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We present radial velocity measurements of the very bright (V ∼ 5.7) nearby F star, DMPP-4 (HD 184960). The anomalously low Ca ii H&K emission suggests mass-loss from planets orbiting a low activity host star. Periodic radial velocity variability with ∼10 m s−1 amplitude is found to persist over a >4 yr time-scale. Although the non-simultaneous photometric variability in four TESS sectors supports the view of an inactive star, we identify periodic photometric signals and also find spectroscopic evidence for stellar activity. We used a posterior sampling algorithm that includes the number of Keplerian signals, N p, as a free parameter to test and compare (1) purely Keplerian models (2) a Keplerian model with linear activity correlation and (3) Keplerian models with Gaussian processes. A preferred model, with one Keplerian and quasi-periodic Gaussian process indicates a planet with a period of |$P_\textrm {b} = 3.4982^{+0.0015}_{-0.0027}$| d and corresponding minimum mass of |$m_\textrm {b}\, \textrm {sin}\, i = 12.2^{+1.8}_{-1.9}$| M⊕. Without further high-time resolution observations over a longer time-scale, we cannot definitively rule out the purely Keplerian model with two candidates planets with |$P_\textrm {b} = 2.4570^{+0.0026}_{-0.0462}$| d, minimum mass |$m_\textrm {b}\, \textrm {sin}\, i = 8.0^{+1.1}_{-1.5}$| M⊕ and |$P_\textrm {c} = 5.4196^{+0.6766}_{-0.0030}$| d and corresponding minimum mass of |$m_\textrm {b}\, \textrm {sin}\, i = 12.2^{+1.4}_{-1.6}$| M⊕. The candidate planets lie in the region below the lower-envelope of the Neptune Desert. Continued mass-loss may originate from the highly irradiated planets or from an as yet undetected body in the system. [ABSTRACT FROM AUTHOR]

NI‐0801 is a fully human monoclonal antibody against chemokine (C‐X‐C motif) ligand 10 (CXCL10), which is involved in the recruitment of inflammatory T cells into the liver. The safety and efficacy of NI‐0801 was assessed in patients with primary biliary cholangitis. In this open‐label phase 2a study, patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid received six consecutive intravenous administrations of NI‐0801 (10 mg/kg) every 2 weeks. Patients were followed up for 3 months after the last infusion. Liver function tests, safety assessments, as well as pharmacokinetic and pharmacodynamic parameters were evaluated at different time points throughout the dosing period and the safety follow‐up period. Twenty‐nine patients were enrolled in the study and were treated with NI‐0801. The most frequently reported adverse events included headaches (52%), pruritus (34%), fatigue (24%), and diarrhea (21%). No study drug‐related serious adverse events were reported. NI‐0801 administration did not lead to a significant reduction in any of the liver function tests assessed at the end of the treatment period (i.e., 2 weeks after final NI‐0801 administration) compared to baseline. Conclusion: Despite clear pharmacologic responses in the blood, no therapeutic benefit of multiple administrations of NI‐0801 could be demonstrated. The high production rate of CXCL10 makes it difficult to achieve drug levels that lead to sustained neutralization of the chemokine, thus limiting its targetability. (Hepatology Communications 2018;2:492‐503) [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is increasing in incidence in the UK. It is the commonest cause of liver-related deaths, predominantly in people below the age of 60. Alcoholic hepatitis (AH) is an acute form of ALD with high mortality when severe. Jaundice and coagulopathy are clinical hallmarks of severe AH. Histology findings are characterised by parenchymal inflammation and hepatocellular damage although biopsy is only required when diagnostic uncertainty exists; clinical findings are usually sufficient for accurate diagnosis. Patients with AH should be stratified as non-severe or severe using non-invasive scoring systems such as the discriminant function or the Glasgow Alcoholic Hepatitis Score. In patients with non-severe AH, abstinence is the mainstay of treatment, and it is important that steps are taken to help patients stop drinking. Severe AH requires specialist treatment. Consensus guidelines recommend the use of prednisolone although this remains subject to clinical trials. Pentoxifylline may have a survival benefit if corticosteroids are contraindicated. Nutritional support and N-acetylcysteine should be considered for use in conjunction with corticosteroids although evidence of benefit is not conclusive. Patients with severe disease who do not respond to therapy within a week have a very poor outcome. Recent data have shown a survival benefit of liver transplantation in this group although this remains experimental at present. Current and future research should focus on targeted therapies for severe AH and those who fail first-line treatment. [ABSTRACT FROM AUTHOR]

Background and aims: Although most cases of hereditary haemochromatosis are associated with homozygosity for the C282Y mutation of the HFE gene, clinical penetrance varies and other genes may modify disease expression. If so, relatives from clinically affected families, by inheriting such genes, may accumulate more iron. To seek evidence for this, we compared iron status and morbidity in unselected first degree relatives of two groups of index cases from South Wales, namely asymptomatic C282Y homozygotes identified by genetic screening of blood donors (n = 56) and C282Y homozygous haemochromatosis patients presenting clinically (n = 60). Methods: All participating relatives had a structured interview, clinical assessment, and laboratory investigations. Health related quality of life was measured (SF - 36 version 2). Results: In total, 92% of 180 eligible first degree relatives were interviewed in the "screened" family group and 85% of 143 eligible relatives in the "patient" group. Of 59 relatives homozygous for C282Y, 76% of men and 32% women had the "iron phenotype" (raised transferrin saturation and serum ferritin). Logistic regression modelling of the iron phenotype risk showed that 42% of the initial model deviance could be explained by homozygosity for C282Y, another 6% by lifestyle factors, and 6% by being mail. Family group membership was not a significant risk factor. Morbidity and SF-36 scores did not differ significantly either between C282Y homozygotes and relatives lacking C282Y, or between C282Y homozygotes from the "screened" and "patient" groups. Serious morbidity (including cirrhosis) was low in both groups of relatives. Conclusions: HFE C282Y homozygosity has a high penetrance for iron accumulation but a low clinical penetrance. Lack of excess morbidity among C282Y homozygous relatives of index cases who presented clinically suggests that residual unknown genetic or environmental factors do not greatly influence clinical outcome among C282Y homozygotes. [ABSTRACT FROM AUTHOR]

Summary. In the UK, 90% of patients with hereditary haemochromatosis (HH) are homozygous for HFE C282Y, as are one in 150 people in the general population. However, only a minority of these will develop clinical haemochromatosis. Iron loss modifies iron accumulation but so may other genetic factors. Haptoglobin (Hp) exists as three major types (Hp 1-1, Hp 2-1 or Hp 2-2) and binds free plasma haemoglobin. In men, Hp 2-2 has been shown to be associated with increased macrophage iron accumulation and serum ferritin concentration. Furthermore, the frequency of Hp 2-2 was shown to be increased in patients with HH. We determined Hp types by phenotyping and genotyping 265 blood donor control subjects and 173 subjects who were homozygous for HFE C282Y. The latter group included 66 blood donors lacking clinical features suggestive of haemochromatosis and without a known family history, and 68 patients presenting clinically with haemochromatosis. Hp 2-2 frequencies did not differ in control subjects and C282Y homozygotes. Hp 2-2 was not a risk factor for disease development in HH. To investigate the relationship between iron accumulation and haptoglobin type, we determined transferrin saturation and serum ferritin concentration in 192 male, first-time blood donors aged 20–40 years who lacked both HFE C282Y and H63D. Transferrin saturation and serum ferritin concentrations did not vary with Hp type. [ABSTRACT FROM AUTHOR]

In northern Europe, about 90% of patients with hereditary haemochromatosis (HH) are homozygous for a single mutation (C282Y) of the HFE gene and approximately 1 in 150 people in the general population carries this genotype. However, the clinical significance of HFE mutations remains uncertain, as is the proportion of people homozygous for C282Y who will develop clinical symptoms leading to a diagnosis of HH. A systematic review of patients with HH over a 2-year period within a defined UK region has revealed that only 1.2% of adult C282Y homozygotes have been diagnosed with iron overload and received treatment. In those in whom body iron load could be estimated, only 51% has more than 4 g iron (the diagnostic threshold for iron overload). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on several cases of liver disease and cirrhosis due to Khat chewing in Somali men.

The article presents a response by the author about his article "Haptoglobin Type Neither Influences Iron Accumilation in Normal Subjects Nor Predicts Clinical Presentation in HFE C282Y Haemochromatosis: Phenotype and Genotype Analysis," published in the "British Journal of Haematology." The author has provided evidence to show that the haptoglobin (Hp) type 2-2 may be associated with iron retention in macrophages and higher serum ferritin concentrations than in other Hp types. Such changes may have long-term consequences resulting from tissue damage due to iron accumulation.

Introduction In recent guidance, NICE (2010) recommend a symptom-triggered (STW) pharmacological dosing regimen to treat AAW as both clinically and cost effective. Supporting evidence is from a small number of studies largely undertaken in specialised addiction units and a paucity of published evidence from other settings remains. With this in mind our liver unit formulated and piloted a STW regimen using chlordiazepoxide (CDP). Our aim was to evaluate STW and explore potential cost savings. Methods The STW regimen allowed a maximum daily dose of 240 mg CDP without specialist review. Pharmacotherapy was tailored to the patient's requirements as determined by the severity of their withdrawal signs and symptoms using a designated questionnaire (modified CIWA-AD). Patients were scored hourly or 4 hourly according to protocol score. Data was collected prospectively over a 10-month period (Nov 09 – Aug 10) and case note review undertaken in those previously admitted with AAW (all managed on a fixed dose regimen). Results 135 individuals had STW, each consuming a mean of 28 units of alcohol/day. Most (n= 78, 58%) were admitted with uncomplicated AAW, although over a third had significant liver disease (n=51, 38%). 6 (4%) had no significant liver disease but other serious co-morbidity requiring admission. 41 (30.4%) were previously admitted with AAW. The mean total dose of CDP prescribed during STW was 70.6 mg c.f. 541.6 mg on a fixed dose regimen. A significant number (n= 53, 39%) of STW patients did not require CDP at all, allowing early discharge. Patients on STW required CPD on average for shorter duration (3.11 days vs 7.52 days for fixed dose regimen). In the group admitted with uncomplicated AAW, we estimate within one ward cost savings of at least £220k per annum in bed days alone. Nursing staff welcomed the STW protocol, citing improved patient care and a reduction in violence and aggressive behaviour on the ward. Conclusion Our results support the recommendations made by NICE (2010) that symptom-triggered regimens are associated with lower doses of benzodiazepines, shorter treatment duration and cost-savings, especially in those with uncomplicated AAW. Designated questionnaires (such as CIWR-AD) are a useful adjunct to clinical experience. [ABSTRACT FROM PUBLISHER]

Introduction Non-alcoholic fatty liver disease (NAFLD) is increasingly common with a prevalence of between 20% and 34% in Europe and the US. There is a close association between NAFLD and other features of the metabolic syndrome such as insulin resistance, hypertension and obesity. We investigated liver health in patients with diabetes, and the effect of lifestyle interventions on liver health in newly diagnosed type 2 diabetics. Methods Patients within 5–8 months of diagnosis of diabetes were identified from four centres in the South West of England. All participants received usual care for patients with diabetes. Patients were randomised to usual care alone (UC), additional dietary advice (D) or additional dietary and exercise advice (D&E). LFTs were measured at baseline and twelve months. Results Median age of participants was 61 years, 36% were female. Alcohol intake was modest and did not differ significantly between groups. Modest reductions in BMI and insulin resistance were seen in groups D and D&E: these were not significant. There was no change in blood pressure. At baseline 24 of 424 patients (5.6%) had any abnormality in liver function. At twelve months this was 15 of 212 patients (7.1%). Increased prevalence was seen in all groups except D. Transaminase levels followed the same trend with regard to prevalence at baseline (2.6%) and 12 months (3.7%). AST:ALT ratio (AAR) increased over twelve months with Pearson correlation of 0.92. In patients with abnormal transaminases non-invasive assessment of fibrosis (NAFLD fibrosis score) demonstrated that 20% of patients were at risk of advanced fibrosis at baseline, climbing to 80% at twelve months, without differences between groups. This is 0.5% and 3% of all participants at baseline and twelve months respectively. Conclusion In newly diagnosed diabetes abnormalities of liver function persist in the first year of diagnosis regardless of lifestyle intervention. Estimation of fibrosis in a subgroup of patients demonstrated increased prevalence of advanced fibrosis over twelve months. This is consistent with rising AAR over the same period for the whole group. Longer-term follow up of these patients is required, but initial data are similar to cohorts described elsewhere in the literature, and reflect a significant risk of liver disease in patients with type 2 diabetes. [ABSTRACT FROM PUBLISHER]

An abstract of the conference paper "Fetal body lymphatic malformation: ultrasound underestimates the extent of infiltration," by C. McCune and colleagues is presented.