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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Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.

BackgroundCOVID-19 is a global pandemic caused by the novel coronavirus SARS-CoV-2. Risk factors and prognostic markers of severe disease remain to be fully determined, although some studies have suggested a correlation between abnormal liver function and adverse outcomes. Further studies are needed to investigate this further.MethodsThis retrospective study enrolled patients with a confirmed diagnosis of COVID-19 who were admitted to Kingston Hospital in the UK. Data collected included age, sex, ethnicity, comorbidity profile, biochemical markers of liver function and the acute phase response, and overall outcome.ResultsBetween 16 March 2020 and 30 April 2020, a total of 343 patients were admitted to the acute medical team at Kingston Hospital. Excluding those with a history of liver disease, 299 patients had liver function tests performed with abnormalities demonstrated in 44.8% of individuals. Derangement of liver function was associated with greater need for ventilatory support (p<0.001), admission to high dependency unit or intensive care (p<0.001) and increased length of hospital stay (p<0.001). Of note, liver dysfunction was more common in those of non-white ethnicity (p=0.007) and correlated with higher levels of C reactive protein (p=0.01) and ferritin (p<0.001).ConclusionAbnormal liver function is associated with a negative outcome among those hospitalised with COVID-19. The cause for this association is unclear, but correlation between abnormal liver function and higher serum levels of acute phase proteins suggest that dysregulation of the immune system in response to SARS-CoV-2 may be contributory.

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