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BACKGROUND AND AIMS: IgG4 sclerosing cholangitis (IgG4-SC) is the biliary component of the multisystem IgG4-related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4-SC in a large Australian cohort. METHODS: We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA-CRN). 39 sites were invited to participate. IgG4-SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes. RESULTS: 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09-67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas. CONCLUSIONS: Our study confirms the preponderance of IgG4-SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.

The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin-bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi-organ failure in patients with acute liver failure and acute-on-chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/beta-hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in-hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi-organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.

Hepatocyte growth factor (HGF) identical to scatter factor (SF) is a glycoprotein involved in the development of a number of cellular phenotypes, including proliferation, mitogenesis, formation of branching tubules and, in the case of tumour cells, invasion and metastasis. This fascinating cytokine transduces its activities via its receptor encoded by the c-met oncogene, coupled to a number of transducers integrating the HGF/SF signal to the cytosol and the nucleus. The downstream transducers coupled to HGF/MET, most of which participate in overlapping pathways, determine the development of the cell's phenotype, which in most cell types is dual.

Any virus that can cause an acute hepatitis will, on occasion, give rise to acute liver failure. Such infections can be separated into those due to the primary hepatitis viral infections A to E and those where hepatitis occurs as part of a systemic viral infection, as with infection with, for instance, Epstein-Barr virus, cytomegalovirus, Varicella zoster virus, adenovirus and Herpes simplex virus. In general, the frequency with which the different hepatitis viruses are responsible for acute liver failure is related to their underlying prevalence in particular countries. An apparent exception is the striking geographical variation in the reported prevalence of acute liver failure due to hepatitis C virus infection, with a much higher proportion of cases generally attributed to this agent in Japan and Taiwan than in Western countries. Recent work has focused on the possible importance of mutant hepatitis B viral strains, co- and super-infection with known hepatitis viruses and certain newly described agents that may account for otherwise unexplained cases of acute liver failure. Despite an improved understanding of the pathogenesis of complicating cerebral oedema and advances in general supportive care, it is likely that the most severely affected patients with acute liver failure due to viral causes will survive only with liver transplantation, at least until approaches for promoting adequate liver regeneration are successfully developed and implemented.

The relative shortage of donor organs and lack of immediate availability mean that many patients with acute liver failure die before orthotopic liver transplantation can be performed. An effective temporary liver support system could improve the chance of survival with or without a transplant being ultimately carried out. Recent technological advances resulting in improved maintenance of hepatocyte viability and function in culture and bioreactor designs which facilitate adequate perfusion of the cellular component and removal of products of cellular metabolism have led to the development of a number of bioartificial devices for liver support. Three such devices have undergone preliminary clinical evaluation in the setting of acute liver failure, with a statistically significant reduction in raised intracerebral pressure along with improvements in consciousness level and some biochemical parameters associated with treatment with one of these. Several other devices with different characteristics have shown promise in vitro and/or in animal models but await clinical evaluation. Several new totally artificial systems have also been described, along with the emergence of isolated hepatocyte transplantation, with reports of successful 'bridging' to liver transplantation. Controlled trials on a multicentre basis in well-defined patient groups and with standardized outcome measures will be required to properly evaluate the clinical value of each of these approaches to providing liver support in acute liver failure and cirrhosis. A better understanding of mechanisms underlying multiorgan failure and of factors inhibiting liver regeneration, thereby allowing a more targeted approach, will be essential to the further development of effective liver support strategies in these settings.