Mirtazapine-induced steatosis
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Mirtazapine is a commonly used drug indicated for the treatment of severe depression. It works as a presynaptic α2-adrenoreceptor antagonist that increases central noradrenergic and serotonergic neurotransmission, and it is metabolized by the p450 cytochrome oxidase system. There is evidence within the literature to suggest a link between antidepressants and increased liver enzymes, although case reports demonstrating a link between mirtazapine specifically and steatosis are sparse. Here, we present a case of mirtazapine-induced steatosis in a 48-year-old office worker. She presented with painless jaundice of 2 days duration and generalized lethargy and peripheral edema present for 3 weeks beforehand. Extensive investigations were undertaken to identify the cause of her jaundice but no biochemical, blood-borne, or anatomical cause could be found. Mirtazapine was subsequently stopped, and her liver function, both clinically and biochemically, improved rapidly. She made a full recovery after discontinuation of her mirtazapine.
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A Case of Acute Hepatitis E Infection in a Patient with Non-Hodgkin Lymphoma Treated Successfully with Ribavirin.

We present the case of a man who, following immunosuppressive treatment for non-Hodgkin lymphoma, became infected with viral hepatitis E. Acute hepatitis E virus infection should be considered in patients with deranged liver function on a background of haematological malignancies or immunosuppression, even without travel to endemic regions. Whilst clearance is usually spontaneous in immune-competent individuals, these at-risk groups may develop a more complicated and protracted disease course. Thus awareness is important as additional treatment with ribavirin or pegylated interferon may be required, as in this case, in order to help achieve eradication.

Improving the management of acute diarrhoea and dehydration in under-5 children in a paediatric referral facility in Lagos, Nigeria.

BACKGROUND: Mortality from acute diarrhoea and dehydration (AD/D) in children is high despite existing management guidelines. AIM: The aim of this study was to identify deficiencies in the management of AD/D by health staff and assess changes in management after a training intervention in a paediatric referral facility in Lagos, Nigeria. METHODS: In a retrospective review of case notes, the management of AD/D was assessed using WHO guidelines as the standard. An e-learning module was developed that directly addressed deficiencies and was used to train health staff. Changes in the management of AD/D were assessed by re-auditing case notes. RESULTS: There were learning needs among health staff in the management of AD/D. Altogether, 34 (97.1%) of 35 residents were trained. Training resulted in modest improvements in the number of children in whom nutritional status was assessed, use of oral rather than intravenous fluids for rehydration and reducing unnecessary laboratory tests. Training resulted in marked improvements in the correct volume of (pre- vs. post-training 6.3% vs. 94.1%, P<0.001) and follow-up of fluid therapy (8.1% vs. 98.0%; P<0.001), prescription of zinc (41.6% vs. 85.1%, P<0.001) and providing advice on when to return after discharge (77.6% vs. 96.0%, P<0.001). Although statistically significant, the minimal improvements in antibiotic use (43.8% vs. 56.6%, P = 0.03), re-starting feeds (10.6% vs. 38.6%, P<0.001) and counselling about feeding (11.8% vs. 33.7%, P<0.001) highlighted areas for further training. CONCLUSIONS: In low-resource countries, clinical auditing and training can significantly improve the management of illnesses that contribute to child deaths and identify areas where further training is required.

Cost and Impact on Patient Length of Stay of Rapid Molecular Testing for Clostridium difficile.

INTRODUCTION: A study was performed to assess the cost of a rapid molecular assay (PCR) for diagnosis of Clostridium difficile infection (CDI) and the impact of its routine use on patient length of stay (LOS) in comparison with cell culture cytotoxin neutralization assay (CCNA). METHODS: From March 2011 to September 2011, Xpert(®) C. difficile (Cepheid, Sunnyvale, CA, USA) PCR was used on patients with suspicion of CDI in two acute care hospitals in Abertawe Bro Morgannwg University Health Board, Swansea, Wales, UK. Test results were used for patient management. LOS and time to reportable result were compared for negative and positive prospective patients tested by PCR and historic control patients tested by CCNA during March 2010 to September 2010. Tests were priced using micro-costing and a cost comparison analysis was undertaken. RESULTS: In total, 506 patients were included. Time to reportable result for PCR samples was 1.53 h compared to 46.54 h for CCNA negatives and 22.45 h for CCNA positives. Patients tested by CCNA stayed 4.88 days longer in hospital compared to PCR patients if they tested positive and 7.03 days if tests were negative. The mean reduction in LOS observed in our study has the potential to generate cost savings of up to £2,292.62 for every patient with suspected CDI, if samples were to be tested routinely with PCR instead of CCNA. CONCLUSION: A rapid molecular test for C. difficile in an acute hospital setting produced quick results that led to a decrease in LOS compared to historic CCNA control patients. This could result in considerable savings through reduced excess inpatient days.

A comprehensive analysis of common genetic variation around six candidate loci for intrahepatic cholestasis of pregnancy.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) has a complex etiology with a significant genetic component. Heterozygous mutations of canalicular transporters occur in a subset of ICP cases and a population susceptibility allele (p.444A) has been identified in ABCB11. We sought to expand our knowledge of the detailed genetic contribution to ICP by investigation of common variation around candidate loci with biological plausibility for a role in ICP (ABCB4, ABCB11, ABCC2, ATP8B1, NR1H4, and FGF19). METHODS: ICP patients (n=563) of white western European origin and controls (n=642) were analyzed in a case-control design. Single-nucleotide polymorphism (SNP) markers (n=83) were selected from the HapMap data set (Tagger, Haploview 4.1 (build 22)). Genotyping was performed by allelic discrimination assay on a robotic platform. Following quality control, SNP data were analyzed by Armitage's trend test. RESULTS: Cochran-Armitage trend testing identified six SNPs in ABCB11 together with six SNPs in ABCB4 that showed significant evidence of association. The minimum Bonferroni corrected P value for trend testing ABCB11 was 5.81×10(-4) (rs3815676) and for ABCB4 it was 4.6×10(-7)(rs2109505). Conditional analysis of the two clusters of association signals suggested a single signal in ABCB4 but evidence for two independent signals in ABCB11. To confirm these findings, a second study was performed in a further 227 cases, which confirmed and strengthened the original findings. CONCLUSIONS: Our analysis of a large cohort of ICP cases has identified a key role for common variation around the ABCB4 and ABCB11 loci, identified the core associations, and expanded our knowledge of ICP susceptibility.

Clinical characteristics of hepatitis E in a "Non-Endemic" population.

Hepatitis E virus (HEV) is a ribonucleic acid (RNA) virus with predominant fecal oral spread. Traditionally in Western Europe it is associated with travel to endemic countries, but an increasing number of locally acquired cases have been reported throughout England. Patients presenting with acute non-travel associated HEV infection in south Wales over a 25-month period were monitored, in an attempt to understand the clinical picture and epidemiology in our patient population. Twenty-four patients were identified with non-travel associated HEV infection and studied prospectively. Patient demographics, symptoms, and serial laboratory results were recorded. There was a male/female ratio of 3:1, with a median patient age of 65.5 years old. Patients developed a significant icteric hepatitis (median peak bilirubin: 139 µmol/L, median peak AST: 1,973 IU/L and ALT: 2,021 IU/L), with liver function remaining abnormal for ∼7 weeks. All patients in whom HEV RNA was isolated were infected with genotype 3. Forty-six percent of patients presented during winter months. The data show a group mortality rate of 4.2%, similar to that reported in endemic countries. HEV results in a severe and occasionally fatal hepatitis. Testing for hepatitis E is now recommended in any patient presenting with acute hepatitis of unknown etiology.

Celiac disease and autoimmune thyroid disease.

Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It probably does not change the natural history of associated autoimmune disorders.

Prospective screening for coeliac disease in patients with Graves' hyperthyroidism using anti-gliadin and tissue transglutaminase antibodies.

INTRODUCTION: Coeliac disease (CD) is associated with autoimmune thyroid disease (AITD) although its prevalence among those with Graves' hyperthyroidism in the UK is unknown. We determined the prevalence and evaluated the role of screening for CD prospectively in a consecutive cohort of patients with Graves' hyperthyroidism using IgA class antibodies to gliadin (AGA) and tissue transglutaminase (anti-tTG). METHODS: All patients with Graves' hyperthyroidism attending the thyroid clinic over a 9-month period were offered screening for CD using AGA (normal < 3 mg/l) and anti-tTG (normal < 15 micro/ml). Comparison was made with an age- and sex-matched healthy control group from the local population whose sera were tested for anti-tTG. In patients with borderline or raised anti-tTG (> 7 micro/ml) endomysial antibody (EmA) was measured. Serum IgA was also measured to exclude IgA deficiency. Patients with raised AGA, raised or borderline anti-tTG, positive EmA, IgA deficiency or haematinic deficiencies were offered endoscopic duodenal biopsy. RESULTS: A total of 115 patients (97 female and 18 male) with Graves' hyperthyroidism were offered screening tests and 111 accepted. AGA was raised in 15 patients, anti-tTG was raised in two (both positive for EmA) and equivocal in six (one positive for EmA). IgA deficiency was present in three. Four patients were known to have haematinic deficiencies. Twenty-five patients were invited and 19 agreed to have endoscopic duodenal biopsy. Three new patients were found to have CD while two patients were already known to have CD, thus five of 111 patients with Graves' hyperthyroidism had CD. One of 115 healthy controls had a strong positive anti-tTG (> 200 micro/ml) and EmA indicating probable CD. CONCLUSIONS: Screening 111 consecutive patients with Graves' hyperthyroidism revealed AGA in 14%, anti-tTG in 2% and IgA deficiency in 3%. Two patients were known to have CD. Screening detected three new cases. The prevalence of CD in patients with Graves' hyperthyroidism was 4.5% as compared with 0.9% in matched healthy controls. Routine screening for CD should be considered.