L-carnitine supplementation in non-alcoholic fatty liver disease: A systematic review and meta-analysis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)dominates the landscape of modern hepatology.Affecting 25%of the general population,there is critical unmet need to identify broadly available,safe and cost-effective treatments.Cumulative evidence in animal and human models suggests that intrahepatic and skeletal muscle fatty acid oxidation is impaired in NAFLD,such that lipid accretion is not matched by efficient utilisation.L-carnitine is a crucial mediator of fatty acid metabolism in vivo,promoting mitochondrial lipidβ-oxidation and enhancing tissue metabolic flexibility.These physiological properties have generated research interest in L-carnitine as a potentially effective adjunctive therapy in NAFLD.AIM To systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry,liver fat and insulin sensitivity in NAFLD.METHODS Search strategies,eligibility criteria and analytic methods were specified a priori(PROSPERO reference:CRD42018107063).Ovid MEDLINE,Ovid EMBASE,PubMed,Web of Science and the Cochrane Library were searched from their inception until April 2019.Outcome measures included serum concentrations of alanine and aspartate aminotransferase(ALT and AST),liver fat and insulin sensitivity assessed by the homeostasis model of insulin resistance(HOMA-IR).A random effects meta-analysis was performed for,ALT,AST and HOMA-IR measures separately.Between-study heterogeneity was measured using I2 statistics.RESULTS Five eligible randomised trials were included in the qualitative and quantitative synthesis(n=338).All of the 5 included trials assessed the effect of L-carnitine on serum ALT,identified from Italy,South Korea and Iran.Weighted mean difference(WMD)for ALT between L-carnitine and control groups after intervention was-25.34 IU/L[95%CI:-41.74-(-8.94);P=0.002].WMD for AST between L-carnitine and control groups was-13.68 IU/L(95%CI:-28.26-0.89;P=0.066).In three studies(n=204),HOMA-IR was evaluated.WMD for HOMA-IR between L-carnitine and control groups was-0.74 units[95%CI:-1.02-(-0.46);P<0.001].Two studies using validated outcome measures reported a significant reduction in liver fat in L-carnitine vs control groups post-intervention(P<0.001).CONCLUSION Pooled results indicate that L-carnitine supplementation attenuates ALT,liver fat and insulin resistance in NAFLD cohorts,confirming a beneficial effect of Lcarnitine for a highly prevalent condition with a growing economic burden.

Prognostic non-invasive biomarkers for all-cause mortality in nonalcoholic fatty liver disease:A systematic review and meta-analysis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)represents a growing public health concern,with patients having higher risk of morbidity and mortality.It has a considerably high prevalence in the general population,estimated 20%-40%in Europe,and is asymptomatic until late in the disease course.It is therefore important to identify and validate tools that predict hard outcomes such as mortality for use in clinical practice in risk-stratifying NAFLD patients.AIM To evaluate available evidence on the use of non-invasive test(s)as prognostic factors for mortality in NAFLD.METHODS We performed electronic searches of Medline and EMBASE(Ovid)until 7^(th)January 2021 of studies in NAFLD populations.Prognostic markers included serum biomarkers,non-invasive scoring systems,and non-invasive imaging.The population included all spectrums of disease severity,including NAFLD and non-alcoholic steatohepatitis(NASH).Outcomes included all-cause,and cardiovascular mortality.All non-invasive tests were synthesised in a narrative systematic review.Finally,we conducted a meta-analysis of non-invasive scoring systems for predicting all-cause and cardiovascular mortality,calculating pooled hazard ratios and 95%confidence(STATA 16.1).RESULTS Database searches identified 2850 studies-24 were included.16 studies reported non-invasive scoring systems,10 studies reported individual biomarkers,and 1 study reported imaging modalities.4 studies on non-invasive scoring systems(6324 participants)had data available for inclusion in the meta-analysis.The non-invasive scoring system that performed best at predicting all-cause mortality was NAFLD fibrosis score(NFS)[pHR 3.07(1.62-5.83)],followed by fibrosis-4 index[pHR 3.06(1.54-6.07)],BARD[pHR 2.87(1.27-6.46)],and AST to platelet ratio index[pHR 1.90(1.32-2.73)].NFS was also prognostic of cardiovascular-related mortality[pHR 3.09(1.78-5.34)].CONCLUSION This study reaffirms that non-invasive scoring systems,especially NFS,are reliable prognostic markers of all-cause mortality and cardiovascular mortality in NAFLD patients.These findings can inform clinical practice in risk stratifying NAFLD patients.

Comparison of the reverse bevel versus Franseen type endoscopic ultrasound needle

BACKGROUND Reverse bevel(RB)needle is widely used for endoscopic ultrasound fine needle biopsy(EUS-FNB).A 3-plane symmetrical needle with Franseen geometry(FG)has recently become available.AIM To compare the clinical efficacy of FG to that of RB needle.METHODS A retrospective cohort study of all adult patients who underwent EUS-FNB for solid and mixed lesions either with 22G RB needle or 22G FG needle between January 2016 and February 2019 was undertaken.All cytology slides were reviewed by an independent gastrointestinal cytopathologist blinded to the needle used and the initial cytology report.The primary and secondary outcomes were to assess the sample adequacy using Euro-cytology criteria and the number of cell clusters,respectively.RESULTS Two hundred and twenty six procedures were included in the study.RB needle was used in 128 procedures and FG needle in 98 procedures.The baseline characteristics of both groups were comparable.On multivariable analysis,FG needle(P=0.02)and location of the lesion(P<0.01)were independently associated with adequate tissue.Further,the use of FG needle(P=0.04)and the size of the lesion(P=0.02)were independently associated with acquisition of increased number of cell clusters.CONCLUSION FG needle is superior to RB needle in acquiring adequate tissue and attaining higher number of cell clusters for solid and mixed lesions.