Variants in ATP8B1, ABCB11, and ABCB4 underlie the most prevalent forms of progressive familial intrahepatic cholestasis. We aim to describe variants in these genes in a cohort of patients with adult‐onset liver disease, and explore a genotype–phenotype correlation. Patients with onset of liver disease aged above 18 who underwent sequencing of cholestasis genes for clinical purposes over a 5‐year period were identified. Bioinformatic analysis of variants was performed. Liver histology was evaluated in patients with variants. Of the 356 patients tested, at least one variant was identified in 101 (28.4%): 46 ABCB4, 35 ABCB11, and 28 ATP8B1. Patients with ABCB4 variants had chronic liver disease (71.7%) and pregnancy‐associated liver dysfunction (75%), with a younger age of onset in more severe genotypes (p = 0.046). ABCB11 variants presented with pregnancy‐associated liver dysfunction (82.4%) and acute/episodic cholestasis (40%), with no association between age of onset and genotype severity. ATP8B1 variants were associated with chronic liver disease (75%); however, they were commonly seen in patients with an alternate etiology of liver disease and variants were of low predicted pathogenicity. In adults with suspected genetic cholestasis, variants in cholestasis genes were frequently identified and were likely to contribute to the development of liver disease, particularly ABCB4 and ABCB11. Variants were often in heterozygous state, and they should no longer be considered recessive Mendelian traits. Sequencing cholestasis genes in selected patients with adult‐onset disease should be considered, with interpretation in close collaboration with histopathologists and geneticists.

End-stage liver disease (ESLD) is a leading cause of morbidity and mortality amongst human immunodeficiency virus (HIV)-positive individuals. Chronic hepatitis B and hepatitis C virus (HCV) infection, drug-induced hepatotoxicity related to combined anti-retro-viral therapy, alcohol related liver disease and non-alcohol related fatty liver disease appear to be the leading causes. It is therefore, anticipated that more HIV-positive patients with ESLD will present as potential transplant candidates. HIV infection is no longer a contraindication to liver transplantation. Key transplantation outcomes such as rejection and infection rates as well as medium term graft and patient survival match those seen in the non-HIV infected patients in the absence of co-existing HCV infection. HIV disease does not seem to be negatively impacted by transplantation. However, HIV-HCV co-infection transplant outcomes remain suboptimal due to recurrence. In this article, we review the key challenges faced by this patient cohort in the pre- and post-transplant period.

Background: Lower respiratory tract infection is a common cause of morbidity and mortality worldwide. A crosssectional study was carried out with an objective to study the antibiogram of Gram-negative isolates of patients with lower respiratory tract infection visiting Kathmandu Model Hospital.Methods: A total of 274 specimens including sputum, endotracheal aspirates, suction tips were cultured as per standard microbiological technique. Antibiotic susceptibility and detection of Extended-spectrum beta- lactamases (ESBLs) were performed following Clinical Laboratory Standard Institute (CLSI 2014) guidelines.Results: Respiratory pathogens were recovered from 24.6% (n=65) cases. Klebsiella pneumoniae (40%) was the commonest isolates. The highest prevalence of multidrug-resistance (69.23%) was observed in Acinetobacter calcoaceticus baumannii complex. Extended-spectrum beta- lactamases were detected in Escherichia coli (n=4), Klebsiella pneumoniae (n=4) and Acinetobacter calcoaceticus baumannii complex (n=1).Conclusions: High prevalence of multidrug-resistance and extended- spectrum beta- lactamase producers were observed in respiratory isolates. For effective management of lower respiratory tract infections, an ultimate and detailed microbiological diagnosis and susceptibility testing is required.