Amanita phalloides is well-established as one of the most poisonous mushrooms; toxicity from ingestion was reported as early as the first century. Although native to Europe, this ectomycorrhizal fungus has been widely spread and is responsible for liver toxicity in many parts of the world. Toxicity is characterized by delayed gastrointestinal symptoms mimicking acute gastroenteritis followed by severe hepatotoxicity and liver failure with consequent multi-organ failure. The primary mechanism of liver toxicity is considered to be the inhibition of RNA polymerase II with consequent hepatocyte apoptosis. Treatment measures include supportive measures such as rehydration and correction of electrolytes on initial presentation, activated charcoal and lavage to decrease absorption, extracorporeal purification methods such as plasmapheresis, fractionated plasma separation and adsorption, and molecular adsorbent recirculating system, as well as drug therapies including antibiotics, N-acetylcysteine, and silibinin. Liver transplantation is required in those with acute liver failure and poor prognostic features. Here, we reviewed the basic biology, pathophysiology, and molecular mechanisms of Amanita phalloides liver toxicity, as well as available treatments.

Summary: Background: Antenatal antiviral therapy (AVT) is effective in preventing mother‐to‐child transmission (MTCT) in chronic hepatitis B (CHB); tenofovir disoproxil fumarate (TDF) is the preferred agent. Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) similar to TDF, with improved bone and renal safety. There are no data on TAF breast milk pharmacokinetics and exposure to breastfeeding infants in CHB.Aim: To assess the pharmacokinetics of TAF/TFV in breastfeeding women with CHB on TAF monotherapy.Methods: Pregnant women with CHB requiring AVT commenced TAF 25 mg daily at third trimester or postpartum. Sample collection occurred while breastfeeding and taking TAF for minimum 4 weeks. Maternal blood, breast milk and infant urine samples were collected. Drug concentrations were measured by LCMS/MS analyses using validated methods. Non‐compartmental analyses were performed to quantify the pharmacokinetic parameters.Results: Eight women provided samples. In breast milk and plasma, median TAF half‐life was 0.81 and 0.94 h, respectively, and C_max 1.69 and 120.5 ng/ml, respectively. Median maternal breast milk to plasma (M/P) ratio of TAF was 0.029; for and TFV it was 2.809. The relative infant dose of TAF was 0.005% of maternal dose, well below safety threshold of 5–10%. TFV was detectable in three out of seven infant urine samples with median steady‐state concentration of 5 ng/ml being 300–2500 times less than reported adult steady‐state urine concentrations in those taking TAF and TDF, respectively.Conclusions: In this first pharmacokinetic study of TAF monotherapy in breastfeeding women with CHB, concentrations of TAF and TFV were low in breast milk with negligible infant exposure, supporting the use of TAF to prevent MTCT.

Background and Aims: Significant barriers exist with hepatitis B (HBV) case detection and effective linkage to care (LTC). The emergency department (ED) is a unique healthcare interaction where hepatitis screening and LTC could be achieved. We examined the efficacy and utility of automated ED HBV screening for Overseas Born (OB) patients. Methods: A novel‐automated hepatitis screening service “SEARCH” (Screening Emergency Admissions at Risk of Chronic Hepatitis) was piloted at a metropolitan hospital. A retrospective and comparative analysis of hepatitis testing during the SEARCH pilot compared to a period of routine testing was conducted. Results: During the SEARCH pilot, 4778 OB patients were tested for HBV (86% of eligible patient presentations), compared with 1.9% of eligible patients during a control period of clinician‐initiated testing. SEARCH detected 108 (2.3%) hepatitis B surface antigen positive patients including 20 (19%) in whom the diagnosis was new. Among 88 patients with known HBV, 57% were receiving medical care, 33% had become lost to follow‐up and 10% had never received HBV care. Overall, 30/88 (34%) patients with known HBV were receiving complete guideline‐based care prior to re‐engagement via SEARCH. Following SEARCH, LTC was successful achieved in 48/58 (83%) unlinked patients and 19 patients were commenced on anti‐viral therapy. New diagnoses of cirrhosis and hepatocellular carcinoma were made in five and one patient(s) respectively. Conclusions: Automated ED screening of OB patients is effective in HBV diagnosis, re‐diagnosis and LTC. Prior to SEARCH, the majority of patients were not receiving guideline‐based care.

Background and Aims: Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post‐partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. Methods: A retrospective analysis of an HBeAg‐positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post‐partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. Results: We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg‐positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29–37), ALT 23 U/L (IQR 17–33) and viral load 8 log ₁₀ IU/mL (IQR 6.3–8.2 log ₁₀ IU/mL). The majority (133/198, 67.2%) received short‐course antiviral therapy to prevent mother‐to‐child transmission, and 109/192 (56.8%) had a post‐partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow‐up 814 days, IQR 405–1531). Multivariate analysis identified baseline viral load <8 log ₁₀ IU/mL (HR 2.426 [1.224–4.809], p = .011), baseline ALT ≥2 ULN (HR 2.726 [1.299–5.721], p = .008) and age <35 (HR 2.859 [1.255–6.513], p = .012) to be positive predictors of HBeAg SC. The ‘SydPreg Score’ estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. Conclusion: The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log ₁₀ IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.

Ménétrier’s disease (MD) is a rare gastropathy characterised by giant rugal folds which can present with nausea, vomiting, abdominal pain and protein losing gastropathy. We report a 21-year-old woman with comorbid MD and ulcerative colitis (UC). Management was complicated by limited treatment options for MD, significant symptom burden, worsening nutrition and difficulty determining which disease was the predominant cause of symptoms. Since age 18 the patient experienced recurrent UC flares characterised by diarrhoea, persistent vomiting and corticosteroid dependence. Endoscopic assessment demonstrated concurrent MD and active UC. Octreotide and cetuximab were trialled given persistent hypoalbuminaemia and suspicion for MD associated protein-losing gastropathy. UC management comprised dose-optimised infliximab and methotrexate. Repeat endoscopic assessment demonstrated improvement in UC without corresponding improvement in symptoms or hypoalbuminaemia. Nasojejunal feeding and parenteral nutrition failed to significantly improve nutritional status and accordingly the patient proceeded to radical total gastrectomy. Postoperatively, MD-associated symptoms and hypoalbuminemia resolved completely.

Background: Screening for viral hepatitis by automatically ordering hepatitis B and C serology on blood samples already collected from patients presenting to the emergency department (ED) is a relatively novel concept, with modest costs involved.Aim: The aim of this study was to determine patient and healthcare worker perspectives of automatic hepatitis screening at a large metropolitan hospital in Sydney, Australia.Methods: In this cross‐sectional survey study, patients admitted via ED and ED healthcare workers (HCWs) were invited to participate. The primary outcome was the level of patient and HCW acceptability of an automatic hepatitis screening process. Secondary outcomes were patient and HCW knowledge of viral hepatitis, perceptions and barriers to ED hepatitis screening in the absence of an automatic process.Results: Ninety‐two percent of 273 patients who participated in the survey wished to know their viral hepatitis status, and 82% found automatic hepatitis B and C testing acceptable as part of their ED blood work. HCWs surveyed (48) believed this strategy would increase testing, as most did not routinely interrogate patients for risk factors or other eligibility criteria for hepatitis testing, as the presenting ED complaint was their priority. Even when indications for testing based on current guidelines were present, few (32%) HCWs initiated testing.Conclusion: Automatic viral hepatitis testing in ED is supported by the majority of patients and HCWs, and the latter believe it would increase testing rates. Increasing identification of patients with hepatitis, if accompanied by effective linkage to care, could facilitate World Health Organization elimination goals.