Lower serum fibroblast activation protein shows promise in the exclusion of clinically significant liver fibrosis due to non-alcoholic fatty liver disease in diabetes and obesity.

UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is common in diabetes and obesity but few have clinically significant liver fibrosis. Improved risk-assessment is needed as the commonly used clinical-risk algorithm, the NAFLD fibrosis score (NFS), is often inconclusive. AIMS: To determine whether circulating fibroblast activation protein (cFAP), which is elevated in cirrhosis, has value in excluding significant fibrosis, particularly combined with NFS. METHODS: cFAP was measured in 106 with type 2 diabetes who had transient elastography (Cohort 1) and 146 with morbid obesity who had liver biopsy (Cohort 2). RESULTS: In Cohort 1, cFAP (per SD) independently associated with median liver stiffness (LSM) ≥ 10.3 kPa with OR of 2.0 (95% CI 1.2-3.4), p=0.006. There was 0.12 OR (95% CI 0.03-0.61) of LSM ≥ 10.3 kPa for those in the lowest compared with the highest FAP tertile (p=0.010). FAP levels below 730 pmol AMC/min/mL had 95% NPV for LSM ≥ 10.3 kPa and reclassified 41% of 64 subjects from NFS 'indeterminate-risk' to 'low-risk'. In Cohort 2, cFAP (per SD), associated with 1.7 fold (95% CI 1.1-2.8) increased odds of significant fibrosis (F ≥ 2), p=0.021, and low cFAP reclassified 49% of 73 subjects from 'indeterminate-risk' to 'low-risk'. CONCLUSIONS: Lower cFAP, when combined with NFS, may have clinical utility in excluding significant fibrosis in diabetes and obesity.

Terlipressin therapy for moderate-to-severe hyponatraemia in patients with liver failure.

BACKGROUND: Hyponatraemia in liver failure is associated with increased morbidity and mortality. Improving serum sodium in liver failure has been observed in patients receiving terlipressin. METHODS: We assessed the response of hyponatraemia in patients with liver failure to terlipressin using comparative retrospective analysis. RESULTS: Twenty-three patients received terlipressin for hyponatraemia after failed conservative management (median age 52 years (27-67), model for end-stage liver disease score 28 (16-38)). The median therapy was 7 days (1-27), with an average total dose of 25 mg (4-90) and a mean follow up of 51 days (5-1248). These patients were compared with 11 hyponatraemic patients managed conservatively during the same period with comparable age, baseline serum sodium and follow up. After 1 week of terlipressin therapy, serum sodium increased from a median of 120 (115-128) to 129 mmol/L (121-144) (P < 0.001), and at the end of terlipressin therapy, the serum sodium had increased significantly to 131 mmol/L (120-148) (P < 0.001). In comparison, in the conservatively managed group, the serum sodium did not increase significantly from the baseline of 123 (117-127) mmol/L. Adverse events occurred in 26% of patients receiving terlipressin, which predominantly pulmonary oedema. Importantly, more hyponatraemic patients treated with terlipressin (48%) were alive compared with the conservative group (18%), despite the latter having a significantly lower baseline median MELD score of 21 (16-30) (P = 0.008). Moreover, the transplant-free survival was higher in the terlipressin (30%) compared with the conservative group (0%). CONCLUSIONS: Terlipressin is effective in treating hyponatraemia in liver failure. Importantly, terlipressin use results in better transplant-free survival but also more adverse events.

Increasing liver transplantation waiting list mortality: a report from the Australian National Liver Transplantation Unit, Sydney.

BACKGROUND: We aimed to describe the demand for liver transplantation (LTx) and patient outcomes on the waiting list at the Australian National Liver Transplantation Unit, Sydney over the last 20 years. METHODS: We performed a retrospective analysis with the data divided into three eras: 1985-1993, 1994-2000 and 2001-2008. RESULTS: The number of patients accepted for LTx increased from 320 to 372 and 548 (P < 0.001) with the number of LTx being performed increasing from 262 to 312 and 452 respectively (P < 0.001). The median adult recipient age increased from 45 to 48 and 52 years (P < 0.001) while it decreased in children from 4 to 2 and 1 years respectively (P = 0.001). In parallel, the deceased donor offers decreased from 1003 to 720 and 717 (P < 0.001). Methods to improve access to donor livers have been used with the use of split livers, extended criteria and non-heart beating donors, resulting in increased acceptance of deceased donor offers by 65% and 115% in the second and third eras when compared with the first era (P < 0.001). However, the adult median waiting time has increased from 23 to 41 and 120 days respectively (P < 0.001). This was associated with increased adult mortality on the waiting list from 23 to 40 and 122 respectively (P < 0.001). CONCLUSIONS: Despite the increasing proportion of donor offers being used, the waiting list mortality is increasing. A solution to this problem is an increase in organ donation to keep pace with the escalating demand for LTx.