Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

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The report, in addressing the unacceptable high mortality of acute liver admissions to hospital reinforces the necessity for an integrated clinical services. The masterplan described is based on regional, geographically sited liver centres, each linked to four to six surrounding district general hospital (DGHs) -a pattern of care similar to that successfully introduced for stroke services. The plan includes establishment of a Lead and Deputy Lead Clinician in each acute hospital, preferably a hepatologist or gastroenterologist with liver interest who will have prime responsibility for organising care of acute liver admissions on a 24/7 basis. Essential for the plan is greater access to Intensive Care Unit/High Dependency Unit (ITU/HDU) facilities in line with Covid-19 experience and associated reconfiguration of emergency care. The report strongly recommends full implementation of the Alcohol Care Teams (ACT) programme in hospitals and improved working links with the acute medical services. The Commission also endorses recommendations from paediatric liver services to improve overall survival figures by earlier diagnosis of biliary atresia based on stool charting and by better care of impaired cognitive ability and developmental mental health problems.

Smooth pursuit eye movements (SPEM) are the conjugate movements used to track the smooth trajectory of small dots. Jerky or 'saccadic' ocular pursuit has been reported in patients with cirrhosis, but no formal assessment of SPEM has ever been undertaken. The aim of this study was to evaluate SPEM in patients with cirrhosis and varying degrees of hepatic encephalopathy. The patient population comprised 56 individuals (31 men, 25 women) of mean age 51.1 (range, 25-70) years, with biopsy-proven cirrhosis, classified, using clinical, electroencephalographic, and psychometric variables, as either neuropsychiatrically unimpaired or as having minimal or overt hepatic encephalopathy; patients were further categorized in relation to their treatment status. The reference population comprised 28 healthy volunteers (12 men, 16 women) of mean age 47.3 (range, 26-65) years. SPEM was assessed using an electro-oculographic technique. Visual inspection of the SPEM recordings showed clear disruption of smooth pursuit in the patients with minimal hepatic encephalopathy, and more pronounced disruption, if not complete loss, of smooth pursuit in patients with overt hepatic encephalopathy. The differences observed in quantifiable SPEM indices between the healthy volunteers/unimpaired patients and those with overt hepatic encephalopathy were significant (P < .05). In conclusion, SPEM performance is impaired in patients with hepatic encephalopathy in parallel with the degree of neuropsychiatric disturbance: the pathophysiology of these changes is unknown, but retinal, extrapyramidal, and attentional abnormalities are likely to play a role. Treatment status confounds the classification of neuropsychiatric status and should be taken into account when categorizing these patients. (HEPATOLOGY 2005;42:772-781.)