Primary sclerosing cholangitis (PSC) is an orphan, cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease. Its pathophysiology is poorly understood. Chronic biliary inflammation is likely driven by immune dysregulation, gut dysbiosis, and environmental exposures resulting in gutliver crosstalk and bile acid metabolism disturbances. There is no proven medical therapy that alters disease progression in PSC, with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses (15-23 mg/kg/day) but not alter transplant-free survival or liver-related outcomes. Liver transplantation is the only option for patients who develop end-stage liver disease

Background and aims Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. Methods We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. Results A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2–15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. Conclusion In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

An increasing number of observational studies have described an association between aspirin use and a reduced risk of incident hepatocellular carcinoma. We performed this meta-analysis to provide a comprehensive and updated aggregate assessment of the effect of aspirin on HCC incidence. Two independent authors performed a systematic search of the literature, utilising the Medline, Embase, Scopus, and PubMed databases. A total of 16 studies (12 cohort studies, and 4 case-control studies) were selected for inclusion, with a large number of studies excluded, due to an overlapping study population. The pooled analysis of cohort studies involving a total population of approximately 2.5 million subjects, 822,680 aspirin users, and 20,626 HCC cases demonstrated a 30% reduced risk of HCC associated with aspirin use (adjusted HR 0.70, 95%CI 0.60–0.81). There was a similar but non-significant association observed across the case-control studies (adjusted OR 0.60, 95%CI 0.32–1.15, p = 0.13), which involved a total of 1961 HCC cases. In a subgroup meta-analysis of patients with cirrhosis, the relationship between aspirin use and incident HCC diminished to non-significance (adjusted HR 0.96, 95%CI 0.84–1.09). Aspirin use was associated with a statistically significant increase in bleeding events when all relevant studies were pooled together (adjusted HR 1.11, 95%CI 1.02–1.22). Prospectively collected data should be sought, to define the optimal patient group in which aspirin is safe and effective for the chemoprophylaxis of HCC.