Obesity and Liver

´El pasado Lunes 26 de junio de 2014 a las 13:00 horas se organizó en el marco de las XIII Jornadas de Avances en Hepatología, la conferencia perteneciente al ciclo de conferencias de IBIMA titulada “Obesity and the Liver”, impartida por el Prof. Guruprasad P. Aithal.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

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

BACKGROUNDNon-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 lipid β-oxidation and enhancing tissue metabolic flexibility. These physiological properties have generated research interest in L-carnitine as a potentially effective adjunctive therapy in NAFLD.AIMTo systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry, liver fat and insulin sensitivity in NAFLD.METHODSSearch 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.RESULTSFive 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).CONCLUSIONPooled results indicate that L-carnitine supplementation attenuates ALT, liver fat and insulin resistance in NAFLD cohorts, confirming a beneficial effect of L-carnitine for a highly prevalent condition with a growing economic burden

Healthcare costs of transarterial chemoembolization in the treatment of hepatocellular carcinoma

Background: A meta-analysis comparing drug-eluting beads transarterial chemoembolization (DEB-TACE) with conventional transarterial chemoembolization (cTACE) has recently been published. On balance, no significant differences were found in terms of objective response and overall survival. The impact on healthcare costs had been studied in small series based on a hypothetical model and was in favor of DEB-TACE. We aimed to evaluate and compare healthcare costs and effectiveness of both modalities in a cohort of patients from Nottingham, UK. Methods: Using a dedicated radiology database, we identified all patients who had undergone cTACE or DEB-TACE between 2006 and 2012 at a single tertiary referral center based in Nottingham. We collected clinical data, including treatment response, postprocedure complications and 30-day mortality. Costing models were constructed to present both our local hospital perspective as well as the national health service position. Results: During our study period, 101 procedures were performed on 43 patients (76 cTACE procedures on 26 patients and 25 DEB-TACE procedures on 17 patients). Overall, 11/26 in cTACE and 5/17 in DEB-TACE group had progressive disease (p=0.52). Adverse events were seen in 6/76 cTACE compared with 7/25 DEB-TACE group (p=0.16). Based on the predetermined standard pathway there was an unadjusted average cost difference of £3770.30 (TACE =£9070.44, DEB-TACE =£5300.14) in favor of the DEB-TACE. Results from our costing models indicated a £2715.33 (95% CI £580.88–4849.77) cost difference in favor of the same procedure. Conclusions: Even when the extra costs of DEB-TACE were considered, the overall treatment costs per patient were lower in relation to cTACE

Metabolic Imaging in Non-Alcoholic Fatty Liver Disease: Applications of Magnetic Resonance Spectroscopy

Non-alcoholic fatty liver disease (NAFLD) is poised to dominate the landscape of clinical hepatology in the 21st century. Its complex, interdependent aetiologies, non-linear disease progression and uncertain natural history have presented great challenges to the development of effective therapies. Progress will require an integrated approach to uncover molecular mediators, key pathogenic milestones and response to intervention at the metabolic level. The advent of precision imaging has yielded unprecedented insights into these processes. Quantitative imaging biomarkers such as magnetic resonance imaging (MRI), spectroscopy (MRS) and elastography (MRE) present robust, powerful tools with which to probe NAFLD metabolism and fibrogenesis non-invasively,in real time. Specific advantages of MRS include the ability to quantify static metabolite concentrations as well as dynamic substrate fluxin vivo. Thus, a vast range of key metabolic events inthe natural history of NAFLD can be explored using MRS. Here, we provide an overview of MRS for the clinician, as well as key pathways exploitable by MRS in vivo. Development, optimisation and validation of multinuclear MRS, in combination with other quantitative imaging techniques, may ultimately provide a robust, non-invasive alternative to liver biopsy for observational and longitudinal studies. Through enabling deeper insight into inflammatory and fibrogenic cascades, MRS may facilitate identification of novel therapeutic targets and clinically meaningful endpoints in NAFLD. Its widespread use in future could conceivably accelerate study design, data acquisition and availability of disease-modifying therapies at a population leve

Obesity is the most common risk factor for chronic liver disease: Results from risk stratification pathway using transient elastography

IntroductionObesity has been associated with liver fibrosis yet guidelines do not emphasise it as an independent risk factor in which to have a high index of suspicion of advanced disease. We aimed to elucidate the effect of a raised body mass index on the risk of liver disease using data from a community risk stratification pathway. MethodsWe prospectively recruited patients from a primary care practice with hazardous alcohol use and/or type 2 diabetes and/or obesity. Subjects were invited for a transient elastography reading. A threshold of ≥8.0kPa defined an elevated reading consistent with clinically significant liver disease. ResultsFive hundred and seventy six patients participated in the pathway of which, 533 patients had a reliable reading and 66 (12.4%) had an elevated reading. Thirty one percent of patients with an elevated reading had obesity as their only risk factor. The proportion of patients with an elevated reading was similar among those with obesity (8.9%) to patients with more recognised solitary risk factors (Type 2 diabetes 10.8%; Hazardous alcohol use 4.8%). Obesity in combination with other risk factors further increased the proportion of patients with an elevated reading. In multivariate logistic regression, increasing BMI and type 2 diabetes were significantly associated with an elevated reading. ConclusionObesity as a single or additive risk factor for chronic liver disease is significant. Future case finding strategies using a risk factor approach should incorporate obesity within proposed algorithms

Biomarkers of idiosyncratic drug-induced liver injury (DILI) - a systematic review

Introduction: Idiosyncratic drug-induced liver injury (DILI) is an unpredictable event, and there are no specific biomarkers that can distinguish DILI from alternative explanations or predict its clinical outcomes. Areas covered: This systematic review summarizes the available evidence for all biomarkers proposed to have a role in the diagnosis or prognosis of DILI. Following a comprehensive search, we included all types of studies in humans. We included DILI cases based on any threshold criteria but excluded intrinsic DILI, commonly caused by paracetamol overdose. We classified studies into diagnostic and prognostic categories and assessed their methodological quality. After reviewing the literature, 14 studies were eligible. Expert Opinion: Diagnostic studies were heterogeneous with regard to the study population and outcomes measured. Prognostic models were developed by integrating novel biomarkers, risk scores, and traditional biomarkers, which increased their prognostic ability to predict death or transplantation by 6 months. This systematic review highlights the case of need for non-genetic biomarkers that distinguish DILI from acute liver injury related to alternative etiology. Biomarkers with the potential to identify serious adverse outcomes from acute DILI should be validated in independent prospective cohorts with a substantial number of cases.This paper was funded by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 821283 (www.imi.europa.eu). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. Translational Safety Biomarker Pipeline (TransBioLine): Enabling develop- ment and implementation of novel safety biomarkers in clinical trials and diagnosis of disease’ — ‘TransBioLine’ (‘action’). Grant Number: 821283

Prevalence and natural history of histologically proven chronic liver disease in a longitudinal cohort of patients with type 1 diabetes

Although a higher prevalence of raised liver enzymes and altered echotexture on ultrasound have been reported in patients with type 1 diabetes mellitus (T1DM), the histological spectrum and natural history of chronic liver disease (CLD) in T1DM is unknown. We investigated the prevalence and outcome of histologically proven CLD in a longitudinal cohort of patients with T1DM. We identified patients who have had liver biopsy from a computerized database (DIAMOND; Hicom Technology, Brookwood, UK) containing longitudinal data for over 95% of type 1 diabetes patients from an overall catchment population of 700,000 people. Gender-matched patients with oral hypoglycemic-treated (T2OH) and insulin-treated type 2 diabetes (T2IN) who had liver biopsy formed two comparative cohorts. We collated clinical and histological data, as well as long-term outcomes of all three groups, and compared T1DM cirrhosis incidence to UK general population data. Of 4,644 patients with T1DM, 57 (1.2%) underwent liver biopsy. Of these, 53.1% of patients had steatosis, 20.4% had nonalcoholic steatohepatitis, and 73.5% had fibrosis on index liver biopsy. Cirrhosis was diagnosed in 14 patients (24.6%) during follow-up. T1DM with age under 55 years had an odds ratio of 1.875 (95% confidence interval: 0.936-3.757) for cirrhosis incidence, compared to the general population. Longitudinal liver-related outcomes were similar comparing the T1DM cohort and respective type 2 diabetes cohorts—when adjusted for important confounders, diabetic cohort type did not predict altered risk of incident cirrhosis or portal hypertension. Conclusion: Type 1 diabetes is associated with a previously unrecognized burden of CLD and its complications. (Hepatology 2014;60:158–168

All-cause mortality in people with cirrhosis compared with the general population: a population-based cohort study

Background: Mortality due to cirrhosis has tripled over the last 30 years in the UK. However, we lack adequate, contemporary, population-based estimates of the excess mortality patients who are at risk compared with the general population. Aim: To determine the overall survival in patients with cirrhosis compared with the general population taking into account the effects of severity and aetiology of disease and comorbidity. Methods: In a cohort study, we identified 4537 people with cirrhosis and a control cohort of 44 403 patients, matched by age, sex and general practice from the UK General Practice Research Database between June 1987 and April 2002. Results: Patients with compensated cirrhosis had a nearly five-fold [hazard ratio (HR) 4.7, 95% confidence interval (CI) 4.4–5.0] increased risk of death, while those with decompensated cirrhosis had a near 10-fold (HR 9.7, 95% CI 8.9–10.6) increased risk compared with the general population. Alcoholic cirrhosis conferred a worse prognosis than non-alcohol-related cirrhosis both in the first year following diagnosis and subsequently. Conclusion: Having a diagnosis of cirrhosis confers a substantial increased mortality risk compared with the general population, even for those with compensated disease, with 5-year survival between that seen for breast and colorectal cancer

1H MRS assessment of lipid composition at 3T and 7T

1H MRS assessment of lipid composition at 3T and 7