Drug-induced liver injury secondary to tamoxifen.

Tamoxifen is a non-steroidal selective oestrogen receptor modulator commonly used in the treatment of breast cancer. It is associated with the development of fatty liver and steatohepatitis however drug-induced liver injury is rare. We report a woman in her 50s who developed malaise with an acute moderate aminotransferase elevation without jaundice 6 months after starting tamoxifen. She was not commenced on any other recent drugs and extensive investigation including infective and autoimmune liver screen, cross-sectional imaging and FibroScan were unremarkable. Liver biopsy revealed moderate lobular hepatitis with hepatocyte drop-out. Tamoxifen was ceased and the liver enzymes showed resolution over the following 3 months and improvement of her symptoms.

Indications and outcomes of transjugular intrahepatic portosystemic shunt insertion in two regional Australian hepatology centres.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapy for complications of portal hypertension but remains underutilised in regional settings. AIMS: The aim of this study is to explore the demographics, indications, outcomes and complications in patients undergoing TIPS in two regional hepatology centres. METHODS: Retrospective analysis was undertaken of all patients undergoing TIPS at two regional centres between January 2017 and March 2023. The primary outcome measures were efficacy and complications of TIPS. Patient demographics (such as age, baseline liver severity scores and aetiology of liver disease) and indications for TIPS are detailed. RESULTS: Forty-eight patients underwent TIPS. Median age was 56 years (interquartile range (IQR): 46-65). The most common indications for TIPS were refractory ascites (n = 17) and failure of secondary prophylaxis of variceal bleeding (n = 13). Cumulative survival at 3 months and 1 year was 93% and 77% respectively. There was no significant difference in outcomes based on TIPS indication. The median number of paracenteses in patients undergoing TIPS for refractory ascites 1 year pre- and post-TIPS were 10 (IQR: 4.5-16) and 2 (IQR: 0-4) respectively (P < 0.001). There were no procedure-related deaths. Inpatient management of liver disease complications had a mean cost of $32 874.67 (SEM: 7779) in 1 year pre-TIPS compared with $12 304.70 (SEM: 3531.1) in 1 year post-TIPS (P < 0.001). CONCLUSIONS: TIPS is a safe and effective treatment to reduce complications of portal hypertension and can be performed successfully in the regional setting.

Mercaptopurine-induced Sweet's syndrome.

Sweet's syndrome is an acute febrile neutrophilic dermatosis. Drug-induced Sweet's syndrome typically occurs soon after drug administration, with rapid resolution of symptoms with cessation of the offending agent. We report a man in his early 40s who presented with fever and widespread erythematous rash on a background of recently diagnosed mild stricturing ileal Crohn's disease. He was commenced on 6-mercaptopurine 12 days before presentation. Skin biopsy demonstrated diffuse infiltration of neutrophils in the upper dermis, dermal oedema, eosinophils and fibrin deposition. Symptoms rapidly improved with cessation of 6-mercaptopurine without requiring systemic corticosteroids.

Transforming growth factor-ß and inflammation in vascular (type IV) Ehlers-Danlos syndrome.

BACKGROUND: Vascular Ehlers-Danlos syndrome (VEDS) causes reduced life expectancy because of arterial dissections/rupture and hollow organ rupture. Although the causative gene, COL3A1, was identified >20 years ago, there has been limited progress in understanding the disease mechanisms or identifying treatments. METHODS AND RESULTS: We studied inflammatory and transforming growth factor-ß (TGF-ß) signaling biomarkers in plasma and from dermal fibroblasts from patients with VEDS. Analyses were done in terms of clinical disease severity, genotype-phenotype correlations, and body composition and fat deposition alterations. VEDS subjects had increased circulating TGF-ß1, TGF-ß2, monocyte chemotactic protein-1, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and leptin and decreased interleukin-8 versus controls. VEDS dermal fibroblasts secreted more TGF-ß2, whereas downstream canonical/noncanonical TGF-ß signaling was not different. Patients with COL3A1 exon skipping mutations had higher plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and VEDS probands had abnormally high plasma C-reactive protein versus affected patients identified through family members before any disease manifestations. Patients with VEDS had higher mean platelet volumes, suggesting increased platelet turnover because of ongoing vascular damage, as well as increased regional truncal adiposity. CONCLUSIONS: These findings suggest that VEDS is a systemic disease with a major inflammatory component. C-reactive protein is linked to disease state and may be a disease activity marker. No changes in downstream TGF-ß signaling and increased platelet turnover suggest that chronic vascular damage may partially explain increased plasma TGF-ß1. Finally, we found a novel role for dysregulated TGF-ß2, as well as adipocyte dysfunction, as demonstrated through reduced interleukin-8 and elevated leptin in VEDS.