Michael Pavlides

Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease

Background & Aims With the increasing prevalence of liver disease worldwide, there is an urgent clinical need for reliable methods to diagnose and stage liver pathology. Liver biopsy, the current gold standard, is invasive and limited by sampling and observer dependent variability. In this study, we aimed to assess the diagnostic accuracy of a novel magnetic resonance protocol for liver tissue characterisation. Methods We conducted a prospective study comparing our magnetic resonance technique against liver biopsy. The individual components of the scanning protocol were T1 mapping, proton spectroscopy and T2⁎ mapping, which quantified liver fibrosis, steatosis and haemosiderosis, respectively. Unselected adult patients referred for liver biopsy as part of their routine care were recruited. Scans performed prior to liver biopsy were analysed by physicians blinded to the histology results. The associations between magnetic resonance and histology variables were assessed. Receiver-operating characteristic analyses were also carried out. Results Paired magnetic resonance and biopsy data were obtained in 79 patients. Magnetic resonance measures correlated strongly with histology (rs = 0.68 p <0.0001 for fibrosis; rs = 0.89 p <0.001 for steatosis; rs = −0.69 p <0.0001 for haemosiderosis). The area under the receiver operating characteristic curve was 0.94, 0.93, and 0.94 for the diagnosis of any degree of fibrosis, steatosis and haemosiderosis respectively. Conclusion The novel scanning method described here provides high diagnostic accuracy for the assessment of liver fibrosis, steatosis and haemosiderosis and could potentially replace liver biopsy for many indications. This is the first demonstration of a non-invasive test to differentiate early stages of fibrosis from normal liver.

Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease

Graphical abstract

Ectopic and Visceral Fat Deposition in Lean and Obese Patients With Type 2 Diabetes

Background Type 2 diabetes (T2D) and obesity are associated with nonalcoholic fatty liver disease, cardiomyopathy, and cardiovascular mortality. Both show stronger links between ectopic and visceral fat deposition, and an increased cardiometabolic risk compared with subcutaneous fat. Objectives This study investigated whether lean patients (Ln) with T2D exhibit increased ectopic and visceral fat deposition and whether these are linked to cardiac and hepatic changes. Methods Twenty-seven obese patients (Ob) with T2D, 15 Ln-T2D, and 12 normal-weight control subjects were studied. Subjects underwent cardiac computed tomography, cardiac magnetic resonance imaging (MRI), proton and phosphorus MR spectroscopy, and multiparametric liver MR, including hepatic proton MRS, T1- and T2*-mapping yielding “iron-corrected T1” [cT1]. Results Diabetes, with or without obesity, was associated with increased myocardial triglyceride content (p = 0.01), increased hepatic triglyceride content (p = 0.04), and impaired myocardial energetics (p = 0.04). Although cardiac structural changes, steatosis, and energetics were similar between the T2D groups, epicardial fat (p = 0.04), hepatic triglyceride (p = 0.01), and insulin resistance (p = 0.03) were higher in Ob-T2D. Epicardial fat, hepatic triglyceride, and insulin resistance correlated negatively with systolic strain and diastolic strain rates, which were only significantly impaired in Ob-T2D (p < 0.001 and p = 0.006, respectively). Fibroinflammatory liver disease (elevated cT1) was only evident in Ob-T2D patients. cT1 correlated with hepatic and epicardial fat (p < 0.001 and p = 0.01, respectively). Conclusions Irrespective of body mass index, diabetes is related to significant abnormalities in cardiac structure, energetics, and cardiac and hepatic steatosis. Obese patients with T2D show a greater propensity for ectopic and visceral fat deposition.

Sex-Specific Differences in Hepatic Fat Oxidation and Synthesis May Explain the Higher Propensity for NAFLD in Men

CONTEXT AND OBJECTIVE In most populations a greater proportion of men have hepatic steatosis than women. Sex-specific differences in hepatic dietary fatty acid (FA) metabolism have not been well characterized. We compared fasting and postprandial hepatic FA synthesis (de novo lipogenesis [DNL]) and oxidation in men and women. PARTICIPANTS AND METHODS Fasting and postprandial hepatic FA metabolism was studied in 22 healthy men (n = 11) and women with similar age, body mass index, and liver fat content using metabolic substrates labeled with stable-isotope tracers ((2)H2O and [U(13)C]palmitate). Dietary FA oxidation was assessed by appearance of (13)C into plasma 3-hydroxybutyrate and breath CO2 as markers of liver and whole-body FA oxidation, respectively. RESULTS Despite similar liver fat content, fasting and postprandial plasma triacylglycerol (TG) concentrations were significantly (P < .05) higher in men compared with women. The appearance of (13)C from dietary FA into plasma 3-hydroxybutyrate and breath CO2 was greater (P < .05) in women compared with men. Although the contribution of DNL into very low-density lipoprotein (VLDL)-TG was similar (∼ 10%) in the fasting state, there was a divergence in pattern over the course of the study, with men maintaining a higher contribution of DNL to VLDL-TG than women (P = .006 time x sex interaction). CONCLUSIONS The combination of lower dietary FA oxidation and a prolonged increase in DNL observed in men may represent partitioning of FA into esterification and storage pathways within the liver, leading to greater VLDL-TG production, and predispose to the sex difference in hepatic steatosis.

Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity.

The diagnosis of non‐alcoholic steatohepatitis and fibrosis staging are central to non‐alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non‐alcoholic steatohepatitis and fibrosis using histology as standard in non‐alcoholic fatty liver disease.

Outcomes after ileal pouch anal anastomosis in patients with primary sclerosing cholangitis

BACKGROUND AND AIMS Outcomes after ileal pouch anal anastomosis (IPAA) are not well established in patients with primary sclerosing cholangitis (PSC). We conducted a comprehensive outcomes assessment in these patients. METHODS A retrospective case note review of complications in all PSC-IPAA (n=21) and matched ulcerative colitis patients with IPAA (UC-IPAA; n=79) after surgery in Oxford (1983-2012) was conducted, and functional outcomes (Öresland score) were evaluated (2012). Quality of life [Cleveland Global Quality of Life Questionnaire, Short Form-36 (SF-36)], and sexual function were also assessed (2012) including patients with PSC-associated UC without IPAA (PSC-UC; n=19). Sub-group analysis of patients with large duct (ld) PSC-IPAA (n=17) was also performed. RESULTS The 1-, 5-, 10- and 20-year risk of acute pouchitis for PSC-IPAA was 10%, 19%, 31% and 65% respectively, compared to 3%, 10%, 14% and 28% in UC-IPAA (p=0.03). More PSC-IPAA (36%) had poor nocturnal pouch function (vs 2% in UC-IPAA; p=0.0016). There were no differences in surgical complications, quality of life or sexual function between the 3 main groups. LdPSC-IPAA had poorer pouch function (Öresland score: 7.7 vs 5.4 in UC-IPAA; p=0.02), and worse quality of life [SF-36 Physical: 42 vs 50.5 in UC-IPAA; 47.7 in PSC-UC; p=0.03 and Mental Health summary scores: 41.6 vs 51.2 in UC-IPAA; 42.3 in PSC-UC; p=0.04]. CONCLUSIONS PSC-IPAA suffer more acute pouchitis and have worse functional outcomes than UC-IPAA. LdPSC-IPAA also have poorer quality of life.

Influence of fat on liver T1 measurements using modified Look-Locker inversion recovery (MOLLI) methods at 3T.

To characterize the effect of fat on modified Look–Locker inversion recovery (MOLLI) T1 maps of the liver. The balanced steady‐state free precession (bSSFP) sequence causes water and fat signals to have opposite phase when repetition time (TR) = 2.3 msec at 3T. In voxels that contain both fat and water, the MOLLI T1 measurement is influenced by the choice of TR.

Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care.

A model for hepatic fibrosis: the competing effects of cell loss and iron on shortened modified Look-Locker inversion recovery T1 (shMOLLI-T1 ) in the liver.

To propose a simple multicompartment model of the liver and use Bloch‐McConnell simulations to demonstrate the effects of iron and fibrosis on shortened‐MOLLI (shMOLLI) T1 measurements. Liver T1 values have shown sensitivity to inflammation and fibrosis, but are also affected by hepatic iron content. Modified Look‐Locker inversion recovery (MOLLI) T1 measurements are biased by the lower T2 associated with high iron.

Hepatic iron is the major determinant of serum ferritin in NAFLD patients

Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD.