Drug-induced liver injury from selective androgen receptor modulators, anabolic-androgenic steroids and bodybuilding supplements in Australia.

BACKGROUND: Reports of DILI due to herbal and dietary supplements have been increasing over time. AIMS: To characterise clinical, laboratory and histopathological phenotypes and outcomes of drug-induced liver injury (DILI) due to anabolic-androgenic steroids (AAS), selective androgen receptor modulators (SARMs), and bodybuilding supplements (BBS) in Australia. METHODS: Retrospective case series. Patients presented to nine Australian tertiary hospitals, 2017-2023. DILI was defined biochemically and patients were included if their treating physician attributed DILI to preceding use of AAS, SARMs or BBS. Primary endpoint was time to normalisation of liver biochemistry. Secondary endpoints were hospitalisation for investigation or management of DILI, death attributable to liver injury, and liver transplantation. RESULTS: Twenty-three cases of DILI were identified, involving 40 drugs: 18 AAS, 14 SARMs and eight BBS. Patients were predominantly male (22/23), with median age 30 years (IQR 26-42). Most were symptomatic (21/23). Median latency of onset was 58 days (IQR 28-112 days) from drug commencement. Most patients (17/23) were admitted to hospital. Based on updated Roussel Uclaf Causality Assessment Method, DILI was possible in 17/23, probable in 2/23 and unlikely in 4/23. Median time to normalisation of liver biochemistry was 175 days (IQR 70-292 days) from presentation. Three (3/23) were treated with corticosteroids, 14/23 were treated for itch, and one (1/23) underwent liver transplantation. There were no deaths. CONCLUSIONS: The prognosis of DILI from AAS, SARMs and BBS is good although liver transplantation may rarely be required. A detailed drug history is important in uncovering DILI due to these supplements.

Clip-and-line traction method for difficult ERCP cannulation due to choledochocoele.

Video 1Clip-and-line traction method for difficult ERCP cannulation due to choledochocoele.

Outcomes of patients with hepaticojejunostomy anastomotic strictures undergoing endoscopic and percutaneous treatment.

Background and study aims The increase in hepaticojejunostomies has led to an increase in benign strictures of the anastomosis. Double balloon enteroscopy-assisted ERCP (DBE-ERCP) and percutaneous transhepatic biliary drainage (PTBD) are treatment options; however, there is lack of long-term outcomes, with no consensus on management. We performed a retrospective study assessing the outcomes of patients referred for endoscopic management of hepaticojejunostomy anastomotic strictures (HJAS). Patients and methods All consecutive patients at a tertiary institution underwent endoscopic intervention for suspected HJAS between 2009 and 2021 were enrolled. Results Eighty-two subjects underwent DBE-ERCP for suspected HJAS. The technical success rate was 77 % (63/82). HJAS was confirmed in 41 patients. The clinical success rate for DBE-ERCP ± PTBD was 71 % (29/41). DBE-ERCP alone achieved clinical success in 49 % of patients (20/41). PTBD was required in 49 % (20/41). Dual therapy was required in 22 % (9/41). Those with liver transplant had less technical success compared to other surgeries (72.1 % vs 82.1 % P  = 0.29), less clinical success with DBE-ERCP alone (40 % vs 62.5 % P  = 0.16) and required more PTBD (56 % vs 37.5 % P  = 0.25). All those with ischemic biliopathy (n = 9) required PTBD for clinical success, required more DBE-ERCP (4.4 vs 2.0, P = 0.004), more PTBD (4.7 vs 0.3, P  < 0.0001), longer treatment duration (181.6 vs 99.5 days P  = 0.12), and had higher rates of recurrence (55.6 % vs 30.3 % P  = 0.18) compared to those with HJAS alone. Liver transplant was the leading cause of ischemic biliopathy (89 %). The overall adverse event rate was 7 %. Conclusions DBE-ERCP is an effective diagnostic and therapeutic tool in those with altered gastrointestinal anatomy and is associated with low complication rates.

Menetrier's disease exacerbating ulcerative colitis and relieved by gastrectomy.

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.

The ideal technique for processing SpyBite tissue specimens: a prospective, single-blinded, pilot-study of histology and cytology techniques.

Background and study aims Diagnostic sensitivity for indeterminate biliary lesions remains suboptimal. Cytology techniques may mitigate the impediment of small cholangioscopic specimens. Our primary aim was to compare cell block cytology (CB) with standard histology for foregut SpyBite (SB) specimens. Our secondary aim was to assess CB in biliary SB biopsies. Patients and methods This was a two-phase prospective pilot study. In phase one, a prospective pilot study, foregut SB specimens from three sites (4 per site per patient per processing technique) were allocated to CB or histology, and assessed by a single, blinded pathologist. The gold standard comprised two standard forceps (CFB) histological specimens per site per patient. Specimen ease of processing, size and number, adequacy for diagnosis and artefact were evaluated. In phase two, CB was used for consecutive patients with indeterminate biliary lesions, and compared with phase one CB results. Results In phase one, 240 SB foregut biopsies were performed in 10 patients, 227 specimens recorded by pathologist. Specimen origin was identified in 100 % and 97 % of histology and CB batches respectively. Specimens were significantly larger in the histology group (2.02 mm vs 1.49 mm, P  < 0.05). There was a trend to less crush artifact with CB, and no difference in processing difficulty. In phase two, 11 patients (63.0 ±12.7 years, 91 % female) underwent SpyGlass (SG) assessment of suspected indeterminate stricture (n = 8) or mass (n = 3), and six underwent SB. All CB specimens were adequate for diagnosis. Specimen parameters were not significantly different from luminal CB outcomes. Conclusions In this pilot study, cell block cytology showed similar results as histological analysis of SpyBite specimens in the analysis of biliary stricture.

Immunity to Vaccine-preventable Viral Infections in Australians Being Evaluated for Liver Transplantation.

BACKGROUND: Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in immunocompromised patients. Current guidelines recommend routine screening and vaccination of all patients before solid organ transplantation. We studied rates of immunity against vaccine-preventable viruses in liver transplantation (LT) recipients. METHODS: We retrospectively studied consecutive adult patients who underwent first deceased donor LT at a single center between August 2008 and October 2017. Viruses studied were hepatitis A (HAV), hepatitis B (HBV), varicella zoster virus (VZV), measles, and mumps. Hepatitis B surface antibody (anti-HBs) <10 IU/mL in HBV surface antigen-negative patients and negative IgG to other viruses was regarded as absent immunity. RESULTS: Five hundred and fifty-five patients underwent LT (72.4% male; median age, 55.0 y). Percentages of patients who lacked immunity to vaccine-preventable infections were HAV (31.8%), HBV (63.8%), measles (1.4%), mumps (6.6%), and VZV (3.8%). Age was positively associated with immunity (from either past exposure or vaccination) against most viruses, including HAV, measles, mumps, and VZV (P < 0.05 for all). In contrast, older age was marginally associated with anti-HBs <10 IU/mL (P = 0.046). No significant changes in immunity rates were observed during the study period. CONCLUSIONS: A substantial number of patients undergoing LT are not immune to vaccine-preventable viruses at the time of assessment. This presents an opportunity for pre-LT vaccination and in particular younger patients may need to be targeted.

Standardization of exhaled breath condensate: effects of different de-aeration protocols on pH and H2O2 concentrations.

Exhaled breath condensate (EBC) analysis is a non-invasive method to repeatedly evaluate airway inflammation. Dissolved carbon dioxide contributes to lowering EBC pH which is reversed by degassing with argon. Hypothetically, argon may also improve biomarker stability by removing reactive gases, since many markers are pH sensitive or easily oxidized. In this study, the influence of two degassing methods was assessed on (i) the volume of EBC, (ii) the EBC pH, and (iii) the concentration of H2O2 in EBC. EBC was collected from 13 healthy subjects and 12 chronic obstructive pulmonary disease subjects over 20 min, then aliquoted and either left on ice or de-aerated with argon by bubbling or surface delivery at 400 ml min(-1) for 0 to 600 s, to quantify the EBC volume loss and the efficiency of pH equilibration. Biomarker stability was measured by H2O2 concentration. Both degassing methods reached a pH equilibrium by 300 s. Bubbling reached pH equilibrium faster (60 s versus 300 s), while having significantly less EBC volume loss (bubbling 3.32 ± 1.31% versus surface 10.74 ± 1.46%, p < 0.0001). The H2O2 concentration was higher in non-degassed samples (0.47 ± 0.18 µM, p = 0.017) but similar in the bubbling and surface degassed samples (0.30 ± 0.08 µM versus 0.31 ± 0.10 µM, p = 0.54). The optimal degassing methods were to bubble the aliquots with argon at 400 ml min(-1) for 60 s or surface degassing for 300 s. Both methods resulted in significantly less EBC volume loss than the commonly adopted method of bubbling for 10 min. There was a significant difference in the H2O2 concentration between the degassed and the non-degassed samples.

Proteomics in detection and monitoring of asthma and smoking-related lung diseases.

Asthma, chronic obstructive pulmonary disease (COPD) and lung cancer cause extensive mortality and morbidity worldwide. However, the current state-of-the-art diagnosis and management schemes of these diseases are suboptimal as the incidence of asthma has risen by 250% over the last two decades and the 5-year mortality rate of lung cancer remains at 88%. Proteomic analysis is at the frontier of medical research and demonstrates tremendous potential in the early detection, diagnosis and staging, as well as providing novel therapeutic targets for improved management of smoking-related lung diseases. Advances in analytical tools, such as 2D gel electrophoresis, mass spectrometry, protein arrays and improved bioinformatics, allow sensitive and specific biomarker/protein profile discoveries and the infusion of new knowledge towards the molecular basis of lung diseases and their progression. Significant hurdles still stand between these laboratory findings and their applications in clinical practice. One of the challenges is the difficulty in the selection of samples that provide scope into the specific disease entity. Induced sputum, bronchoalveolar lavage, exhaled breath and exhaled breath condensate are methods of sampling airway and lung fluids that can serve as a window to assess the microenvironment of the lungs. With better study design standardization and the implementation of novel technologies to reach the optimal research standard, there is enough reason be optimistic about the future of proteomic research and its clinical implications.