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Background and Aims: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis with no established clinical guidelines. We sought to define the clinical outcomes of patients presenting with HH managed with current standards-of-care. Method(s): International Classification of Diseases-10 codes identified cirrhotic patients with HH presenting to 3 tertiary centres (Melbourne, Australia) from 2010 to 2018. HH was defined as pleural effusion in the absence of cardiopulmonary disease. Medical records were reviewed to determine baseline characteristics and survival. Primary outcome was 12-month mortality. The Kaplan-Meier method was used to calculate survival probability. Result(s): 83 patients were included. Median age was 59 years (IQR 54-63), 57% were male and median MELD score was 29 (IQR 25-33). Common causes of cirrhosis were viral (33%), alcohol (27%) and nonalcoholic fatty liver disease (19%); 29% had hepatocellular carcinoma. Pleural effusions were typically right-sided (83%) and 73% had concurrent ascites. There were 169 hospital admissions for HH over the study period. Median length of stay was 11 days and 22% required intensive care unit admission. 89% and 7% patients were prescribed diuretics and non-selective beta-blockers respectively at presentation. Diuretic therapy alone was commenced in 13 (8%) presentations while 120 (71%) received diuresis and pleurocentesis (median 3L drained); 17% required blood products to facilitate pleurocentesis. 23 patients received intercostal drain insertion, 1 pleurodesis and 10 proceeded to transjugular intrahepatic portosystemic shunt insertion. 31 (37%) patients underwent liver transplantation (OLT). Significant complications were observed in 45% of admissions, including: infection [n = 25], hepatic encephalopathy [n = 19] and pneumothorax [n = 11]. 86% patients required re-admission within 6-months of index admission. The 12-month mortality rate was 29% (n = 24) and probability of transpla

Background: EDP-305 is an oral FXR agonist being developed for the treatment of nonalcoholic steatohepatitis (NASH) In the INTREPID study, EDP-305 was investigated in subjects with primary biliary cholangitis (PBC) Methods: Subjects with confirmed PBC diagnosis with or without an inadequate response to ursodeoxycholic acid (UDCA) were randomized to receive EDP-305 2 5mg or 1mg, or placebo (PBO), for 12 weeks Liver enzymes and safety/tolerability were assessed at baseline (BL) through week 12 The primary endpoint of the study was the proportion of subjects with at least 20% reduction in alkaline phosphatase (ALP) from pre-treatment value, or normalization of ALP, at week 12 (NCT03394924) Results: A total of 68 subjects were randomized: mean age of 56 years; 98% women; 95% on stable UDCA dose, and mean ALP at 300U/l In the intentto-treat (ITT) analysis, EDP-305 resulted in ALP response of 45% (n=14/31, p=0 106) and 46% (n=13/28, p=0 063) in the 1 mg and 2 5 mg treatment arms, respectively, compared to 11% (n=1/9) in the PBO arm Absolute changes from baseline in ALP were statistically significant at week 12 in both the EDP-305 1 mg arm (p=0 017) and the 2 5 mg arm (p= 0 021) compared to the change from baseline in the PBO arm There was also a statistically significant reduction from baseline in serum ALT, AST and GGT compared to PBO in both the EDP-305 1 mg arm and the 2 5 mg arm In addition to reduction in GGT, EDP-305 exhibited evidence of target engagement with reduction in C4 ranging from 18-60% Overall, EDP-305 was generally safe, with the most common (>=10% or >1 subject/arm) TEAEs including pruritus, GI-related symptoms, headache and insomnia Pruritus was present in 71% of the subjects in the 2 5mg arm, 47% in the 1mg arm and 33% in the PBO arm Pruritus led to treatment discontinuation in 3% of subjects with 1mg and 18% with 2 5mg Treatment with EDP-305 had no apparent effect on lipids Conclusion(s): The INTREPID study showed numerically higher response rates wi

Nivolumab is an immune checkpoint inhibitor used to treat multiple solid-organ malignancies. While many of its immune-related adverse events are well established, nivolumab-induced sclerosing cholangitis remains poorly characterised, with no defined diagnostic criteria. Moreover, data regarding long-term outcomes are particularly lacking. We present a biopsy-proven case of nivolumab-induced sclerosing cholangitis, which uniquely captures 18 months of follow-up post-treatment. Our case highlights key features of intrahepatic subtype sclerosing cholangitis and suggests durable response to corticosteroid therapy.

Due to advances in modern medicine, liver transplantation has revolutionised the prognosis of many previously incurable liver diseases. This progress has largely been due to advances in immunosuppressant therapy. However, despite the judicious use of immunosuppression, many liver transplant recipients still experience complications such as rejection, which necessitates diagnosis via invasive liver biopsy. There is a clear need for novel, minimally-invasive tests to optimise immunosuppression and improve patient outcomes. An emerging biomarker in this ''precision medicine'' liver transplantation field is that of donor-specific cell free DNA. In this review, we detail the background and methods of detecting this biomarker, examine its utility in liver transplantation and discuss future research directions that may be most impactful.

BACKGROUND & AIMS: Portal hypertension contributes to the pathogenesis of malnutrition and sarcopenia in cirrhosis via multiple mechanisms. Terlipressin is a vasopressin analogue that we administer via continuous outpatient infusion, as a bridge to transplantation in patients with hepatorenal syndrome or refractory ascites. We describe, for the first time, the impact of outpatient terlipressin on nutritional and muscle parameters. METHODS: Nutrition (subjective global assessment), handgrip strength, dietary intake (energy, protein), frequency of paracentesis and severity of liver disease (model for end-stage liver disease score) were prospectively recorded at terlipressin commencement and follow-up (transplantation, cessation or census date). RESULTS: Nineteen patients were included (89% male, median age 59.6 years, median model for end-stage liver disease score 24), of whom 12 had hepatorenal syndrome and 7 had refractory ascites. All patients were malnourished at baseline, 63% (n = 12) had sarcopenic-range grip strength, and mean paracentesis frequency was 2.86 ± 1.62/month. Median duration of terlipressin was 51 days (interquartile range 29-222). Fourteen patients (74%) were transplanted, 2 delisted (10%) and 3 (16%) continued terlipressin. Energy and protein intake improved significantly following terlipressin, from 17.94 ± 5.43 kcal/kg to 27.70 ± 7.48 kcal/kg, and 0.74 ± 0.28 g/kg to 1.16 ± 0.31 g/kg, respectively (both p < 0.001). Handgrip strength increased from 25.36 ± 8.13 kg to 28.49 ± 7.63 kg (p = 0.001). Linear regression analysis demonstrated hand grip strength increased 0.075% for every 1-day of terlipressin (p = 0.005). The frequency of large-volume paracentesis reduced by 46%, to 1.57 ± 1.51/month (p = 0.001). CONCLUSION: Continuous terlipressin infusion reduces the complications of portal hypertension and is associated with an improvement in nutritional and muscle parameters in patients on the liver transplant waiting list, in whom such characterist

BACKGROUND: Acute liver failure (ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain. AIM: To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia. METHODS: The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults (> 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival (OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988-2001. RESULTS: Paracetamol was the most common aetiology of acute liver failure, accounting for 50% of cases, with an increased incidence compared with the historical cohort (P = 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival (TFS) improved significantly compared to the historical cohort (52% vs 38%, P = 0.032). TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF (P < 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients (25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and 72% respectively. CONCLUSION: Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.

The bioremediation potential of a contaminated oil sands site can be increased through an understanding of the indigenous microbial communities present and a knowledge of which amendments should be added to encourage the growth of the desired populations. Laboratory experiments are described which can save time, money and resources in the gathering of the required data. Bench tests combining conventional biotreatability studies with molecular techniques can be applied to contaminants such as hydrocarbons and metals. An example is presented to assess the potential for the biological reduction of perchloroethylene (PCE) and other chlorinated aliphatic hydrocarbons in contaminated soil and groundwater using two different carbon sources, lactate and molasses, a redox agent and a combination of these as amendments. The results showed that the removal efficiency of PCE was higher using molasses rather than lactate as a co-substrate, and that the use of molasses with the redox agent improved the dechlorination process in most treatments. The microbial profile of samples from various tailings ponds in the Athabasca Basin, Canada was studied based on DNA fingerprinting. Experimental tailings pond microcosms were created using the tailings sediment capped with the corresponding tailings water and incubated under aerobic and anaerobic conditions. The microbial populations in the microcosms, in particular in sediments, were similar to those derived from the source material after 20 months of incubation, indicating that the populations were stable and in equilibrium and that bench-scale microcosm studies have the potential for bioremediation investigations. Biofilms were seeded from tailings ponds for in vitriol growth and the microbial profile of the biofilm population was determined based on polymerase chain reaction and DNA sequencing, The results showed a diverse microbial population with the identification of many bacterial and a few archaea genera, some of which have known, The bioremediation potential of a contaminated oil sands site can be increased through an understanding of the indigenous microbial communities present and a knowledge of which amendments should be added to encourage the growth of the desired populations. Laboratory experiments are described which can save time, money and resources in the gathering of the required data. Bench tests combining conventional biotreatability studies with molecular techniques can be applied to contaminants such as hydrocarbons and metals. An example is presented to assess the potential for the biological reduction of perchloroethylene (PCE) and other chlorinated aliphatic hydrocarbons in contaminated soil and groundwater using two different carbon sources, lactate and molasses, a redox agent and a combination of these as amendments. The results showed that the removal efficiency of PCE was higher using molasses rather than lactate as a co-substrate, and that the use of molasses with the redox agent improved the dechlorination process in most treatments. The microbial profile of samples from various tailings ponds in the Athabasca Basin, Canada was studied based on DNA fingerprinting. Experimental tailings pond microcosms were created using the tailings sediment capped with the corresponding tailings water and incubated under aerobic and anaerobic conditions. The microbial populations in the microcosms, in particular in sediments, were similar to those derived from the source material after 20 months of incubation, indicating that the populations were stable and in equilibrium and that bench-scale microcosm studies have the potential for bioremediation investigations. Biofilms were seeded from tailings ponds for in vitriol growth and the microbial profile of the biofilm population was determined based on polymerase chain reaction and DNA sequencing, The results showed a diverse microbial population with the identification of many bacterial and a few archaea genera, some of which have known