Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs).

Characterisation of the Serum Metabolic Signature of Cholangiocarcinoma in a United Kingdom Cohort.

Background: A distinct serum metabonomic pattern has been previously revealed to be associated with various forms of liver disease. Here, we aimed to apply mass spectrometry to obtain serum metabolomic profiles from individuals with cholangiocarcinoma and benign hepatobiliary diseases to gain an insight into pathogenesis and search for potential early-disease biomarkers.

Methods: Serum samples were profiled using a hydrophilic interaction liquid chromatography platform, coupled to a mass spectrometer.

The Plasma and Serum Metabotyping of Hepatocellular Carcinoma in a Nigerian and Egyptian Cohort using Proton Nuclear Magnetic Resonance Spectroscopy.

Background/aims: Previous studies have observed disturbances in the H nuclear magnetic resonance (NMR) blood spectral profiles in malignancy. No study has metabotyped serum or plasma of hepatocellular carcinoma (HCC) patients from two diverse populations. We aimed to delineate the HCC patient metabotype from Nigeria (mostly hepatitis B virus infected) and Egypt (mostly hepatitis C virus infected) to explore lipid and energy metabolite alterations that may be independent of disease aetiology, diet and environment.

From decentralization to commonization of HIV healthcare resources: keys to reduction in health disparity and equitable distribution of health services in Nigeria.

Access to quality care is essential for improved health outcomes. Decentralization improves access to healthcare services at lower levels of care, but it does not dismantle structural, funding and programming restrictions to access, resulting in inequity and inequality in population health. Unlike decentralization, Commonization Model of care reduces health inequalities and inequity, dismantles structural, funding and other program related obstacles to population health.

Hepatic steatosis and fibrosis: Non-invasive assessment.

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality.

Urinary Metabotyping of Hepatocellular Carcinoma in a UK Cohort Using Proton Nuclear Magnetic Resonance Spectroscopy.

Background: Discriminatory metabolic profiles have been described in urinary H nuclear magnetic resonance (NMR) spectroscopy studies of African patients with hepatocellular carcinoma (HCC). This study aimed to assess similarities in a UK cohort, where there is a greater etiological diversity.

Methods: Urine from cirrhosis and HCC patients was analyzed using a 600 MHz H NMR system.

Urinary metabolic profiling by H NMR spectroscopy in patients with cirrhosis may discriminate overt but not covert hepatic encephalopathy.

To date urinary metabolic profiling has been applied to define a specific metabolic fingerprint of hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of other complications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinary proton nuclear magnetic resonance (H-NMR) spectra were acquired and NMR data from 52 patients with cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls were compared.

A longitudinal study of patients with cirrhosis treated with L-ornithine L-aspartate, examined with magnetization transfer, diffusion-weighted imaging and magnetic resonance spectroscopy.

The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T- and T-weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences.

Changes in Liver Volume in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy.

Aim: Liver volumetric analysis has not been used to detect hepatic remodelling during antiviral therapy before. We measured liver volume (LV) changes on volumetric magnetic resonance imaging during hepatitis C antiviral therapy.

Methods: 22 biopsy-staged patients (median [range] age 45(19-65) years; 9F, 13M) with chronic hepatitis C virus infection were studied.

Hepatocellular carcinoma: Review of disease and tumor biomarkers.

Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial.

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians.

Magnetic resonance spectroscopy (MRS) provides a non-invasive 'window' on biochemical processes within the body. Its use is no longer restricted to the field of research, with applications in clinical practice increasingly common. MRS can be conducted at high magnetic field strengths (typically 11-14 T) on body fluids, cell extracts and tissue samples, with new developments in whole-body magnetic resonance imaging (MRI) allowing clinical MRS at the end of a standard MRI examination, obtaining functional information in addition to anatomical information.

Plasma Lipid Profiling in a Rat Model of Hepatocellular Carcinoma: Potential Modulation Through Quinolone Administration.

Background/aims: The primary aim of this study was to characterise the blood metabolic profile of hepatocellular carcinoma (HCC) in a rat model, and the secondary aim was to evaluate the effect of the quinolone, norfloxacin on metabolic profiles and exploring the role that gut sterilisation may have on HCC development.

Methods: HCC was induced in 10 Fischer rats by administration of intra-peritoneal diethylnitrosamine (DEN) and oral N-nitrosomorpholine. Plasma was collected upon sacrifice.

Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis.

Background & Aims: Predicting survival in decompensated cirrhosis (DC) is important in decision making for liver transplantation and resource allocation. We investigated whether high-resolution metabolic profiling can determine a metabolic phenotype associated with 90-day survival.

Methods: Two hundred and forty-eight subjects underwent plasma metabotyping by (1)H nuclear magnetic resonance (NMR) spectroscopy and reversed-phase ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS; DC: 80-derivation set, 101-validation; stable cirrhosis (CLD) 20 and 47 healthy controls (HC)).

Reasons why West Africa continues to be a hotbed for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) exhibits a huge disease burden on West Africa, with a large proportion of all HCC cases worldwide occurring in the sub-region. The high HCC prevalence is due to the endemicity of a number of risk factors, most notably hepatitis B, C and HIV. West African HCC also displays a poor prognosis.

Nigerian response to the 2014 Ebola viral disease outbreak: lessons and cautions.

The Ebola virus disease outbreak that initially hit Guinea, Liberia and Senegal in 2014 was projected to affect Nigeria very badly when the first case was reported in July 2014. However, the outbreak was effectively and swiftly contained with only eight deaths out of 20 cases, confounding even the most optimistic predictions of the disease modelers. A combination of health worker and public education, a coordinated field epidemiology and laboratory training program (with prior experience in disease outbreak control in other diseases) and effective set-up of emergency operations centers were some of the measures that helped to confound the critics and contain what would have been an otherwise deadly outbreak in a densely populated country with a highly mobile population.

Magnetic Resonance Imaging: Principles and Techniques: Lessons for Clinicians.

The development of magnetic resonance imaging (MRI) for use in medical investigation has provided a huge forward leap in the field of diagnosis, particularly with avoidance of exposure to potentially dangerous ionizing radiation. With decreasing costs and better availability, the use of MRI is becoming ever more pervasive throughout clinical practice. Understanding the principles underlying this imaging modality and its multiple applications can be used to appreciate the benefits and limitations of its use, further informing clinical decision-making.

Quantitative magnetic resonance imaging in patients with cirrhosis: a cross-sectional study.

Cerebral magnetic resonance imaging was undertaken, at 3 Tesla field strength, employing magnetization transfer (MT) and diffusion-weighted imaging (DWI) sequences, in 26 patients with well-compensated cirrhosis, free of overt hepatic encephalopathy. Results were compared to those from 18 aged-matched healthy volunteers. Cerebral magnetization transfer ratios (MTR) were reduced in the frontal white matter, caudate, putamen and globus pallidus in patients with cirrhosis, compared to healthy controls, while the apparent diffusion coefficients (ADC) on DWI were significantly increased in the genu and body of the corpus callosum.

Liver and spleen transient elastography and Acoustic Radiation Force Impulse Measurements. Performance and comparison of measurements in the same area concurrently assessed for liver fibrosis by biopsy.

Purpose: The estimation of the degree of liver fibrosis is important for prognosis, surveillance, and treatment of chronic liver disease. Although liver biopsy is the gold standard for diagnosis, it is subject to sampling error, while ultrasound-based techniques, such as Acoustic Radiation Force Impulse (ARFI) and transient elastography, have gained popularity. However, no previous comparative study has performed these ultrasound techniques at the time of biopsy.

Sustainable Health Development Goals (SHDG): breaking down the walls.

The world's governments failed to achieve the Health for All 2000 goals from the Alma Ata Declaration of 1978. Although a lot of milestones have been covered since 2000, the world's governing authorities are unlikely to achieve the current Millennium Development Goals (MDGs) which expire by the end of this year. The inability to achieve these goals may be linked to the multiplicity of health-related directives and fragmentation of health systems in many countries.

PCSK9, apolipoprotein E and lipoviral particles in chronic hepatitis C genotype 3: evidence for genotype-specific regulation of lipoprotein metabolism.

Background & Aims: Hepatitis C virus (HCV) associates with lipoproteins to form "lipoviral particles" (LVPs) that can facilitate viral entry into hepatocytes. Initial attachment occurs via heparan sulphate proteoglycans and low-density lipoprotein receptor (LDLR); CD81 then mediates a post-attachment event. Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels.

Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function.

Proton pump inhibitors (PPI) have been associated with infectious complications in cirrhosis, but their impact on distal gut microbiota composition and function is unclear. We aimed to evaluate changes in stool microbiota composition and function in patients with cirrhosis and healthy controls after omeprazole therapy. Both 15 compensated cirrhotic patients and 15 age-matched controls underwent serum gastrin measurement, stool microbiota profiling with multitagged pyrosequencing, and urinary metabolic profiling with NMR spectroscopy to assess microbial cometabolites before/after a 14-day course of 40 mg/day omeprazole under constant diet conditions.

Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans.

Unlabelled: There is no clinically applicable biomarker for surveillance of hepatocellular carcinoma (HCC), because the sensitivity of serum alpha-fetoprotein (AFP) is too low for this purpose. Here, we determined the diagnostic performance of a panel of urinary metabolites of HCC patients from West Africa. Urine samples were collected from Nigerian and Gambian patients recruited on the case-control platform of the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) program.

Omega-3 fatty acids and/or fluvastatin in hepatitis C prior non-responders to combination antiviral therapy - a pilot randomised clinical trial.

Background & Aims: Hepatitis C virus (HCV) utilises cholesterol and lipoprotein metabolism for replication and infectivity. Statins and omega-3 (n-3) polyunsaturated fatty acids (PUFA) have been shown to have antiviral properties in vitro. This open label pilot study evaluated the efficacy of fluvastatin (Lescol(®) 40-80 mg) and n-3 PUFA (Omacor(®) 1 g and 2-4 g) on HCV-RNA and lipoviral particles (LVP) in difficult to treat prior non-responders.