Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans.

Diagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (DO; n = 133) and follow-up (n = 120), acute non-DILI at onset (NDO; n = 63) and follow-up (n = 42), and healthy volunteers (HV; n = 104). Area under the receiver operating characteristic curve (AUC) for cytoplasmic aconitate hydratase, argininosuccinate synthase, carbamoylphosphate synthase, fumarylacetoacetase, fructose-1,6-bisphosphatase 1 (FBP1) across cohorts achieved near complete separation (range: 0.94-0.99) of DO and HV. In addition, we show that FBP1, alone or in combination with glutathione S-transferase A1 and leukocyte cell-derived chemotaxin 2, could potentially assist in clinical diagnosis by distinguishing NDO from DO (AUC range: 0.65-0.78), but further technical and clinical validation of these candidate biomarkers is needed.

The diversity and management of chronic hepatitis B virus infections in the United Kingdom: a wake-up call.

BACKGROUND: Through migration, diversity of chronic hepatitis B virus (HBV) infection has changed, affecting disease burden and control. We describe clinical and viral characteristics of chronic HBV in the United Kingdom. METHODS: A total of 698 individuals with chronic HBV infection were recruited from referral liver centers. Demographic, clinical, and laboratory data were collected. RESULTS: Sixty-one percent of patients were male, 80% were not born in the United Kingdom, and the largest ethnicity was East/Southeast Asian (36%). Twenty-two percent were hepatitis B e antigen (HBeAg) seropositive; 20.4% (59/289) had cirrhosis and 10 (1.7%) had hepatocellular carcinoma. Genotype D was most common (31%) followed by A, C, B, and E (20%, 20%, 19%, and 9%, respectively). Genotype was significantly associated with country of birth, length of time in the United Kingdom, HBeAg status, and precore and basal core promoter mutations. One-third were on treatment, with men independently more likely to be treated. Only 18% of those on treatment were on recommended first-line therapies, and 30% were on lamivudine monotherapy. Among treated individuals, 27% had antiviral drug resistance. Testing rates for human immunodeficiency virus, hepatitis C virus, and delta coinfections were low. CONCLUSIONS: We demonstrated diversity of chronic HBV infections in UK patients, suggesting that optimal management requires awareness of the variable patterns of chronic HBV in countries of origin. We also found less-than-optimal clinical management practices, possible gender-based treatment bias, and the need to improve testing for coinfections.

Feasibility and experience of nurse-led ultrasound-guided percutaneous liver biopsy.

The demand for collaborative and innovative clinical practitioners to act as leaders in healthcare remains strong as many challenges are faced including rising costs, shortage of professionals, the introduction of new technology and difficulties with access to care. Nurses in advanced nursing practice are well positioned to respond to this, playing a key role in building nursing knowledge, advancing the nursing profession and contributing to sustainable and effective healthcare systems. Percutaneous liver biopsy (PLB) is an essential tool used for diagnosis and management in liver disease, being most commonly performed by consultant gastroenterologists, hepatologists and radiologists. While invasive and with complications PLB is a simple, cost-effective procedure that can be undertaken at the bedside. Our study demonstrates that an advanced nurse practitioner (ANP) with a sound working knowledge of hepatology and familiarity with indications, methods and risks of PLB procedure can be trained to perform ultrasound-guided liver biopsy both safely and effectively.

The "jaundice hotline" for the rapid assessment of patients with jaundice.

PROBLEM: Patients with jaundice require rapid diagnosis and treatment, yet such patients are often subject to delay. DESIGN: An open referral, rapid access jaundice clinic was established by reorganisation of existing services and without the need for significant extra resources. BACKGROUND AND SETTING: A large general hospital in a largely rural and geographically isolated area. KEY MEASURES FOR IMPROVEMENT: Waiting times for referral, consultation, diagnosis, and treatment, length of stay in hospital, and general practitioners' and patients' satisfaction with the service. STRATEGIES OF CHANGE: Referrals were made through a 24 hour telephone answering machine and fax line. Initial assessment of patients was carried out by junior staff as part of their working week. Dedicated ultrasonography appointments were made available. EFFECTS OF CHANGE: Of 107 patients seen in the first year of the service, 62 had biliary obstruction. The mean time between referral and consultation was 2.5 days. Patients who went on to endoscopic retrograde cholangiopancreatography waited 5.7 days on average. The mean length of stay in hospital in the 69 patients who were admitted was 6.1 days, compared with 11.5 days in 1996, as shown by audit data. Nearly all the 36 general practices (95%) and the 30 consecutive patients (97%) that were surveyed rated the service as above average or excellent. LESSONS LEARNT: An open referral, rapid access service for patients with jaundice can shorten time to diagnosis and treatment and length of stay in hospital. These improvements can occur through the reorganisation of existing services and with minimal extra cost.