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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 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.

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.

Individually, higher body mass index (BMI) and alcohol consumption increase the risk of liver disease. Evidence of a joint association is mixed; however, previous studies have not used causal inference methods robust to confounding and reverse causation. Understanding any true effect is key to developing effective interventions to reduce liver disease. To investigate the joint association of BMI and alcohol consumption with liver injury biomarkers and incident liver disease using factorial mendelian randomization (MR). A population-based cohort study (Copenhagen General Population Study) recruited a random sample of Copenhagen, Denmark, residents aged 20 years or older of white, Danish descent (N = 98 643) between November 25, 2003, and July 1, 2014. Data were also obtained from ongoing links to national registers, and then analyzed from September 30, 2016, to April 23, 2018. High and low BMI and alcohol consumption categories from baseline-measured or self-reported observational data and genetic variants predicting BMI and alcohol consumption. Plasma biomarkers of liver injury (alanine aminotransferase [ALT] and γ-glutamyltransferase [GGT]) and incident cases of liver disease from hospital records were the outcomes. Of the 98 643 individuals recruited, 91 552 (54 299 [45.2%] women; mean [SD] age, 58 [13.05] years) with no baseline liver disease were included in main analyses. Individuals had a mean (SD) BMI of 26.2 (4.3) and consumed a mean (SD) of 10.6 (10.2) U/wk of alcohol. In factorial MR analyses, considering the high BMI/high alcohol group as the reference, mean circulating ALT and GGT levels were lowest in the low BMI/low alcohol group (ALT: -2.32%; 95% CI, -4.29% to -0.35%, and GGT: -3.56%; 95% CI, -5.88% to -1.24%). Individuals with low BMI/high alcohol use and high BMI/low alcohol use also had lower mean circulating ALT levels (low BMI/high alcohol use: -1.31%; 95% CI, -1.88% to -0.73%, and high BMI/low alcohol use: -0.81%; 95% CI, -2.86% to 1.22%) and GGT levels (low BMI/high alcohol use: -0.91%; 95% CI, -1.60% to -0.22%, and high BMI/low alcohol use: -1.13%; 95% CI, -3.55% to 1.30%) compared with the high BMI/high alcohol use reference group. These patterns were similar in multivariable factorial analyses. For incident liver disease (N = 580), factorial MR results were less conclusive (odds ratio of liver disease vs high BMI/high alcohol group: 1.01; 95% CI, 0.84 to 1.18, for the low BMI/high alcohol group, 1.22; 95% CI, 0.56 to 1.88 for the high BMI/low alcohol group, and 0.99 (95% CI, 0.41 to 1.56 for the low BMI/low alcohol group). Interventions to reduce both BMI and alcohol consumption might reduce population levels of biomarkers of liver injury more than interventions aimed at either BMI or alcohol use alone. However, it is not clear whether this intervention will directly translate to a reduced risk of liver disease.

Fibrotest (FT) and Actitest (AT) are biochemical markers of fibrosis and activity for use as a non-invasive alternative to liver biopsy in patients with chronic hepatitis C virus (HCV). The aim of this study was to perform an external validation of FT and AT and to study the discordances between FT/AT and liver biopsy in patients with chronic hepatitis C. A total of 519 consecutive patients with chronic HCV were prospectively included in five centers, with liver biopsy and biochemical markers taken at the same day. Fifteen patients were excluded because their biopsies could not be interpreted. Diagnostic accuracies were assessed by receiver operating characteristic (ROC) curve analysis. Median biopsy size was 15 mm (range: 2-58), with 9 portal tracts (1-37) and 1 fragment (1-12). 46% (230/504) were classified F2-F4 in fibrosis and 39% A2-A3 in activity. FT area under ROC curve for diagnosis of activity (A2-A3), significant fibrosis (F2-F4), and severe fibrosis (F3-F4) were 0.73 [0.69-0.77], 0.79 [0.75-0.82], and 0.80 [0.76-0.83], respectively. Among the 92 patients (18%) with 2 fibrosis stages of discordance between FT and biopsy, the discordance was attributable to FT in 5% of cases, to biopsy in 4%, and undetermined in 9%. This prospective independent and multicenter study confirms the diagnostic value of FT and AT found in the princeps study and suggests that FT and AT can be an alternative to biopsy in most patients with chronic HCV.

Background Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. Methods/design The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. Discussion Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. Trial registration ClinicalTrials.gov, ID: NCT03282955 . Registered on 14 September 2017.

These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease.

Purpose The aim of our study was to propose a strategy based on indocyanine green (ICG) (SBI) to provide better clinical guidelines for transarterial chemoembolization (TACE) treatments for Barcelona clinic liver cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. Materials and Methods From October 2005 to December 2012, 112 BCLC stage C HCC patients initially treated with TACE were investigated, randomly divided into a training cohort (n = 79) and validation cohort (n = 33). In training group, the patients were grouped based on their 15 minutes ICG retention rate (ICG R15), different chemo drugs and dose of lipidol in TACE. Overall survival (OS) and progression‐free survival (PFS) were analyzed in subgroups. Strategy based on ICG was built and verified in validation group. Results For those patients with ICG R15 values >10%, the lipiodol ≤10 mL group showed better survival than the lipiodol >10 mL group. For those patients with ICG R15 values ≤10%, the group that received triple‐drug chemotherapy treatments with lipiodol diameter ratio values between 1 and 3 showed better survival than the other group. Patients who conformed with the SBI had better survival times than those who did not conform with the SBI, in both the training cohort (median OS 10.3 vs 5.1 months; P < .001; median PFS, 3.3 vs 2.1 months; P = .006) and the validation cohort (median OS 8.9 vs 7.1 months; P = .087; median PFS, 6.6 vs 2.3 months; P < .001). Conclusions The SBI is suitable and may provide survival benefits for TACE treatments in BCLC stage C HCC patients. In this study, we proposed a new indocyanine green (ICG)‐based treatment strategy, which was suitable and might provide survival benefits for transarterial chemoembolization treatments in Barcelona clinic liver cancer stage C hepatocellular carcinoma patients. For those patients with ICG retention rate (ICG R15) values greater than 10%, the lipiodol dose should be reduced to no more than 10 mL, and for those patients with ICG R15 values less than 10%, maintain the LDR value between 1 and 3 and use a triple chemotherapy drug regimen.

ObjectiveType 2 diabetes is an important risk factor for non-alcoholic fatty liver disease (NAFLD), but current guidelines provide conflicting recommendations on whether diabetic patients should be screened for NAFLD. We therefore studied the strategy of screening diabetic patients by FibroScan.DesignLiver fat and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) by FibroScan at a diabetic centre for patients from primary care and hospital clinics. Probe-specific LSM cut-offs were used to detect advanced fibrosis.ResultsOf 1918 patients examined, 1799 (93.8%) had valid CAP and 1884 (98.2%) had reliable LSM (1770 with the M probe and 114 with the XL probe). The proportion of patients with increased CAP and LSM was 72.8% (95% CI 70.7% to 74.8%) and 17.7% (95% CI 16.0% to 19.5%), respectively. By multivariable analysis, female gender, higher body mass index, triglycerides, fasting plasma glucose and alanine aminotransferase (ALT) and non-insulin use were associated with increased CAP. Longer duration of diabetes, higher body mass index, increased ALT and spot urine albumin:creatinine ratio and lower high-density lipoprotein-cholesterol were associated with increased LSM. Ninety-four patients (80% had increased LSM) underwent liver biopsy: 56% had steatohepatitis and 50% had F3-4 disease.ConclusionsDiabetic patients have a high prevalence of NAFLD and advanced fibrosis. Those with obesity and dyslipidaemia are at particularly high risk and may be the target for liver assessment. Our data support screening for NAFLD and/or advanced fibrosis in patients with type 2 diabetes.