Intragroup divergence ranged from 08 ± 05 (%  standard deviatio

Intragroup divergence ranged from 0.8 ± 0.5 (%  standard deviation) for subgenotype D6 to 3.0 ± 0.3 for D8. Inter-subgenotype divergence mostly ranged 4–7.5%. Phylogenetic analysis of genotype D showed separation into six distinct clusters (subgenotypes D1,

D2, D3/D6, D4, D5 and D7/D8) with good bootstrap support. The mean intergroup divergence between D3 and D6 was the lowest and fell below the threshold of 4%, which is required to define a subgenotype, suggesting that subgenotypes D3 and D6 belong to one subgenotype. “D8” is a genotype D/E recombinant, which clusters with D7. A number of signature amino acids were found Navitoclax in all four open reading frames that could differentiate the subgenotypes, which also showed distinct geographical distribution. There are six and not eight subgenotypes of D, D1–D6, which can be differentiated by distinct clustering with high bootstrap support and signature amino acids. Subgenotypes D3 and “D6” should be reclassified as a single subgenotype D3 and it would be more correct to classify “D8” as a genotype D/E recombinant rather than a subgenotype. “
“Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver disease characterized

by progressive destruction of the interlobular bile ducts that eventually leads to cirrhosis. Due to its hallmark serological signature, the antimitochondrial antibody (AMA) and similarly associated disease-specific T cell response, PBC is often selleck considered a model autoimmune disease. Despite this, immunosuppressive therapies are ineffective for PBC and the only approved medical treatment is the hydrophilic bile acid, ursodeoxycholic acid (UDCA).1 A biochemical response to UDCA with normalization of alkaline phosphatase (ALP) is not achieved in some 30–40% of patients with PBC. Whilst it is established that responders to UDCA have a normal life expectancy, non-responders are at an increased risk of progression to liver transplantation or death.2,3 For this reason, the impetus for the discovery of adjuvant or alternative medical therapies for PBC persists. The potential efficacy of

farnesoid X (FXR) receptor agonists such as obeticholic acid (OCA) are currently being evaluated in international multi centre trials with promising results in this group of refractory PBC patients.4 OCA is the first-in class agonist ZD1839 cost of the nuclear receptor farnesoid X, which controls bile acid synthesis and bile flow in the liver. The potential role of fibrate therapy in PBC first became evident in the early 1990s when patients receiving fibrates for hypercholesterolemia were noted to have a reduction in their serum total ALP. In 1993, Day and colleagues demonstrated that this change resulted from reduced hepatic production of ALP.5 More recently, fibrates have been shown to activate peroxisome proliferator-activated receptor α (PPARα) and upregulate the expression of multiple drug resistance gene-3 (MDR3), both of which potentially ameliorate hepatic inflammation.

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