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Sebastiana Atzori,1,2 Yasmin Pasha,1 James B Maurice,1,3 Simon D Taylor-Robinson,1 Louise Campbell,1,4 Adrian KP Lim1,5 1Department of Surgery and Cancer, Imperial College London, London, W1 1NY, UK; 2Department of Medicine, Sassari University Hospital, Sassari, 07100, Italy; 3UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, London, NW3 2QG, UK; 4Office of the Clinical Director, Tawazun Health, London, W1G 9QN, UK; 5Department of Imaging, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, W6 8RF, UKCorrespondence: Sebastiana Atzori, Department of Medicine, Sassari University Hospital, Via Enrico de Nicola, Sassari, 07100, Italy, Tel +39 3483359085, Email sebastiana_atzori@yahoo.itPurpose: The Controlled Attenuation Parameter (CAP score) is based on ultrasonic properties of retropropagated radiofrequency signals acquired by FibroscanTM (Echosens, Paris, France). Since ultrasound propagation is influenced by the presence of fat, CAP score was developed to quantify steatosis. The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy.Patients and Methods: A total of 150 patients underwent same-day liver biopsy and measurement of hepatic steatosis with Fibroscan. Only examinations with 10 satisfactory measurements, and an inter-quartile range of less than 30% of the median liver stiffness values were included for data analysis. Histological staging was then correlated with median values and Spearman correlation calculated. P values of < 0.05 were considered statistically significant.Results: For diagnosis of hepatic steatosis (HS), CAP could predict the steatosis S2 with AUROC 0.815 (95% CI 0.741– 0.889), sensitivity (0.81) and specificity (0.73) when the optimal cut-off value was set at 288 dB/m. CAP detected histological grade S3 with AUROC 0.735 (95% CI 0.618– 0.851), sensitivity (0.71) and specificity (0.74), with a cut-off value of 330 dB/m. The AUROC for steatosis grade S1 was 0.741 (95% CI 0.650– 0.824), with a cut-off value of 263 dB/m with sensitivity 0.75 and specificity 0.70. Univariate analysis showed a correlation between CAP and diabetes (p 0.048).Conclusion: The performance of CAP to diagnose steatosis severity decreases as steatosis progresses. CAP is associated with diabetes but not other clinical factors and parameters of the metabolic syndrome.Keywords: fibroscan, steatosis, diabetes, ballooning, liver, fibrosis

BACKGROUND: In sub-Saharan Africa (SSA), malaria remains a public health problem despite recent reports of declining incidence. Severe malaria is a multiorgan disease with wide-ranging clinical spectra and outcomes that have been reported to vary by age, geographical location, transmission intensity over time. There are reports of recent malaria epidemics or resurgences, but few data, if any, focus on the clinical spectrum of severe malaria during epidemics. This describes the clinical spectrum and outcomes of childhood severe malaria during the disease epidemic in Eastern Uganda. METHODS: This prospective cohort study from October 1, 2021, to September 7, 2022, was nested within the 'Malaria Epidemiological, Pathophysiological and Intervention studies in Highly Endemic Eastern Uganda' (TMA2016SF-1514-MEPIE Study) at Mbale Regional Referral Hospital, Uganda. Children aged 60 days to 12 years who at admission tested positive for malaria and fulfilled the clinical WHO criteria for surveillance of severe malaria were enrolled on the study. Follow-up was performed until day 28. Data were collected using a customized proforma on social demographic characteristics, clinical presentation, treatment, and outcomes. Laboratory analyses included complete blood counts, malaria RDT (SD BIOLINE Malaria Ag P.f/Pan, Ref. 05FK60-40-1) and blood slide, lactate, glucose, blood gases and electrolytes. In addition, urinalysis using dipsticks (Multistix® 10 SG, SIEMENS, Ref.2300) at the bedside was done. Data were analysed using STATA V15.0. The study had prior ethical approval. RESULTS: A total of 300 participants were recruited. The median age was 4.6 years, mean of 57.2 months and IQR of 44.5 months. Many children, 164/300 (54.7%) were under 5 years, and 171/300 (57.0%) were males. The common clinical features were prostration 236/300 (78.7%), jaundice in 205/300 (68.3%), severe malarial anaemia in 158/300 (52.7%), black water fever 158/300 (52.7%) and multiple convulsions 51/300 (17.0%), impaired consciousness 50/300(16.0%), acidosis 41/300(13.7%), respiratory distress 26/300(6.7%) and coma in 18/300(6.0%). Prolonged hospitalization was found in 56/251 (22.3%) and was associated with acidosis, P = 0.041. The overall mortality was 19/300 (6.3%). Day 28 follow-up was achieved in 247/300 (82.3%). CONCLUSION: During the malaria epidemic in Eastern Uganda, severe malaria affected much older children and the spectrum had more of prostration, jaundice severe malarial anaemia, black water fever and multiple convulsions with less of earlier reported respiratory distress and cerebral malaria.

Loving Your Liver. The Complete Guide to Liver Detox is a comprehensive guide to liver “maintenance”. Written in a simple and intuitive way, it helps understand what the liver is, what it does, how it works, how it is affected by our lifestyle, the most common diseases that can affect it and most importantly, how to take care of it. Of course, the key to a good liver detox lies in nutrition and for this very reason the learning journey with Hrvoje Miletic and Simon Taylor-Robinson ends with a section entirely dedicated to a number of delicious recipes that are good for the liver without sacrificing taste. Hrvoje Miletic is a noted food expert in Croatia and across Europe. He holds international diplomas in culinary affairs and in management. Hrvoje’s experience in the United Kingdom and across Europe has moulded his culinary experience and flair. He is currently a food researcher and entrepreneur, using his skills to help people lead a healthy lifestyle. His considerable expertise is reflected in the book. Simon Taylor-Robinson is a medical doctor. He trained as a gastroenterologist and hepatologist. He has conducted medical research on liver disease with projects around the world. During his career, he has combined being a clinical doctor with liver expertise with being a medical researcher and a teacher at the undergraduate and postgraduate level. He also holds several honorary Professorial appointments at institutions in sub-Saharan Africa and in Asia.

It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled ‘Jinyoung Byan’; the correct spelling is ‘Jinyoung Byun’ as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused.

Background: The quality of life and life expectancy of individuals living with HIV has improved significantly. This improvement is largely due to the use of Highly Active Anti-Retroviral Therapy (HAART). The effect of prolonged usage of this therapy on the menstrual function of the females within the reproductive age range is poorly understood. Methodology: A cross-sectional comparative study that involved women within the reproductive age range of 15-45 years. The women were grouped into A, B and C categories. Group A had HIV positive women already on Anti-Retroviral (ARV) therapy. Group B were HIV positive women naïve to anti-retroviral drugs at the time of recruitment. Group C comprised of HIV negative women within the reproductive age range not being managed for infertility. Results: The mean age of the participants across the study groups were respectively 32 years, 33.4 years and 37.58 years. The average weight among participants in the study was 66.38 kg, with a range of 53- 94 kg. The average duration of use of ARVs was 81.12 months (6.7 years). The mean CD4 values across the study population who were HIV positive were 725 and the average viral load was 20 copies per ml. The commonest menstrual abnormality was oligomenorrhea, occurring in close to 25% of respondent who were HIV positive and on ARVs. Menstrual abnormality was more in the HIV positive women receiving antiretroviral drugs than in the other two cohorts. (p=0.007). Conclusion: Long term usage of some first line highly active anti-retroviral therapy is associated with increased menstrual abnormality.

Non-alcoholic fatty liver disease (NAFLD) is increasing in prevalence around the world. It is associated with the metabolic syndrome with cardiovascular disease the most usual cause of death. Clinical methods used to screen for NAFLD on a preliminary basis include the use of multiple algorithms, based on non-invasive serum biomarkers. The presence of NAFLD has been linked to surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification scores. The issue of whether NAFLD is a cardiovascular risk factor itself needs to be fully determined, but it frequently coexists with insulin resistance, the metabolic syndrome and type 2 diabetes. There is no specific medical treatment for NAFLD and the evidence is incomplete with respect to the efficacy of interventions that reduce cardiovascular risk. Management of patients with NAFLD should involve identification of risk factors with key points being lifestyle change and the treatment of underlying diabetes, dyslipidemia and hypertension. Managing big data - which must be achieved and validated in advance as much as possible – should be processed by comprehensive computational epidemiology and “-omics” approaches, taking into account advanced research challenging heterogeneity. Validation and replication are mandatory before utilizing “-omic” biomarkers in diagnostics to identify patients at risk of advanced disease, including coronary heart disease.

Background: Doctors are often ill-prepared to become patients, despite knowing the technicalities of surgical procedures and the day-to-day workings of hospital life intimately. Surrendering the decision-making process to other healthcare professionals can be an unnerving process for many of those who are medically qualified. Aims: Although the sequelae of prostatectomy have often been written about, little is in the literature from medically-qualified patients about their personal experiences of the procedure. We aimed to highlight areas where communication between medically-qualified patients and their carers may be strengthened. Methods and Results: We present a personal perspective of the emotional issues surrounding a potential cancer diagnosis, the experience of having a prostatectomy and what the hospital encounters were like in reality with a viewpoint of informing the medical profession in providing better patient information when they ask “what will it be like?” From this perspective, the critical role of the cancer specialist nurse is highlighted as the lynch pin in providing a continuing source of information to medically-qualified patients and in not treating them as omniscient, simply because of a medical degree. Conclusions: Prostatectomy is a common procedure, but often questions about recovery after the procedure including impotence and incontinence are left unanswered in dealing with medically-qualified colleagues when they are patients. Human behaviour is predictable and medically-qualified patients are just as apt to forget what is said to them as anyone else. However, the central role of the cancer specialist nurse as the bridge between the medical team and the patient should not be underestimated.

Background Human infection with Opisthorchis viverrini, a carcinogenic liver fluke inhabiting the biliary tree, is endemic in South-East Asia. Chronic infection is associated with a fatal complication, cholangiocarcinoma, a late-presenting and aggressive malignancy. Currently, annual mortality rates from cholangiocarcinoma mirror trends in incidence, due in part to limited availability of efficient prognostic and early diagnostic biomarkers. With ability to detect thousands of urinary metabolites using metabonomics, the urine metabolome holds great potential in providing an insight into system-level alterations in carcinogenesis and in identifying metabolic markers altered in response to disturbed homeostasis. Methods Global molecular profiling using reversed-phase ultra-performance liquid-chomatography mass spectrometry (RP-UPLC-MS) was utilised to acquire the urinary spectral profile of 137 Thai subjects (48 at high risk of infection, 41 with O. viverrini infection, 34 periportal fibrosis and 14 cholangiocarcinoma) from Khon Kaen, Thailand. Results Multivariate statistical analysis identified perturbation in several molecular classes related to purine metabolism and lipid metabolism in the cholangiocarcinoma urine metabolome. These markers mainly reflect changes in energy metabolism to support proliferation (increased fatty acid oxidation and purine recycling), DNA methylation and hepatic injury. Conclusions Several metabolites of biological interest were discovered from this proof-of-principle dataset. Augmenting these findings is essential to accelerate the development of urinary metabolic markers in cholangiocarcinoma.

Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.

Cholangiocarcinoma (CCA) is a tumor with increasing prevalence around the world. The prevalence of CCA is highest in East Asia and most significantly in the countries through which the Mekong River flows, owing to the presence of liver flukes, which are consumed in raw fish dishes. Outside Asia, the causes of bile duct cancers for the most part are unknown. In this review, we assess the current state of knowledge in both fluke-associated and sporadic CCA, from etiological, diagnostic, and treatment perspectives.