Identification of two novel subtypes of hepatitis C virus genotype 8 and a potential new genotype successfully treated with direct acting antivirals.

BACKGROUND: Hepatitis C virus (HCV) has a high genetic diversity and is classified into 8 genotypes and over 90 subtypes with some endemic to specific world regions. This could compromise direct-acting antiviral (DAA) efficacy and global HCV elimination. METHODS: We characterised HCV subtypes 'rare' to the UK (non-1a/1b/2b/3a/4d) by whole genome sequencing via a national surveillance programme. Genetic analyses to determine the genotype of samples with unresolved genotypes were undertaken by comparison with ICTV HCV reference sequences. RESULTS: Two HCV variants were characterised as being closely related to the recently identified genotype 8 (GT8), with >85% pairwise genetic distance similarity to GT8 sequences and within the typical inter-subtype genetic distance range. The individuals infected by the variants were UK residents originally from Pakistan and India. In contrast, a third variant was only confidently identified to be more similar to GT6 compared to other genotypes across 6% of the genome and was isolated from a UK resident originally from Guyana. All three were cured with pangenotypic DAAs (Sofosbuvir + Velpatasvir or Glecaprevir + Pibrentasvir) despite the presence of resistance polymorphisms in NS3 (80 K/168E), NS5A (28 V/30S/62L/92S/93S) and NS5B (159F). CONCLUSIONS: This study expands our knowledge of HCV diversity by identifying two new GT8 subtypes and potentially a new genotype.

Detection and validation of serum C-reactive protein and procalcitonin as diagnostic markers for bacterial infections in patients with cirrhosis of liver.

Background: The role of inflammatory markers like CRP and procalcitonin in predicting various outcomes in patients with cirrhosis is gaining lot of attention. There is a need for extensive studies, to be carried out in India as there is no adequate literature available on the subject. Objectives: To assess the predictive validity of c-reactive protein and procalcitonin in predicting bacterial infection and mortality in patients with cirrhosis. Materials and methods: A prospective observational study conducted in the Department of Hepatology, at Madras Medical College, Chennai. Patients admitted to the Hepatology ward from March2016 to February 2017with acute decompensation of liver cirrhosis were studied. The serum procalcitonin level was assessed by Electro Chemi Luminescence Immuno Assay (Eclia) with a measuring range of 0.02-75ng/ml. and C-Reactive Protein level was assessed by ImmunoTurbido Kumaragurubaran Sivanesan, Narayanasamy Krishnasamy, Shanthiselvi, Chezhian Annasamy, Senthilkumar Ramalingam, Akilandeswari Alagan Ramasamy, Premkumar Krishnamoorthy, Jaiganesh Mohan. Detection and validation of serum Creactive protein and procalcitonin as diagnostic markers for bacterial infections in patients with cirrhosis of liver. IAIM, 2017; 4(4): 53-62. Page 54 Metric Assay, with a measuring range of 1.00-200mg/l. The utility of CRP and procalcitonin in predicting the infection and mortality was assessed by Receiver Operative curve (ROC) analysis. Results: Procalcitonin had a better predictive validity than C-reactive protein in predicting the bacterial infection in the study population as indicated by their AUC curve as 0.99 (95% CI 0.99, 1.00, p value <0.001), for Procalcitonin and 0.84 (95% CI 0.76, 0.92, p value <0.001) for C-reactive protein. In predicting the mortality, C-reactive protein had a better predictive validity when compared to Procalcitonin as indicated by their AUC curve as 0.804 (95% CI 0.68, 0.92, p value <0.001) for Creactive protein and 0.63 (95% CI 0.48, 0.77, p value <0.001) for Procalcitonin. Conclusion: More than one third of hospitalized Cirrhosis patients had infection and mortality rate was just over 20%. PCT has shown better predictive validity as compared to CRP in predicting infection, but CRP had better predictive validity in predicting mortality.