Acute-on-chronic liver failure: Controversies and consensus.

Acute-on-chronic liver failure (ACLF) is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease. Consequences include high short-term morbidity, mortality, and healthcare resource utilisation. ACLF encompasses a dysregulated, systemic inflammatory response, which can precipitate extra hepatic organ failures. Common precipitants include infection, alcoholic hepatitis, and reactivation of viral hepatitis although frequently no cause is identified. Heterogenous definitions, diagnostic criteria, and treatment guidelines, have been proposed by international hepatology societies. This can result in delayed or missed diagnoses of ACLF, significant variability in clinical management, and under-estimation of disease burden. Liver transplantation may be considered but the mainstay of treatment is organ support, often in the intensive care unit. This review will provide clarity around where are the controversies and consensus in ACLF including: Epidemiology and resource utilisation, key clinical and diagnostic features, strategies for management, and research gaps.

Healthcare utilisation and costing for decompensated chronic liver disease hospitalisations at a Victorian network.

BACKGROUND: The economic burden of decompensated chronic liver disease (CLD) on Australian healthcare services is poorly characterised. AIMS: To evaluate the in-patient healthcare utilisation costs associated with decompensated CLD at Monash Health, an Australian tertiary healthcare service. METHODS: The current retrospective cost analysis examined patients with decompensated CLD admitted between 1 January 2012 and 31 December 2018. Hospitalisations were identified using CLD-specific International Classification of Diseases, Tenth Revision, codes. Cost measures were estimated using the Victorian Weighted Inlier Equivalent Separation funding data based on the Australian Refined Diagnosis Related Groups cost weights. RESULTS: There were 707 hospitalisations in 435 adult patients. The mean age was 56.7 ± 11.7 years and the mean length of stay was 10.28 ± 11.2 days. Median survival was 31 months (interquartile range, 2-94 months) and 177 (40.8%) patients died within 1 year of admission. The cost of admission varied according to decompensation: hepatorenal syndrome ($20 162 AUD), variceal bleed ($16 630 AUD), spontaneous bacterial peritonitis ($12 664 AUD), hepatic encephalopathy ($9973 AUD) and ascites ($9001 AUD). There was no significant difference in the admissions or 30-day readmission rate from 2012 to 2018 financial year (FY). The total adjusted cost of cirrhotic admissions per year increased by 78% from FY2012 to FY2018. CONCLUSION: Hospital admission and readmission for decompensated CLD is common and associated with 40.8% 1-year mortality and high costs. Clearer delineation of goals of care and alternative ambulatory care models for decompensated CLD are urgently required to reduce the high costs and burden on health services.

Survival outcomes and predictors of mortality, re-bleeding and complications for acute severe variceal bleeding requiring balloon tamponade.

BACKGROUND: Acute severe variceal bleeding (AVB) refractory to medical and endoscopic therapy is infrequent but associated with high mortality. Historical cohort studies from 1970-1980s no longer represent the current population as balloon tamponade is no longer first-line therapy for variceal bleeding; treatments including vasoactive therapies, intravenous antibiotics, endoscopic variceal band ligation are routinely used, and there is improved access to definitive treatments including transjugular intrahepatic portosystemic shunts. However, only a few studies from the current era exist to describe the practice of balloon tamponade, its outcomes, and predictors with a requirement for further updated information. AIM: To describe current management of AVB requiring balloon tamponade and identify the outcomes and predictors of mortality, re-bleeding and complications. METHODS: A retrospective multi-centre cohort study of 80 adult patients across two large tertiary health networks from 2008 to 2019 in Australia who underwent balloon tamponade using a Sengstaken-Blakemore tube (SBT) were included for analysis. Patients were identified using coding for balloon tamponade. The primary outcome of this study was all-cause mortality at 6 wk after the index AVB. Secondary outcomes included re-bleeding during hospitalisation and complications of balloon tamponade. Predictors of these outcomes were determined using univariate and multivariate binomial regression. RESULTS: The all-cause mortality rates during admission and at 6-, 26- and 52 wk were 48.8%, 51.2% and 53.8%, respectively. Primary haemostasis was achieved in 91.3% and re-bleeding during hospitalisation occurred in 34.2%. Independent predictors of 6 wk mortality on multivariate analysis included the Model for Endstage Liver disease (MELD) score (OR 1.21, 95%CI 1.06-1.41, P = 0.006), advanced hepatocellular carcinoma (OR 11.51, 95%CI 1.61-82.20, P = 0.015) and re-bleeding (OR 13.06, 95%CI 3.06-55.71, P < 0.001). There were no relevant predictors of re-bleeding but a large proportion in which this occurred did not survive 6 wk (76.0% vs 24%). Although mucosal trauma was the most common documented complication after SBT insertion (89.5%), serious complications from SBT insertion were uncommon (6.3%) and included 1 patient who died from oesophageal perforation. CONCLUSION: In refractory AVB, balloon tamponade salvage therapy is associated with high rates of primary haemostasis with low rates of serious complications. Re-bleeding and mortality however, remain high.

Metal stents are safe and cost-effective for preoperative biliary drainage in resectable pancreaticobiliary tumours.

BACKGROUNDS: To compare the complication rates and overall costs of self-expandable metal stents (SEMS) and plastic stents (PS) in clinically indicated preoperative biliary drainage (PBD) prior to a pancreatoduodenectomy (PD). METHODS: We conducted an Australian multicentre retrospective cohort study using the databases of four tertiary hospitals. Adult patients who underwent clinically indicated endoscopic PBD prior to PD from 2010 to 2019 were included. Rates of complications attributable to PBD, surgical complications and pre-operative endoscopic re-intervention were calculated. Costing data were retrieved from our Financial department. RESULTS: Among the 157 included patients (mean age 66.6 ± 9.8 years, 45.2% male), 49 (31.2%) received SEMS and 108 received PS (68.8%). Baseline bilirubin was 187.5 ± 122.6 µmol/L. Resection histopathology showed mainly adenocarcinoma (93.0%). Overall SEMS was associated less complications (12.2% vs. 28.7%, p = 0.02) and a lower pre-operative endoscopic re-intervention rate (4.3 vs. 20.8%, p = 0.03) compared with PS. There was no difference in post-PD complication rates. On multivariate logistic regression analysis, stent type was an independent risk factor of PBD complication (OR of SEMS compared to PS 0.24, 95% CI 0.07-0.79, p = 0.02) but not for any secondary outcome measures. Upfront material costs were $56USD for PS and $1991USD for SEMS. Accounting for rates of complications, average costs were similar ($3110USD for PS and $3026USD for SEMS). CONCLUSION: In resectable pancreaticobiliary tumours, SEMS for PBD was associated with reduced risk of overall PBD-related complications and pre-surgical endoscopic reintervention rates and was comparable to PS in terms of overall cost.

Antenatal maternal hepatitis B care is a predictor of timely perinatal administration of hepatitis B immunoglobulin.

BACKGROUND: Mother-to-child transmission of hepatitis B virus continues to occur despite universal recommendations for neonatal immune prophylaxis therapy (IPT) and infant vaccination. AIM: To characterise the risk factors for failure to provide timely IPT and completion of the infant hepatitis B vaccination schedule for children born to mothers with chronic hepatitis B (CHB). METHODS: We conducted a retrospective cohort study to assess compliance with universal guidelines for neonatal IPT for children born to CHB mothers at Monash Health, Australia from 2008 to 2013. These mothers were invited to participate in a telephone interview regarding post-partum hepatitis B virus (HBV) care and infant vaccination status. Multivariate logistic regression analysis was utilised to identify the predictors for engagement with specialist HBV care, timely administration of IPT, completion of HBV vaccination schedule and serological testing of the baby. RESULTS: A total of 451 CHB mothers delivered 454 live births. HBV immunoglobulin (HBIg) was dispensed within 12 h in 79.52% of births. HBIg was not administered to eight neonates. Of the 451 women, 125 were interviewed: 88.8% of babies completed the vaccine schedule, and 19.2% of infants had post-vaccination testing. Antenatal HBV care was independently associated with a greater likelihood of timely HBIg administration (odds ratio 1.64, P = 0.04, 95% CI: 1.03-2.61). There were no significant predictors for engagement with specialist HBV care, vaccine coverage or serological testing of the baby. CONCLUSION: Targeted interventions to improve timely HBIg and completion of the vaccine schedule are recommended. All pregnant women with CHB should be referred for HBV-specific antenatal care regardless of viral replicative status.

Primary seroresponses to double-dose compared with standard-dose hepatitis B vaccination in patients with chronic kidney disease: a systematic review and meta-analysis.

Background: Clinical guidelines recommend double-dose hepatitis B vaccination for patients requiring dialysis, due to an increased risk of hepatitis B infection and reduced vaccine responsiveness. There are no recommendations for patients with chronic kidney disease (CKD) prior to dialysis. Methods: We performed a systematic review and meta-analysis of randomized and quasi-randomized trials comparing efficacy (seroresponses) and harms of double-dose compared with standard-dose hepatitis B vaccination in patients with CKD, including those requiring dialysis. A systematic literature search (CENTRAL, MEDLINE and EMBASE) was performed using a predetermined search strategy. Relative risks were calculated from pooled data using a random-effects model with subgroup analysis by dialysis requirement and vaccine type. Results: Seven studies (501 patients) fulfilled review criteria: four in patients receiving dialysis and three in patients not receiving dialysis. The incidence of seroconversion was not increased with double-dose vaccination overall [risk ratio (RR) 1.17, 95% confidence interval (CI) 0.98-1.39], by dialysis requirement or vaccine type. The incidence of seroprotection (reported by only four studies) was increased with double-dose vaccination overall (RR 1.53, 95% CI 1.17-2.00) but not by dialysis requirement. Adverse events were not reported by treatment arm, precluding comparison. The overall quality of included studies was moderate to low. Conclusions: The current data do not support clinical guideline recommendations for administering double-dose vaccination for patients with CKD as seroconversion was not improved and seroprotection was inadequately assessed. Large high-quality studies are required to overcome the current evidence gap regarding vaccine dosing in CKD.