. Trial registration IRCT20100524004010N24 , this trial was retrospectively registered on May 14, 2018.

Fish oil has been used effectively in the treatment of cardiovascular disease via triglyceride reduction and inflammation modulation. This study aimed to assess the effects of fish oil on patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. Eighty participants with NAFLD associated with hyperlipidemia were randomly assigned to consume fish oil (n=40, 4 g/d) or corn oil capsules (n=40, 4 g/d) for 3 months in a double-blind, randomized clinical trial. Blood levels of lipids, glucose and insulin, liver enzymes, kidney parameters and cytokines at baseline and the end of the study were measured. Seventy people finished the trial. Plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid significantly increased in the fish oil group after intervention. After adjustment for age, gender and BMI, fish oil significantly decreased fasting serum concentrations of total cholesterol, triglyceride, apolipoprotein B and glucose (by (mean±SD) 0.49±0.43 mmol/L, 0.58±0.89 mmol/L, 0.28±0.33 g/L and 0.76±0.56 mmol/L, respectively, P<0.05), as well as alanine aminotransferase and γ-glutamyl transpeptidase levels (by (median (interquartile)) 9.0(0.5, 21.5) and 7.0(2.2, 20.0) IU/L, respectively, P<0.05), significantly increased serum adiponectin levels (by 1.29±0.62 μg/mL, P<0.001), and reduced serum levels of tumor necrosis factor α, leukotrienes B4, fibroblast growth factor 21 (FGF21), cytokeratin 18 fragment M30 and prostaglandin E2 (by 1.70±1.18 pg/mL, 0.59±0.28 ng/mL, 121±31 pg/mL, 83±60 IU/L and 10.9±2.3 pg/mL, respectively, P<0.001). Corn oil had no effect except for increasing serum creatinine concentrations by 7.7±8.9 μmol/L (P=0.008). The effects of fish oil on lipids, glucose and γ-glutamyl transpeptidase were positively correlated with the reductions of serum FGF21 and prostaglandin E2 concentrations after adjustment for age, gender and BMI (r = 0.275 to 0.360 and 0.261 to 0.375, respectively, P<0.05). In conclusion, our findings suggest that fish oil can benefit metabolic abnormalities associated with NAFLD treatment. ChiCTR-TRC-12002380.

Background The real-world incidence of chronic liver damage after transarterial chemoembolization (TACE) is unclear. LiverT, a retrospective, observational study, assessed liver function deterioration after a single TACE in real-world hepatocellular carcinoma (HCC) patients in US practice. Methods Eligible HCC patients identified from Optum’s integrated database using standard codes as having had an index TACE between 2010 and 2016 with no additional oncologic therapy in the subsequent 3 months. At least one laboratory value (bilirubin, albumin, aspartate transaminase [AST], alanine transaminase [ALT], international normalized ratio [INR]) was required at baseline and the acute (≤29 days after TACE) and chronic (30–90 days after TACE) periods. Due to lack of universally accepted liver function deterioration criteria, clinically meaningful changes in laboratory parameters were pre-defined by authors (FP, RM, and SO). Results Of the 3963 TACE patients, 572 were eligible for analyses. Deterioration of liver function from baseline occurred in the acute period and persisted in the chronic period (bilirubin 30 and 23%, albumin 52 and 31%, AST 44 and 25%, ALT 43 and 25%, INR 25 and 15%, respectively). In a subgroup analysis, a higher proportion of patients with diabetes had deterioration in AST and ALT. Conclusions A clinically meaningful proportion of real-world HCC patients had deterioration of liver function-related laboratory values 30–90 days after a single TACE in modern US practice. Future electronic health record research may help determine causality. The present findings highlight the need for the careful selection of patients for TACE, which is important to help optimize the benefit of the overall HCC treatment course.

ObjectiveData on serial liver biochemistries of patients infected by different human coronaviruses (HCoVs) are lacking. The impact of liver injury on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains unclear.DesignThis was a retrospective cohort study using data from a territory-wide database in Hong Kong. COVID-19, severe acute respiratory syndrome (SARS) and other HCoV patients were identified by diagnosis codes and/or virological results. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2 × upper limit of normal (ie, 80 U/L). The primary end point was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation and/or death.ResultsWe identified 1040 COVID-19 patients (mean age 38 years, 54% men), 1670 SARS patients (mean age 44 years, 44% men) and 675 other HCoV patients (mean age 20 years, 57% men). ALT/AST elevation occurred in 50.3% SARS patients, 22.5% COVID-19 patients and 36.0% other HCoV patients. For COVID-19 patients, 53 (5.1%) were admitted to ICU, 22 (2.1%) received invasive mechanical ventilation and 4 (0.4%) died. ALT/AST elevation was independently associated with primary end point (adjusted OR (aOR) 7.92, 95% CI 4.14 to 15.14, p<0.001) after adjusted for albumin, diabetes and hypertension. Use of lopinavir–ritonavir ±ribavirin + interferon beta (aOR 1.94, 95% CI 1.20 to 3.13, p=0.006) and corticosteroids (aOR 3.92, 95% CI 2.14 to 7.16, p<0.001) was independently associated with ALT/AST elevation.ConclusionALT/AST elevation was common and independently associated with adverse clinical outcomes in COVID-19 patients. Use of lopinavir–ritonavir, with or without ribavirin, interferon beta and/or corticosteroids was independently associated with ALT/AST elevation.

Background. Invasive fungal infection (IFI) following liver transplant is associated with significant morbidity and mortality. Antifungal prophylaxis is rational for liver transplant patients at high IFI risk. Methods. In this open-label, noninferiority study, patients were randomized 1:1 to receive intravenous micafungin 100 mg or center-specific standard care (fluconazole, liposomal amphotericin B, or caspofungin) posttransplant. The primary endpoint was clinical success (absence of a proven/probable IFI and no need for additional antifungals) at end of prophylaxis (EOP). Noninferiority (10% margin) of micafungin vs standard care was assessed in the per protocol and full analysis sets. Safety assessments included adverse events and liver and kidney function tests. Results. The full analysis set comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease score ≥20. At EOP (mean treatment duration, 17 days), clinical success was 98.6% for micafungin and 99.3% for standard care (Δ standard care – micafungin [95% confidence interval], 0.7% [−2.7% to 4.4%]) in the per protocol set and 96.5% and 93.6%, respectively (−2.9% [−8.0% to 1.9%]), in the full analysis set. Incidences of drug-related adverse events for micafungin and standard care were 11.6% and 16.3%, leading to discontinuation in 6.4% and 11.6% of cases, respectively. At EOP, liver function tests were similar but creatinine clearance was higher in micafungin- vs standard care–treated patients. Conclusions. Micafungin was noninferior to standard care as antifungal prophylaxis in liver transplant patients at high risk for IFI. Adverse event profiles and liver function at EOP were similar, although kidney function was better with micafungin. Clinical Trials Registration. NCT01058174.

Reference intervals (RIs) are significant means for health evaluation, prognosis, diagnosis, and monitoring of adverse events. The RIs are affected by ethnicity, age, gender, geographic area, diet, socioeconomic, and physical situation. This study aimed to determine RIs of commonly used liver function tests (LFT) for healthy adults in Ibb City, middle of Yemen. A total of 390 participants aged between 18 and 70 were selected and administered a questionnaire. Blood specimens were assembled after an overnight fast, and the sera were separated for analysis of common LFT (DBIL, TBIL, ALB, TP, ALP, AST, and ALT) using Mindray BS-240 Automatic Clinical Chemistry Analyzer. The data were computed by GraphPad Prism 8.0.1. This study revealed that RIs for males and females of DBIL, TBIL, ALB, ALP, and ALT were significantly higher in males than females. Although RIs for TP and AST were higher in males than females, the difference was non-significance. Notably, most of the RIs in our study were different than those from other countries, either higher or lower. In conclusion, this study has established a panel of locally relevant RIs for commonly used LFT in adults, Ibb City, which may help interpret laboratory results for healthy adults and patients.

Background Accurate estimation of the hepatic functional reserve before liver resection is important to avoid post-hepatectomy liver failure (PHLF). The aim of the present study was to evaluate the association of indocyanine green retention test with portal pressure by the cause of cirrhosis (non-viral vs. viral) and assessed postoperative outcomes including incidence of PHLF in patients with viral and non-viral cirrhosis. Methods The cohort includes 50 consecutive patients with liver cirrhosis scheduled for liver resection for primary liver tumors at the Lausanne University Hospital between 2009 and 2018. Results There were 31 patients with non-viral liver cirrhosis (Non-virus group) and 19 with viral liver cirrhosis (virus group). The indocyanine green retention rate at 15 min (ICG-R15) ( p  = 0.276), Hepatic Venous Portal Gradient (HVPG; p  = 0.301), and postoperative outcomes did not differ between the non-virus group and viral group. ICG-R15 and HVPG showed a significant linear correlation in all patients (Spearman’s rank correlation coefficient, ρ  = 0.599, p  < 0.001), the non-virus group ( ρ  = 0.555, p  = 0.026), and the virus group ( ρ  = 0.534, p  = 0.007). A receiver operating characteristic curve analysis showed that ICG-R15 was a predictor for presence of portal hypertension (PH; HVPG ≥ 12 mmHg) (area under the curve [AUC] = 0.780). The cut-off value of ICG-R15 for predicting the presence of PH was 16.0% with 72.3% of sensitivity and 79.0% of specificity. Conclusions The ICG-R15 level was associated with portal pressure in both patients with non-virus cirrhosis and patients with virus cirrhosis and predicts the incidence of PH with relatively good discriminatory ability. Clinical trial number https://clinicalTrials.gov(ID:NCT00827723) Local ethics committee number CER-VD 251.08

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a clinical pathological syndrome characterized by steatosis and fat accumulation in liver parenchymal cells in patients without a history of excessive alcohol drinking. Currently, there is no definitive treatment for MASLD, and its prevalence increases with age and obesity, and after menopause. Among the ways to treat it, we can mention regular sports exercises and the use of natural supplements. Therefore, the aim of this research is to investigate and compare the effects of aerobic-resistance training with royal jelly supplementation on changes in paraoxonase 1, oxidized LDL, liver function, and lipid profile in postmenopausal women with Dysfunction-Associated Steatotic Liver Disease. Materials and Methods: This semi-experimental study involved 23 women with Dysfunction-Associated Steatotic Liver Disease with an average weight (71.34 ± 11.63 kg), age (48.54 ± 3.88 years), and body mass index (27.63 ± 4.20 kg/m2). They were randomly divided into two groups: exercise + supplement (n = 12) and exercise + placebo (n = 11). Both groups performed eight-station resistance exercises (8–12 repetitions in 2–4 sets) for 8 weeks, with three sessions per week (for 35–40 min, from 10-15 RPE), and then, for 10–15 min of active rest, they performed aerobic exercises with an intensity of 40–85% of the target heart rate, in two-minute intervals with 45 s of active rest. Royal jelly supplement (500 mg on training days, before each training session) was consumed. Blood sampling was done before and 48 h after the last training session. Statistical analysis was performed using a variance test with repeated measures (two groups × two stages of pre-test-post-test) in SPSS software (Version 26) with a significance level of p < 0.05. Results: The results of the statistical analysis show that the effects of eight weeks of exercise + supplement and exercise + placebo on PON1, oxLDL, lipid profiles (HDL, LDL, TC, and TG), and liver enzymes (ALT, AST) in women with non-alcoholic fatty liver showed a significant difference (p < 0.05). The results show a significant increase in PON1 (p = 0.008) and HDL (p = 0.005) in the exercise + supplement group compared to the exercise + placebo group. But significant decreases in oxLDL (p = 0.031), TC (p = 0.045), TG (p = 0.013), LDL (p = 0.027), ALT (p = 0.015) and AST (p = 0.009) were observed in the exercise + supplement group compared to the exercise + placebo group (<0.05). The results show a significant increase in PON1 (p = 0.008) and HDL (p = 0.005) in the exercise + supplement group compared to the exercise + placebo group. However, significant decreases in oxLDL (p = 0.031), TC (p = 0.045), TG (p = 0.013), LDL (p = 0.027), ALT (p = 0.015), and AST (p = 0.009) was observed in the exercise + supplement group compared to the exercise + placebo group. Conclusions: Based on the results, it can be concluded that aerobic-resistance exercises with the addition of royal jelly can probably be an efficient and recommended strategy to minimize the harmful effects of Dysfunction-Associated Steatotic Liver Disease by affecting the activity of liver enzymes, paraoxonase 1, LDL oxidation, and lipid profile. Although exercise alone also yielded favorable results, according to the findings of this research, it can be said that exercise, combined with the use of royal jelly supplements, may have more positive effects on reducing liver complications and improving body function. However, in order to obtain more accurate scientific evidence, it is necessary to investigate more doses and timing of royal jelly in future studies.

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and may influence the outcome of critical illness. Although abnormal liver function tests (LFTs) are frequent in the intensive care unit (ICU), the contribution of MASLD to organ-specific hepatic vulnerability and mortality remains unclear. This study aimed to evaluate whether pre-existing metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with baseline and new-onset liver function test (LFT) abnormalities and with intensive care unit (ICU) outcomes in non-cirrhotic medical ICU patients. Materials and Methods: We conducted a retrospective cohort study of adult non-cirrhotic patients admitted to a tertiary medical ICU between December 2020 and December 2023, who underwent hepatobiliary ultrasonography within six months before admission. MASLD was defined as hepatic steatosis with ≥1 cardiometabolic risk factor. The baseline and 72 h LFTs, injury patterns, and ICU outcomes were compared between MASLD and non-MASLD patients. Logistic regression was used to identify the independent predictors of new-onset LFT elevation and ICU mortality. Results: Among 609 patients, MASLD was diagnosed in 240 (39.4%). LFT elevation at admission was more frequent in patients with MASLD (52% vs. 39%, p = 0.03), driven mainly by higher alkaline phosphatase (ALP). At 72 h, ALP (96 [67–146] vs. 85 [60–137]) and gamma-glutamyl transferase (GGT) (50 [27–123] vs. 42 [20–100]) levels remained higher in patients with MASLD (p < 0.01), although rates of new-onset LFT elevation were similar (p > 0.05). Compared to non-MASLD patients, those with MASLD more often required invasive mechanical ventilation (IMV) (64% vs. 33%), central venous catheterization (70% vs. 44%), CRRT (28% vs. 10%), blood product replacement (50% vs. 28%), and developed nosocomial infections (44% vs. 29%) (p < 0.05 for all); however, MASLD was not an independent predictor of mortality. The independent risk factors for mortality were IMV, shock, and higher APACHE II scores. Conclusions: common among medical ICU patients and is associated with a cholestatic biochemical profile and poor ICU outcomes. However, early hepatic injury and ICU mortality are primarily determined by systemic severity and organ support requirements, not the MASLD itself.

IntroductionThe management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of misoprostol in treating patients with NASH.MethodsIn this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis.ResultsA total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25–64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months’ treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However, misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group.ConclusionImprovement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group.Trial registration numberNCT05804305.